Excision of limbal dermoids. We reviewed the clinical files of 10 patients who had undergone excision of unilateral epibulbar limbal dermoids. Preoperatively, all of the affected eyes had worse visual acuity (P less than .02) and more astigmatism (P less than .01) than the contralateral eyes. Postoperatively, every patient was cosmetically improved. Of the eight patients for whom both preoperative and postoperative visual acuity measurements had been obtained, in six it had changed minimally (less than or equal to 1 line), and in two it had improved (less than or equal to 2 lines). Surgical complications included persistent epithelial defects (40%) and peripheral corneal vascularization and opacity (70%). These complications do not outweigh the cosmetic and visual benefits of dermoid excision in selected patients. 
Bell's palsy. A diagnosis of exclusion. In cases of acute unilateral facial weakness, a careful and systematic evaluation is necessary to identify the cause. Idiopathic facial paralysis (Bell's palsy) is a diagnosis of exclusion. It is also the most common cause of unilateral facial weakness seen by primary care physicians. The most important aspect of initial treatment is eye protection. Administration of systemic oral corticosteroids may lessen severity and duration of symptoms. 
Retained endobronchial foreign body removal facilitated by steroid therapy of an obstructing, inflammatory polyp. Oral and topical steroids were used to induce regression in an inflammatory, obstructing endobronchial polyp caused by a retained foreign body. The FB (a peanut half), which had been present for over six months, was then able to be easily and bloodlessly retrieved with fiberoptic bronchoscopy. 
Recurrent buccal space abscesses: a complication of Crohn's disease. A patient is described with generalized gastrointestinal involvement by Crohn's disease. Symptoms of recurrent ulceration and mucosal tags are well-described oral manifestations of Crohn's disease; however, in our patient recurrent facial abscesses, which required extraoral drainage, also developed. This complication has not previously been reported. 
Intracranial fibromatosis. Fibromatoses are uncommon infiltrative lesions affecting musculoaponeurotic structures, most often of the limbs and trunk. Lesions involving the cranial cavity are rare and require the same aggressive surgical management as elsewhere in the body. This case illustrates their clinical and neuroradiological features and underscores the necessity for aggressive resection to avoid recurrence. The literature is reviewed. 
The effect of intrathecal morphine on somatosensory evoked potentials in awake humans. Although the effect of systemic opioids on somatosensory evoked potentials has been well described, little is known about the interaction between intrathecally administered opioid analgesics and somatosensory evoked potentials. Accordingly, the influence of intrathecally administered morphine on posterior tibial nerve somatosensory cortical evoked potentials (PTSCEPs) was investigated in 22 unpremedicated, awake, neurologically normal patients scheduled to undergo elective abdominal or pelvic procedures. Patients were randomly assigned to receive either preservation-free intrathecal morphine sulfate (ITMS) or placebo. After baseline PTSCEP, heart rate and, mean blood pressure were recorded, ITMS (15 micrograms.kg-1) was injected via standard dural puncture with the patient in the lateral position. PTSCEPs, heart rate, and mean blood pressure were recorded again at 5, 10, 20, 30, 60, 90, and 120 min. Control patients were treated identically (including position, sterile preparation, and subcutaneous tissue infiltration with local anesthetic), except for lumbar puncture, and were unaware of their randomization. Before administration of ITMS, PTSCEP P1, N1, P2, N2, and P3 latencies were 39.4 +/- 3.2, 47.6 +/- 3.9, 59.2 +/- 3.2, 70.4 +/- 3.7, and 84.6 +/- 5.5 ms, (mean +/- standard deviation), respectively. The corresponding P1-N1, N1-P2, and P2-N2 amplitudes were 2.4 +/- 1.1, 2.4 +/- 1.1, and 2.3 +/- 0.9 microV, respectively. There were no significant changes over time between the control and ITMS groups. PTSCEPs resulting from left-sided stimulation were not different from those elicited by right-sided stimulation. All ITMS patients had intense postoperative analgesia for at least 24 h. It is concluded that ITMS does not affect PTSCEP waveforms in the 35-90 ms latency range during the awake state. 
The 29th Rovenstine lecture: clinical challenges for the anesthesiologist. In conclusion, I hope that my comments have reaffirmed your biases or, even more importantly, stimulated you to think in a different way about the information explosion in our specialty and medicine in general. I believe our specialty is in a golden era that will benefit from the past and be nourished by new discoveries and understanding. We as clinicians must accept the challenge of recognizing what new information deserves incorporation into our practice, what old information deserves to be sustained, and what merits new scrutiny and perhaps should be discarded. If I had one wish, it would be that anesthesiologists would never lose their zeal to be students--their thirst for new information--as the continuum of anesthesia education is indeed a life-long process. That wish, ladies and gentlemen, is my challenge to all anesthesiologists. 
Mortality in patients treated with flecainide and encainide for supraventricular arrhythmias. In a recent clinical trial, the class Ic antiarrhythmic drugs encainide and flecainide were found to be associated with an increased mortality risk in patients with new myocardial infarction and ventricular arrhythmias. The purpose of this study was to assess whether an increased mortality risk also accompanied the use of these drugs to treat patients with supraventricular arrhythmias. Data were obtained from the respective pharmaceutical sponsors on the mortality observed with each drug in United States and foreign protocols enrolling patients with supraventricular arrhythmias. Mortality in the encainide population (343 patients) and the flecainide population (236 patients) was compared with that in a research arrhythmia clinic, the Duke population (154 patients). Nine deaths occurred in the combined encainide-flecainide population and 10 deaths occurred in the Duke population; the follow-up periods averaged 488 days and 1,285 days, respectively. The 6-year survival functions of these 2 populations, estimated by the Kaplan-Meier technique, did not differ significantly (p = 0.62). The hazard ratio for the combined encainide-flecainide population relative to the Duke population was estimated to be 0.6 with a 95% confidence interval of 0.2, 1.7. These descriptive comparisons did not demonstrate any excess mortality when flecainide and encainide were used in patients with supraventricular arrhythmias. 
Approaches to immunotherapy of cancer: characterization of lymphokines as second signals for cytotoxic T-cell generation. Lymphokines, the soluble molecules produced by cells of the immune system, regulate cell-cell interactions and, consequently, the functional status of the immune system. Altering immunoregulatory pathways with lymphokines in vivo may provide a mechanism for controlling a variety of immunologic disorders. Although normally produced in vivo in very small quantities, the widespread availability of recombinant lymphokines has made it possible to study the molecular signals involved in production of lymphocyte effectors with activity against tumor. For example, interleukin-2-based cancer immunotherapy programs have, in certain clinical situations, suggested that immunologic intervention can influence the regression of metastatic cancer. Ultimately the successful application of these biologic agents requires an understanding of the interaction between the immune system and tumor on a molecular level. To induce a given biologic effect, it is necessary both to classify the required lymphokines and to identify the relevant effector cell populations. This review will examine the progress made in identifying the requirements for lymphokine-induced cytotoxic T-lymphocyte function. 
Retinal artery obstruction and atheromas associated with non-Hodgkin's large cell lymphoma (reticulum cell sarcoma). A 71-year-old woman developed branch retinal artery obstruction as the presenting manifestation of a large cell non-Hodgkin's lymphoma. Multifocal chorioretinal scars were present in the same eye. She experienced progressive visual loss accompanied by development of multiple yellow retinal arterial wall plaques, extension of retinal opacification into other quadrants, and increasing vitreous cellular infiltration. Clinical diagnoses included branch retinal arterial obstruction caused by toxoplasmosis retinitis, multifocal choroiditis and panuveitis simulating the presumed ocular histoplasmosis syndrome, vitiliginous chorioretinitis, and the acute retinal necrosis syndrome. Four months after onset, the right eye was blind and was enucleated. Histopathologic examination revealed extensive lymphomatous infiltration and necrosis of the retina and optic nerve. The retinal arteries were partly obstructed by lymphomatous infiltration and atheromas. Subsequently, the left eye and central nervous system were involved by lymphoma. 
The 'tonic' pain-related behaviour seen in mononeuropathic rats is modulated by morphine and naloxone. This study investigated the sensitivity to pharmacological manipulations of a rating method, adapted from the formalin test, to measure the tonic component of the pain-related behaviour induced by creating a peripheral mononeuropathy with 4 loose ligatures around the common sciatic nerve. Although the adequacy of opioid substances in alleviating neuropathic pain is highly controversial, the effects of morphine (1 mg/kg i.v.) and naloxone (1 mg/and 3 micrograms/kg i.v.) were tested 1-2 weeks after the nerve ligatures were established, when pain-related behaviours were well developed. Morphine (1 mg/kg i.v.) induced a potent and prolonged decrease in the pain-rating score at week 2 after surgery. Either at week 1 or week 2, naloxone elicited a bidirectional dose-dependent action: a further increase in the pain-rating score with the high dose (1 mg/kg i.v.), and a paradoxical decrease in the score with the low dose of 3 micrograms/kg i.v. These effects are comparable to those already described in several rat models of inflammatory pain and, in the same model of neuropathy, using a phasic nociceptive test, the measure of the vocalization to paw pressure. A few differences in the effects of naloxone on tonic and phasic pain are noted and discussed. 
Examination of cardiorespiratory changes during upper gastrointestinal endoscopy. Comparison of monitoring of arterial oxygen saturation, arterial pressure and the electrocardiogram. Critical events including hypoxaemia, arrhythmias and myocardial ischaemia may occur more frequently during endoscopic procedures than during anaesthesia. A study was undertaken to assess the cardiovascular changes and to evaluate suitable monitoring techniques to detect critical events during sedation and endoscopy. Twenty patients scheduled to undergo a prolonged endoscopic procedure which required deep sedation were studied. Continuous recordings of electrocardiogram, heart rate and arterial oxygen saturation were made and arterial pressure was recorded at one-minute intervals. The study commenced immediately before administration of sedatives, continued for the duration of the examination and for one hour following the examination. Oxygen saturation decreased in all patients during the examination to a mean of 82.9% (SD 11.9), and remained below baseline for the duration of the examination and into the recovery period. Statistically significant increases and reductions of systolic arterial pressure and rate-pressure product were found during the procedures compared with baseline values recorded before administration of sedatives. Sixteen of the 20 patients developed tachycardia during the examination. Ten patients developed ectopic foci which were supraventricular, ventricular or both in origin. Electrocardiogram changes resolved during the recovery period. Myocardial ischaemia was assessed by S-T segment depression and a significant correlation was found between S-T segment depression and hypoxaemia, although the magnitude of the S-T depression was small and may not have been detected clinically. No correlation was found between S-T segment depression and arterial pressure, heart rate or rate-pressure product. 
Hepatic transmethylation and blood alcohol levels. Golden Syrian hamsters that have elevated hepatic alcohol dehydrogenase activity were divided into four groups and group-fed on four different liquid diets for five weeks. Group I was fed a control diet formulated for hamsters. Group II was fed the control diet containing 20 micrograms of 4 methylpyrazole per litre. Group III was fed the hamster ethanol liquid diet (ethanol amounting to 36% of total calories). Group IV was fed the ethanol diet to which 4-methylpyrazole (20 micrograms/litre) was added. Groups I, II and III were group-fed the amount consumed by Group IV on a daily basis. Upon killing the animals, blood alcohol levels were found to be elevated in Group IV but not in Group III. Hepatic methionine synthetase (MS) was inhibited in Group IV. Betaine-homocysteine methyltransferase was induced in this group to compensate for the MS inhibition and liver betaine was lowered reflecting this induction. None of these changes were seen in Group III. Since none of the animals showed an aversion to their respective diets and gained weight normally, these data indicate that it was the elevated blood levels of ethanol rather than nutritional factors that were related to the changes in methionine metabolism. 
Memory T cells represent the predominant lymphocyte subset in acute and chronic liver inflammation. T cells can be divided into two main phenotypic subpopulations-i.e., the CD45RA-positive (2H4-positive) "naive" subset and the CD45RO-positive (UCHL1-positive) "memory" subset. In light of this recent functional reinterpretation of T-lymphocyte subpopulations, we reinvestigated the composition of the inflammatory infiltrate in liver biopsy specimens from patients with acute and chronic hepatitis. In normal liver, the few scattered mononuclear cells present in portal tracts and in the intralobular parenchyma consisted of both CD45RA-positive (2H4-positive) naive and CD45RO-positive (UCHL1-positive) memory T cells. In inflammatory liver diseases, portal tract and periportal and intralobular areas of inflammation consisted virtually only of CD45RO-positive (UCHL1-positive) memory T cells, which strongly expressed the CDw29 (4B4) antigen, and the adhesion molecules LFA-1, CD2, LFA-3, CD44 and VLA-4 and the activation marker human leukocyte antigen-DR. These results indicate that activated memory T cells represent the predominant subpopulation of lymphocytes in areas of liver inflammation. Memory T cells strongly express various homing receptors and adhesion molecules, which probably allow them to accumulate at inflammatory sites and to strengthen interaction with target cells. Furthermore, the increased number of memory T cells with enhanced interferon-gamma production in areas of liver inflammation may contribute to the maintenance and up-regulation of immune responses occurring in inflammatory liver diseases. 
Inflammatory properties of neutrophil-activating protein-1/interleukin 8 (NAP-1/IL-8) in human skin: a light- and electronmicroscopic study. Neutrophil-activating protein-1/interleukin 8 (NAP-1/IL-8), purified to homogeneity from lipopolysaccharide-stimulated human peripheral blood monocytes, was injected intracutaneously into human skin. Sequential biopsy specimens were taken in order to investigate the sequence of ultrastructural changes induced by the cytokine. Whereas intracutaneous injection of 100 ng of NAP-1/IL-8 per site caused no macroscopic changes, by histology infiltration with polymorphonuclear leukocytes (PMN) and monocytes was present within 1 h and increased at 3 and 5 h. No lymphocyte infiltration was noted. The first ultrastructural changes (30 min) consisted of the presence of cytoplasmic 7-nm microfilament bundles, as well as numerous protrusions of the luminal plasma membrane of endothelial cells (EC). As a striking feature, multiple 100- to 160-nm electron lucent vesicles could be observed in the EC cytoplasm. These structures differed from plasmalemmal vesicles and suggest secretory activity. When PMN and monocytes appeared in the vascular lumen (1 h and later), the number of 100-160-nm electron-lucent vesicles had decreased significantly. In contrast to C5a-injected skin sites, mast cell degranulation was absent. 
Bronchogenic carcinoma with chest wall invasion. Bronchogenic carcinoma with chest wall involvement continues to present a major clinical challenge. We have treated 52 patients since 1973, excluding those with superior sulcus tumors. There were 37 male and 15 female patients with an average age of 62.9 years. Chest pain was an initial symptom in 37%. All patients had negative mediastinoscopy results. Squamous cell carcinoma was present in 53% and adenocarcinoma in 35%. The median number of ribs resected was two (range, one to six), and only 2 patients required chest wall reconstruction. Pathologic staging was T3 N0 M0 in 83% and T3 N1 M0 in 17%. Operative mortality was 3.8%. Absolute 5-year survival was 26.3%. Patients who had N1 disease had a 5-year survival of only 11%. Radiation therapy was employed in 46% for positive nodes or close margins. Bronchogenic carcinoma with chest wall invasion remains potentially curable if N2 nodes are not involved. The role of radiation therapy has not been clearly defined. Morbidity and mortality should be minimal. 
Electronic weaponry--a question of safety [published erratum appears in Ann Emerg Med 1991 Sep;20(9):1031] Electronic weapons represent a new class of weapon available to law enforcement and the lay public. Although these weapons have been available for several years, there is inadequate research to document their safety or efficacy. Two of the most common, the TASER and the stun gun, are reviewed. The electronic weapon was initially and still is approved by the US Consumer Product Safety Commission; its approval was based on theoretical calculations of the physical effects of damped sinusoidal pulses, not on the basis of animal or human studies. These devices are widely available and heavily promoted, despite limited research into their safety or efficiency and despite recent animal studies documenting their potential for lethality. 
Operative management of acoustic neuromas: the priority of neurologic function over complete resection. The objective of surgical management of acoustic tumors is to remove them entirely and preserve facial nerve function and hearing when possible. A dilemma arises when it is not possible to remove the entire tumor without incurring additional neurologic deficits. Twenty patients who underwent intentional incomplete surgical removal of an acoustic neuroma to avoid further neurologic deficit were retrospectively reviewed. They were divided into a subtotal group (resection of less than 95% of tumor) and a near-total group (resection of 95% or more of tumor) and were followed yearly with either computed tomography or magnetic resonance imaging. The subtotal group was planned and consisted of elderly patients (mean age, 68.5 years) with large tumors (mean, 3.1 cm). The near-total group consisted of younger patients (mean age, 45.8 years) and smaller tumors (mean, 2.3 cm). The mean length of followup for all patients was 5.0 years. Ninety percent of patients had House grade I or II facial function post-operatively. Radiologically detectable tumor regrowth occurred in only one patient, who was in the subtotal resection group. Near-total resection of acoustic tumor was not associated with radiologic evidence of regrowth of tumor for the period of observation. Within the limits of the follow-up period of this study, subtotal resection of acoustic neuroma in elderly patients was not associated with clinically significant recurrence in most patients and produced highly satisfactory rates of facial preservation with low surgical morbidity. 
Torsades de pointes occurring in association with terfenadine use. Torsades de pointes is a form of polymorphic ventricular tachycardia that is associated with prolongation of the QT interval. Although found in many clinical settings, torsades de pointes is most often drug induced. This report describes the first association (exclusive of drug overdose) of symptomatic torsades de pointes occurring with the use of terfenadine in a patient who was taking the recommended prescribed dose of this drug in addition to cefaclor, ketoconazole, and medroxyprogesterone. Measured serum concentrations of terfenadine and its main metabolite showed excessive levels of parent terfenadine and proportionately reduced concentrations of metabolite, suggesting inhibition of terfenadine metabolism. We believe that a drug interaction between terfenadine and ketoconazole resulted in the elevated terfenadine levels in plasma and in the cardiotoxicity previously seen only in cases of terfenadine overdose. 
Asymptomatic celiac and superior mesenteric artery stenoses are more prevalent among patients with unsuspected renal artery stenoses. The prevalence of unsuspected renal artery stenosis among patients with peripheral vascular disease has been reported to be as high as 40%, but the prevalence of asymptomatic celiac and superior mesenteric artery stenoses in these patients is not known. The biplane aortograms of 205 male patients who were military veterans and had aneurysms or occlusive disease were independently reviewed, and medical records were studied to determine associated coronary disease, risk factors, and patient outcome. Fifty-six patients (27%) had a 50% or greater stenosis in the celiac or superior mesenteric artery, and seven patients (3.4%) had significant stenoses in both mesenteric arteries. Patients with celiac or superior mesenteric artery stenoses were older (p = 0.002) and had a higher prevalence of hypertension (p = 0.029) than those without significant mesenteric stenoses. Fifty of the 205 patients had significant renal artery stenoses, and 20 had advanced (greater than 75% diameter loss) renal stenoses. Ten of the 20 patients (50%) with advanced renal stenoses had a concomitant celiac artery stenosis, compared to 40 of the 185 patients (22%) who did not have advanced renal stenoses (p = 0.011). In the present study asymptomatic celiac or superior mesenteric artery stenoses were common among male veterans evaluated for peripheral vascular disease, but the prevalence of significant stenoses in both the celiac and superior mesenteric arteries was low. The prevalence of significant celiac stenosis was higher in patients with advanced (greater than 75%) renal artery stenoses who might be considered for prophylactic renal revascularization. Lateral aortography with evaluation of the celiac artery is always appropriate in these patients. 
Brain-stem auditory evoked responses in 56 patients with acoustic neurinoma. The brain-stem auditory evoked responses (BAER's) recorded from 56 patients with acoustic neurinomas were analyzed. Ten of the patients had intracanalicular tumors and 46 had extracanalicular tumors. It was possible to obtain BAER's following stimulation of the affected side in 28 patients and after stimulation of the unaffected side in all 56. Five patients (11%) had normal BAER's following stimulation of both sides; three of these patients had intracanalicular tumors. Among BAER's obtained following stimulation of the affected ear, the mean interpeak latency (IPL) for peaks I to III associated with extracanalicular tumors was significantly prolonged relative to controls (p less than 0.001), and linear regression analysis revealed a significant positive correlation between tumor size and IPL of peaks I to III (p less than 0.05). Analysis of the 56 BAER's recorded after stimulation of the unaffected side revealed a significant positive correlation between the IPL's of peaks III to V and tumor size (p less than 0.001). This correlation was not strengthened when accounting for the degree of brain-stem compression. Finally, evidence of preserved function within the auditory pathway, even in the presence of partial hearing loss, is presented. This finding suggests that more patients might benefit from surgical procedures that spare the eighth cranial nerve. 
First heterotransplantation of a human carcinoid tumor into nude mice. The first successful heterotransplantation of a human carcinoid tumor into nude mice is reported. CSH, a voluminous hepatic metastasis of a primary bronchial carcinoid tumor (CSB) was resected and transplanted into three irradiated nude (Swiss-nu/nu) mice both by subcutaneous (SC) and intramuscular (IM) routes; the success rate was five of six. Heterotransplanted tumors took 4 to 5 months to appear in the mice and 1 month to attain a width of 0.5 cm. Both human and mouse tumors (named CSH-SC and CSH-IM) were studied by light and electron microscopy. They were Grimelius-positive, neuron-specific enolase-positive, and bombesin-negative by immunocytochemistry. Furthermore, CSH-SC cells presented characteristic (pear-shaped, rod-shaped, or tadpole-shaped) neurosecretory granules. Although CSB and CSH were slightly serotonin positive by immunocytochemistry, only a few serotonin-positive cells were found in CSH-SC and none in CSH-IM, suggesting partial loss of differentiation or an increase in serotonin catabolism during transplantation. 
A prospective evaluation of the immediate reproducibility of the signal-averaged ECG. The purpose of this investigation was to prospectively evaluate the immediate reproducibility of the signal-averaged electrocardiogram (SAECG). A total of 114 patients undergoing evaluation for ventricular arrhythmias were enrolled in this protocol. Two consecutive SAECG's (40 Hz bidirectional high-pass filtering with a computer-automated system) were performed 10 minutes apart. Abnormal SAECG parameters were defined as (1) vector QRS duration more than 120 msec, (2) terminal root mean square (RMS) voltage less than 20 microV, and (3) low-amplitude signal (LAS) duration more than 40 msec. An SAECG was defined as abnormal if at least one vector parameter was abnormal. There was close correlation between vector parameters during the two SAECG observations: QRS duration had the highest reproducibility (r2 = 0.97, p less than 0.001) followed by terminal RMS voltage (r2 = 0.92, p less than 0.001), and LAS duration (r2 = 0.90, p less than 0.001). The mean (+/- SD) percentage of change between the two recordings was 2% +/- 2% of the QRS duration, 13% +/- 22% for terminal RMS voltage, and 7% +/- 11% for LAS duration. The reproducibility of an initially normal SAECG was 92% and of an initially abnormal SAECG, 96%. Seventeen patients (15%) had a change in one of the three vector parameters between the two recordings. There were no clinically significant differences between the 17 patients in whom the SAECG was nonreproducible and the 97 patients in whom the SAECG was reproducible. However, reproducibility was significantly higher in patients with an initially normal versus an initially abnormal SAECG (92% vs 76%, p = 0.03). 
Hypertension, lipoprotein(a), and apolipoprotein A-I as risk factors for stroke in the Chinese. We analyzed the serum concentrations of lipids and lipoproteins and the prevalence of other risk factors in a case-control study of 304 consecutive Chinese patients with acute stroke (classified as cerebral infarction, lacunar infarction, or intracerebral hemorrhage) and 304 age- and sex-matched controls. For all strokes we identified the following risk factors: a history of ischemic heart disease, diabetes mellitus, or hypertension; the presence of atrial fibrillation or left ventricular hypertrophy; a glycosylated hemoglobin A1 concentration of greater than 9.1%; a fasting plasma glucose concentration 3 months after stroke of greater than 6.0 mmol/l; a serum triglyceride concentration 3 months after stroke of greater than 2.1 mmol/l; and a serum lipoprotein(a) concentration of greater than 29.2 mg/dl. We found the following protective factors: a serum high density lipoprotein-cholesterol concentration of greater than 1.59 mmol/l and a serum apolipoprotein A-I concentration of greater than or equal to 106 mg/dl. The patterns of risk factors differed among the three stroke subtypes. When significant risk factors were entered into a multiple logistic regression model, we found a history of hypertension, a high serum lipoprotein(a) concentration, and a low apolipoprotein A-I concentration to be independent risk factors for all strokes. The attributable risk for hypertension was estimated to be 24% in patients aged greater than or equal to 60 years. In this population, in which cerebrovascular diseases are the third commonest cause of mortality, identification of risk factors will allow further studies in risk factor modification for the prevention of stroke. 
Prevalence of air bronchograms in small peripheral carcinomas of the lung on thin-section CT: comparison with benign tumors. Despite improved techniques--such as bronchoscopy and percutaneous needle biopsy--to evaluate pulmonary nodules, there are still many cases in which surgical resection is necessary before carcinoma can be differentiated from benign lesions. The present study was undertaken to determine if the presence of an air bronchogram or air bronchiologram (patent visible bronchus or bronchiole) is useful in distinguishing small lung cancers from benign nodules. Thin-section chest CT scans were obtained in patients with 20 peripheral lung cancers less than 2 cm in diameter (18 adenocarcinomas, one squamous cell carcinoma, and one large cell carcinoma) and 20 small benign nodules (eight hamartomas, seven tuberculomas, two foci of aspergillosis, one focus of cryptococcosis, one chronic focal interstitial pneumonitis, and one plasma cell granuloma). The images were compared with regard to the patency of any bronchus or bronchiole within the lesions. After surgical resection, the specimens were inflated with agar and sectioned transversely to correlate gross morphology and low-power histologic sections with the CT appearance. An air bronchogram or air bronchiologram was seen in the tumors on 65% of CT scans and 70% of histologic sections. Benign nodules had a patent bronchus or bronchiole on CT scans and histologic sections in only one case (5%). These findings suggest that the presence of an air bronchogram in a lung nodule is a useful finding to help differentiate adenocarcinomas from benign lesions. 
Long-term spinal administration of morphine in cancer and non-cancer pain: a retrospective study. Records of 313 patients who had been treated with spinal morphine via an implanted Port-A-Cath were reviewed. In 284 cases the Port-A-Cath was implanted for epidural delivery of morphine in patients with cancer-related pain. These patients were treated for a mean of 96 (range 1-1215) days. There was a wide variation in dose requirements, minimum daily dose ranging from 0.5 to 200 mg and maximum daily dose from 1 to 3072 mg. However, there was no clear trend to increasing dose as period of epidural morphine administration increased. The most frequent complications were pain on injection (12.0% incidence), occlusion of the portal system (10.9%), infection (8.1%) and leakage of administered morphine such that it did not all reach the epidural space (2.1%). In all but 1 case infections were limited to the area around the portal or along the catheter track. All infections resolved without sequelae following removal of the portal and/or administration of antibiotics. In 17 patients Port-A-Caths were implanted for the intrathecal delivery of morphine to control cancer-related pain. These patients also exhibited wide variations in morphine dose requirements. Port-A-Caths were also implanted for delivery of spinal morphine in 12 patients with chronic pain which was not related to cancer and which failed to respond to other therapies. These patients were treated for a mean of 155 (range 2-575) days. Port-A-Caths were removed from 7 of these patients, primarily due to infection (2 cases) and inadequate pain relief and pain on injection (2 cases). 
Real-time ultrasound for the detection of deep venous thrombosis. PURPOSE: Accurate diagnosis of deep venous thrombosis (DVT) is a clinical problem in emergency practice. A prospective trial was conducted comparing real-time ultrasound with contrast venography in the diagnosis of proximal DVT. METHODS: Seventy patients whose clinical presentations mandated diagnostic evaluation for DVT had real-time ultrasound of the involved leg followed by contrast venography. Initial readings of ultrasound and venography were compared with each other and with final readings to assess reliability of interpretation. RESULTS: Final ultrasound readings agreed with final venogram readings in all patients. Negative initial ultrasound readings agreed with final venogram readings in 56 of 56 patients (negative predictive value, 100%; 95% confidence interval, 94 to 100). Eighteen patients had positive initial ultrasound readings compared with 14 who had positive final venogram readings (positive predictive value, 78%; 95% confidence interval, 55 to 91). CONCLUSION: Negative real-time ultrasonography reliably excludes proximal DVT. Positive ultrasound reliably diagnoses proximal DVT only in experienced hands. 
Single- versus dual-chamber sensor-driven pacing: comparison of cardiac outputs. Previous studies have shown that single-chamber sensor-driven pacing improves exercise tolerance for patients with chronotropic incompetence. However, long-term single-chamber pacing has a number of inherent problems that limit its usefulness. Although sensor-driven dual-chamber pacing largely obviates the problems inherent with single-chamber sensor-driven pacing, the physiologic benefit of dual-chamber sensor-driven pacing has not yet been demonstrated. Accordingly, the purpose of this study was to compare exercise-induced cardiac output for patients with chronotropic incompetence, after programming their pacemakers to either a simulated sensor-driven single or simulated dual-chamber mode. Cardiac output was measured noninvasively at rest and peak exercise using standard Doppler-derived measurements, obtained in a blinded fashion. At rest the Doppler-derived resting VVI and DDD cardiac outputs were 4.49 +/- 0.3 L/min and 4.68 +/- 0.3 L/min, respectively. At peak exercise, the DDD cardiac output was 5.07 +/- 0.5 L/min, whereas the simulated activity VVI and DDD cardiac outputs were 6.33 +/- 0.6 L/min and 7.41 +/- 0.70 L/min, respectively. Analysis of variance showed that there was an overall significant difference in cardiac output from rest to peak exercise (p less than 0.001). However, only the simulated activity DDD cardiac output was significantly different from its respective control value (p less than 0.05). Thus this study shows for the first time that the addition of rate responsiveness to dual-chamber pacing results in a significant improvement in cardiac output for patients with chronotropic incompetence. 
FDP D-dimer induces the secretion of interleukin-1, urokinase-type plasminogen activator, and plasminogen activator inhibitor-2 in a human promonocytic leukemia cell line. We studied the effect of fibrinogen degradation products D, E, and D-dimer on a human promonocytic leukemia cell line, NOMO-1. After exposure to a 10(-5)-mol/L fragment D or D-dimer, the cells displayed macrophage-like characteristics, such as adherence to plastic surfaces, and showed approximately a twofold increase in response to the nitroblue tetrazolium reduction test. The secretion of interleukin-1 alpha (IL-1 alpha) into the medium was markedly stimulated by a 10(-5)-mol/L fragment D, E, and D-dimer, whereas a significant increase in IL-1 beta secretion was observed only in D-dimer-stimulated cells. In addition, D-dimer induced a rapid increase in urokinase-type plasminogen activator on day 1 (0.52 +/- 0.02 ng/mL v 0.07 +/- 0.01 ng/mL in the control culture) and a slow increase in plasminogen activator inhibitor-2 on day 5 (3.9 +/- 1.6 ng/mL v 1.2 +/- 0.2 ng/mL in the control culture). An increase in tissue factor (TF) was also demonstrated on the cell surface of NOMO-1 cells exposed to fragment D or D-dimer by indirect immunofluorescence using an anti-TF monoclonal antibody. Scatchard plot analysis showed that fragment D and D-dimer bound to the NOMO-1 cells with a kd of 3.3 nmol/L and 2.7 nmol/L, respectively. These results suggest that fragment D-dimer specifically stimulates cells of monocyte-macrophage lineage to secrete key substances that regulate blood coagulation, fibrinolysis, and inflammation. 
Stereotactic management of colloid cysts: factors predicting success. Stereotactic aspiration is a valuable surgical alternative for colloid cysts when used alone or in conjunction with microsurgical resection. Since 1981, the authors have performed computerized tomography (CT)-guided stereotactic aspiration as the initial procedure in 22 patients with colloid cysts; stereotactic aspiration alone was successful in 11 patients (50%). Of the 11 patients in whom aspiration failed, stereotactic endoscopic resection was attempted in three and was successful in one. Seven patients required a craniotomy and microsurgical removal of the cyst performed via a transcortical approach. The preoperative CT appearance in eight cases of a hypodense or isodense cyst correlated favorably with successful aspiration of the cyst in six patients. A hyperdense appearance on the preoperative CT scan in 14 cases was associated with subtotal aspiration in 13 patients; five required craniotomy for removal. Preoperative magnetic resonance (MR) imaging in eight patients provided excellent anatomical definition of the cyst and its relationship to other structures of the third ventricle, but it was not possible to correlate successful aspiration with cyst appearance on MR images with short or long relaxation time sequences. The authors' 9-year experience suggests that preoperative CT studies accurately determine size, predict viscosity, and help to define a group of colloid cyst patients for whom stereotactic cyst aspiration will likely be successful. Unsuccessful stereotactic aspiration was related to two features: the high viscosity of the intracystic colloid material (nine patients), or deviation of the cyst away from the aspiration needle due to small cyst volume (two patients). Because of its simplicity and low risk, stereotactic surgery can be offered to selected patients as the initial procedure of choice. Craniotomy can be reserved for those whose imaging studies predict failure or for those whose cyst cannot be aspirated. 
Cranial magnetic resonance imaging in chronic demyelinating polyneuropathy. Twenty one patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and five patients with chronic demyelinating polyneuropathy associated with benign monoclonal paraproteinaemia none of whom had signs or symptoms of central nervous system disease, had cranial magnetic resonance imaging (MRI) on a 1.5 Tesla unit. Areas of increased white matter signal intensity were seen in one of 10 patients aged less than 50 years and in five of 16 patients aged more than 50 years. In only two of the patients (8%), neither of whom had paraproteinaemia, did the appearance strongly suggest demyelination. The only clinical variable that predicted MRI changes was age (p less than 0.01). 
Bleeding patterns during continuous combined estrogen-progestogen therapy. Bleeding and climacteric symptoms were recorded in two groups of postmenopausal women receiving either continuous combined estradiol and norethisterone acetate or estradiol and cyproterone acetate. Out of a sample of 99 postmenopausal women aged 45 to 54 years, 86 completed a 2-year, double-blind, placebo-controlled study. Comparison of the bleeding patterns in the two groups revealed a statistically significant difference: More women in the estradiol-cyproterone acetate group experienced bleeding and for a longer duration. Thirteen women in the estradiol-norethisterone acetate group were amenorrheic, compared with two in the other group. The Kupperman index score in both groups declined to about 30% to 40% of initial values (p less than 0.001). The hot flushes in both treatment groups decreased to a highly significant degree (p less than 0.001), to a value below 20% of baseline values. We conclude that a continuous combination of estrogen and progestogen can produce amenorrhea and symptomatic relief. However, the progestogen components seem to differ in their ability to control bleeding. 
Impaired hepatic handling and processing of lysophosphatidylcholine in rats with liver cirrhosis. Lysophosphatidylcholine is a major metabolic product in the plasma and cellular turnover of phospholipids, with well-known membrane-toxic and proinflammatory properties. Because the liver plays a key role in plasma lysophosphatidylcholine removal and biotransformation and because virtually nothing is known of these processes in a diseased organ, the hepatobiliary metabolism of lysophosphatidylcholine was investigated in rats with carbon tetrachloride-induced liver cirrhosis. Twelve adult male Wistar rats with histologically confirmed cirrhosis and 8 control animals were fitted with jugular and biliary catheters and allowed to recover. The animals were kept under constant IV infusion of taurocholate (1 mumol/min). Two microcuries of sn-1[14C]palmitoyl-lysophosphatidylcholine was administered as a single bolus. The fate of the injected radioactivity, including removal from plasma, uptake, and subcellular location in the liver and molecular and aggregative forms, was studied by combined chromatographic and radiochemical methods. Major findings were (a) that lysophosphatidylcholine has a prolonged permanence in plasma of cirrhotic rats, due both to decreased hepatic clearance and to depressed conversion into phosphatidylcholine; (b) that the rate of lysophosphatidylcholine acylation is much slower in the cirrhotic than in the normal liver, both at the microsomal and at the cytosolic level; (c) that cytosolic lysophosphatidylcholine in the cirrhotic liver, but not in the normal liver, is predominantly non-protein bound; (d) that the strict molecular selectivity of lysophosphatidylcholine acylation observed in controls is partially lost in cirrhosis; and (e) that a consistent fraction of lysophosphatidylcholine is converted into triacylglycerols in cirrhotics but not in controls. These findings show a profound derangment of lysophosphatidylcholine handling and processing in the cirrhotic liver, which is of potential pathogenetic significance. 
The value of single versus multiple sections for detection of lymph node metastasis. This study was undertaken to determine the value of serial sectioning of lymph nodes as an aid in optimally examining cervical specimens for metastasis. The presence or absence of lymph node metastasis in 802 lymph nodes obtained from 51 consecutive neck dissection specimens were initially determined by the routine method, examination of one section from each node. This examination revealed 40 lymph nodes with metastatic involvement. Further study of the 716 lymph nodes that were initially interpreted as free of tumor by serial sectioning added only two positive nodes. Thus, serial sectioning did not contribute significantly to the detection of lymph node metastasis. 
Cytotoxic activity in plasma from patients with amyotrophic lateral sclerosis. The present study evaluates an assay of cytotoxic effect of plasma from patients with amyotrophic lateral sclerosis. Plasma from 20 recently diagnosed ALS patients induced hemolysis of normal red blood cells with a significantly greater intensity than that of normal controls. After at least 1 month of treatment with prednisone and azathioprine, the hemolytic activity of ALS plasma was reduced but was still higher than that of control plasma. 
Multiple giant cell tumors and Paget disease of bone: radiographic and clinical correlations. The clinical and radiographic findings of four patients with multicentric giant cell tumor (GCT) of bone and Paget disease were retrospectively reviewed. Three patients underwent magnetic resonance (MR) imaging evaluation; all patients underwent computed tomography (CT). The MR characteristics of the bone component in pagetic GCT appeared to reflect the pagetic phase; a sclerotic pattern was largely represented by hypointense marrow signal intensity on images obtained with both long and short repetition times (TRs) and echo times (TEs). Conversely, a tumor appearing in a mixed pagetic phase demonstrated more heterogeneous signal intensity with all pulse sequences. Extensive soft-tissue components, noted in all cases, showed largely intermediate signal intensity on short TR/TE images and foci of increased signal intensity on longer TR/TE images. In most cases, dramatic reduction in tumor bulk was noted with the use of steroids alone. An awareness of this entity is important because the appearance of lytic lesions with soft-tissue extension in patients with Paget disease does not necessarily imply a grave prognosis. Serial CT or MR imaging is helpful in monitoring the remissions and exacerbations that reflect response to therapy in Paget disease and GCT. 
Magnetic resonance assessment of the postoperative spine. Degenerative disc disease. The magnetic resonance (MR) imaging findings in patients after surgery for degenerative disc disease in the lumbar and cervical spine are discussed. In the lumbar spine, changes seen in the immediate postoperative period, use of Gd-DTPA in distinguishing scar and disc and postoperative complications are reviewed. In the cervical spine, operative approaches and types, the appearance of bony stenosis, and disc herniations are demonstrated. 
Urethroplasty using the pedicled island flap technique in complicated urethral strictures. Many techniques have been described for the repair of recurrent urethral strictures. Experience with 1-stage correction of hypospadias and epispadias, using a vascularized island flap technique, has led to its increased application for complicated adult urethral strictures. The advantage of the vascularized island flap technique is that reconstruction can be completed with only 1 operation, and it provides good subjective and objective results. Analysis of 50 consecutive cases treated by this approach has proved its validity. Of the 50 cases fistulas occurred in 20%, of which 12% required surgical correction, and stricture recurred in 32%. The largest proportion of recurrence was noted in patients who were primarily treated with 3 or more urethrotomies within a short time. Therefore, we recommend open surgical repair when 1 or 2 internal urethrotomies fail to produce a good result. 
Bullous pemphigoid autoantibodies, HIV-1 infection and pruritic papular eruption. Bullous pemphigoid (BP)-type autoantibodies were found by Western blot (WB) analysis of epidermal extracts in the serum of 38% of HIV-seropositive patients compared with 21% of HIV-seronegative patients with chronic pruritus and 76% of patients with BP. They were further identified as BP autoantibodies (BPab) by immunoprecipitation and immunoelectron microscopy. Their incidence increased from 21% in HIV infection stage II to 37% and 43% in stages III and IV, respectively. Of the patients suffering from HIV-related chronic pruritic papulovesicular eruption. 75% showed circulating BPab as compared with 29% in those without skin problems (P = 0.0066) and, among them, 30% met the diagnostic criteria for BP when histology, WB, immunofluorescence and immunoelectron microscopy techniques were used. In conclusion, this study identifies an autoimmune skin reaction that may account for, or be related to, the distressing pruritic eruptions occurring in HIV-infected patients. 
Molecular characterization of a region of DNA associated with mutations at the agouti locus in the mouse. Molecular characterization of a radiation-induced agouti (a)-locus mutation has resulted in the isolation of a segment of DNA that maps at or near the a locus on chromosome 2 in the mouse. This region of DNA is deleted in several radiation- or chemical-induced homozygous-lethal a-locus mutations and is associated with specific DNA structural alterations in two viable a-locus mutations. We propose that DNA probes from this region of chromosome 2 will be useful for ultimately characterizing the individual gene or genes associated with a-locus function. 
Fatty acids in human platelets and plasma. Fish oils decrease sensitivity toward N2 microbubbles. Platelet aggregation induced by N2 microbubbles (simulating microbubbles developed during deep diving) was measured in seven volunteers before and after intake of ethyl-eicosapentaenoate (-EPA, 3.5 g/day) and ethyl-docosahexaenoate (-DHA, 2.5 g/day) for 2 wk. The relative content of arachidonic acid (AA) decreased in platelets from all individuals, whereas the content of EPA and DHA increased. The decrease of AA was almost identical with the increase of EPA plus DHA. In plasma the AA content was unchanged, while EPA and DHA increased. The N2 microbubble-induced aggregation showed a significant negative correlation with the DHA content both in platelets and in plasma. Less aggregation was also observed with high EPA content in platelets or plasma. A significant correlation between AA content in platelets and aggregation was seen. Intake of marine oils may be beneficial to divers under deep diving and to patients during extracorporeal circulation, because this may reduce the microbubble-induced aggregation. 
Midventricular obstruction associated with chronic systemic hypertension and severe left ventricular hypertrophy. Midventricular obstruction is an uncommon finding previously defined by catheterization and angiographic techniques in patients with hypertrophic cardiomyopathy. This study describes the clinical and echocardiographic findings of 10 consecutive patients (mean age 73 years) with severe concentric left ventricular (LV) hypertrophy and the unusual finding of a dynamic systolic obstruction located in the midportion of the left ventricle. All patients were known to have chronic hypertension, and none had a history or family history of hypertrophic cardiomyopathy. In each case, a well-defined, high velocity, turbulent jet was identified by Doppler color flow imaging and subsequently confirmed with conventional Doppler techniques. Septal and posterior wall thickness averaged 1.67 and 1.57 cm, respectively. Mean LV mass index was 199 g/m2 and ejection fraction averaged 78%. Peak systolic velocity obtained by continuous-wave Doppler averaged 2.7 m/s and appeared as either a "late-peaking" or a "spike and dome" configuration. Seven of 10 patients gave a history of syncope or severe presyncope at the time of echocardiographic examination. At a mean follow-up of 1 year, syncope or presyncope had resolved in 5 patients in whom medication was adjusted based on the ultrasound study, but persisted in 2 patients in whom diuretic therapy was continued. It is concluded that obstruction to systolic flow can occur at the mid-LV level in some patients with severe concentric LV hypertrophy and avoidance of medication known to lower LV volume may relieve symptoms of transient inadequate cardiac output. 
The impact of nonidentical ABO cadaveric renal transplantation on waiting times and graft survival. Blood type O recipients of cadaveric renal transplants have longer pretransplant waiting periods than blood type A, B, and AB recipients. To evaluate reasons for and consequences of this discrepancy, we studied both the frequency of various donor and recipient blood type combinations and their outcomes. Among 37,659 cadaveric renal transplants performed during 1983 through 1989, there were 2,625 transplants (7%) received by patients of compatible but nonidentical blood types. Of 18,575 type O donor organs, 16,784 were received by type O patients for a recipient to donor ratio of 0.9. The corresponding ratios were greater than 1.0 for all other blood types (1.02 for blood type A, 1.14 for type B, and 2.18 for type AB). This causes blood type O patients to have a lower access to transplantation and to have significantly longer waiting times than patients of all other blood types. This inequality of access diminished significantly (P less than 0.001) over the years, but did not resolve by 1989. Analysis of relative risk for first graft loss by multiple regression (Cox) showed that transplantation across compatible blood types had a 9.1% higher risk (P less than 0.1) than that of transplantation among identical blood types. Cadaveric renal transplantation within identical blood types optimizes access to transplantation and avoids further aggravating past disadvantages for blood type O recipients. 
Results of a recently instituted programme of thrombolytic therapy in acute lower limb ischaemia. Twenty-eight patients with acute lower limb ischaemia received low dose intra-arterial thrombolytic therapy over a 2-year period. Eighteen patients received streptokinase and ten patients received recombinant tissue plasminogen activator (rTPA). Indications included arterial thromboemboli and graft failures. Mean ischaemic times were similar in both groups. Treatment time to achieve lysis was significantly less with rTPA (P less than 0.01). Subsequent vascular procedures, including angioplasty or reconstruction, were undertaken in 36 per cent of patients. Arterial puncture site bleeding occurred in eight (29 per cent) patients. Three (11 per cent) patients suffered rethrombosis after initial successful lysis. All rethromboses were successfully lysed with rTPA. There were two major amputations. Five (18 per cent) patients died, all lytic failures in the streptokinase treatment group. There were no cerebral haemorrhagic events and no patient died as a result of thrombolytic therapy. Good clinical outcome was obtained in nine of 18 patients treated with streptokinase and in nine of ten patients treated with rTPA. Intra-arterial thrombolysis provides effective therapy with high rates of limb salvage and a low mortality rate. This study suggests that rTPA may be a more effective agent, causing less morbidity, than streptokinase. 
Metastatic melanoma to the heart presenting with ventricular tachycardia. Intraventricular tumors in adults are uncommon, and the association of these with ventricular tachycardia is even more rare. We report a case of an intracardiac metastatic melanoma in a woman who presented with syncope due to ventricular tachycardia. 
Risk stratification after myocardial infarction. Clinical overview. Many patients with an acute myocardial infarction can be stratified into subgroups that are at high risk for morbidity and mortality on the basis of clinical characteristics that indicate recurrent myocardial ischemia, persistent left ventricular dysfunction, and/or recurrent cardiac arrhythmias. In patients with uncomplicated myocardial infarction the assessment of symptoms, physical findings, and ECG changes during predischarge exercise testing often identifies patients at increased risk for further cardiac events. Because of the suboptimum sensitivity and specificity of the exercise ECG for detecting myocardial ischemia, myocardial perfusion imaging with 201Tl and/or assessment of global and segmental ventricular function by two-dimensional echocardiography or radionuclide cineangiography during or immediately after exercise are often added to the predischarge risk stratification. 
Recurrent pericarditis and cardiac tamponade in a patient with hypocomplementemic urticarial vasculitis syndrome. We describe a patient with hypocomplementemic urticarial vasculitis syndrome complicated by recurrent pericarditis and cardiac tamponade. The episodes of pericarditis were associated with urticarial vasculitis, hypocomplementemia, and circulating IgG antibodies to the collagen-like region of Clq. Histopathologic examination of the skin and pericardium demonstrated vasculitis associated with immunoglobulin and complement deposition suggesting an immune complex mediated etiology. Recurrent pericarditis should be included in the clinical spectrum of hypocomplementemic urticarial vasculitis syndrome. 
Symptomatic benefit of supplemental oxygen in hypoxemic patients with chronic lung disease. We have compared the symptomatic benefit of air and oxygen at rest in hypoxemic patients with chronic obstructive airway disease (COAD) or interstitial lung disease (ILD). A total of 12 severely disabled patients with COAD (mean +/- SEM, PaO2, 50.3 +/- 3.7 mm Hg) and 10 with ILD (PaO2, 48.0 +/- 3.1 mm Hg) received 28% oxygen and air by Venturi face mask, each gas on two occasions, in a double-blind randomized fashion. SaO2 increased (p less than 0.01) in both groups during oxygen breathing: COAD, 85.1 +/- 2.3% versus 93.1 +/- 1.4%; ILD, 85.5 +/- 1.7% versus 94.7 +/- 0.9%. The patients with COAD stated that air helped their breathing on 15 of 24 occasions and that oxygen helped on 22 of 24 occasions (p less than 0.05). In the patients with ILD the values were 6 of 20 and 13 of 20 occasions, respectively (p less than 0.05). In both groups of patients the severity of breathlessness recorded on a 100-mm visual analog scale was significantly (p less than 0.05) lower during oxygen breathing: COAD, 29.6 +/- 4.5 versus 45.6 +/- 6.0; ILD, 30.2 +/- 5.1 versus 48.1 +/- 4.4. Ventilation measured by magnetometers was significantly lower during oxygen breathing in the patients with COAD (8.2 +/- 1.0 versus 9.3 +/- 1.1 L/min; p less than 0.05), but the difference between oxygen and air in patients with ILD was not statistically significant (9.3 +/- 1.3 versus 11.2 +/- 1.6 L/min; p greater than 0.05). 
Mitomycin C as an adjuvant treatment to resected gastric cancer. A 10-year follow-up. Seventy consecutive patients were entered in a two-arm randomized trial after surgical resection for locally advanced gastric cancer. In the first arm, 37 patients were included as a control group, receiving no further treatment after surgery. In the second arm, 33 patients were treated with adjuvant chemotherapy consisting of mitomycin C (MMC), 20 mg/m2 administered intravenously once every 6 weeks for four consecutive cycles. All patients in both arms were followed in the same way for 5 years. At 5 years 23 of 37 patients in the control arm and 7 of 33 patients in the treatment arm were dead because of relapse. Actuarial survival curve was statistically significant in favor of patients given adjuvant MMC (p less than 0.001). After 10 years follow-up, 31 of 37 patients in the control arm and 16 out of 33 patients in the treatment arm were dead because of relapse, the statistical differences continuing in the actuarial survival curve in favor of treated patients (p less than 0.01). The best advantages of adjuvant treatment were observed in the T3N0M0 stage. The most frequent relapse site was the peritoneal cavity and the relapse pattern shows special decrease in liver metastases in treated patients. Toxicity was acute and mild. No delayed toxicity or second malignancies were observed. These data suggest that adjuvant MMC after resected surgery of gastric cancer is a successful treatment and its effects are still evident after 10 years of follow-up. 
Mucin-producing tumor of the pancreas. A new pancreatic tumor, called mucin-producing tumor, has received great attention in Japan. These tumors are found inside the pancreatic duct and produce large quantities of copious mucus. The authors examined 22 cases of these tumors histologically and histochemically. In 12 malignant cases, the tumors inside the ducts consisted of cancerous lesions over small areas along with papillary or atypical hyperplasia. Tumors in ten benign cases mainly consisted of papillary hyperplasia. Except for three patients with carcinoma in situ, cancerous tumors infiltrated the pancreatic parenchyma and, in some cases, were observed invading the bile duct or duodenum. A mucous histochemical study showed evidence of sialomucin in malignant cases; neutral mucin was dominant in benign cases. Characteristics of this disease were also compared with 13 cases of mucinous cystic neoplasm. From the results, it was concluded that these two diseases can be classified into the same conceptual category. 
A rat model of acute liver necrosis induced by a monoclonal antibody to liver-specific antigen and complement. Acute massive hepatic injury was induced in rats by a monoclonal antibody against a rat liver-specific membrane antigen, and its histological characteristics were investigated. A single intravenous injection of murine ascites containing a monoclonal antibody produced numerous hemorrhagic foci of degenerated and necrotic liver cells predominantly in zones 1 (the periportal area) and 2 (the area of transition between the periportal zone and the perivenular zone) of the liver lobule within 10 min. Massive hepatocellular necroses were observed 1 hr later, but no inflammatory cell infiltration occurred in and around the necrotic foci. Immunohistological study demonstrated marked deposition of the third component of the complement system in the necrotic area. Serum complement activity was sharply decreased immediately after the injection of the antibody, suggesting that the hepatic necrosis is ascribable to a complement-mediated immune attack on the liver cell membrane induced by the antigen-antibody reaction. The hepatic necrosis in response to monoclonal-antibody injection did not progress to a chronic disease and healed almost completely, changing to scar tissues within 2 wk. Although it is not clear whether this hepatic injury has any clinical relevance, this antibody/complement model may be useful for investigating the cause and therapy of hepatic diseases such as fulminant hepatitis. 
Preserved action of a rectus muscle after transection by an encircling solid silicone band. We present a case of anterior migration of a solid silicone band through a lateral rectus muscle. In this patient the action of the lateral rectus was preserved, and this is demonstrated photographically. The possible reasons for this rare complication and the possible mechanism by which lateral rectus activity remained intact are explained. 
Clinical features of Behcet's disease. Report of four cases. Behcet's disease is a multisystem inflammatory disorder of unknown etiology. The unifying histologic reaction pattern is a leukocytoclastic vasculitis that affects predominantly the skin, oral mucosa, and eyes. Many other sites of involvement have been reported but are inconsistently found in individual patients. Early recognition and treatment of Behcet's disease may help prevent devastating permanent sequelae such as blindness. Because oral involvement is often the first manifestation of this disorder, dental practitioners are in a unique position to help these patients. We report four cases of Behcet's disease in North American patients. Diagnostic criteria and treatment options are reviewed. 
Recombinant granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation for lymphoid cancer. BACKGROUND. The period of neutropenia after autologous bone marrow transplantation results in substantial morbidity and mortality. The results of previous phase I-II clinical trials suggest that recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) may accelerate neutrophil recovery and thereby reduce complications in patients after autologous bone marrow transplantation. METHODS. We conducted a randomized, double-blind, placebo-controlled trial at three institutions. The study design and treatment schedules were identical, and the results were pooled for analysis. One hundred twenty-eight patients were enrolled. Sixty-five patients received rhGM-CSF in a two-hour intravenous infusion daily for 21 days, starting within four hours of the marrow infusion, and 63 patients received placebo. RESULTS. No toxic effects specifically ascribed to rhGM-CSF were observed. The patients given rhGM-CSF had a recovery of the neutrophil count to 500 x 10(6) per liter 7 days earlier than the patients who received placebo (19 vs. 26 days, P less than 0.001), had fewer infections, required 3 fewer days of antibiotic administration (24 vs. 27 days, P = 0.009), and required 6 fewer days of initial hospitalization (median, 27 vs. 33 days; P = 0.01). There was no difference in the survival rate at day 100. CONCLUSIONS. In patients undergoing autologous bone marrow transplantation for lymphoid neoplasia, rhGM-CSF significantly lessens morbidity. Further studies will be required to establish its optimal dosage and schedule of administration. 
Candida tropicalis and Candida albicans fungemia in children with leukemia. The records were reviewed for all patients hospitalized at a pediatric oncology center for complications of leukemia (n = 822) or lymphoma (n = 290) during an 8-year period. The results of surveillance cultures (throat, rectal, and urine) and blood cultures were analyzed to identify cases of Candida tropicalis and C. albicans colonization and/or fungemia. None of the patients with lymphoma who had positive surveillance cultures for C. albicans (n = 89) or C. tropicalis (n = 23) had fungemia. Among patients with leukemia, significant fungal infection was documented in 12 of 107 colonized with C. tropicalis (11.2%) versus 14 of 700 (2%) colonized with C. albicans (P less than 0.001). The two groups of children with fungemia were similar in primary diagnoses (predominantly acute lymphoblastic leukemia) and in the frequency of several known risk factors for infection, including the duration of neutropenia (absolute neutrophil counts, less than 500/microliters). Patients with C. tropicalis fungemia all had disseminated disease compared with nine of 14 patients with C. albicans fungemia. Also, subcutaneous abscesses were unique to patients with C. tropicalis in this series. Two patients in each group died of their infection; central nervous system involvement was present in both fatal cases of C. tropicalis fungemia. A high index of suspicion and the early institution of appropriate antifungal therapy are critical to the successful management of these infections in patients with leukemia. 
Prognostic importance of collateral flow and residual coronary stenosis of the myocardial infarct artery after anterior wall Q-wave acute myocardial infarction. Residual high-grade coronary stenosis and collateral flow are frequent findings in the chronic phase after a Q-wave acute myocardial infarction (AMI). The prognostic importance of a residual stenosis of the infarct artery and of collateral flow to the infarct area was analyzed in a group of 102 young patients (mean age 35 years, range 22 to 39) who had survived an anterior wall Q-wave AMI. Patients whose only significant lesion (greater than 50% luminal diameter reduction) was in the proximal portion of the left anterior descending artery were enrolled in the study. A 50 to 74% diameter stenosis was present in 33 of 102 patients (32%), 43 (42%) had a 75 to 99% stenosis and 26% had a total occlusion of the infarct vessel. Collateral vessels, which were evaluated by a scoring system, were present in 52 of 102 patients (51%). Four percent had only faint (score 1), 17 of 102 patients (17%) had moderate and 32 patients (31%) had good collateral flow (score greater than 4). The 8-year cumulative mortality was 15.2%--an eightfold increase compared with the age-matched general population. No patient with less than 75% stenosis died during follow-up, whereas the cumulative 8-year mortality was 23 and 17% in patients with a 75 to 99% stenosis or total occlusion, respectively (p less than 0.01). Patients with at least moderate collateral flow had a mortality rate of 21%, versus 8% for patients without or with faint collateral flow (p less than 0.05). 
Late bleeding after rhytidectomy from injury to the superficial temporal vessels. Five healthy, normotensive women, whose mean age was 49.8 years, developed expanding hematomas between 8 and 10 days (average 9 days) after rhytidectomy. In each patient, the bleeding vessel could be identified: In two, it was the parietal branch of the superficial temporal artery; in two, it was the parietal branch of the superficial temporal vein; and in one, it was the superficial temporal artery immediately before its branching. Contributing factors may have been sudden physical exertion in four of the five patients and in another salicylate ingestion. Several measures can help avoid late bleeding from the superficial temporal vessels or their branches; not using a too potent vasoconstrictive agent (epinephrine) in the local anesthetic so that the vessels will be easier to visualize; not injecting the local anesthetic too deeply or incising to deeply; dividing and ligating the superficial temporal vessel and its major branches if injured; using bipolar coagulation on small branches; and instructing patients repeatedly not to engage in strenuous activity or to ingest salicylates for at least 2 weeks after operation. 
Dietary fiber and bowel function in tube-fed patients. In tube-fed patients, dietary fiber is often used to manage constipation/diarrhea. Dietary fiber consists of water-soluble and insoluble plant compounds that are resistant to digestion by small-bowel enzymes but are fermented to varying degrees by colonic bacteria. Many physiologic effects of fiber may be related to the degree of fermentation. Few controlled studies of fiber-containing tube feedings have been performed. These studies have limitations and are nondefinitive as to whether fiber prevents or controls constipation/diarrhea. Constipation in tube-fed patients has not been shown to respond to mixed soluble/insoluble fiber in the few studies performed to date. Likewise, fiber may be of only limited benefit in controlling diarrhea in acute illness because of such factors as stress or medication. Fiber does play a role in maintaining gut integrity in all patients, whether they have diarrhea or not. Fiber may be recommended as part of a standard tube-feeding regimen to help assure gut mucosal integrity but not specifically to treat constipation/diarrhea. Further studies are necessary before the role of fiber in the management of constipation/diarrhea in tube-fed patients is determined. 
Hepatosplenic candidiasis: successful treatment with fluconazole. PURPOSE: To determine if fluconazole is effective treatment for hepatosplenic candidiasis that has not resolved with amphotericin B and flucytosine treatment. PATIENTS AND METHODS: Six patients (ages 3 to 44) with acute leukemia and hepatosplenic candidiasis who did not respond to prior antifungal therapy were treated with fluconazole. RESULTS: All six patients had fever and three had nausea and vomiting; computed tomographic (CT) scan showed lucencies in the liver in six, lucencies in the spleen in five, and lucencies in the kidneys in three. Prior therapy with 1.6 to 4 g of amphotericin B in the five adults and 526 mg of amphotericin B in the child (with the addition of flucytosine in four) failed to improve clinical symptoms or lucencies in the liver, spleen, and kidneys seen on CT scan. Fluconazole was given at a dose of 200 to 400 mg daily (70 to 100 mg in the child) for 2 to 14 months. All patients had resolution of fever and other symptoms in 2 to 8 weeks. Improvement of the lesions noted on CT scan was seen in 4 to 8 weeks in all patients. Total resolution of lesions noted on CT scan occurred by 4 weeks in two patients, but took 4 to 5 months for three patients and 13 months for one patient. Three patients had relapse of their acute leukemia and two died, presumably cured of their candidiasis. Two patients underwent successful bone marrow transplantation without relapse of their candidiasis. CONCLUSION: Fluconazole appears to be useful in the treatment of hepatosplenic candidiasis that has not resolved with amphotericin B and flucytosine therapy. 
Abnormal vascular responses to supine exercise in hypertrophic cardiomyopathy. BACKGROUND. Exercise hypotension has been documented in hypertrophic cardiomyopathy. It is not the result of an inability to augment cardiac output but instead relates to an inappropriate and exaggerated decrease in systemic vascular resistance at high work loads. METHODS AND RESULTS. To enable us to examine the behavior of the peripheral vasculature during exercise, 103 consecutive patients underwent maximal symptom-limited supine bicycle exercise with measurement of forearm blood flow. A minimum reduction of 12% from the basal value was defined as a normal response based on the study of 25 normal controls. In the patients, two patterns of forearm blood flow were observed. Sixty-four patients had an appropriate reduction in forearm blood flow of 40 +/- 16% from resting flow. In 39 patients, the forearm blood flow either failed to decrease or increased with exercise by 45 +/- 105% of the resting value. Patients with an abnormal forearm vasodilator response were younger (31 +/- 13 versus 46 +/- 14 years), and more of them had a family history of hypertrophic cardiomyopathy and sudden death than did those with a normal vasoconstrictor response (16 of 39 versus eight of 64). Left ventricular end-diastolic cavity dimensions were smaller in those with an abnormal forearm blood flow response, but other clinical, echocardiographic, and arrhythmic variables were similar. To assess the relation of abnormal peripheral vascular responses to erect exercise blood pressure response, patients underwent treadmill exercise testing with careful monitoring of systolic blood pressure response. Thirty-eight patients had significant exercise hypotension with failure of the systolic blood pressure to increase during progressive exercise (n = 6) or an abrupt decrease in systolic blood pressure (20-60 mm Hg) from the peak value (n = 32); 65 patients had a normal exercise blood pressure response, but 18 of these patients had an oscillation in systolic blood pressure of 10 mm Hg or more early in the recovery phase. Thirty-one of 39 patients with an abnormal forearm blood flow response demonstrated exercise hypotension during the erect exercise testing, and the remaining eight patients had a normal exercise blood pressure response; however, five of these eight had abnormal oscillations in blood pressure during recovery (r = 0.61, p less than 0.001). CONCLUSIONS. The relation of abnormal peripheral vascular responses to exercise hypotension confirms the observation of hemodynamic instability in patients with hypertrophic cardiomyopathy. The finding of abnormal vascular responses in patients known to be at increased risk (young age and a family history of hypertrophic cardiomyopathy and sudden death) suggests that hemodynamic mechanisms may be important in the occurrence of sudden death in hypertrophic cardiomyopathy. 
Surgical intensive care unit resource use in a specialty referral hospital: I. Predictors of early death and cost implications. The rationing of medical care prioritizes the need for early predictors of death in the surgical intensive care unit (SICU). We prospectively studied 100 consecutive SICU admissions, looking for predictors of early death in the SICU and the cost implications of these findings. Serial APACHE II scores on days 1, 3, and 5 were subjected to multinomial logistic regression analysis to determine significant predictors of death in the SICU on day 1. Survivors had significantly lower (p less than 0.05) mean day-1 APACHE II scores than had nonsurvivors (13.6 vs 22.1). Half of the patients with scores greater than 18 died, and all patients with scores on day 1 of 25 or greater died. Significant predictors of death on SICU day 1 were APACHE II scores, Acute Physiology Score, Glasgow Coma Score, creatinine level, and Chronic Health Evaluation Score. Forty-one patients had been transferred from community hospitals as a results of acute illness; this population accounted for two thirds of the deaths in the SICU. Ten of 18 nonsurvivors were predicted on day 1, with these patients incurring a total cost of approximately $1 million. If therapy had been modified on days 5, 10, or 15, the potential cost savings would have been $340,000, $240,000, or $140,000, respectively. Integration of the results of this study into the management decision-making process and treatment guidelines may reduce the cost of care in the SICU. 
Aortoiliac dissection after percutaneous insertion of an intra-aortic balloon pump. Aortic or aortoiliac dissection may complicate percutaneous intra-aortic balloon pump insertion in various ways. Thrombosis can escape clinical recognition if no major obstruction develops. Death due to perforation after dissection is not uncommon. In this case study, aortoiliac dissection led to bilateral iliac artery stenosis, an unusual complication of percutaneous femoral cannulation for insertion of a balloon pump. 
Effects of heart rate and pulmonary artery pressure on Doppler pulmonary artery acceleration time in experimental acute pulmonary hypertension. Chronic pulmonary hypertension in humans is characterized by shortening of the pulmonary artery acceleration time as measured by Doppler echocardiography, such that the higher the pulmonary artery pressure, the shorter the pulmonary acceleration time. Increases in heart rate are also known to produce decreases in the pulmonary artery acceleration time. To explore the relationship between mean pulmonary artery pressure, heart rate, and Doppler pulmonary artery acceleration time, experimental acute pulmonary hypertension was created in nine Duroc swine, either by infusion of Sephadex beads with embolization of the pulmonary arterial circulation or by partially occluding the main pulmonary artery 8 to 10 cm distal to the pulmonic valve. Pulmonary artery Doppler flow velocity recordings and invasive pressure measurements were made at baseline and at paced atrial rates ranging from 60 to 160 beats per minute, in 20-beat increments. The results in this acute animal model reveal that increases in heart rate produced significant decreases in Doppler pulmonary artery acceleration time at mean pressures below 25 mm Hg. However, with mean pulmonary artery pressures greater than 25 mm Hg, both heart rate and increases in pulmonary artery pressure had no significant effect on acceleration time. 
Hypo-fibrinolysis in patients with hypertension and elevated cholesterol. To test the hypothesis that increased blood pressure and hyperlipidaemia result in changes in the fibrinolytic system, 84 subjects with both hypertension and elevated serum cholesterol levels (the high risk group) were compared with 55 controls matched with respect to age, sex and body mass index (BMI). Plasminogen activator inhibitor (PAI-1), and tissue plasminogen activator (tPA) antigen and activity were measured before and after venous occlusion. In the high risk group, tPA activity was significantly lower both before and after venous occlusion and PAI-1 levels were significantly higher. In a multivariate analysis the triglyceride levels, diastolic blood pressure and cholesterol levels were independently associated with the PAI-1 levels. Diastolic blood pressure was independently and inversely associated with resting tPA activity. We conclude that patients with hypertension and hyperlipidaemia have a reduced activity of the fibrinolytic system, an effect which is unrelated to differences in age, sex, smoking or BMI. 
Doppler ultrasound and the silent ductus arteriosus. A clinically undetectable, small ductus arteriosus was identified by Doppler ultrasonography in 21 individuals. Infants were excluded from the study and no patient had pulmonary hypertension. Persistence of the ductus arteriosus is likely to be more common than shown by less sensitive diagnostic methods. Some patients considered to have infective endocarditis with a normal heart may have a silent ductus arteriosus. Evidence of such an association would justify ligation or antibiotic cover as prophylactic measures. 
Tears of the retinal pigment epithelium: occurrence in association with choroidal effusion. Two patients developed large tears of the retinal pigment epithelium associated with choroidal effusion. One tear occurred after combined cataract/filtration surgery complicated by postoperative choroidal detachment; the second developed in a patient with idiopathic uveal effusion syndrome. Weakness of the junctions of the pigment epithelial cells secondary to the accumulation of fluid in the subretinal or suprachoroidal space may result in tearing of the retinal pigment epithelium as it is stretched. 
Cell kinetics of gastrointestinal tumors after different nutritional regimens. A preliminary report. Forty-four cases of different untreated gastrointestinal tumors were studied with regard to cell kinetic activity. As a pilot experiment, we also determined the 3H-TdR Labeling Index (LI) in 28 patients in basal conditions and after 15 days of nutritional manipulation with prevalently lipid-based or glucose-based feeding to ascertain whether selective nutritional regimens could affect tumor proliferation. Preliminary results from this study indicate that a kinetic perturbation is induced in tumor cells by nutritional manipulation. Lipid-based feeding seems to produce effects similar to those of chemical or physical anticancer agents, thus suggesting a possible supporting role of nutritional manipulation in cancer treatment strategy. 
HBV-DNA-related hepatocellular carcinoma occurring in childhood. Report of three cases. In a series of 325 HBV chronically infected children observed over an 18-year period, three developed HCC. These three children were born in southern Italy, a region characterized by a high endemic HBV infection rate; each had been infected perinatally, developed an acute hepatitis, and became a chronic carrier. Two of the three with cirrhosis were HBsAg positive at the time their HCC was detected. The remaining case had seroconverted to HBsAb but HBV-DNA integration could be demonstrated in the absence of cirrhosis; moreover HBV antigens were not expressed in the tissue of this case. The interval between HBV infection and HCC appearance in these three cases ranged from six to 11 years. A similarity between these three Italian cases and the majority of HCC arising in chronically infected children in the Far East is noted. 
Localized recurrent postoperative pernio associated with leukocytoclastic vasculitis. A patient with recurrent pernio of the right ankle for 21 years after surgery had a leukocytoclastic vasculitis localized in the area. We suggest that the various histologic descriptions of pernio in the literature and in this case represent different levels of severity of the disease. 
Intraoral reconstruction with a microvascular peritoneal flap. The microvascular peritoneal flap offers a new reconstructive option for closure of intraoral defects. The flap is easy to raise, and donor-site morbidity is low. Unlike fascial flaps, in which the raw surface may take weeks to "mucosalize," the peritoneal surface heals primarily. Finally, the rectus muscle effectively covers all forms of mandibular reconstruction, and the reliable skin paddle makes possible the closure of substantial cutaneous defects. 
Interrelation of analgesia and uterine activity in women with primary dysmenorrhea. A preliminary report. The interrelation between uterine activity and pain from primary dysmenorrhea has been of interest for many years. Objective studies of uterine activity during non-steroidal antiinflammatory drug therapy have supported the assertion that uterine activity causes pain and that reducing that activity leads to pain reduction. Unfortunately, those studies could not refute the counter-assertion that reductions in uterine activity come about because of reduced pain through central analgesia and not by direct pharmacologic action. In an effort to clarify this question, a small number of women were studied using intrauterine pressure recording and analysis to evaluate objective changes in uterine physiology during transcutaneous electrical nerve stimulation (TENS) therapy for dysmenorrhea. The preliminary studies indicated that despite successful subjective therapy with TENS, intrauterine pressure parameters remained steady or showed signs of worsening. These findings indicate that TENS provides pure analgesia by an alteration of the body's ability to receive or perceive the pain signal rather than by a direct uterine effect. It appears that the reduction in uterine activity seen in objective drug studies represents direct drug action rather than a change from reduced pain through central analgesic effects. 
Flow characteristics of enteral feeding with psyllium hydrophilic mucilloid added. One therapy for managing diarrhea in patients in intensive care units who are receiving enteral nutrition is administration of psyllium hydrophilic mucilloid (PHM). This laboratory study was conducted to determine whether the addition of PHM (Metamucil) to enteral feeding formula (Entrition) adversely affected the flow characteristics of the feeding formula through a small-bore feeding tube. Descriptive data were obtained from 72 trials of feeding formula with varied infusion rates, formula osmolality and temperature, and PHM concentrations. Two thirds (n = 48) of the trials were successful (PHM did not clog the tubing and obstruct flow). The remaining one third of the trials (n = 24) were unsuccessful. Successful formula infusion was influenced by formula temperature and osmolality but not by infusion rate, PHM concentration, or flow interruption. If formula with PHM was followed by formula without PHM, the infusion was successful regardless of infusion rate or formula osmolality. Thus, the data from this laboratory study indicate that when therapeutic doses of PHM are prescribed, it is feasible for PHM to be mixed in room-temperature feeding formula and infused without clogging the feeding tube. 
The role of growth hormone and insulin-like growth factor-I in experimental renal growth and scarring. Recent evidence suggests a causal link between early renal/glomerular hypertrophy and late kidney scarring and glomerular sclerosis. Insulin-like growth factor-I (IGF-I) is a growth-promoting peptide likely to play a role in the development of kidney growth. We observed an increased renal IGF-I content in two experimental models of accelerated kidney growth in the rat. By contrast, diabetic renal hypertrophy is abolished in the absence of growth hormone (GH). Dietary protein manipulations affect the expression of compensatory renal growth (CRG), as well as renal IGF-I content. The renotrophic effect of a high-protein diet on CRG seems GH-dependent and IGF-I-mediated. GH also appears to have a permissive role on the development of progressive renal scarring following extensive renal ablation in rats, as dwarf rats seem somewhat resistant to the development of accelerated scarring and renal failure. 
Prognosis in T2N0M0 stage I breast carcinoma: a 20-year follow-up study. In a study of prognosis in node-negative breast carcinoma, we investigated 293 T2N0M0 patients treated by mastectomy and axillary dissection with a median follow-up of 19.8 years. The probability of surviving 20 years considering all causes of death was 41.3% +/- 3.0%. Recurrence-free survival (Kaplan-Meier estimate) was 68.6% +/- 3% at 10 years and 63.2% +/- 3.1% at 20 years. The estimated probability of cure determined by the method of Brinkley and Haybittle was 63% (95% confidence interval [Cl], 55% to 72%). Prognosis was related to primary tumor size with the best separation (P = .06) when tumors from 2.1 to 3.0 cm (33% chance of recurrence at 20 years) and from 3.1 to 5.0 cm (44% chance of recurrence at 20 years) were compared. The histologic tumor type was prognostically important. Recurrence at 20 years was not significantly different for patients with invasive duct (34%) and lobular (42%) carcinoma. Women with special types (medullary, mucinous, papillary, etc) of carcinoma had a 25% chance of recurrence. Subsequent contralateral breast carcinoma was diagnosed in 29 patients, and four of these were fatal, accounting for only 4.6% of breast carcinoma deaths. Thirty-two patients (10.9%) developed a nonmammary malignant neoplasm (NMMN) after the ipsilateral breast carcinoma, and 69% of these lesions were fatal. Although the chances of recurrence at 20 years related to tumor size and type did not differ statistically in the series, there were trends that suggest that T2N0M0 patients can be stratified into recurrence risk groups based on tumor size and histologic type. These factors should be taken into consideration in the design and analysis of clinical adjuvant therapy trials. Measures for the early detection of common NMMNs should be included in the routine follow-up of T2N0M0 breast carcinoma patients. 
Serum endothelin-1 concentrations and cold provocation in primary Raynaud's phenomenon To determine whether the vasoconstriction in Raynaud's phenomenon is associated with raised concentrations of the endothelium-derived vasoconstrictor endothelin (ET-1), responses to cold pressor testing were examined in 7 subjects with primary Raynaud's phenomenon and in 7 control subjects. Baseline serum ET-1 levels (pg/ml), as measured by radioimmunoassay, were three times higher in Raynaud's subjects (5.3 [SEM 1.7] pg/ml) than in controls (1.7 [0.3]). With progressive local cooling digital arterial pulsatility, as measured by plethysmography, fell earlier and to a greater extent in Raynaud's subjects than in controls, with a half-maximum decrement in pulsatility occurring at 27 [2.6] degrees C and 18 [0.5] degrees C, respectively. Temperature reduction sufficient to cause loss of pulsatility in the Raynaud's subjects produced increases in ET-1 concentrations in both groups that were greater in Raynaud's (10.3 [4.4] pg/ml) than in control subjects (2.7 [0.9] pg/ml). Serum ET-1 in the contralateral arm rose in parallel to but to a lesser extent than that in the cold-challenged arm. Increases in ET-1 concentrations were temporally related to loss of pulsatility but followed the onset of symptoms. Thus the increased basal and stimulated serum endothelin concentrations in Raynaud's disease are associated with the enhanced, prolonged vasospasm of this disorder. 
Embolization of arteriovenous malformations with peripheral aneurysms using ethylene vinyl alcohol copolymer. Report of three cases. The authors report three cases of arteriovenous malformations (AVM's) with aneurysms arising from the feeding artery; all were successfully treated with a new nonadhesive liquid embolic material, ethylene vinyl alcohol copolymer (EVAL). In two patients the AVM's were totally removed without difficulty, and in one the AVM was managed conservatively after embolization. No new neurological deficits appeared during or after embolization. After road-mapping techniques, EVAL was injected slowly until the feeding artery and aneurysm were completely obliterated. This embolic agent is easy to handle and is considered safe compared with other adhesive liquid embolic agents, such as isobutyl-2-cyanoacrylate or n-butyl cyanoacrylate. It is concluded that EVAL is an excellent agent for embolizing an AVM with a peripheral aneurysm on the feeding artery. 
Duodenal obstruction by a nondeflating Foley catheter gastrostomy tube. We report the case of a 36-year-old mentally retarded man who presented to our emergency department after one day of vomiting and one episode of coffee-ground emesis. The Foley catheter used as his gastrostomy tube was found to be obstructing the duodenum, and the balloon could not be deflated. Removal was accomplished by rupturing the balloon by endoscopy. Our case illustrates one of many possible complications of feeding gastrostomy tubes. 
Soft tissue sarcomas of the chest wall. Results of surgical resection. Primary soft tissue sarcomas of the chest wall are uncommon, and data concerning treatment and results are sparse. Most studies have categorized these tumors as truncal sarcomas and inferred a poor prognosis. To assess the results of surgical treatment, we reviewed our 40-year experience. Methods: Records of 189 patients admitted to our institution from 1948 to 1988 were reviewed. Pathologic material was available for review in the 149 cases (79%) that comprise this report. Survival was calculated by the Kaplan-Meier method, with comparisons by log-rank analysis and significance defined as p less than 0.05. Results: Ages ranged from 3 weeks to 86 years (median, 38 years); the ratio of male to female patients was 2:1. The initial complaint was mass or pain in 97% of the cases. Ninety sarcomas (60%) were high grade and 59 (40%) were low grade. Histologic types were as follows: desmoid tumor (n = 32, 21%); liposarcoma (n = 23, 15%); rhabdomyosarcoma (n = 18, 12%); fibrosarcoma (n = 17, 11%); embryonal rhabdomyosarcoma (n = 14, 9%); malignant peripheral nerve tumor (n = 13, 9%); malignant fibrous histiocytoma (n = 11, 7%); spindle cell sarcoma (n = 4, 3%); tenosynovial sarcoma (n = 3, 3%); hemangiopericytoma (n = 3, 3%); alveolar soft part sarcoma (n = 3, 3%); and other types (n = 12, 9%). Resection was the primary treatment in 140 cases (94%). Local recurrence developed in 27%. Metastases occurred in 52 (35%) of the cases (metachronous in 42, synchronous in 10) and were more common in patients with high-grade disease (46/90, 51%) than in those with low-grade disease (6/59, 10%). Overall 5-year survival was 66%. Five-year survival rate for those with high-grade sarcomas (49%) was significantly lower than that for low-grade sarcomas (90%, p less than 0.0001). Tumor size and age of patient were not prognostic. Conclusions: Survival of patients with primary soft tissue sarcomas of the chest wall after resection is similar to that of patients with sarcomas of the extremities. Resection alone provides acceptable survival (90% at 5 years) for those with low-grade sarcomas, but adjuvant treatment should be considered for those with high-grade sarcomas. 
Cephalometric measurements in snorers, non-snorers, and patients with sleep apnoea. Cephalometry is often used to assess patients with sleep apnoea but whether these measurements differ from those in non-apnoeic snorers and how they are influenced by age is not clear. Cephalometric radiographs of patients with sleep apnoea were compared with those of snorers without sleep apnoea and those of non-snorers. Fifty two snorers with suspected sleep apnoea had a conventional sleep study and were divided into two groups: those with an apnoea-hypopnoea index greater than 10/h (n = 40, sleep apnoea group) and those whose apnoea-hypopnoea index was 10/h or less (n = 12, snorer group). The cephalometric measurements in these patients were compared with those of 34 non-snoring control subjects. Controls were subdivided into two groups: control group 1 included 17 subjects similar in age to the sleep apnoea and snorer groups (mean (SD) age 50.0 (10.9), 50.7 (9.4), and 50.6 (9.7) years); control group 2 included 15 young men (25.4 (2.6) years). The distance from the mandibular plane to the hyoid bone (MP-H) and the length of the soft palate were greater in the patients with sleep apnoea (28.7 (7.8) and 43.6 (5.0) mm) than in the snorers (23.7 (4.2) and 40.3 (4.9 mm). The MP-H was similar in snorers and age matched control subjects, but was significantly greater in the older than in the younger control subjects (22.1 (6.1) vs 17.0 (6.8]. The soft palate was longer in subjects who snored (both sleep apnoea patients and snorers) than in control subjects. The MP-H distance significantly correlated with age for all subjects (snorers and controls) and for the control subjects alone. This study shows that non-apnoeic snorers have cephalometric abnormalities that differ from those of patients with sleep apnoea and that cephalometric values are influenced by the subject's age. 
Intravascular stents in the management of superior vena cava syndrome. Superior vena cava syndrome can be effectively palliated with the use of intravascular stents. Adjunctive modalities which may be utilized prior to stent placement are thrombolytic therapy and balloon angioplasty. Six patients with an underlying malignancy were treated with these modalities. Complete resolution of symptoms occurred in five patients, and partial resolution occurred in the sixth. Two of the patients who had initial, complete resolution of symptoms had recurrences. One involved rethrombosis of the superior vena cava which occurred twice and required percutaneous thrombectomy, and the second involved restenosis requiring a percutaneous transluminal angioplasty of the SVC just distal to the stent. Both of these patients with second procedures, again, had complete resolution of symptoms. Intravascular stents are a valuable additional treatment of superior vena cava syndrome. 
Chemicals and environmentally caused diseases in developing countries. This chapter discusses international aspects of diseases resulting from exposure to chemical pollutants in the environment, with an emphasis on developing countries. These countries share many of the same problems of air, water, and pesticide pollution that face the more industrialized countries. In developing countries, however, the problems are compounded by a number of unique situations, viz., economic priorities, high burden of infectious diseases, impoverishment, and absence of a regulatory framework for the disposal of toxic chemicals. This discussion emphasizes the importance of interactions among toxicants, malnutrition, and infectious diseases for both urban and rural populations insofar as these interactions contribute to disease. Toxicants not only produce disease directly but also exacerbate diseases with other causes. Specific examples from developing countries demonstrate how human health effects from exposures to environmental chemicals can be assessed. While they do not strictly fall under the rubric of "developing countries," the public health consequences of inadequate control of environmental pollution in the East European countries should demonstrate the magnitude of the problem, except that in developing countries the public health consequence of environmental chemicals will be aggravated by the widespread malnutrition and high prevalence of infectious diseases. Much needs to be done before we can adequately quantify the contribution of environmental chemicals to morbidity and mortality in developing countries with the level of sophistication now evident in the charting of infectious diseases in these countries. 
Acute spinal cord injury: magnetic resonance imaging correlated with myelopathy. Thirty-one patients (29 males and two females, 13-87 years of age (mean, 46.7 years] with acute spinal cord injury were studied by MR (magnetic resonance) imaging and the results were correlated with neurological findings. Magnetic resonance images were obtained with a 0.5 T superconductive MR scanner (Phillips Gyroscan S5). Initial imaging was performed within 24 hours after trauma in 13 patients, 1-7 days in 13 patients and 7-14 days in five patients. Twenty-six patients underwent follow-up examinations with MR imaging. Cord abnormalities including cord compression (23 patients), cord swelling (seven patients), and abnormal signal intensities on either T1 or T2-weighted images (26 patients) were observed on initial examination. Multivariate analysis showed that cord compression and abnormal intensities on T1-weighted images were important prognostic indicators. Hyperintensity on T2-weighted images was non-specific but correlated well with clinical recovery. Magnetic resonance imaging is useful in predicting the prognosis and for planning treatment following spinal cord injuries. 
Can vitamin D deficiency produce an unusual pain syndrome? An unusual pain occurred in five patients in the presence of compromised vitamin D status and resolved 5 to 7 days after supplementation with vitamin D in the form of ergocalciferol. The pain had a hyperesthetic quality and did not respond to the use of analgesics, including opiate derivatives. Treatment with therapeutic levels of a tricyclic antidepressant did not bring relief of symptoms. In one case, months after treatment and subsequent improvement of vitamin D status and pain, the vitamin D status again declined and the pain recurred. The pain again resolved with vitamin D replacement and improvement of levels. There may be a pain syndrome associated with vitamin D depletion that appears as hyperesthesia worsened by light, superficial pressure or even small increments of movement. This pain restricts mobility and function and may lead to further complications, such as pressure sores. 
Operations for Wolff-Parkinson-White syndrome. Forty-six patients with symptomatic tachycardia underwent operations to divide 55 atrioventricular accessory pathways. Mean age was 29 years (range 11 to 63). Ten patients (22%) had associated cardiac disease, including two with a congenital diverticulum of the coronary sinus and six (13%) who had concomitant surgical procedures. A bipolar hand-held electrode was used in 22 operations, and simultaneous multisite mapping in the last 24 operations. Ten patients (22%) had multiple accessory pathways. A modified endocardial approach was used. The overall patient success rate was 93% with 91% to 93% of accessory pathways successfully divided. The perioperative morbidity was 17%. There were two reoperations. There were no early or late deaths. Patients have been followed up for a mean of 16 months. There were five recurrences of preexcitation (two early, three late). Two of these patients (both with a congenital diverticulum of the coronary sinus) had reoperation. One patient had late recurrence of atrial fibrillation. Operation for the Wolff-Parkinson-White syndrome has a high probability of success with a low operative risk. 
Oral contraceptives and coronary heart disease. In industrialized countries, coronary heart disease (CHD) is a major public health problem for both men and women. Preventive strategies for reducing the excessive mortality and morbidity associated with CHD involve the identification and modification of metabolic factors believed to be involved in the disease process. Three major areas of concern are lipid metabolism, carbohydrate metabolism and the hemostatic system. The steroid hormones contained in oral contraceptives (OCs) have been shown to interfere in all three areas. In many instances OCs have been shown to alter metabolic markers for CHD in directions associated with increased risk. Although evidence is lacking that such changes induce CHD in users of modern, low-dose OCs, it would be prudent to develop formulations with a minimal impact on metabolic risk markers. There is increasing evidence that many of the metabolic disturbances seen in CHD patients share a common origin, and the development of risk-free OCs is likely to require investigation into complex interrelationships. 
Demonstration of myocardial reperfusion injury in humans: results of a pilot study utilizing acute coronary angioplasty with perfluorochemical in anterior myocardial infarction. Reperfusion may limit the amount of potentially salvageable myocardium through the introduction of cellular elements into previously ischemic but viable myocardium (reperfusion injury). It has been demonstrated that intracoronary infusion of a 20% intravascular perfluorochemical emulsion (Fluosol) significantly reduces infarct size and results in improved left ventricular function in the canine model. This pilot study was performed to explore the existence of myocardial reperfusion injury in humans. Utilizing Fluosol as a probe in conjunction with emergency coronary angioplasty, 26 patients presenting within 4 h with a first anterior myocardial infarction were randomized to emergency angioplasty or angioplasty followed by a 30-min intracoronary infusion of Fluosol at 40 ml/min. Global and regional ventricular function were assessed immediately and a mean of 12 days after successful angioplasty with contrast ventriculography. Infarct size was semiquantitated with thallium-201 single-photon emission computed tomography (SPECT) images before discharge. Twelve patients (six undergoing angioplasty alone, six treated with angioplasty and Fluosol) had an occluded infarct-related vessel (Thrombolysis in Myocardial Infarction [TIMI] grade 0 to 1) at the time of emergency catheterization and were included in the final analysis. At 12 days after successful angioplasty, the improvement in regional ventricular function was greater in patients receiving adjunctive therapy with intracoronary Fluosol versus those undergoing angioplasty alone utilizing both the radial shortening and centerline method, respectively (23 +/- 3.1% vs. 8 +/- 2.3%, p less than 0.02; and -1.6 +/- 0.4 vs. -2.9 +/- 0.2 SD/chord, p less than 0.05). 
The rectus abdominis free flap in head and neck reconstruction. The rectus abdominis musculocutaneous free flap, based on the deep inferior epigastric artery and vein, has been used widely in reconstruction of the breast and extremities. The number of reports on its applications in the head and neck is limited. The rectus abdominis free flap is one of the most versatile soft-tissue flaps. The deep inferior epigastric artery and vein are long, large-diameter vessels that are ideal for microvascular anastomoses. The area of skin that can be transferred is probably the largest of all flaps presently in use. The versatility of this donor site is due to the ability to transfer large areas of skin with varying thicknesses and varying amounts of underlying muscle. We have successfully used this flap in 15 consecutive patients to reconstruct defects of the neck, face, mouth, pharynx, skull base, and scalp. No major complications involving either the recipient or donor sites occurred. The literature on the use of the rectus abdominis flap in head and neck reconstruction is reviewed in detail. The advantages and disadvantages of this soft-tissue free flap are thoroughly discussed in an effort to better define its proper place among the reconstructive options available to the head and neck surgeon. 
Effect of dietary proteins and lipids in patients with membranous nephropathy and nephrotic syndrome. Twenty-four patients with idiopathic membranous nephropathy, long-lasting nephrotic syndrome and serum creatinine less than 2 mg/dl ate sequentially, in a randomized cross-over design, a normal protein diet containing 1.1 +/- 0.3 g/kg/day of proteins and a low protein diet containing 0.7 +/- 0.1 g/kg/day of protein, each diet for a period of 3 months. Both diets were low in fat (less than 30% of total calories) and cholesterol (less than 200 mg/day) content and rich in polyunsaturated fatty acids and in linoleic acid (10% of energy). Random assignment to one of the two 3 month diet periods was done after a RUN-IN period of at least one month on the hypolipidic normal protein diet. Glomerular filtration rate (inulin clearance), 24 hour urinary protein loss and serum albumin concentration did not significantly differ at the end of the two diet periods, indicating that long-term restriction of protein intake does not modify GFR or urinary protein loss in nephrotic patients. Serum total and LDL-cholesterol and daily proteinuria were significantly lower at the end of both diet periods than at the beginning and at the end of the RUN-IN period. We suggest that these changes were a consequence of the manipulation of dietary fat intake. 
Ofloxacin versus parenteral therapy for chronic osteomyelitis. We conducted a randomized comparison of oral ofloxacin (400 mg twice a day) and parenteral agents (cefazolin, 1.0 g intravenously every 8 h, or ceftazidime, 2.0 g intravenously every 12 h) in biopsy-confirmed, nonprosthesis osteomyelitis. A total of 19 subjects received ofloxacin for an average of 8 weeks, and 14 received parenteral antibiotics for an average of 4 weeks; both therapies were well tolerated. Infections were due to Staphylococcus aureus (40%), Enterococcus spp. (3%), Pseudomonas aeruginosa (15%), and other gram-negative organisms (42%). At the completion of therapy, one P. aeruginosa infection in the ofloxacin group persisted and the organism acquired resistance, accompanied by a resistant Acinetobacter superinfection. In the parenteral group, one S. aureus infection persisted, and there was a resolved superinfection due to S. aureus as well. Eighteen-month follow-up data have been obtained. Among those treated with ofloxacin, four subjects whose initial response to therapy was successful suffered relapses of infection, three due to S. aureus and one due to P. aeruginosa, while in the parenteral group, one subject with a P. aeruginosa infection relapsed. Long-term response to therapy was successful for 14 of 19 (74%) subjects who received ofloxacin and 12 of 14 (86%) who received parenteral antibiotics; the difference was not significant. Oral ofloxacin appears comparable to parenteral antibiotics in chronic osteomyelitis due to susceptible organisms, and oral ofloxacin offers advantages in economics and convenience. 
Auditory screening of infants. Within the last 20 years, infant hearing screening has progressed from a laudable goal to a state-mandated reality in many areas of the United States. The high risk register provides a means by which history and neonatal physical examination can be used to identify the infant at risk for hearing loss. Two procedures (crib-O-gram and auditory brainstem-evoked response) have been the most common methods of screening for hearing loss in the newborn or in intensive care nurseries. Evoked cochlear emissions reportedly are identifiable in 90 to 100% of normal-hearing infants. This observation has lead to the use of evoked otoacoustic emissions as a hearing screening procedure with infants. 
SWIFT trial of delayed elective intervention v conservative treatment after thrombolysis with anistreplase in acute myocardial infarction. SWIFT (Should We Intervene Following Thrombolysis?) Trial Study Group. OBJECTIVE--To see whether early elective angiography with a view to coronary angioplasty or bypass grafting of a stenosed infarct related vessel would improve outcome in acute myocardial infarction treated by thrombolysis with anistreplase. DESIGN--Randomised study of two treatment strategies with analysis of results over 12 months. SETTING--21 district hospitals and regional cardiac centres in Britain and Ireland. SUBJECTS--800 of 993 patients presenting with clinical and electrocardiographic features of acute myocardial infarction up to three hours after the onset of major symptoms. TREATMENT STRATEGIES--Intravenous anistreplase 30 units followed by a standard regimen of heparin, warfarin, and timolol and (in patients so randomised) early angiography plus appropriate intervention. MAIN OUTCOME MEASURE--Death or reinfarction within 12 months. RESULTS--397 patients were randomised to receive early angiography plus appropriate intervention (coronary angioplasty in 169 cases, coronary grafting in 59) and 403 patients to receive conservative care (of these, 12 had angioplasty and seven bypass grafting during the initial admission). By 12 months mortality (5.8% (23 patients) in the intervention group v 5.0% (20) in the conservative care group; p = 0.6) and rates of reinfarction (15.1% (60 patients) v 12.9% (52); p = 0.4) were similar in the two groups. No significant differences in rates of angina or rest pain were found at 12 months. Left ventricular ejection fraction at three and 12 months was the same in both groups. Median hospital stay was longer in the intervention group (11 days v 10 days; p less than 0.0001). CONCLUSION--For most patients given thrombolytic treatment for acute myocardial infarction a strategy of angiography and intervention is appropriate only when required for clinical indications. 
Chondromyxoid fibroma: radiographic appearance in 38 cases and in a review of the literature [published erratum appears in Radiology 1991 Aug;180(2):586] Thirty-eight cases of histologically confirmed chondromyxoid fibroma were reviewed and their radiographic features recorded. These findings, coupled with a review of the English-language medical literature, suggest that this rare, benign bone tumor has a characteristic but not specific radiographic appearance and may often mimic more common tumors. Chondromyxoid fibroma may occur anywhere in the skeleton, but almost half of the cases occur around the knee. The possibility of chondromyxoid fibroma should always be considered when a focal bone lesion is evaluated that has geographic bone destruction, a sclerotic rim, lobulated margins, and septation. The diagnosis of chondromyxoid fibroma is most likely when the patient is in the 2nd decade of life. 
Role of bile acids in splanchnic hemodynamic response to chronic portal hypertension. Previous studies from our laboratory suggest that humoral factors, namely glucagon, can account for approximately 30% of the splanchnic vasodilation in rats with prehepatic portal hypertension. A reduced vascular sensitivity to norepinephrine, vasopressin, and angiotensin II may contribute to the splanchnic vasodilation. However, neither glucagon nor an altered vasoconstrictor sensitivity can fully account for the splanchnic vasodilation observed in portal hypertensive subjects. Therefore, the present study was designed to examine the role of bile acids in the splanchnic hyperemia of portal hypertension since (1) serum bile acids are elevated in portal hypertensive subjects and (2) bile acids are potent intestinal vasodilators. Prehepatic portal hypertension was induced in Sprague-Dawley rats by surgical constriction of the portal vein. Ten to 14 days after the induction of portal hypertension, the enterohepatic circulation of control and portal hypertensive rats was surgically interrupted. The animals were placed in Bollman restraint cages and allowed to recover. Eighteen to 24 hr later, the rats were anesthetized with sodium pentobarbital and regional blood flow measured with radiolabeled microspheres. Normal and portal hypertensive animals without bile fistula served as controls. Plasma bile acid levels measured by radioimmunoassay were approximately 3.8 times higher in portal hypertensive animals than in control. Bile duct cannulation effectively depleted both normal and portal hypertensive animals of their circulating bile acid pool and significantly reduced portal venous inflow in portal hypertensive but not in control rats. A role for bile acids as partial mediators of the splanchnic hyperemia of portal hypertension is suggested since bile acid depletion did not completely abolish the gastrointestinal hyperemia. 
Risk factors for injurious falls: a prospective study. We conducted a prospective study of the consequences of falls in 325 elderly community-dwelling persons, all of whom had fallen in the previous year. We contacted subjects every week for one year to ascertain falls and to determine the circumstances and consequences of falls. Only 6% of 539 falls resulted in a major injury (fracture, dislocation, or laceration requiring suture), but over half (55%) resulted in minor soft tissue injury. One in ten falls left the faller unable to get up for at least 5 minutes, and one in four falls caused subjects to limit their activities. The risk of injury per fall was about the same regardless of the number of falls a person had during follow-up. The risk of major injury was increased (age- and sex-adjusted odds ratio: 5.9, 95% confidence interval: 2.3-14.9) in falls associated with loss of consciousness compared to nonsyncopal falls. In multivariate analyses of nonsyncopal falls, the risk of major injury per fall was higher in persons having a previous fall with fracture (6.7; 2.1-21.5), a slower Trail Making B time (1.9; 1.1-3.2), and in Whites (18.4; 7.5-44.6). The risk that a nonsyncopal fall would result in minor injury (versus no injury) was increased in persons with a slower hand reaction time (1.8; 1.0-3.2) decreased grip strength (1.5; 1.0-2.3), in Whites (2.0; 1.0-3.7), in falls while using stairs and steps (2.2; 1.0-5.0), and turning around or reaching (3.5; 1.7-7.3). Our findings suggest that neuromuscular and cognitive impairment, as well as the circumstances of falls, affect the risk of injury when a fall occurs. 
The day-long antianginal effectiveness of nitroglycerin patches. A double-blind study using dose-titration. This study was designed to determine the day-long antianginal effectiveness of nitroglycerin patches in the nitrate-exposed patient, as well as the doses required. Eight men with chronic stable angina, a positive treadmill test, and demonstrated responsiveness to long-term oral isosorbide dinitrate were studied after they had been taking effective doses of isosorbide dinitrate three times a day for at least two weeks. Treadmill exercise bouts were performed every 1 to 2 hours over 1 day, after the 8 am application of active nitroglycerin patches in a previously titrated dose, and on another day after application of placebo patches. Mean necessary effective patch dose was 125 sq cm (60 to 220 sq cm). Mean exercise duration to angina rose from 271 to 480 s (p less than 0.001) 1 hour after active patches, while resting systolic blood pressure fell from 122 mm Hg to 100 mm Hg (p less than 0.001). (After placebo patches: +19 s and -2 mm Hg, respectively.) Active patches were superior to placebo throughout the day, but in declining degree (by 94 s at 7 pm, p less than 0.05). Thus, nitroglycerin patches can provide a significant day-long antianginal effect in the patient with long-term exposure to nitrate. However, the need for large doses and individual titration may make this therapy impractical. 
Laser cordectomy for T1 glottic carcinoma: a 10-year experience and videostroboscopic findings. Fifty-three patients underwent laser cordectomy for T1 glottic squamous cell carcinoma between January 1980 and December 1989--sixteen after having undergone unsuccessful radiation and thirty-seven who had no previous treatment. There was a 51% five-year cure rate in the irradiated group vs. 62% in the nonirradiated group. Extension of tumor to the anterior commissure resulted in a higher failure rate. Patients experienced an overall 5-year cure rate of 98% after surgical or radiation salvage of unsuccessful laser cordectomies. Six patients had preoperative and postoperative videostrobolaryngoscopy. The most common postoperative problem with voice was a breathiness that did not resolve in any of the patients. All patients had absent or moderately reduced amplitude and mucosal wave patterns and imcomplete glottic closure proportional to the amount of cordal tissue removed. Despite it seemingly poor results in carefully selected patients, laser cordectomy is still indicated without compromising the ultimate oncologic results. Advantages over radiation therapy or conservation laryngeal surgery include a short treatment time, requiring only an outpatient surgical procedure at the time of the initial diagnostic and/or staging laryngoscopy, and the avoidance of potential radiation side effects or surgical complications. However, patients should be advised the possibility of persistent postoperative breathy dysphonia, in addition to the possibility of further treatment to effect a long-term cure. 
Crossover ilioprofunda reconstruction: an expanded role for obturator foramen bypass. The standard obturator foramen bypass extends from the aorta or iliac artery to the ipsilateral superficial femoral or popliteal artery. This operation has been both effective and versatile as an indirect bypass procedure for circumventing difficult vascular problems in the femoral triangle. A case is presented of a patient whose limb was salvaged by an obturator foramen bypass from the contralateral iliac artery to the profunda femoris artery. This unique case is compared to other published cases to emphasize the potential advantages of the profunda femoris as the preferred graft outflow in selected cases of arterial reconstruction through the obturator foramen. 
Antibiotic treatment of bacterial gastroenteritis. Antibiotic treatment is important in certain etiologies of bacterial gastroenteritis, both for clinical improvement and for eradication of the causative organism from stools, which is important epidemiologically. The etiology, however, is seldom known at presentation in sporadic cases of diarrhea. Thus the decision to initiate antibiotic therapy and the choice of the specific antimicrobial agents should be made on a clinical basis, before culture results are available. 
Regulation of B cell antigen receptor signal transduction and phosphorylation by CD45. CD45 is a member of a family of membrane proteins that possess phosphotyrosine phosphatase activity, and is the source of much of the tyrosine phosphatase activity in lymphocytes. In view of its enzymatic activity and high copy number, it seems likely that CD45 functions in transmembrane signal transduction by lymphocyte receptors that are coupled to activation of tyrosine kinases. The B cell antigen receptor was found to transduce a Ca(2+)-mobilizing signal only if cells expressed CD45. Also, both membrane immunoglobulin M (mIgM) and CD45 were lost from the surface of cells treated with antibody to CD45, suggesting a physical interaction between these proteins. Finally, CD45 dephosphorylated a complex of mIg-associated proteins that appears to function in signal transduction by the antigen receptor. These data indicate that CD45 occurs as a component of a complex of proteins associated with the antigen receptor, and that CD45 may regulate signal transduction by modulating the phosphorylation state of the antigen receptor subunits. 
Multicenter evaluation of efficacy, tolerability and safety of a new first-line antihypertensive drug, isradipine, in a Latin-American population. Isradipine, a new antihypertensive dihydropyridine calcium antagonist, was evaluated for its efficacy, tolerability, and safety in 91 ambulatory patients who had mild-to-moderate hypertension. The design of the present study included a two-week wash-out period after confirmation of disease, followed by 12 weeks of active treatment with 2.5 mg isradipine twice daily. Patients were switched from other antihypertensive drugs, mainly diuretics and beta-blockers. The dose of isradipine remained virtually unchanged throughout the study and resulted in a mean decrease of 22 mm Hg in systolic blood pressure (SBP) (P less than .00001) and 19 mm Hg in diastolic blood pressure (DBP) (P less than .00001). Heart rate was unchanged (difference of -1 beats/min), as was the mean body weight of the study patients. Isradipine was generally well tolerated. Side effects were few and, when present, tended to diminish and eventually disappear during the treatment period. All of the clinical laboratory parameters tested and electrocardiograph intervals remained unchanged. In conclusion, these results indicate that isradipine is a novel drug which is highly effective and well tolerated in the treatment of mild to moderate hypertension in this group of patients. 
Diagnosis and management of chronic hypertension in pregnancy. Pregnancies complicated by chronic hypertension are at increased risk for the development of superimposed preeclampsia, abruptio placentae, and poor perinatal outcome. The frequency of these complications is particularly increased in patients with severe hypertension and those with preexisting cardiovascular and renal disease. Such women should receive appropriate antihypertensive therapy and frequent evaluations of maternal and fetal well-being. In contrast, in patients with mild essential chronic hypertension, the maternal and perinatal benefits from antihypertensive medications are highly controversial. A review of the literature revealed two placebo-controlled studies, four trials comparing treatment versus no medication, and three comparisons of methyldopa and oxprenolol. In only one of these studies were subjects randomized in the first trimester. No differences in pregnancy outcome were found with the use of antihypertensive drugs. Evaluation of the woman with chronic hypertension who is considering pregnancy should begin before conception to establish the cause and severity of the hypertension. Appropriate management should include frequent evaluation of maternal and fetal well-being; antihypertensive medications may be useful in patients with severe disease as well as in those with target organ involvement. 
Gastroesophageal reflux and upper airway diseases. GER can have important impacts on the upper airway passages, and in turn, upper airway obstruction can certainly aggravate reflux. This relationship should be considered in the newborn or young infant, faced with a sudden life-threatening event, and in the older child or adult presenting with chronic head and neck complaints, either unexplained or unresponsive to adequate medical therapy. A causal relationship may be difficult to establish, based first on clinical expertise as a guideline, on laboratory tests, among which pharyngeal pH monitoring could be promising, and on response to medical antireflux therapy. A better understanding of the significance of high levels of reflux and defective acid clearance, as well as a more precise knowledge of the maturation and functioning of upper airway protective mechanisms, would open the way to more accurate diagnostic procedures, to a more reliable definition of the abnormal, and to greater efficiency in the management of these patients. 
Emergency management of the nondeflating Foley catheter balloon. Inability to remove a self-retaining (Foley) catheter may result from failed attempts to deflate its balloon. In this article, the authors review the causes of inability to deflate Foley catheters as well as the various techniques for their removal. 
Post-prandial worsening of angina: all due to changes in cardiac output? BACKGROUND--The precise mechanism leading to the post-prandial worsening of angina has yet to be adequately defined. It has been attributed to an increase in double product but is perhaps more likely to be related to an increase in cardiac output after food. This study was designed to evaluate the effects of food on patients' exercise tolerance and compare these with changes in haemodynamic variables. METHODS--23 patients with chronic stable angina who had post-prandial worsening of their angina were studied. The patients were evaluated on two occasions and at each visit they underwent two symptom limited treadmill exercise tests. They remained fasting on the first visit and were given a 1400 kcal meal 60 minutes before the second exercise test on the second visit. Time to onset of 1 mm ST segment depression, heart rate, systemic arterial blood pressure, and cardiac output were measured at rest and during exercise. RESULTS--There were no differences in any of the variables during the two exercise tests on the day the patients remained fasting. After the meal exercise tolerance fell significantly by 136 seconds and the stage at which 1 mm ST segment depression was first seen was also significantly reduced. Resting cardiac output increased significantly by 0.86 1/min with the patients sitting and by 0.89 1/min standing. The exercise times after food were significantly related to cardiac output even when fasting times were taken into account. Resting heart rate increased significantly by 8.3 beats per minute sitting and 10.4 beats per minute standing. There was little change in blood pressure and no evidence that the double product predicted the post-prandial exercise time. CONCLUSIONS--Worsening of angina was related to the increase in cardiac output after a meal and successful treatment will depend upon the prevention of this increase. 
Headache spectrum in Arnold-Chiari malformation. Exertional headaches in patients with Arnold-Chiari malformation (ACM) are well described. We report four patients with Type I ACM and recurrent headaches. These patients presented, respectively, with low spinal fluid pressure headache, migraine without aura, migraine with aura, and migraine with prolonged aura. This report suggests the need for observing patients with recurrent headaches for any physical stigmata of craniovertebral junction anomalies, and the need to exclude ACM in such patients. Possible implications of the association between ACM and different types of headaches are discussed. 
Influence of type of prosthesis on late results after combined mitral-aortic valve replacement. The influence of type of prosthesis on the late outcome of patients with combined mitral-aortic valve replacement was analyzed by comparing, at a 14-year follow-up, patients receiving two biological prostheses (group 1; n = 135), two mechanical prostheses (group 2; n = 221), or a mechanical prosthesis in the aortic position and a bioprosthesis in the mitral position (group 3; n = 97). No difference was found among the three groups in terms of actuarial survival and incidence of and freedom from valve-related deaths, thromboemboli, and hemorrhages. Patients with biological prostheses had a significantly greater incidence of structural valve deterioration, reoperations, and overall complications when compared with patients with only mechanical prostheses. The results of an extended follow-up of patients with combined mitral-aortic valve replacement indicate that mechanical prostheses perform better in the long-term owing to their superior durability when compared with biological valves. The use of bioprostheses should be confined to old patients with limited life expectancy because of their cardiac disease, provided that anticoagulants are not used. Combination of mechanical and biological prostheses in the same patient should be avoided because the advantages of each type of prosthesis are lost. 
CT appearance of splenic injuries managed nonoperatively. This essay illustrates the appearance of the traumatized spleen on CT scans obtained during the course of conservative treatment. Although the CT appearance of acute rupture of the spleen has been adequately described, little has been reported about the appearance of the spleen as it heals after trauma. Examples of CT studies of splenic injuries illustrate the various changes in appearance over time in the traumatized spleen that is treated nonoperatively. 
Progress in cancer. Definite progress has been made against cancer since the National Cancer Act was passed in 1971. Physicians are giving increased attention to cancer prevention. The exciting changes in molecular biology provide increased knowledge about basic mechanisms in tumor growth and metastases. Detailed discussions of two common solid cancers--breast and colorectal--attest to continuing advances in cancer diagnosis and treatment. All of these augur well for further progress in oncology. Continued research, basic and clinical, is mandatory. 
Percutaneous posterolateral lumbar discectomy and decompression with a 6.9-millimeter cannula. Analysis of operative failures and complications. The operative failures and complications of percutaneous posterolateral lumbar discectomy were analyzed in 100 patients who had a herniated nucleus pulposus and were prospectively studied and treated with use of a 6.9-millimeter outer-diameter (4.9-millimeter inner-diameter) sheath and manual insertion of the instruments. Twelve operations were considered to have failed, regardless of the length of postoperative follow-up or the incidence of reinjury; eleven patients had a repeat operation at the index level, and one patient was a chronic drug-abuser. In eight of the eleven patients, subsequent laminectomy was successful. Two patients had a psoas hematoma and one had a transitory sensory and distal motor deficit; all of these complications resolved without sequelae. There were no major complications, including superficial or deep infection, and no patient had neurovascular compromise. 
Palliation of proximal malignant biliary obstruction by endoscopic endoprosthesis insertion. For four years up to December 1987, 190 patients (median age 73 years) with proximal malignant biliary obstruction were treated by endoscopic endoprosthesis insertion. Altogether 101 had cholangiocarcinoma, 21 gall bladder carcinoma, 20 local spread of pancreatic carcinoma, and 48 metastatic malignancy. Fifty eight patients had type I, 54 type II, and 78 type III proximal biliary strictures (Bismuth classification). All patients were either unfit or unsuitable for an attempt at curative surgical resection. A single endoprosthesis was placed initially, with a further stent being placed only if relief of cholestasis was insufficient or sepsis developed in undrained segments. The combined percutaneous-endoscopic technique was used to place the endoprosthesis when appropriate, after failed endoscopic endoprosthesis insertion or for second endoprosthesis placement. Full follow up was available in 97%.Thirteen patients were still alive at the time of review and all but one had been treated within the past six months. Initial endoprosthesis insertion succeeded technically at the first attempt in 127 patients, at the second in 30, and at a combined procedure in a further 13 (cumulative total success rate 89% - type I: 93%; type II: 94%; and type III: 84%). There was adequate biliary drainage after single endoprosthesis insertion in 152 of the 170 successful placements, giving an overall successful drainage rate of 80%. Three patients had a second stent placed by combined procedure because of insufficient drainage, giving an overall successful drainage rate of 82% (155 of 190). The final overall drainage success rates were type I: 91%; type II: 83%; and type III: 73%. The early complication rates were type I: 7%; type II: 14%; and type III: 31%. 
Complications after intravesical instillation of bacillus Calmette-Guerin: rhabdomyolysis and metastatic infection. Two cases of adverse reaction to bacillus Calmette-Guerin (BCG) bladder instillations are reported. In both cases transient fevers and systemic symptoms developed following the instillations. After an additional instillation 1 patient had high fevers, severe myalgias and profound weakness followed by rhabdomyolysis and anuric renal failure, which required 3 weeks of hemodialysis before recovery. Extensive evaluation revealed no cause other than the BCG instillations. In the other patient a firm subcutaneous nodule gradually developed on the chest wall, which contained nonviable acid fast bacilli. 
Recurrence of ectopic pregnancy: the role of salpingitis. We evaluated the role of salpingitis on the recurrence of ectopic pregnancy from a historical cohort of 2501 women who had undergone laparoscopic examination for acute salpingitis. We used pregnancy (N = 2899) as the unit of analysis and a modified conditional logistic regression to estimate a pairwise odds ratio as a measure of the recurrence of ectopic pregnancy. Among the second or higher order of pregnancy, the recurrence was 21.7%. For pregnancies with a prior uterine pregnancy, the ectopic pregnancy rate increased with prior salpingitis scores constructed from a combination of prior salpingitis episodes and severity (0 score, 2.7%; 1 to 2 scores, 4.8%; and greater than or equal to 3 scores, 12.1%). For those with a prior ectopic pregnancy, the rate did not increase with prior salpingitis scores (score 0, 20.0%; score 1 or 2, 19.2%; and score greater than or equal to 3, 26.9%). The adjusted pairwise odds ratio was 2.2 and was practically unchanged (2.1) after additional adjustment with prior salpingitis scores. These findings confirm salpingitis as a risk factor for first ectopic pregnancy, but once a woman had an ectopic pregnancy, previous salpingitis might not add any incremental risk. 
Effectiveness of nitrous oxide in a rural EMS system. Prehospital systems need a safe, effective analgesic agent for the treatment of patients suffering from pain. Recent studies have documented the efficacy of nitrous oxide in urban and rural settings. This study reviews the findings on 200 patients (157 trauma, 23 medical, 18 musculoskeletal problems) who received nitrous oxide during a 28-month period in a rural EMS system. Eighty-five percent of the patients reported pain relief. Only minor side effects were noted. Patient satisfaction was high, and there was no abuse noted among personnel. 
Iatrogenic epidermoid cyst of the parotid region following ear surgery. Iatrogenic implantation of squamous epithelium may result in formation of an epidermoid cyst. These cysts have been described in various sites around the head and neck following otological procedures. A case of iatrogenic epidermal cyst in the parotid region following repeated myringoplasty is reported. The clinical features and differential diagnosis are discussed. 
Epidural blood patch for treatment of subarachnoid fistula in children. A subarachnoid-cutaneous fistula developed in two children after the placement of a catheter in the subarachnoid space for drainage of cerebrospinal fluid. The management of this iatrogenic complication with epidural blood patch is described. 
The value of estrogen and progesterone receptor determinations in advanced breast cancer. Estrogen receptor level but not progesterone receptor level correlates with response to tamoxifen. Four hundred fifteen patients with metastatic breast cancer with known hormone receptor status received primary treatment with tamoxifen. Measured values for the estrogen receptor (ER, i.e., with estrogen binding) followed a continuous distribution (range, 3 to 1000 fmol/mg of protein). These values correlated positively with age. The response to treatment with tamoxifen correlated with the ER level, with response rates of approximately 80% when the ER level was greater than 30.1 fmol/mg of protein. Two hundred eighteen (218 of 415, 52%) patients had progesterone receptor (PR) values greater than 10 fmol/mg. The PR positivity correlated with the ER level. Patients with PR levels greater than 10 fmol/mg of protein (124 of 226, 55%) had a significantly higher response rate than those with values less than 10 fmol/mg of protein (45 of 189, 24%). However, in a multivariate analysis including both receptor levels, age, site, and number of metastases, only the ER level was significant in predicting the response to treatment with tamoxifen. A quantitative estimation of the ER level thus is the best predictor of response to hormonal treatment with tamoxifen for advanced breast cancer. 
Regional intravenous ketanserin and guanethidine therapy in Raynaud's phenomenon. The authors report the results of a study of 25 patients with Raynaud's phenomenon (primary, posttraumatic, and secondary to diffuse connective tissue diseases) treated with regional intravenous injections of guanethidine or ketanserin. These two drugs were chosen because of the different etiopathologic profiles of the conditions. All the patients showed a substantial clinical improvement with a remission of trophic lesions. Conditions secondary to connective tissue disorders did not demonstrate much improvement based on instrumental data alone, possibly because of the intrinsic limitations of the techniques used for evaluating peripheral blood flow. This specific type of pharmaceutical treatment appeared to be especially suitable for this disease owing to a combination of therapeutic efficacy and a substantial reduction in the total dosage for each patient. 
The axial load teardrop fracture. A biomechanical, clinical and roentgenographic analysis. The anteroinferior cervical vertebral body corner fracture was originally described by Schneider and Cann as the "teardrop" fracture. This report analyzes the biomechanical, clinical, and roentgenographic features of 55 such fractures obtained from the National Football Head and Neck Injury Registry. Teardrop fractures resulting from tackle football characteristically occurred in players attempting to make a tackle in which initial contact was made with the top or crown of the helmet. There were two fracture patterns associated with the anteroinferior corner (teardrop) fracture fragment: 1) the isolated fracture, which is usually not associated with permanent neurologic sequelae; and 2) the three-part, two-plane fracture in which there is an associated sagittal vertebral body fracture as well as fracture of the posterior neural arch. This latter pattern was almost always associated with permanent neurologic sequelae, specifically quadriplegia. Axial loading of the cervical spine was clearly identified as a mechanism of injury for both fracture patterns. Roentgenographic examination must include both anteroposterior and lateral views with computed tomography or tomography as necessary to determine the presence of the sagittal vertebral body fracture and the integrity of the posterior neural arch. 
Facial weakness. A comparison of clinical and photographic methods of observation. The search for an internationally acceptable facial grading system has resulted in an assessment of existing methods by several investigators. These studies were based on observations of video film taken of patients with varying degrees of facial malfunction. Although the grading systems were evaluated, the use of videotape has never been compared with clinical examination and its suitability for this type of work is, therefore, unknown. We used nine facial grading systems to compare the results of clinical observation with those of photographic methods of presentation. The latter included videotape, photographic slides, and a combination of the two. The correlation between clinical examination findings and findings of any of the photographic methods was poor, suggesting the need for a standard form of presentation when grading patients. The most consistent results were found with either clinical examination or photographic slides; videotape was the least reliable. 
Pattern of simulated snoring is different through mouth and nose. Cineradiography of the pharynx during simulated snoring was done in 6 healthy volunteers, and supraglottic pressure and flow rate were recorded in 12 others. We observed, immediately before snoring, a decrease in the sagittal diameter of the oropharynx followed, during snoring, by high-frequency oscillations of soft palate and pharyngeal walls. The pattern of soft palate oscillations was different while snoring through the nose or mouth. During inspiratory snoring through the nose, the soft palate remained in close contact with the back of the tongue and only the uvula presented high-frequency oscillations. Snoring through the mouth resulted in ample high-frequency oscillations of the whole soft palate. Frequency of airflow and supraglottic pressure oscillations was less (P less than 0.05) during mouth (28.2 +/- 7.5 Hz) than during nasal snoring (77.8 +/- 36.7 Hz). This difference may be related to the smaller oscillating mass (i.e., uvula) during nasal snoring. At variance with our previous data, which showed that snoring during sleep, in both heavy (nonapneic) snorers and obstructive sleep apnea patients, was systematically preceded by flow limitation, this was not true during simulated snoring. 
Defining the proper role for self-administered sublingual nitroglycerin. A survey of physicians and patients. Within a half-year period, we encountered six cases of patients harmed by the adverse effects of self-administered nitroglycerin--syncope, delayed definitive medical care, and the worsening of nonischemic symptoms. We therefore surveyed 112 patients after a remote myocardial infarction, and 121 cardiologists and internists, regarding the use of sublingual nitroglycerin. Of the physicians, 84 percent routinely prescribed nitroglycerin to patients after a myocardial infarction, and 79 percent of the patients had the tablets available (83 percent of these, at all times). Most patients used the tablets less than once per month, and 37 percent of the patients who always carried nitroglycerin had not used it at all during the preceding year. Although 89 percent of the patients claimed to know when to use the drug, 57 percent had used it or would use it for symptoms such as dizziness, rapid heartbeat, or presyncope. All patients having nitroglycerin claimed it relieved their symptoms, even if the relief was only partial, the time elapsed until relief could not be specified, and the symptoms were of a type unlikely to be relieved by the drug. We suggest that the practice of routinely prescribing nitroglycerin to patients after a myocardial infarction should be reassessed. 
Clinical course and roentgenographic changes of osteonecrosis in the femoral condyle under conservative treatment. The history of osteonecrosis in the femoral condyle of the knee was observed in 15 knees in 14 patients, averaging 62.8 years in age (range, 23-79 years). There were nine women and five men. The average follow-up period was 4.9 years (range, one to 12 years). Spontaneous osteonecrosis was found in 11 patients and steroid-induced osteonecrosis in three. The medial femoral condyles were involved in 13 knees and the lateral femoral condyles in two. The maximum width of the lesion was measured on anteroposterior roentgenograms and an osteonecrotic lesion less than 10 mm wide was rated as small. Cases of small osteonecrotic lesions displayed no remarkable changes with respect to stages and limb alignment. The average size of the steroid-induced osteonecrotic lesions was significantly larger than that of the spontaneous type. The size of the osteonecrotic lesions at the follow-up examination was compared to that observed at the initial diagnosis in 12 knees. Eight of these lesions displayed increases in dimension of more than 18% over the initial size at diagnosis. 
Safety and cost effectiveness of combined coronary angiography and angioplasty. If coronary angioplasty can be safely performed at the time of the initial diagnostic catheterization, it may result in shorter hospitalization stays and lower overall costs. Combined coronary angiography and angioplasty was performed electively on 733 patients between January 1, 1984, and September 1, 1988. These patients were divided into three major subgroups based upon their indications for angioplasty: 444 (61%) procedures were performed for restenosis; 190 (26%) procedures were performed in patients for unstable angina; and 99 (13%) procedures were performed in patients without unstable angina or previous angioplasty. A subset of 219 patients from this study who underwent elective combined coronary angiography and angioplasty during 1986 were compared with a matched population of 191 patients from the angiography and angioplasty as separate procedures). The success and complication rates were similar for both of these groups. Patients who underwent the combined procedure were hospitalized for a mean of 4.6 days with average total charges of $11,128, compared with 8.0 days and $13,160 for patients undergoing separate procedures (p less than 0.001). Significant savings were also realized with respect to total contrast dose, fluoroscopic time, and total procedural time. Thus in informed patients with suitable coronary anatomy, the strategy of combined angiography and angioplasty may present an opportunity for decreasing hospitalization stay, reducing total charges for revascularization, and reducing radiation exposure without compromising the safety or effectiveness of the procedure. 
Prospective study of porous-coated anatomic total hip arthroplasty. Seventy-five uncemented porous-coated total hip prostheses were implanted in 64 patients. The results were reviewed after a mean follow-up period of 47 months (range, 40-64 months). The mean preoperative rating was fair, and the mean postoperative rating was excellent. There were six dislocations. Ten patients had mild thigh pain at one year; by two years, the pain had resolved in six patients. Neither moderate nor severe limp nor significant loosening of beads was observed. Only one patient had progressive radiolucent lines. The high rate of dislocation may be related to a compromise of acetabular position to obtain bony fixation in acetabula early in the series. The clinical results were encouraging. 
Comparison of the effects of torasemide and furosemide in nonazotemic cirrhotic patients with ascites: a randomized, double-blind study. In a randomized double-blind trial we compared the effects of torasemide, a new loop diuretic, and furosemide in nonazotemic cirrhotic patients with ascites during a 3-day period in association with potassium canrenoate (200 mg/day) administration. Doses of loop diuretics administered in this trial (10 and 25 mg/day of torasemide and furosemide, respectively) had been shown to be equipotent in healthy subjects. Torasemide induced significantly greater natriuresis than furosemide (p less than 0.02), with a twofold greater percentage increase in basal values (day 1: 130% vs. 50%; day 2: 104% vs. 42%; and day 3: 65% vs. 26%, respectively). Body weight loss was significantly higher during torasemide (p less than 0.02) administration, and the overall decrease at the end of the treatment was twice as high for furosemide (2.5 +/- 0.6 kg vs. 1.3 +/- 0.4 kg, respectively). Diuresis was also higher during torasemide administration, but the difference was not significant (p = 0.08). The extent of kaliuresis observed during the two treatments was almost identical despite the striking differences in the natriuretic response. The effects of the two treatments on plasma electrolytes, creatinine clearance, blood urea nitrogen, mean arterial pressure, heart rate and plasma arginine vasopressin concentration were similar. Both drugs caused increases in plasma renin activity at the end of the treatment, whereas plasma aldosterone concentration slightly increased only after torasemide administration. Despite the presence of a trend toward a more pronounced effect on these parameters after torasemide administration, no significant difference between the two treatments was observed. 
Reduction in the frequency of ventricular late potentials after acute myocardial infarction by early thrombolytic therapy. Ventricular late potentials are strong predictors of arrhythmic events after acute myocardial infarction (AMI). To assess the effect of intravenous thrombolysis on the incidence of ventricular late potentials, 223 consecutive patients surviving a first AMI were included in the present study: 59 patients (53 men, 6 women, mean age +/- standard deviation 55 +/- 10 years) received intravenous recombinant tissue-type plasminogen activator (100 mg over 3 hours, group A) and 164 patients (123 men, 41 women, mean age 61 +/- 11 years) received conventional medical treatment (group B). A time-domain signal-averaged electrocardiogram and a high-resolution beat-to-beat recording (gain 10(6), filters 100 to 300 Hz) were performed at 10 +/- 3 days after AMI. There was no difference between group A and B patients in terms of AMI location (anterior in 28 of 59 vs 80 of 164, difference not significant [NS]), mean left ventricular ejection fraction (55 +/- 10 vs 55 +/- 13%, NS), or presence of heart failure (New York Heart Association class III or IV in 12 of 59 vs 40 of 164, NS). The incidence of ventricular late potentials was 10% (6 of 59) in group A and 24% (39 of 164) in group B (p less than 0.05). Among the 146 patients who underwent coronary arteriography, the incidence of ventricular late potentials was 13% (10 of 80) in patients with a patent infarct-related artery and 26% (17 of 66) in patients with an occluded infarct-related artery (p less than 0.05). 
Aztreonam monotherapy as prophylaxis in transurethral resection of the prostate: a multicenter study. The efficacy and safety of aztreonam in the prophylaxis of urinary tract infection following transurethral resection of the prostate (TURP) in patients with preoperatively sterile urine were studied in a multicenter trial including 300 patients at six Italian urology centers. The present report describes the first 192 patients enrolled in the protocol. Aztreonam or placebo was administered to each patient in three doses, which were given at the induction of anesthesia and 8 and 16 hours later. The development of bacteriuria was monitored by cultures of urine obtained before surgery, 3 days later, at removal of the bladder catheter, at discharge from the hospital, and at a follow-up visit 39-46 days after surgery. A febrile peak was observed for 6% of aztreonam-treated patients and for 20.9% of the placebo group (P less than .005), while bacteriuria was reported in 17.9% and 59.3% of these groups, respectively (P less than .001). From our data, TURP appears to be a clean-contaminated procedure requiring antibiotic prophylaxis, and aztreonam appears to reduce significantly the incidence of postoperative bacteriuria after this surgical procedure. 
Ocular findings in Turcot syndrome (glioma-polyposis). Turcot syndrome is a hereditary condition characterized by multiple, adenomatous gastrointestinal polyps associated with neuroepithelial tumors of the central nervous system. The authors examined a patient with Turcot syndrome who had multiple regions of congenital hypertrophy of the retinal pigment epithelium (CHRPE) with areas of surrounding hypopigmentation in the fundi of both eyes. Multiple, bilateral patches of CHRPE have been reported in patients with familial adenomatous polyposis and Gardner syndrome. This finding is thought to be a sensitive and specific clinical marker for these conditions and useful for predicting the presence and development of colorectal polyposis. Our findings provide further evidence that familial adenomatous polyposis, Gardner syndrome, and Turcot syndrome may be related conditions representing the variable phenotypic expression of a single, autosomal dominant genetic disorder. Children and young adults with multiple patches of CHRPE and a family history of adenomatous polyposis may be at increased risk for the development of central nervous system tumors as well as gastrointestinal polyps. 
Hemobilia due to vasculitis of the gall bladder in a patient with mixed connective tissue disease. A 30-year-old woman with mixed connective tissue disease presented with acute abdominal pain and signs of blood loss. At cholecystectomy she appeared to have lost a considerable amount of blood into the biliary tract due to bleeding of the gall bladder. Microscopic examination showed vasculitis of the gall bladder wall. Hemobilia has not been described before as a complication in mixed connective tissue disease. 
Use of a marshmallow bolus for evaluating lower esophageal mucosal rings. Sixty-three patients (35 women, 28 men; mean age 55 yr) with lower esophageal mucosal ring shown radiographically were examined with a semi-solid bolus consisting of a portion of a standard marshmallow. The most common symptom was dysphagia, present in 46 (73%) patients. Impaction of the marshmallow bolus by the ring occurred in 40 (63%) of the 63 patients, and produced symptoms in 27 (68%) of these 40 patients. Nine (14%) rings were detected radiographically only with a solid bolus; eight of these patients had dysphagia and seven rings were 20 mm or less in caliber. Impaction related to ring caliber, and was found in all 17 (100%) rings that were 13 mm or less in diameter, in 17/24 (71%) 14- to 19-mm rings, and in 6/22 (27%) rings 20 mm or more in caliber. Endoscopy in 23 patients detected 16 (70%) rings, and also depended on ring caliber: less than or equal to 13 mm, 6/6 (100%); 14-19 mm, 5/9 (56%); greater than or equal to 20 mm, 5/8 (63%). Marshmallow impaction occurred in 17 (74%) of 23 patients who had endoscopy; three of the 23 patients had normal endoscopy. In conclusion, radiographic examination supplemented by the use of a marshmallow bolus best detects lower esophageal mucosal ring. 
Role of duplex scanning for the detection of atherosclerotic renal artery disease. To assess the accuracy of renal artery duplex scanning for the purpose of diagnosing atherosclerotic renal artery stenosis, we compared the findings of renal arteriograms to the results of duplex scanning in 41 patients. Using an increase of renal artery peak systolic flow velocity of greater than 180 cm/sec, duplex scanning was able to discriminate normal from diseased renal arteries with a sensitivity of 95% and a specificity of 90%. Using the principle that blood flow velocity across a stenosis is roughly proportional to the degree of stenosis, it appeared that a ratio of the peak velocity in the renal artery to the aorta (RAR) of greater 3.5 predicted a greater than 60% diameter reduction of that renal artery, which is felt to be a significant stenosis. Forty-eight vessels were classified as having a greater than 60% diameter reduction by arteriography. Using the RAR of greater than 3.5, duplex scanning agreed in 44 renal arteries (sensitivity 92%). In the 26 renal arteries where arteriography showed a less than 60% diameter reduction, duplex scanning agreed in 16 vessels and correctly detected a focal narrowing in nine of the remaining ten vessels. Ten of 11 occluded renal arteries were correctly identified by duplex scanning. Duplex scanning determined the location of the renal artery lesion with an accuracy of 95% (kappa 0.74). Since duplex scanning can accurately demonstrate and locate focal renal artery stenosis, we believe it may become an accurate screening test for renovascular hypertension. 
Histopathological validation of high frequency epicardial echocardiography of the coronary arteries in vitro. The accuracy and reliability of measurement of coronary artery dimensions and detection of atherosclerotic lesions by high frequency epicardial echocardiography were compared with histopathological results. Ten pressure perfused human hearts were examined in vitro with a 10 MHz (Diasonics) transducer and a 7.5 MHz (Vingmed/Sonotron) transducer. There was close agreement between ultrasound and pathological measurements of coronary artery luminal diameter. Qualitative changes in wall structure such as diffuse wall thickening and calcification were readily identified; however, the resolution of the transducers was not high enough accurately to measure wall dimensions in normal coronary arteries. Coefficient of variation measurements for intra and inter observer variability (5.2% and 6.9% respectively) showed excellent reproducibility. The technique was accurate in identifying atherosclerotic lesions, imaging arteries distal to an occlusion, locating deeply sited arteries, and identifying complete obliteration of an artery. Intraoperative video playback and transducer miniaturisation may minimise problems caused by cardiac movement and restricted access. With these developments intraoperative assessment of coronary artery disease may become a real possibility. 
The natural history of diabetic femoral neuropathy Diabetic femoral neuropathy is an uncommon, unpleasant and sometimes disabling condition, on account of both pain and muscular atrophy, whose long-term prognosis has not previously been documented. We have reviewed a group of 27 patients up to 14 years (median 62 months) after diagnosis; 18 of these were re-examined after an average of nearly 4 years (median 45 months). The condition was more common in non-insulin-dependent diabetics (88 per cent), in men (59 per cent) and in older patients (median age at diagnosis 64 years). The neuropathy was bilateral (10 cases) or unilateral (17 cases); five patients with unilateral neuropathy developed femoral neuropathy on the opposite side, usually within a few weeks of the first episode. Recovery was apparent after 3 months and usually complete by 18 months; only two of the 27 patients had severe relapses. No patients remained disabled, although there were minor residual symptoms and signs in half of the patients (2 cm reduction in thigh circumference and diminished reflexes). The outlook for femoral neuropathy, even in its most severe form, is therefore very good: residual features are demonstrable but do not cause symptoms, and relapses after the first few weeks are very rare. 
Effects of a multidimensional cardiopulmonary rehabilitation program on psychosocial function. The effects of participation in a structured, outpatient cardiac rehabilitation program on psychosocial function after acute myocardial infarction or coronary artery bypass surgery, or both, were evaluated prospectively in 141 patients who were married or living with "a significant other" (89% men, mean [+/- standard deviation] age 63 +/- 9 years old). Forty-one patients who were participants in a 3-month cardiac rehabilitation program were compared with 100 patients who did not participate in a formal program. On average, patients in both groups were well educated, older Caucasians who had minimal cardiac dysfunction (New York Heart Association class I or II). Patients in the 2 groups were not different at baseline in sociodemographic or clinical characteristics or in any of the dependent measures of anxiety, depression, psychosocial adjustment to illness or marital adjustment. Six months after initial testing, patients who attended cardiac rehabilitation were significantly less anxious (F[1,139] = 5.09, p = 0.03), less depressed (F[1,139] = 8.39, p = 0.004), had better psychosocial adjustment (F[1,139] = 5.87, p = 0.02), and were more satisfied with their marriages (F[1,139] = 8.6, p = 0.004) than nonparticipants. The findings support the effectiveness of group cardiac rehabilitation for this subgroup of patients in facilitating their psychosocial recovery after an acute cardiac event. 
Plasma norepinephrine concentrations during resuscitation in the dog. The objective of this study was to evaluate whether the adrenal glands contribute to the increase in plasma norepinephrine concentrations during cardiopulmonary resuscitation, by releasing norepinephrine and/or by secreting epinephrine that facilitates the release of norepinephrine from sympathetic nerve endings via stimulation of presynaptic beta receptors. The experiments were performed in adrenalectomized and in sham-operated dogs. In adrenalectomized dogs the increase in plasma norepinephrine concentrations during cardiopulmonary arrest and basic life support (BLS) was markedly smaller than in sham-operated dogs. Intravenous infusion of physiologic doses of epinephrine during BLS in adrenalectomized animals did not influence the plasma norepinephrine concentrations. These data indicate that, as suggested by others, the marked increase in plasma norepinephrine concentrations during BLS in dogs is mainly of adrenomedullary origin. They also suggest that presynaptic facilitation of norepinephrine release by epinephrine is not important, but further experiments using higher doses of epinephrine are necessary. 
Defective lymphokine-activated killer cell generation and activity in acute leukemia patients with active disease. In 26 myeloid and lymphoid acute leukemia patients at presentation the capacity to generate interleukin-2 (IL-2)-induced lymphokine-activated killer (LAK) cells effective against the natural killer (NK)-resistant Raji cell line, as well as the susceptibility of the blasts to normal peripheral blood (PB) LAK cells and to autologous LAK effectors was analyzed. The overall PB LAK activity against Raji cells was significantly lower in acute leukemia patients compared with normal controls (mean, 1,473 +/- 971 SD LU/10(8) LAK effectors v 3,340 +/- 1,862; P less than .001). The sensitivity of the blasts to autologous LAK cells was also significantly lower than to normal LAK effectors (517 +/- 593 LU/10(8) LAK effectors v 1,304 +/- 1,066; P less than .01). When the data were analyzed independently, four patterns of behavior could be recognized. The relatively largest group (9 of 26) included patients in whom effective LAK cells could be generated against the Raji line, but in whom the blasts were resistant to autologous PB-LAK effectors while being susceptible to normal LAK cells (defective specific LAK activity). In 5 of 26 cases, an incapacity to generate LAK activity against both allogeneic and autologous target cells was observed (defective LAK generation). In six further cases, the blasts were resistant to both allogeneic and autologous LAK populations, though the latter were effective against the Raji line (resistant blasts). The same defects could also be shown with bone marrow-derived LAK cells. Only in six cases did the leukemic blasts appear susceptible to autologous and allogeneic LAK cells. In four patients the analysis could be repeated at remission, and in three a restoration of the LAK function against the primary blasts was recorded. In the 10 cases studied at relapse, the blasts were resistant to autologous LAK effectors in nine and to normal LAK in seven. These data demonstrate that in most acute leukemia patients with active disease, a defect of the LAK machinery, either a deficient generation of LAK cells or the resistance of the blasts to LAK effectors, may be documented, pointing therefore to a possible contributory role of the LAK system in the control of leukemic cell growth. In view of the frequent normalization of the autologous LAK activity at the time of remission, immunotherapy with IL-2/LAK cells should be primarily aimed to patients with minimal residual disease. 
Pharyngeal pouch carcinoma: two unusual cases. Two patients with carcinomata arising in pharyngeal pouches are reported. In one, the tumour was detected preoperatively by a contrast radiographic study. In the second the lesion was a carcinoma in situ. The English literature is reviewed with reference to these two unusual features. 
Middle ear inflammatory mediators and cochlear function. Sensorineural hearing loss (SNHL) has been documented in patients with otitis media. Despite a number of clinical and pathologic works dealing with this common problem, animal studies searching for possible relationships between the middle ear inflammation and cochlear function remain insufficient. Bacterial inoculation and ototoxins and inflammatory products in the middle ear cavity cause SNHL in rodents. Human serum albumin placed in the middle ear cavity in chinchillas also produces SNHL, owing to the effects of nonspecific inflammation in the middle ear cavity. Most of the middle ear inflammatory mediators enter the inner ear through the round window route, and alteration of the permeability of the round window membrane plays an important role in causing cochlear dysfunction. Although an immunologic response in the middle ear plays an important role in otitis media, the immunologic response in the inner ear as it relates to middle ear inflammatory mediators requires further study. 
Cerebrospinal fluid leaks and meningitis in acoustic neuroma surgery. Cerebrospinal fluid leaks and associated meningitis are the most common life-threatening complications of surgery for acoustic neuromas. This retrospective study reviews 319 patients who had surgery for 321 acoustic tumors at the Sunnybrook Health Sciences Center, University of Toronto, from April 1975 to March 1990. Cerebrospinal fluid leaks occurred after 13.4% of primary tumor operations. Surgical repair was required in 6.2% of all patients; 4.4% needed more than one operation. Meningitis occurred in 5.3% of all patients. These complications were more common in larger tumors and after the combined translabyrinthine middle fossa approach. Transnasopharyngeal eustachian tube obliteration was used to stop recurrent cerebrospinal fluid leaks in two patients. 
Progesterone receptor gene restriction fragment length polymorphisms in human breast tumors. We examined the progesterone receptor (PgR) gene in tissue from both primary human breast tumors and normal placentas, detecting restriction fragment length polymorphisms (RFLPs) with the restriction endonucleases Pst I/Sst I and HindIII. There was a general agreement of the Pst I and Sst I polymorphisms in any individual tumor, suggesting that they define two alleles in the human PgR locus, one being characterized by a deletion of about 300 base pairs with respect to the other. Both primary human breast tumor specimens (n = 36) and human term placentas (n = 48) displayed similar allele frequencies and typical mendelian distribution of these Pst I/Sst I alleles. The previously reported HindIII PgR RFLP was also investigated in 132 breast tumors. The HindIII PgR gene RFLP did not display typical mendelian distribution in the breast tumors; the factors affecting the HindIII allele frequencies are presently unknown. Neither the HindIII RFLP nor the deletion defined by Pst I and Sst I correlated with PgR expression as determined by a ligand-binding assay, suggesting that neither is related to the heterogeneity of PgR expression seen in breast tumors. 
Destructive lesions in demyelinating disease. Three cases are presented in which clinical and radiological features suggested the diagnosis of glioma but surgical biopsy revealed a demyelinating process, with tissue destruction and cyst formation in two. One patient had clinically definite multiple sclerosis. Two had probable acute disseminated encephalomyelitis. Treatment with high dose steroids is appropriate when there is clinical or investigative evidence to suggest the presence of demyelinating disease, before deciding on biopsy. 
Transmural distribution of myocardial edema by NMR relaxometry following myocardial ischemia and reperfusion. To determine the distribution and extent of myocardial edema resulting from ischemia and reperfusion, seven open-chest dogs underwent occlusion of the left circumflex coronary artery for 2 hours (group I), and 10 underwent occlusion for 2 hours and reperfusion for 2 hours (group II). Proton nuclear magnetic resonance spectroscopy (T1 and T2 relaxation times) and percent water content were determined to quantitate the amount of edema. There was a transmural increase of the T1 relaxation time of the central ischemic zone in groups I and II, although this increase was significantly greater in group II in both the subendocardium (group I = 707.8 +/- 12.5 msec, group II = 813.2 +/- 36.2 msec; p less than 0.01) and subepicardium (group I = 641.7 +/- 20.5 msec, group II = 760.5 +/- 34.7 msec; p less than 0.01). These increases were also observed in the T2 weighted relaxation time in the subendocardium (group I = 54.7 +/- 0.8 msec, group II = 78.7 +/- 6.3 msec; p less than 0.005) and subepicardium (group I = 54.0 +/- 1.4 msec, group II = 73.1 +/- 4.0 msec; p less than 0.001). Transmural differences were evident between the myocardial layers with increased T1 relaxation times (p less than 0.01) in the subendocardium in both groups. Similar increases were noted in the percent water content of the myocardium. Thus T1 and T2 relaxation times lengthened with an increase in myocardial water content following occlusion, and these relaxation times were augmented by reperfusion. We conclude that ischemia-induced edema occurs in a transmural distribution from subendocardium to subepicardium following occlusion, and this edema is further enhanced by reperfusion. 
Tubal occlusion after inguinal hernia repair. A case report. Midtubal occlusion and infertility occurred subsequent to an inguinal hernia repair. Recognition of the traumatic etiology is important because other causes of midtubal obstruction, such as endometriosis, tuberculosis and adenomatoid tumor of the oviduct, may be considered contraindications to reconstructive surgery. Once recognized, the condition is highly amendable to microsurgical reconstruction. 
Role of fine catheter peritoneal cytology and laparoscopy in the management of acute abdominal pain. Laparoscopy and fine catheter peritoneal cytology (FCPC) have been advocated as aids in the assessment of acute abdominal pain. In all, 411 patients admitted to a district general hospital during a 10-month period were managed using a standard protocol incorporating these techniques. After initial assessment by a surgical registrar, 151 patients were excluded from further progress through the protocol (age less than 16 years, definite diagnosis made or contraindication to FCPC. The remaining 260 patients were placed in one of four management groups: (A) urgent operation (23 patients); (B) 'look and see' (40 patients); (C) 'wait and see' (59 patients); (D) urgent operation not indicated (138 patients). Eighty-eight of 99 patients (88 per cent) in groups B and C, where the need for operation was uncertain, underwent successful FCPC and 39 patients (39 per cent) underwent laparoscopy. In these patients the initial registrar management decision proved to be incorrect in 33 cases (33 per cent), but by following the protocol the number of management errors actually made was reduced to 13 (13 per cent, P less than 0.001). This would have been reduced to 8 per cent if the protocol had not been violated in five patients. This study demonstrates the effectiveness of a protocol using FCPC and laparoscopy to improve the management of patients with acute abdominal pain. 
Association between the acquired immunodeficiency syndrome and infection with Salmonella typhi or Salmonella paratyphi in an endemic typhoid area. Eight cases of typhoid and paratyphoid fever were identified during a 4-year period in a cohort of 117 patients who were positive for human immunodeficiency virus in Lima, Peru. Asymptomatic patients with human immunodeficiency virus infection and patients with the lymphadenopathy syndrome had a typical clinical presentation and response to therapy. Patients with the acquired immunodeficiency syndrome who were culture positive for Salmonella typhi or Salmonella paratyphi presented with fulminant diarrhea and/or colitis; the two patients for whom at least 2 months of follow-up were available relapsed. In our cohort there were 0.06 cases of typhoid or paratyphoid per patient year of observation; this rate is approximately 60 times that in the general population in Lima, and 25 times that in the 15- to 35-year-old age group. Our data indicate that patients who are positive for human immunodeficiency virus are at significantly increased risk for infection with S typhi and S paratyphi, and suggest that the clinical presentation of these diseases in patients with the acquired immunodeficiency syndrome differs from that seen immunocompetent hosts. 
The roles of extracorporeal shock wave lithotripsy and percutaneous nephrostolithotomy in the management of pyelocaliceal diverticula. Various combinations of extracorporeal shock wave lithotripsy (ESWL*) and percutaneous nephrostolithotomy were used in the treatment of 40 stone-containing caliceal diverticula in 39 patients (16 men and 23 women). Only 1 of 26 patients (4%) treated with ESWL as a single modality became stone-free, although 9 (36%) became asymptomatic. Ten patients undergoing ESWL primarily eventually required percutaneous nephrostolithotomy due to persistence of symptoms and all became stone-free. A total of 14 patients underwent a percutaneous approach as a single modality, and the diverticula in 13 of these patients became stone-free, although 2 patients did have residual parenchymal fragments. Therefore, 21 of 24 patients (87.5%) became completely free of stones using the percutaneous approach. All patients managed with percutaneous nephrostolithotomy became free of symptoms. The complex nature of access during percutaneous nephrostolithotomy favors a 1-stage approach with direct puncture into the stone-containing diverticulum. Simultaneous fulguration of the diverticulum at percutaneous nephrostolithotomy is favored, since all 17 patients in whom this technique was used had complete obliteration of the diverticulum on followup contrast studies. These data suggest that caliceal diverticula should be managed with percutaneous nephrostolithotomy, since ESWL monotherapy is unlikely to produce a stone-free or symptom-free status. 
Five-year survival for cisplatin-based chemotherapy versus single-agent melphalan in patients with advanced ovarian cancer and optimal debulking surgery. The purpose of this study was to evaluate 5-year survival and 5-year progression-free survival in previously untreated patients with advanced ovarian cancer treated with single-agent melphalan in which very few patients underwent optimal debulking surgery (less than 2 cm residual) as compared with the patients treated with Cisplatin-based chemotherapy in which most patients underwent optimal debulking surgery. Significant increases in 5-year survival and 5-year progression-free survival were noted as we changed from the melphalan trial, in which only 14% underwent optimal debulking surgery, to PAC-H, in which 57% and the PAC trial in which 90%, respectively, underwent optimal debulking surgery. However, for those patients whose tumors were optimally debulked in the three trials, there were no statistically significant differences in median survival, median progression-free survival, 5-year survival, or 5-year progression-free survival in those patients treated with melphalan, PAC-H, or PAC. Without optimal debulking surgery, Cisplatin-based multiagent chemotherapy offered a small survival advantage. These results are similar to that reported by Gruppo Interregionale Cooperativo Oncologico Ginecologia, in which survival curves were identical for all the subgroups of chemotherapy regimens for those patients with residual disease less than 2 cm at the onset of chemotherapy whether they received (1) cyclophosphamide; (2) cyclophosphamide and Adriamycin; (3) cyclophosphamide, Adriamycin, and Cisplatin; (4) cyclophosphamide, Adriamycin, and hexamethylmelamine; (5) Cisplatin and cyclophosphamide; (6) low-dose Cisplatin; (7) high-dose Cisplatin; or (8) carboplatin. 
Menstrual symptoms in women with pelvic endometriosis. OBJECTIVE--To investigate menstrual symptoms in relation to pelvic pathology. DESIGN--A prospective questionnaire-based study. SETTING--Aberdeen Royal Infirmary, Scotland. SUBJECTS--1250 questionnaires were sent out prior to planned admission and 1200 women (96%) brought the completed questionnaires. They comprised 598 women undergoing laparoscopic sterilization, 312 having laparoscopy because of infertility, 156 having laparoscopy because of chronic pelvic pain and 134 women undergoing abdominal hysterectomy for dysfunctional uterine bleeding. MAIN OUTCOME MEASURES--The occurrence of dysmenorrhoea, menorrhagia, menstrual regularity, premenstrual spotting, deep dyspareunia and pelvic pain in women with either endometriosis and post infective pelvic adhesions or a normal pelvis. RESULTS--Menorrhagia, menstrual irregularity and premenstrual spotting occurred with equal frequency in all groups. Deep dyspareunia, pain after intercourse and recurrent pain unrelated to menstruation or coitus was more common in women with endometriosis and those with post infective pelvic adhesions than in those with a normal pelvis. Dysmenorrhoea appears to be more prevalent among women having endometriosis. CONCLUSIONS--Menstrual symptoms, while raising a high index of suspicion for endometriosis, are not entirely reliable as indicators of disease. Dysmenorrhoea is the most common reported symptom in endometriosis sufferers. Diagnostic laparoscopy should be considered before institution of treatment in women complaining of pelvic pain and menstrual symptoms. 
In vitro maturation of mononuclear phagocytes and susceptibility to HIV-1 infection. In the present report, we have studied the in vitro transition of normal blood monocytes to macrophages by changes in cell morphology, and the expression of surface antigens with a panel of monoclonal antibodies. The maturation process was accompanied by notable changes in cell-surface markers in a time-dependent manner. The percentage of cells expressing CD11c, ICAM-1, HLA-DR, and Fc receptor class III increased while the CD4 and CD35 expression was markedly decreased. After demonstrating that in vitro monocytes mature to macrophages in a recognizable manner, we studied the susceptibility to HIV-1 infection at time points representing different stages of cell maturation. The results show that monocyte/macrophages are susceptible to HIV-1 infection at all stages of differentiation. However, the kinetics of virus replication depends on the degree of maturation at the time of infection. Two major patterns of replication were observed: Infection of monocytes resulted in efficient virus production measurable by reverse transcriptase activity in culture supernatant, whereas infection of fully differentiated macrophages yielded low but sustained virus release only demonstrable by p24 antigen assay. We were not able to detect differences in the capacity of the virus to infect and replicate in monocyte/macrophages with respect to cellular origin of the virus isolate and whether the viruses were laboratory-adapted strains or low-passaged patient isolates. 
Strategy for management of distal ileal Crohn's disease. We have determined the outcome of a defined policy for the management of distal ileal Crohn's disease using a prospective computer-based analysis of 139 patients diagnosed between 1970 and 1988 with a mean follow-up of 10 years. The policy in outline consists of conservative treatment for acute obstructive episodes, resection or strictureplasty for recurrent obstructive episodes, surgical treatment for abscess and fistula formation and specific medical treatment (corticosteroids, immunosuppressive therapy or metronidazole) for symptomatic non-obstructive disease. Twenty-nine patients had a benign course without resection. The remainder were treated surgically at some time but only 28 of these patients had specific treatment before operation. Thirty-three needed more than one resection and five needed more than three surgical procedures. Immediate, early or delayed surgical treatment did not affect the reoperation rates or the long-term outcome. Eleven patients died, ten of causes unrelated to Crohn's disease. Of the 128 living patients, 114 are fit and well, and only two are currently taking specific medication. Fourteen are unwell of whom six either need or have refused further surgery which could restore them to good health. This management policy has achieved excellent long-term results in nearly all patients, and our findings suggest that the timing of surgery and its nature are more important in determining outcome than specific medical therapy. 
Diphenhydramine toxicity in three children with varicella-zoster infection. Diphenhydramine hydrochloride is an antihistamine with anticholinergic properties that is frequently used both orally and topically for the temporary relief of pruritus. Significant systemic absorption may occur following topical administration of diphenhydramine in patients with varicella-zoster lesions. We describe three children with varicella-zoster infection (VZI) who developed bizarre behavior as well as visual and auditory hallucinations following topical applications of large amounts of diphenhydramine to the majority of skin surfaces. In two cases, oral diphenhydramine was also administered. Serum diphenhydramine concentrations approximated or exceeded those previously reported. In each case, a complete resolution of mental status abnormalities occurred within 24 hours after discontinuation of all diphenhydramine-containing products. Pharmacists and other health professionals should be aware of the potential toxicity of topical diphenhydramine in patients with VZI. 
Symptomatic cerebral vasospasm following tumor resection: report of two cases. The authors report two cases of symptomatic cerebral vasospasm following resection of an acoustic neuroma and a left sphenoid wing meningioma. Vascular spasm was documented by transcranial Doppler and angiography studies. Both patients responded to hypervolemic therapy. Possible mechanisms contributing to this rare complication are discussed. 
Posterior cricoarytenoid activity in normal adults during involuntary and voluntary hyperventilation. The effect of isocapnic hypoxia and hyperoxic hypercapnia on the electrical activity of the posterior cricoarytenoid (PCA) muscle was determined in eight normal adult humans by use of standard rebreathing techniques and was compared with PCA activity during voluntary hyperventilation performed under isocapnic and hypocapnic conditions. PCA activity was recorded with intramuscular hooked-wire electrodes implanted through a fiberoptic nasopharyngoscope. During quiet breathing in all subjects, the PCA was phasically active on inspiration and tonically active throughout the respiratory cycle. At comparable increments in respiratory output, hypercapnia, hypoxia, and voluntary hyperventilation appeared to be associated with similar increases in phasic or tonic PCA activity. During quiet breathing, the onset of phasic PCA activity usually occurred before inspiratory airflow and extended beyond the start of expiratory airflow. The duration of phasic PCA preactivation and postinspiratory phasic PCA activity remained unchanged during progressive hypercapnia and progressive hypoxia. The results, in combination with recent findings for vocal cord adductors, suggest that vocal cord position throughout the respiratory cycle during hyperpnea is actively controlled by simultaneously acting and antagonistic intrinsic laryngeal muscles. 
Isolated cryptococcosis of the adrenal gland. A case of isolated adrenal cryptococcosis is reported. A patient with a history of diabetes mellitus had symptoms of left flank pain. Roentgenological and sonographic findings of the adrenal gland were indicative of a malignant tumour. Tissue obtained from surgery showed fungal granuloma and a poorly encapsulated cryptococcal organism was identified by special stains. A post-operative serum cryptococcal antigen test was positive, and the patient was successfully treated with surgery and a course of amphotericin B. After a 7-month follow-up period, there is no evidence of recurrence or dissemination. 
Dexamethasone therapy in neonatal chronic lung disease: an international placebo-controlled trial. Collaborative Dexamethasone Trial Group. In a multicenter trial of steroid therapy for chronic neonatal oxygen dependence, 287 neonates were randomly allocated from around 3 weeks of age, to dexamethasone or placebo. Active treatment significantly reduced the duration of further assisted ventilation among infants who were ventilator dependent at entry (median days for survivors, 11 vs 17.5). There were no statistically significant differences between the total groups of survivors in time receiving supplemental oxygen and length of stay in hospital, although the trend favored the dexamethasone group. Twenty-five infants in each group died prior to hospital discharge; most were ventilator dependent at trial entry. Open treatment with steroids was later given to 18% in the active group and to 43% in the placebo group. There was no evidence of serious side effects; in particular, infection rates were similar in the two groups. 
Hemodynamic consequences of desmopressin administration after cardiopulmonary bypass. Desmopressin acetate is used to reduce blood loss after cardiac surgery. However, there have been reports that hypotension can occur with infusion of desmopressin and that postoperative blood loss is not reduced. In this randomized, double-blinded study, we investigated the effects of desmopressin on hemodynamics, coagulation, and postoperative blood loss in patients undergoing primary elective coronary artery bypass grafting (CABG). After reversal of heparin effect, 20 patients received desmopressin 0.3 micrograms.kg-1, infused over 15 min, and 20 patients received a placebo. Desmopressin produced a small but significant decrease in diastolic blood pressure when compared with the placebo (50.8 mmHg vs. 57.6 mmHg for the desmopressin- and placebo-treated groups, respectively; P = 0.0372). A 20% or greater decrease in mean arterial pressure was observed in 7 of 20 patients receiving desmopressin, whereas only one patient in the placebo-treated group experienced a decrease of this magnitude (P = 0.0177). Reductions in arterial pressure were secondary to decreases in systemic vascular resistance (SVR) (mean SVR before and after the drug infusion, 1,006 and 766 dyn.s.cm-5, respectively, for the desmopressin-treated group; and 994 and 1,104 dyn.s.cm-5, respectively, for the placebo-treated group; P = 0.0078). 
Cutaneous metastasis from papillary carcinoma of the thyroid gland. Cutaneous metastases from carcinoma of the thyroid gland are rare. We present the clinical, histologic, and immunohistochemical features of a solitary metastasis from papillary carcinoma of the thyroid. Our results indicate that this tumor can produce epithelial mucin and, therefore, must be differentiated from other metastatic carcinomas and from primary apocrine tumors of the skin. Positive staining for thyroglobulin confirmed the diagnosis in this case. 
Fibrous lesions of the gingiva: a histopathologic analysis of 204 cases. Two hundred four cases of fibrous lesions of the gingiva were studied histologically for the presence of calcified tissue, the nature of the connective tissue, the type of keratinization, and the degree of epithelial thickness. Initially these lesions were subcategorized into four specific entities, namely fibrous epulis, fibroepithelial polyp, calcifying fibroblastic granuloma, and ossifying fibrous epulis. It was found that 46.5% of the lesions contained calcifications. The connective tissue was represented predominantly by either the collagenous type (50.5%) or the mixed (cellular and collagenous) type (44.6%). It was also found that 36% of the lesions were ulcerated, and, of these, 79.5% were associated with the cellular type of connective tissue and calcifications. In an attempt to subcategorize the fibrous lesions into specific entities, it was found that 32 cases (15.7%) had mixed features. This fact supports the suggestion that these lesions are stages in the spectrum of a single disease process and should collectively be termed fibroblastic gingival lesions. However, it is also suggested that the two terms, namely peripheral fibroma and fibrous epulis with and without ossification, should be retained whereas the usage of other terminologies should be avoided. 
Significance of ipsilateral breast tumour recurrence after lumpectomy. Breast cancer treatment trials from the US National Surgical Adjuvant Breast and Bowel Project have established breast-conserving operations as a replacement for radical mastectomy (NSABP B-04), and have shown that in terms of survival free from distant disease there was no significant difference between lumpectomy, lumpectomy plus breast irradiation, and total mastectomy (NSABP B-06). 9-year follow-up data from B-06 are used here to address the issue of ipsilateral breast tumour recurrence (IBTR) and the development of distant disease, a question with important clinical and biological implications. A Cox regression model on fixed co-variates (ie, features such as tumour type or size present at surgery and not subsequently alterable) and on IBTR, which is time dependent and not fixed, revealed that the risk of distant disease was 3.41 times greater after adjustment for co-variates in patients in whom an IBTR developed. IBTR proved to be a powerful independent predictor of distant disease. However, it is a marker of risk for, not a cause of, distant metastasis. While mastectomy or breast irradiation following lumpectomy prevent expression of the marker they do not lower the risk of distant disease. These findings further justify the use of lumpectomy. 
Prevalence of peripheral neuropathy in the Parsi community of Bombay. We carried out a door-to-door survey to screen for neurologic diseases, including peripheral neuropathy, in a community of 14,010 Parsis living in housing colonies in Bombay, India. The most common neurologic disorder was peripheral neuropathy with 334 cases (2,384 cases/100,000 population). The most common neuropathy was compressive, with diabetes the most common noncompressive etiology. There was no leprosy, and nutritional neuropathies were rare. 
A pilot study of neoadjuvant chemotherapy with 5-fluorouracil and cisplatin with surgical resection and postoperative radiation therapy and/or chemotherapy in adenocarcinoma of the esophagus. Fifteen patients with potentially resectable adenocarcinoma of the esophagus were treated with two cycles of preoperative chemotherapy with 5-fluorouracil (5-FU) and cisplatin (DDP). Response to chemotherapy was evaluated by comparative barium swallow, computerized chest tomography, esophagoscopy, and change in clinical symptomatology. Eleven patients (73%) were resected, two (13%) were explored and found inoperable, and two (13%) were not subjected to surgery (one because of death related to toxicity and one due to progressive disease). Ten of eleven patients (91%) had gross residual tumor. One patient (9%) had residual microscopic disease only. One patient (7%) had complete clinical responses (CCR), five (33%) had partial clinical response (PCR), and nine (60%) had no response (NR). Five of 15 patients (or 45% of resected patients) remain free of disease. Median survival time was 18.47 months for all patients and 23.83 months for resected patients. 
Duodenobronchial fistula. Duodenobronchial fistulas are an extremely rare subgroup of abdominobronchial fistulas, which include bronchobiliary, gastrobronchial, enterobronchial, colobronchial, and splenobronchial fistulas. Only one case of a duodenobronchial fistula has been previously reported. Duodenobronchial fistulas occur as a complication of a duodenal injury. The characteristic symptoms are a cough that produces copious bilious secretions, shortness of breath, and fever. The diagnosis is made by contrast gastrointestinal studies. Treatment requires an abdominal approach with interruption of the fistula at its duodenal origin and control of the inciting inflammatory process. With prompt diagnosis and treatment, thoracic drainage or pulmonary resection should not be needed. 
Peritoneopericardial diaphragmatic hernia discovered at coronary bypass operation. A 68-year-old man was discovered to have a large peritoneopericardial hernia when operated on for coronary artery bypass. Such hernias are very unusual. The pathogenesis, clinical presentation, and management of this problem are discussed. 
Acute necrotizing pancreatitis: management by planned, staged pancreatic necrosectomy/debridement and delayed primary wound closure over drains. We reviewed our recent experience with management of 23 consecutive patients with acute necrotizing pancreatitis. All patients had documented necrotizing pancreatitis with parenchymal or peripancreatic necrosis. Our method of treatment has evolved from our previous approach of controlled open lesser sac drainage (marsupialization) to staged necrosectomy/debridement with delayed primary closure over drains. With this latter approach, hospital mortality was 4 of 23 patients (17 per cent), but significant morbidity still occurred in 12 of 23 patients (52 per cent). However, recurrent intra-abdominal abscess before discharge occurred in only one patient. We believe that this operative approach toward the severely ill patient with acute necrotizing pancreatitis who requires operative intervention will minimize the occurrence of intra-abdominal sepsis. 
CT of the pancreas in children. CT has become a frequently used imaging method for evaluating suspected pancreatic disease in children. Although the spectrum of CT findings in pancreatic disease is well documented in adults, there is a paucity of such information in children. Familiarity with CT patterns of pancreatic disease in childhood is important for diagnosis. In this essay, we illustrate the CT findings of pancreatic lesions in children. 
Pectus excavatum: a 15-year perspective. Pectus excavatum is relatively uncommon. Our experience with 177 children during a 15-year period produced changes in our surgical technique, which now includes a small transverse incision, minimal subcutaneous flap elevation, a muscle-relaxing incision over the fifth costal cartilage, complete resection of involved cartilage, use of Adkins' strut, suspension of sternum to strut, taut reefing of intercostal muscle, no tubes or drains, epidural analgesia, a patient-controlled analgesia device postoperatively, and eventual strut removal. Use of the evolved technique gives excellent cosmetic results, good functional results with minimal discomfort, and a shorter convalescent period. 
False aneurysm of the right internal mammary artery. False aneurysm of the internal mammary artery is an uncommon complication of median sternotomy. Clinical and radiological findings of 2 such cases are presented. At operative exploration neither was directly related to the presence of a sternal wire. 
Hypercarbic acidosis reduces cardiac resuscitability. BACKGROUND AND METHODS: Marked increases in myocardial hypercarbia and acidosis accompany cardiac arrest and resuscitation. To investigate whether hypercarbic acidosis independent of oxygenation is of itself detrimental to cardiac resuscitation, three groups of six Sprague-Dawley rats were ventilated with gas mixtures containing concentrations of inspired CO2 (FICO2) of 0.0, 0.3, or 0.5, with oxygen fractions held constant at 0.5. After 4 mins of ventricular fibrillation, mechanical chest compressions were initiated with a pneumatic thumper; 2 mins later, transthoracic defibrillation was attempted. RESULTS: Each animal ventilated with FICO2 of 0.0 or 0.3 was successfully resuscitated. However, none of the animals ventilated with FICO2 of 0.5, in which aortic pH was less than 6.67 and aortic PCO2 was greater than 200 torr (greater than 26.7 kPa), was resuscitated (p less than .001). This finding contrasted with a second control group of seven identically treated animals which, in the absence of cardiac arrest, demonstrated no adverse effects after ventilation with an FICO2 of 0.5. CONCLUSIONS: Increases in FICO2 to levels of 0.5 under conditions of constant arterial oxygenation and controlled coronary perfusion pressure preclude successful resuscitation in this rodent model of CPR. 
Endoscopic balloon dilatation as a therapeutic option in the management of intestinal strictures resulting from Crohn's disease. Endoscopic balloon dilatation was undertaken in seven patients who presented with obstructive symptoms resulting from Crohn's disease. Five patients had strictures from recurrent disease at the site of an ileotransverse anastomosis, one had duodenal stenosis and one a colonic stricture. The procedures were performed under intravenous sedation on one to four occasions (median 2) and were uncomplicated. Sustained improvement over an 18-24-month follow-up period was achieved in five patients, but dilatation was unsuccessful in two cases. Endoscopic balloon dilatation is a safe and effective option in selected patients with intestinal strictures resulting from Crohn's disease and may overcome the need for surgery. 
Definitive diagnosis of breast implant rupture by ultrasonography. Silicone breast implantation is entering its fourth decade. Our ability to monitor the integrity of "old" prostheses is questioned. Clinical and mammographic examinations are reliable indicators of implant rupture only if there has been gel migration away from the implant pocket. Ultrasonography is presented as a reliable, sensitive method of evaluation of implant integrity. It should be considered the definitive study of prosthesis integrity. When sonography is added to mammographic and clinical examination, the preoperative evaluation of symptomatic augmented breasts is complete. Ultrasonography may be considered with mammography in the routine breast examination of all previously augmented patients. 
External fistulas arising from the digestive tract. External abdominal fistulas that arise from the digestive tract are associated with high mortality and prolonged morbidity in terms of infection, malnutrition, and skin excoriation. Such external fistulas most commonly follow anastomotic leak after gastrointestinal surgery. We identified 58 patients seen over a 5-year period at the University of Louisville Hospitals because of external abdominal fistulas that arose from the stomach (8), duodenum (4), small intestine (26), colon (14), biliary tract (9), and pancreas (7). Fifteen patients had multiple fistulas and 32 had high-output fistulas (greater than 200 mL/day). Closure was achieved in 48 patients, and eight of the 10 patients whose fistulas remained open died. Overall mortality was 19%. Principles of management include control of infection, correction of fluid and electrolyte imbalance, nutritional support, proper wound care, and often operative intervention. Multiple staged operations over many months were particularly important in managing complex wounds with large abdominal wall defects and multiple fistulas. Fistula closure is the ultimate goal, and patience is important to achieve it. 
Neurogenic pulmonary edema: treatment with dobutamine. In the case of a patient with complicating subarachnoid hemorrhage, an infusion of dobutamine was followed by a massive diuresis and regression of severe neurogenic pulmonary edema. It is suggested that the reduction in total peripheral vascular resistance and the increase in cardiac contractility accounts for the observed beneficial effect and indicate that dobutamine is a suitable drug for the treatment of neurogenic pulmonary edema. 
Rhabdomyolysis and cutaneous necrosis following intravenous vasopressin infusion. A continuous IV infusion of vasopressin was administrated to a patient with cirrhosis of the liver and acute gastrointestinal bleeding from esophageal varices. In the first 24 hours, the patient developed rhabdomyolysis and cutaneous necrosis. Stopping vasopressin infusion resulted in relief of these lesions. The rarity of these complications suggests an idiosyncratic reaction of susceptible individuals that may be related to previous vascular disease or a failure in baroreceptor regulation. 
Health benefits of aerobic exercise. Regular aerobic exercise has significant cardiovascular benefits, including a reduction in incidence of and mortality from coronary artery disease--probably because of positive effects on blood lipid levels and blood pressure. Aerobic exercise can also be an important adjunct to a weight-loss program. Many persons who continue an exercise program do so because of its positive mental benefits, including reduction in anxiety and depression and modulation of stress levels. Aerobic exercise has a place in the management of diabetes, pregnancy, and aging. The problems associated with aerobic exercise are minimal compared with its benefits. 
Low back pain: review of diagnosis and therapy. Low back pain is a patient complaint frequently encountered in the emergency department setting. The disease entity is often a diagnostic challenge with a subtle presentation, but can be accompanied by significant neurovascular complications. Current topics of controversy include the utility of radiologic evaluation, pharmacologic and holistic treatment strategies, as well as guidelines for urgent referral of patients with lumbar pain. 
Color Doppler imaging provides accurate assessment of orbital blood flow in occlusive carotid artery disease. Color Doppler imaging was used to evaluate the hemodynamics of the ophthalmic vasculature in a case of complete internal carotid artery occlusion. This procedure, which allows rapid, noninvasive imaging, showed a partial ophthalmic artery obstruction with absent flow in the central retinal artery, central retinal vein, and nasal posterior ciliary arteries. Although altered perfusion of the retinal vessels may be evaluated clinically, assessment of blood flow in the ophthalmic and ciliary arteries previously could be evaluated only indirectly by intravenous fluorescein angiography. The color Doppler imaging findings were confirmed by intravenous fluorescein angiography and carotid arteriography. Color Doppler imaging represents a noninvasive method to diagnose abnormal blood flow of the ophthalmic artery and its branches and to evaluate serial changes of the circulation in a noninvasive manner. 
Association of hypovolemia after subarachnoid hemorrhage with computed tomographic scan evidence of raised intracranial pressure. Hypovolemic patients are more likely to suffer delayed cerebral ischemia and infarction after a subarachnoid hemorrhage (SAH). Prompt recognition and correction of hypovolemia may improve the outcome. We have identified computed tomographic (CT) scan findings that increase the probability of a patient presenting with hypovolemia soon after an SAH. The plasma volume (PV) of 25 patients admitted within 96 hours of an SAH was measured using radioiodinated serum albumin. The normal PVs were measured in an outpatient setting 6 months later or predicted from their total body water. Nine patients (36%) were found to be hypovolemic, defined as a fall in PV exceeding 10% of the normal PV (mean fall, 18 +/- 2%). Sixteen patients were normovolemic or hypervolemic (mean PV, +9 +/- 2%). The basal cisterns were compressed or obliterated on the CT scans of all hypovolemic patients compared with 12.5% of normovolemic patients (chi-square, 14.52; P less than 0.01). The probabilities of a patient being hypovolemic if the CT scan indicated raised intracranial pressure were high: hydrocephalus, P = 0.80; compression of the basal cisterns, P = 0.82; and compression of the basal cisterns associated with intracerebral hematoma or midline shift, P = 1.00. Patients with an SAH and radiological evidence of raised intracranial pressure should be considered at particular risk for systemic hypovolemia. 
Benign spinal nerve sheath tumors: their occurrence sporadically and in neurofibromatosis types 1 and 2. Benign spinal nerve sheath tumors (neurofibromas and schwannomas) often occur on dorsal nerve roots sporadically or in neurofibromatosis types 1 and 2. These are histologically benign tumors, and distinction between them is frequently not made by clinicians. To determine if there is a correlation between the histological pattern of benign spinal nerve sheath tumors and the type of neurofibromatosis, the clinical and pathological features of these tumors (86 surgical specimens and five autopsies) in 68 patients were reviewed. The patients were classified into one of four categories: neurofibromatosis type 1, neurofibromatosis type 2, uncertain, or sporadic. The diagnostic criteria used for neurofibromatosis types 1 and 2 were established by the National Institutes of Health. Patients who did not fulfill criteria for either neurofibromatosis type 1 or 2 but who had multiple nervous system tumors or other stigmata of neurofibromatosis were designated "uncertain." Spinal nerve sheath tumors were considered sporadic in 42 cases (40 schwannomas and two neurofibromas). In the 14 patients with neurofibromatosis type 1, all spinal nerve sheath tumors were neurofibromas. In six of the seven patients with neurofibromatosis type 2, all spinal nerve sheath tumors were schwannomas. One patient with neurofibromatosis type 2 had a spinal nerve sheath schwannoma and a tumor with features of both tumor types. The authors conclude that spinal nerve sheath tumors in patients with neurofibromatosis type 1 are neurofibromas. In contrast, spinal nerve sheath tumors occurring in neurofibromatosis type 2 or sporadically are most frequently schwannomas. The distinct histological features of these tumors may reflect different pathogenetic mechanisms even though they arise at identical sites in neurofibromatosis types 1 and 2. 
The effect of decompression on the natural course of spinal stenosis. A comparison of surgically treated and untreated patients. The clinical course of 19 untreated patients with spinal stenosis (mean age, 60 years) was compared with that of 44 patients treated surgically (mean age, 65 years). The time of follow-up was 31 and 53 months, respectively. About 80% of the patients had neurogenic intermittent claudication. In the follow-up, one third of the treated and one half of the untreated patients still had neurogenic claudication. By visual analogue-scale estimation, 60% of those treated surgically and 33% of the untreated patients felt better. Fifty-eight percent of the untreated patients were unchanged. Neurophysiologic changes showed progression in almost all cases; it was more pronounced in the treated patients. No proof of severe deterioration was found in the untreated patients, and observation for 2-3 years seems to be a good alternative to surgery. 
Continuous monitoring of cerebral oxygenation in acute brain injury: injection of mannitol during hyperventilation. Global cerebral oxygenation, perfusion pressure, and expired pCO2 were continuously monitored in 10 adults with acute severe closed head trauma. Cerebral oxygenation was monitored by fiberoptic catheter oximetry, which allowed simultaneous measurements of arterial and jugular bulb oxyhemoglobin saturation. Intracranial pressure levels over 20 mm Hg were recorded several times in all patients, in spite of sedation, muscle paralysis, and profound hyperventilation. Intracranial hypertension was frequently associated with oligemic cerebral hypoxia, identified as abnormally low jugular oxygen saturation in the presence of normal arterial oxygenation. Intracranial hypertension was then managed with intravenous administration of mannitol boluses, which yielded simultaneous decreases in intracranial pressure and increases in cerebral oxygenation to highly statistically significant levels. Monitoring cerebral oxygenation was clinically useful because it allowed identification of impaired cerebral oxygenation even when cerebral perfusion pressure was normal. It is therefore proposed as a new monitoring technique, to supplement conventional monitoring of cerebral perfusion pressure. 
Chronic central nervous system effects of acute organophosphate pesticide intoxication. The Pesticide Health Effects Study Group. Acute organophosphate pesticide poisonings cause substantial morbidity and mortality world wide; however, whether organophosphates cause chronic neurological sequelae has not been established. To see whether single episodes of acute unintentional organophosphate intoxication lead to chronic neuropsychological dysfunction, we carried out a retrospective study of agricultural workers in Nicaragua who had been admitted to hospital between July 1, 1986, and July 31, 1988, for occupationally related organophosphate intoxication. This "poisoned" group (36 men) was tested on average about two years after the episode of pesticide poisoning and compared with a matched control group. The poisoned group did much worse than the control group on all neuropsychological subtests, with significantly worse performance on five of six subtests of a World Health Organisation neuropsychological test battery and on 3 of 6 additional tests that assessed verbal and visual attention, visual memory, visuomotor speed, sequencing and problem solving, and motor steadiness and dexterity. Differences in neuropsychological performance could not be explained by other factors. The findings of a persistent decrease in neuropsychological performance among individuals with previous intoxication emphasise the importance of prevention of even single episodes of organophosphate poisoning. 
Preoperative and intraoperative fine needle aspiration cytology of pancreatic lesions. The aim of the present study was to describe our experience from 1976 through 1988 with fine needle aspiration (FNA) cytology of pancreatic lesions in 90 patients. Fine needle aspirations were performed preoperatively under ultrasound guidance (USG) in 46 patients, under computed tomographic guidance (CTG) in seven patients, and intraoperatively in 37 patients. Based on histologic, cytologic, and clinical findings, final diagnoses were reached in 80 patients, of whom 62 had malignant pancreatic disease (MPD) and 18 had benign pancreatic disease (BPD). The accuracy of cytologic diagnoses was verified by histologic, cytologic, and clinical findings. In 62 patients with MPD, the cytologic findings suggested malignancy in 54 patients, suspected malignancy in five, and did not reveal malignancy in three patients. Among 18 patients with BPD, all of the cytologic findings were reported as benign. The sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy for intraoperative FNA cytologic results were 96%, 100%, 100%, 91%, and 97%, respectively, and for USG FNA cytologic results were 94%, 100%, 100%, 78%, and 95%, respectively. No complications followed the procedure. Conclusions: Both transabdominal percutaneous imaging-guided and intraoperative FNA cytology of pancreatic lesions are simple, safe, and highly accurate methods in differentiation of benign from malignant pancreatic lesions. 
Stress erosive gastritis. Bleeding from stress erosive gastritis continues to be a potential problem in critically ill and injured patients, but fortunately its incidence has decreased dramatically over the last decade. The explanation for this circumstance is probably multifactorial, but clearly relates to our increased knowledge of its pathophysiology. This understanding has led to the routine use of measures to reduce intragastric acidity (luminal acid being a prerequisite for stress ulcer to occur), coupled with improved techniques for the treatment of shock and the accompanying gastric mucosal hypoperfusion (another prerequisite for the formation of stress ulcers). A number of measures have been used to lower intragastric acidity with H2 receptor blockers emerging as the agents of choice to accomplish this goal. In the unlikely event that bleeding occurs despite these prophylactic measures, aggressive medical management will result in cessation of hemorrhage in over 80% of patients. In those few individuals requiring surgery to control bleeding, no operation has emerged as the recognized procedure of choice. Thus, we believe that a conservative operative approach is indicated in this setting and recommend vagotomy and pyloroplasty with oversewing of the bleeding erosions as appropriate therapy for most patients requiring surgical intervention. 
Autonomic function in Friedreich's ataxia. Autonomic function studies were performed on 15 patients with Friedreich's ataxia, and the results compared with those of 76 healthy subjects. There was an increase in resting supine heart rate, attributed to cardiac abnormalities. Other tests of sympathetic and parasympathetic function were normal. The normal autonomic function studies are consistent with the pathological findings of degeneration predominantly of large diameter myelinated fibres with sparing of small myelinated and unmyelinated fibres. 
Tracheostomal stenosis after immediate tracheoesophageal puncture. The incidence of tracheostomal stenosis in a group of patients after total laryngectomy with or without pharyngectomy plus immediate tracheoesophageal or tracheogastric puncture was compared with that of a control group without puncture. The stenosis rate of the puncture group was significantly higher than that of the control group (19% vs 6%). The other probable etiologic factors for stomal stricture were similar in both groups. Analysis of the risk factors in the puncture group suggested a higher tendency of stenosis in females (43% vs 16%) and in patients receiving postoperative radiotherapy (29% vs 14%), although the difference failed to reach statistical significance. 
Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). SHEP Cooperative Research Group OBJECTIVE.--To assess the ability of antihypertensive drug treatment to reduce the risk of nonfatal and fatal (total) stroke in isolated systolic hypertension. DESIGN.--Multicenter, randomized, double-blind, placebo-controlled. SETTING.--Community-based ambulatory population in tertiary care centers. PARTICIPANTS.--4736 persons (1.06%) from 447,921 screenees aged 60 years and above were randomized (2365 to active treatment, 2371 to placebo). Systolic blood pressure ranged from 160 to 219 mm Hg and diastolic blood pressure was less than 90 mm Hg. Of the participants, 3161 were not receiving antihypertensive medication at initial contact, and 1575 were. The average systolic blood pressure was 170 mm Hg; average diastolic blood pressure, 77 mm Hg. The mean age was 72 years, 57% were women, and 14% were black. INTERVENTIONS.--Participants were stratified by clinical center and by antihypertensive medication status at initial contact. For step 1 of the trial, dose 1 was chlorthalidone, 12.5 mg/d, or matching placebo; dose 2 was 25 mg/d. For step 2, dose 1 was atenolol, 25 mg/d, or matching placebo; dose 2 was 50 mg/d. MAIN OUTCOME MEASURES.--Primary.--Nonfatal and fatal (total) stroke. Secondary.--Cardiovascular and coronary morbidity and mortality, all-cause mortality, and quality of life measures. RESULTS.--Average follow-up was 4.5 years. The 5-year average systolic blood pressure was 155 mm Hg for the placebo group and 143 mm Hg for the active treatment group, and the 5-year average diastolic blood pressure was 72 and 68 mm Hg, respectively. The 5-year incidence of total stroke was 5.2 per 100 participants for active treatment and 8.2 per 100 for placebo. The relative risk by proportional hazards regression analysis was 0.64 (P = .0003). For the secondary end point of clinical nonfatal myocardial infarction plus coronary death, the relative risk was 0.73. Major cardiovascular events were reduced (relative risk, 0.68). For deaths from all causes, the relative risk was 0.87. CONCLUSION.--In persons aged 60 years and over with isolated systolic hypertension, antihypertensive stepped-care drug treatment with low-dose chlorthalidone as step 1 medication reduced the incidence of total stroke by 36%, with 5-year absolute benefit of 30 events per 1000 participants. Major cardiovascular events were reduced, with 5-year absolute benefit of 55 events per 1000. 
A randomized clinical trial of ampicillin, gentamicin and clindamycin versus cefotaxime and clindamycin in children with ruptured appendicitis. This prospective, randomized, double-blind study compares the efficacy, safety and cost-effectiveness of ampicillin, gentamicin and clindamycin (AGC) or cefotaxime and clindamycin (CC) for the treatment of children with complicated appendicitis. Ninety-seven children were randomized. Forty-seven were assigned to the AGC regimen and 50 received CC. Forty-two patients in the AGC group had an appropriate therapeutic outcome, whereas 48 of 50 children who received CC completed the trial successfully (p = NS). There were no differences between the groups with reference to the duration of antibiotic administration, fever, leukocytosis or length of hospitalization. Complications of therapy were uncommon and neither regimen demonstrated a significant advantage from an economic standpoint. We concluded that, in childhood, complicated appendicitis can be treated with either CC or AGC with equal efficacy. 
The clinical diagnosis of splenomegaly. Assessing for the presence of splenomegaly is an important component of the physical examination. Although several methods of palpation and percussion of the spleen have been described, until recently they have not been validated by noninvasive imaging techniques such as ultrasonography, radionuclide scanning, and computed tomography that offer objective means to assess splenomegaly. We review the literature comparing various physical examination techniques with noninvasive imaging modalities and conclude that palpation and percussion of the spleen are complementary but frequently insensitive and that further studies are needed to evaluate the efficacy of specific diagnostic methods. 
The failed ulnar nerve transposition. Etiology and treatment. Various procedures have been recommended for the treatment of cubital tunnel syndrome. Simple decompression in situ, medial epicondylectomy, subcutaneous transposition, intramuscular transposition, and submuscular transposition all have their advocates. The results of the surgical treatment for cubital tunnel syndrome are related to the severity of the compressive neuropathy at the time of diagnosis and to the adequate decompression of the nerve at all sites of potential compression at the time of surgical treatment. Fourteen patients who had previously undergone surgical treatment for cubital tunnel syndrome were evaluated because of persistent pain, paresthesia, numbness, and motor weakness. All patients had documented persistent compression of the ulnar nerve on clinical and electromyographic evaluation. The indication for repeat surgical exploration in all patients was unremitting pain despite nonoperative treatment. All patients had been treated by neurolysis and submuscular transposition of the ulnar nerve as described by Learmonth. The causes of continued pain after initial surgery included retention of the medial intermuscular septum, dense perineural fibrosis of the nerve after intramuscular and subcutaneous transposition, adhesions of the nerve to the medial epicondylectomy site, and recurrent subluxation of the nerve over the medial epicondyle after subcutaneous transposition. Revision surgery was found to be highly successful for relief of pain and paresthesias; however, the recovery of motor function and return of sensibility were variable and unpredictable. 
Role of calcium channel blockers in protection against experimental renal injury. The available evidence indicates that the first generation calcium channel blocker verapamil has a protective effect against both acute and chronic renal failure. At the cell membrane, verapamil helps minimize the effects of excess calcium influx after ischemic injury, evidenced by reduced uptake of 45Ca, thus lessening tubular injury from both calcium-activated phospholipases and mitochondrial calcium overload. In experimental chronic renal failure, the long-term administration of verapamil protects against renal dysfunction and damage, independent of any effect on systemic mean arterial pressure. Protective effects of verapamil are delineated in several models, supporting the presented hypothesis of the pathogenesis of renal failure. 
Clinical significance of small-intestinal microsporidiosis in HIV-1-infected individuals To assess the importance of microsporidiosis of the small intestine in the pathogenesis of chronic diarrhoea in HIV-1-infected individuals, duodenal biopsy samples from the following three patient groups were prospectively evaluated for bacterial, viral, and parasitic pathogens by standard methods, and for microsporidia by light microscopy: 55 consecutive HIV-1-antibody-positive subjects with unexplained diarrhoea of at least 3 weeks duration (group A); 38 HIV-1-seropositive subjects without diarrhoea (group B) who consecutively underwent upper gastrointestinal endoscopy for various reasons; and 7 patients without known risk factors for HIV infection with chronic unexplained diarrhoea (group C). In groups A and B most subjects had had previous AIDS-defining opportunistic infections and the median peripheral blood CD4 lymphocyte count was less than 0.1 x 10(9)/l. Microsporidia were detected as the single pathogen in 15 of the group A compared with 1 (in whom diarrhoea subsequently developed) of the group B patients (p = 0.001) and none of the group C patients. With the exception of 4 of the group A patients, no other intestinal pathogens were identified in any of the patients. The median peripheral blood CD4 count was significantly lower in patients with detectable microsporidia than in those without microsporidiosis (0.03 x 10(9)/l vs 0.06 x 10(9)/l; p = 0.03); in all patients with microsporidiosis, the CD4 count was equal to or less than 0.1 x 10(9)/l. 13 patients with microsporidiosis were treated with metronidazole, in 10 of whom treatment led to a substantial improvement or disappearance of diarrhoea within days of starting therapy, but did not result in eradication of the parasite in the 5 patients who underwent repeat biopsy. The findings suggest that small-intestinal microsporidiosis is an important cause of chronic unexplained diarrhoea in HIV-1-infected individuals with pronounced cellular immune deficiency. This infection should therefore be added to the list of AIDS-defining opportunistic infections. 
Differences in vascular reactivity in models of ischemic acute renal failure. To determine the mechanism of observed differences in vasoreactivity in norepinephrine-induced (NE) and renal artery clamp (RAC) models of ischemic acute renal failure (ARF), induction renal blood flow (RBF) was measured and vascular reactivity examined one week thereafter in NE- and RAC-ARF rat kidneys that had identical levels of renal dysfunction. Morphology also was compared at 48 hours and one week. In NE-ARF, RBF was 14% during 90 minutes of induction and by 60 minutes post-NE infusion was only 18% of baseline. In contrast, in RAC-ARF RBF was effectively 0 for 75 minutes but returned to 95% of baseline by 60 minutes after clamp release. At one week there was a paradoxical increase in renovascular resistance (RVR) to renal perfusion pressure (RPP) reduction in the autoregulatory range and an augmented vasoconstriction to renal nerve stimulation (RNS) in NE-ARF, but no change in RVR and minimal reduction in RBF to these same respective stimuli in RAC-ARF (both different at P less than 0.001). NE-ARF were more sensitive to intrarenal norepinephrine than RAC-ARF kidneys (P less than 0.001). Neither NE- nor RAC-ARF kidneys responded to endothelium-dependent acetylcholine (ACh). Vasodilation to endothelium-independent prostacyclin (PGI2) in NE- was similar to sham-ARF, but there was an attenuated response in RAC-ARF kidneys (P less than 0.001). Morphology at 48 hours showed smooth muscle necrosis in half of the resistance vessels in RAC- but in less than 10% of those in NE-ARF. Except for a slightly greater frequency of tubular casts at 48 hours in RAC-ARF, tubular injury was indistinguishable. It is concluded that NE-ARF has evidence of a predominant functional endothelial vascular injury while RAC-ARF has both morphologic and functional evidence of a predominant smooth muscle injury. Differences in vascular injury between the two models, at least in part, may be the consequence of differences in severity of initial ischemia and/or the rates of recovery of RBF; however, an additional or separate toxic effect of infused NE cannot be excluded. 
S100 protein-positive sustentacular cells in malignant and locally aggressive adrenal pheochromocytomas. The absence or presence of S100-positive sustentacular cells has been previously shown to be correlated with benign and malignant pheochromocytomas and paragangliomas. We evaluated a total of 17 malignant and recurrent or locally aggressive adrenal pheochromocytomas for their quantity of sustentacular cells. An absence of sustentacular cells was demonstrated in the majority of malignant cases, while the locally aggressive or recurrent group usually contained an abundance of these cells. However, in one malignant case a constant moderate number of sustentacular cells in the primary site and in two sequential metastases was found. We conclude that the absence of sustentacular cells in pheochromocytomas may indicate a lesion with a greater potential for metastasis and that sustentacular cells, when they are present in a malignant pheochromocytoma, are an integral part of the tumor. 
Nd-YAG laser hyaloidotomy for malignant glaucoma following one-piece 7 mm intraocular lens implantation. Three cases of malignant glaucoma following extracapsular cataract extraction with 7 mm one-piece posterior chamber intraocular lens implantation are presented. Nd-YAG laser hyaloidotomy was successfully performed in all eyes, but was difficult and required several sessions in two eyes. In the third eye, which had a sector iridectomy, laser hyaloidotomy applied over the edge of the lens optic through the iridectomy resulted in brisk deepening of the anterior chamber and reduction of intraocular pressure. We propose that the one-piece 7 mm optic posterior chamber intraocular lens may constitute an obstacle to successful hyaloidotomy, mainly owing to its large size, as it may block aqueous percolation from the vitreous into the anterior chamber. Eyes prone to develop malignant glaucoma after surgery should have a sector or large peripheral iridectomy to facilitate postoperative Nd-YAG laser hyaloidotomy if required. 
Emergency pulmonary resection for pneumonia. High morbidity and mortality. Emergency pulmonary resection was performed because of complicated pneumonia in eight patients (5 pneumonectomies, 2 lobectomies, 1 bilobectomy) over a 2-year period. The patients' age range was 5 months to 43 years. The indications were rapid aggravation of respiratory insufficiency in children with staphylococcal pneumonia and enlarging pneumatoceles, and massive hemoptysis in patients with chronic destructive pneumonia. Two patients died after pneumonectomy, one from contralateral aspiration and one from cardiogenic shock. Postoperative complications occurred in four cases--bronchopleural fistula and pyopneumothorax in three and thoracic empyema with massive chest-wall infection in one. Only two patients had an uneventful postoperative course. Complications of pulmonary necrosis in pneumonia may dictate urgent pulmonary resection, often pneumonectomy. Surgery will be life-saving in most cases, but high morbidity is to be expected. 
Myocardial rupture. Your patient's survival may depend on you. Myocardial rupture is the second leading cause of in-hospital death from acute myocardial infarction. It is most likely to occur in the elderly, women, and patients with transmural infarction and no previous history of angina. A high index of suspicion is critical to the diagnosis. Myocardial rupture should be suspected when recurrent chest pain or hemodynamic instability develops after myocardial infarction. Rapid intervention and appropriate infarct-limiting therapy may reduce the mortality rate of this catastrophic complication. 
Abdominal wall Actinomyces abscess associated with an intrauterine device. A case report. An abdominal wall Actinomyces abscess occurred in a woman with an intrauterine device. Contributing factors were local trauma, spread from surrounding colonized body sites and symbiotic growth of other anaerobes. The diagnosis was based on the histologic finding of the sulfur granule. Special studies may be needed to distinguish this condition from other, similar ones (Nocardia, botryomycosis). 
Radionuclide assessment of ventricular function and risk stratification after myocardial infarction. Prognosis after acute myocardial infarction is determined primarily by left ventricular function and by the extent to which additional coronary obstructions jeopardize viable myocardium. Radionuclide ventriculography is well suited for noninvasive assessments of resting and exercise ventricular function after acute myocardial infarction. The prognostic importance of resting left ventricular function after acute myocardial infarction is well established. Several studies have reported the prognostic utility of submaximal exercise radionuclide ventriculography at the time of hospital discharge. Patients with globally depressed left ventricular function after acute myocardial infarction are at increased risk for cardiac death, while patients with normal resting ventricular function but abnormal function during exercise appear to be at risk for nonfatal ischemic events. The development of gated tomographic techniques and new radiopharmaceuticals will make available more accurate and detailed assessments of ventricular function and combined assessments of function and perfusion. These new developments require further investigation but appear to be promising new techniques with the potential for providing improved assessments of prognosis after acute myocardial infarction. 
Intracerebral hemorrhage after lumbar myelography with iohexol: report of a case and review of the literature. Intracranial hemorrhage is an uncommon complication of dural puncture. In most instances, hematomas are subdural; they may be unilateral or bilateral. Rarely are intraparenchymal cerebral hemorrhages related to dural puncture. This report describes a delayed occurrence of bilateral intraparenchymal hemorrhages in a 38-year-old woman 7 days after lumbar myelography with iohexol. A review of the literature is presented. 
Is the serum cholesterol-coronary heart disease relationship modified by activity level in older persons? Although coronary heart disease remains a leading cause of death and disability in old age, the relationship of serum cholesterol level to risk of coronary heart disease in old age is controversial. Data for 2,388 white persons aged 65-74 who participated in the National Health and Nutrition Examination Survey (NHANES) I Epidemiologic Follow-up Study (NHEFS) were examined to determine the relationship of serum cholesterol level to coronary heart disease incidence and whether activity level would modify this relationship. While there was no overall relationship between serum cholesterol level and coronary heart disease risk in either men or women, the relationship between serum cholesterol level and coronary heart disease differed within activity groups. For persons who were more active, serum cholesterol level was associated with a graded increase in risk of coronary heart disease, from 1.3 (95% CI 0.7, 2.3) in those with serum cholesterol level of 4.7-5.1 to 1.7 in those with serum cholesterol level of 6.2 mmol/L or more (95% CI 1.0, 2.7), when compared with those with serum cholesterol level below 4.7. For the least active persons, all levels of cholesterol were associated with a significant inverse relative risk, including cholesterol of 6.2 mmol/L or more (Relative risk = 0.4 (95% CI 0.2, 0.7]. These data suggest that factors such as activity level may modify the serum cholesterol-coronary heart disease association in old age. The serum cholesterol-coronary heart disease association in more active older persons resembles that seen in younger populations, whereas the association in less active persons is that of serum cholesterol level and risk of cancer or death. The modification of the serum cholesterol-coronary heart disease association by activity level may have implications for appropriate clinical management as well as appropriate design of research studies of this association. 
Elevated brain concentrations of 1,4-benzodiazepines in fulminant hepatic failure BACKGROUND. Increased gamma-aminobutyric acid (GABA) neurotransmission has been implicated in the pathogenesis of hepatic encephalopathy. The mechanism by which GABA-ergic activity is increased in hepatic failure is unclear, but recent studies in animals with encephalopathy due to fulminant hepatic failure suggest that GABA-ergic neurotransmission may be increased by the presence of elevated concentrations of benzodiazepine agonists such as diazepam and N-desmethyldiazepam. METHODS AND RESULTS. Samples of frontal cortex were obtained at autopsy from 11 patients with hepatic encephalopathy who died of acetaminophen-induced fulminant hepatic failure and 8 patients who died of cardiovascular disease or trauma. None of the 19 patients had received benzodiazepines while hospitalized. Chromatographic analyses of extracts of these samples revealed 4 to 19 peaks representing substances that inhibited the binding of a radiolabeled imidazobenzodiazepine ([3H]flumazenil) to its receptors. Several of these peaks had retention times corresponding to those of known 1,4-benzodiazepines. Ultraviolet- and mass-spectroscopic analysis confirmed that two of these peaks represented diazepam and N-desmethyldiazepam. The patients who died of fulminant hepatic failure could be divided into two groups: six who had had significantly elevated brain concentrations (2-fold to 10-fold higher than normal) of substances inhibiting the binding of [3H]flumazenil and five who had normal concentrations. CONCLUSIONS. Brain concentrations of substances inhibiting the binding of [3H]flumazenil to its receptors are increased in some patients with hepatic encephalopathy due to fulminant hepatic failure. The origin of these substances is unknown, but these findings provide a rational basis for trials of benzodiazepine-receptor antagonists in the management of this disorder. 
Detection of hepatitis B virus DNA in paraffin-embedded liver tissues in chronic hepatitis B or non-A, non-B, hepatitis using the polymerase chain reaction. We developed a polymerase chain reaction assay for the direct detection of hepatitis B virus in paraffin-embedded liver tissue and applied this assay to determine whether hepatitis B virus DNA exists in livers with chronic hepatitis non-A, non-B. Fifty five liver biopsy samples were studied: 11 from patients with HBeAg-positive chronic hepatitis (paraffin-embedded) and 44 from patients with chronic hepatitis non-A, non-B (21 paraffin-embedded; 25 fresh frozen). Thirty three (75%) of the non-A, non-B cases were positive for hepatitis C virus antibodies. Approximately 1 to 10 ng of DNA was extracted from the paraffin-embedded tissue and amplified using oligonucleotide (23-mer) primers specific for the S gene (positions 261 to 692). The beta-globin gene was used as an internal control for sensitivity because this is a single copy gene and allows for relative quantification. In each of the chronic hepatitis B livers, the expected 432-base-pair amplification product for hepatitis B virus DNA and beta-globin gene product were both detected. On the other hand, in the 21 paraffin-embedded chronic hepatitis non-A, non-B livers, no hepatitis B virus DNA was detected, although beta-globin gene was observed in all. Furthermore, in all 25 frozen non-A, non-B livers, beta-globin gene was observed, but no hepatitis B virus band was seen. The limit of detection of hepatitis B virus DNA by this method was estimated to be one genomic copy of hepatitis B virus DNA per cell. 
Ovulation induction by step-down administration of purified urinary follicle-stimulating hormone in patients with polycystic ovarian syndrome. The step-down method can be an alternative method of ovulation induction in women with PCOS. This protocol can induce ovulation with a smaller dose of FSH and with lower incidence of excessive ovarian enlargement in comparison with the traditional fixed-dose administration method. 
Fluoxetine in the treatment of borderline and schizotypal personality disorders. Twenty-two patients meeting the criteria for borderline or schizotypal personality disorder or both participated in a prospective, nonblind 12-week trial of fluoxetine. There were significant reductions in self-injury and in scores on the Hopkins Symptom Checklist regardless of diagnosis. The results suggest that controlled trials of fluoxetine and investigations of the serotonergic system in these disorders would be useful. 
Atypical polypoid dermatofibroma: report of two cases. Two cases of a hitherto undescribed special variant of dermatofibroma are reported. A man and a woman, aged 57 and 52 years, respectively, had slowly growing cutaneous tumors on the lower extremities. The tumors were exophytic and polypoid, 10 and 6 cm in maximal diameters, respectively; they were covered by rough nonulcerated skin and were joined by a short pedicle to an indurated base. Histologic examination showed some features of an otherwise conventional dermatofibroma, whereas the polypoid component was hypercellular and showed striking atypia and scattered mitotic figures. After 32 and 28 months' follow-up, the lesions did not recur after surgical excision. We suggest the term atypical polypoid dermatofibroma to summarize the special clinicopathologic features of these tumors. 
Pelvic fracture from major blunt trauma. Outcome is determined by associated injuries. Pelvic hemorrhage has been implicated as the cause of death in 50% of patients who die following pelvic fractures. To establish correlates of morbidity and mortality from pelvic fractures due to blunt trauma, we reviewed 236 patients treated during 4 years. The average age of the 144 men and 92 women was 31.5 years, the average Injury Severity Score was 21.3, the average blood requirement was 5 units, and the average hospital stay was 16.8 days. One hundred fifty-two patients (64.4%) were injured in motor vehicle accidents, 33 (14%) had motor vehicle-pedestrian accidents, 16 (6.8%) had crush injuries, 12 (5.1%) each had either motorcycle accidents or falls, and 11 (4.6%) had miscellaneous accidents. Eighteen patients (7.6%) died, with seven (38.9%) deaths due to hemorrhage. Only one death was caused by pelvic hemorrhage. Other deaths were due to hemorrhage from other sites (6), head injury (5), sepsis or multiple-organ failure (4), pulmonary injury (1), and pulmonary embolus (1). None of the septic deaths was related to a pelvic hematoma. Multivariate multiple regression analysis showed that the severity of injury was correlated with indices of severity of pelvic fractures such as fracture site (p less than 0.0001), fracture displacement (p less than 0.005), pelvic stability (p less than 0.0001), and vector of injury (p less than 0.01). However death could not be predicted on the basis of these indices of severity (p greater than 0.28). Of the nine patients who underwent pelvic arteriography, three required embolization of actively bleeding pelvic vessels, but seven had intra-abdominal hemorrhage that required laparotomy, and eight developed a coagulopathy. Massive bleeding from pelvic fractures was uncommon, and the major threat of hemorrhage was from nonpelvic sites. Furthermore, although injury severity was correlated with the severity of the pelvic fracture, hospital outcome was determined by associated injuries and not by the pelvic fracture. 
Risk assessment and control of waterborne giardiasis. BACKGROUND: Waterborne giardiasis has been increasing in the United States with 95 outbreaks reported over the last 25 years. The Safe Drinking Water Act has mandated control of this pathogen. METHODS: A risk assessment model was developed to estimate risk of infection after exposure to treated waters containing varying levels of Giardia cysts. The model was defined by a dose-response curve developed from human feeding studies for Giardia and assumed 2L of water consumption per day. Data on concentrations and distribution of the organism in source waters were used to assess exposure after varying reductions achieved through treatment. RESULTS: In surveys reporting prevalence and levels of Giardia cyst contamination, average levels of cysts in surface waters ranged from 0.33 to 104/100L; from pristine watersheds (protected from all human activity) 0.6 to 5/100L. Yearly risks were 4.8 x 10(-3) for systems using polluted waters and 1.3 x 10(-4) for pristine waters with a 10(-3) treatment reduction. CONCLUSION: Public Health officials will need to work with the water industry to ensure a risk of less than 1/10,000 for source waters with 0.7 to 70 cysts per 100 liters through treatment achieving reduction of 10(-3) to 10(-5), respectively, of Giardia cysts. 
Subarachnoid hemorrhage from multiple neurofibromas of the cauda equina: case report. The authors report a case of spinal subarachnoid hemorrhage caused by neurofibromas of the cauda equina. An examination of the literature revealing 13 similar cases and an analysis of this case showing three neurofibromas of the cauda equina prompted an hypothesis emphasizing the origin of bleeding and the difficulties associated with a correct diagnosis. 
Deletion of mitochondrial DNA in patients with combined features of Kearns-Sayre and MELAS syndromes. A 9-year-old girl and an 11-year-old boy had ptosis, progressive external ophthalmoplegia, pigmentary retinopathy, and sensorineural hearing loss. The girl had diabetes mellitus and the boy had hypoparathyroidism. Both children also developed recurrent vomiting and cerebral infarcts with lactic acidosis. Muscle biopsy specimens showed ragged-red fibers and Southern analysis demonstrated a distinct heteroplasmic deletion of muscle mitochondrial DNA in each patient but no evidence of the point mutation in the transfer RNALeu(UUR) gene recently identified in mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). These 2 children had combined features of Kearns-Sayre syndrome and MELAS, suggesting that mitochondrial DNA deletions occasionally can have pleomorphic clinical expression. 
Prevalence, onset, and risk of psychiatric disorders in men with chronic low back pain: a controlled study. This study used structured diagnostic interviews and DSM-III criteria to assess lifetime prevalence and pre-morbid risk of psychiatric disorder in a sample of men with long-standing chronic back pain (CLPB) attending a primary care clinic. A control group of age and demographically matched men without history of back pain was also studied. Compared to controls, men with CLBP had significantly higher lifetime rates of major depression (32% vs. 16%), alcohol use disorder (64.9% vs. 38.8%), and a major anxiety disorder (30.9% vs. 14.3%). Almost all CLBP men ever experiencing a mood disorder reported recurrent, not single, episodes. The 6 month point prevalence of major depression, but not other disorders, was also significantly elevated for men with CLBP. In CLBP, the first episode of major depression generally (58.1%) followed pain onset. While the initial major depressive episode usually commenced within the first 2 years of established pain, late onset mood disorder was also common. By comparison in most cases (81%) onset of alcohol use disorders considerably preceded pain. When an age-matching procedure was used to gauge relative vulnerability to psychiatric illness in patients and controls, CLBP patients had significantly higher pre-pain rates of alcohol use disorder but not depression. After age of pain onset, CLBP subjects had over 9 times the risk of developing major depression, but had similar rates of developing alcoholism. We conclude that (1) alcohol use disorders rather than depression may increase risk of developing CLBP, and (2) risk of new onset and recurrent major depression remains high for men throughout their pain career. This suggests that psychological adaptation to long-standing pain may be less successful than previously thought, especially with regard to recurrent mood disorder. 
A 'unified theory' of prion propagation. There is now very persuasive evidence that the transmissible agent for spongiform encephalopathies such as scrapie, consists of a modified form of the normal host protein PrPc, devoid of any nucleic acid. On the other hand, because there are many different strains of scrapie agent with distinct phenotypes which can be propagated in animals homozygous for the PrPc gene, it has been suggested that a nucleic acid must be a component of the agent. Can the two views be reconciled?. 
Analysis of the enhancer element that controls expression of sevenless in the developing Drosophila eye. The sevenless gene encodes a protein-tyrosine kinase receptor expressed in a complex pattern during the development of the Drosophila melanogaster eye. We have previously shown that this pattern is regulated transcriptionally by an enhancer located in the body of the sevenless gene. Here we extend our analysis of the sevenless enhancer, defining a 475-base-pair fragment that contains elements necessary for the correct qualitative and quantitative expression of the sevenless gene. Within this fragment are sequence elements conserved in the sevenless gene of a distantly related Drosophila species and protected from DNase I digestion by nuclear extracts isolated from adult heads and imaginal discs. Partial deletions of the 475-base-pair fragment result in preferential loss of expression in different subsets of cells. These results suggest that the normal pattern of expression is generated by the combined action of separate cell-specific regulatory elements. 
Helicobacter pylori gastritis mimicking gastric carcinoma at CT evaluation. The abdominal computed tomographic (CT) scans from 61 patients with biopsy-proved Helicobacter (formerly Campylobacter) pylori gastritis were retrospectively reviewed. The CT scans were interpreted on the basis of the original report of the findings at CT examination and without knowledge of the results of biopsy. Of 19 patients (31%) with gastric abnormalities at CT, 14 (74%) had inflammatory changes initially reported as suspicious for gastric malignancy; malignancy was entertained as the primary diagnosis in four of those patients. In five of the 19 abnormal cases (26%), the diagnosis with CT was gastritis. The two major patterns of severe H pylori infection identified were (a) circumferential antral wall thickening and (b) thickening of the posterior gastric wall along the greater curvature, with or without evidence of ulceration. Thickening averaged 1.5-2.0 cm in cases suspicious for malignancy. The majority of abnormalities involved the gastric antrum (68%). No cases demonstrated significant adenopathy, obliteration of fat planes, or invasion of adjacent organs. 
Non-ominous micrometastases of gastric cancer. So-called R2 or wider meticulous node dissection was performed in 1368 patients with resected gastric cancer invading beyond the submucosa but without distant metastases. Survival rates were similar in subsets of patients with or without microscopic node metastases and macroscopically normal lymph nodes. The extent of node metastases has previously been shown to be one of the two most important prognostic factors in gastric cancer without distant metastases, and its lack of impact in these patient groups was not explained by the imbalance of other prognostic factors. The findings indicate that micrometastases of gastric cancer are curable by a wide node dissection made in the absence of palpable abnormality. They also offer the possibility that an extensive node dissection may yield good stage-specific survival rates, in part because of upstaging of patients. The findings should influence the recording of node metastases for evaluation of stage-specific treatment results and for research purposes. 
Excess mortality associated with diuretic therapy in diabetes mellitus OBJECTIVE. To determine whether the high mortality among diabetic patients receiving treatment for hypertension can be explained by associated risk factors or must be attributed to a deleterious effect of antihypertensive treatment. DESIGN. Cohort analytic study with a median follow-up of 4.5 years. SETTING. Outpatients with diabetes and severe retinopathy who were enrolled in a multicenter, randomized clinical trial of laser treatment to prevent blindness had ophthalmologic examinations every 4 months and annual medical examinations that included measurement of blood pressure and recording of anti-hypertensive treatment. Only 5.5% of the patients were unavailable for follow-up. When a patient died, the circumstances surrounding the death were reviewed and classified by a mortality review committee. PARTICIPANTS.--There were 759 participants in the study; they were white, were aged 35 to 69 years, and had normal serum creatinine levels at the baseline examination. MEASUREMENTS AND MAIN RESULTS.--Patients were classified into five groups according to information recorded at the baseline and first annual follow-up examinations: normotensive (diastolic blood pressure less than 90 mm Hg), untreated hypertensive, hypertensive treated by diuretics alone, hypertensive treated by other agents alone, and hypertensive treated by both agents. Cardiovascular mortality was higher in patients treated for hypertension than in patients with untreated hypertension. The excess was primarily found in patients treated with diuretics alone, although that group had the lowest blood pressure with treatment. After adjusting for differences in risk factors, cardiovascular mortality was 3.8 times higher in patients treated with diuretics alone than in patients with untreated hypertension (P less than .001). CONCLUSIONS.--In individuals with diabetes, intervention with diuretics to reduce hypertension is associated with excess mortality. Until there is a clinical trial showing a beneficial effect of diuretic treatment in diabetic patients, there is urgent need to reconsider its continued usage in this population. 
Radiation and pagetic osteogenic sarcomas. Radiation and pagetic osteogenic sarcomas should be distinguished from classical osteogenic sarcoma. Both occur in older patients with significantly greater comorbidity. Roentgenographically, radiation osteogenic sarcoma is typically sclerotic, whereas pagetic osteogenic sarcoma is lytic and associated with pathologic fracture. Radical resections give the best result, local control, and survival. Chemotherapy has not proven effective to date. Improvements in tumor imaging and more intensive chemotherapy regimens may permit limb-sparing surgery. Overall results remain poor, with approximately 15% five-year survival in each condition. 
Phase II trial of pentostatin in refractory lymphomas and cutaneous T-cell disease. Thirty-seven patients with refractory lymphoma or cutaneous T-cell lymphoma were treated with 2'-deoxycoformycin (pentostatin; dCF), 5 mg/m2 intravenous (IV) bolus for 3 consecutive days of every 3-week cycle in this Eastern Cooperative Oncology Group (ECOG) trial. Included were 25 with the diagnosis of non-Hodgkin's lymphoma, three with Hodgkin's disease, eight with cutaneous T-cell lymphoma (CTCL), and one with unknown subtype, of whom 31 were considered eligible. The majority had failed at least two, but no more, conventional chemotherapy regimens. Ten (32%) of the eligible patients had a partial response (PR), including patients with nodular poorly differentiated lymphocytic (NPDL), nodular mixed (NM), diffuse poorly differentiated lymphocytic (DPDL), or diffuse histiocytic (DH), lymphoma mixed-cellularity (MC), Hodgkin's disease, and unknown subtype, and in four patients with CTCL. The overall median time to treatment failure (TTF) was only 1.3 months, but the range extended to 57.3 months. The overall response duration was 16.0 months, and the range extended to 53.4 months. Overall median survival was 2.7 months, with the range extending to 63.2 months. The majority of patients had no toxicity, but there were some instances of severe or life-threatening events. Four fatal toxicities occurred, in two patients with underlying pulmonary conditions and two with prior cardiac histories. From this study, we conclude that dCF is active in refractory lymphomas and CTCLs, should be avoided in patients with a history of serious pulmonary or cardiac diseases, and warrants consideration for incorporation of a low-dosage schedule into conventional combination chemotherapy regimens, including its use with biologic response modifiers. 
Causes of blindness and visual handicap in the Central African Republic. The causes of bilateral blindness (best visual acuity less than 3/60) in 1371 people in the Central African Republic seen between 1985 and 1989 who attended eye clinics in 10 out of the 16 prefectures across the country are given. The main causes of bilateral blindness were cataract (51%), glaucoma (12.7%), and onchocerciasis (8.1%). In 710 patients with unilateral blindness the main causes were cataract (38%), glaucoma (10%), iritis (7.5%), and trauma (6.3%). Bilateral blindness in children was rarely seen. The causes of visual impairment (vision between 6/18 and 3/60) in 424 patients were cataract, including aphakia (38%), maculopathy (14%), and onchocerciasis (7%). 
Mechanisms of gastroduodenal protection by sucralfate. Over the past 5-10 years, a number of studies have shown that topical sucralfate enhances a number of gastric and duodenal mechanisms, e.g., the "mucus-bicarbonate barrier," mucosal hydrophobicity, mucosal blood flow, cell viability, and local production of prostaglandins, as well as endogenous mediators of tissue injury and repair. It seems likely that the complex actions of sucralfate are in part related to direct interaction between the drug or its components (aluminum, sucrose, and sulfate) and gastric mucosal tissues, and in part related to effects of the drug on the various mucosal mediators of tissue injury and repair. Local actions may play a role in accelerating healing of ulcer-damaged mucosa, but this does not explain the protective actions of sucralfate on normal mucosa. Thus sucralfate appears to enhance the protective function of the "mucus-bicarbonate" barrier by actions on both components. This may depend in part on an interaction with the unstirred layer overlying gastric epithelium. Sucralfate has also been shown to increase the hydrophobicity of mucus gel. There is little doubt that sucralfate increases local production and release of protective prostaglandins (PGs), but the precise role played by these agents in mediating mucosal protection and in chronic ulcer healing remains uncertain. Currently, the mechanism of action of sucralfate on vascular integrity remains unknown and the role of PGs in this protective function is unclear. There is little evidence that epidermal growth factor plays any role in mediating mucosal protection by sucralfate, but it may be important in its ulcer-healing action. Sucralfate has been shown to be truly "cytoprotective" in that it protects isolated epithelial cells from damage by noxious agents. In animals treated with sucralfate, the surface epithelial cells were disrupted, but necrotic lesions in the deep proliferative zone were virtually absent. It seems likely that investigations of the actions of sucralfate and its components will move ever closer to defining the target cells, the intracellular events, and the mediators that bring about its protective and ulcer-healing activity. 
Histological grading and bromodeoxyuridine labeling index of astrocytomas. Comparative study in a series of 60 cases. The histological grade and the bromodeoxyuridine (BUdR) labeling index of 60 astrocytomas of "ordinary" cell types (fibrillary, protoplasmic, gemistocytic, and anaplastic astrocytomas and glioblastomas) were compared to determine whether the grading system reflects the proliferative potential of the tumors. The tumor grade was based on the presence or absence of four criteria (nuclear abnormalities, mitosis, necrosis, and vascular endothelial proliferation): Grade 1, no criterion, Grade 2, one criterion, Grade 3, two criteria; and Grade 4, three or four criteria. The BUdR labeling index, or percentage of S-phase cells, was calculated in paraffin-embedded tumor sections after in situ labeling by intraoperative intravenous infusion of BUdR, 200 mg/sq m. Exponential regression analyses showed a positive correlation between the histological grade and labeling index (r = 0.88, p less than 0.001) that was stronger than the correlations between log labeling index and age (r = 0.55, p less than 0.001) and between grade and age (r = 0.55, p less than 0.001). These results indicate that the histological grading system reflects the proliferative potential of "ordinary" astrocytomas. 
Acid perfusion test and 24-hour esophageal pH monitoring with symptom index. Comparison of tests for esophageal acid sensitivity. The acid perfusion (Bernstein) test and esophageal pH monitoring are the two most popular tests for identifying esophageal acid sensitivity in difficult cases of reflux disease. Therefore, we prospectively compared these test results in 75 consecutive noncardiac chest pain patients who had both an acid perfusion test and chest pain during 24-hr pH testing. A positive acid perfusion test was defined by the replication of the patient's typical chest pain twice by the acid infusion. Esophageal pH testing identified abnormal amounts of acid reflux and correlated symptoms with acid reflux--the "symptom index." Fifteen patients (20%) had a positive acid perfusion test while 45 patients (59%) had a positive symptom index (range 6-100%). Only 9/34 (26%) patients with abnormal reflux had a positive acid perfusion test. Although it had excellent specificity (83-94%), the acid perfusion test had poor sensitivity (32-46%) when compared to the symptom index regardless of the percent positive cutoff level. The best positive predictive value for the acid perfusion test was 87%, but this occurred when the test sensitivity was 32%. Modifying the end point of a positive acid perfusion test to include heartburn improves the sensitivity (52-67%) while markedly compromising specificity and positive predictive value. Thus, esophageal pH monitoring correlating symptoms with acid reflux is superior to the acid perfusion test for identifying an acid sensitive esophagus in patients with noncardiac chest pain. 
Acute infectious erythemas in children: a clinico-microbiological study. One-hundred children with an acute illness comprising fever and widespread erythematous rash were prospectively studied to determine whether clinical presentations are helpful in defining the causative agent and to identify the most appropriate microbiological specimens. An infectious agent was identified in 65 children; 72% were viruses, 20% were bacteria, 5% were Mycoplasma pneumoniae and in 3% both viruses and bacteria were detected. The most common infectious agents were picornaviruses, an atypical presentation of measles and Group A beta-haemolytic Streptococcus. Different patterns of rash occurred with each of these infections. The clinical presentation of a child with an acute febrile illness and rash was unhelpful in defining the causative agent. Routine management should include a throat swab for bacterial investigation and in selected cases a blood sample for IgM viral titres. 
Serum cholesterol concentration and coronary heart disease in population with low cholesterol concentrations. OBJECTIVE--To examine the relation between serum cholesterol concentration and mortality (from coronary heart disease and from other causes) below the range of cholesterol values generally seen in Western populations. DESIGN--Prospective observational study based on 8-13 years of follow up of subjects in a population with low cholesterol concentrations. SETTING--Urban Shanghai, China. SUBJECTS--9021 Chinese men and women aged 35-64 at baseline. MAIN OUTCOME MEASURE--Death from coronary heart disease and other causes. RESULTS--The average serum cholesterol concentration was 4.2 mmol/l at baseline examination, and only 43 (7%) of the deaths that occurred during 8-13 years of follow up were attributed to coronary heart disease. There was a strongly positive, and apparently independent, relation between serum cholesterol concentration and death from coronary heart disease (z = 3.47, p less than 0.001), and within the range of usual serum cholesterol concentration studied (3.8-4.7 mmol/l) there was no evidence of any threshold. After appropriate adjustment for the regression dilution bias, a 4 (SD 1)% difference in usual cholesterol concentration was associated with a 21 (SD 6)% (95% confidence interval 9% to 35%) difference in mortality from coronary heart disease. There was no significant relation between serum cholesterol concentration and death from stroke or all types of cancer. The 79 deaths due to liver cancer or other chronic liver disease were inversely related to cholesterol concentration at baseline. CONCLUSION--Blood cholesterol concentration was directly related to mortality from coronary heart disease even in those with what was, by Western standards, a "low" cholesterol concentration. There was no good evidence of an adverse effect of cholesterol on other causes of death. 
The value of tests predicting renovascular hypertension in patients with renal artery stenosis treated by angioplasty. The aim of this study was to evaluate tests predicting renovascular hypertension. This was done by relating the results of renal vein renin tests, the captopril test, and renal scintigraphic tests to the blood pressure outcome 12 months after relief of renal artery stenosis by percutaneous transluminal renal angioplasty in 31 patients. Cure was seen in eight (26%). Improved blood pressure was obtained in 12 patients (39%), and in 11 patients (35%), the result for blood pressure was a failure. The accuracies of the two mathematical models used to analyze the renal vein renin assays were 44% and 60%. The captopril test showed a sensitivity of 36% and an accuracy of 43%. Renal captopril technetium Tc 99m-labeled pentetic acid scintigraphy gave a sensitivity of 60%. Stepwise logistic regression analysis of clinical variables in relation to blood pressure response revealed age as the only factor significantly related to blood pressure outcome. We conclude that the tests used are unfit for helping select patients for percutaneous transluminal renal angioplasty and that age may have an important influence on outcome. 
Surgical approaches to congenital atresia of the external auditory canal. During the past 4 years, 22 patients with congenital atresia of the external auditory canal underwent 24 initial operations by either an anterior or transmastoid approach. No attempt at randomization was made, but the two groups were similar in number and pathology (in 14 cases approach was anterior and in 10 cases approach was transmastoid). Followup ranged from 6 months to 4 years. Hearing results were similar in the two groups (71% with air-bone gap less than 30 dB). There were no instances of facial nerve injury or sensorineural hearing loss. Facial nerve monitoring was used. Complications of stenosis and drainage were more common with the transmastoid approach. In both groups, hearing results were accomplished with the patients' intact ossicles or prosthetic reconstructions. Meticulous soft-tissue technique, with split-thickness grafts covering all exposed bone, is the key to preventing stenosis. For the three cases of patients with thick, acellular atresia plates, a different approach was developed. Maintaining proper orientation during the medial dissection is more difficult in these cases. By opening the antrum primarily and identifying the lateral canal, ossicles, and facial nerve, an ear canal can then be created anteriorly with these landmarks in view. An intact canal wall-like procedure is carried out. Although hearing results are similar, the anterior approach, because of fewer postoperative complications, is now our procedure of choice. Proper orientation and soft-tissue technique are the keys to successful correction of the congenitally atretic ear canal. 
Hypoxic exposure and activation of the afterdischarge mechanism in conscious humans. After voluntary hyperventilation, normal humans do not develop a significant ventilatory depression despite low arterial CO2 tension, a phenomenon attributed to activation of a brain stem mechanism referred to as the "afterdischarge." Afterdischarge is one of the factors that promote ventilatory stability. It is not known whether physiological stimuli, such as hypoxia, are able to activate the afterdischarge in humans. To test this, breath-by-breath ventilation (VI) was measured in nine young adults during and immediately after a brief period (35-51 s) of acute hypoxia (end-tidal O2 tension 55 Torr). Hypoxia was terminated by switching to 100% O2 (end-tidal O2 tension of first posthypoxic breath greater than 100 Torr). Brief hypoxia increased VI and decreased end-tidal CO2 tension. In all subjects, termination of hypoxia was followed by a gradual ventilatory decay; hyperoxic VI remained higher than the normoxic baseline for several breaths and, despite the negative chemical stimulus of hyperoxia and hypocapnia, reached a new steady state without an apparent undershoot. We conclude that brief hypoxia is able to activate the afterdischarge mechanism in conscious humans. This contrasts sharply with the ventilatory undershoot that follows relief of sustained hypoxia, thereby suggesting that sustained hypoxia inactivates the afterdischarge mechanism. The present findings are of relevance to the pathogenesis of periodic breathing in a hypoxic environment. Furthermore, brief exposure to hypoxia might be useful for evaluation of the role of afterdischarge in other disorders associated with unstable breathing. 
Celiac axis and superior mesenteric artery injury associated with left radical nephrectomy for locally advanced renal cell carcinoma. The superior mesenteric artery and celiac axis were inadvertently ligated during left radical nephrectomy for a large upper pole renal carcinoma with massive perihilar and periaortic adenopathy. Computer-generated 3-dimensional illustrations created from the computerized tomography scan demonstrated the close proximity between these visceral branches and the adenopathy mass complex, and showed how this bulky disease may interfere with surgical anatomy. When left radical nephrectomy is performed for locally advanced and/or bulky node-positive renal neoplasms, surgeons must be cognizant of the location of the major visceral arterial branches and possible anatomical distortions. 
Effects of a minimally supervised exercise program for mentally retarded adults. Previous exercise studies that attempted to improve the cardiovascular fitness (CVF) of mentally retarded (MR) adults were flawed with methodological shortcomings that prevented conclusive results. At issue in these training studies were fitness test validity and reliability, exactness of duration and intensity of training, and an inordinate amount of supervision. Therefore, we sought to determine whether moderately MR adults (seven males, five females; IQ = 61 +/- 3, age = 25 +/- 3 yr) could improve their CVF through a minimally supervised 16-wk training program. Each subject repeated exercise tests twice on two different modes of exercise, the treadmill (TM) and Schwinn Air-Dyne ergometer (SAE), before training to ensure validity and reliability of initial CVF levels. Intensity and frequency of exercise were closely monitored. An observer was present during the training bouts, but, following initial instructions, no additional encouragement or instructions were given. Although the training program significantly increased peak VO2 (29.2 +/- 8 to 33.5 +/- 9 ml.kg-1.min-1) and peak ventilation (73 +/- 26 to 81 +/- 231.min-1) when assessed on the TM, significant changes in these same parameters were not seen when assessed on the SAE. The importance of these results was discussed. 
Cardiac surgery in the octogenarian: perioperative outcome and clinical follow-up The perioperative and follow-up results of cardiac operations employing extracorporeal circulation and cold cardioplegic arrest were examined in 191 consecutive patients greater than or equal to 80 years of age having surgery over a 5 year period (1982 to 1986). Most patients had severe preoperative symptoms with functional class III (39.8%) or IV (57.1%) limitation. The overall 30 day postoperative cardiac mortality rate was 15.7%. The total in-hospital mortality rate was 18.8%; the mean postoperative hospital stay was 16.4 +/- 13.3 days. The perioperative mortality rate for elective operations was as follows: coronary artery bypass (5.6%), aortic valve replacement (9.6%), aortic valve replacement with coronary bypass (17.9%) and mitral valve surgery with or without coronary bypass (21.4%). Urgent operations were performed in 39 patients (20.4%) with a total perioperative mortality rate of 35.9%; urgent coronary artery bypass was performed in 26 patients (67%) with an in-hospital mortality rate of 23.1%. Clinical evidence of left ventricular failure, functional class IV symptoms, left ventricular ejection fraction less than 50%, mitral valve repair or replacement for severe mitral regurgitation and urgent operation were associated with an increased perioperative mortality rate. Follow-up study in all 155 patients surviving postoperative hospitalization at 22.6 +/- 14.8 months showed significant improvement in symptom status in all surgical subgroups. There were 18 follow-up deaths (11.6%); 10 were noncardiac. The actuarial survival rate of the entire study group was significantly better than that in age- and gender-matched control subjects (p = 0.037). 
Interethnic differences in pain perception. While several investigators have reported relationships between ethnic background and expression of pain, such relationships are in fact highly problematical. Few studies of pain and ethnicity have used quantitative measures of pain combined with multivariate methods of data analysis. Most have focussed on populations which, unlike many in the United States today, are characterized by highly distinct ethnic groups. The study reported here interviewed 536 persons recently treated for forms of cancer known to cause significant pain. Pain was assessed using standard, well validated instruments, including Graphic Rating Scales anchored in several alternative time-frames and the McGill Pain Questionnaire. The study took place in an area with a low proportion of recent immigrants and only small concentrations of distinct ethnic minorities. No statistically significant relationships were observed between ethnic identity and measures of pain sensation. However, pain described in affective terms according to the McGill Pain Questionnaire did vary among ethnicities. This observation suggests that cultures associated with specific ethnic identities still condition individual expression of pain despite the high degree of assimilation that has occurred among ethnic groups in the United States. 
The role of platelet activating factor and its antagonists in shock, sepsis and multiple organ failure. PAF has been implicated as a mediator of shock, sepsis and MOF. The results of experimental data demonstrate that PAF induces changes characteristic of endotoxemia and sepsis, including systemic hypotension and diffuse microvascular leakage. These effects are prevented by PAF antagonists. PAF induces many of the characteristic changes of MOF, including functional impairment in the lung, kidney, gastrointestinal tract and heart. PAF antagonists will inhibit these adverse effects. PAF antagonists are now being manufactured by a number of pharmaceutical companies studying the beneficial effects of PAF antagonists in human disease. Data from these studies promise valuable information with significant clinical relevance to the practicing surgeon. 
A comparison of tocopherol and tocotrienol for the chemoprevention of chemically induced rat mammary tumors. Two forms of vitamin E, tocopherol and tocotrienol, were tested for chemopreventive activity in two chemically induced rat mammary-tumor models. When mammary tumors were induced by 7,12-dimethylbenz(a)anthracene (DMBA, 50 mg/kg), only the tocotrienol group had a statistically significant increase in tumor latency. There was no effect of either compound on tumor multiplicity. When tumors were induced by N-nitrosomethylurea (NMU, 30 mg/kg), neither analogue of vitamin E modified latency, whereas tocotrienol increased tumor multiplicity. In summary, neither vitamin analog had a major impact on mammary-tumor development after tumor induction with either DMBA or NMU. 
Increased negative inotropic effect of calcium-channel blockers in hypertrophied and failing rabbit heart. The effects on ventricular function of calcium channel blockers and isoproterenol were studied in isovolumically beating perfused control rabbit hearts and in hearts subjected to a double pressure plus volume overload studied at the early phase of heart failure. In control hearts, isoproterenol produced an increase of systolic ventricular function and relaxation that was maximal at 10(-7) M. In failing hearts, inotropic state increase in response to isoproterenol was significantly smaller (P less than .01) with no observed lusitropic effect. In control hearts, verapamil and diltiazem produced dose-dependent decreases of ventricular function which were larger with verapamil than with diltiazem (median drug concentration50 of developed pressure was, respectively, 1163 +/- 131 nM and 4524 +/- 451 nM, P less than .001). In failing hearts, contractility decrease was larger than in control hearts (median drug concentration50 of developed pressure was 604 +/- 69 nM and 2691 +/- 580 nM with verapamil and diltiazem, respectively). In contrast, Ro 40-5967, a new calcium-channel blocker, did not produce reductions of inotropic state with concentrations up to 10(-5) M. All three calcium-channel blockers produced a 2-fold increase of coronary flow at 10(-6) M. We conclude that the deleterious effect of verapamil and diltiazem in heart failure is due, at least in part, to a direct depressant effect of these drugs on contractility, which is larger than in control hearts. Additionally, the in vivo sympathetic compensation is probably reduced, as indicated by the decreased ventricular responsiveness to isoproterenol. 
Heart transplantation in children: an international survey. A survey of cardiac transplantation in children provided data from 381 transplantations in 362 patients from 32 centers in the United States and ten international centers. The number of transplantations continues to increase, in part because of transplantations in infants with hypoplastic left heart syndrome and patients with congenital defects. The immunosuppression regimens were more uniform than in the 1985 survey, and triple therapy was most common. Actuarial survival rates were 85% at 1 month, 72% at 1 year, 64% at 3 years, and 60% at 5 years. However, these improved rates are still not equal to the survival of the overall cardiac transplant population, in part because of lower survival rates in neonates. Ventricular dysfunction and rejection, rather than infection, were the leading causes of death. Rejection and infection were the most frequent complications. Also common were hypertension (39%) and seizures (25%), whereas coronary artery disease (8%) was unusual. Functional results were excellent in 85%, and only 7% were disabled. Questions concerning growth rates and many other aspects cannot yet be answered. However, it is apparent that cardiac transplantation in the pediatric population is a very worthwhile endeavor. 
Practical phlebology. Sclerotherapy of large veins. A practical, step-by-step guide for the sclerotherapy of large varicose veins is offered. First, an orientation regarding the place of sclerotherapy and surgery in the total treatment of varicose veins is given, with a practical clinical classification of varicose veins. This is followed by a detailed discussion of patient education before sclerotherapy, material to be used with recommended concentrations, injection technique, compression after sclerotherapy, instructions to the patient after injection, and procedures at subsequent visits. 
Nuclear magnetic resonance spectroscopy study of human brain after cardiac resuscitation. We used 31P nuclear magnetic resonance spectroscopy to study the cerebral metabolic function of eight patients with severe postischemic anoxic encephalopathy secondary to cardiac arrest. Spectroscopy was performed at 18 +/- 13 and 64 +/- 20 hours after resuscitation. Glasgow Coma Scale scores at the time of initial and repeat spectroscopy were 3.6 +/- 1.2 and 3.5 +/- 1.2, respectively. In those patients whose spectra were of adequate quality to monitor pH, all demonstrated tissue alkalosis in at least one brain region. The mean brain pH at initial spectroscopy was 7.14 +/- 0.09 and was significantly alkalotic when compared with age- and sex-matched normal controls (pH = 6.98 +/- 0.04, p less than 0.0001). Five of the eight patients showed at least one region of persistent alkalosis at repeat spectroscopy, whereas one patient demonstrated severe acidosis with a pH of 6.42. Spectra demonstrated marked metabolic heterogeneity, ranging from normal in appearance to complete obliteration of all high-energy phosphates with only inorganic phosphate remaining. 
Supraciliary hemangiopericytoma. A 10-year-old black girl complaining of pain and decreased vision in the left eye was found to have a smoothly elevated ciliochoroidal mass involving the superonasal quadrant of the left eye. The mass appeared circumscribed and uniformly dense by computed tomography. The tumor was hyperintense to vitreous and cerebral white matter on T1-weighted magnetic resonance imaging but was hypointense to vitreous and hyperintense to white matter on T2-weighted magnetic resonance imaging. Results of gross examination of the enucleated eye showed a sharply circumscribed, tan, intraocular mass arising equatorially. Results of histopathologic examination showed a well-vascularized spindle cell proliferation with a sinusoidal pattern characteristic of hemangiopericytoma. This is the third reported case of intraocular hemangiopericytoma and the first in a pediatric patient. 
Problems in the definition and treatment of early gastric cancer. Radical operation with extensive dissection of lymph nodes (R1, 48 patients; R2, 196 patients; R3, one patient) was performed in 245 out of 247 patients with early gastric cancer. The 5-year survival rate was only 73.2 per cent in the 34 patients with lymph node metastases (31.8 per cent). Analysis of factors influencing recurrence revealed that not only lymph node metastases but also the depth of cancer invasion could affect prognosis in early gastric cancer. This study suggests that radical operation with complete dissection of the first and second group of lymph nodes (R2 resection) is a safe and appropriate treatment even for early gastric cancer. We propose that the definition of early gastric cancer be modified to 'carcinoma with invasion confined to the mucosa or submucosa and without evidence of lymph node metastases'. 
Resection of residual mediastinal germ cell masses with the Cavitron ultrasonic surgical aspirator. Residual mediastinal masses after chemotherapy for germ cell tumors should be resected. Complete excision of bulky residual masses may sometimes be difficult because of problems with exposure in the region of the great vessels and important nerves. Two cases are presented in which the Cavitron ultrasonic surgical aspirator (Valleylab Inc., Surgical Systems Division, Stamford, Conn.) facilitated excision of large masses after intensive chemotherapy. We found that the collapsed pseudocapsule remaining after aspiration of tumor mass allowed early improved exposure and safer dissection from neighboring vessels and neural structures. Complete excisions were accomplished and no viable tumor was found, so that the patients were spared the immediate need for further therapy. Both had uneventful recoveries. 
Risk factors for stroke as predictors of platelet membrane fluidity in Alzheimer's disease. We have previously reported that increased platelet membrane fluidity identifies a subgroup of patients with Alzheimer's disease who have distinct clinical features including an earlier age of symptomatic onset, a more rapidly progressive cognitive decline, and a decreased prevalence of focal electroencephalographic findings. In the current study, these patients also exhibited a decreased prevalence of risk factors for stroke compared with patients who had normal platelet membrane fluidity. Our findings suggest that the platelet membrane abnormality describes a clinical subgroup of patients with Alzheimer's disease who are less likely to have coexisting cerebrovascular disease than the remaining patients who meet clinical consensus criteria for probable Alzheimer's disease. 
Results of total knee arthroplasty using the posterior stabilized condylar prosthesis. A report of 137 consecutive cases. One hundred thirty-seven consecutive posterior stabilized total knee arthroplasties (TKAs) were reviewed. Average age of the patient was 61.1 years and length of postoperative follow-up period was 29.2 months. Patients were evaluated using the Hospital for Special Surgery (HSS) knee rating scores. Average preoperative scores improved from 52 to 92, postoperatively. Ninety-eight percent of patients had no pain or mild occasional pain postoperatively compared with 99% of patients experiencing severe to disabling pain preoperatively. Complications included one myocardial infarction, two deep venous thrombosis, one urinary tract infection, one patellar dislocation, and four wound problems. There were two incidences of seroma, one hematoma, and one deep infection requiring revision after joint debridement and systemic antibiotics. Also noted was one incidence of ligamentous laxity and one patella fracture. 
Precordial ST segment depression predicts a worse prognosis in inferior infarction despite reperfusion therapy. The Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) Study Group. The impact of associated precordial ST segment depression in inferior myocardial infarction on angiographic and clinical outcomes after thrombolytic therapy and selective coronary angioplasty was studied in 583 patients with acute myocardial infarction. Anterior infarction (Group I), inferior infarction with precordial ST segment depression (Group II) and inferior infarction without precordial ST segment depression (Group III) were present in 289, 135 and 159 patients, respectively. Precordial ST segment depression was more frequent in circumflex than right coronary infarct-related arteries (44 [71%] of 62 versus 91 [40%] of 230; p = 0.000). Although acute patency rates were not statistically different, there was a trend toward different patency rates at day 7 (Group I 88%, Group II 84%, Group III 80%; p = 0.089) partly because of insignificantly higher reocclusion rates in inferior infarction without precordial ST segment depression (Group I 11%, Group II 10%, Group III 18%, p = 0.104). Infarct zone regional wall motion (standard deviations/chord) in inferior infarction was lower with precordial ST segment depression, both acutely (Group I -2.8 +/- 0.9, Group II -2.5 +/- 1.2, Group III 2.0 +/- 1.1; p = 0.000) and at day 7 (Group I -2.2 +/- 1.1, Group II -2.3 +/- 1.1, Group III -1.9 +/- 1.3; p = 0.011). Precordial ST segment depression was associated with a lower ejection fraction in inferior infarction both acutely (Group I 47 +/- 11%, Group II 53 +/- 11%, Group III 58 +/- 9%; p = 0.000) and at day 7 (Group I 49 +/- 12%, Group II 53 +/- 10%, Group III 58 +/- 8%; p = 0.000). Complication rates tended to be higher in inferior infarction when precordial ST segment depression was present. Mortality rates for Groups I, II and III were 8%, 6% and 5%, respectively. These results suggest that precordial ST segment depression in inferior infarction predicts a worse ventriculographic and clinical outcome despite reperfusion therapy. 
Synergistic effect of intraperitoneally administered calcium channel blockade and recombinant tissue plasminogen activator to prevent adhesion formation in an animal model. Previous reports have shown the benefits of calcium channel blockers and recombinant tissue plasminogen activator to prevent postoperative adhesion formation in animal models. To assess the potential benefit of synergistic therapy for the prevention of postoperative adhesion formation, these agents were studied in a rabbit uterine horn model. Four groups of New Zealand White rabbits (n = 8 per group) had a bilateral devascularization injury to the uterine horns. Before closure saline solution, verapamil hydrochloride (2.5 mu/kg/hour), recombinant tissue plasminogen activator (4 mg total dose), or a combination of verapamil and recombinant tissue plasminogen activator at the stated doses were instilled by means of an Alzet osmotic pump x 200 hours. Adhesion scores were evaluated after this time period by estimating the total uterine horn surface involved in adhesions at a terminal laparotomy and by clinically grading the response to determine whether minimal adhesions formed. Results of the total uterine horn surface scores were (mean score +/- SE): saline solution, 44% +/- 3.7%; verapamil, 19% +/- 4.8%; recombinant tissue plasminogen activator, 11% +/- 3.6%; combined, 3% +/- 1% (p less than 0.01 to control and p less than 0.05 to single-drug therapy). Results of the number of animals per group with minimal adhesions were as follows: saline solution, 0; verapamil, 1; recombinant tissue plasminogen activator, 3; combined, 8 (P less than 0.01). These results show a synergistic benefit of verapamil and recombinant tissue plasminogen activator to prevent postsurgical adhesion formation when delivered via the intraperitoneal route. 
Myonecrosis and myofibrosis as complications of sickle cell anemia. Painful crises in sickle cell anemia are associated with infarction and subsequent fibrosis of many different organs. Myonecrosis secondary to muscle infarction during a crisis and subsequent fibrosis are often not recognized as complications of sickle cell anemia. We describe four patients, all of whom had recurrent episodes of symmetric proximal muscle pain and swelling as prominent features of their crises. Muscle biopsies showed acute myonecrosis with a minimal inflammatory reaction as well as myofibrosis with abundant collagen deposition. Chronic sequelae consisted of muscle induration, atrophy, and contractures. 
Effect of chronic ethanol feeding on high density lipoprotein subfractions in rats. We have reported previously that chronic alcohol consumption in the rat produced elevated total serum high density lipoprotein (HDL) fraction, but HDL particles of the alcohol-fed rat were deficient in apolipoprotein (apo) E. In that report, serum HDL particles were prepared by successive ultracentrifugation method and there were concerns that the apo E deficiency in HDL particles was artificially produced by centrifugal forces. In the present report, apo Al affinity column chromatography was used instead of successive ultracentrifugation and it likewise yielded HDL particles from alcohol-fed rats that exhibited lower apo E: apo Al ratio than HDL from control rats (0.185 +/- 0.016 vs. 0.303 +/- 0.017, respectively). When the total serum lipoprotein fraction (d less than 1.21) was analyzed by high performance liquid chromatography (HPLC), both HDL and VLDL peaks were higher in alcohol-fed rats than controls. The size of apo E deficient HDL particles from alcohol-fed rats determined by HPLC did not differ from that of normal HDL particles. When HDL (1.063 less than d less than 1.21) was subfractionated into HDL2 (1.063 less than d less than 1.125) and HDL3 (1.125 less than d less than 1.21), only HDL2 of alcohol-fed rats showed lowered apo E: apo Al ratio when compared with same HDL subfraction of control animals. Therefore, the molecular structure of only HDL2 (but not HDL3) was affected by alcohol-feeding. Another HDL subpopulation which is enriched with apo E, i.e. HDL1 (1.054 less than d less than 1.063), was also prepared. 
Use of echocardiography for patient management in chronic ischemic heart disease. Myocardial ischemia causes regional myocardial contractile and relaxation abnormalities. The extent of ischemia is determined by the distribution and severity of coronary artery stenoses. In coronary heart disease, two powerful predictors of prognosis are the coronary anatomy and ventricular function. Management in coronary heart disease is directed by accurate diagnosis and individualized objectives. Echocardiography at rest and exercise, combined with Doppler and color flow imaging, are properly applied to the differential diagnosis of common clinical syndromes in ischemic heart disease, the identification of the proximal coronary arteries, and the effects of ischemia and prior infarction. Subsequent use of coronary arteriography partially depends on the philosophy regarding the applicability of coronary surgery or angioplasty in an individual patient. Prediction of multivessel, left main, or proximal left anterior descending coronary artery disease by extensive wall motion abnormalities or an abnormal left ventricular ejection fraction may direct the clinician to coronary arteriography to select among coronary surgery, angioplasty, or medical management. 
Treatment of advanced-stage Hodgkin's disease: alternating noncrossresistant MOPP/CABS is not superior to MOPP. One hundred twenty-five assessable patients with advanced-stage Hodgkin's disease were randomized to receive mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) or MOPP alternating with lomustine (CCNU), doxorubicin, bleomycin, and streptozocin (CABS). The median follow-up is 7.7 years. The complete response rate was 60 of 66 MOPP-treated patients (91%) and 54 of 59 MOPP/CABS-treated patients (92%) (difference not significant). The level of the disease-free survival curve at longest follow-up is 65% for MOPP-treated patients and 72% for MOPP/CABS-treated patients (difference not significant). The overall survival at 12 years is projected at 68% for MOPP-treated patients and 54% for MOPP/CABS-treated patients (difference not significant). Thus, there were no significant differences in efficacy between MOPP and MOPP/CABS. However, MOPP/CABS was more emetogenic than MOPP, and four MOPP/CABS-treated patients went on to develop secondary acute leukemia. No MOPP-treated patients developed leukemia. High initial erythrocyte sedimentation rate (ESR) and high platelet counts adversely affected treatment outcome. MOPP-treated patients who received greater than 81% of the projected dose intensity of vincristine over the first three cycles had significantly improved disease-free survival rates over those receiving less than 81%. MOPP/CABS-treated patients who received greater than 82% of the projected dose intensity of vincristine had significantly better overall survival than those who received less than 82%. Disease-free survival on both arms was significantly better in patients who received greater than 84% of the projected dose intensity of all agents. The effect of dose intensity was particularly apparent in patients with poor prognostic factors where those who received greater than 84% of the projected dose intensity of all agents had significantly improved disease-free and overall survival. 
HLA-DR expression on the microvasculature of portal tracts in idiopathic portal hypertension. Immunohistochemical characteristics and relation to portal phlebosclerosis. We recently reported that HLA-DR antigen was expressed on the microvasculature of portal tracts more frequently in idiopathic portal hypertension (IPH) than in normal livers or in other hepatic diseases, and that this HLA-DR expression may be involved in the development of the portal venopathy characteristic of IPH. The present study was performed to evaluate the relationship between the HLA-DR expression and portal tract lesions, as well as to investigate the immunohistochemical characteristics of the HLA-DR-positive microvasculature using liver wedge biopsy specimens obtained from 32 patients with IPH. According to the degree of phlebosclerosis of the portal veins, the portal tracts were divided into three groups: mild, moderate, and severe. The microvasculature in portal tracts was positive for HLA-DR in 21 (66%) of the 32 specimens and in 133 (44%) of 302 portal tracts. In the 21 specimens, there was no significant difference in the prevalence of HLA-DR-positive microvasculature among the three groups: it occurred in 57 (66%) of 86 portal tracts in the mild group, 53 (61%) of 87 portal tracts in the moderate group, and 23 (49%) of 47 portal tracts in the severe group. The HLA-DR-positive microvasculature was positive for type IV collagen and receptors of Ulex europaeus lectin I, suggesting that HLA-DR-positive microvessels are blood vessels. These findings suggest that HLA-DR antigen is already expressed on portal microvessels in the incipient stage of IPH, and that HLA-DR expression persists during the progression of portal phlebosclerosis. The HLA-DR expression may be an initiating factor leading to immunologic assault on portal microvessels in IPH. 
A prospective comparison of thromboembolic stockings, external sequential pneumatic compression stockings and heparin sodium/dihydroergotamine mesylate for the prevention of thromboembolic complications in urological surgery. Deep venous thrombosis and pulmonary emboli are reported to occur in up to 66% of the patients undergoing a major urological operation. Thromboembolic stockings, external sequential pneumatic compression stockings and anticoagulant agents, such as heparin sodium plus dihydroergotamine mesylate, have been suggested to decrease the risk of deep venous thrombosis and pulmonary emboli. A total of 74 evaluable patients undergoing a major urological operation was randomized to receive either thromboembolic stockings, external sequential pneumatic compression stockings, or heparin plus dihydroergotamine as prophylaxis against deep venous thrombosis and pulmonary emboli. 111Indium-labeled platelet scans, performed preoperatively and on days 1, 3 and 6 postoperatively, were used to diagnose deep venous thrombosis and pulmonary emboli. Mean patient age was 63 years and all but 1 operation was performed for neoplastic disease. Deep venous thrombosis was detected in 5 of 25 patients (20%) with thromboembolic stockings, 3 of 24 (12.5%) with external sequential pneumatic compression stockings and 2 of 25 (8%) with heparin plus dihydroergotamine. There was no difference in blood loss or complications among the groups. Although statistical significance among the treatment groups was not reached in this study, the trend to a decrease in deep venous thrombosis and pulmonary emboli with external sequential pneumatic compression stockings and heparin plus dihydroergotamine, and an absence of an increase in morbidity in these groups supports the use of these modalities to decrease the morbidity and mortality of deep venous thrombosis and pulmonary emboli. 
Why don't all heavy snorers have obstructive sleep apnea? Patients with obstructive sleep apnea (OSA) and heavy snorers without apnea both show intrathoracic suction pressures during sleep that exceed their static upper airway closing pressures. Complete airway occlusion, however, occurs only in the former patient group. We hypothesized that the kinetic properties of the airflow would be different in these two types of patients because of differences in upper airway morphology. The pharyngeal computed tomography (CT) was used to measure the cross-sectional areas of the upper airways in 15 patients with OSA, 25 nonapneic heavy snorers, and 14 control subjects while they were awake. Nocturnal breathing was monitored with the static charge-sensitive bed (SCSB). The patients with OSA had a narrower airspace at the velopharyngeal (VP) level than the controls (p less than 0.01); the nonapneic snorers did not differ from the other groups. At the tongue base (TB) and the hyoid bone (HB) levels there was no difference between the OSA and the control groups, but the nonapneic snorers had narrower airways at both of these levels compared with control subjects (p less than 0.01) and at the hyoid bone level compared with the OSA group (p less than 0.05). The VP/HB ratio was the parameter that best distinguished the patients with OSA from the nonapneic snorers (lower in the OSA group, p less than 0.001). We suggest that airway collapse during sleep is favored by a narrow velopharynx associated with large hypopharynx. Some heavy snorers may not have an oropharyngeal collapse because the peak inspiratory suction pressure could already be damped down at the level of the relatively narrow hypopharyngeal airways. 
Internal mammary artery subclavian vein fistula following internal jugular vein catheterization. A case report and review of the literature. We have recently treated a patient with an arteriovenous fistula that developed after a right internal jugular vein catheterization. The patient was found to have a pulsatile hematoma and a bruit five days after removal of a temporary pacemaker catheter. Digital subtraction arteriography documented a fistula between the right internal mammary artery and subclavian vein. The fistula was surgically repaired via the cervical route. To our knowledge, an arteriovenous fistula between the internal mammary artery and subclavian vein has not been previously described as a complication of a percutaneous internal jugular vein catheterization. 
Animal model of gluten induced enteropathy in mice. The aim of our experiments was to produce a local T cell mediated immune response to gliadin in the mouse small intestine as a possible animal model of gluten sensitive enteropathy, coeliac disease. BALB/c and BDF1 mice were immunised systemically with gliadin in complete Freund's adjuvant. The jejunal mucosa was challenged by feeding a gluten containing diet, and villus and crypt lengths, crypt cell production rate, and intraepithelial lymphocyte counts were determined to assess mucosal cell mediated immunity. In some animals permeability and local immunity were modulated by concurrent intestinal anaphylaxis or a graft versus host reaction. There were no changes in the jejunal mucosa of BALB/c mice fed a gluten containing diet after having been parenterally immunized. When, however, mice were parenterally immunised with gliadin, fed a gluten containing diet, rendered hypersensitive to helminth antigen by infection with the nematode parasite Nippostrongylus brasiliensis, and challenged intravenously to produce intestinal anaphylaxis crypt cell production rate was significantly higher than in ovalbumin immunized controls at 12 days after parasite challenge. Finally, graft versus host reaction was induced in BDF1 mice that had been parenterally immunised with gliadin and were on a gluten containing diet. Two weeks later these mice had significantly longer crypts and a higher crypt cell production rate and intraepithelial lymphocyte count than control, unimmunized mice with graft versus host reaction. We conclude that active immunization with gliadin does not in itself produce intestinal cell mediated immunity to gliadin contained in the diet, or enteropathy. 
Adrenal suppression and growth retardation after injection of periocular capillary hemangioma with corticosteroids. Adrenal suppression and/or growth retardation were noted in two patients after injection of periocular capillary hemangiomas with corticosteroids. Parents should be warned of these two potential complications of intralesional corticosteroid therapy. Baseline and posttreatment adrenal function should be monitored. If iatrogenic adrenal suppression occurs, supplemental systemic corticosteroids may be necessary in situations involving systemic stress such as infection or surgery. 
Idiopathic myointimal hyperplasia of mesenteric veins. Nonthrombotic occlusion or stenosis of the mesenteric veins is a rare cause of intestinal ischemia that usually occurs in association with systemic vasculitis. The current report includes four male patients with segmental ischemic colitis caused by idiopathic myointimal hyperplasia in the small mesenteric veins and their intramural branches; neither vasculitis nor arterial involvement were present. Three of the four patients were less than or equal to 38 years of age; the fourth was 67. All four patients were previously healthy and had no history of drug use of any kind. Clinical findings included abdominal pain, diarrhea, bloody stools, and colonic strictures discovered by barium enema. The intima of the mesenteric and intestinal mural veins was focally thickened by a marked increase in cells and matrix between the endothelium and internal elastic lamina, whereas the vessel walls external to the thickened intima appeared normal. Histochemistry and immunoreactivity with antibodies to muscle-specific actins (HHF-35) disclosed that the intimal thickening was caused by proliferation of smooth muscle cells in a proteoglycan matrix. All patients recovered completely after segmental resection of the ischemic portion of the colon and had no recurrence of intestinal symptoms on follow-up of up to 7 years. These unusual venous lesions do not appear to have been previously described; their etiology and pathogenesis remain unknown. 
Ten-year follow-up of patients with secondary amenorrhea and normal prolactin. A group of 46 patients with secondary amenorrhea without galactorrhea or hyperprolactinemia were studied retrospectively after being clinically categorized into four groups with the use of progesterone-induced uterine bleeding and measurement of serum gonadotropins and prolactin levels. The ability to have regular spontaneous menstrual cycles and to conceive was assessed after a follow-up period of 10 years. Patients who had been classified as having hypothalamic pituitary "failure" (hypoestrogenic amenorrhea) with low levels of circulating estradiol had a greater rate of recovery of spontaneous ovulation and menses when compared with patients who had been classified as having only hypothalamic pituitary dysfunction (euestrogenic amenorrhea). The patients with diagnosis of hyperandrogenic chronic anovulation or polycystic ovary syndrome generally required clomiphene citrate for induction of ovulation and almost all the patients with premature ovarian failure (hypergonadotropic amenorrhea) remained estrogen-deficient and unable to ovulate. Hyperprolactinemia or an identifiable pituitary adenoma has not developed in any of the patients to date. 
Could recurrent cholangitis after Roux-en-Y hepaticojejunostomy be explained by motor intestinal anomalies? A manometric study. The aim of this study was to describe the motor patterns found in two patients with recurrent cholangitis episodes after Roux-en-Y hepaticojejunostomy. In one patient, cholangitis was due to a stenosis of the anastomosis between the limb and the left intrahepatic bile duct, while motility of the limb, duodenum, and distal jejunum was normal. In the second patient, no anatomical explanation was found for cholangitis attacks. However, although the duodenal motor activity was normal, the motility of the limb and of the jejunum below the jejunojejunal anastomosis was grossly abnormal: permanent minute rhythm, phase IIIs absent or rare and slowly propagated, all motor abnormalities that could promote bacterial overgrowth in the limb. This stresses the interest in performing motor studies of the Roux-limb when cholangitis remains unexplained after Roux-en-Y hepaticojejunostomy. 
Tissue eosinophilia and eosinophil degranulation in orbital pseudotumor. To investigate the participation of the eosinophil in orbital pseudotumor, the authors studied surgical biopsy specimens from nine patients with pseudotumor. Surgical biopsy specimens of orbital tissue from four patients with Graves' ophthalmopathy and autopsy specimens of orbital tissue from six patients without orbital diseases served as controls. Eosinophil infiltration and degranulation were assessed by immunofluorescence staining of formalin-fixed, paraffin-embedded tissues for the cytotoxic eosinophil granule major basic protein. Eosinophil infiltration and extracellular major basic protein deposition were evident in all orbital pseudotumor specimens. In contrast, no eosinophil infiltration or extracellular major basic protein deposition was present in any of the ten control specimens. These findings indicate that eosinophil degranulation is found in orbital pseudotumor, and they also identify yet another clinical entity where eosinophil infiltration and degranulation are associated with fibrosis. 
Arteriovenous fistulas complicating biopsy of renal allografts: treatment of bleeding with superselective embolization. The use of superselective embolization was assessed as a treatment for bleeding from postbiopsy arteriovenous fistulas (AVFs) in renal transplants. AVFs commonly occur after biopsy procedures in renal transplants, but severe bleeding is rare. Transcatheter embolization can be used to control bleeding, but unless it is sufficiently selective, the procedure results in loss of significant amounts of renal parenchyma. During a 4-year period, embolization procedures were attempted in seven patients 30-65 years old. All had AVFs shown on arteriography. Five patients underwent embolization; occlusion occurred only in the branch supplying the AVF. In one patient with three large AVFs, two were found to have occluded the day after embolization was attempted. In another, an AVF occluded when superselective catheter position was achieved but before embolization. Catheter manipulation in these cases may have precipitated occlusion. In five cases, coaxial embolization techniques were used. Embolization materials consisted of coils in three cases: 0.038 in. (0.97 mm) in one case, 0.025 in. (0.64 mm) in one case, 0.018 in. (0.46 mm) in one case; 0.038 in. (0.97 mm) coils and gelatin foam particles in one case; and localized contrast extravasation in one case. Serum creatinine level was measured before and after embolization in all patients, and radionuclide studies were undertaken in three cases. In all patients, bleeding was effectively controlled. None of the patients showed an increase in serum creatinine level after embolization, and in four, significant improvement was seen. Nuclear medicine studies showed no loss of renal function and a dramatic improvement in one patient. No complications due to the procedure were seen. Our experience suggests that superselective embolization with coaxial catheter techniques is an effective method of treating bleeding from postbiopsy AVFs in renal transplants with minimal loss of renal parenchyma. 
Effect of preexisting brain ischemia on sympathetic nerve response to intracranial hypertension. The performance of the sympathetic nervous system during sustained moderate cerebral ischemia (CI) was examined in the present study. For this purpose, a Cushing response was elicited repeatedly during incomplete global CI in anesthetized artificially ventilated cats after vagotomy and baroreceptor denervation. In control animals without CI, sympathetic activity in response to brief elevation of intracranial pressure (ICP) showed a well-repeatable two-phase reaction. During CI there was a progressive deterioration of background sympathetic nerve discharge (SND) over a period of 30 min. SND response to repeated elevation of ICP was initially similar to control response but later with progression of CI was seriously changed. 1) Instead of the usual hyperactivation, sympathetic nerve activity was depressed during intracranial hypertension. 2) The characteristic desynchronized activity either appeared later during the reperfusion period or remained absent. The progressive loss of SND response to raised ICP in developed CI was compared with the changes seen in experiments in which repeated ICP elevations were superimposed on asphyxia. These findings suggest that the sympathetic component of the Cushing reaction strongly depends on the actual state of brain stem autonomic circuits and may be seriously altered in pathological situations involving ischemic brain injury. 
Free magnesium levels in normal human brain and brain tumors: 31P chemical-shift imaging measurements at 1.5 T. We have studied a series of normal subjects and patients with brain tumors, by using 31P three-dimensional chemical shift imaging to obtain localized 31P spectra of the brain. A significant proportion of brain cytosolic ATP in normal brain is not complexed to Mg2+, as indicated by the chemical shift delta of the beta-P resonance of ATP. The ATP beta-P resonance position in brain thus is sensitive to changes in intracellular free Mg2+ concentration and in the proportion of ATP complexed with Mg because this shift lies on the rising portion of the delta vs. Mg2+ titration curve for ATP. We have measured the ATP beta-P shift and compared intracellular free Mg2+ concentration and fractions of free ATP for normal individuals (n = 6) and a limited series of patients with brain tumors (n = 5). In four of the five spectra obtained from brain tissue containing a substantial proportion of tumor, intracellular free Mg2+ was increased, and the fraction of free ATP was decreased, compared with normal brain. 
Otolaryngologic manifestations of gastroesophageal reflux. The exact incidence of gastroesophageal reflux (GER) is unknown, although it is estimated that at least 25% of patients with GER have head and neck symptoms alone. These symptoms may consist of one or more of the following: excess salivation, hoarseness, "post-nasal drip," voice change, persistent coughing, food sticking in the throat, globus hystericus, otalgia, throat clearing, neck pain, sore throats, the sensation of a lump in the throat, choking spells, and bronchospasm. Carcinoma of the larynx and upper aerodigestive tract may be a consequence of chronic reflux. GER, especially when the classic symptoms of reflux are absent, is frequently overlooked as a cause of these problems. This article reviews the symptoms and pathophysiology of these conditions. The diagnostic and therapeutic modalities available to us in managing these patients are also discussed. 
The current status of maternal and fetal blood flow velocimetry. Significant progress has been achieved in regard to normative data for uteroplacental and fetal blood flow velocity and the factors which may affect these observations. Associations have been demonstrated between abnormal indices of maternal and fetal blood flow velocity and pregnancy-induced hypertension, fetal growth retardation, fetal blood gas measures, and intrapartum clinical fetal distress. However, in general, the predictive power is modest and no evidence has yet been provided to indicate that these measures can be used as a screening test in the general obstetric population. Continuing research is highly desirable. At the present time, the use of Doppler assessment of blood flow in pregnancy should be limited to the investigational setting. 
Central retinal vein occlusion associated with drusen of the optic disc. A 43-year-old man had gradual visual changes OD. Funduscopic examination revealed central retinal vein occlusion OD. Complete ocular examination revealed bilateral drusen of the optic disc, confirmed by b-scan ultrasonography. Complete systemic evaluation showed no other etiology for the central retinal vein occlusion. Over a ten-year follow-up, in the absence of systemic disease or other local ocular anomalies, we concluded that central retinal vein occlusion can arise from external compression secondary to drusen of the optic disc. 
Congenital sideroblastic anaemia in two girls. Transfusion dependent congenital sideroblastic anaemia occurred in infancy in two unrelated girls. One girl developed early organ failure which was not prevented by standard chelation treatment. The combination of modest iron burden and putative intrinsic mitochondrial dysfunction could have accounted for the clinical picture. The other girl remained well, receiving regular transfusion and standard chelation treatment. She had normal liver function and no other evidence of organ damage. The syndrome is unlikely to be due to extreme lyonisation in carriers of the usual X-linked condition. The contrasting clinical patterns seen in these two patients suggest that transfusion dependent congenital sideroblastic anaemia may comprise a heterogeneous group of disorders. It is suggested that such children be carefully monitored for evidence of increasing iron overload so that organ damage can be prevented. 
Novel therapy for the treatment of human carcinoid. Development of effective treatment for patients with carcinoid tumors has been hampered by lack of an experimental model. The authors have established the only long-term cell line of a functioning human pancreatic carcinoid tumor (BON) that produces tumors in nude mice. In this study the authors examined the effect of three agents, alpha-interferon (IFN), a somatostatin analog, SMS 201-995 (SMS), and an inhibitor of polyamine biosynthesis, alpha-difluoromethylornithine (DFMO), on the growth of BON tumors. BON was implanted bilaterally as 3-mm2 pieces (subcutaneously [sc]) into male BALB/c nude mice. In the first study, 23 mice were randomized to four groups: control, IFN (1 x 10(6) units, sc, four times a day), IFN + SMS (300 micrograms/kg, intraperitoneally, three times a day), and IFN + 3% DFMO in drinking water. Treatments were initiated on day of tumor implantation. In the second study, mice were randomized to six groups: control, IFN, SMS, DFMO, IFN + SMS, IFN + DFMO, and IFN + SMS + DFMO. Treatments were started on day 15 after tumor implantation. Tumor area and body weights were measured weekly. In both studies mice were killed on day 28 after BON implantation and tumors removed, weighed, and analyzed for DNA and RNA content. In the first study, IFN either alone or in combination with SMS or DFMO suppressed BON tumor growth. When treatment was initiated after established tumor growth (study 2), however, the only effective treatments for suppression of growth of BON were IFN + DFMO and IFN + DFMO + SMS. 
Magnetic resonance imaging of human spinal cord infarction. Magnetic resonance images obtained in two cases of spinal cord infarction are described: one with hemorrhagic thoracic cord infarct, the other with ischemic cervical cord infarct with sequential magnetic resonance imagings. An enlarged cord with strand-shape or longitudinal hypointensity on both T1- and T2-weighted images was noticed in the hemorrhagic infarct; hypointensity on the T2-weighted image was thought to be due to hemosiderin, which shortens T2 relaxation. In the ischemic infarct, a small, round area of hypointensity on T1-weighted images, and of hyperintensity on T2-weighted images, noted 9 hours postictus ("early infarct") changed on the 22nd day to a cephalocaudal strandlike hypointensity on T1-weighted image, which was enhanced by Gd-DTPA. The hypointensity suggested "pencil-like softening" in "medium" age infarct. On postictal day 49, it showed an extensive homogeneous hypointensity involving several segments of the cord on T1-weighted images and hyperintensity on T2-weighted images with negative Gd-DTPA enhancement suggesting "late transverse infarct." We considered that these changes are of value in diagnosing spinal cord infarcts on magnetic resonance imagings. 
High rate of portal thrombosis after splenectomy in patients with esophageal varices and idiopathic portal hypertension. Data on 126 consecutive patients who were admitted to our clinics from January 1979 to May 1989 were scrutinized to assess changes in portal hemodynamics following splenectomy. Two groups were classified: (1) a group of 106 patients with cirrhosis of the liver and (2) a group of 20 patients with idiopathic portal hypertension (IPH). Portal thrombosis was present in five (25.0%) of the 20 patients with IPH and in two (1.8%) of the 106 patients with cirrhosis of the liver. As seen on celiac arteriography, the mean (+/- SD) diameter of the trunk of the splenic artery and vein was 8.99 +/- 1.55 and 16.2 +/- 3.6 mm, respectively, in patients with IPH, while it was 7.94 +/- 1.28 and 14.2 +/- 3.1 mm, respectively, in patients with cirrhosis of the liver. Changes in portal venous pressure were 78.4 +/- 59.4 mm H2O in patients with IPH and 43.5 +/- 38.7 mm H2O in patients with cirrhosis of the liver. There were no significant differences in the maximum level of thrombocytes in patients with IPH or in those patients with cirrhosis of the liver. These events suggest that portal thrombosis can occur with a significantly higher incidence in patients with IPH than in those patients with cirrhosis of the liver after splenectomy, and a decrease in blood flow in the portal vein may be closely linked to the formation of portal thrombosis after splenectomy in patients with IPH. Preoperative examination of portal hemodynamics must be thorough. 
Stress-induced gastroduodenal lesions and total parenteral nutrition in critically ill patients: frequency, complications, and the value of prophylactic treatment. A prospective, randomized study. OBJECTIVE: To assess the frequency, complications, and value of prophylactic treatment of stress-induced gastroduodenal lesions. DESIGNS: Patients were prospectively randomized to treatment with total parenteral nutrition, either alone, with sucralfate, or with ranitidine. SETTING: A multidisciplinary ICU from a tertiary care referral center. PATIENTS: Ninety-seven patients submitted to prolonged mechanical ventilation, with normal hepatic and renal function, in metabolic stress, and receiving total parenteral nutrition. INTERVENTIONS: On admission, we determined the Acute Physiology and Chronic Health Evaluation II score and the catabolic index score. We also performed an endoscopic examination on day 3, every 7 days subsequently, and whenever needed. Thirty patients received total parenteral nutrition alone. Twenty-four patients received total parenteral nutrition and sucralfate (1 g by nasogastric tube every 4 hrs). Nineteen patients received total parenteral nutrition and ranitidine (50 mg iv every 6 hrs). MAIN RESULTS: The overall occurrence rate of gastroduodenal mucosal damage was 29.6%. The overall frequency rate for stress ulcerations was 15.6% and was 6.2% for stress hemorrhage. There were no deaths secondary to stress hemorrhage. The difference in the frequency of stress-induced mucosal lesions and stress hemorrhage between the studied groups was not statistically significant. CONCLUSIONS: Additional prophylaxis to total parenteral nutrition in the form of sucralfate and ranitidine to prevent acute upper gastrointestinal bleeding is not required in this group of ICU patients. 
Intraperitoneal thrombolytic agents in relapsing or persistent peritonitis of patients on continuous ambulatory peritoneal dialysis. Urokinase or streptokinase was instilled intraperitoneally as an adjunct to the antibiotic therapy in 16 episodes of relapsing or persistent peritonitis in CAPD patients. In eight patients the combination of antibiotics and intraperitoneal thrombolytic agents resulted in clearing of the infection with no recurrences. The treatment failed in eight other patients, who had their peritoneal catheters removed. Six of the last eight patients had either abdominal wall abscesses or persistence of the bacteria on the wall of the peritoneal catheter. Elevated post-intraperitoneal instillation peritoneal fluid neutrophil counts and positive post-instillation peritoneal fluid cultures predicted failure of the intraperitoneal instillation of thrombolytic agents in most instances. Intraperitoneal instillation of urokinase or streptokinase may help cure approximately 50% of the episodes of relapsing for persistent peritonitis. Post-instillation peritoneal fluid cell counts and cultures should be monitored. Radiologic investigation for abdominal wall or intraabdominal abscesses is indicated if intraperitoneal instillation of urokinase or streptokinase fails to eradicate peritonitis. 
Expression of c-jun, jun-B, and c-fos proto-oncogenes in human primary melanocytes and metastatic melanomas. Analysis of the regulation of c-jun, jun-B, and c-fos RNA transcript expression was performed in human primary melanocytes and metastatic melanoma cell strains. The medium requirements for human melanocyte in vitro growth are phorbol esters, agents that elevate intracellular cAMP levels, hormones, and growth factors. Cellular jun, jun-B, and c-fos gene expression are known to be affected by growth promoting agents. In primary melanocytes, the expression of c-jun, jun-B, and c-fos RNA transcripts was dependent on the growth-promoting agents present in the medium. Uniformly high c-jun, jun-B, and c-fos RNA transcript levels were observed in melanocytes cultivated in complete medium. Higher levels of c-jun RNA transcripts and low levels of c-fos RNA transcripts were observed in melanocytes cultivated in plain medium. In contrast, a range of c-jun, jun-B, and c-fos RNA transcript levels was detected in metastatic melanoma cell strains cultivated in medium with or without serum. In general, an increase in jun-B and c-fos RNA transcript expression and a decrease in c-jun RNA transcript expression was observed in metastatic melanomas compared to neonatal melanocytes. These data suggest a potential role for c-jun, jun-B, and c-fos genes in the transformation of melanocytes to malignant melanoma. 
Pain characterization in cancer patients and the analgetic response to epidural morphine. In 48 patients with pain related to malignancy, a pain characterization was performed during oral opioid therapy. After an optimal epidural morphine regimen had been established, the alteration in pain relief was evaluated by means of a visual analogue scale. The CSF and plasma morphine concentrations at minimum steady state were then analysed in 28 patients and related to the degree of pain relief. The efficacy of the spinal treatment ranked in the following order: somatic greater than visceral greater than radiating = 0, but the difference was only significant between the somatic and radiating pain groups. There was a tendency for continuous pain to be better relieved than intermittent pain. No correlations were found between the CSF or plasma morphine concentrations and the degree of pain relief, suggesting that not all pain impulses are modulated in a dose-dependent manner by morphine at the spinal level. Pain characterization may be instrumental in providing an optimal spinal opioid analgesia in malignancy. Moreover, there is a need for better defined diagnostic criteria for clinical pain characterization. 
Diagnosis of genetic disease by primer-specified restriction map modification, with application to cystic fibrosis and retinitis pigmentosa Detection of small alterations or abnormalities in genomic DNA (eg, point mutations or small deletions) has become increasingly important in the diagnosis of genetic disease and polymorphism. When a mutation or polymorphism creates a new restriction endonuclease site, it can easily be identified by polymerase chain reaction (PCR) amplification of the DNA region of interest, followed by digestion with the restriction endonuclease. However, useful restriction sites are the exception, and a variety of specialised techniques have been developed to identify subtle DNA abnormalities. We have shown that where a DNA mutation does not create a useful novel restriction site, such a site can be introduced by PCR and specially chosen primers. The approach is simple and inexpensive and should be broadly applicable in the diagnosis of genetic polymorphism and mutation. The technique is illustrated here by the three base-pair deletion responsible for most cases of cystic fibrosis and by detection of the point mutation in the rhodopsin gene that has been associated with some cases of autosomal dominant retinitis pigmentosa. 
Percutaneous mitral valvuloplasty following surgical repair of sinus venosus atrial septal defect. Mitral valvuloplasty performed 5 y after repair of a sinus venosus ASD was difficult because of a thickened septum, but resulted in improved mitral valve opening and did not lead to ASD. Thus, prior repair of a sinus venosus ASD may not be an absolute contraindication to mitral valvuloplasty. 
Value of quantitative nucleolar features in the preoperative cytological diagnosis of follicular neoplasias of the thyroid. Nucleolar prevalence, size, and outline were investigated on cytological material from cold thyroid nodules obtained by fine needle aspiration. The percentage of nucleolated nuclei in follicular adenoma (32 cases) was less than in follicular carcinoma (26 cases). In adenoma most nuclei contained one nucleolus, and nuclei with two or more nucleoli were less common than in carcinoma where most cases showed the highest nucleolar diameter values. There was some overlap between adenomas and carcinomas, however, when the mean of the 10 largest values of the major nucleolar diameter was considered. In follicular carcinoma the percentage of marginated nucleoli--that is, those touching the nuclear membrane--was, in general, greater than 20%; in adenoma the values were equal to or lower than 16%. The overlap index showed that the percentages of marginated nucleoli and nucleolated nuclei are the two best discriminatory features between adenoma and carcinoma. 
Experimental arterial thrombosis in nonhuman primates. The baboon offers many advantages as an experimental animal to study vascular disease, thrombus formation and dissolution, effects of mediating variables, and the relative efficacy of therapeutic interventions. Each specific application for testing therapeutic agents may require testing in somewhat different model systems. For example, although the arteriovenous vascular graft model is efficient, cost effective, and well adapted to study of interventions for acute arterial thrombosis, surgical endarterectomy extends the evaluation to include interactions with the injured vascular wall. As the antithrombotic products of genetic engineering and molecular biology emerge, it will be increasingly important to have relevant, reproducible, and quantitative approaches to evaluate their effects in vivo. 
Respiratory-related recruitment of the masseter: response to hypercapnia and loading. To test the hypothesis that a muscle that closes the jaw, the masseter, can be recruited by ventilatory stimuli, we studied the electromyographic activation of the masseter and genioglossus in seven normal awake males who were exposed in random order to progressive hyperoxic hypercapnia, inspiratory threshold loading (-40 cmH2O), and combined hypercapnia and loading. With hypercapnia, the masseter was generally recruited after the genioglossus had been activated. Once recruited, activation of both muscles increased linearly with increasing CO2. Combined hypercapnia and loading produced more activation than either stimulus alone. These data indicate that the masseter is activated by ventilatory stimuli that activate the genioglossus. Earlier recruitment of the genioglossus suggests that activation of the masseter serves to stabilize the mandible and allow the genioglossus to function as a more efficient dilator of the upper airway. 
Acute pandysautonomic neuropathy. Acute pandysautonomic neuropathy is characterized by severe postganglionic sympathetic and parasympathetic dysfunction, with relative or complete sparing of motor and sensory function. Of four reported cases with sural nerve biopsies, two were normal and two abnormal, revealing loss of small myelinated and unmyelinated fibers. We present a patient with pandysautonomic neuropathy and elevated CSF protein whose sural nerve biopsy showed active axonal degeneration. 
Aseptic meningitis following cardiac transplantation: clinical characteristics and relationship to immunosuppressive regimen. Neurologic disorders are uncommon but alarming complications of cardiac transplantation. Of 29 patients from the Utah Cardiac Transplant Program (UCTP) who had lumbar puncture because of change in neurologic function, or to assess fever of uncertain etiology, CSF pleocytosis was present in 14 patients, 4 of whom had an active infectious process involving the nervous system. In 10 other patients, CSF pleocytosis with negative cultures appeared following treatment with OKT3 monoclonal antibody. The most prominent clinical signs of this aseptic meningitis syndrome are fever and transient cognitive dysfunction. 
Extubation after transsternal thymectomy for myasthenia gravis: a prospective analysis. Recommendations concerning postoperative extubation after thymectomy for myasthenia gravis are presently based upon retrospective chart reviews. We present the results of a prospective investigation of time to extubation after thymectomy for 14 patients over a 12-month period based upon a protocol that included preoperative immunologic therapy, combined epidural and general anesthesia, postoperative epidural narcotic analgesia, and a standardized approach to discontinuation of ventilatory support. After a neurologist took measures to optimize preoperative neuromuscular function, all 14 patients received agents to produce lumbar epidural anesthesia and light general anesthesia. Muscle relaxants were avoided in all but one patient. Postoperative analgesia was initially maintained with epidural hydromorphone, then therapy was switched to patient-controlled intravenous morphine sulfate. Criteria for weaning from mechanical ventilation, first measured at the end of anesthesia, were partial pressure of oxygen (arterial) greater than or equal to 90 mm Hg (fraction of inspired oxygen = 0.40), partial pressure of carbon dioxide (arterial) less than or equal to 50 mm Hg, pH greater than or equal to 7.30, and respiratory rate less than or equal to 30 breaths/min. If these criteria were not met, ventilatory support was continued postoperatively with intermittent mandatory ventilation, and the patient was weaned gradually from this support. Criteria for extubation included meeting the criteria for weaning, vital capacity greater than or equal to 10 mL/kg, and inspiratory pressure better than -30 cm H2O. Criteria for reintubation included tachypnea (respiratory rate greater than 40 breaths/min), respiratory acidosis not due to narcotics, or vital capacity less than or equal to 8 mL/kg. The mean time to extubation was 9 hours (range, 0.75 to 25 hours). Mean preoperative vital capacity was 2.59 +/- 0.64 L (range, 1.90 to 4.20), which decreased approximately 50% to 1.19 +/- 0.39 L (range, 0.70 to 2.0) at the time of extubation. No patient required reintubation. Half of the patients required postoperative anticholinesterase therapy based upon serial neurologic examinations; there were no instances of cholinergic crisis. Thirteen patients returned to the ward on the first postoperative day, and one on the second day. Thirteen patients preferred epidural analgesia to patient-controlled analgesia. The time to extubation and average length of stay in an intensive care setting were markedly reduced compared to those reported in previous retrospective studies. We conclude that a multidisciplinary approach that optimizes neuromuscular function and decreases poststernotomy pulmonary insult will shorten the time to extubation and decrease the length of stay in the intensive care or recovery room after thymectomy. 
The use of potassium-titanyl-phosphate laser for laparoscopic removal of ovarian endometrioma. From January 1989 through January 1990, 31 patients thought to have ovarian endometrioma at ultrasonography were treated by operative laparoscopy and potassium-titanyl-phosphate laser. The endometriomas ranged from 2 to 9.2 cm in diameter by preoperative transvaginal ultrasonography. The operative procedure used was a three-puncture technique with a 600 micron fiber attached to a potassium-titanyl-phosphate laser. The power setting was 10 W with a continuous pulse. In all cases endometriomas were opened, drained, and irrigated, and the potassium-titanyl-phosphate laser was used to vaporize or remove the entire cyst lining. The ovarian edges were inverted with the laser at the end of the procedure. With one exception, there was no recurrence of endometrioma at 1, 3, and 6 months after the procedure, on the basis of transvaginal ultrasonography or laparoscopy. In one case, 4 months after the initial laparoscopic procedure, exploratory laparotomy was performed for resection of a large, recurrent endometrioma. The use of the potassium-titanyl-phosphate laser allows the laparoscopic surgeon an aggressive approach to ovarian endometriomas that in the past necessitated exploratory laparotomy. 
Localization and needle aspiration of breast lesions: complications in 370 cases. A prospective study of the immediate complications of 370 consecutive breast-imaging procedures (203 wire localizations and 167 radiographically or sonographically guided fine-needle aspirations) is reported. Vasovagal reactions occurred in 27 (7%) of 370 cases, ranging in severity from syncope (four of 370, 1%) to mild light-headedness. These vasovagal reactions were independent of procedure type or use of local anesthesia, but were more common in younger patients. Other complications included prolonged (5 min or longer) bleeding (three of 370, 1%) and extreme pain (two of 370, 1%). One patient was found to have malignant hypertension. We conclude that wire localizations and imaging-guided aspirations are generally well tolerated procedures. However, vasovagal reactions are frequent enough to warrant close observation of patients. Radiologists and breast-imaging personnel should be able to recognize and treat vasovagal reactions. 
Occult pontine glioma in a patient with hemifacial spasm. Hemifacial spasm due to an intracranial mass lesion is rare. We describe a 29-year-old man with hemifacial spasm successfully treated with botulinum A toxin injections for 2 years. The development of acquired diplopia secondary to acquired sixth cranial nerve palsy prompted investigation. Computed tomography done at the time of original diagnosis and on three other occasions (concentrating on the brain stem and cerebellopontine angle) failed to demonstrate an intracranial mass lesion. Magnetic resonance imaging (MRI) showed a large mass lesion in the pons presumed to be a glioma. Patients with hemifacial spasm who have atypical features, especially those with associated neurologic findings, should be screened for tumours. Our case illustrates the superiority of MRI in demonstrating pontine gliomas causing hemifacial spasm. 
Imaging of myocardial infarction in dogs and humans using monoclonal antibodies specific for human myosin heavy chains. The use of three different monoclonal antibodies specific for human ventricular myosin heavy chains in the visualization of the location and extent of necrosis in dogs with experimental acute myocardial infarction and in humans is described. Using a classic immunohistochemical method or ex vivo analysis of heart slices in dogs with acute myocardial infarction subjected to intravenous injection of unlabeled antimyosin antibodies or antimyosin antibodies labeled with indium-111, it was observed that all antibody fragments specifically reached the targeted necrotic zone less than 2 h after antibody injection and remained bound for up to 24 h. In a limited but significant number of cases (5 of the 12 humans and 11 of 43 dogs), it was possible to image the necrotic zone in vivo as early as 2 to 4 h after antibody injection. In other cases, individual blood clearance variations retarded or even prevented in vivo necrosis detection. Higher antimyosin fixation values were obtained in the necrotic zones in dogs with a rapid blood clearance relative to that of the other dogs. It is concluded that antimyosin antibodies always reached necrotic areas within 2 h. If blood clearance was rapid, in vivo imaging of the necrotic area was possible 2 to 6 h after necrosis, even in humans. In some cases, however, uncontrolled individual variations in the timing required for sufficient blood clearance hampered this rapid in vivo detection of myocardial necrosis. 
Primary vesicoureteric reflux: treatment with subureteric injection of Polytef paste. A series of 34 children with 40 primary refluxing ureters were treated endoscopically with a subureteric injection of polytetrafluoroethylene paste (Polytef). The amount injected ranged between 0.1 and 0.8 ml (mean 0.3). A single injection cured the reflux in 26 ureters (65%) and the grade of reflux improved in a further 9 ureters. Seven ureters required a second injection and reflux was cured in 6 of these. The overall cure rate was therefore 80% after the second injection. There was one complication due to self-limiting ureteric obstruction following injection. The procedure is quick, easy to perform and effective. We have some reservations about the long-term efficiency and safety of subureteric Polytef injection in children. 
Serum biomarkers in metastatic renal cell carcinoma. To identify possible clinically valuable markers of metastatic renal cell carcinoma, we measured the serum concentrations of several commercially available biomarkers in 117 patients with this disease. The alpha-fetoprotein level was measured in 75 patients and was elevated in 8 (11%); elevation did not correlate with the presence of liver metastasis. Beta subunit of human chorionic gonadotropin levels increased in 8 of 83 patients tested (10%). C-terminal parathyroid hormone levels were measured in 79 patients and were elevated in 15 (19%); their serum creatinine level was normal. Thirteen of this group had normal serum calcium levels, whereas 7 patients with hypercalcemia and no clinically evident bone metastasis had normal parathyroid hormone levels. In only 2 of 72 patients, serum lactate dehydrogenase and its isoenzyme 1 were elevated. Only 1 of 85 patients had mildly elevated serum carcinoembryonic antigen, in contrast to 3 of 7 patients with metastatic transitional cell carcinoma of the renal pelvis who had moderately elevated carcinoembryonic antigen. Elevations in alpha-fetoprotein, human chorionic gonadotropin, and parathyroid hormone correlated with the course of the disease in 13 patients for whom follow-up measurements were available; measurement of these markers, however, is only useful in a small proportion of patients with metastatic renal cell carcinoma. 
Bladder instillations of trisdine compared with catheter introducer for reduction of bacteriuria during intermittent catheterisation of patients with acute spinal cord trauma. An open, prospective, randomised trial was conducted to compare the incidence of significant bacteriuria following 2 methods of intermittent urethral catheterisation in patients with acute spinal cord trauma. Twenty-two patients were catheterised with a Nelaton catheter and 50 ml of Trisdine were instilled into the bladder and left there immediately prior to withdrawal of the catheter. Fifteen patients were catheterised with a Nelaton catheter with a special introducer to improve asepsis (O'Neil catheter). The mean incidence of significant bacteriuria in males and females who received Trisdine bladder instillations was 0.58 and 0.48% per catheterisation respectively; in males and females catheterised with the O'Neil catheter it was 1.16 and 2.93% per catheterisation respectively. The instillation of Trisdine into the bladder after each passage of a catheter resulted in a significantly lower incidence of bacteriuria compared with that which resulted from the use of the O'Neil catheter. The former method is therefore to be preferred for aseptic intermittent urethral catheterisation in patients with acute spinal cord trauma. 
Bio-medicus ventricular assist device for salvage of cardiac surgical patients Over a 5-year period, 41 (1%) of 4,193 patients undergoing cardiac operations underwent intraoperative or early postoperative insertion of a Bio-Medicus ventricular assist device when it became apparent that the patient could not otherwise survive. Fourteen patients were in cardiogenic shock and 7 were in cardiac arrest at the time of initiation of their primary cardiac surgical procedure, and in no instance was the device planned as a bridge to cardiac transplantation. Bleeding, sepsis, and thromboembolism were frequent postoperative complications. Central nervous system deficits were observed in 16 patients during their postoperative course. Eight patients (19.5%) were long-term survivors. Of the preoperative risk factors evaluated only age was significantly associated with survival, with 7 (33%) of the 21 younger (39 to 63 years) patients surviving. Blood product usage and hospital cost were analyzed in an attempt to assess cost/effectiveness of use of this device for attempted salvage of such desperately ill patients. 
Estimation of Doppler gradients at rest and during exercise in patients with recoarctation of the aorta. In patients with suspected recoarctation of the aorta the estimation of the pressure difference between the arms and legs is an important part of the examination. Because this difference is often augmented when the circulation is stressed by exercise, exercise tests are a useful part of the evaluation. Doppler echocardiography was used to estimate this pressure difference in 16 adult patients in whom simultaneous pressure and Doppler recordings were made both at rest and during exercise. There was a close correlation between the invasive peak instantaneous gradient and the Doppler gradient both at rest and during exercise. There was only a moderate correlation between the invasive peak to peak gradient and the Doppler gradient at rest and during exercise. Doppler echocardiography is recommended as an easy and accurate method of estimating the peak instantaneous gradient both at rest and during exercise in patients with suspected recoarctation. 
Stimulation of protein, RNA, and nucleotide synthesis in lymphocytes after abdominal surgery is not affected by postoperative amino acid supply. The effects of abdominal surgery on protein, RNA, and de novo purine nucleotide synthesis in lymphocytes, and modification of these changes by postoperative amino acid supply, were investigated in 24 patients undergoing cholecystectomy (n = 12) or removal of gastric cancer (n = 12). Mono-nuclear cells were isolated from the peripheral venous blood and incubated with radioactive tracers in vitro. Protein and RNA synthesis, as measured using [14C] glycine and [3H]uridine, respectively, increased postoperatively. Nucleotide synthesis determined by the incorporation of radioactivity from [14C] glycine into nucleotides increased simultaneously. The concentration of 5-phosphoribosyl 1-pyrophosphate (PRPP) estimated by the incorporation of [14C]adenine into nucleotides also increased. These changes were greater and of longer duration in patients with cancer operation than in those with cholecystectomy. In neither case were they affected by the amount of amino acid intake, or increases in energy intake. These results suggest that abdominal surgery stimulates protein and ribonucleic acid (RNA) synthesis in lymphocytes. Increased RNA synthesis may be ensured by increased synthesis of nucleotides, and increased PRPP concentrations appear to regulate the rate of nucleotide synthesis. The responses are apparently dependent upon the severity of surgery, but unrelated to the amount of amino acid supplied postoperatively. 
Aminophylline in the outpatient management of decompensated chronic obstructive pulmonary disease. The objective of this study was to determine if IV aminophylline reduces the risk of relapse after treatment of decompensated COPD in an ED. Forty-six visits in which IV aminophylline was given (T visits) were compared with an equal number of visits in which it was withheld (N visits) with respect to pretreatment serum theophylline level, number of treatments with nebulized bronchodilators and use of parenteral beta-adrenergic drugs, IV corticosteroids and prednisone. The difference in 48-h relapse rates for T and N visits was examined by McNemar's test. No differences were found between T and N visits with respect to vital signs, pretreatment FEV1, arterial blood gas values, hematocrit level or blood leukocyte count. The 48-h relapse rate for T visits (22.2 percent) was significantly higher than for N visits (6.7 percent; p = 0.035). Aminophylline does not appear to be beneficial for outpatients with decompensated COPD and may be harmful. 
Reduction of gonadotropin-releasing hormone pulse frequency is associated with subsequent selective follicle-stimulating hormone secretion in women with polycystic ovarian disease. Polycystic ovarian disease (PCO) is characterized by hyperandrogenism, ovulatory dysfunction, and altered gonadotropin secretion. Mean plasma FSH concentrations are low, while LH is elevated in a majority of patients. LH pulsatile secretion has been shown to occur at rapid follicular phase frequencies (approximately one pulse per h) in PCO, suggesting persistent rapid frequency GnRH secretion in this disorder. Anovulatory women with PCO were given estradiol (E2; Estraderm skin patches) and progesterone (P; vaginal suppositories) to produce midluteal concentrations for 21 days. The aim was to determine if E2 and P would slow LH (GnRH) pulse frequency and if this would result in augmented FSH secretion and follicular development after withdrawal of E2 and P. Plasma LH was measured every 10 min for 8 h before, during (days 10 and 20), and 7 days after withdrawal of E2 and P (day 28). On each of these study days FSH was measured hourly, and E2 and P were measured every 2 h. After sampling, GnRH (25 and 250 ng/kg, iv) was given to assess pituitary responsiveness. Follicular development was monitored by vaginal ultrasound through day 34 of the study. Basal LH frequency was 8.5 +/- 0.5 pulses/8 h (mean +/- SEM). During E2 and P, LH pulse frequency fell to 3.3 +/- 1.0 (10 days) and 2.3 +/- 0.8 (20 days), 39% and 27% of the basal value, respectively, and subsequently increased to 5.6 +/- 0.7 (66% of basal) 7 days after withdrawal of E2 and P. LH pulse amplitude (basal, 7.2 +/- 1.5 IU/L) was not reduced until day 20, but remained suppressed (3.9 +/- 1.1 IU/L) on day 28. As a result, mean LH (basal, 21.0 +/- 3.5 IU/L) fell progressively during E2 and P, to 3.8 +/- 1.2 IU/L on day 20, and remained low (39% of basal) 7 days after steroid withdrawal. Mean plasma FSH (basal, 7.1 +/- 0.9 IU/L) also fell during steroid administration, but in contrast to LH, had risen to 93% of the basal value by 7 days after E2 and P. LH release in response to exogenous GnRH revealed marked initial responses which did not decrease until day 20, but remained suppressed (8% of basal) after withdrawal of E2 and P. FSH responses were also suppressed on day 20, but had increased to 75% of the basal value by day 28. Initiation of follicular development occurred in all patients, and the lead follicle measured 12.3 +/- 0.8 mm 13 days post-E2 and P. Ovulation occurred in one patient.(ABSTRACT TRUNCATED AT 400 WORDS). 
Circumspinal decompression for thoracic myelopathy due to combined ossification of the posterior longitudinal ligament and ligamentum flavum. Ossification of the posterior longitudinal ligament (OPLL) combined with ossification of the ligamentum flavum (OLF) in the thoracic spine can result in serious myelopathy, leading to circumferential compression of the spinal cord in advanced stages of the disease. The authors performed circumspinal decompression (circumferential decompression of the spinal cord) on these patients. This operation consists of two steps: posterior and lateral decompression of the spinal cord by removal of the OLF (first step) and anterior removal of the OPLL for anterior decompression (second step), followed by interbody fusion. In the first step, two deep parallel gutters, covering the extent of the OPLL to be removed anteriorly, are drilled down from the rear into the vertebral body along both sides of the dura to easily and safely remove the OPLL anteriorly at the second step. In the second step, the surgical approach varies according to the affected level; costotransversectomy in the upper thoracic spine and standard thoracotomy in the middle or lower thoracic spine. According to the authors, circumspinal decompression is not an easy procedure, but from their results in 10 patients, they identify it as a radical and promising surgical procedure. 
Clinical, laboratory, roentgenographic, and electrocardiographic findings in patients with acute pulmonary embolism and no pre-existing cardiac or pulmonary disease. The history, physical examination, chest radiograph, electrocardiogram and blood gases were evaluated in patients with suspected acute pulmonary embolism (PE) and no history or evidence of pre-existing cardiac or pulmonary disease. The investigation focused upon patients with no previous cardiac or pulmonary disease in order to evaluate the clinical characteristics that were due only to PE. Acute PE was present in 117 patients and PE was excluded in 248 patients. Among the patients with PE, dyspnea or tachypnea (greater than or equal to 20/min) was present in 105 of 117 (90 percent). Dyspnea, hemoptysis, or pleuritic pain was present in 107 of 117 (91 percent). The partial pressure of oxygen in arterial blood on room air was less than 80 mm Hg in 65 of 88 (74 percent). The alveolar-arterial oxygen gradient was greater than 20 mm Hg in 76 of 88 (86 percent). The chest radiograph was abnormal in 98 of 117 (84 percent). Atelectasis and/or pulmonary parenchymal abnormalities were most common, 79 of 117 (68 percent). Nonspecific ST segment or T wave change was the most common electrocardiographic abnormality, in 44 of 89 (49 percent). Dyspnea, tachypnea, or signs of deep venous thrombosis was present in 107 of 117 (91 percent). Dyspnea or tachypnea or pleuritic pain was present in 113 of 117 (97 percent). Dyspnea or tachypnea or pleuritic pain was present in 113 of 117 (97 percent). Dyspnea or tachypnea or pleuritic pain or atelectasis or a parenchymal abnormality on the chest radiograph was present in 115 of 117 (98 percent). In conclusion, among the patients with pulmonary embolism that were identified, only a small percentage did not have these important manifestations or combinations of manifestations. Clinical evaluation, though nonspecific, is of considerable value in the selection of patients in whom there is a need for further diagnostic studies. 
Management of osteogenic sarcoma in children and adolescents. The management of osteogenic sarcoma in children has made a fantastic step on the survival rate, but there still remains unexpected late metastatic recurrence even in initially good responders to chemotherapy and lower survival rate in the bad responder group. Therefore, the research on etiology and on the understanding and rating of oncologic power of the tumoral cells as well as other kinds of treatment (vaccine, immunotherapy, and other types of chemotherapy) must be increased. The initial function after replacement is good and is often excellent but increasing deterioration is noticed during each follow-up evaluation. A considerable effort is still to be done for bone and joint replacement. Biocompatible material with mechanical strength and resistance to wear will be used for a long time because of the young age of the patients. There must be better use and understanding of the allograft revascularization, as well as a better biologic connection between the bone host and replacement device. This will probably be used in the future with less cement and more of a modular system. The final prognosis will remain for a long time in the perfect cooperation between the various members of the teams (oncologist, surgeon, imager, pathologist, and research team) who treat the patients. 
The morbidity of long-term seizure monitoring using subdural strip electrodes. The authors report a prospective study of morbidity associated with long-term seizure monitoring using subdural strip electrodes. Three hundred fifty patients were divided into two groups: 175 patients received antibiotics intravenously during the entire period that the electrodes were implanted, and 175 patients received one dose of antibiotics on the morning of surgery. In the group given continuous antibiotic coverage there were two cases of meningitis, both treated without sequelae. In the group receiving one dose of antibiotics, one patient had a brain abscess and three had superficial wound infections. There were no other instances of major morbidity or mortality in either group of patients. The total morbidity rate for both serious and minor complications was 0.85%. 
Predictors of event-free survival after balloon aortic valvuloplasty. BACKGROUND. Balloon aortic valvuloplasty was developed as an alternative to aortic-valve replacement in selected elderly patients with aortic stenosis. The use of this procedure is limited, however, by a high incidence of restenosis. METHODS. Between December 1985 and April 1989, valvuloplasty was performed in 205 patients. We evaluated 40 demographic and hemodynamic variables as univariate predictors of event-free survival by Cox regression analysis and identified independent predictors of event-free survival by stepwise multivariate analysis. RESULTS. Early hemodynamic results indicated a decrease in the peak transaortic-valve pressure gradient from 67 +/- 28 to 33 +/- 15 mm Hg after valvuloplasty and an increase in aortic-valve area from 0.6 +/- 0.2 to 0.9 +/- 0.3 cm2 (P less than 0.001 for both comparisons). The rate of event-free survival (defined as survival without recurrent symptoms, repeated valvuloplasty, or aortic-valve replacement) was 18 percent over the mean (+/- SD) follow-up period of 24 +/- 12 months (range, 1 to 47). Significant predictors of event-free survival included the left ventricular ejection fraction and the left ventricular and aortic systolic pressure before valvuloplasty, and the percent reduction in the aortic-valve pressure gradient; the pulmonary-capillary wedge pressure was inversely associated with event-free survival. Although the predicted event-free survival rate for the entire patient group was 50 percent at one year (95 percent confidence interval, 43 to 57 percent) and 25 percent at two years (95 percent confidence interval, 19 to 31 percent), the probability of event-free survival at one year varied between 23 and 65 percent when patients were stratified according to three independent predictors: the aortic systolic pressure, the pulmonary-capillary wedge pressure, and the percent reduction in the peak aortic-valve gradient. CONCLUSIONS. The most important predictors of event-free survival after balloon aortic valvuloplasty were related to base-line left ventricular performance. The best long-term results after valvuloplasty were observed among patients who would also have been expected to have excellent long-term results after aortic-valve replacement. 
Microangiopathy of the brain, retina, and ear: improvement without immunosuppressive therapy. We describe a pregnant young woman with branch retinal arteriolar occlusions, encephalopathy, and hearing loss in whom we demonstrated a patent foramen ovale. She improved while receiving anticoagulants and no immunosuppressive therapy. The microangiopathic syndrome of retinopathy, encephalopathy, and deafness may be due to a disturbance of coagulation and/or microembolism. 
Eosinophilic pustular folliculitis. Eosinophilic pustular folliculitis is characterized by the spontaneous development of recurrent, sterile papules, pustules, and plaques on the face, trunk, arms, and occasionally the palms and soles. Although the large majority of the reported cases have occurred in Eastern Asians, most patients in the United States have been infants or men seropositive for human immunodeficiency virus. We describe a North American woman with eosinophilic pustular folliculitis who was neither seropositive for human immunodeficiency virus nor of Asiatic descent. 
Delirium and lactic acidosis caused by ethanol and niacin coingestion. A 44-year-old male presented to the emergency department with altered mental status. He was receiving niacin therapy for hypercholesterolemia, and 16 hours earlier had ingested a large quantity of wine. Past medical history was otherwise unremarkable; physical examination revealed paranoid ideation and asterixis. Laboratory evaluation was significant for metabolic acidosis with a calculated anion gap of 39. Liver enzymes were elevated, and lactic acid level was 9.5 mmol/L (normal: 0.5 to 2.2 mmol/L). White blood cell count was 23,100, but all cultures were negative, and all other diagnostic studies, including bilirubin, prothrombin time, and ammonia were normal. The patient recovered rapidly with hydration and administration of thiamine and magnesium. After psychiatric evaluation, a diagnosis of toxic delirium due to niacin and ethanol coingestion was made. This is the first case reporting toxic delirium and lactic acidosis due to niacin and ethanol coingestion. This occurred in the absence of significant hepatic impairment. Possible mechanisms for the observed derangements are discussed. 
Treatment of bacterial skin and soft tissue infections. Bacterial skin infections occur commonly and range in severity from mild to life threatening. The severity of skin infections, and their management and prognosis, can depend on the mechanism of infection, the skin structures involved and the infecting organism or organisms. Primary skin infections result from invasion of microorganisms through tiny breaks in the epidermis or from the spread of microorganisms through the bloodstream. Secondary infections arise from pre-existing trauma, burns or surgical wounds; infections involving the soft tissues underlying the skin are also discussed. These also frequently occur in areas of trauma, operation or ischemia. The cause, bacteriologic factors and management of skin infections were studied, with special attention to pyodermas, infections of the foot in diabetic patients and necrotizing soft tissue infections. Choice of appropriate antibiotic agents depends in large part on the infecting organism and patterns of antibiotic susceptibility. In necrotizing soft tissue infections, survival or limb salvage may depend on prompt surgical intervention. In these instances and in some of advanced primary skin infections in which bacteremia is involved, parenteral antibiotics are required. The available options are discussed and a report on the data with the combination agent ticarcillin disodium and clavulanate potassium is presented. 
Iliac artery stenosis or obstruction after unsuccessful balloon angioplasty: treatment with a self-expandable stent. Obstruction or stenosis of the iliac artery was treated by placement of a self-expandable stent in 91 patients. A total of 100 lesions was treated. All patients had had poor results of balloon angioplasty including residual stenosis, iliac occlusion, and dissection. The stent used in all cases was a self-expandable stainless steel endoprosthesis mounted on a 7- or 9-French catheter and covered by an invaginated tubular rolling membrane. The diameter of the expanded stent varied from 7 to 12 mm. A total of 129 stents was placed. Technical success was 97%. Thromboses occurred immediately after placement in two patients and within the first month in six; these were mainly due to residual obstruction. Eighty-two (93%) of 88 patients with a follow-up longer than 3 months had no recurrent symptoms. Restenosis caused by intimal hyperplasia inside the stent occurred in 10 patients; these required repeated intervention in only four cases. In the remaining six patients, no further complications occurred. Our results show that self-expanding endoprostheses are of value for improving the results of inadequate percutaneous transluminal angioplasty. 
Pulmonary hypertension and polymorphonuclear leukocyte elastase after esophageal cancer operations. To evaluate the role of polymorphonuclear leukocyte (PMN) elastase in pulmonary impairment occurring after operation for esophageal cancer, 10 patients were randomized preoperatively into two equal groups. One group received a placebo infusion and the other, an infusion of the PMN elastase inhibitor ulinastatin. In the placebo group, the mean plasma PMN elastase level increased from 154 +/- 23 micrograms/L preoperatively to 449 +/- 56 micrograms/L at 6 hours postoperatively (p less than 0.01), whereas the mean plasma fibronectin concentration decreased from 490 +/- 70 micrograms/mL preoperatively to 265 +/- 81 micrograms/L on postoperative day 2 (p less than 0.01). The mean pulmonary vascular resistance increased markedly from 151 +/- 24 dynes.s.cm-5.m-2 preoperatively to 284 +/- 76 dynes.s.cm-5.m-2 at 6 hours postoperatively (p less than 0.01). In the group given ulinastatin, 150,000 units every 12 hours from the start of the operation, the mean PMN elastase value at 6 hours postoperatively was lower (275 +/- 66 micrograms/L; p less than 0.01) and the fibronectin level on postoperative days 1 and 2, higher (p less than 0.05). A lower pulmonary vascular resistance was noted into day 2 (p less than 0.05). Our results suggest that PMN elastase may participate in the development of postoperative pulmonary impairment. 
Platelet angiotensin II binding sites in normotensive and hypertensive women. Specific binding of angiotensin II (AII) to platelets was measured in 89 women, 25 nulliparous non-pregnant women and 64 primigravida in the third trimester of pregnancy. There was significantly lower binding in the 25 pregnant women who were normotensive (2.3 fmol/10(9) cells) when compared with the non-pregnant women (9.0 fmol/10(9) cells P less than 0.001). Significantly higher platelet AII binding levels were found in the 39 women who had pregnancy induced hypertension (PIH) (5.5 fmol/10(9) cells) when compared with the 25 normotensive pregnant women (P less than 0.001). Of the 39 women with PIH, platelet AII binding was higher in the 23 women who had pre-eclampsia (7.0 fmol/10(9) cells), when compared with the 16 who had non-proteinuric PIH, (4.6 fmol/10(9) cells) although the difference was not statistically significant (P less than 0.04). The pressor response to AII is also diminished in pregnancy, yet less so if pregnancy induced hypertension develops. Platelets may provide a readily accessible tissue with which to study AII responsiveness in pregnancy. 
Gastrointestinal cytology. Since the development of the fiberoptic endoscope, laboratories have received cytologic specimens obtained from all segments of the gastrointestinal tract in increasing numbers to identify infectious agents and neoplasms. Adenocarcinomas generally are easily diagnosed and distinguished from reparative atypia, but their precursor lesions, dysplasia and adenomas, provide greater interpretive challenges. The same is true for such entities as malignant lymphomas. Most mesenchymal tumors remain outside the diagnostic capabilities of most cytologists. 
Modulation of alpha smooth muscle actin and desmin expression in perisinusoidal cells of normal and diseased human livers. It has been suggested that perisinusoidal liver cells (PSC) play a pivotal role in the pathogenesis of fibrocontractive changes. Using light and electron microscopic immunolocalization techniques, a series of 207 normal and pathologic human liver specimens were evaluated for the expression of alpha smooth muscle (SM) actin and desmin in this and other nonparenchymal cell types. In normal adult liver tissue, PSCs were practically devoid of desmin and exceptionally stained for alpha-SM actin, whereas this actin isoform frequently was encountered in PSCs from the embryonic to the adolescent period. A broad spectrum of pathologic conditions was accompanied by the presence of alpha-SM actin containing PSCs; these were detected preferentially in periportal or perivenular zones according to the predominant location of the underlying hepatocellular damage. The occurrence of this PSC phenotype generally was associated with fibrogenesis and was in some cases detected earlier than overt collagen accumulation. Fibrous bands subdividing liver tissue in cirrhosis and focal nodular hyperplasia, as well as desmoplastic reaction to malignant tumors, contained alpha-SM actin-rich cells admixed with variable proportions of cells coexpressing desmin. In end stages, this population was less numerous than in active fibrotic or cirrhotic processes. Using immunogold electron microscopy, alpha-SM actin was localized in microfilament bundles of typical PSCs. Our results are compatible with the assumption that the appearance of alpha-SM actin and desmin-expressing myofibroblasts results at least in part from a phenotypic modulation of PSCs. 
Breast cancer screening in a biracial community: the Charleston tricounty experience. Breast cancer remains a major cause of death among women in South Carolina. Mammography, breast self-examination, and clinical breast examination are effective methods for early detection and subsequent mortality reduction. The Tricounty Breast Cancer Screening Survey assessed knowledge of these methods and recommendations among 503 women in the Charleston area. While 57% of all respondents reported performing breast self-examination at least once per month, 13% of blacks and 6% of whites reported that they do not know how to perform the procedure. Clinical breast examinations within the past year were reported by 69%, yet 11% of blacks and 4% of whites reported that they had never had the examination. More than one third (40%) of all 503 women reported ever having had a mammogram, and 22% reported having had one within the past year. However, 18% of the blacks and 5% of whites reported never having heard of the procedure. The major barriers to mammography appear to be the belief that women do not need regular mammograms and the lack of recommendations by their physicians. Survey results support the need for educating women about what the procedures are, the importance of using them regularly, and the means to comply with them. 
Skin test reactivity in patients suffering from lung and breast cancer. Mast cells and histamine-mediated reactions may be altered in patients with cancer. In an attempt to characterize the possible skin defects in patients with cancer, we tested 22 patients suffering from lung cancers, 30 from breast cancers, and 30 age-matched normal individuals, using several compounds, in investigating the pathophysiology of the skin response. Histamine hydrochloride (10 and 100 mg/ml) and codeine phosphate (9%) were tested by prick test. Substance P (50 and 500 ng per injection site), phentolamine (20 micrograms per injection site), and carbachol (1 microgram per injection site) were tested by intradermal skin tests. Skin mast cells were also microscopically examined in 10 patients with lung cancer, five with breast cancer, and 10 normal subjects. The mean wheal sizes induced by all the tested substances were similar in patients with cancer and chronic bronchitis and in normal individuals. The flare to histamine, codeine phosphate, and substance P was completely abolished in 7/22 patients with lung cancer, but the lack of flare was not related to the age of the patients, nor to the staging of cancer, nor to metastasis. The mean numbers of alcian blue-stained or toluidine blue-stained positive mast cells were similar in normal subjects and in subjects with cancer. This study does not confirm the skin hyporeactivity of patients with cancer. 
Decreased fibrinolytic activity and increased platelet function in hypertension. Possible influence of calcium antagonism. Twelve patients with mild hypertension were compared, after 14 days of placebo, with an age- and gender-matched group of 12 healthy volunteers for platelet aggregability and fibrinolytic activity. Following this, 10 of the 12 hypertensives were treated with the calcium antagonist isradipine for 12 months. Blood was drawn for determinations of platelet aggregation and fibrinolytic activity after two weeks and 12 months of treatment. Platelet aggregation tended to increase in the hypertensives compared with controls, indicated by a lowering of the adenosine diphosphate (ADP) threshold value for irreversible aggregation. Tissue-plasminogen activator (t-PA) activity was significantly decreased in hypertensives compared to controls (P less than .05). During therapy, platelet aggregation decreased and t-PA activity increased (P less than .05). The present data suggest that fibrinolytic activity is decreased and platelet aggregation increased in mild hypertension. Besides the blood pressure-lowering effect, isradipine may protect against thromboembolic diseases by modifying platelet function and fibrinolytic activity. 
How mothers keep their babies warm. Details of room temperature, clothing, and bedding used by night and by day and in winter and in summer were recorded for 649 babies aged 8 to 26 weeks. Room temperature at night was significantly related to outside temperature and duration of heating. Total insulation was significantly related to outside temperature and to minimum room temperature, but there was wide variation in insulation at the same room temperature. High levels of insulation for a given room temperature were found particularly at night and in winter, and were associated with the use of thick or doubled duvets and with swaddling. At least half the babies threw off some or all of their bedding at night, and at least a quarter sweated. Younger mothers and mothers in the lower social groups put more bedclothes over their babies, and the latter also kept their rooms warmer. Many mothers kept their babies warmer during infections. 
Use of hearing aids by patients with closed mastoid cavity. Twenty-five patients who had undergone a closed-cavity tympanomastoidectomy in our Unit and wore a hearing aid in the operated ear were reviewed, and information was recorded on the use of the aid, and the patients' impression about it. The information obtained was analysed and compared with similar data from 39 hearing aid users of similar age with no history of ear surgery. Eighty per cent of the patients with a closed mastoid cavity were satisfied with the aid, and no significant difference was found between the two groups regarding the impression about the aid (chi square 3.06, p = 0.08), or the problems with it, which, in most of the cases, were related to several changes of mould (chi square 2.19, p = 0.13). The various recorded parameters are discussed, and it is concluded that the patients with a closed mastoid cavity can tolerate a hearing aid in the operated ear at least as well as the control subjects with no ear surgery. 
T-cell receptor delta gene recombination in common acute lymphoblastic leukemia: preferential usage of V delta 2 and frequent involvement of the J alpha cluster. A high frequency (greater than 80%) of acute lymphoblastic leukemias (ALL) exhibit a recombination of the T-cell receptor (TCR) delta chain locus. Interestingly, distinct TCR delta elements are preferentially used in immunologic subtypes. In a recent series of 201 children with common ALL (cALL) we observed a TCR delta rearrangement in 162 patients, 57% of the latter showing a hybridization pattern in Southern blots suggestive of a V delta 2 to D delta 3 recombination. To verify this interpretation and to elucidate in more detail the diversity of this common type of TCR delta recombination we amplified and sequenced the junctional region of nine cALL patients and cell line REH-6 by polymerase chain reaction (PCR). A V delta 2 D delta 3 recombination was confirmed in all cases; convincing evidence for the participation of D delta 1 or D delta 2 elements was not obtained. Eight of nine patients and REH-6 showed complete 5' D delta 3 boundaries within V delta 2 D delta 3 segments, a limitation of junctional diversity also detected in 50% of peripheral blood cell clones derived from two healthy probands. Notably, sequence identity at the V delta 2 D delta 3 junction was demonstrated for a cALL and one of the control clones. Another group of 35 of 162 cALL patients was characterized by V delta 2 rearrangements and biallelic deletion of J delta and C delta sequences. Using a J alpha consensus primer, PCR-directed sequence analysis demonstrated V delta 2 D delta 3 J alpha recombinations in all four cases analyzed by this approach. The J alpha segments of these patients differed, but were identical or homologous to published J alpha elements. Our data suggest a recombination pathway of the TCR delta/alpha locus leading to chimeric TCR alpha molecules, containing V delta and, remarkably, also D delta sequences. 
Antiproliferative effects of cytokines on squamous cell carcinoma. A panel of 12 squamous cell carcinoma of the head and neck (SCCHN) cell lines has been used to determine sensitivity of tumor cells to cytokines, tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), and interferon alfa (IFN-alpha) in vitro. Antiproliferative activity of these cytokines on squamous cell carcinoma of the head and neck monolayers was measured in a colorimetric MTT [3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide]-based assay. All 12 cell lines tested were sensitive to IFN-gamma, with the 50% inhibitory dose (ID50) ranging from 0.07 +/- 0.001 to 104 +/- 4.6 U/mL. The TNF-alpha showed antiproliferative activity on three cell lines at relatively high doses (ID50 from 55 +/- 4.1 to 847.10 +/- 10 U/mL), and IFN-alpha was growth inhibitory in only one line (ID50 = 1211 +/- 46.2 U/mL). The combination of IFN-gamma and TNF-alpha had a synergistic antiproliferative effect on eight cell lines and an additive effect on two cell lines. In two cell lines, the effect of the combination was equal to that of IFN-gamma alone. A combination of IFN-alpha and TNF-alpha resulted in cell growth inhibition in six of the seven lines tested, and this effect was synergistic. These in vitro studies indicate that combinations of IFN-gamma and TNF-alpha or IFN-alpha and TNF-alpha may be more growth inhibitory against squamous cell carcinoma of the head and neck and at lower doses than each of these cytokines used singly. 
Acid perfusion test and 24-hour esophageal pH monitoring with symptom index. Comparison of tests for esophageal acid sensitivity. The acid perfusion (Bernstein) test and esophageal pH monitoring are the two most popular tests for identifying esophageal acid sensitivity in difficult cases of reflux disease. Therefore, we prospectively compared these test results in 75 consecutive noncardiac chest pain patients who had both an acid perfusion test and chest pain during 24-hr pH testing. A positive acid perfusion test was defined by the replication of the patient's typical chest pain twice by the acid infusion. Esophageal pH testing identified abnormal amounts of acid reflux and correlated symptoms with acid reflux--the "symptom index." Fifteen patients (20%) had a positive acid perfusion test while 45 patients (59%) had a positive symptom index (range 6-100%). Only 9/34 (26%) patients with abnormal reflux had a positive acid perfusion test. Although it had excellent specificity (83-94%), the acid perfusion test had poor sensitivity (32-46%) when compared to the symptom index regardless of the percent positive cutoff level. The best positive predictive value for the acid perfusion test was 87%, but this occurred when the test sensitivity was 32%. Modifying the end point of a positive acid perfusion test to include heartburn improves the sensitivity (52-67%) while markedly compromising specificity and positive predictive value. Thus, esophageal pH monitoring correlating symptoms with acid reflux is superior to the acid perfusion test for identifying an acid sensitive esophagus in patients with noncardiac chest pain. 
A randomized trial of alternating chemotherapy versus best supportive care in advanced non-small-cell lung cancer. From April 1985 to September 1988, 128 patients with advanced non-small-cell lung cancer (NSCLC) were enrolled in a prospective randomized trial evaluating chemotherapy (arm A) versus best supportive care (arm B). Chemotherapy consisted of cyclophosphamide 500 mg/m2 intravenously (IV) day 1, epirubicin 50 mg/m2 IV day 1, and cisplatin 80 mg/m2 IV day 1 (CE'P regimen) alternating every 4 weeks with methotrexate 30 mg/m2 IV day 1, etoposide 200 mg/m2 IV day 1, and lomustine (CCNU) 70 mg/m2 orally day 1 (MEC' regimen) until progression. Of the 123 patients (62 treated and 61 controls) eligible for survival, 115 were fully evaluable for response (58 treated and 57 controls). Response rates were 21% partial response, 53% stable disease, and 26% progressive disease in arm A, and 47% stable disease and 53% progressive disease in arm B. Median survival was 34.3 weeks (range, 4.3 to 218.6+ weeks) in arm A versus 21.1 weeks (range, 4.3 to 188.6 weeks) in arm B; the difference was not significant at P = .153 (Mantel-Cox). Subgroups of patients retrospectively analyzed by age, performance status, stage M0/M1, and weight loss or not showed no significant difference in survival. Poor-risk patients (at least two of the following: poor performance status, stage M1, weight loss) of arm A survived significantly longer than poor-risk patients of arm B (23.6 weeks v 12.4 weeks, Mantel-Cox P = .008); a significant difference in survival was also observed between nonsquamous cell patients of arm A and those of arm B (median survival, 38.6 weeks v 16.7 weeks; Mantel-Cox P = .041). Toxicity on the chemotherapy arm was hematologic (World Health Organization [WHO] grade greater than 3) in 12% of CE'P and in 13% of MEC' courses and gastroenteric (WHO grade greater than 3) in 24% of CE'P courses and in 8% of MEC' courses. Our alternating treatment was not significantly superior to supportive care. It is likely that certain subgroups of the NSCLC category may have an advantage with chemotherapy. 
Effect of tocotrienols on hepatocarcinogenesis induced by 2-acetylaminofluorene in rats. The effects of tocotrienols on hepatocarcinogenesis in rats fed with 2-acetylaminofluorene (AAF) were followed morphologically and histologically for a period of 20 wk. No differences between treated and control rats in the morphology and histology of their livers was observed. Cell damage was extensive in the livers of AAF-treated rats but less extensive in the AAF-tocotrienols-treated rats when compared with normal and tocotrienols-treated rats. 2-Acetylaminofluorene significantly increases the activities of both plasma and liver microsomal gamma-glutamyltranspeptidase (GGT) and liver microsomal UDP-glucuronyltransferase (UDP-GT). Tocotrienols administered together with AAF significantly decrease the activities of plasma GGT after 12 and 20 wk (P less than 0.01, P less than 0.002, respectively) and liver microsomal UDP-GT after 20 wk (P less than 0.02) when compared with the controls and with rats treated only with tocotrienols. Liver microsomal GGT also showed a similar pattern to liver microsomal UDP-GT but the decrease was not significant. These results suggest that tocotrienols administered to AAF-treated rats reduce the severity of hepatocarcinogenesis. 
Effect of thrombolysis on the evolution of late potentials within 10 days of infarction. Patients with late potentials in the signal averaged electrocardiogram are more at risk of lethal arrhythmias in the period after acute myocardial infarction. To test the effects of thrombolysis on the incidence and evolution of late potentials, 158 consecutive patients were prospectively studied during the first 10 days after acute myocardial infarction. The study population consisted of two groups: 93 control patients treated conservatively and 65 patients treated with intravenous thrombolysis. Recordings of signal averaged electrocardiogram were obtained within two days and 7-10 days after infarction. The incidence of late potentials in the first two days after infarction was not significantly different in the thrombolytic and control groups (14% v 11.8%). By 7-10 days the incidence of late potentials among patients who underwent thrombolysis remained unchanged (14%); however, it increased significantly in the control group (11.8% to 22.5%). Thus thrombolysis seems to reduce the evolution of late potentials within 10 days of infarction. Because the risk of fatal arrhythmias is higher in patients with late potentials this study may partly explain the reduced mortality after thrombolysis. 
Inflammatory pseudotumor of the choroid plexus in Sjogren's disease. We report an unusual case of inflammatory pseudotumor of the choroid plexus of the right lateral ventricle, manifesting as an intraventricular mass and causing unilateral hydrocephalus in a 48-year-old man who suffered from Sjogren's disease and subacute cutaneous lupus erythematosus. The lesion obliterated the normal choroidal architecture by a mixed chronic inflammatory process that was associated with reactive connective tissue changes. Immunohistochemical studies showed no light-chain restriction in the cells, and residual islands of transthyretin-positive epithelial cells were identified, implicating the choroid plexus origin of the mass. 
Colic medication and apparent life-threatening events. Eight infants with histories of apnea and cyanosis were referred to the Southwest SIDS Research Institute for evaluation of apparent life threatening events (ALTE). All of the infants had been treated for colic with a 1:1 concentration of dimenhydrinate (Dramamine) and phenobarbital, hyoscyamine sulfate, atropine sulfate and scopolamine hydrobromide (Donnatal). The medication was pre-mixed by local pharmacists. A comprehensive work-up failed to reveal a cause for the ALTE in any infant. The Dramamine/Donnatal mixture was withdrawn and polygraphic evaluation was conducted. Cardiorespiratory abnormalities were identified in all eight infants and significant gastroesophageal reflux (GER) was documented in four. The possibility that colic medication contributes to cardiorespiratory instability and GER in vulnerable infants requires serious consideration and further evaluation. 
A direct correlation of the resolution of pseudophakic cystoid macular edema with acetazolamide therapy. We report the case of a patient with pseudophakic cystoid macular edema whose visual acuity improved promptly with oral administration of 500 mg of acetazolamide extended-release capsules BID for two weeks. However, vision worsened again within two weeks of discontinuation of the treatment. On resumption of acetazolamide therapy for three weeks, and its slow withdrawal during the following three weeks, the macular edema eventually resolved, and vision returned to normal. Our observation provides a direct correlation of the resolution of pseudophakic cystoid macular edema with acetazolamide therapy and shows the importance of tapering the doses of this regimen. 
Prevalence of migraine in low-tension glaucoma and primary open-angle glaucoma in Japanese. We studied the prevalence of migraine in low-tension glaucoma (LTG) and primary open-angle glaucoma (POAG). Seventy seven Japanese patients with LTG, 73 with POAG, and 75 normal subjects were randomly selected and tested with a headache questionnaire. The prevalence of headache with or without typical migrainous features (unilateral headache or ocular pain, nausea, vomiting, and visual disturbance before headache) was 51% in LTG, 42% in POAG, and 44% in normal patients. The prevalence of headache with two migrainous features or more (probable migraine) was 17% in LTG, 11% in POAG, and 12% in normal subjects. The prevalence of headache with three migrainous features (classical migraine) was 5% in LTG, 3% in POAG, and 3% in normal subjects. There was no statistically significant difference in the prevalence of any types of migraine between the three groups of patients (p greater than 0.05). These results suggest there is no significant relationship between migraine and LTG or POAG in Japanese patients. 
Cervical esophageal motility: evaluation with US in progressive systemic sclerosis. High-resolution ultrasound (US) showed that initial peristalsis propelled ingested soda smoothly and rapidly in 20 volunteers without symptoms who met both manometric and radionuclide esophageal scintigraphic (RES) criteria for normal motility. Twenty-eight patients with progressive systemic sclerosis were classified according to results of RES as follows: group 1, normal esophageal motility (three patients [11%]); group 2, hypomotility of the esophagus, excluding the cervical esophagus (18 patients [64%]); and group 3, hypomotility of the cervical esophagus (seven patients [25%]). In the seven patients of group 3, US demonstrated that an incomplete peristalsis sequence or a feeble peristalsis propelled the soda in a slow and/or to-and-fro motion with low velocities. In the other 21 patients (75%), the soda passed through the esophagus smoothly and rapidly. Retention of soda in the cervical esophagus was not limited to patients with hypomotility of the cervical esophagus. It is concluded that US is useful in evaluation of cervical esophageal motility. 
Pretranslational regulation of albumin synthesis in tumor-bearing mice. The role of anorexia and undernutrition. Hepatic albumin synthesis, serum albumin turnover, and hepatic albumin messenger RNA (mRNA) content were evaluated in mice bearing a transplantable low differentiated tumor (MCG 101). Results obtained on tumor-bearing mice were compared with results obtained from non-tumor-bearing animals that were either freely fed, food restricted so that their body composition was similar to tumor-bearing animals (pair-weighed), fed a protein-free diet for 5 days, or fasted for 48 hours. Tumor-bearing animals became hypoalbuminemic (33 +/- 5 vs. 44 +/- 3 g/L in freely fed mice), which could be explained by both depressed albumin synthesis (1.95% +/- 0.20% vs. 2.67% +/- 0.27%/h in freely fed mice) and increased albumin degradation. Pair-weighed and protein-calorie malnourished controls had reductions in albumin synthesis (1.81% +/- 0.18% and 1.67% +/- 0.17%/h, respectively) similar to tumor-bearing animals, and the starved controls had the lowest synthetic rates (1.07% +/- 0.10%/h). Albumin degradation was increased only in tumor-bearing animals. Hepatic albumin mRNA in undernourished animals was less (tumor bearing, 32% +/- 5%; pair weighed, 47% +/- 4%; 48 hours fasted, 18% +/- 2%; and protein-calorie malnourished, 26% +/- 3%) than 50% of the mRNA content in the livers of freely fed control mice. Messenger RNA-directed synthesis of albumin in vitro was also depressed to a variable degree in tumor-bearing and malnourished non-tumor-bearing controls. The hypoalbuminemia in tumor-bearing animals could not be prevented by daily injections of a prostaglandin synthesis inhibitor (indomethacin, 1 microgram/g body wt), but the hepatic acute phase protein serum amyloid P decreased from 157 +/- 12 to 103 +/- 9 micrograms/mL in indomethacin-treated tumor-bearing mice (P less than 0.01). It is concluded that increased albumin degradation seen in tumor-bearing animals cannot be explained by associated malnutrition, whereas tumor-associated malnutrition can explain to a large extent the depressed albumin synthesis. Decreased albumin synthesis in tumor-bearing animals correlated in part with a decreased quantity of liver albumin mRNA. The results of the current study are consistent with either a reduced transcription of the albumin gene or a change in albumin mRNA processing and stability communicated by anorexia and malnutrition. 
Cogan's syndrome complicated by lacunar brain infarcts. Cogan's syndrome, nonsyphilitic interstitial keratitis with vestibuloauditory dysfunction, is an uncommon disease of young adults, probably a manifestation of vasculitis. A 32 year old woman with this syndrome developed a thalamic syndrome with amnesia and dysphasia due to lacunar infarcts. 
Impact of autologous bone marrow infusion on hematopoietic recovery after high-dose cyclophosphamide, etoposide, and cisplatin. Because of potential tumor contamination and inadequacy of current purging technique of bone marrow in patients with solid tumors, we investigated an alternative approach to high-dose therapy without autologous bone marrow (ABM) infusion. Three levels of nonmyeloablative doses of cyclophosphamide 4.5 to 5.25 g/m2, etoposide 750 to 1,200 mg/m2, and cisplatin 120 to 165 mg/m2 (CVP) were administered to patients with metastatic solid tumors. Patients were randomized to ABM (n = 46) or no-ABM (NABM) (n = 46) infusion after CVP to study the impact of ABM on hematopoietic recovery, morbidity, and mortality. All patients had ABM harvested, underwent conventional chemotherapy, and then received CVP. Seventy-three patients received two courses of similar doses. The following were the median days to absolute neutrophil count (ANC) of 0.1 x 10(9)/L: for the ABM arm, 19, 21, and 19 and for the NABM arm, 23, 20, and 21 at levels 1, 2, and 3, respectively, during course 1 (P = .01, .80, and .01, respectively). During course 2, ANCs to 0.1 x 10(9)/L and 0.5 x 10(9)/L were attained significantly faster at levels 1 and 3 in the ABM arm. ANC to 1.0 x 10(9)/L was comparable in both arms. Incidence of infection and duration of fever were similar in both arms. Although mortality and the incidence of delayed hematopoietic recovery were more frequent in the NABM arm, this was not statistically significant. Platelet recovery was consistently prolonged in course 2 in both arms, with demonstrable benefit of ABM in course 2 when dose levels were collectively considered. We conclude that (1) ABM enhanced recovery of ANC to 0.1 x 10(9)/L; (2) ABM did not decrease the incidence of infections and the duration of fever; and (3) CVP can be safely given without ABM to carefully selected patients. 
Prevalences of endoscopic and histological findings in subjects with and without dyspepsia OBJECTIVE--To examine the association between dyspeptic symptoms and endoscopic and histological diagnoses. DESIGN--Cross sectional study of people with dyspepsia and controls matched for age and sex identified by questionnaire survey of all inhabitants aged 20 to 69. Endoscopy and histological examination was performed with the examiner blind to whether or not the patient had dyspepsia. SETTING--Population based survey in Sorreisa, Norway. SUBJECTS--All people with dyspepsia and age and sex matched people without dyspepsia were offered endoscopy. A total of 309 people with dyspepsia and 310 without dyspepsia underwent endoscopy, giving 273 matched pairs. MAIN OUTCOME MEASURES--Prevalences of endoscopic and histological diagnoses made according to internationally accepted standards. RESULTS--In all, 1802 of 2027 (88.9%) people returned the questionnaire. Of the 163 subjects who refused endoscopy, 114 were controls. Of five endoscopic and four histological diagnoses only peptic ulcer disease, endoscopic duodenitis, and active chronic gastritis were diagnosed significantly more often in people with dyspepsia. In all, 30% to 50% of the diagnoses of mucosal inflammation and peptic ulcer disease were made among subjects without dyspepsia, and only 10% of both those with and those without dyspepsia had normal endoscopic findings. CONCLUSIONS--The diagnostic findings, with possible exceptions of peptic ulcer disease and endoscopic duodenitis, showed no association of clinical value with dyspeptic symptoms. The small number of "normal" endoscopic findings in both those with and those without dyspepsia challenge well accepted endoscopic and histological diagnostic criteria with relation to the upper gastrointestinal tract. 
Transcription, storage and release of atrial natriuretic factor in the failing human heart. 1. In this study the relationship between the synthesis of atrial natriuretic factor at the level of atrial natriuretic factor mRNA and the atrial storage and circulating plasma levels of atrial natriuretic factor were investigated in 15 patients with heart failure. The patients underwent right and left heart catheterization before cardiac surgery for valve replacement or coronary artery bypass grafting. 2. Plasma concentrations of atrial natriuretic factor were correlated to atrial levels of atrial natriuretic factor mRNA. Atrial levels of atrial natriuretic factor mRNA and plasma concentrations of atrial natriuretic factor exhibited a close correlation to both pulmonary artery pressure and left atrial pressure. No relationship, however, could be found between the right atrial content of atrial natriuretic factor and both the expression of atrial natriuretic factor mRNA in the atria and the plasma levels of atrial natriuretic factor. 3. From these data it may be concluded that increased plasma levels of atrial natriuretic factor in the pressure- and/or volume-overloaded heart are associated with an elevated level of atrial natriuretic factor mRNA. We suggest that not only plasma levels of atrial natriuretic factor but also the expression of atrial natriuretic factor in the atrial are related to left ventricular filling pressures in the failing human heart. 
Intracerebral Hodgkin's disease in a human immunodeficiency virus-seropositive patient. Intracerebral involvement of Hodgkin's disease (HD) is rarely described, with only 42 cases in the literature. Since the outbreak of the acquired immune deficiency syndrome (AIDS) epidemic, there has been an increasing number of human immunodeficiency virus (HIV)-infected (HIV+) persons who have diffuse non-Hodgkin's lymphoma and, more recently, atypical aggressive HD. The authors report the case of a patient with a history of intravenous drug abuse (IVDA) and Stage IVB HD who, after a drug-induced clinical remission, had intracerebral mixed-cellularity HD. This appears to be the first report of intracerebral HD in a person who is HIV+. 
Lack of induction of suppressor T cells by intestinal epithelial cells from patients with inflammatory bowel disease. The mechanisms underlying the chronic unrelenting inflammatory response seen in inflammatory bowel disease (IBD) are poorly understood. We have recently proposed a novel role for the normal intestinal enterocyte, that of antigen presenting cell. However, in contrast to conventional antigen presenting cells, normal enterocytes appear to selectively activate CD8+ antigen nonspecific suppressor T cells. To determine whether failure of this process may be occurring in inflammatory bowel disease, freshly isolated enterocytes from small and large bowel from normal patients, patients with Crohn's disease, ulcerative colitis, and inflammatory (diverticulitis, ischemic colitis, and gold induced colitis) controls were co-cultured with allogeneic T cells in a modified mixed lymphocyte reaction. In contrast to normal enterocytes, 42/42 Crohn's and 35/38 ulcerative colitis-derived epithelial cells stimulated CD4+ T cells, whereas 65/66 and 9/9 normal and inflammatory control enterocytes, respectively, stimulated CD8+ T cells (as previously described), suggesting that the results seen were not just a reflection of underlying inflammation. Furthermore, IBD enterocytes from both histologically involved and uninvolved tissue were similar in their ability to selectively activate CD4+ T cells, speaking for a more global defect in epithelial cells in IBD. Finally, activated T cells from IBD epithelial cell-stimulated mixed lymphocyte cultures displayed potent T helper activity in an antigen nonspecific fashion. Taken together, these data suggest that there may be an intrinsic defect in epithelial cells from patients with IBD, resulting in the inability to normally stimulate suppressor T cells in an antigen overloaded environment. 
Leukoaraiosis and ventricular enlargement in patients with ischemic stroke. We studied the relationship between ventricular size and nonspecific periventricular lucency on computed tomograms (leukoaraiosis) in 192 patients with ischemic stroke. Leukoaraiosis did not occur in 21 patients less than 50 years of age; ventricular size could not be measured in an additional 29. Leukoaraiosis was graded from 0 to 4 on a semiquantitative scale; bicaudate, frontal horn, and posterior horn indices were used as measures of ventricular size. Patients with leukoaraiosis were older (difference between means 7 years, t = 5.3, df = 140, p less than 0.0001) and had larger bicaudate indices (difference between means 0.023, t = 3.54, df = 140, p = 0.0007) than patients without leukoaraiosis. Multiple regression analysis demonstrated that the effects of age and leukoaraiosis were independent. No effect of lesion type (cortical or lacunar infarct, or both) on bicaudate index could be demonstrated. Larger values for the bicaudate index were associated with a predominantly anterior location of leukoaraiosis. The frontal horn and occipital horn indices increased with age, but we could not find an effect of leukoaraiosis on these indices. 
Canadian Atrial Fibrillation Anticoagulation (CAFA) Study. The Canadian Atrial Fibrillation Anticoagulation Study was a randomized double-blind placebo-controlled trial to assess the potential of warfarin to reduce systemic thromboembolism and its inherent risk of hemorrhage. As a result of the publication of two other "positive" studies of similar design and objective, this study was stopped early before completion of its planned recruitment of 630 patients. There were 187 patients randomized to warfarin and 191 to placebo. Permanent discontinuation of study medication occurred in 26% of warfarin-treated and 23% of placebo-treated patients. The target range of the international normalized ratio was 2 to 3. For the warfarin-treated patients, the international normalized ratio was in the target range 43.7% of the study days, above it 16.6% of the study days and below it 39.6% of the study days. Fatal or major bleeding occurred at annual rates of 2.5% in warfarin-treated and 0.5% in placebo-treated patients. Minor bleeding occurred in 16% of patients receiving warfarin and 9% receiving placebo. The primary outcome event cluster was nonlacunar stroke, noncentral nervous systemic embolism and fatal or intracranial hemorrhage. Events were included in the primary analysis of efficacy if they occurred within 28 days of permanent discontinuation of the study medication. The annual rates of the primary outcome event cluster were 3.5% in warfarin-treated and 5.2% in placebo-treated patients, with a relative risk reduction of 37% (95% confidence limits, -63.5%, 75.5%, p = 0.17). 
The importance of adequate anticoagulation to prevent early thrombosis after stenting of stenosed venous bypass grafts. Stent implantation in native coronary arteries may be complicated by acute thrombosis, despite the use of stringent anticoagulation. Thrombotic occlusion of stented venous grafts may occur less frequently, possibly because of the larger caliber of these grafts. We report our experience with 46 stents (Wallstent, Medinvent, Lausanne, Switzerland) implanted in 35 lesions of 24 consecutive patients (mean age 64 years, range 43 to 75). Two overlapping stents were implanted in seven patients, and three overlapping stents were positioned in two. After implantation, activated partial thromboplastin time was maintained at two to three times the control level by intravenous administration of heparin (160 to 550 mg daily) until thrombotest values were reduced 5% to 10% by acenocoumarol. Impending thrombotic occlusion was recognized in two suboptimally anticoagulated patients: patient A after implantation of four stents and patient B after anticoagulation therapy was discontinued because of acute upper gastrointestinal bleeding. Coronary artery bypass grafting was performed successfully in both patients. A third patient had a myocardial infarction on day 7 after stent implantation, in spite of adequate anticoagulation and optimal medical drug therapy. It is concluded that stringent anticoagulation therapy appears mandatory to maintain graft patency after stent implantation. 
Blood pressure during pregnancy in Canadian Inuit: community differences related to diet. OBJECTIVE: To assess a possible relation between the incidence of hypertension during pregnancy and the consumption of fatty acids found in fish and sea mammals. DESIGN: Retrospective survey of pregnancy-induced hypertension; prospective diet survey. SETTING: Inuit women from seven communities in the Keewatin region of the Northwest Territories. PATIENTS: All women from Arviat (formerly Eskimo Point), Baker Lake, Chesterfield Inlet, Coral Harbour, Repulse Bay, Sanikiluaq and Whale Cove who gave birth between Sept. 1, 1984, and Aug. 31, 1987. MAIN OUTCOME MEASURES: All blood pressure measurements recorded during the pregnancy, incidence of pregnancy-induced hypertension in the seven communities, harvest of country food (food obtained from the land or sea rather than bought in a store) for six of the communities, self-reported consumption of fish, sea mammals and terrestrial mammals by a subgroup of the subjects and levels of phospholipid fatty acids in cord serum samples from a subgroup of the infants. MAIN RESULTS: Significantly lower mean diastolic blood pressure values during the last 6 hours of pregnancy were noted for the women from the three communities with a higher consumption of fish and sea mammals (78.2 [95% confidence limits (CL) 76.6 and 79.9] mm Hg) than for those from the four communities with a lower consumption of such food (81.5 [95% CL 80.1 and 82.9] mm Hg) (p less than 0.005). The relation between community diet type and blood pressure was independent of other factors. Correspondingly, the women from communities with a lower consumption of marine food were 2.6 times more likely to be hypertensive during the pregnancy than those from communities with a higher consumption of marine food (p less than 0.007). Parity (p less than 0.05) and prepregnancy weight (p less than 0.005) were also significantly associated with pregnancy-induced hypertension; however, the relation between hypertension and community diet type remained significant in logistic regression analysis (odds ratio 2.56, p = 0.03). The differences between the community groups were substantiated by the results of the diet survey, the levels of eicosapentaenoic acid (EPA) in the cord serum phospholipids and the harvest data. CONCLUSIONS: Increased consumption of fish may be beneficial for women at risk for hypertension during pregnancy. A prospective randomized trial of fish or EPA supplementation during pregnancy is warranted. 
Prevention of chronic Pseudomonas aeruginosa colonisation in cystic fibrosis by early treatment. To assess whether chronic pulmonary colonisation with Pseudomonas aeruginosa in cystic fibrosis is preventable, 26 patients who had never received anti-pseudomonas chemotherapy were randomly allocated to groups receiving either no anti-pseudomonas chemotherapy or oral ciprofloxacin and aerosol inhalations of colistin twice daily for 3 weeks, whenever Ps aeruginosa was isolated from routine sputum cultures. During the 27 months of the trial, infection with Ps aeruginosa became chronic in significantly fewer treated than untreated subjects (2 [14%] vs 7 [58%]; p less than 0.05) and there were significantly fewer Ps aeruginosa isolates in routine sputum cultures in the treated group (49/214 [23%] vs 64/158 [41%]; p = 0.0006). Thus, chronic colonisation with Ps aeruginosa can be prevented in cystic fibrosis by early institution of anti-pseudomonas chemotherapy. 
Primary biliary cirrhosis: relation between hepatic function and pulmonary function in patients who never smoked. We studied the relationship between selected variables of hepatic and pulmonary function in 47 patients with primary biliary cirrhosis, who were participating in a prospective study to assess sequential pulmonary function at yearly intervals. An additional 20 patients with primary biliary cirrhosis, who were liver transplant candidates awaiting transplantation, were studied. None of the 67 patients ever smoked cigarettes. Severity of primary biliary cirrhosis was characterized by histological stage and the Mayo risk score derived from a Cox regression model that used the following variables: serum bilirubin and serum albumin levels, age, prothrombin time and clinical severity of edema. Pulmonary function assessment included key variables describing expiratory airflow (forced expiratory volume in 1 sec divided by forced vital capacity) and efficiency of gas exchange (steady-state diffusing capacity for carbon monoxide). We found a significant relationship between histological stage of primary biliary cirrhosis and steady-state diffusing capacity (p = 0.02) and between the Mayo risk score for disease severity and steady-state diffusing capacity (p = 0.03). Progressive deterioration of steady-state diffusing capacity was associated with increasing severity of primary biliary cirrhosis. No relationship existed between pulmonary function and the presence of sicca complex or Sjogren's syndrome or the clinical manifestations of portal hypertension (e.g., esophageal varices, ascites and splenomegaly). No significant relationship existed between expiratory airflow and severity of primary biliary cirrhosis. We conclude that in patients with primary biliary cirrhosis who have never smoked, a statistically significant relationship exists between the severity of the liver disease and the efficiency of gas exchange measured by steady-state diffusing capacity. 
Access to health care. One neurologist's perspective. Millions of residents of the United States have difficulty obtaining health care. Barriers impeding access to care include poverty, physical unavailability of health care services, absence of health insurance, and physicians unwilling to care for uninsured patients. Many patients do not successfully use health services because of educational, cultural, and language barriers. A major access barrier is lack of health insurance. Over 30 million people in the United States have none, the so-called medically indigent. Among them are over 3 million people with neurologic disorders. They have additional barriers to overcome because often they cannot work, cannot drive, have difficulty using public transportation, and have major cognitive and communication impairments. Medical and governmental bodies are debating solutions to the health care access crisis. Physicians should actively participate in this national debate. Neurologists should address the special needs of patients with neurological disorders. 
Effects of enflurane on inducibility of ventricular tachycardia. The effects of enflurane on cardiac electrophysiologic parameters and on inducibility of ventricular tachycardia (VT) by programmed stimulation were studied in 12 patients (11 men, 1 woman, mean age +/- standard deviation 55 +/- 8 years) with drug refractory sustained monomorphic VT who underwent transcatheter ablation with high-energy direct-current shocks. One catheter ablation procedure was performed in 10 patients, whereas 2 ablation sessions were necessary in 2 patients. Programmed ventricular stimulation was performed on 2 separate days (mean interval 19). There were 2 baseline studies, 1 several days before ("baseline study I") and the second at the beginning of the ablation procedure ("baseline study II") while the patient was awake and nonsedated. The third programmed stimulation study was done 15 to 30 minutes after administration of anesthesia with enflurane, oxygen and nitrous oxide ("enflurane study"). Rate of sinus rhythm, QRS duration, PQ interval and ventricular effective refractory period were unaltered, whereas QTc interval increased significantly after initiation of anesthesia. Before and after induction of general anesthesia, clinical VT was inducible in all patients. However, in 1 patient, induction of VT was only possible by pacing in the left ventricle after enflurane administration. Based on these data, it is concluded that general anesthesia with enflurane, oxygen and nitrous oxide has no marked influence on inducibility of clinical VTs. Therefore, this type of anesthesia may be useful for nonpharmacologic, ablative procedures requiring general anesthesia. 
Endometrial adenocarcinoma in Norway. A study of a total population. Fifteen hundred sixty-six patients with adenocarcinoma of the endometrioid type (AC) were studied. These accounted for 78.9% of all 1985 patients with confirmed endometrial carcinoma diagnosed in Norway in the period 1970 through 1978. Four hundred and sixty-nine patients (29.9%) had well-differentiated tumors, 677 (43.2%) were moderately and 420 (26.8%) poorly differentiated. Eighty-one percent of the patients had surgicopathologic Stage I disease, 11% Stage II, 6% Stage III, and 2% Stage IV. Mean age at diagnosis was 62.1 years (range, 36 to 91). The crude 5-year and 10-year survival rates for all patients were 74.1% and 62.2%, respectively. Five-year crude survival was 86.8% for Grade 1 and 58.3% for Grade 3 tumors. The 5-year crude survival for patients with intramucosal tumors was 88.7% as opposed to 46.9% for patients with tumors infiltrating to the serosa. Sixty-six percent of the patients with vessel invasion survived for 5 years in contrast to 88.6% for patients without vessel invasion. Histologic grade, myometrial infiltration, vessel invasion, and lymphocyte reaction surrounding the tumor were strongly interrelated. Multivariate analysis showed that the age of the patient at the time of diagnosis was the most important single prognostic factor. Disregarding age, survival in operated patients was more dependent on the depth of myometrial invasion than on grade and stage of disease. 
Pain threshold levels and coping strategies among patients who have chest pain and normal coronary arteries. Patients with noncardiac chest pain (NCCP) tend to show lower pain threshold levels for esophageal balloon distention than do patients with other painful gastrointestinal disorders and healthy controls. The NCCP patients also report greater usage of negative pain-coping strategies, less ability to perform specific behaviors to decrease pain, and higher levels of clinical pain than do other patient and healthy control groups. Behavioral treatments produce significant decreases in pain and disruption of daily activities. Further effort is needed, however, to develop treatments for NCCP that are based on knowledge of the behavioral manifestations of this disorder and the afferent mechanisms involved in perception of visceral pain. 
Periosteal suspension of the lower eyelid and cheek following subciliary exposure of facial fractures. Following craniofacial procedures that involve stripping of the periosteum and soft tissue over the zygomatic maxillary complex, descent of soft tissue with a decrease in anterior projection over the malar area and increase in fullness in the nasolabial fold have been seen to be a problem by these authors. Simple repositioning of the soft tissues to their normal anatomic position may be used to alleviate this problem. 
Noncemented porous-coated anatomic total hip arthroplasty. In 1984, as an alternate to the acrylic fixation of the components of total hip arthroplasty, the use of an uncemented porous-coated anatomic (PCA) hip system with a beaded porous coating to achieve biologic fixation was initiated. Since then, 44 patients with cementless acetabular components and 35 patients with cementless femoral components have been followed for a minimum of 24 months and an average of 37 months. Harris hip scores averaged 90.5 at most recent follow-up intervals. No reoperations were necessary for failures of fixation or change in position of the acetabular component. Ominous roentgenographic signs such as progressive bead shedding, progressive radiolucencies, or progressive component migration have not occurred. Two femoral component revisions have been necessary: one for intractable pain and one for pain and roentgenographic loosening. Although thigh pain has been prevalent (20%), all patients have been accommodated and have retained stable hip scores. Progressive radiolucencies and progressive implant subsidence have been rare occurrences. The authors continue to use the cementless acetabular component in all cases of total hip arthroplasty in which initial stability can be obtained. It is their preference to cement the femoral component in patients over 65 or when initial stability cannot be achieved. 
Immunologic effects of interferon. Interferons can be defined as a family of induced proteins sharing the capacity to exert pleiotropic effects on cell functions and to render cells resistant to virus infection. They are activating genes coding for a number of enzymes, most of which have not yet been characterized, and also by enhancing the synthesis of cell surface components. This enables interferons to modulate the immune response at different levels. This article will focus on the effects of interferon on antigen presentation, regulation of the immune response, activation of macrophage functions, and on its role in the pathogenesis of some diseases. 
Clinical implications of seizures in neurosarcoidosis. Seizures are a recognized manifestation of neurosarcoidosis, but their clinical relevance is not well established. We reviewed the characteristics, clinical correlations, and prognosis of seizures in 79 patients with neurosarcoidosis. Thirteen (15%) of the 79 patients had seizures, and in eight patients (10%) a seizure was the first manifestation of neurosarcoidosis. These seizures were generalized tonic-clonic seizures in 12 patients (92%) and partial seizures in four patients (31%). The patients with neurosarcoidosis with seizures were more likely to have a progressive or relapsing clinical course and intracranial mass lesions (four patients [31%]), encephalopathy or vasculopathy (eight patients [62%]), or hydrocephalus (five patients [38%]). These central nervous system disorders, rather than the seizures per se, were responsible for most of the serious morbidity and the two deaths (15%) among our patients with seizures. Indeed seizure control was good in 11 (85%) of 13 patients treated with combinations of steroids and antiepileptic medications. Seizures are an important sign in neurosarcoidosis because they are associated with more severe and progressive or relapsing forms of central nervous system sarcoidosis and may be an early manifestation of such disorders. 
Small hepatocellular carcinoma treated with percutaneous ethanol injection: MR imaging findings. Fifty-seven magnetic resonance (MR) imaging examinations were obtained at 0.5 T in 19 patients before and after percutaneous ethanol injection (PEI) for 23 hepatocellular carcinoma (HCC) lesions less than 3.5 cm in diameter. Seventeen patients also underwent MR imaging 6 months after completion of therapy. In 11 patients, computed tomography was performed before and after treatment. After PEI, fine-needle biopsy specimens were obtained in all cases. Before treatment, HCC lesions had low signal intensity on T1-weighted images in 13 cases, had the same signal intensity as normal liver parenchyma in six, and had high signal intensity in four; all 23 tumors had high signal intensity on T2-weighted images. After treatment and at 6-month follow-up, all 21 lesions that contained no malignant cells at fine-needle biopsy had high signal intensity on T1-weighted images and had low signal intensity on T2-weighted images. The remaining two HCC lesions in which tumor necrosis was not achieved with PEI displayed a different MR pattern, since the residual neoplastic tissue showed no change in signal intensity on either T1- or T2-weighted images. The authors conclude that MR imaging may be useful for evaluating the effectiveness of PEI in achieving tumor regression. 
Nicotine induced gastric injury. A quantitative macroscopic and microscopic analysis of the protective effects of sucralfate and feeding. Nicotine, while an important component of cigarettes, does not cause gross gastric mucosal damage, although its microscopic effect remains unknown. We have evaluated the histology and the microvascular permeability of (a) the effect of nicotine alone or in combination with ethanol on the gastric mucosa of rats and (b) the effect of feeding and sucralfate on the mucosa of rats treated with nicotine and ethanol. Mucosal injury was assessed histologically by the depth of injury and microvascular permeability by the leakage of fluorescein isothiocyanate-labelled albumin. Our results show that nicotine induced microscopic mucosal damage and accentuated the damage induced by alcohol. The damaging effects on mucosa of nicotine and ethanol, alone or in combination, were reduced by pretreatment with sucralfate. Similarly, feeding reduced the degree of mucosal injury. Nicotine and ethanol increased leakage of albumin into the interstitium and the leakage was reduced after sucralfate pretreatment. This study substantiates the adverse effect of smoking on mucosal damage. Vascular factors are probably involved in the pathogenesis. 
Characterization of human renal fibroblasts in health and disease: II. In vitro growth, differentiation, and collagen synthesis of fibroblasts from kidneys with interstitial fibrosis. Fibroblast cultures from normal human kidneys (NKF cells) and kidneys affected with interstitial fibrosis (FKIF cells) were analyzed for in vitro growth, differentiation dynamics, and collagen synthesis. FKIF cells are characterized by hyperproliferative growth, resulting in a prolonged mitotic lifespan, by an altered differentiation pattern, and by the expression of the FKIF cell-specific protein "fibrosin" (molecular weight 53 kd, isoelectric point [pi] 6.1). Furthermore, FKIF cells synthesize four to five times more total collagen per cell as compared with NKF cells, and the relative amounts of the collagen types produced (type I, III, and V) are significantly different from controls. Thus, the in vitro cell system of FKIF cells may help to elucidate the underlying mechanisms triggering the induction and progression of renal interstitial fibrosis in vivo. 
Deformity correction and long-term survival in an infant with iniencephaly. Case report. The authors describe the case of a male infant who was diagnosed prenatally as having iniencephaly. Since birth, the child has grown, thrived, and undergone two successful operations to correct his cervical deformity. This case demonstrates that the iniencephaly defect is not uniformly fatal and that neurosurgical intervention may offer significant improvement in the cervical deformity. 
Circadian variation in the frequency of onset of chest pain in acute myocardial infarction. The time of onset of chest pain was studied prospectively in 1154 consecutive patients admitted to a coronary care unit with myocardial infarction during a five year period. Statistical analysis confirmed a previous finding in a retrospective study of a bimodal frequency distribution with peaks in the time of onset of chest pain between 2330 and 0030 hours and between 0630 and 0830 hours. 
Angiotensin converting enzyme inhibitors, regional vascular hemodynamics, and the development and prevention of experimental genetic hypertension. During the development of hypertension in young spontaneously hypertensive rats (SHR) vascular resistance is increased, particularly in the renal circulation, and, to a lesser extent, in the splanchnic bed. Treatment with angiotensin converting enzyme inhibitors in young SHR reverses the renovascular abnormalities more effectively than simple vasodilators, suggesting that the resistance changes may depend on angiotensin II. Perindopril treatment during the development of hypertension causes a reduction in blood pressure as a result of a fall in total peripheral resistance, which persists long after treatment is stopped. These long-term effects can be prevented by replacing angiotensin during perindopril treatment. Not all organs share the long-term resistance changes following perindopril treatment, which are most marked in the renal, splanchnic, and cerebral circulations. The heterogeneous patterns of regional vascular resistance during the development and after prevention of hypertension with angiotensin converting enzyme inhibitors in SHR suggest that local factors, for example, angiotensin II related to the tissue renin-angiotensin system or local adrenergic activity, may be important in the genesis of high blood pressure in this genetic model. 
Is premedication with oral glycopyrrolate as effective as oral atropine in attenuating cardiovascular depression in infants receiving halothane for induction of anesthesia? The authors conducted a double-blind study to compare premedication with oral glycopyrrolate and oral atropine in prevention of bradycardia and hypotension during induction of anesthesia with halothane-N2O in 90 outpatient infants and children aged 1-18 mo who were randomized into three groups to receive either an oral placebo, oral atropine (0.02 mg/kg), or oral glycopyrrolate (0.05 mg/kg) approximately 1 h before induction of anesthesia. Heart rate and mean arterial pressure were measured before drug administration, just before induction of anesthesia, and every minute until surgical stimulation occurred. Glycopyrrolate, at the dose used, was significantly less effective than atropine in attenuating bradycardia during induction; neither glycopyrrolate nor atropine altered the incidence or degree of hypotension. Antisialagogic activity and side effects were comparable, except for significantly more flushing with atropine. 
Case report: epidural and bilateral retroorbital hematomas complicating sickle cell anemia. Early in the course of a painful crisis, a 19-year-old man with known sickle cell anemia (SCA) developed a clinical picture that resembled either early cavernous sinus thrombosis or retroorbital and bifrontal microinfarcts. A brain computer tomography scan demonstrated bilateral retroorbital hemorrhages along with a left frontal epidural hematoma. In the absence of trauma, thrombocytopenia, or any other detectable hemostatic defect, this type of hemorrhagic manifestation in the setting of SCA has not, to our knowledge, been previously reported in the literature. 
Classic and vigorous achalasia: a comparison of manometric, radiographic, and clinical findings. Compared with classic achalasia, vigorous achalasia has been defined as achalasia with relatively high esophageal contraction amplitudes, often with minimal esophageal dilation and prominent tertiary contractions on radiographs, and with the presence of chest pain. However, no study using current manometric techniques has compared manometric, radiographic, and clinical findings in vigorous and classic achalasia or questioned the usefulness of making this distinction. Fifty-four cases involving patients with achalasia whose radiographic and manometric studies were performed within 6 months of each other were available for review. Patients with vigorous achalasia (n = 17), defined by amplitude greater than or equal to 37 mm Hg, and patients with classic achalasia (n = 37), defined as amplitude less than 37 mm Hg, had substantial overlap in radiographic parameters of esophageal dilation, tortuosity, and tertiary contractions. Manometric properties of repetitive waves and lower esophageal sphincter pressure and clinical aspects of chest pain, dysphagia, heartburn, and satisfactory responses to pneumatic dilation were similar in both forms of achalasia. A separate analysis of patients with mean contraction amplitude greater than 60 mm Hg revealed similar findings. It is concluded that use of amplitude as a criterion for classifying achalasia is arbitrary and of dubious value. 
Prevalence of obesity in American Indians and Alaska Natives. Obesity is an important risk factor for cardiovascular diseases and non-insulin-dependent diabetes, which are chronic diseases that afflict American Indians and Alaska Natives today. Because American Indians are not represented in most national health and nutrition surveys, there is a paucity of data on actual prevalence of obesity in American Indians. We estimated prevalence of overweight and obesity for American Indian adults, school-age children, and preschool children from existing data. The prevalence of obesity in adults was estimated from self-reported weights and heights obtained from a special survey of American Indians performed as part of the 1987 National Medical Expenditure Survey. Prevalence of obesity in American Indians was 13.7% for men and 16.5% for women, which was higher than the US rates of 9.1% and 8.2%, respectively. Obesity rates in American Indian adolescents and preschool children were higher than the respective rates for US all-races combined. 
Dipyridamole echocardiography test. A new tool for detecting jeopardized myocardium after thrombolytic therapy. BACKGROUND. We wished to assess whether dipyridamole echocardiography test (DET) can detect jeopardized myocardium after thrombolytic therapy. METHODS AND RESULTS. Seventy-six consecutive patients with a first acute myocardial infarction (AMI) were treated with 2 million IU urokinase i.v. within 4 hours of the onset of AMI and underwent high-dose (as much as 0.84 mg/kg over 10 minutes) DET 8-10 days after AMI. The results were correlated to the anatomy of the infarct-related vessel (IRV). In patients with positive DET, we evaluated the wall motion score index (WMSI; a semiquantitative integrated estimation of extent and severity of the stress-induced dyssynergy). WMSI was derived by summation of individual segment scores divided by the number of interpreted segments. In a 13-segment model, each segment was assigned a score ranging from 1 (normal) to 4 (dyskinetic). Fifty-three patients had positive results on DET. Of these, 42 had dipyridamole-induced new wall motion abnormalities (WMAs) confined to the infarct zone or adjacent segments. In these patients, mean WMSI increased from 1.46 +/- 0.26 (at resting conditions) to 1.73 +/- 0.35 (at peak dipyridamole) (p less than 0.01), whereas no significant change was detected in negative patients (1.6 +/- 0.34 versus 1.57 +/- 0.34, p = NS). Coronary angiography showed a patent IRV (TIMI grade 2 or 3) in 53 patients and no or minimal reperfusion (TIMI grade 0 or 1) in 23 patients. A patent IRV with critical residual stenosis was found in 35 of 42 patients with dipyridamole-induced WMAs in the infarct zone and in 18 of 34 patients without WMAs (p less than 0.05). Among the 23 patients with occluded IRVs, nine had collateral flow to the distal vessel; six of these had a positive DET. Thus, the sensitivity and specificity for identifying a critically stenotic but patent IRV or the presence of a collateral-dependent zone were 66% and 93%, respectively. In a subset of nine patients with a positive DET in the infarct zone or adjacent segments, DET and a control coronary angiography were repeated 1-3 months after an angiographically successful (residual stenosis, 50% or less) coronary angioplasty in the IRV. The repeat DET was negative in eight patients (all with patent IRV at control angiography) and again positive in one patient, who showed restenosis at angiography. The WMSI, at resting conditions was similar before and after angioplasty, whereas it differed significantly at peak dipyridamole (1.7 +/- 0.2 versus 1.4 +/- 0.2, p less than 0.01). CONCLUSIONS. DET can identify the anatomy of the IRV, and dipyridamole-induced WMAs within the infarct zone detect regions with jeopardized myocardium that may benefit from intervention. 
Symptoms associated with tamoxifen treatment in postmenopausal women. Adjuvant breast cancer therapy with tamoxifen is associated with greater disease-free survival and possibly overall survival. Long-term treatment, possibly of indefinite duration, is being evaluated. Compliance with long-term therapy will depend largely on the nature and severity of tamoxifen's side effects. We evaluated the symptoms associated with tamoxifen therapy in 140 postmenopausal women with axillary node negative breast cancer in remission (mean years since menopause, 9.3) enrolled in a placebo-controlled, randomized toxicity study. Tamoxifen recipients reported moderated or severe vasomotor symptoms up to 17%, and gynecologic symptoms up to 4% more frequently than placebo subjects. Persistent vasomotor, gynecologic, or other major side effects were reported by 48% of tamoxifen recipients, and by 21% of placebo subjects. These carefully collected data suggest significant perceived symptom 'cost' of tamoxifen therapy in postmenopausal women, of a magnitude likely to compromise long-term compliance. 
Prognostic factors in Japanese patients with colorectal cancer: the significance of large bowel obstruction--univariate and multivariate analyses. In order to define prognostic factors in colorectal carcinoma, univariate and multivariate analyses were carried out on data from 113 Japanese patients treated in a typical general hospital in Japan. In the univariate analysis, a poor prognosis was seen in those with poorly differentiated adenocarcinoma, in tumors that perforated the visceral peritoneum or that invaded directly other organs or structures (T4), in metastasis to the nodes along the main vascular pedicle (N3), in lymphatic permeation, in blood vessel invasion, in peritoneal dissemination, in Dukes C stage, and in those with lesions presenting with large bowel obstruction. Of these, only lymph node metastasis and peritoneal dissemination had an independent prognostic significance when a multivariate Cox analysis was performed. The significant risk factors related to an obstructing tumor were determined by multivariate logistic regression analysis. The significant variables were patient's age, nodal involvement and peritoneal dissemination. Since lymph node metastasis and peritoneal dissemination proved significant in both multivariate analyses, we propose that the presence of large bowel obstruction is not an independent prognostic factor in patients with colorectal carcinoma. In poor-risk patients who have an obstructing tumor, a staged operation should be attempted for definitive curative surgery. 
Loiasis in endemic and nonendemic populations: immunologically mediated differences in clinical presentation. To define the clinical spectrum of loiasis more precisely and to begin to assess the immunologic basis for the difference in clinical manifestations between visitors to endemic areas and natives of these areas, 51 West African patients with loiasis were evaluated and compared with 42 infected expatriates. Microfilaremia was present in 90% and Calabar swellings in only 16% of the endemic patients. Conversely, only 10% of the expatriates were microfilaremic while 95% complained of Calabar swellings. The endemic population showed significantly decreased levels of peripheral blood eosinophils, parasite-specific IgG, and lymphocyte proliferation to parasite antigens compared with the nonendemic population. These findings support the hypothesis that differences in the modulation of the immune response to parasite antigen are responsible for the observed differences in clinical presentation between expatriate and endemic populations with loiasis. 
Prevalence of gastroesophageal reflux in elderly patients in a primary care setting. Despite the aging of our population, there remains a paucity of information about gastroesophageal reflux (GER) in the elderly. To assess the prevalence and characteristics of GER within this patient population, questionnaires evaluating symptoms associated with GER were administered to 313 consecutive patients 62 yr old or older from a primary care setting. Fourteen percent of these patients reported having at least weekly heartburn. Ambulatory 24-h esophageal pH monitoring was accomplished in 54 of the 313 patients surveyed. Twenty percent (11/54) of this subgroup exhibited increased acid contact time (pH less than 4 for more than 6% of the monitoring period). Twenty-two percent (12/54) complained of heartburn, yet only six individuals (11%) exhibited both symptomatic and objective indications of acid reflux. Surprisingly, 31% (17/54) of the patients studied exhibited significant alkalinity within the distal esophagus (pH greater than 8 for greater than 1.5% of the monitoring period). Whereas 29% of these patients (5/17) reported heartburn, 40% of those reporting heartburn (2/5) had acid GER as well as excessive alkalinity. In contrast to patients with acid GER--none of whom reported pulmonary symptoms--24% (4/17) of these patients with esophageal alkalinity reported wheezing, nocturnal cough, or paroxysmal nocturnal dyspnea. Of the four patients with significant distal esophageal exposure to both acid and alkali, two reported heartburn and a third reported dysphagia. In addition to the somewhat higher prevalence of acid reflux than anticipated, a surprisingly high prevalence of esophageal alkalinity was observed. 
Availability and use of hepatitis B vaccine in laboratory and nursing schools in the United States. Hepatitis B is a well-documented occupational hazard for health care workers, including both laboratory and nursing personnel. Since the development of effective hepatitis B vaccines, the Immunization Practices Advisory Committee (ACIP) has recommended that health care workers receive the vaccine. In this study, 78 laboratory training programs and 83 nursing training programs were surveyed regarding availability and usage of hepatitis B vaccine. The hepatitis B vaccine was made available to students in 81 percent of the laboratory programs and 23 percent of the nursing programs. In those programs making the vaccine available, only 59 percent of the laboratory programs and 5 percent of the nursing programs reported a high (greater than 75 percent) use by students. Concern about cost and payment for the vaccine was the most common reason (80 percent) noted by laboratory schools that did not have hepatitis B vaccination programs for students. Of the nursing schools that did not have vaccine programs, 58 percent had not yet considered a program. At laboratory schools with vaccination programs, who paid for the vaccine (hospital or school versus student) was among the most important determinants for vaccine usage by students. These findings point out that some laboratory schools and many nursing schools have not applied the ACIP recommendations to their own programs. Educational efforts and creative payment plans for the vaccine are needed to increase the availability and use of hepatitis B vaccine among laboratory and nursing students. 
Analysis of retroviral sequences in the spinal form of multiple sclerosis. The polymerase chain reaction was used, in a blind study, to look for retroviral sequences in DNA extracted from the peripheral blood mononuclear cells of 11 patients with the spinal form of multiple sclerosis (MS). Control subjects consisted of 7 patients with other neurological diseases and 5 healthy blood donors. Three sets of oligonucleotides were used. They could detect all known human oncoretroviruses, lentiviruses, or spumaretroviruses. The primers recognized conserved sequences in the long terminal repeats of the proviral DNA. Control experiments showed that the primers crossreacted within the human immunodeficiency virus or human T-cell lymphotropic virus group and that they provided the expected level of sensitivity. Therefore the assay could have detected not only known human retroviruses but also new related members. In spite of this, no retroviral sequences were detected in either the MS or the control specimen. 
A controlled clinical trial of E5 murine monoclonal IgM antibody to endotoxin in the treatment of gram-negative sepsis. The XOMA Sepsis Study Group OBJECTIVE: To assess the efficacy of adjunctive monoclonal antibody antiendotoxin immunotherapy in patients with gram-negative sepsis. DESIGN: Double-blind, randomized, placebo-controlled trial. SETTING: Thirty-three university-affiliated centers, including Veterans Affairs, community, and municipal hospitals. PATIENTS: Hospitalized adults with signs of gram-negative infection and a systemic septic response. INTERVENTION: Patients were assigned to receive either 2 mg/kg of a murine monoclonal antibody directed against gram-negative endotoxin (E5) or placebo. A second infusion was administered 24 hours later. MAIN OUTCOME MEASURES: Mortality over the 30-day study period, resolution of organ failures, and safety. RESULTS: Four hundred eighty-six patients were enrolled. Three hundred sixteen had confirmed gram-negative sepsis (54% bacteremic, 46% nonbacteremic). The survival difference was not statistically significant for all patients. Among patients with gram-negative sepsis who were not in shock at study entry (n = 137), E5 treatment resulted in significantly greater survival (relative risk, 2.3; P = .01). Resolution of individual organ failures was more frequent among these patients, occurring in 19 (54%) of 35 patients in the E5 group vs eight (30%) of 27 in the placebo group (P = .05). Four reversible allergic reactions occurred among 247 patients (1.6%) receiving E5. No other toxicity was identified. CONCLUSIONS: Treatment with E5 antiendotoxin antibody appears safe. It reduces mortality and enhances the resolution of organ failure among patients with gram-negative sepsis who are not in shock when treated. 
Prevention of insulitis and diabetes onset by treatment with complete Freund's adjuvant in NOD mice. In studies of immune cell defects in autoimmune diabetes mellitus, we observed that complete Freund's adjuvant (CFA) prevented the onset of diabetes when injected into 8- to 10-wk-old prediabetic nonobese diabetic (NOD) mice. The prevalence of the onset of diabetes in the CFA-injected versus uninjected NOD mice was 2 of 81 (2.5%) vs. 231 of 379 (61%) among females and 2 of 44 (4.5%) vs. 83 of 336 (25%) among males, respectively. The incidence of histologically identifiable insulitis was significantly reduced in CFA-treated prediabetic female NOD mice (18%) compared with the incidence in female age-matched controls (70%). Splenocytes or Mac-(1+)-enriched splenocytes from CFA-treated NOD mice, when cotransferred with splenocytes from diabetic mice, reduced the incidence of diabetes provoked by diabetic splenocytes in vivo. In the spleen, CFA injection induced sustained increases in cell proliferation and an associated major increase in the numbers of an immature cell type that expressed the Mac-1 surface antigen. In CFA-treated NOD mice, lymphocytes derived from the spleen failed to respond in vitro to stimulation by the mitogen concanavalin A or by anti-CD3. When cocultured, Mac-1+ cells, enriched from the splenocytes of CFA-treated mice, suppressed concanavalin A- or anti-CD3-induced proliferation of T lymphocytes derived from either the spleen or thymus of untreated NOD mice. Therefore, treatment with CFA prevents the development of diabetes, and concomitantly, insulitis while stimulating the generation of splenic suppressor cells that are capable of suppressing diabetogenic T-lymphocyte function in vivo and in vitro. 
Intermittent injection vs patient-controlled analgesia for sickle cell crisis pain. Comparison in patients in the emergency department. BACKGROUND.--The purpose of this study is a prospective assessment of morphine sulfate administration by intermittent intravenous (IV) injections (Int-IV) vs patient-controlled analgesia (PCA) in patients in the emergency department (ED) with sickle cell crisis pain. METHODS.--Patients were at bed rest and received intravenous hydration. Linear analog scale for pain intensity and verbal pain scale, level of alertness, and vital signs were assessed prior to therapy, every 60 minutes thereafter, and at the time of discharge from the ED. Patients were randomized to Int-IV or PCA. During phase 1, patients in the Int-IV group received morphine sulfate 4 mg IV every 30 to 60 minutes as necessary for a linear analog scale for pain intensity greater than 50 mm. The patients in the PCA group received morphine sulfate 2 mg bolus then 1.0 mg with a 6-minute lockout. During phase 2, patients in the Int-IV group received morphine sulfate 8 mg IV every 30 to 60 minutes as necessary for a linear analog scale for pain intensity greater than 50 mm. The patients in the PCA group received morphine sulfate 5 mg bolus then 2.7 mg with a 10-minute lockout. Data were analyzed by unpaired t test, general linear modeling, Mann-Whitney U test, and chi 2 test. RESULTS.--During phase 1, 10 patients (28.3 +/- 7.3 years) received Int-IV and 10 patients (33.9 +/- 12.5 years) received PCA. Treatment groups did not differ significantly regarding duration of pain, amount of morphine administered, linear analog scale for pain intensity, verbal pain scale, level of alertness, or vital signs except for a significantly lower final respiratory rate with Int-IV. In phase 2, 12 patients (28.4 +/- 5.6 years) received Int-IV and 13 patients (26.8 +/- 8.1 years) received PCA. The PCA groups had a significantly shorter elapsed time between onset of pain and treatment (7.3 +/- 6.5 hours) when compared with the Int-IV group (18 +/- 16.9 hours). Treatment groups did not differ significantly with respect to total amount of morphine administered, linear analog scale for pain intensity, verbal pain scale, vital signs, or level of alertness. The PCA group had a significant reduction in length of stay in the ED during phase 2 when compared with phase 1. The ED discharge rate and the incidence of side effects did not differ significantly between groups. CONCLUSION.--At both the low- and high-dose regimens, PCA is equally safe and effective and may be used in place of Int-IV administration of morphine in the ED treatment of sickle cell crisis pain. 
Alcohol consumption of patients with supraventricular tachyarrhythmias other than atrial fibrillation. We studied the recent alcohol consumption and other possible precipitating factors in 99 consecutive patients (53 men and 46 women) all under 65 years of age with sustained re-entry and automatic supraventricular tachyarrhythmias and compared them with those of two groups of controls. One control group was derived from the Emergency Room patients and matched for age and sex; the other group (44 men, 22 women, mean age 48.7 years) was randomly selected from the general out-of-hospital population. There were 50 patients with supraventricular tachycardia, 30 with atrial flutter, and 19 with paroxysmal atrial tachycardia. Coronary heart disease (14% of patients), hypertension (10%), and dilated cardiomyopathy (6%) were the most prevalent cardiovascular diseases associated with the arrhythmias. The self-reported alcohol consumption of patients with arrhythmias during the week preceding the arrhythmia did not differ significantly from that of hospital or population controls, although significantly more patients than controls had liver enzyme levels above normal; neither were there any significant differences between the groups regarding prevalence for alcoholism as judged by the CAGE questionnaire. The results were essentially similar when patients with supraventricular tachycardia and those with intra-atrial tachyarrhythmias (flutter and paroxysmal tachycardia) were separately compared with the controls. We conclude that alcohol consumption, although a risk factor for atrial fibrillation, is not associated with the induction of other supraventricular tachyarrhythmias in patients of working age. 
Mineral spirits inhalation associated with hemolysis, pulmonary edema, and ventricular fibrillation. A previously healthy 42-year-old woman developed severe dyspnea, chest discomfort, and malaise several hours after prolonged exposure to concentrated vapors from mineral spirits. On the way to the hospital, she sustained a cardiopulmonary arrest; on arrival several minutes later, she was found to be in ventricular fibrillation and was resuscitated. Her hospital course included slowly resolving cardiac abnormalities, amnesia, noncardiogenic pulmonary edema, abrupt hemolytic anemia, sustained rhabdomyolysis, and other metabolic abnormalities. It is highly probable that this syndrome represented acute and near-lethal toxicity caused by the inhalational exposure to the petroleum distillate known as mineral spirits. It is important that physicians be aware of this syndrome in order to recognize it on presentation and to warn patients of the risk of such toxic exposure. 
Refractory chronic bacterial prostatitis: a re-evaluation of ciprofloxacin treatment after a median followup of 30 months. A total of 16 men suffering from refractory chronic bacterial prostatitis caused by Escherichia coli was treated with ciprofloxacin for 4 weeks. After a median followup of 30 months (range 21 to 36 months) 10 of the 16 patients were considered cured as judged by bacteriological results and clinical symptoms. In 2 men a second ciprofloxacin regimen obviously showed success also. In 2 patients ciprofloxacin therapy failed and in 2 therapy had to be discontinued due to side effects of the central nervous system. 
Prevention and treatment of pregnancy-associated hypertension: what have we learned in the last 10 years? High blood pressure (BP) complicates approximately 10% of all pregnancies. Hypertension in pregnancy falls into four categories: (1) preeclampsia-eclampsia, (2) chronic hypertension of whatever cause, (3) preeclampsia-eclampsia superimposed to chronic hypertension or renal disease, and (4) transient or late hypertension (gestational hypertension). Preeclampsia, the association of hypertension, proteinuria, and edema, accounts for more than 50% of all the hypertensive disorders of pregnancy and is a major cause of fetal and maternal morbidity and mortality. Unfortunately, distinguishing between preeclampsia and other causes of hypertension on clinical grounds can be difficult because of the lack of specific tests for differential diagnosis. Increased vascular resistance has been claimed as the primary cause of preeclampsia; however, a variable hemodynamic profile with relatively high cardiac outputs, normal filling pressures, and inappropriately high systemic vascular resistances is now reported by most investigators. Imbalance between vasodilator and vasoconstrictor eicosanoids may account for platelet activation and increased responsiveness to pressor peptides. Altered prostacyclin (PGI2) to thromboxane A2 (TxA2) ratio in maternal uteroplacental vascular bed may favor local platelet activation and vasoconstriction contributing to placental insufficiency and fetal distress. Alternatively, recent evidence seems to suggest that fetal umbilical placental circulation may be the site of the primary vascular injury. Whether low-dose aspirin prevents preeclampsia because it inhibits the excessive maternal TxA2 or whether the partial inhibition of fetal TxA2 is also of therapeutic value remains to be established. Treatment of severe hypertension in pregnancy is probably important to prevent cardiac failure or cerebrovascular accidents in the mother. The need for pharmacological therapy of mild to moderate hypertension is still debated, since no formal studies are available to clarify whether pharmacological treatment in such instances effectively reduces maternal or fetal risk. For the treatment of preeclampsia, hydralazine and nifedipine may be used when delivery is not applicable. Labetalol and diazoxide are effective for hypertensive emergencies. Life-threatening hypertension that does not respond to more conventional therapy is an indication for the use of sodium nitroprusside. For chronic hypertension, alpha-methyldopa remains the treatment of choice; if ineffective, hydralazine or beta-blockers are suitable. Effectiveness and safety of other molecules remain elusive. 
Desmoplastic small cell tumors of the peritoneum coexpressing mesenchymal and epithelial markers. Desmoplastic small cell tumors arising diffusely within the abdomen and lacking an apparent organ of origin are rare. Most previously reported cases occurred in children, but young adult patients also have been described. Light microscopic examination shows the tumors to be composed of nests of small cells surrounded by an abundant desmoplastic stroma. Immunohistochemical findings reveal multidirectional differentiation with coexpression of cytokeratin, milk fat globule, neuron-specific enolase, Leu-7, desmin, and vimentin. Electron microscopic examination demonstrates paranuclear condensations of intermediate filaments. The authors describe two patients who died of their disease, despite aggressive chemotherapy and surgical intervention. 
Ethnic differences in mortality from ischaemic heart disease and cerebrovascular disease in England and Wales. OBJECTIVE--To examine mortality from ischaemic heart disease and cerebrovascular disease in England and Wales by country of birth of the deceased. DESIGN--Standardised mortality ratios were computed by country of birth groups for ischaemic heart disease and cerebrovascular disease for 1979-83 and 1970-2 by using the five year age-sex specific rates for England and Wales for 1979-83 as standard. SETTING--England and Wales 1970-2 and 1979-83. RESULTS--In 1979-83 mortality from ischaemic heart disease was highest in men and women born in the Indian subcontinent (standardised mortality ratio 136 and 146 respectively). Young Indian men suffered the greatest excess (313 at ages 20-29). Other groups with raised mortality included Irish, Scottish, and Polish born immigrants. Those born in the Caribbean, the old Commonwealth, west Europe, and the United States had low death rates. In England and Wales mortality from ischaemic heart disease declined by 5% in men and 1% in women between 1970-2 and 1979-83, with greatest percentage declines in immigrants born in the United States, South Africa, the old Commonwealth, the Caribbean, and France. immigrant groups with raised mortality in the earlier period showed little improvement, and mortality from ischaemic heart disease increased among Indians (6% in men and 13% in women). In 1979-83 mortality from cerebrovascular disease was highest in Caribbeans (standardised mortality ratios 176 in men and 210 in women), followed by Africans, Indians, and Irish. Rates were low in west Europeans. Mortality from stroke declined by 28% overall in this period, a rate of decline shared by most groups. Men from the Indian subcontinent showed a decline of only 3%. CONCLUSION--In the 1980s mortality from ischaemic heart disease and cerebrovascular disease differed significantly between ethnic groups in England and Wales. In general, ethnic groups that experienced lower mortality from ischaemic heart disease in the 1970s showed the greatest improvement over the following decade. 
Botulinum toxin treatment of tremors. We report the results of an open trial of botulinum toxin (Botox) in the treatment of 51 patients with disabling tremors, classified as dystonic (14), essential (12), combination of dystonic and essential (22), parkinsonian (1), peripherally induced (1), and midbrain (1). The average age of the patients was 55.8 years, and duration of symptoms was 13.9 years. During a total of 160 treatment visits, an average of 242 +/- 75 units of Botox was injected per visit in cervical muscles of 42 patients with head tremor and 95 +/- 38 in forearm muscles of 10 patients with hand tremor; one patient was injected in both. The average peak effect for all patients was rated as 3.0 (0 to 4 scale). Thirty-five (67%) patients improved (peak effect greater than or equal to 1). The average latency from injection to response was 6.8 days, and the average duration of maximum improvement was 10.5 weeks. Local complications, lasting an average of 20.6 days, were noted in 17 (40%) patients injected for head tremor, consisting chiefly of dysphagia in 12 (29%), transient neck weakness in four (10%), and local pain in two (5%). Six (60%) patients with hand tremor had transient focal weakness. EMG recordings showed decreased amplitude of EMG bursts after Botox treatment. The results of this pilot study indicate that Botox injections can be used to control tremor in patients in whom other forms of therapy have failed. 
Chickenpox pneumonia, its complications and management. A report of three cases, including the use of extracorporeal membrane oxygenation. We report three cases of chickenpox pneumonia in adults, all of whom required intermittent positive pressure ventilation. One patient developed a variety of complications, and another, a pregnant woman, required extracorporeal membrane oxygenation. 
A prospective evaluation of the effect of tumor cell DNA content on recurrence in colorectal cancer. Tumor cell DNA (ploidy) content was measured prospectively in samples from 320 patients resected for colorectal cancer with a minimum follow-up time of 2 years. All patients were followed and those with recurrence were investigated carefully. There was no correlation between tumors with an abnormal cellular DNA content (aneuploid or tetraploid) and patient age, sex, tumor site, pathologic stage, or histologic grade. In 236 patients who underwent potentially curative operations, 75 (32%) had local and/or distant recurrence. The recurrence rate was significantly higher (test statistic, 4.3; P = 0.04) for those patients with aneuploid tumors (52 of 142, 37%) compared with those with diploid tumors (23 of 94, 24%). The subgroups of patients where ploidy exerted an effect were in patients with Stage B tumors or mobile tumors and in patients over 65 years of age. Further analysis showed that there was a twofold increase in local recurrence and a threefold increase in distant recurrence in patients with aneuploid tumors, but no excess of patients who had both local and distant recurrence. Measurement of DNA ploidy can identify a group of patients undergoing curative surgery for colorectal cancer at high risk for recurrence. In combination with clinicopathologic factors, DNA ploidy may be useful in analyzing the results of trials and in planning adjuvant therapy. 
Emergency treatment of headache. Headache is a frequent presenting complaint in the emergency department. Once a diagnosis is established, and significant organic disease can be ruled out, relief of pain must be addressed. Referral for follow-up care and narcotic habituation is a recurrent problem for the emergency physician. This article discusses the differential diagnosis of headache, evaluation of the emergency room patient, and treatment of the patient with headache. 
Gene deletions force nonsecretory alpha-chain disease plasma cells to produce membrane-form alpha-chain only. We studied a case of nonsecretory alpha-chain disease. The proliferating plasma cells contained a short transcript coding for a truncated membrane-form alpha 1-chain. The productive alpha-gene bore several noncontiguous deletions affecting the VHDJH and CH1 regions. Two deletions were accompanied with peculiar insertions containing duplications. The first insertion contained an acceptor splice site and was present in part in the mature transcript, thus coding for an abnormal aminoterminal peptide. Another deletion located 3' to CH3 eliminated the polyadenylation site of secreted-form alpha-mRNA. As a result, only membrane-form alpha mRNA was present in the tumoral plasma cells, thus explaining the nonsecretory phenotype of the disease. Comparison of cDNA and genomic sequences showed that the previously undescribed human alpha membrane region is encoded by a single exon, beginning with two alternate acceptor splice sites, and comprises either 65 or 71 amino acids. 
Anterior sternal retraction for reoperative median sternotomy. The incidence of reoperative median sternotomy for repeat cardiac surgery is increasing. Reoperative median sternotomy is associated with a higher morbidity and mortality than first-time cardiac surgery. A portion of this morbidity and mortality may be due to direct injury to the heart and great vessels in the process of reopening the sternum. We report a new technique utilizing anterior sternal retraction that allows division of adhesions between the undersurface of the sternum and the heart and great vessels under direct vision. This technique enables the surgeon to minimize the risk of serious injury to these underlying structures during reoperative cardiac surgery. 
Physical overdistension converts ventricular cardiomyocytes to acquire endocrine property and regulate ventricular atrial natriuretic peptide production. Atrial natriuretic peptide (ANP) is present in adult atria but at very low concentrations in normal adult mammalian ventricles. In the atria, the production of ANP is regulated by physical distension of the atrial wall. The same phenomenon was investigated in the ventricles of rats and men. Cardiac tissues from human ventricular aneurysm (n = 5), spontaneously hypertensive rats (n = 30), and rats that had overloaded left ventricles induced by surgery (n = 84) were studied with the methods of light microscopic immunocytochemistry, electron microscopic immunogold staining, and RNA-RNA tissue in situ hybridization. It was found that the levels of ANP gene expression, ANP immunoreactivity, and ANP-containing specific granules in the overburdened ventricles were elevated and their degrees of fluctuation were directly proportional to the force of physical distension applied to the ventricular cardiomyocytes. In rats, ANP mRNA and ANP immunoreactivity returned to the control level seven days after the ventricular overload was surgically released. The changes of ANP and its mRNA in the ventricles were related more closely to the changes of intraventricular pressure than to cardiocytic hypertrophy. In addition, ANP immunoreactivity was demonstrated in Purkinje cells and periarteriolar cardiomyocytes in the ventricles of normotensive rats. In conclusion, physical overstretch of the ventricle wall is likely to be the triggering factor affecting ventricular cardiomyocytes to acquire endocrine property, and also to regulate the production of ventricular ANP, thereby contributing to the control of the blood volume and the blood pressure. 
Functional outcomes of children with sickle-cell disease affected by stroke. The nature and degree of functional recovery after stroke in children with sickle-cell disease (SCD) has not been extensively investigated. The purpose of this study was to evaluate retrospectively the functional status of 14 SCD children who had had strokes and to compare them with age-matched and gender-matched SCD children who had not had strokes. By doing so, we would be able to quantify the eventual physical and cognitive functional outcomes of survivors of stroke secondary to SCD and assess the impact of stroke on these patients. These children (five boys and nine girls) with SCD and stroke(s) were 11.6 +/- 4.3 years of age (range five to 18 years). They experienced one to three strokes at a mean age of 6.1 +/- 5.2 years (range one to 17 years). A series of tests were administered to these subjects to evaluate physical and psychosocial functions. These tests were performed at least one year after the latest stroke. This study showed that all of the SCD-stroke children were physically independent. Only a few had impairments of hand functions and mild difficulties in self-care activities. However, most of these children demonstrated intellectual deficits ranging from borderline to moderate mental retardation, reduced language functions ranging from low normal to retarded range, and problems in adjustment. Intelligence quotient of the children with SCD-stroke(s) was significantly lower than those of age-matched and gender-matched nonstroke SCD children, suggesting that stroke caused an adverse effect on the cognitive functioning of these children. The results indicate that in the SCD-stroke children psychosocial deficits outweighed physical disabilities. 
Acute appendicitis. A 5-year review. A startling 31 per cent rate of perforated appendicitis in 1984 prompted a 5-year review at the Guthrie Medical Center. An increase over previous rates of 13 per cent and 0 per cent in 1964 and 1944 was confirmed in this study. Perforation accompanied 44 of 240 cases of appendicitis (18.3%); diagnostic accuracy in 295 cases undergoing operation was 81.4 per cent. Groups at risk for perforation were patients in the first decade of life (34.3% with perforations) and those over 50 years of age (48% perforated). Perforation rates were generally inversely related to accuracy. Accuracy was poorest in women in the second to fourth decade or those in the mid-portion of the menstrual cycle. When the appendix was not perforated, complications occurred in 8.7 per cent of patients while 29.5 per cent with a perforation had a complication. The mean hospital stay was prolonged by 2.5 days if the appendix was perforated. An increased awareness of the risk by both the public and physicians is essential to reduce the number of perforations. 
Intrarenal pressure following pyeloplasty or percutaneous surgery. In a study of 37 patients it was shown that recording the intrapelvic pressure is a safe and reliable means of judging the best time to remove a nephrostomy tube. No post-operative complications were encountered and the procedure has the added advantage of avoiding the use of X-rays. 
Oncocytic metaplasia of the pharynx. Oncocytic metaplasia of the pharynx has been infrequently described, with only two previous cases in the literature. With the advent of panendoscopy during the last decade, however, a better understanding of this histopathologic diagnosis is desirable. Thirty-three cases are reviewed, with thirty occurring in the nasopharynx. This was most commonly discovered as an unrelated finding during endoscopic evaluation of a head and neck mass or malignancy in twenty-two patients, either histologically after random biopsy or after biopsy of small but visible lesions. An additional eight cases manifested otitis media or eustachian tube dysfunction. The histology, terminology, and benign clinical nature of these lesions are discussed. 
Pituitary hyperplasia and gigantism in mice caused by a cholera toxin transgene. Cyclic AMP is thought to act as an intracellular second messenger, mediating the physiological response of many cell types to extracellular signals. In the pituitary, growth hormone (GH)-producing cells (somatotrophs) proliferate and produce GH in response to hypothalamic GH-releasing factor, which binds a receptor that stimulates Gs protein activation of adenylyl cyclase. We have now determined whether somatotroph proliferation and GH production are stimulated by cAMP alone, or require concurrent, non-Gs-mediated induction of other regulatory molecules by designing a transgene to induce chronic supraphysiological concentrations of cAMP in somatotrophs. The rat GH promoter was used to express an intracellular form of cholera toxin, a non-cytotoxic and irreversible activator of Gs. Introduction of this transgene into mice caused gigantism, elevated serum GH levels, somatotroph proliferation and pituitary hyperplasia. These results support the direct triggering of these events by cAMP, and illustrate the utility of cholera toxin transgenes as a tool for physiological engineering. 
Balloon dilatation of the aortic valve in the fetus: a report of two cases. Because they had irreversible damage to the left ventricular myocardium none of 12 patients with critical aortic stenosis diagnosed prenatally survived after postnatal treatment. This experience prompted three attempts at intrauterine balloon dilatation of the aortic valve in two fetuses with this condition. On each attempt the balloon catheter was successfully delivered to the left ventricle. In the first fetus the aortic valve was not crossed and the fetus died the next day. In the second fetus the balloon was correctly positioned across the aortic valve and inflated in the valve ring. After delivery, a further balloon angioplasty was performed; this relieved the stenosis but the patient died five weeks later from persisting left ventricular dysfunction related to endocardial fibroelastosis. Balloon angioplasty is feasible in fetal life but the prognosis depends on the ability of the relief of stenosis to limit, prevent, or allow regression of left ventricular damage before delivery. 
New method for dealing with late-presenting spontaneous esophageal ruptures. A new technique is described for dealing with late-presenting spontaneous esophageal ruptures. This method requires only a short period of general anesthesia to drain the periesophageal abscess by a drainage tube inserted into the abscess cavity from the esophagus with the aid of a gastroscope and fluoroscopy. Gastric fluids are diverted from the esophageal rupture with a gastrostomy, and a jejunostomy is used for enteral feeding. The esophagus is retained, and closure of the fistula with resumption of normal swallowing is documented with serial sinograms. 
Alfentanil for urgent caesarean section in a patient with severe mitral stenosis and pulmonary hypertension. We present the case of a parturient with severe mitral stenosis and pulmonary hypertension who received general anaesthesia using alfentanil for urgent Caesarean section. Alfentanil promoted haemodynamic stability and allowed immediate postoperative extubation. Epidural morphine provided postoperative analgesia. This combination permitted early ambulation and prevention of thromboembolism. A disadvantage of this technique, neonatal respiratory depression, was promptly reversed with a single dose of naloxone. The anaesthetic management of mitral stenosis in pregnancy is discussed and the neonatal pharmacokinetics of maternally administered alfentanil are presented. 
Homozygosity for a newly identified missense mutation in a patient with very severe combined immunodeficiency due to adenosine deaminase deficiency (ADA-SCID). We have identified a previously unrecognized missense mutation in a patient with severe combined immunodeficiency due to adenosine deaminase deficiency (ADA-SCID). The mutation is a G646-to-A transition at a CG dinucleotide and predicts a glycine-to-arginine substitution at codon 216. Computer analysis of secondary structure predicts a major alteration with loss of a beta-pleated sheet in a highly conserved region of the protein. The basepair substitution also generates a new site for the restriction enzyme BstXI in exon 7 of the genomic DNA. Digestion of genomic DNA from the patient and from his parents revealed that he was homozygous for the mutation and that his mother and father were carriers. This mutation in homozygous form appears to be associated with very severe disease, since the patient had perinatal onset of clinical manifestations of SCID, the highest concentration of the toxic metabolite deoxyATP in nine patients studied, and a relatively poor immunologic response during the initial 2 years of therapy with polyethylene glycol-adenosine deaminase. Analysis of DNA from 21 additional patients with ADA-SCID and from 19 unrelated normals revealed that, while none of the normal individuals showed the abnormal restriction fragment, two of the 21 patients studied were heterozygous for the G646-to-A mutation. 
Spontaneous abdominal arteriovenous fistulae: report of eight cases and review of the literature. The spontaneous rupture of an abdominal aneurysm into an adjacent major vein results in a profound and rapidly worsening haemodynamic disturbance. Survival depends on prompt diagnosis and closure of the fistula at operation. Eight cases are reported and modes of presentation, diagnostic criteria and management principles are reviewed in a detailed analysis of 148 cases in the English literature. 
Hypoxaemia after nebulised salbutamol in wheezy infants: the importance of aerosol acidity. The effect of nebulised iso-osmolar, preservative free, but acidic salbutamol solution was studied in 34 acutely wheezing infants aged 1-17 months. Transcutaneous oxygen pressure (TcPO2) and oxygen saturation (SO2) fell significantly during the first five minutes after nebulisation with further deterioration at 15-20 minutes. Ten of these infants were followed up for another two hours and showed slight improvement. Even after the second hour TcPO2 had not reached baseline values. Three months later the response to salbutamol and a placebo of equal acidity (pH 3.9) was studied in 11 infants from the same group, now free of symptoms. Lung function tests were included and showed no significant changes in specific conductance and volume corrected maximum expiratory flows (Vmax at functional residual capacity/thoracic gas volume). However, hypoxaemia occurred after the acidic placebo with a significant drop of TcPO2 (mean 0.9 kPa); SO2 decreased similarly but this did not reach significance. After salbutamol there was a further significant deterioration of mean TcPO2 (1.4 kPa) and of SO2. These results show that beside a possible pharmacological effect of salbutamol the acidity of the aerosol also induces hypoxaemia in infants. 
Noninvasive quantification of regional myocardial blood flow in coronary artery disease with oxygen-15-labeled carbon dioxide inhalation and positron emission tomography. BACKGROUND. Oxygen-15-labeled water is a diffusible, metabolically inert myocardial blood flow tracer with a short half-life (2 minutes) that can be used quantitatively with positron emission tomography (PET). The purpose of this study was to validate a new technique to quantify myocardial blood flow (MBF) in animals and to assess its application in patients. METHODS AND RESULTS. The technique involves the administration of 15O-labeled carbon dioxide (C15O2) and rapid dynamic scanning. Arterial and myocardial time activity curves were fitted to a single tissue compartment tracer kinetic model to estimate MBF in each myocardial region. Validation studies consisted of 52 simultaneous measurements of MBF with PET and gamma-labeled microspheres in nine closed-chest dogs over a flow range of 0.5-6.1 ml/g/min. A good correlation between the two methods was obtained (y = 0.36 + 1.0x, r = 0.91). Human studies consisted of 11 normal volunteers and eight patients with chronic stable angina and single-vessel disease, before and after intravenous dipyridamole infusion. In the normal group, MBF was homogeneous throughout the left ventricle both at rest and after administration of dipyridamole (0.88 +/- 0.08 ml/g/min and 3.52 +/- 1.12 ml/g/min, respectively; p less than or equal to 0.001). In patients, resting MBF was similar in the distribution of the normal and stenotic arteries (1.03 +/- 0.23 and 0.93 +/- 0.21 ml/g/min, respectively). After dipyridamole infusion, MBF in normally perfused areas increased to 2.86 +/- 0.83 ml/g/min, whereas in the regions supplied by stenotic arteries it increased to only 1.32 +/- 0.27 ml/g/min (p less than or equal to 0.001). CONCLUSIONS. PET with C15O2 inhalation provides an accurate noninvasive quantitative method for measuring regional myocardial blood flow in patients. 
Steps towards cost-benefit analysis of regional neurosurgical care OBJECTIVE--To determine the cost of averting death or severe disability by neurosurgical intervention. DESIGN--Retrospective analysis of one year's admissions for neurosurgery; comparison of outcome with expected outcome in the absence of neurosurgical intervention and with the cost of neurosurgery. SETTING--Wessex Neurological Centre. PATIENTS--1026 Patients were admitted to the neurosurgical service in 1984. Of 1185 admissions, 978 case records were available and outcome was known in 919. MAIN OUTCOME MEASURES--Outcome was assessed with the Glasgow outcome scale, modified as necessary, from the case notes, or by letter follow up to the general practitioner. Expected outcomes for each of the 54 diagnoses were derived from both published reports where available and an expert panel of 18 consultant neurosurgeons. The cost of the neurosurgical service for 1983-4 was known from a separate study and the cost per patient was calculated using the length of stay. RESULTS--The cost of neurosurgery in 1983-4 was 1.8 million pounds. In all, 243 deaths or severe disabilities were estimated to have been averted at an average cost of 7325 pounds (range 5000 pounds to 70,000 pounds). The overall cost per quality adjusted life year (QALY) was 350 pounds (range 34 pounds to greater than 400,000 pounds). The cost of long term care for severely disabled survivors is at least 18-fold greater than the cost of neurosurgical intervention to avert such disability. CONCLUSIONS--In Britain neurosurgery is not expensive in comparison with the costs and benefits of other areas of medicine, and the cost per QALY is unexpectedly low except for severe diffuse head injury, malignant brain tumors, and cerebral metastases. The neurosurgical budget should be assessed in the context of managing a patient in hospital and subsequently in the community. 
Uncompacted inner myelin lamellae in inherited tendency to pressure palsy. Nerves in patients with inherited tendency to pressure palsy (ITPP) are susceptible to degrees of traction or compression which in nonaffected persons do not induce neuropathic symptoms or deficits, conduction block of fibers, or electromyographic changes characteristic of the disorder. Two observations suggest a widespread asymptomatic abnormality of nerves: 1) low conduction velocity of clinically unaffected nerves, and 2) focal thickenings (tomacula) on teased myelinated fibers of clinically unaffected sural nerves. Sural nerves from five patients and five healthy subjects were assessed for morphologic abnormality in ITPP that might account for the susceptibility of nerves to compression. Teased nerve fibers showed a higher frequency of segmental demyelination or remyelination, or both (p less than 0.003). The mean frequency of fibers showing focal myelin thickenings was 57 +/- 10% in ITPP and 0% in controls. In electron micrographs, regions of uncompacted myelin lamellae, usually affecting the innermost lamellae and extending for a variable distance averaging 9 +/- 4 microns were seen in 11 +/- 4% of fibers in ITPP. None were found in the control nerves. The finding of uncompacted myelin lamellae may suggest an abnormality of myelin composition or of interaction of Schwann cells and axons accounting for the increased susceptibility to pressure palsy, tomaculous formation, or demyelination. From electron microscopic evaluation of serial skip sections we infer that myelin of tomaculae is in continuity with internodal myelin and is reduplicated (full-thickness or cleaved layers are longitudinally or circumferentially folded-back on themselves). 
Molecular characterization of the mouse mannose-binding proteins. The mannose-binding protein A but not C is an acute phase reactant. Mannose-binding proteins play a role in first line host defense against a variety of pathogens. We report the molecular cloning of two mouse mannose-binding proteins designated A and C based on their close identity with their rat homologues. The deduced amino acid sequence of the mouse mannose-binding proteins, as with rat and the human forms, have an NH2 terminus that is rich in cysteine that stabilizes a collagen alpha helix followed by a carboxyl- terminal carbohydrate binding domain. We further show that the mouse mannose-binding protein A mRNA, as with the human, is induced like the acute phase reactant serum amyloid P protein, yet the expression of mouse mannose-binding protein C mRNA is not regulated above its low baseline level. The expression of both mannose-binding proteins A and C mRNA is restricted to the liver under basal and stress conditions. 
Chagas' cardioneuropathy: effect of ganglioside treatment in chronic dysautonomic patients--a randomized, double-blind, parallel, placebo-controlled study. To date, there is no effective pharmacologic treatment for Chagas' cardioneuropathy, one of the most common causes of congestive heart failure and sudden death in the world. Fifty-eight adults with positive serology for Chagas' disease and abnormal autonomic nervous system tests participated in this placebo-controlled clinical trial with Cronassial (mixed gangliosides), 40 mg daily intramuscular injection for 4 or 8 weeks. We measured postural response (heart rate, systolic and diastolic arterial blood pressure changes in response to standing); heart rate changes induced by cough and hyperventilation reflex tests; dizziness on standing; number of stress-induced arrhythmias; and periodic acid-Schiff (PAS)-positive T-lymphocyte percentage in blood samples. Cronassial is safe and significantly improves systolic blood pressure (p = 0.050) and double product responses to postural stress (p = 0.028), hyperventilation heart rate response (p = 0.007), frequency of dizziness episodes (p less than 0.001), number of arrhythmias (p = 0.033), and percentage of PAS-positive T-lymphocyte counts (p less than 0.001) compared with placebo. 
Biliary patency imaging after endoscopic retrograde sphincterotomy with gallbladder in situ. Clinical impact of nonvisualization. We prospectively performed nuclear biliary patency imaging (HIDA scanning) in 62 patients who had undergone endoscopic retrograde sphincterotomy for management of pancreaticobiliary disease with their gallbladders in situ. Elective cholecystectomy was not recommended because of advanced age, comorbidity, or absence of gallstones. All patients had patent cystic ducts at endoscopic retrograde cholangiopancreatography balloon cholangiography. Eighteen (29.1%) of 62 patients had nonvisualizing HIDA scans, and in 44 (70.9%) of 62 visualization was normal or delayed. Six cholecystectomies were required for colic (n = 1), acute cholecystitis (n = 4), and acute cholecystocholedochal fistula with cholangitis (n = 1). Among the patients with cholelithiasis and nonvisualization (n = 13), five (38.5%) required surgery, whereas only one (4.8%) of 21 patients with cholelithiasis and visualization required surgery. Nonvisualizing HIDA scans are frequent (30%) after endoscopic retrograde sphincterotomy and have no clinical relevance in patients without cholelithiasis but predict the need for cholecystectomy within 16 months in 38.5% of patients with cholelithiasis. 
Anterograde amnesia with fornix damage following removal of IIIrd ventricle colloid cyst. Two patients developed anterograde amnesia following the apparently uncomplicated transcallosal-transventricular removal of a colloid cyst. Damage to the fornical columns was demonstrated on CT and MRI scans, whilst other memory related structures were entirely normal. Longitudinal neuropsychological evaluation, over 12-24 months, has revealed a very similar pattern of deficit in the two cases: verbal memory has remained persistently impaired whilst nonverbal anterograde memory has improved to some degree. Formal tests of remote public (famous faces and events) and personal autobiographical memory have supported the clinical impression that neither patient has a temporally extensive retrograde amnesia. These findings address the role of the fornix, and the dissociation of memory processes in humans. 
High-dose melphalan with 6-hydroxydopamine-purged autologous bone marrow transplantation for poor-risk neuroblastoma. Long-term results are presented of 28 patients who were diagnosed with neuroblastoma at more than 12 months of age and who received melphalan 180 mg/m2 (n = 6) or 240 mg/m2 (n = 22) to consolidate remissions of Stage IV disease or to control refractory disease. Twenty-four patients also received dianhydrogalactitol 180 to 240 mg/m2, and 11 received total body irradiation 450 to 600 cGy. Autologous bone marrow transplantation (ABMT) was performed with marrow that was unpurged (n = 2) or purged ex vivo (n = 26) with 6-hydroxydopamine (6-OHDA) 20 micrograms/ml plus ascorbate 200 micrograms/ml. The median time to an absolute neutrophil count of 500/microliters was 21 days and to self-sustaining platelet counts more than 20,000/microliters, 28 days. One patient required infusion of unpurged reserve marrow. Two groups of patients underwent ABMT: (1) 17 patients (Group I) who were in first remission a median of 7 months after diagnosis; and (2) 11 patients (Group II) who had refractory disease or were in second remission. For Group I, event-free survival was 29% at 12 months and 6% at 24 months post-ABMT. All Group II patients died of disease or ABMT-related toxicity. Overall, of the 28 patients, one is a long-term relapse-free survivor; five died of ABMT-related toxicity; ten patients with tumors present at ABMT had progressive disease within 6 months of ABMT; and 12 patients with no measurable disease at ABMT relapsed 4 to 32 months (median, 12) post-ABMT. Among the latter, six relapses involved the primary site, and six were restricted to distant sites. These results--in accord with the long-term outcome in other series--suggest that for neuroblastoma high-dose melphalan cannot be relied on to ablate residual disease or to salvage patients with refractory tumors. In addition, the pattern of relapse in several patients could be explained by infusion of incompletely purged autografts; this would support recent laboratory evidence that 6-OHDA/ascorbate is a suboptimal purging method. 
Malignant biliary obstruction complicated by ascites: transjugular insertion of an expandable metallic endoprosthesis. Although the transjugular approach has long been used to provide safe access to the liver, it has not been used for placement of stents in biliary obstruction. The recent development of an expandable metallic endoprosthesis now makes this method more feasible. The case of a patient with malignant biliary obstruction complicated by ascites is presented herein. Palliation was achieved with an expandable biliary endoprosthesis placed by the transjugular-hepatic vein approach. 
Time spent caregiving and help received by spouses and adult children of brain-impaired adults. Caregivers for brain-impaired adults differ in living arrangements, amount of time spent giving care, and assistance received from family and friends and from paid help depending on their kin relationship and employment status. Spousal caregivers devote large amounts of time to caregiving, and husbands spend no less time than wives. Most caregivers receive little assistance from other family members and friends, but husbands receive more than others. Employed spouses receive more paid help than those without jobs, but employment does not affect the amount of paid help received by adult daughters. 
Epilepsy and brain tumors: implications for treatment. Primary intraparenchymal tumors of the brain are important etiologic factors in partial or focal epilepsy. Indolent low-grade gliomas may be associated with a long-standing seizure disorder refractory to medical treatment. Surgical resection of the neoplasm and the epileptogenic area may render patients seizure-free. Removal of the tumor alone may also be associated with an excellent survival rate and surgical outcome. Conventional neurosurgical procedures are restricted in patients with tumors that are deep-seated lesions or involve functional cerebral cortex. Computer-assisted stereotactic surgical procedures have been developed for biopsy and resection of intra-axial brain-mass lesions. Stereotactic tumor resection may allow pathological determination of intracranial lesions and produce a worthwhile reduction in seizure activity in some patients with intractable partial epilepsy. 
Labyrinthitis ossificans: histopathologic consideration for cochlear implantation. Labyrinthitis ossificans may be a hindrance to cochlear implantation by making electrode insertion difficult. We performed a histopathologic study of 24 temporal bones with labyrinthitis ossificans from multiple causes. The organ of Corti was graphically reconstructed and the degree of obstruction was estimated for each millimeter of the cochlea. Correlations were calculated between the degree of new bone formation and the cause, patient's age and sex, and time from the original temporal bone insult. Our results demonstrate that complete cochlear ossification is rare. The scala tympani in the basal turn of the cochlea is the most frequent area of ossification, regardless of the cause of the labyrinthitis ossificans. Meningogenic labyrinthitis, usually a childhood disease, was associated with the greatest amount of ossification. When ossification resulted from tympanogenic labyrinthitis, the scala tympani was completely ossified near the round window niche in all temporal bones. Neo-ossification of the basal turn associated with otosclerosis was limited to the proximal 6 mm of the scala tympani in all cases. Three temporal bones had a patent round window niche and basal turn, but significant apical and middle-turn ossification. Peripheral sensorineural elements were severely degenerated in the region of the ossification in all specimens, and spiral ganglion cell counts were decreased. 
Fume fever and reactive airways dysfunction syndrome in a welder. I have reported a case of fume fever and concurrent reactive airways dysfunction syndrome (RADS) after welding. The RADS should be added to the list of potential hazards associated with welding. 
Carcinoma (malignant mixed mullerian [mesodermal] tumor) of the uterus and ovary. Correlation of clinical, pathologic, and immunohistochemical features in 29 cases. We examined the histologic, immunohistochemical, and clinical features of a series of 23 endometrial, five cervical, and one ovarian carcinosarcomas (malignant mixed mullerian [mesodermal] tumors) and nine associated distant peritoneal metastases. The primary tumors all showed epithelial differentiation (cytokeratin and/or epithelial membrane antigen expression) of the carcinomatous component, while sarcomatous areas showed epithelial differentiation in all but one case. The metastases showed uniform staining for cytokeratin (eight of eight cases) and epithelial membrane antigen (eight of eight cases), including the spindle cell component that was present in four of nine cases. Desmin significantly changed the interpretation of rhabdomyosarcoma differentiation by refuting putative rhabdomyoblasts in two cases and identifying rhabdomyoblasts in two other cases where they were unrecognized on hematoxylineosin staining. S100 protein was positive in all five cases with chondrosarcoma differentiation. Muscle-specific actin and vimentin were positive in the sarcomatous component of all cases and in the carcinomatous component of seven and 10 cases, respectively. After immunostaining, heterologous elements were present in 18 of 29 cases (11 cases of rhabdomyosarcoma, three cases of chondrosarcoma, three cases of mixed rhabdomyosarcoma and chondrosarcoma, and one case of liposarcoma). Only six of 27 patients with follow-up were disease free for 12 months or longer (associated with stage I or II disease, smaller size, no lymphatic invasion in the resection specimen, and no invasion of the outer two thirds of myometrium). Presence and type of heterologous elements, grade of sarcomatous or carcinomatous components, histologic type of carcinomatous component, gross appearance, presence of necrosis, or use of chemotherapy or radiotherapy did not affect outcome. Carcinosarcomas are clinically aggressive distinctive mixed epithelial-stromal neoplasms with histologic and immunohistochemical features that overlap with metaplastic carcinoma in many cases. 
Cytokines and the pathogenesis of neuroborreliosis: Borrelia burgdorferi induces glioma cells to secrete interleukin-6. Lyme disease is a multisystemic disease caused by a tickborne spirochete, Borrelia burgdorferi. Neuroborreliosis is characterized by intrathecal production of antibodies specific for the spirochete. This suggests that spirochetal infection of the central nervous system produces conditions that support the maturation of B lymphocytes to immunoglobulin-secreting cells. Interleukin 6 (IL-6) stimulates B cell differentiation into antibody-secreting cells. The present study was undertaken to determine whether B. burgdorferi can stimulate cells of central nervous system origin to secrete IL-6. C6 rat glioma cells cultured with spirochetes induced secretion of IL-6 activity. Peak stimulation was achieved at 24 h with 25 spirochetes per glioma cell. Glioma cells were also stimulated to produce IL-6 by interleukin 1 and tumor necrosis factor. That very few spirochetes are found in Lyme disease patients suggests that biologic amplification factors derived from the organism or the host, or both, are responsible for the pathogenesis of this disease. IL-6 can now be added to the growing list of such factors. 
Cataract extraction after brachytherapy for malignant melanoma of the choroid. Thirteen eyes of 55 consecutive patients treated with brachytherapy for malignant melanoma of the choroid developed postirradiation cataracts. Cataract development was more common in older patients and in patients with larger and more anterior tumors. Eleven eyes had extracapsular cataract extraction and intraocular lens implantation. Initial visual improvement occurred in 91% of eyes, with an average improvement of 5.5 lines. Visual acuity was maintained at 20/60 or better in 55% of the eyes over an average period of follow-up of 24 months (range, 6 to 40 months). These data suggest that, visually, cataract extraction can be helpful in selected patients who develop a cataract after brachytherapy for malignant melanoma of the choroid. 
Familial aneurysms of the interventricular septum. Congenital aneurysms of the interventricular septum were found in a 29 year old man and his four year old son. Both were symptom free. In both, M mode and cross sectional echocardiography showed an aneurysm in the mid-muscular trabecular portion of the ventricular septum with considerable paradoxical motion of the aneurysmal segment. Otherwise the chamber dimensions, intracardiac structures, and cardiac function were normal for age. Congenital aneurysm of the interventricular septum is rare and these familial cases may be unique. 
Clinical significance of aortic graft dilation. To determine if there is a relationship between aortic graft dilation and graft complications, 443 serial ultrasound studies performed on 106 patients were analyzed. Of 443 studies, 243 were done retrospectively on 59 patients from 3 to 144 months (mean, 38 months) after graft implantation. Forty-seven additional patients were studied prospectively, with direct measurement of external graft diameter after aortic clamp release. Subsequent ultrasound examinations at 3, 6, 9, and 12 months and then annually (n = 200) were routinely performed. Mean follow-up was 12 months (range, 3 to 48). Knitted double velour Dacron prostheses were used in all cases reported in this study. This cohort was culled from our ongoing graft surveillance program, which includes grafts of other materials and manufacturers. Comparison of the manufacturer's recorded box size with follow-up ultrasound measurements in all cases demonstrated a mean increase in graft diameter of 3.7 mm (23%). Little dilation occurred after 1 year. In 47 patients with direct graft diameter measurements taken after declamping, an immediate mean increase of 1.7 mm (11%) was noted. Dilation was not related to surgical indication (aneurysm vs occlusive disease) or hypertension. Analysis of the 10% segment of the series with the greatest dilation (mean, 39%) did not demonstrate a predilection for graft complications. No significant dilation was noted in the single cases encountered of femoral and iliac anastomotic aneurysms and perigraft seroma. Although dilation of knitted Dacron grafts is to be anticipated, no association between graft dilation and graft complications was found in this series. 
Electrophysiologic analysis of early Parkinson's disease. We have been interested in the application of quantitative measures of motor performance as a possible means of early detection of Parkinson's disease. To assess motor function, we have measured movement time (the physiologic correlate of bradykinesia) and reaction time (simple and directional choice) with an upper limb motor task, and tremor with accelerometry and electromyographic recordings. In this report we describe preliminary data from a Parkinson's disease patient group with symptoms of fewer than 2 years' average duration (compared with an age- and gender-matched normal control group) which indicate that precise, quantitative tests of motor function can detect the slight deviations from normal that are present in early Parkinson's disease. It appears that tests of bradykinesia are most sensitive, and detection of rest tremor is most specific. These tests may be applicable in screening individuals who are suspected of having or are "at risk for" Parkinson's disease and other related disorders. 
Natural history and prognostic variables in primary sclerosing cholangitis. The clinical features at the time of presentation and the outcome in 126 patients with primary sclerosing cholangitis were studied to clarify the natural history and prognosis in symptomatic and asymptomatic individuals. The median age of the patients at the time of presentation was 36 years, 62% were male, and 16% were asymptomatic. The median follow-up from time of presentation was 5.8 years. There were more patients who had liver transplants (21%) than patients who died of liver-related disease (16%); the estimated median survival to these end points was 12 years. Cholangiocarcinoma was found in 8 patients and in 23% of those undergoing liver transplantation. Asymptomatic patients had milder disease than symptomatic patients, but in a univariate analysis the presence of symptoms was not prognostically significant. On multivariate analysis, the following independent prognostic factors were found: hepatomegaly, splenomegaly, serum alkaline phosphatase, histological stage, and age. These features were combined to produce a prognostic model that should be valuable in the stratification of patients in clinical trials and in the timing of liver transplantation, particularly in those patients seen soon after presentation. 
Psychological aspects of orthognathic surgery: how people respond to facial change. This study was undertaken to explore the motivations and problems shared by adult orthognathic surgical patients over the age of 25. Objective findings included demographic information and reasons for seeking surgery. The majority of 65 respondents cited functional problems as their primary reason for seeking treatment. Eighty-nine percent were pleased with esthetic changes, and 83% responded that the functional problem had been corrected. For most, the greatest discomfort related to the surgery was the postoperative intensive care unit. Two of the most common side effects of the surgery were the loss of sensation in the lips and chin area and a short period of depression. Women had depression more often than men but were more enthusiastic about the final results of the procedure. Two major areas of interest to surgeons emerged from the research. First, although women have functional problems, the majority seem to have a desire for cosmetic improvement. Having a functional problem seemed to provide the psychological permission necessary to spend the time and money for a cosmetic change. The second point focused on the need for good communication between surgeon and patient. The patients who were more positive toward the procedure and more satisfied with the results were those who were better informed and who thought they had a good system of communication with the orthodontist, surgeon, and their respective staffs. 
Secondary ischaemia in rabbit skin flaps: the roles played by thromboxane and free radicals. 1. Biochemical mechanisms of ischaemia were investigated in rabbit skin flaps subjected to 2 h of primary ischaemia then, 24 h later, to 4 h of secondary ischaemia. During secondary ischaemia, flaps underwent either total ischaemia (arterial and venous blood supply occluded) or partial ischaemia (vein only occluded). Some of these flaps were treated at the time of reperfusion with the free-radical scavenger superoxide dismutase (EC 1.15.1.1) and/or the thromboxane synthetase inhibitor UK-38,485. 2. After 30 min of reperfusion, superoxide dismutase treatment significantly reduced blood thromboxane levels, elevated during ischaemia. Superoxide dismutase also reduced tissue levels of malonyldialdehyde and xanthine oxidase, indicators of free-radical damage, and restored the depleted tissue levels of superoxide dismutase. 3. UK-38,485 treatment failed to significantly alter any of these tissue free-radical parameters, although this agent significantly reduced blood thromboxane levels. 4. Combined superoxide dismutase plus UK-38,485 treatment was not significantly better than either treatment alone with respect to any parameter. 5. Partial ischaemia led to consistently higher levels of tissue free radicals and blood thromboxane than did total ischaemia. Thus partial ischaemia appears to result in greater free-radical damage than total ischaemia. 6. These results are consistent with the hypothesis that thromboxane acts as a mediator for free-radical damage in the ischaemic changes within the flap. 
Experimental arterial thrombosis in nonhuman primates. The baboon offers many advantages as an experimental animal to study vascular disease, thrombus formation and dissolution, effects of mediating variables, and the relative efficacy of therapeutic interventions. Each specific application for testing therapeutic agents may require testing in somewhat different model systems. For example, although the arteriovenous vascular graft model is efficient, cost effective, and well adapted to study of interventions for acute arterial thrombosis, surgical endarterectomy extends the evaluation to include interactions with the injured vascular wall. As the antithrombotic products of genetic engineering and molecular biology emerge, it will be increasingly important to have relevant, reproducible, and quantitative approaches to evaluate their effects in vivo. 
Low-grade, latent prostate cancer volume: predictor of clinical cancer incidence? We hypothesize that each cell in low-grade (Gleason grade 1-3) prostate cancer tissue is at risk of transformation into a cell which produces a high-grade (Gleason grade 4-5) clinical cancer after a short period of growth. As a consequence, the volume of low-grade, latent cancer tissue in the prostate glands of men at any age determines their incidence rate for high-grade, clinical cancer a few years later. Autopsy and incidence data for both white men and black men support this conclusion, with a tumor growth period of about 7 years. The transformation rate is similar for black men and for white men, about 0.024 high-grade cancers per year per cm3 of low-grade, latent cancer volume. Our hypothesis explains the infrequent occurrence of clinical cancer despite the high prevalence of latent cancer, the steep rise of clinical cancer incidence with age despite the slow rise of latent cancer prevalence with age, and the disparities in clinical cancer incidence among some populations despite their similar latent cancer prevalence. This hypothesis suggests that low-grade cancer volume is a critical determinant of clinical cancer risk. 
The antifibrillatory actions of UK-68,798, a class III antiarrhythmic agent. The electrophysiologic and antifibrillatory properties of UK-68,798 were studied in vivo in a conscious canine model of sudden coronary death. Electrophysiologic testing was performed on conscious male mongrel dogs (14.5-21.5 kg) 3 to 5 days after surgical induction of an anterior myocardial infarction by occlusion (2 h)-reperfusion of the left anterior descending coronary artery. Compared to saline-treated control animals, UK-68,798 at a dose of 0.9 mg/kg i.v. did not (P = .083) suppress the induction of ventricular tachycardia by programmed electrical stimulation. Six of 12 UK-68,798-treated dogs remained inducible, whereas 10 of 12 vehicle-treated dogs responded to electrical induction of arrhythmia. When compared to predrug inducibility, UK-68,798 significantly (P = .007) reduced the incidence of programmed electrical stimulation-induced ventricular tachycardia. In five of the six dogs inducible after UK-68,798 administration, the cycle length of the induced ventricular tachycardia was prolonged (P = .007) compared to the predrug cycle length. Heart rate, PR interval and QRS duration were not affected by UK-68,798 administration. The rate-corrected QT interval was prolonged (P less than .05) by UK-68,798. The ventricular effective refractory period was increased by UK-68,798 (158 +/- 7 msec, predrug vs. 185 +/- 7 msec, postdrug). Subsequent to programmed electrical stimulation, a 150 microA anodal current was applied to the luminal surface of the left circumflex coronary artery to induce transient episodes of posterolateral ischemia in response to electrolytic injury of the vessel wall. 
Use of leucocyte alkaline phosphatase (LAP) score in differentiating malignant from benign paraproteinaemias. The leucocyte alkaline phosphatase (LAP) score of peripheral blood neutrophils was examined in 20 patients with multiple myeloma and compared with the score in 18 patients with monoclonal gammopathy of undetermined significance (MGUS). The mean (95% confidence limit) LAP score in those with multiple myeloma was 186 (169-218) compared with 92 (64-120) in the MGUS group. In the multiple myeloma group all but one patient had a high LAP score, irrespective of disease. No cause for raised LAP, such as infection, was present in any of the patients with multiple myeloma. In the MGUS group six patients had a raised LAP score; in two of them another cause for such a rise was present (autoimmune haemolytic anaemia and primary thrombocythaemia). In neither group did the LAP score correlate with duration of the disease, bone marrow plasma cell count, paraprotein concentration, haemoglobin, total white cell or neutrophil count. It is concluded that a normal LAP count in patients with paraproteinaemia suggests a benign condition, but a raised count does not indicate a malignant condition. 
ATP-dependent K+ channels modulate vasoconstrictor responses to severe hypoxia in isolated ferret lungs. In normo- and hypoglycemic ferret lungs, the pulmonary vascular response to severe hypoxia (PiO2 less than or equal to 10 mmHg) is characterized by an initial intense vasoconstriction followed by marked vasodilation, whereas in hyperglycemic lungs, vasodilation is minimal, causing vasoconstriction to be sustained. In contrast, the response to moderate hypoxia is characterized by a slowly developing sustained vasoconstriction which is unaffected by glucose concentration. To determine the role of ATP-dependent K+ (KATP) channels in these responses, we examined the effects of cromakalim, which opens KATP channels, and glibenclamide, which closes them. During steady-state vasoconstriction induced in isolated ferret lungs by moderate hypoxia, cromakalim caused dose-dependent vasodilation (EC50 = 7 x 10(-7) M) which was reversed by glibenclamide (IC50 = 8 x 10(-7) M), indicating that KATP channels were present and capable of modulating vascular tone. During severe hypoxia in hypoglycemic lungs [( glucose] less than 1 mM), glibenclamide markedly inhibited the secondary vasodilation. Raising perfusate glucose concentration to 14 +/- 0.4 mM had the same effect. As a result, initial vasoconstrictor responses were well sustained. However, neither glibenclamide nor hyperglycemia affected vasoconstrictor responses to moderate hypoxia or KCl, indicating that effects during severe hypoxia were not due to nonspecific potentiation of vasoconstriction. These findings suggest that in the ferret lung (a) severe hypoxia decreased ATP concentration and thereby opened KATP channels, resulting in increased K+ efflux, hyperpolarization, vasodilation, and reversal of the initial vasoconstrictor response; and (b) hyperglycemia prevented this sequence of events. 
Colonoscopic surveillance after polypectomy: considerations of cost effectiveness. OBJECTIVE: To assess the cost effectiveness of the current recommendation that persons who have had an adenomatous colon polyp removed have periodic colonoscopic surveillance at fixed and regular intervals. DESIGN: Cost-effectiveness analysis using data from the medical literature in a simulation model to estimate the costs of and the risk for perforation associated with periodic colonoscopic surveillance for a 50-year-old man followed for 30 years. MAIN RESULTS: A program of colonoscopy every 3 years would incur cumulatively a 1.4% risk for colon perforation, a 0.11% risk for perforation-related death, and direct physician costs of $2071 for colonoscopy (discounted at 5%). If a 50-year-old man's cumulative remaining risk for death from cancer is 2.5% after the removal of a single small adenoma and if effectiveness of colonoscopic surveillance every 3 years is 100%, then one death from cancer could be prevented by doing 283 colonoscopies, incurring 0.6 perforations, 0.04 perforation-related deaths, and direct physician costs of $82,000. If surveillance were 50% effective and the cumulative remaining risk for death from cancer were 1.25%--a plausible scenario--1131 colonoscopies would be required to prevent one death from cancer, incurring 2.3 perforations, 0.17 perforation-related deaths, and physician costs of $331,000. CONCLUSIONS: The cost effectiveness of colonoscopic surveillance is very sensitive to estimates of the cumulative remaining risk for death from cancer after polypectomy as well as to surveillance efficacy. For persons whose remaining risk for death from cancer may be low, such as persons with a single small adenoma, recommendations for colonoscopic surveillance at fixed and regular intervals may be excessively costly. 
Screening blood donors for gastrointestinal illness: a strategy to eliminate carriers of Yersinia enterocolitica. Recent reports of fatal transfusion-associated Yersinia enterocolitica sepsis prompted a study of the feasibility of adding a question to the routine donor health history as a method of reducing this risk. In three American Red Cross blood centers, 11,323 donors were asked one of two questions about gastrointestinal symptoms during their health history screenings. Affirmative responses were obtained from 0.6 or 4.0 percent of the donors, depending on how the question was asked. In one center, more than 6 percent of donors gave affirmative answers. The efficacy of asking a relatively simple question about gastrointestinal symptoms as a way of preventing Y. enterocolitica should be evaluated further, because relatively large numbers of donors may respond affirmatively. Other methods of reducing the risk of transfusion-associated Y. enterocolitica infection should be pursued. 
Single-center comparison of results of 1000 prenatal diagnoses with chorionic villus sampling and 1000 diagnoses with amniocentesis. Large multicenter studies have confirmed the safety and accuracy of chorionic villus sampling as a prenatal genetic diagnostic procedure, but there have been few single-center evaluations. We report our experience with 1000 consecutive chorionic villus sampling procedures compared with 1000 consecutive amniocentesis procedures during the same period. The procedures were performed by the same genetic counselors, sonographers, obstetricians, and laboratory personnel. Indications for referral, demographic characteristics of patients, numbers of attempts per patient, fetal loss rates, laboratory results, and evaluation of accuracy are included. Analysis of all data suggests that chorionic villus sampling is a safe and accurate alternative to amniocentesis in our community-based teaching hospital. 
Immunocytochemical panel for the identification of malignant cells in serous effusions. The cytologic diagnosis of malignancy in serous effusions can be challenging. An immunocytochemical (ICC) panel using commercially available antibodies (to carcinoembryonic antigen [CEA], epithelial membrane antigen [EMA], B72.3, Leu-M1, cytokeratin [CK], leukocyte common antigen [LCA], S-100 protein, and vimentin) was applied to cell blocks fixed in methyl Carnoy's solution that were from 55 consecutive pleural, peritoneal, and pericardial fluid specimens. The results were correlated with data from clinical records and routine cytologic studies. Final cytologic diagnoses included 26 of adenocarcinoma and 1 of mesothelioma. The remaining 28 cases were considered to be benign (reactive) proliferations. EMA, CEA, B72.3, and Leu-M1 were present in 96%, 77%, 58%, and 42% of adenocarcinomas, respectively. These determinants were absent in the mesothelioma and the reactive effusions, although anti-CEA yielded strong background staining of inflammatory cells. The CK markers identified malignant cells in 93% of cases, but consistently stained mesothelial cells as well. Antivimentin strongly labeled mesothelial cells in all cases, with weak to absent staining of malignant cells. In 3 of 26 carcinoma cases (12%), the ICC panel identified malignant cells that were not recognized initially on routine cytologic examination. In 1 of 26 cases (4%), the panel was falsely negative. Use of this approach can improve the diagnostic accuracy of cytologic examination of serous fluids. The ICC panel is especially helpful when atypical mesothelial proliferation is present, or in cases that are clinically suspect for malignancy, but cytologically negative because there are only a few malignant cells, or those that are cytologically bland. 
Failure to awaken after general anaesthesia secondary to paradoxical venous embolus. A patient is presented who failed to regain consciousness after an apparently uneventful nine-hour revision of a total hip replacement. There were no clinically important haemodynamic changes during the operation, and oxygen saturation, capnography and acid base balance were normal throughout. Postop CT of the head showed a large left MCA infarct with midline shift. At autopsy, the patient was found to have a previously unsuspected patent foramen ovale, and a venous embolus in the left internal carotid artery, which probably had originated from the periprostatic venous plexus with a large infarct in the distribution of the left anterior and middle cerebral arteries. The authors conclude that massive paradoxical venous emboli can occur during surgery with minimal haemodynamic changes. 
Gastric ulcer healing: a comparison of enprostil versus ranitidine. Enprostil is a synthetic prostaglandin E2 analogue with gastric antisecretory and mucosal protective properties. We compared the effects of enprostil and ranitidine on the healing of gastric ulcers and the subsequent relapse rates over 6 months. Patients (N = 156) were recruited for a double-blind study from 12 centers in Europe; 71 were randomly assigned to oral treatment with 35 micrograms enprostil twice daily and 85 to 150 mg ranitidine twice daily for up to 8 weeks. Both groups were of similar demography; their healing rates were also similar. Cumulative intent-to-treat healing rates were at 4 weeks enprostil 48%, ranitidine 41%: at 6 weeks enprostil 65%, ranitidine 68%; and at 8 weeks enprostil 72%, ranitidine 80%. Of those patients who met all protocol criteria and completed treatment, and were endoscoped at the prescribed times, healing rates were at 4 weeks enprostil 55%, ranitidine 54%, at 6 weeks enprostil 75%, ranitidine 84%; and at 8 weeks enprostil 80%, ranitidine 90%. Relief of pain was rapid and similar in both groups. The incidence of adverse events was low and similar in the two groups. The treatment-free relapse rate at 6 months was enprostil 64%, ranitidine 49%; the median times to relapse were 169 and 203 days, respectively. Enprostil and ranitidine appear to be equally effective in healing gastric ulcers. 
Coordinate occupancy of AP-1 sites in the vitamin D-responsive and CCAAT box elements by Fos-Jun in the osteocalcin gene: model for phenotype suppression of transcription. Osteocalcin, a bone-specific protein and marker of the mature osteoblast, is expressed only in nonproliferating osteoblasts in a mineralizing extracellular matrix, while type I collagen is expressed in proliferating cells. The nuclear proteins encoded by the c-fos and c-jun protooncogenes are expressed during the proliferation period of osteoblast phenotype development. We present evidence that AP-1 (HeLa cell-activating protein 1) sites residing within two promoter elements of the osteocalcin gene bind the Fos-Jun protein complex: the osteocalcin box (OC box; nucleotides -99 to -76), which contains a CCAAT motif as a central element and influences tissue-specific basal levels of osteocalcin gene transcription, and the vitamin D-responsive element (VDRE; nucleotides -462 to -440), which mediates enhancement of osteocalcin gene transcription. Gel electrophoretic mobility-shift analysis demonstrated high AP-1 binding activity in proliferating osteoblasts and dramatic changes in this activity after the down-regulation of proliferation and the initiation of extracellular-matrix mineralization in primary cultures of normal diploid osteoblasts. Methylation interference analysis established at single nucleotide resolution that purified recombinant Fos and Jun proteins bind in a sequence-specific manner to the AP-1 sites within the VDRE and OC box. Similarly, an AP-1 motif within a putative VDRE of the alkaline phosphatase gene, which is also expressed after the completion of proliferation, binds the Fos-Jun complex. These results support a model in which coordinate occupancy of the AP-1 sites in the VDRE and OC box in proliferating osteoblasts may suppress both basal level and vitamin D-enhanced osteocalcin gene transcription as well as transcription of other genes associated with osteoblast differentiation--a phenomenon we describe as phenotype suppression. This model is further supported by binding of the Fos-Jun complex at an AP-1 site in the type alpha I collagen promoter that is contiguous with, but not overlapping, the VDRE. Such a sequence organization in the collagen VDRE motif is compatible with vitamin D modulation of collagen but not with osteocalcin and alkaline phosphatase expression in proliferating osteoblasts. 
Pentoxifylline in the treatment of vascular impotence--case reports. Vascular impotence is a common medical problem for which available therapies are limited. Three impotent patients observed in the authors' practice who were receiving pentoxifylline for treatment of claudication of the lower extremities spontaneously reported improved sexual function. A controlled trial of pentoxifylline for vascular impotence may be warranted. 
Polycystic ovary syndrome: abnormalities and management with pulsatile gonadotropin-releasing hormone and gonadotropin-releasing hormone analogs. Ovulation induction with pulsatile gonadotropin-releasing hormone achieves high ovulatory and pregnancy rates in hypogonadotropic hypogonadism while limiting the occurrence of ovarian hyperstimulation and multiple pregnancy. However, this form of therapy is apparently less effective in polycystic ovary syndrome. The administration of a gonadotropin-releasing hormone analog for 4 to 8 weeks before the initiation of pulsatile gonadotropin-releasing hormone ovulation induction can temporarily correct endocrine abnormalities of polycystic ovary syndrome, such as excessive luteinizing hormone and androgen secretion, and improve ovulatory and pregnancy rates in these patients. For optimal results, this pretreatment should probably be repeated before each pulsatile gonadotropin-releasing hormone ovulation induction cycle. Obesity is associated with a lower success rate, and spontaneous abortion remains a prominent complication in polycystic ovary syndrome even after gonadotropin-releasing hormone analog suppression. With this regimen the risks of ovarian hyperstimulation and multiple pregnancy are virtually abolished. Thus, pulsatile gonadotropin-releasing hormone appears to be highly effective and safe for ovulation induction in patients with polycystic ovary syndrome also, provided that this treatment is preceded by pituitary-ovarian suppression with a gonadotropin-releasing hormone analog. 
Antineutrophil cytoplasmic autoantibody-associated diseases: a pathologist's perspective. Antineutrophil cytoplasmic autoantibodies (ANCA) are a useful diagnostic serologic marker for the most common forms of necrotizing vasculitis, provide a means of categorizing vasculitides so that diagnostically useful shared pathologic and clinical characteristics can be recognized, and offer insight into the pathogenesis of previously idiopathic diseases. ANCA-associated vasculitides can be categorized into a number of distinctive clinicopathologic categories, eg, Wegener's granulomatosis, Churg-Strauss syndrome, pulmonary renal syndrome, microscopic polyarteritis nodosa, leukocytoclastic angiitis, and necrotizing and crescentic glomerulonephritis. At least the latter four syndromes can also be caused by other ANCA-negative immunopathogenic mechanisms, eg, immune complex deposition. Therefore, thorough diagnostic classification requires both an assessment of clinicopathologic category, as well as an assessment of immunopathologic category. Although different ANCA-associated vasculitic syndromes have distinctive clinical and pathologic features, all ANCA-associated vasculitides share a number of common pathologic features, ie, focal distribution, necrosis, and neutrophil infiltration. ANCA assays have very good sensitivity and specificity for ANCA-associated diseases, but the prevalence of these diseases in the patient population being analyzed must be taken into consideration when determining the predictive value of a test result. As with all serologic tests, ANCA results must be integrated with other clinical and pathologic data in order to reach the most accurate diagnostic conclusion. 
Chronic xerostomia increases esophageal acid exposure and is associated with esophageal injury. OBJECTIVE: To assess the effects of chronic xerostomia on parameters of gastroesophageal reflux and esophagitis. DESIGN: Observational study of a cohort of male patients with xerostomia and age-matched control subjects. SETTING: Tertiary-care Veterans Affairs Medical Center. SUBJECTS: Sixteen male patients with chronic xerostomia secondary to radiation for head and neck cancers or medications. Nineteen age-matched male control subjects with comparable alcohol and smoking histories. MEASUREMENTS AND MAIN RESULTS: Esophageal motility was similar in patients with xerostomia and controls. Clearance of acid from the esophagus and 24-hour intraesophageal pH were markedly abnormal in patients with xerostomia. Symptoms and signs of esophagitis were significantly more frequent in subjects with xerostomia. CONCLUSIONS: Chronic xerostomia may predispose to esophageal injury, at least in part, by decreasing the clearance of acid from the esophagus and altering 24-hour intraesophageal pH. Esophageal injury is a previously unreported complication of long-term salivary deficiency. 
An immunohistochemical study of sarcomatoid liver carcinomas. Six cases of primary hepatic carcinomas with a significant amount of sarcomatoid elements were examined by using immunohistochemical stainings. Four of the six cases were associated with ordinary hepatocellular carcinoma (HCC), one with cholangiocellular carcinoma (CCC), and one with mixed HCC and CCC. Alpha-fetoprotein and alpha-1-antitrypsin were negative in sarcomatoid cells of all cases; vimentin stained positively in sarcomatoid tumor cells in two of the six cases; and cytokeratin (CK8) was detected in five cases. The CK8 was not detected in tumor cells of two cases of hepatic angiosarcoma, two of metastatic leiomyosarcomas, and one of metastatic fibrosarcoma, although vimentin stained positively in all these true sarcomas. It was concluded that sarcomatoid dedifferentiation of liver carcinomas might derive from both HCC and CCC. In addition CK8 might be an excellent marker to make a differential diagnosis of sarcomatoid cancers from true metastatic or primary sarcomas of the liver. 
Outcome after emergency surgery for cancer of the large intestine. The data for 77 patients with colorectal cancer who underwent emergency surgery for acute intestinal obstruction (57 patients) or perforation (20 patients) within 24 h of admission were evaluated. The patients were older and had more advanced disease than patients undergoing elective surgery for colorectal cancer. Emergency surgery for carcinoma of the right colon consisted of primary resection in 95 per cent of cases and was followed by a 28 per cent mortality rate. Perforated tumours of the left colon and rectum were managed by primary resection in 82 per cent of cases with a 22 per cent mortality rate. In contrast, obstructing tumours of the left colon and rectum were treated by primary resection in 38 per cent of cases with a 6 per cent mortality rate, and by primary decompression in 62 per cent of cases with a 25 per cent mortality rate. The overall postoperative mortality rate was 23 per cent and increased with advanced tumour disease, perforation and peritonitis. Cardiac decompensation and intraabdominal sepsis were the major causes of death. Although the long-term survival rate following emergency surgery was worse than after elective surgery, improvements in outcome should be achieved by better management of the initial emergency situation. 
Pain threshold levels and coping strategies among patients who have chest pain and normal coronary arteries. Patients with noncardiac chest pain (NCCP) tend to show lower pain threshold levels for esophageal balloon distention than do patients with other painful gastrointestinal disorders and healthy controls. The NCCP patients also report greater usage of negative pain-coping strategies, less ability to perform specific behaviors to decrease pain, and higher levels of clinical pain than do other patient and healthy control groups. Behavioral treatments produce significant decreases in pain and disruption of daily activities. Further effort is needed, however, to develop treatments for NCCP that are based on knowledge of the behavioral manifestations of this disorder and the afferent mechanisms involved in perception of visceral pain. 
Acute venous thrombosis. Therapeutic choices for superficial and deep veins. Superficial thrombophlebitis is common in varicose veins or veins that have undergone trauma from catheters or intravenous medications. Pain and tenderness, warmth, and erythema are diagnostic features. A compression bandage and nonsteroidal antiinflammatory agent are often all that is required for treatment. Deep vein thrombosis occurs in veins beneath the deep fascia of the leg or in the pelvis or abdomen. It is often asymptomatic but must be treated to prevent pulmonary embolization and postthrombotic syndrome. Standard therapy is administration of heparin sodium for 5 days, followed by tapering and discontinuation. Warfarin sodium (Coumadin, Panwarfin, Sofarin) is sometimes given simultaneously. Longer courses of anti-coagulation therapy are necessary in patients with an ongoing risk of recurrence. 
Cost effectiveness of prophylactic intravenous immune globulin in chronic lymphocytic leukemia [see comment] BACKGROUND. A recent randomized controlled trial of intravenous immune globulin in patients with chronic lymphocytic leukemia and hypogammaglobulinemia demonstrated a statistically significant reduction in the rate of bacterial infections among patients who received intravenous immune globulin. We used decision-analysis techniques to determine whether prophylactic intravenous immune globulin is likely to result in an overall clinical benefit to patients who receive this treatment and to examine its cost effectiveness. METHODS. We constructed a model to compare two strategies: treatment with intravenous immune globulin at a dose of 400 mg per kilogram of body weight every three weeks and no immune globulin therapy. Baseline estimates of the efficacy of intravenous immune globulin were derived from the published results of the randomized trial. The costs of treatment, complications, and infections were estimated on the basis of component costs. Health outcomes were measured in terms of gains in quality-adjusted life expectancy. RESULTS. Intravenous immune globulin therapy can result in a loss of quality-adjusted life expectancy when the inconvenience of treatment is taken into account. If the inconvenience of treatment is not considered, therapy results in a gain of 0.8 quality-adjusted days per patient per year of therapy at a cost of $6 million per quality-adjusted life-year gained. CONCLUSIONS. Decision-analysis modeling may be applied to the results of randomized controlled trials to assess the potential clinical and financial effects of adopting the intervention in medical practice. In the case of intravenous immune globulin therapy in patients with chronic lymphocytic leukemia and hypogammaglobulinemia, this type of analysis suggests that treatment might not result in improved quality or length of life and that it is extraordinarily expensive in comparison with other treatments generally accepted as cost effective. 
Abnormal perception of visceral pain in response to gastric distension in chronic idiopathic dyspepsia. The irritable stomach syndrome. Sensory and pressure responses to gastric distension were evaluated in 24 consecutive patients suffering from chronic idiopathic dyspepsia and 20 healthy subjects. A latex balloon was placed in the proximal stomach and inflated by increments of 100 ml of air up to a maximal volume of 800 ml. Symptom response and intragastric pressure-volume curve were recorded during the gradual balloon distension. Thirteen of the 24 patients experienced pain at a distension volume less than or equal to 400 ml of air, but only one of the 20 controls (P less than 0.001). Intragastric pressure-volume curves were similar in patients and controls, and in patients with and without abnormal pain threshold, suggesting that a compliance defect was not the cause of the sensory anomaly. Gastric emptying of solids and liquids was measured in 20 of the 24 patients using a dual isotopic technique; psychological status was also evaluated in 18 patients using the Mini-Mult test. The frequency of the sensory anomaly was not different in patients with (7/14) or without (4/6) gastric stasis, but was lower in patients with (5/13) than in those without psychological disturbances (5/5, P less than 0.01). Thus, a primary visceral sensory anomaly, either alone or in conjunction with motility disturbances, can play an important role in chronic idiopathic dyspepsia and must be taken in account for further therapeutic research. 
A study of nonbacterial agents of acute lower respiratory tract infection in Thai children. From January 1986 to December 1987, 596 children less than 5 years of age with lower respiratory tract infection (LRI)--manifested as laryngitis, croup, bronchitis, bronchiolitis, and pneumonia--were studied for evidence of infection with respiratory tract viruses Mycoplasma pneumoniae, and Chlamydia trachomatis. Of the 596 children in the study, 315 were ambulatory and 281 were hospitalized. Virologic studies included isolation and rapid diagnosis of virus from specimens of nasopharyngeal aspirate (NPA) and serologic studies of blood samples. Cultures of NPA for C. trachomatis were performed for children less than 6 months of age who had pneumonia. Of the LRI cases, 45% were associated with viral infections of the respiratory tract and 12.1% were associated with C. trachomatis. Respiratory syncytial virus (RSV) accounted for 45.2% of infections with viral agents and was associated with acute bronchitis, acute bronchiolitis, and pneumonia. Parainfluenza type 3 virus was the most common virus found in conjunction with laryngitis and croup. The incidence of infections due to RSV peaked in July and August, while that of infections due to parainfluenza viruses peaked in February and March; influenza viruses and adenoviruses were isolated throughout the year. 
Febrile seizure. Caring for patients--and their parents. Management of febrile seizure involves diagnosis and treatment of the underlying cause and assessment of risk factors for recurrence. What should physicians tell anxious parents about this frightening occurrence? Is prophylaxis with anticonvulsant agents appropriate? The authors address these questions and discuss the changing approach to management of febrile seizure. 
Prospective blinded trial of the colonoscopic miss-rate of large colorectal polyps. We prospectively studied the colonoscopic miss-rate of large colorectal polyps in a blinded trial featuring tandem colonoscopy. Sixty-three lesions greater than or equal to 1 cm in size were discovered and none were missed. Confidence intervals of 95% are a miss-rate of 0 to 4.6%. We conclude that less than 5% of large colorectal polyps are missed during the index colonoscopic examination in a well-prepared colon. 
Symptomatic cerebral swelling complicating diabetic ketoacidosis documented by intraventricular pressure monitoring: survival without neurologic sequela. A six-year-old boy developed symptomatic cerebral swelling four hours after the initiation of treatment for newly diagnosed diabetes mellitus complicated by ketoacidosis. Ventriculostomy documented intracranial pressure over a two-day period. Increased intracranial pressure unresponsive to controlled hyperventilation and sedation was treated by administering a diuretic and by drainage via a ventriculostomy. Intracranial pressure monitoring was a useful adjunct in management of this rare, but often lethal, complication of diabetes mellitus. One year later, both school performance and the results of a neurologic examination were normal. 
Predicting left heart failure after a myocardial infarction: a preliminary study of the value of echocardiographic measures of left ventricular filling and wall motion. Heart failure occurs from both systolic and diastolic dysfunction. To determine whether simple Doppler echocardiographic measures of left ventricular filling could improve upon the ability of systolic function to predict heart failure after infarction, patients with acute myocardial infarction were studied within the first 36 hours by Doppler and two-dimensional echocardiography. Forty-eight patients who did not have heart failure before the Doppler echocardiographic study and who did not have myocardial revascularization, moderate or severe mitral regurgitation, or other complications during recovery were monitored for 6 months or to the onset of heart failure (n = 10). The univariate predictors of heart failure were age (p less than 0.05), anterior infarction (p less than 0.05), early diastolic peak filling velocity (p = 0.05), filling velocity with atrial systole (p less than 0.05), the ratio of these velocities (p less than 0.001), the percentage of filling with atrial systole (p less than 0.001), and the wall motion score index (p less than 0.001). However, the only independent predictors of heart failure by use of multivariant stepwise logistic regression analysis were the wall motion score index (p less than 0.05) and either the ratio of early and late peak filling velocities (p less than 0.001) or the percentage of filling with atrial systole (p less than 0.001). The combined use of a measure of systolic function and measures of the relative contribution of atrial systole to ventricular filling were useful predictors in identifying patients likely to develop subsequent heart failure after myocardial infarction. 
Clinical patterns of paediatric urolithiasis. A series of 270 paediatric stone patients was studied retrospectively according to the clinical pattern of urolithiasis (age and sex, stone location, stone analysis, recurrence rate) and aetiology of stone disease (infection, anatomical, metabolic or idiopathic). Infection stones occurred earliest and more commonly in males and were usually upper tract struvite calculi related to Proteus infection. Anatomical stones were most commonly associated with pelviureteric junction (PUJ) obstruction and had a high recurrence rate, despite surgical correction of obstruction. Idiopathic stones most resembled those found in adult urolithiasis by virtue of occurring latest, being sited in the ureter more often and being more frequently composed of calcium oxalate. Metabolic stones were most frequently calcium phosphate or cystine and virtually all were renal. They comprised the smallest group but had the highest recurrence rate. 
Desflurane is a trigger of malignant hyperthermia in susceptible swine. Desflurane (difluoromethyl 1-fluoro 2,2,2-trifluoroethyl ether: CF2-H-O-CFH-CF3) is a potent inhalation anesthetic agent being investigated for possible clinical use. The authors examined the effects of this agent on normal swine and those from a special breeding program that were considered purebred for susceptibility to malignant hyperthermia (MH). Animals were exposed to 1 or 2 MAC or both doses of desflurane and observed for changes in end-tidal CO2, arterial blood gases, lactate, catecholamines, core temperature, blood pressure, and heart rate. All normal swine tolerated exposure to desflurane without clinical signs of MH, but significant changes in heart rate and blood pressure were noted. In contrast, of six MH susceptible swine tested, two had unequivocal MH reactions to deflurane, defined by significant increases of end-tidal CO2 (greater than 50 mmHg), an increase in PaCO2 (greater than 70 mmHg), a decrease in blood pH (less than 7.30), an increase in blood lactate concentration, and an increase in core temperature. Two other susceptible swine showed equivocal signs of MH but not until desflurane had been administered for 40-60 min. Finally, two other susceptible swine showed no signs of MH after 60 min of exposure to 2 MAC desflurane. These latter four animals all developed episodes of MH immediately after intravenous succinylcholine (2 mg/kg). The increased PaCO2, blood lactate concentrations, and temperature, and the decrease in pH induced by desflurane, were successfully treated with dantrolene and supportive measures. All surviving animals were biopsied 1 to 2 weeks after the exposure to desflurane for in vitro contracture testing to confirm MH susceptibility. 
Improved specificity of myocardial thallium-201 single-photon emission computed tomography in patients with left bundle branch block by dipyridamole. Reduced septal uptake of thallium-201 during exercise is frequently observed in patients with left bundle branch block (LBBB) and normal coronary arteries. This may reflect normal coronary autoregulation in response to lower septal oxygen demand; thus, dipyridamole, which uniformly exploits flow reserve, would be more accurate for diagnosis of coronary artery disease (CAD). Sixteen patients with LBBB underwent exercise and dipyridamole thallium-201 single-photon emission computed tomography and coronary angiography within 3 months. Sensitivity for detection of left anterior descending CAD (greater than 50% stenosis) was 0.83 for exercise and 1.00 for dipyridamole. Specificity was 0.30 (visual) or 0.20 (quantitative analysis) for exercise and 0.80 (visual) or 0.90 (quantitative) for dipyridamole (p less than 0.05). Dipyridamole combined with quantitative analysis also improved specificity of CAD detection overall (p less than 0.01). These data demonstrate that pharmacologic vasodilation is more accurate than exercise when diagnosing CAD by myocardial perfusion scintigraphy in patients with LBBB. 
Depression and chronic fatigue in the patient with chronic pain. Chronic benign pain is commonly associated with chronic fatigue and depression. Depression and chronic fatigue syndrome are also associated with each other and often include pain. Psychologic factors are prominent in these conditions, and they may share neurobiologic factors as well. Management requires separately addressing each component of patients' distress and usually includes physical rehabilitation, education, administration of nonhabituating medications and often counseling. Depression may be a favorable prognostic sign, as it suggests a treatable condition and provides incentive for recovery. 
Prognostic factors in papillary carcinoma of the thyroid. In a retrospective study of 119 patients, followed for 1 to 30 years after treatment of a papillary carcinoma of the thyroid, the authors searched for possible prognostic factors of the risk of recurrence. Microcarcinomas, anaplastic tumors and Hurthle cell carcinomas were excluded from the study. In a univariate analysis, age (greater than 45 years), sex (male), loss of histologic differentiation, size (greater than 3 cm), presence of carcinomatous lymphangitis, extrathyroid extension, and presence of metastasis at diagnosis were associated with a higher recurrence rate; type of growth and multifocality were not significant. In a multivariate analysis (logistic regression), age, size, and carcinomatous lymphangitis were significant predictors for women, whereas metastasis at diagnosis and cystic growth were significant for men. 
Local thrombin synthesis and fibrin formation in an in vitro thrombosis model result in platelet recruitment and thrombus stabilization on collagen in heparinized blood The role of the local synthesis of thrombin in platelet recruitment and thrombus stabilization in heparinized blood was examined in vitro. Mural thrombosis was visualized and measured in a thin, rectangular, collagen-coated capillary under controlled rheological conditions by using fluorescence digital videomicroscopy and fluorescence microphotometry. Thrombin activity was inhibited in heparinized blood by the synthetic competitive inhibitor, D-phenylalanyl-L-prolyl-L-arginyl chloromethylketone (FPRCH2Cl), resulting in a marked reduction in the rate of platelet accumulation on collagen surfaces, indicating a role for thrombin in platelet recruitment. Similar although lesser effects were observed by reducing thrombin synthesis with antibodies to factors II and X. To decouple the role of thrombin in platelet recruitment by direct stimulation of platelet activity from its role in thrombus stabilization via fibrin formation, thrombosis was measured in heparinized blood treated with the tetrapeptide glycyl-prolyl-arginyl-proline, which inhibits fibrin monomer assembly into fibrin. The ultimate level but not the initial rate of platelet accumulation was reduced markedly, indicating a role for fibrin in thrombus stabilization against hemodynamic forces. Scanning electron micrographs demonstrated fibrin stands in the heparinized control samples but not in the heparinized samples with glycyl-prolyl-arginyl-proline. These results demonstrate a role for the local action of thrombin synthesized on the surfaces of thrombi even under conditions when the thrombin exerts no bulk effect, such as under heparin anticoagulation. Furthermore, this role appears to be a result of both platelet recruitment and thrombus stabilization. 
Correlation between molecular and clinical events in the evolution of chronic myelocytic leukemia to blast crisis. A patient with typical Philadelphia chromosome (Ph1)-positive chronic myelocytic leukemia (CML) was studied during sequential phases of disease: (1) initial chronic phase; (2) myeloid blast crisis; (3) second chronic phase; and (4) accelerated disease. A point mutation in the coding sequence of the p53 gene first appeared concomitantly with the blast crisis and then disappeared with the re-establishment of a second chronic phase. The chromosomal concomitant of the molecular alteration was a deletion of 17p. These observations suggest that abnormalities of the p53 anti-oncogene are temporally related to the clinical progression of some cases of CML and are probably responsible for the development of blast crisis in these cases. 
Detection of silent myocardial ischemia in diabetes mellitus. The prevalence of silent myocardial ischemia and its relation to autonomic dysfunction and pain threshold was studied in 58 men with diabetes mellitus and without cardiac symptoms. All patients underwent 48-hour ambulatory electrocardiographic monitoring and exercise testing after assessment of their autonomic function and pain threshold. Silent myocardial ischemia, defined as greater than or equal to 1 mm of ST-segment depression on either exercise testing or ambulatory electrocardiographic monitoring, was corroborated by exercise-induced reversible defect(s) on tomographic thallium scintigraphy. Autonomic function was assessed by heart rate response to: (1) Valsalva maneuver, (2) deep breathing, and (3) upright posture, as well as by diastolic blood pressure response to sustained handgrip and systolic blood pressure response to upright posture. Autonomic dysfunction was defined as greater than or equal to 2 abnormal responses. Pain threshold measurements were performed using electrical cutaneous stimulation of both forearms. Of the 58 diabetic patients, 21 were found to have autonomic dysfunction (36%). Silent myocardial ischemia was detected in 10 patients (17%), and was significantly more frequent in patients with than without autonomic dysfunction (38 vs 5%, p = 0.003). There was no difference in the electrical pain threshold or tolerance in subjects with and without silent myocardial ischemia. It is concluded that silent myocardial ischemia in asymptomatic diabetic men occurs frequently and in association with autonomic dysfunction, suggesting that diabetic neuropathy may be implicated in the mechanism of silent myocardial ischemia. 
Use of prophylactic otic drops after tympanostomy tube insertion. In a 1-year prospective study, 60 patients with chronic serous otitis media underwent bilateral tympanocentesis with tube insertion. The right ear was treated with dexapolyspectran (a solution consisting of polymyxin B sulfate, neomycin sulfate, sulfonamide, and hydrocortisone) intraoperatively and for 72 hours afterward, and the left ear served as the control. All patients were followed up at weekly intervals for the first month. Five (8.3%) out of 60 experimental ears had purulent otorrhea within the first 14 days after surgery, compared with eight (13.3%) out of 60 control ears. Statistical analysis showed no difference between the two groups. 
Pancreatic islet cell carcinoma with hypercalcemia: complete remission 5 years after surgical excision and chemotherapy. A 45-yr-old man who presented with hypercalcemia was found to have an abdominal mass that was a pancreatic islet cell carcinoma. Although clinical features were suggestive of primary hyperparathyroidism, his parathyroid hormone level was not elevated. The patient underwent a radical resection of the pancreatic neoplasm which was situated in the tail of the gland. After surgery, the serum calcium fell within the normal range, suggesting that the tumor was responsible for production of a parathyroid hormone-like substance. Because of malignant histologic features of the lesion, a chemotherapeutic regimen including 5-fluorouracil and streptozotocin was indicated. Five years later, the tumor has remained in total remission. 
Rapid detection of the A----G(8344) mutation of mtDNA in Italian families with myoclonus epilepsy and ragged-red fibers (MERRF). We devised a rapid PCR-based method to screen for an A----G transition at nucleotide 8344 of the human mitochondrial tRNA(Lys) gene, which was recently reported, by Shoffner and co-workers, to be associated with myoclonus epilepsy and ragged-red fibers (MERRF), a maternally transmitted mitochondrial encephalomyopathy (Shoffner et al. 1990). We confirmed this association in five of seven Italian MERRF pedigrees. The mutation was specific for the MERRF trait, because it was never found in mtDNA of non-MERRF individuals, including 14 normal and 110 diseased controls. Our study corroborates the idea that the A----G(8344) mutation is the most frequent and widespread genetic cause of MERRF. 
"Ex vivo" release of eicosanoid from human brain tissue: its relevance in the development of brain edema. The specific mechanism underlying the genesis of vasogenic brain edema is still debated: the role of arachidonic acid is considered extremely important, as it is a possible activator of self-maintaining reactions enhancing the release of vasoactive and cytotoxic compounds. The relationship between arachidonic acid metabolism and brain edema has been studied primarily in brain tissue samples or in the extracellular fluid, whereas the residual capacity of perilesional tissue to synthesize and release eicosanoids has not been investigated. In the present study, perilesional samples of brain tissue were available from 4 patients operated on for brain metastasis, from 8 patients who had malignant neuroepithelial tumors, from 4 with meningiomas, and from 5 with subarachnoid hemorrhage. A brain edema index was calculated from the preoperative computed tomographic scan. The "ex vivo" method allowed determination of the residual capacity of endogenous arachidonic acid metabolism. The edema index is significantly higher in patients with brain metastasis (6.5 +/- 0.8) and neuroepithelial tumors (3.6 +/- 0.2) than in those with meningiomas (1.5 +/- 0.06), subarachnoid hemorrhage (1.7 +/- 0.18), and in controls. In patients with metastatic and neuroepithelial tumors there is a significant correlation between peritumoral brain edema and the capacity to synthesize leukotriene C4 (P less than 0.05); the capacity to synthesize leukotriene C4 is also significantly elevated after subarachnoid hemorrhage (13.91 +/- 2.6 ng/ml of incubation medium) when compared with control cases (5.56 +/- 0.91). The capacity to synthesize prostacyclin is significantly higher in patients with brain metastasis than in those with neuroepithelial tumors and meningiomas (P less than 0.05). 
Pentoxifylline restores intestinal microvascular blood flow during resuscitated hemorrhagic shock. We studied the intestinal microvascular blood flow responses to hemorrhage and resuscitation with pentoxifylline by in vivo video microscopy. Male Sprague-Dawley rats were hemorrhaged to 50% of baseline mean arterial pressure for 45 minutes and then blindly randomized to receive pentoxifylline (25 mg/kg bolus + 0.2 mg/kg/minute) or an equivalent volume of saline plus return of shed blood and an additional bled volume of Ringer's lactate solution. Hemorrhage caused intestinal microvascular blood flow to decrease to 10% to 15% of baseline values. In the control group, resuscitation restored cardiac output and mean arterial pressure to baseline values, but intestinal microvascular blood flow remained at 30% of baseline values. In contrast, addition of pentoxifylline to the resuscitation regimen resulted in an immediate hyperemic response with an increase in intestinal microvascular blood flow to significantly greater than baseline values followed by return to baseline. Arteriolar dilation was not responsible for the improvement in flow implicating improved flow dynamics between erythrocytes, granulocytes, and vascular endothelia within the microcirculation. We conclude that addition of pentoxifylline to resuscitation from hemorrhagic shock restores intestinal microvascular blood flow. 
The acute and chronic antihypertensive effects of ketanserin cannot be explained by blockade of vascular serotonin, type 2, receptors or alpha 1-adrenergic receptors. The mechanism underlying the antihypertensive effect of acute and chronic administration of ketanserin was investigated in eight hypertensive patients. Intrabrachial artery infusions of serotonin and the selective alpha 1-adrenergic receptor agonist methoxamine were given before and 1 hour after a single oral dose of 20 mg ketanserin and after 4 weeks of treatment with 20 to 40 mg twice daily. Blood pressure was reduced by ketanserin both after the initial dose (p less than 0.01) and after 4 weeks of treatment (p less than 0.01). During placebo, serotonin, 1 ng/kg/min, increased forearm blood flow by 51% +/- 9% (p less than 0.01), whereas the highest dose induced a decrease in flow (-33% +/- 6%; p less than 0.01). Methoxamine elicited a vasoconstriction (p less than 0.001). These effects of serotonin and methoxamine were not influenced by either the initial dose of ketanserin or after 4 weeks of treatment. It is concluded that serotonin cannot be considered a general endogenous pressor agent in these patients. The antihypertensive effects of ketanserin cannot be attributed to either vascular alpha 1-receptor or serotonin, type 2, receptor blockade. 
Liver transplantation after paracetamol overdose. OBJECTIVE--To evaluate the role of liver transplantation after paracetamol overdose. DESIGN--Prospective study of consecutive candidates for transplantation and performance of transplantation over 18 months. SETTING--Liver unit, King's College Hospital, London. MAIN OUTCOME MEASURES--Fulfilment of indicators of poor prognosis, selection for transplantation, transplantation, survival. RESULTS--30 of 37 patients considered to have a reasonable prognosis with intensive medical care survived. Of 14 of 29 patients considered to have a very poor prognosis and registered for urgent liver transplantation, six received liver transplants, four of whom survived, while seven died and one survived without a transplant. Three of 15 patients with poor prognostic indicators but not selected for transplantation survived. CONCLUSION--Liver transplantation will have a definite but limited role in the management of fulminant hepatic failure induced by paracetamol. 
The perils of Pauline: visual loss in a tippler [clinical conference] A 31-year-old alcoholic woman who smoked had subacute visual loss. She was treated for tobacco-alcohol amblyopia with subsequent improvement in vision. 
Lack of impact of early antibiotic therapy for streptococcal pharyngitis on recurrence rates. To determine whether recurrence rates for group A beta-hemolytic streptococcal (GABHS) pharyngitis are related to the time of initiation of antibiotic therapy, we randomly assigned 113 patients with GABHS pharyngitis either to a group that began a 10-day course of penicillin V at the time of diagnosis or to a group that began the same antibiotic regimen after a dealy of 48 hours. Follow-up throat culture specimens were obtained 4 days, 2 months, and 4 months after the completion of antibiotic therapy, as well as during any interim episodes of acute pharyngitis. Serotyping of all GABHS isolates was performed to distinguish between recurrences with homologous serotypes and new acquisitions with heterologous serotypes. There was no significant difference between the two treatment groups in age, gender, duration of illness before enrollment in the study, initial clinical presentation, or compliance. Of the 50 patients in the immediate-treatment group, 6 (12%) had homologous serotypes of GABHS isolated on one of the follow-up throat cultures. Of the 63 patients in the delayed-treatment group, 9 (14%) had homologous serotypes of GABHS isolated on one of the follow-up throat cultures. These data indicate that a 48-hour delay in the initiation of penicillin therapy for GABHS pharyngitis does not reduce the recurrence rate. 
Endocrine and reproductive dysfunction following fractionated total body irradiation in adults. The endocrine and reproductive sequelae of total body irradiation for haematological malignancy have been studied in 21 patients (11 male) who were treated with 10 Gy in five fractions or 12 or 13.2 Gy in six fractions over 3 days. Eighteen patients (eight male) aged 16-49 years underwent dynamic tests of the hypothalamic-pituitary axis with insulin hypoglycaemia, thyrotrophin releasing hormone (TRH) and gonadotrophin releasing hormone stimulation and basal measurement of prolactin, sex steroids and thyroid hormones. Growth hormone responses (mean peak 64 +/- 36 mU/l, range 21-146 mU/l) and cortisol responses (mean peak 831 +/- 122 nmol/l, range 626-1105 nmol/l) were all within the normal range. Two patients had minimally elevated serum prolactin levels (445 and 588 mU/l, normal less than 350 mU/l). Serum thyroxine levels (57-133 nmol/l) were normal but six patients had elevated basal thyrotrophin (TSH) levels (6-9 mU/l) and seven had an exaggerated TSH response to thyrotrophin releasing hormone, indicating radiation-induced damage to the thyroid. Amenorrhea developed within 3 months of irradiation in all females and oestradiol levels were low, at 37-108 pmol/l (mean 58 +/- 22 pmol/l). Severe oligospermia or azoospermia was noted in men tested 5-70 months after irradiation and testicular volume was below the normal adult range in five of seven men assessed. Serum testosterone levels (12.4-35 nmol/l) were normal. Gonadotrophin-releasing hormone-stimulated gonadotrophin levels were elevated in all patients. However, two men have fathered two children each; one has refused semen analysis, but the other has a sperm count of 7 x 10(6)/ml (60 per cent motile, 20 per cent abnormal forms) 70 months after irradiation. When given by the above fractionated regimens, the endocrine sequelae of total body irradiation are limited to gonadal failure requiring oestrogen replacement in women and severe impairment of fertility in men. Subclinical thyroid dysfunction has been seen in 39 per cent of patients there is no evidence of direct damage to the hypothalamic pituitary axis. 
Steroid-responsive tubular aggregate myopathy. We report a man with an acute myalgia/cramp syndrome and tubular aggregates on his muscle biopsy. He was placed on prednisone and was found to be exquisitely sensitive to the drug, with changes of only 5 mg precipitating recurrence of symptoms. He was eventually tapered off all steroids, without symptoms, and repeat biopsy showed no tubular aggregates. We recommend similar patients be given a trial of high-dose steroids. 
Does racial variation in risk factors explain black-white differences in the incidence of hypertensive end-stage renal disease? Prospectively collected data on the incidence of treated hypertensive end-stage renal disease (HT-ESRD) were analyzed to investigate whether the higher rate of HT-ESRD in blacks compared with whites is due to differences in putative ESRD risk factors. The overall age-adjusted relative risks of HT-ESRD for black compared with white residents in the Maryland Regional ESRD Registry (Network 31) Catchment Area were 7.4 (95% confidence interval, 5.9 to 9.4) and 9.9 (95% confidence interval, 7.4 to 13.1) for men and women, respectively. In a population level analysis, race-specific HT-ESRD incidence rates in the black and white populations of 13 regions in Network 31 were related to the prevalence of putative ESRD risk factors in those populations. The latter were estimated from the 1981-1982 Maryland Statewide Household Hypertension Survey. Black populations had a 5.6-fold (95% confidence interval, 3.9 to 8.1) higher unadjusted incidence of HT-ESRD than white populations. The HT-ESRD incidence in a population was also directly related to that population's prevalence of hypertension, severe hypertension, and diabetes mellitus and inversely related to measures of socioeconomic status and mean age at diagnosis of hypertension. When adjusted simultaneously for age, prevalence of hypertension, severe hypertension, diabetes, and level of education, the risk of HT-ESRD was still 4.5 (95% confidence interval, 3.2 to 6.2) times higher for black compared with white populations. Our findings failed to support the hypothesis that race-related differences in the prevalence, severity, or age at onset of hypertension, in the prevalence of diabetes or in socioeconomic status, explain the well-recognized black-white differences in the HT-ESRD incidence. 
The prevalence of oral lesions in HIV-infected homosexual and bisexual men: three San Francisco epidemiological cohorts. To establish the prevalence of HIV-related oral lesions, we performed oral examinations of members of three San Francisco epidemiological cohorts of homosexual and bisexual men over a 3-year period. Hairy leukoplakia, pseudomembranous and erythematous candidiasis, angular cheilitis, Kaposi's sarcoma, and oral ulcers were more common in HIV-infected subjects than in HIV-negative subjects. Among HIV-infected individuals, hairy leukoplakia was the most common lesion [20.4%, 95% confidence interval (CI) 17.5-23.3%] and pseudomembranous candidiasis was the next most common (5.8%, 95% CI 4.1-7.5%). Hairy leukoplakia, pseudomembranous candidiasis, angular cheilitis and Kaposi's sarcoma were significantly more common in patients with lower CD4 lymphocyte counts (P less than 0.05). The prevalence of erythematous candidiasis and Kaposi's sarcoma increased during the 3-year period. Careful oral examinations may identify infected patients and provide suggestive information concerning their immune status. 
The effect of streptokinase on chest pain in acute myocardial infarction. Treatment with intravenous streptokinase is known to restore blood flow to the ischaemic myocardium in patients with acute myocardial infarction. However, little is known about its effect on chest pain. In a retrospective cohort study, 76 patients treated with streptokinase were compared to 76 patients not treated with streptokinase. All patients had acute myocardial infarction and less than 6 h of cardiac symptoms. Patients treated with streptokinase had a significantly lower need for nicomorphine (median 20 mg) than patients not treated with streptokinase (median 41 mg). Correspondingly, the median duration (3.5 h) of pain was reduced significantly in patients treated with streptokinase compared to patients not treated (24 h). We conclude that intravenous streptokinase given in the acute phase of myocardial infarction is effective in reducing the duration of cardiac chest pain. 
Cure of early-stage Hodgkin's disease with subtotal nodal irradiation. Ninety-four consecutive patients with Stage I or II Hodgkin's disease who presented supradiaphragmatically were treated with radiation therapy alone at the Mallinckrodt Institute of Radiology from January 1978 through December 1986. Fifty-two patients (55%) were staged pathologically, and 42 (45%) were staged clinically. The latter included lymphangiography and/or abdominal computed tomographic scan. Most patients with B symptoms and/or bulky disease were excluded from this series. Seventy-four patients were treated with subtotal nodal irradiation (mantle and periaortic fields). The spleen was treated if the patient had not undergone splenectomy. Twenty patients received mantle irradiation only. No patient received total nodal irradiation. All patients had an initial complete response. With a minimum follow-up of 7 months (median, 7.7 years; seven patients died before 3 years of follow-up, but all other patients had at least 3 years of follow-up), 81 patients (86%) remained disease-free. Six of 52 (12%) of the pathologically staged group had a relapse, as did seven of 42 (17%) of the clinically staged group (P = 0.68). Eight of 57 Stage I patients versus five of 37 Stage II patients had a relapse (P greater than 0.99). Analysis of disease-free survival by age, histologic findings, sex, and sites of involvement did not predict relapse. The pelvis was the most common site of failure (nine patients, 10%). However, only three patients (3%) failed in the pelvis alone. These results indicate that patients who, after adequate clinical staging with selective use of staging laparotomy, are found to have Stage I and II Hodgkin's disease may be treated with subtotal nodal irradiation with a high rate of cure. 
Prolonged hemorrhagic shock does not impair regeneration of plasma coagulant masses in the rabbit. BACKGROUND AND METHODS: Twelve adult male albino rabbits were assigned alternately to normotensive and hypotensive groups to assess the effect of hypovolemic shock on spontaneous correction of dilutional coagulopathy. All animals underwent dilutional exchange transfusion with 200 mL of rabbit RBCs and 5% human albumin. Half the animals were then acutely hemorrhaged and subsequent aliquots of blood removed as needed to maintain the mean arterial pressure at 40 mm Hg. RESULTS: By 6 hr after production of dilutional coagulopathy, masses and plasma concentrations of fibrinogen and Factor II had increased modestly but significantly, and Factor VII mass and concentration and in vitro coagulation had returned almost to normal; plasma volume was unchanged in the normotensive animals. In the hypovolemic shock animals, where coagulant mass regeneration was as rapid as in the normotensive animals, a doubling of total plasma volume (p less than .01) prevented the concentrations of fibrinogen and Factor II, and hence the coagulation times, from improving. CONCLUSIONS: Dilutional coagulopathy corrects spontaneously within hours. Normovolemic shock prolongs dilutional coagulopathy not by impairment of factor regeneration but because of further (internal) dilution due to plasma expansion. Rapid correction of dilutional coagulopathy is likely to necessitate cryoprecipitate administration. 
Genetics of colon cancer. Strikingly rapid advances in the identification of genetic events that are important in colonic carcinogenesis have been made in the past several years. Specific inherited (adenomatous polyposis coli gene) and acquired (ras gene point mutations; c-myc gene amplification; allelic deletion at specific sites on chromosomes 5, 17, and 18) genetic abnormalities appear to be capable of mediating steps in the progression from normal to malignant colonic mucosa. Understanding these genetic factors and how they influence cellular function will have a profound effect on medical practice. High-risk populations will be (and are being) identified by genetic markers, thus allowing prevention and screening to be more precisely targeted to the population at risk; intervention strategies will be designed on the basis of the known cellular defects of neoplastic colonic mucosa; and new molecular preventive and therapeutic approaches can be developed. 
Rare intrathoracic complications in acute pancreatitis. Ascites and pleural effusions may complicate pancreatitis but pericarditis with pericardial effusion and tamponade is rare and necrosis of mediastinal fat has not been described before. All these complications occurred in the case reported here. 
Receptors for tumor necrosis factor on neoplastic B cells from chronic lymphocytic leukemia are expressed in vitro but not in vivo. Recombinant tumor necrosis factor-alpha (TNF-alpha) is a cytokine that induces proliferation of neoplastic B cells from patients with chronic lymphocytic leukemia (CLL). To gain insight into the mechanisms involved in regulating TNF responsiveness, we have examined TNF receptor expression on neoplastic B-CLL cells. We have demonstrated that freshly isolated neoplastic B cells from patients with CLL did not express TNF receptors. After 1 day of incubation in culture medium, TNF receptors were detectable in the range of 540 to 1,500/cell. Kinetic experiments revealed that receptor expression was half-maximal after 3 hours of culturing and required de novo protein synthesis. The Scatchard plots of TNF-alpha binding indicated a single set of high-affinity TNF receptors with a dissociation constant of 70 pmol/L. TNF receptor expression in vitro was found in all examined cases. All cytokines tested, with the exception of IL-2, did not influence the expression of TNF receptors. The TNF receptor expression is enhanced in B-CLL cells cultured in the presence of interleukin-2 when compared with the receptor expression of cells cultured in medium alone. Our data suggest that neoplastic B-CLL cells in patients with stable disease do not express TNF receptors in vivo and that an unknown mechanism suppressing TNF receptor expression in vivo may play a role in growth regulation of neoplastic B cells. 
Balloon angioplasty for recurrent coarctation of aorta. Immediate and long-term results BACKGROUND. As angioplasty techniques have been refined and larger low-profile balloons developed, a nonsurgical approach to recoarctation has become available. Several reports have documented both the efficacy and safety of this procedure. However, there are little data available on the long-term follow-up of these patients. This report details the initial results and long-term evaluation of both the relief of obstruction and the presence of hypertension after balloon angioplasty for recurrent coarctation. METHODS AND RESULTS. Balloon angioplasty for recurrent coarctation of the aorta was performed 29 times in 26 patients at a median age of 4 years and 9 months (range, 4 months to 29 years), with eight patients less than 1 year old. Initial surgical techniques were end-to-end anastomosis in 11 patients, subclavian flap aortoplasty in 11 patients, and patch aortoplasty in four patients. Angioplasty was performed at a median interval of 2 years and 7 months (range, 4 months to 23 years) after surgery. Mean peak systolic pressure difference across the coarctation decreased from 40.0 +/- 16.8 to 10.3 +/- 9.5 mm Hg (p less than 0.05) after the initial angioplasty, and mean diameter of the aortic lumen at the coarctation site increased from 5.8 +/- 3.5 to 9.0 +/- 4.3 mm (p less than 0.05). There was no mortality, and only one patient developed an aneurysm (4%). Three patients underwent repeat angioplasty for a pressure difference of more than 20 mm Hg. Long-term follow-up is available on 24 of 26 patients with a mean follow-up of 42 +/- 24 months (range, 12-88 months). Mean peak systolic pressure difference across the area of coarctation decreased from 40.3 +/- 17.4 before angioplasty to 8.5 +/- 8.3 mm Hg after final angioplasty (p less than 0.05) and 7.5 +/- 7.5 mm Hg at follow-up. Mean peak systolic blood pressure in the upper extremities decreased from 133.1 +/- 14.9 before angioplasty to 111.1 +/- 14.1 mm Hg at long-term follow-up (p less than 0.05). CONCLUSIONS. Balloon angioplasty should be considered the treatment of choice for relief of recurrent aortic coarctation. 
Syringomyelia secondary to congenital intraspinal lipoma. Preoperative evaluation using serial magnetic resonance imaging was performed on an infant with lumbosacral lipoma. Syrinx formation arising just above the lipoma was observed in conjunction with rapid growth of the lipoma. Definite shrinkage of syringomyelia was obtained after radical excision of the lipoma. The syrinx formation was possibly caused by compression from the extramedullary lipoma. 
Loss of the endothelin signal pathway in C6 rat glioma cells persistently infected with measles virus. Endothelin 1 causes a strong Ca2+ signal in C6 rat glioma cells as measured by fura-2 fluorescence. This endothelin 1-induced Ca2+ signal was not observed when the cells were persistently infected with a measles virus strain of subacute sclerosing panencephalitis (SSPE, strain Lec). Binding of 125I-labeled endothelin 1 to the C6/SSPE cells was less than 5% of the binding to the C6 control cells, suggesting that the impairment in signal transduction was due to a loss of binding sites for endothelin 1. Treatment of the C6/SSPE cells with measles antiserum resulted in the loss of expression of viral proteins located in the membrane as well as inside the cells (antigenic modulation), but it restored neither the endothelin 1-induced Ca2+ rise nor the 125I-endothelin 1 binding. Cocultivation of uninfected C6 cells with C6/SSPE cells (9:1 ratio) resulting in contact-mediated transmission of measles virus showed that the 125I-endothelin 1 binding activity was gradually lost as a consequence of persistent virus infection. 
Cerebrovascular accidents complicating pregnancy and the puerperium. The decreasing incidence of direct causes of maternal death over the past half century has led to a heightened awareness of nonobstetric factors responsible for maternal mortality. For example, cerebrovascular accidents are an important nonobstetric cause of maternal morbidity and mortality. During the 6.5-year period from 1984 to mid-1990, we encountered 15 women in whom pregnancy or the puerperium was complicated by an acute cerebrovascular accident. Six of these women had hemorrhagic strokes and nine had ischemic strokes. During this same time, approximately 90,000 women were delivered at Parkland Memorial Hospital, and thus the incidence of stroke was about one in 6000 pregnancies. Chronic hypertension or preeclampsia was causative in three cases of hemorrhagic stroke. It is important that 20% of the women died as a result of stroke, and of the 12 survivors, 40% have residual neurologic deficits. An aggressive work-up to define the etiology of stroke is necessary in order to implement cause-specific management, with subsequent reduction in morbidity and mortality. 
Clinical results of mitral valve replacement with and without preservation of the posterior mitral valve leaflet and subvalvular apparatus. In this study we attempted to investigate the importance of posterior leaflet preservation during mitral valve replacement (MVR). One hundred and forty randomly selected patients with isolated mitral insufficiency were studied, half of whom had MVR with preservation of the posterior leaflet (Group I), whereas in the other half conventional MVR was performed, without preservation of the posterior leaflet (Group II). Within these two groups there were no in hospital deaths, but 5 patients in Group II were admitted to the hospital with congestive heart failure and 3 of them died after approximately 6 months. Long term mortality rate was 4.2% in Group II. Ejection fraction (EF) decreased postoperatively from 56% to 50% in Group I (p less than 0.05), and from 59% to 49% in Group II (p less than 0.05). Fifteen patients in each group and aged below 30 with sinus rhythm and in the first functional capacity according to the New York Heart Association classification (NYHA) were subjected to exercise study, 18 months after the operation. After exercise EF increased from 47% to 64% in Group I and decreased from 51% to 47% in Group II. These findings suggested that MVR with the preservation of the chordae tendineae can be done with a low morbidity and mortality rate in the early and late postoperative period. 
Platelet-activating factor produces shock, in vivo complement activation, and tissue injury in mice. We previously showed that TNF and endotoxin (LPS) synergize to activate the complement system and produce shock and bowel injury in normal mice. However, C5-deficient mice were protected from these adverse effects. In this study, we show that in mice, platelet-activating factor (PAF) antagonist prevents TNF- and LPS-induced complement activation, bowel injury, and death, indicating that PAF mediates the actions of TNF and LPS. We then examined the role of the complement system in PAF-induced shock and tissue injury. We found that 1) PAF (3 micrograms/kg) induces shock, hemoconcentration, bowel necrosis, and death in normal mice, whereas C5-deficient mice are protected from these effects. (Protection was abrogated when the dose of PAF was raised to 5 micrograms/kg.) Furthermore, when C5-deficient mice were reconstituted with normal serum, they also developed shock, bowel injury, and death in response to PAF. Thus, C5 is required for PAF to induce injury. 2) PAF activates the complement system in vivo, but not in vitro. The mechanism of complement activation by PAF is unclear. Inasmuch as PAF stimulates neutrophils to release protease that may activate the complement system, we examined the effect of neutrophil depletion on PAF-induced injury and complement activation. We found that neutrophil depletion fails to prevent PAF-induced complement activation, although PAF-induced lethality is much reduced. We conclude that PAF causes complement activation, and acts in synergy with active complement fragments to produce shock and tissue injury. Neutrophils probably do not play the pivotal role in PAF-induced complement activation. 
Evaluation of the Graseby PCAS. A clinical and laboratory study. The Graseby patient-controlled analgesia system was evaluated in the laboratory and in clinical use. The problems encountered with eight examples used to treat 510 patients are reported. Laboratory performance revealed the unit to be accurate at infusion volumes of 1 and 2 ml. 
Occupational and industrial toxin exposures and the gastrointestinal tract. Gastrointestinal Toxicology Subcommittee of the American College of Gastroenterology Patient Care Committee. The subcommittee on Gastrointestinal Toxicology of the Patient Care Committee of the American College of Gastroenterology has reviewed potential effects of exposures to occupational and industrial hazards on the gastrointestinal tract, liver and pancreas. This review is presented to 1) share clinical data concerning gastrointestinal toxicology, 2) emphasize the paucity of available information to the practicing clinician, and 3) stimulate basic research interest in this field. 
Necrotizing fasciitis. Ten cases of necrotizing fasciitis are reviewed. Three patients died but only two of these deaths were due to uncontrolled septicaemia. All isolated organisms were sensitive to a combination of piperacillin and ampicillin which we now regard as the initial antibiotic combination of choice. Prompt and aggressive surgical debridement remains the cornerstone of management. 
Breast specimen microcalcifications: radiographic validation and pathologic-radiologic correlation. A prospective analysis of specimens from location and biopsy of mammographically suspect microcalcifications in 108 patients was carried out to determine if microcalcifications were lost during histopathologic processing and the clinical relevance of such loss. Nine hundred sixty-eight paraffin blocks were prepared from 425 gross tissue slices containing calcifications identified at radiography of the specimens. Calcium was apparently lost both during preparation of the blocks (13.6%) and after slide preparation (12.6%), for a total possible loss of 26.2%. All specimens demonstrated calcification histologically. One pathology report was amended because of information obtained after recuts, but all cancers were detected on original slides whether or not calcifications were identified initially. The results indicate that, by following the suggestions offered to ensure adequate histopathologic sampling of calcification seen at mammography, most if not all of the calcification present can be detected on the original slide. 
A cluster of related zinc finger protein genes is deleted in the mouse embryonic lethal mutation tw18. We report that a number of related zinc finger protein genes are closely linked on mouse chromosome 17. At least four of these genes are transcribed in the 8.5-day postcoitum embryo and are deleted in the t complex early acting embryonic lethal mutation tw18. We have evidence that additional finger protein genes are located in this region. These findings demonstrate that related finger protein genes can be clustered in the murine genome and identify genes that may be considered as candidates for the tw18 mutation. 
Remote cortical dysfunction in aphasic stroke patients. We studied the effect of deep-seated left hemispheric lesions on cortical blood flow in 18 right-handed aphasic stroke patients. Regional cerebral blood flow was measured at rest and during the performance of a functional naming test using the two-dimensional xenon-133 inhalation method. Compared with 10 controls, at rest the patients showed regional cortical hypoperfusion in the left frontoparietal region. In the controls, activation patterns from the rest to the test condition involved mainly the left hemisphere areas. In the patients, a lack of blood flow change was observed in several areas that were usually hypoperfused at rest. However, in patients with slight verbal expression disorders there were obvious blood flow increases in other brain regions in both hemispheres. Such cortical functional reorganization and the presence of a remote cortical dysfunction could play a role in the pathophysiology of language disorders. 
In vitro perfused-superfused cat carotid body for physiological and pharmacological studies. An in vitro perfused carotid body preparation was developed to study its chemosensory responses to physiological and pharmacological stimuli. The carotid bifurcation with the carotid body was vascularly isolated and excised from pentobarbital sodium-anesthetized cats. The CB was perfused in a chamber by gravity (80 Torr) with modified Tyrode's solution (N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid-NaOH at pH 7.40) equilibrated at a given Po2 and superfused with the same medium at (Po2 of 20 Torr). The temperature was maintained at 35.5 +/- 0.5 degrees C. The frequency of chemosensory discharges (CD) was recorded from the whole carotid sinus nerve (n = 24), and the responses were tested by repeated interruptions of perfusate flow (SF), perfusion with hypoxic medium, and injections of nicotine and cyanide (0.1 nmol to 1 mumol) and hypercapnic medium. During hyperoxic perfusion, SF resulted in a sigmoidal increase in CD, reaching a maximum that was 23.6 +/- 4.4-fold greater than the basal activity. Restoration of flow returned CD promptly to basal values. After normoxic perfusion, SF led to a similar maximal activity more rapidly, but the duration was shorter. Reduction of the perfusate PO2 (Po2 from 450 Torr to 150, 30, and less than 10 Torr) caused a nonlinear increase in CD. CO2 stimuli (PCo2 38-110 Torr) resulted in a linear increase in CD. Nicotine or cyanide increased CD in a dose-dependent manner. The preparation retained its initial responsiveness for 2-3 h, making extensive experimental studies feasible. 
Evaluation of three oral dosages of ondansetron in the prevention of nausea and emesis associated with cyclophosphamide-doxorubicin chemotherapy. We assessed the antiemetic efficacy and safety of three different oral doses of ondansetron (GR 38032F), a novel serotonin type-3 receptor antagonist, in three consecutive series of 20 breast cancer patients receiving cyclophosphamide-doxorubicin-based chemotherapy for the first time. Patients received oral doses of 8 mg, 4 mg, or 1 mg of ondansetron three times daily for 2 days, with the first dose given 30 minutes before the cyclophosphamide infusion. We then evaluated the efficacy of a conventional antiemetic regimen of intravenous lorazepam, metoclopramide, and diphenhydramine given before chemotherapy and 10 mg prochlorperazine given orally twice on study day 1 and three times on study day 2 in a fourth series of 20 patients with comparable characteristics. The number of emetic episodes, assessment of nausea and appetite, and adverse events were recorded throughout the 2-day study period. Pretreatment and posttreatment clinical laboratory data were also collected. No emesis was observed during the 2-day study period in 17 (85%), 13 (65%), and 11 (55%) patients treated with 8-mg, 4-mg, and 1-mg ondansetron doses, respectively, and in seven (35%) patients who received conventional therapy. The incidence and intensity of nausea were lower with increasing doses of ondansetron and were lower than in the conventional group. Ondansetron-related side effects were generally mild and reversible and did not appear to increase in a dose-dependent manner. These effects included headache, stomach cramps, diarrhea, fatigue, and elevated serum transaminase concentrations. One patient who received three 1 mg doses of ondansetron experienced tremors and muscle twitching. Oral ondansetron is an effective and safe antiemetic for patients receiving noncisplatin cyclophosphamide-doxorubicin-based chemotherapy, and its antiemetic activity appears to be dose-related. 
Germ cell tumors masquerading as central nervous system sarcoidosis. The diagnosis of central nervous system sarcoidosis is uncertain without typical multisystem involvement. We describe two patients with isolated central nervous system mass lesions whose biopsy results were consistent with sarcoidosis. After a progressive clinical course, they were found to have diencephalic germinomas. Germ cell tumors, in particular, should be considered in the differential diagnosis of central nervous system sarcoidosis as they are potentially treatable, occur in intracranial locations favored by sarcoidosis mass lesions, and may be surrounded by granulomatous inflammation that can be mistaken for the noncaseating granulomas of sarcoidosis. 
Circulating ICAM-1 isoforms: diagnostic prospects for inflammatory and immune disorders. Intercellular adhesion molecule-1 (ICAM-1, CD54) is an important early marker of immune activation and response. Evidence on its role has come from immunohistological staining of tissues, since no free circulating ICAM-1 has been detected. By means of monoclonal antibodies against ICAM-1 and a sensitive chemiluminescence technique, free circulating ICAM-1 was detected in serum from sixteen healthy young volunteers. The concentrations varied among the subjects. Non-denaturing gel separation methods showed that ICAM-1 circulates in at least three isoforms, the proportions of which also varied. These findings have important implications for the investigation, diagnosis, and therapeutic monitoring of various inflammatory, neoplastic, and immune disorders. 
Biology of pancreatic cancer. Pancreatic cancer is the fifth leading cause of death from malignant disease in Western society. Apart from the fortunate few patients who present with a resectable small pancreatic adenocarcinoma, conventional treatment offers no hope of cure and has little palliative value. Over the past two decades major steps have been made in our understanding of the biology of pancreatic growth and neoplasia. This review sets out to explore these advances, firstly in the regulation of normal pancreatic growth, and secondly the mechanism which may be involved in malignant change of the exocrine pancreas. From an understanding of this new biology, new treatment strategies may be possible for patients with pancreatic cancer. 
Microanalysis of bile acid composition in intrahepatic calculi and its etiological significance. Brown pigment stones in the intrahepatic bile ducts were compared with those found in the extrahepatic bile ducts with special reference to the bile acids modified by bacterial intervention, that is, unconjugated, glucuronidated, secondary, and ketonic bile acid fractions. The former showed significantly lower amounts of total bile acids (P less than 0.01) and lower proportions of unconjugated bile acid fraction (P less than 0.01), secondary bile acid fraction (P less than 0.05), and ketonic bile acid fraction (P less than 0.05) to total bile acids than the latter. The discriminant analysis using these bile acid parameters led to complete separation between intrahepatic and extrahepatic stones in the case of brown pigment stones. In contrast, cholesterol stones in the intrahepatic bile ducts showed the bile acid composition close to those found in the extrahepatic ducts and gallbladder. The above data show that the bacterial infection plays a less important role in the formation and ensuing growth of most intrahepatic brown pigment stones than in extrahepatic stones, and that factors other than or in addition to bacterial infection are involved. 
A prospective study of respiratory failure after high-risk surgery on the thoracoabdominal aorta. From June 1960 to September 1990, 1414 patients underwent repair of thoracoabdominal aortic aneurysms, of whom 112 (8%) had pulmonary complications requiring respiratory support with tracheostomy; subsequently 45 (40%) died in the hospital. We determined by stepwise logistic regression analysis, in a prospective study of high-risk type I and II thoracoabdominal aortic aneurysms repairs, the independent predictors of respiratory failure, defined as respiratory ventilation exceeding 48 hours after operation. In 98 patients studied, 38 (39%) were women, 60 (61%) were men, 54 (55%) had type II thoracoabdominal aortic aneurysms, 34 (35%) had aortic dissection, 19 (19%) were nonsmokers, 40 (41%) exsmokers, and 39 (40%) active smokers. Before operation, 55 (56%) had chronic pulmonary disease with respiratory failure developing in 58% (p = 0.0005 versus no chronic pulmonary disease, 10/43, 23%), and of the 26 patients in the lower quarter of forced expiratory volume (1 sec) (FEV1 less than or equal to 1.45 L) respiratory failure developed in 61% (p = 0.035). In-hospital survival was 98% and 83% (p = 0.008), respectively, and cumulative survival at 6 months by Kaplan-Meier analysis was 96% and 80% (p = 0.004, log-rank test), respectively, for patients without respiratory failure (N = 56/98, 57%) and with respiratory failure (N = 42/98, 43%). On univariate analysis, the following were associated with respiratory failure (p less than 0.05): FEV1, FEV1% predicted, FVC, FEF25, FEF25% predicted, FEF25-75, FEF25-75% predicted, PaCO2 Pao2, symptoms, smoking history, chronic pulmonary disease, cryoprecipitate volume, postoperative neuromuscular deficit, cardiac complications, reoperation for bleeding, renal complication, stress ulceration, postoperative creatinine level, postoperative dialysis, and postoperative encephalopathy. The independent predictors of respiratory failure were (p less than 0.05): chronic pulmonary disease, smoking history, cardiac and renal complications. In patients with chronic pulmonary disease, the only independent predictor was FEF25 (p = 0.030). These observations may be of value in selecting patients for elective operation. 
Nonpharmacologic treatment of periodic leg movements in sleep. The effects of a 30-minute stimulation of the dorsiflexors of the feet and toes before bedtime were investigated in eight patients with periodic leg movements in sleep (PLMS). None were taking medications at the time of the investigation. All subjects were treated with the EMS-250 Neuromuscular Stimulator, which has a maximum output per channel of 1.5mA and a frequency of 47Hz. Stimuli were delivered via a pulse train (on for 1.5sec and off for 1.8sec). A single all-night polysomnogram after this stimulation showed that all patients responded to stimulation, with reduction of leg movements from an average pretreatment PLMS index of 44.6 per hour to a posttreatment PLMS index of 14 per hour (p less than .01). Nocturnal leg movements were primarily reduced during the non-REM sleep. Multiple indices of sleep continuity did not change significantly, although there was a trend toward better sleep consolidation. 
Absent or reversed end diastolic flow velocity in the umbilical artery and necrotising enterocolitis. Absent or reversed end diastolic flow (AREDF) velocities in the umbilical artery were identified in 25 high risk pregnancies. In six pregnancies the fetus was abnormal and all but one of these ended in perinatal death. Of the 19 morphologically normal fetuses, three died in utero and there were four neonatal or infant deaths. The mortality rate was 48% for all pregnancies and 37% for those with morphologically normal fetuses. There was a highly significant increased risk for the development of necrotising enterocolitis in these morphologically normal fetuses with AREDF (53%) compared with controls (6%) who did have umbilical artery end diastolic flow velocities in fetal life. There were no significant differences between the matched pairs for parameters of neonatal outcome chosen to reflect neonatal morbidity. These findings demonstrate the close association between AREDF and necrotising enterocolitis that appears to be independent of other variables such as degree of growth retardation, prematurity, and perinatal asphyxia. 
The contributions of interpersonal conflict to chronic pain in the presence or absence of organic pathology. This study investigated the influences of social support and interpersonal conflict on chronic pain in patients with arthritis or with myofascial disorders. Measures of social support, conflict, and pain were drawn from subscales of the McGill Pain Questionnaire, the Multidimensional Pain Inventory, the Family Environment Scale, and the Interpersonal Relationship Inventory. Patients with myofascial disorders reported significantly worse pain (sensory and affective), higher depression scores, more interpersonal conflict, and less support from others than patients with arthritis, but did not differ from them on personality traits. Also, the contributions of conflict to pain were found to depend on the nature of the chronic disorder and on the source of the conflict, i.e., significant other, family, or social network members. For patients with arthritis, less intense pain (sensory and affective) was associated with higher family conflict. Less intense sensory pain in arthritis was also associated with more punishing responses from the significant other to pain. For patients with myofascial disorders, more intense affective pain was associated with higher social network conflict. Social support did not significantly contribute to pain for either group. Thus, chronic painful disorders may differ on the influences that social relationships have on pain. The implications of these differences for treatment are discussed. 
Total avulsion of an osseointegrated screw. The close union achieved between pure grade titanium and healthy bone makes dislocation a rare event. We report the case of the total avulsion of an apparently well-integrated implant from a healthy mastoid bone. 
Uniparental heterodisomy for chromosome 14 in a phenotypically abnormal familial balanced 13/14 Robertsonian translocation carrier. A 9-year-old mentally retarded girl with multiple congenital anomalies was found to carry a balanced 13/14 Robertsonian translocation [45,XX,t(13q14q)] which was also present in her father. Her mother carried a balanced reciprocal translocation between chromosomes 1 and 14 [46,XX,t(1;14) (q32;q32)]. Both of her parents were phenotypically normal. Molecular studies were carried out to determine the parental origin of chromosomes 1, 13, and 14 in the patient. Using probes for D14S13 and D14S22, we could show that the patient inherited both chromosomes 14 from her father and none from her mother. Similar studies using probes for chromosomes 1 (D1S76) and 13 (D13S37) loci showed the presence of both maternal and paternal alleles in the patient. Our findings indicate that paternal uniparental heterodisomy for chromosome 14 most likely accounts for the phenotypic abnormalities observed in our patient. It is suggested that uniparental disomy may be the basis for abnormal development in at least some phenotypically abnormal familial balanced-translocation carriers. 
Sleep difficulties, pain and other correlates. A multiple regression analysis was used with variables relevant to sleeping problems from a large community health survey in South Australia. The variables that were found to be most strongly correlated with sleep problems were, in order of importance, pain, anxiety, age, somatic health and annual household income, all of which accounted for 22% of the variance. Weight problems, depression and sex of the respondent were not so important in this analysis. Arthritis, which often increases with age, appeared to be most strongly associated with pain, explaining in part why sleeping problems increase with age. Anxiety, pain and poor somatic health were most strongly associated with lying awake at night or sleeping badly, and anxiety and pain were most strongly correlated with taking longer to get to sleep. Poor somatic health and anxiety were most strongly associated with waking early, and age and pain were the most important variables in taking tablets to aid sleep. 
Long-term patient-controlled analgesia in children. Three children who received patient-controlled analgesia for periods of up to 41 days are described. In each case patient-controlled analgesia allowed pain control to be achieved in difficult situations. No patient developed tolerance or clinical signs of dependence. This use of long-term patient-controlled analgesia warrants further evaluation. 
Transmission of infectious diseases in outpatient health care settings. Increased provision of health care in outpatient settings and concerns about occupational transmission of infections have focused attention on the risk of transmission of infectious diseases in ambulatory health care settings. In contrast to inpatient nosocomial infections, infections transmitted in outpatient settings are neither systematically monitored nor likely to be detected by routine qi surveillance. To better define the spectrum of such events, we reviewed the literature to identify cases and clusters of infections associated with outpatient health care. In this review, we identified and epidemiologically characterized 53 such reports that occurred from 1961 through 1990. Transmission occurred in general medical offices, clinics, and emergency departments (23); ophthalmologists' offices and clinics (11); dental offices (13); and alternative-care settings (six). Our findings suggest that inpatient infection-control practices should be extended to outpatient health care settings by assigning specific responsibility for infection control and by adapting surveillance methods and prevention measures. 
Staphylococcus epidermidis induces complement activation, tumor necrosis factor and interleukin-1, a shock-like state and tissue injury in rabbits without endotoxemia. Comparison to Escherichia coli. Tumor necrosis factor (TNF) and IL-1 are thought to mediate many of the pathophysiologic changes of endotoxemia and Gram-negative bacteremia. In these studies, heat-killed Staphylococcus epidermidis were infused into rabbits to determine whether an endotoxin (LPS)-free microorganism also elicits cytokinemia and the physiologic abnormalities seen in Gram-negative bacteremia. S. epidermidis induced complement activation, circulating TNF and IL-1, and hypotension to the same degree as did one-twentieth the number of heat-killed Escherichia coli. Circulating IL-1 beta levels had a greater correlation coefficient (r = 0.81, P less than 0.001) with the degree of hypotension than TNF levels (r = 0.48, P less than 0.02). Leukopenia, thrombocytopenia, diffuse pulmonary capillary aggregation of neutrophils, and hepatic necrosis with neutrophil infiltration were observed to the same extent after either S. epidermidis or E. coli infusion. However, S. epidermidis infusion did not induce significant (less than 60 pg/ml) endotoxemia, whereas E. coli infusion resulted in high (11,000 pg/ml) serum endotoxin levels. S. epidermidis, E. coli, LPS, or S. epidermidis-derived lipoteichoic acid (LTA) induced TNF and IL-1 from blood mononuclear cells in vitro. E. coli organisms and LPS were at least 100-fold more potent than S. epidermidis or LTA. Thus, a shock-like state with similar levels of complement activation as well as circulating levels of IL-1 and TNF were observed following either S. epidermidis or E. coli. These data provide further evidence that host factors such as IL-1 and TNF are common mediators of the septic shock syndrome regardless of the organism. 
Portal vein thrombosis complicating endoscopic variceal sclerotherapy. Convincing further evidence. Portal vein thrombosis occurred in a patient who bled from gastric varices that developed after obliteration of esophageal varices by endoscopic sclerotherapy. This complication was recognized only at surgery when thrombectomy and endovenectomy preceded the successful placement of an end-to-side portocaval shunt. At histopathology, the presence of an amorphous, eosinophilic material staining negatively for fibrin and similar to sclerosant injected at sclerotherapy was observed within the clot. This latter finding, previously unreported, provides convincing evidence for the causal relationship of portal vein thrombosis to endoscopic sclerotherapy. 
Prevention of perioperative deep vein thrombosis in general surgery: a multicentre double blind study comparing two doses of Logiparin and standard heparin. H.B.P.M. Research Group. A total of 1290 patients were enrolled in a randomized multicentre double blind study in order to investigate the use of two doses of a new low molecular weight heparin, Logiparin, in the prevention of deep vein thrombosis (DVT) in general surgery. Patients who were included had no contraindication to heparin therapy and had at least one of the recognized risk factors for DVT. Patients were randomized to receive unfractionated heparin (UH) 5000 units b.d., Logiparin 2500 units daily or Logiparin 3500 units daily. Each treatment was given subcutaneously 2 h before surgery and continued for 7-10 days. Daily 125I-labelled fibrinogen uptake tests (FUTs) were performed from day 2 to day 7 to detect DVT, and phleboangiography was used to confirm the diagnosis. The wound was examined on a daily basis to check for haematoma formation, and all patients were followed up for 1 month after operation. All three treatment arms were well matched for age, sex, weight, diagnosis and type of operation performed. The three major inclusion criteria in the trial were malignancy, age over 60 years and a history of varicose veins. Positive FUTs (UH = 4.2 per cent, Logiparin 2500 units daily = 7.9 per cent, Logiparin 3500 units daily = 3.7 per cent) and positive angiograms (UH = 3.0 per cent, Logiparin 2500 units daily = 5.6 per cent, Logiparin 3500 units daily = 2.3 per cent) were significantly more common in the Logiparin 2500 units daily group than in the UH and Logiparin 3500 units daily groups. The rates of major complications (severe haemorrhage, death, pulmonary embolism, reintervention) were similar in the three groups. 
Treatment of pulmonary endometriosis with a long-acting GnRH agonist. We report the case of a patient who was successfully treated with a long-acting GnRH agonist for pulmonary endometriosis. This 28-year-old woman had symptomatic pleural endometriosis, documented by biopsies, as well as symptomatic pelvic endometriosis. Two surgical procedures, consisting of excision of pleural endometriotic tissue and partial pleurectomies, failed to relieve her chest symptoms. Little relief was achieved with pseudopregnancy treatment. Satisfactory symptomatic improvement was obtained with danazol, but this medication had to be discontinued because of severe side effects. Trial of a GnRH agonist, leuprolide acetate, achieved complete remission of her chest symptoms; in addition, the patient became pregnant immediately after cessation of therapy. Gonadotropin-releasing hormone agonist therapy may be an important therapeutic alternative for women with pulmonary endometriosis who cannot tolerate danazol treatment and in whom surgical therapy fails to relieve the chest symptoms. 
One hundred ten consecutive primary orthotopic liver transplants under FK 506 in adults. An account is given of the 6- to 12-month survival, and causes of failure in 110 consecutive patients who underwent primary liver transplantation under treatment from the outset with FK 506 and steroids. The patient survival is 92.7%, and the first graft survival is 87.3%. At a very high frequency, the patients achieved good graft function, and they had a relatively low morbidity that was partially ascribable to minimal use and early discontinuance (in 60% of cases) of steroids. Renal dysfunction and other adverse findings were largely confined to patients with poor initial graft function and consequent apparent alteration of the kinetics of FK 506 elimination, causing functional overdosage. Results compare very favorably with our past record using conventional immunosuppression, and support the belief that FK 506 is a superior immunosuppressive agent which is suitable for chronic administration. 
Hepatic perfusion index (HPI) in mesenteric angina and following successful revascularization. This is a case report of a 45 year old man who had previously undergone a small bowel resection for acute mesenteric ischaemia. He subsequently suffered from mesenteric angina due to stenosis of the origin of the superior mesenteric artery and intermittent claudication due to aorto-iliac atheroma. The patient underwent a successful aorto-bifemoral Y graft and small bowel revascularization with a saphenous vein graft between the Y graft and the accessible proximal portion of the superior mesenteric artery. Before vascular reconstruction, the hepatic perfusion indices (HPI) in both the fasted and fed states were elevated; after mesenteric revascularization the HPI values were substantially lowered. The hepatic perfusion index may, by demonstrating functional abnormality, be useful in the diagnosis of mesenteric ischaemia and also in the assessment of treatment. Further evaluation of HPI in patients with suspected mesenteric ischaemia is therefore required. 
Diagnosis and management of Kawasaki disease. Kawasaki disease is an acute vasculitis characterized by mucosal inflammation, rash, cervical adenopathy, indurative edema of the hands and feet, and late membranous desquamation of the fingertips. Early cardiac effects include myocarditis (occasionally with congestive heart failure), pericardial inflammation, and, rarely, valve involvement. Coronary artery aneurysms are a long-term concern because coronary thrombosis with myocardial infarction can be a late manifestation. The origin of Kawasaki disease is unknown, but an infectious agent is most likely. Management consists of aspirin for control of fever and inflammatory manifestations and intravenous gamma globulin for the prevention of coronary aneurysm formation. Careful late follow-up is required, especially for patients with persistent coronary abnormalities. Giant aneurysms (greater than 8 mm) are more likely to progress to coronary obstructive disease, and coronary bypass grafts have been required for some patients. Late coronary artery manifestations in patients with mild early coronary dilatation have not been described. However, since long-term epidemiologic studies have not yet been performed, it is prudent to consider childhood Kawasaki disease to be a potential risk factor for coronary disease, especially in atherosclerosis-prone Western societies. 
Characterization of in vivo expression of the human papillomavirus type 16 E4 protein in cervical biopsy tissues. The role of human papillomavirus (HPV) proteins in the pathogenesis of cervical intra-epithelial neoplasia (CIN) and invasive cervical cancer is poorly understood. To characterize E4 protein expression in 49 paraffin-embedded cervical biopsies representing different histopathologic grades of disease, antibodies were elicited to a synthetic peptide corresponding to amino acids 20-34 of a protein predicted to be encoded by the HPV 16 E4 open reading frame. The E4 protein was detected throughout the spectrum of CIN, from CIN1 to CIN3. Expression was localized to the cell nucleus, primarily in the superficial layers of the squamous cervical epithelium. Ultrastructural studies showed that the E4 protein was organized into compact, intranuclear arrays 25-35 nm in diameter. E4 protein expression was also demonstrated in some histologically normal tissues containing HPV 16 DNA, but not in any of five cervical cancers containing HPV 16 DNA. These results suggest that E4 protein expression may precede development of light microscopic tissue abnormalities, that it may continue through the spectrum of CIN, and that expression of this protein may be reduced or terminated in invasive cancer. The function of this protein remains unknown, but its nuclear localization may be consistent with a role in viral maturation. 
Discontinuation of lithium treatment in remitted bipolar patients: relationship between clinical outcome and changes in sleep-wake cycles. In this preliminary report, we describe four patients in whom long-term lithium therapy was discontinued, combined with actigraphic monitoring to assess changes in motor activity and the sleep-wake cycle. Two patients experienced rapid relapse of manic symptomatology, while two remained stable throughout a 1-year follow-up. Actigraphic monitoring revealed disintegration of the sleep-wake cycle and increased motor activity in the relapsed patients only. It is suggested that actigraphic recordings can be used to monitor lithium discontinuation. 
Conventional blood conservation techniques in 500 consecutive coronary artery bypass operations. With use of a nonpharmacological, simple, and inexpensive program for blood conservation, 500 consecutive patients underwent elective coronary artery bypass grafting without need of homologous red cell transfusions in 493 (98.6%). At least one internal mammary artery was grafted in all but 1 patient, with supplemental saphenous vein grafts. Intraoperatively, autologous heparinized blood was removed before bypass and retransfused at the conclusion of extracorporeal circulation. The volume remaining in the oxygenator and tubing set was returned without cell processing or hemofiltration. Using the hard-shell cardiotomy reservoir from the heart-lung machine, autotransfusion of the shed mediastinal blood was continued hourly up to 18 hours after operation. The mean postoperative mediastinal blood loss was 643 +/- 354 mL, whereas 624 +/- 296 mL was autotransfused. Thirteen patients (2.6%) needed reexploration for bleeding, of whom 7 (7/500, 1.4%) received homologous blood. No other patients required red cell transfusions. In addition, 9 patients were given a mean of 2.6 units of fresh frozen plasma because of suspected coagulopathy. No platelets were transfused, and no cryoprecipitate therapy was undertaken. Thus, in total, 484 patients (96.8%) were not exposed to any homologous blood products during the hospital stay. At discharge, the mean hemoglobin concentration was 121 +/- 14 g/L (12.1 +/- 1.4 g/dL) and the hematocrit, 0.36 +/- 0.04. Postoperative complications were few. There was one in-hospital death (0.2%). 
Natural history of gastro-oesophageal reflux disease without oesophagitis. This retrospective study was undertaken to characterise the clinical course and reflux pattern of patients with gastro-oesophageal reflux without evidence of oesophagitis. We investigated 33 patients (12 women, 21 men; mean age 36 years) with typical symptoms, a negative oesophagoscopy, and a 24 hour oesophageal pH-metry indicative of pathological gastro-oesophageal reflux. All patients received antacids or prokinetic drugs or both for three to six months. Nineteen of 33 patients still had symptoms at the end of treatment, of whom five had developed erosive changes of the oesophageal mucosa. The other 14 discontinued treatment and remained asymptomatic during a six month follow up period. Comparison of the pretreatment pH-metry data of the 19 symptomatic patients and the 14 asymptomatic patients showed no differences in the pattern of gastro-oesophageal reflux in the two groups. We conclude that in a substantial proportion of patients with pathological reflux without oesophagitis symptoms may persist and mucosal lesions may develop during conventional treatment without any apparent change in the reflux. Patients who developed endoscopic oesophagitis did not have a more severe pretreatment pattern of gastro-oesophageal reflux when compared with those who did not develop oesophageal mucosal damage. 
Copper loading of hearts increases postischemic reperfusion injury. We studied the role of copper as a potential mediator of postischemic reperfusion injury in the isolated, perfused rat heart. Hearts were equilibrated with Krebs-Henseleit buffer for 10 minutes and then loaded with copper by way of perfusion with buffer containing 20 microM copper(II)-bis-histidial for 30 minutes. Control hearts were perfused with Krebs-Henseleit buffer alone during the loading period. Hearts than were washed with buffer for 10 minutes and subjected to 20 minutes of normothermic global ischemia followed by 30 minutes of reperfusion. Atomic absorption spectroscopy revealed a 67% increase in total copper content in loaded hearts by the end of the wash. By the end of the 30-minute period of reperfusion, control hearts demonstrated a 50-60% recovery of myocardial function as determined by peak systolic pressure, contractility, and heart rate. In contrast, copper-loaded hearts exhibited virtually no functional recovery within the 30-minute time period. Using salicylate as a probe, we determined that peak and duration of .OH formation appears to be increased in copper-loaded hearts during reperfusion. Furthermore, efflux of lactic dehydrogenase was significantly increased in copper-loaded hearts. Our results clearly demonstrate that increasing cardiac content of copper results in enhanced postischemic reperfusion injury associated with increased formation of .OH, thus suggesting an important catalytic role for this transition metal. 
Gastric cancer in Scotland: changing epidemiology, unchanging workload. OBJECTIVE--To determine the changes in incidence of and mortality from gastric cancer in Scotland between 1978 and 1987 and in the operative workload in Lothian between 1979 and 1988. DESIGN--Analysis of national incidence statistics for gastric cancer derived from the Scottish national cancer registry, deaths from gastric cancer recorded by the registrar general for Scotland, and Lothian surgical audit data. SETTING--Scotland and Lothian Health Board area. PATIENTS--Patients in Scotland with gastric cancer during 1978 to 1987 inclusive; patients in Scotland with gastric cancer recorded on their death certificate as cause of death during 1978 to 1987; patients who had an operation in Lothian for gastric cancer during 1979 to 1988. MAIN OUTCOME MEASURES--Changes in incidence of and mortality from gastric cancer in Scotland from 1978 to 1987 and in the number of operations performed for gastric cancer in Lothian from 1979 to 1988. RESULTS--Mortality from gastric cancer in Scotland fell by about 25% over the 10 years. The incidence and standardised incidence of gastric cancer showed a marginal decline of about 9%. The differences in trends between incidence and mortality were significant (p less than 0.05). CONCLUSIONS--This study shows that the surgical workload associated with gastric cancer is not declining. This is because the incidence has remained almost static, which may be due to the relative increase in the numbers of older people in the population, who are at greater risk of developing gastric cancer. Gastric cancer should not be regarded as a disease in decline. Incidence and workload should determine resources allocated to this disease rather than mortality statistics. 
Mucin-hypersecreting tumor of the pancreas with mucin extrusion through an enlarged papilla. Patient records, imaging films, macroscopic and microscopic features, and clinical follow-up data of seven Japanese patients with a mucin-hypersecreting tumor of the pancreas were reviewed. The mucin-hypersecreting tumor was defined as an enlarged major or minor papilla with a dilated orifice and visible mucin oozing on endoscopy. The series consisted of six men and one woman ranging from 47 to 79 yr old. The excretion of mucin through a patulous orifice of the enlarged ampulla of Vater was seen in six patients and of the enlarged minor papilla in the other patient with pancreas divisum. The main pancreatic duct was dilated in all patients. Amorphous mucin was seen in the dilated duct of five patients, and papillary nodules were present in two patients. Computed tomography and/or ultrasonography showed dilatation of the main pancreatic duct with multilocular cysts in six patients and with a solid tumor in the other patient. The tumor was located diffusely in the main pancreatic duct in one patient, whereas it was confined to branches in the head (four patients), body (one patient), or tail (one patient) of the pancreas in the six other patients. Histopathologic diagnosis was a cyst lined by hyperplastic mucus-secreting epithelium in one patient, mucinous cystadenoma in two, and mucinous cystadenocarcinoma in two. Five patients underwent resection and have survived for 1-46 months after the operation. The authors would like to emphasize this endoscopic syndrome because about half of mucin-hypersecreting tumors are malignant with a favorable prognosis. 
The correlation between immunological reaction in the arterial wall and the time course of the development of cerebral vasospasm in a primate model. To investigate the role of immunological reactions in the development of cerebral vasospasm after subarachnoid hemorrhage (SAH), the authors studied the correlation between immune/inflammatory reactions in the arterial wall and the time course of vasospasm in primates. Twenty monkeys were divided into four groups of 5 animals each: 1) a control group of sham-operated animals, 2) animals subjected to angiography 3 days after the induction of SAH (3-day SAH), 3) animals subjected to angiography 7 days after SAH (1-week SAH), and 4) animals subjected to angiography 7 and 14 days after SAH (2-week SAH). To induce SAH, the main cerebral arteries on the right were dissected free of the arachnoid, and an autologous blood clot was placed around the arteries. To evaluate vasospasm, all animals underwent a baseline angiogram before SAH; angiography was repeated at different intervals in each group, as outlined above. Histopathological changes and the deposition of the immunoglobulin IgG in the arterial wall were evaluated immunohistochemically in each group. The cerebral arteries on the side of the clot showed evidence of mild vasospasm (-24.6% reduction) on the angiogram performed on Day 3, severe vasospasm (-51.7%) on Day 7, and mild vasospasm (-12.8%) on Day 14. The infiltration of inflammatory cells was most marked in the spastic arterial wall in the 1-week SAH group. In the 2-week SAH group, severe myonecrosis and intimal disruption were observed, even in the vessels that showed only mild vasospasm, and the inflammatory reactions had almost abated. 
Decreasing survival benefit from cardiac transplantation for outpatients as the waiting list lengthens. Many patients are accepted for cardiac transplantation during a period of clinical instability associated with a high risk of death, even though most can be discharged home to await transplantation. As the waiting lists lengthen, priority is awarded solely on the basis of the waiting time of outpatients, who now usually undergo transplantation after they have already survived a major period of jeopardy. To determine the impact of the current waiting times and priority system on the previously expected benefit offered by transplantation, 1-year actuarial survival without transplantation was recalculated after each month without transplantation for 214 potential candidates with an ejection fraction of 0.17 +/- 0.05 discharged on tailored medical therapy after evaluation. These data were compared with the 1-year survival data of 88 outpatients who underwent transplantation. Actuarial survival after 1 year was 67% on tailored therapy compared with 88% after transplantation (p = 0.009). Death without transplantation was sudden in 43 of 51 patients, resulting from hemodynamic decompensation in 8. For outpatients already surviving 6 months without transplantation, actuarial survival over the next 12 months was 83% without transplantation. Thus, the expected improvement in survival after transplantation would be only 5% over the subsequent year for patients waiting 6 months, which is the waiting time for many outpatients. Such patients should be reevaluated to determine whether transplantation remains indicated during the next year. 
Occipital meningoceles in patients with the Dandy-Walker syndrome. Occipital cephaloceles in the Dandy-Walker syndrome are not rare. To date, 28 cases have been reported. We report on 8 cases of associated occipital meningocele, totalling 16% of all patients with the Dandy-Walker syndrome in our series. In all patients, communication existed between the posterior fossa cyst and the occipital meningocele. In 2 patients, the occipital meningocele disappeared after cerebrospinal fluid shunting and never required surgical repair. It appears that the cranial defect had ossified and resulted in self-closure. Poor intellectual development in persons with the Dandy-Walker syndrome is associated with the presence of other central nervous system and systemic abnormalities and not with occipital meningoceles alone. 
Application of intermediate biomarkers to studies of cancer prevention in the gastrointestinal tract: introduction and perspective. In this article, abnormalities in the proliferation and differentiation of gastrointestinal cells are described in diseases that increase predisposition to gastrointestinal cancer. Recent findings related to the effects of calcium on gastrointestinal cell proliferation, differentiation, and tumor occurrence in rodent models and in human subjects are summarized. 
Nutritional support of patients with cancer of the gastrointestinal tract. Malnutrition is extremely common in patients with malignant disease. Whereas the causes are multifactorial, the predominant factor is the imbalance between nutrient intake and host nutrient requirements. Furthermore, the evidence suggests that cachexia is related to abnormal changes in host intermediary metabolism induced by host-tumor interactions, and endogenous peptides such as TNF may be important mediators. The role of nutritional therapy in cancer patients remains to be defined. Clearly, patients with severe malnutrition benefit from nutritional intervention. However, the benefit of nutritional therapy in less severe cases of malnutrition as an adjuvant to oncologic therapy has yet to be established. 
Carpal tunnel syndrome: objective measures and splint use. One hundred five adults with carpal tunnel syndrome (CTS) were studied to assess the efficacy of a neutral-angle wrist splint, and to identify criteria for splint referral. Ten observations before and after treatment were analyzed with descriptive and inferential statistics. After splint use, 67% of the subjects reported symptom relief. T-test comparison of sensory latency of values before and after treatment indicated improvement for the total group. Chi-square and t-tests failed to reveal significant differences between relief and no-relief groups for gender, affected hand, presence of concomitant conditions, duration of symptoms before treatment, age, length of time between pretreatment and posttreatment nerve conduction testing, initial nerve latency of motor and sensory fibers, or the difference between pretreatment and posttreatment sensory latencies. A significant difference was found for motor latency; the relief group improved and the no-relief group deteriorated. Data suggest that splinting is most effective if applied within three months of symptom onset. Those with damage to the wrist structures or median nerve were least responsive to splinting. 
Short-term antibiotic treatment in Whipple's disease. We report the results of short-term antibiotic treatment in 19 patients with Whipple's disease (WD). The diagnosis was based on clinical features and on a characteristic small bowel biopsy. Patients received treatment for a mean of 7.9 weeks (range 4-20). Fourteen were treated with de-methyl-chlortetracycline (600 mg/day), and 1 also received chloramphenicol (1 g/day); 1 was treated with ampicillin (2 g/day), and 4 were treated with amoxicillin (1.5 g/day). In all patients, the clinical response was rapid and excellent, body weight increased significantly, diarrhea subsided, and fecal fat values returned to normal. Intestinal biopsies obtained after treatment was completed showed significant improvement based on a decrease in the number of macrophages staining positive with periodic acid-Schiff (PAS), normalization of villous structure, and decreased dilatation of lymphatic channels; free bacilli were absent, as shown both by light and electron microscopy. Seventeen patients have been followed for a mean of 99.4 months (range 6-300). Two died 30 and 72 months after diagnosis of Whipple's disease, 1 of laryngeal carcinoma and the other of colonic carcinoma. Fifteen patients are in excellent health. Three patients treated with tetracycline have had clinical and/or histologic relapses. In our experience, short-course antibiotic treatment with tetracycline or ampicillin and derivatives can be effective in WD, with few relapses and excellent outcome. No neurologic symptoms, either initially or during follow-up were observed. 
Prevalence of dementia in the 'oldest old' of a Dutch community. OBJECTIVE: To estimate the prevalence rate of dementia in subjects 85 years of age and over. DESIGN: A two-phase design with the Mini-Mental State Examination (MMSE) in the screening phase and the Geriatric Mental State Schedule (GMS) in the diagnostic phase. SETTING: Community survey including subjects in residential care. SUBJECTS: All (n = 1,259) inhabitants of Leiden, The Netherlands, aged 85 years and over on December 1, 1986. First phase participation rate was 71% (17% dropout due to death); second phase participation rate was 82%. MAIN OUTCOME MEASURE: DSM-III diagnosis of dementia without further specification of the etiology of the dementia. RESULTS: An overall prevalence rate of 23% (95% C.I.: 19%-26%) was found. This included 12% mild dementia, 7% moderate and 4% severe dementia. The prevalence rate was higher among women (24%) than among men (18%). It increased with age from 19% (95% C.I.: 16%-22%) in the group of 85-89 years to 32% (95% C.I.: 26%-39%) in the group of 90-94 years to 41% (95% C.I.: 25%-58%) in the 95+ group. CONCLUSION: A fifth of the 85+ and a third of the 90+ population suffer from dementia with an indication that half of the 95+ population is affected. With the expected steep rise in the number of the oldest old, dementia will stay a major health problem in the near future. 
Mastoid misery: quantifying the distress in a radical cavity. Seventy-eight mastoid cavities were studied in 39 patients who required revision surgery for troublesome symptoms. A retrospective questionnaire was used to assign a symptom score to each patient in his pre and post-operative condition. The 5 leading symptoms of pain, wax, discharge, smell and giddiness were reviewed. A score of 15 points represented the worst case and zero the best. The average improvement after surgery was 4.7 points. Hearing was not considered in this study. 
Efficacy and cost effectiveness of adjuvant chemotherapy in women with node-negative breast cancer. A decision-analysis model. BACKGROUND. In 1988 the National Cancer Institute issued a Clinical Alert that has been widely interpreted as recommending that all women with node-negative breast cancer receive adjuvant chemotherapy. Acceptance of this recommendation is controversial, since many women who would not have a recurrence would be treated. METHODS. Using a decision-analysis model, we studied the cost effectiveness of chemotherapy in cohorts of 45-year-old and 60-year-old women with node-negative breast cancer by calculating life expectancy as adjusted for quality of life. The analysis evaluated different scenarios of the benefit of therapy: improved disease-free survival for five years, with a lesser effect on overall survival (base line); a lifelong benefit from chemotherapy; and a benefit in disease-free survival with no change in overall survival by year 10. The base-line analysis assumed a 30 percent reduction in the relative risk of recurrence for five years after treatment. RESULTS. For the 45-year-old woman, the base-line analysis found an average lifetime benefit from chemotherapy of 5.1 quality-months at a cost of $15,400 per quality-year. The 60-year-old women gained 4.0 quality-months at a cost of $18,800 per quality-year. Under the more and less optimistic scenarios, the benefit of chemotherapy varied from 1.4 to 14.0 quality-months for both groups. CONCLUSIONS. Chemotherapy substantially increases the quality-adjusted life expectancy of an average woman at a cost comparable to that of other widely accepted therapies. This benefit decreases markedly if the changes in long-term survival are less than in disease-free survival. Given its uncertain duration, the benefit may be too small for many women to choose chemotherapy. Selective use of chemotherapy to maximize the benefit to individual patients may be possible with refinements in risk stratification and explicit assessment of the patients' risk preferences. 
Civilian craniocerebral gunshot wounds. Experience with 120 patients who incurred a gunshot wound to the head with dural penetration is presented. All of the patients were managed by a standard resuscitation protocol and assigned a clinical grade based on their level of consciousness both at the time of presentation and at 2 to 4 months after injury. Fifty patients (42%) underwent surgery. Twenty-eight patients (23%) had a good recovery, 19 (16%) were moderately disabled, 6 (5%) were severely disabled, and 67 (56%) died. All patients who were alert and awake with a normal or near normal neurological examination at the time of admission survived with a good outcome. All but 4 patients who were comatose at the time of admission died. Nine patients, however, who were not comatose at the time of admission died from potentially preventable causes. In 3 of these patients, a more aggressive diagnostic approach (including cerebral angiography) may have altered their ultimate outcome. An expeditious approach to the trauma victim with a comprehensive management scheme after injury may have altered the course in the remainder of these patients. 
Total androgen ablation: European experience. The EORTC GU Group. Zoladex plus flutamide significantly delays the time to progression (subjective, objective, first progression) compared with orchiectomy, but no difference in survival (death from all causes or from malignant disease) could be detected. Thus, a delay in the appearance of progression has not improved survival. In fact, the duration of survival after progression tends to be shorter on Zoladex plus flutamide. There is thus no evidence to suggest any survival benefit with Zoladex plus flutamide. The quality control of our data revealed acknowledged problems in defining responses in patients with advanced prostate cancer. The review of the Bone Scan Committee provided the data for Tables 5 to 7. These data must provoke some reflections and emphasize once again the heterogeneity of the studied patient population. Table 4 on pain response after 4 weeks is just one of the many items to be analyzed by the committees for response criteria and quality of life. We expect that the other trials face similar problems. More work and patience are needed to obtain a firm answer to this clinical problem. These efforts will never be wasted, however, because the combined results of these trials will increase our knowledge of the treated history of prostate cancer and will, we hope, indicate a net treatment benefit in some subsets of patients. An individually tailored treatment for each patient selected from the anonymous mass of cases of advanced prostate cancer would be the highest reward of our continued collaboration with all the study groups. 
Use of modified diets in nursing homes. Randomly chosen medical charts of 212 elderly subjects in 11 nursing homes were reviewed to determine which characteristics of the subjects were most closely associated with their diet prescriptions. The chart reviews indicated that 104 (49.0%) of the 212 subjects had some type of nutrient-modified diet prescription. Eight patients who were tube fed were not included in subsequent analyses. Sodium restriction was the most common modification (60 [29.4%] of the remaining 204 patients) and calorie-controlled diets were also common (52 [25.5%] of the patients). Of the 55 patients with hypertension, 31 (56.4%) had no sodium restriction. Only 10% of all low-sodium diets limited sodium to 2 g per day. Of the 38 patients with diabetes, 7 (18.4%) had no prescription for calorie control, and there was no indication that increased dietary fiber was encouraged for diabetic patients. Only one of the 121 subjects with a diagnosis of coronary heart disease or atherosclerosis had a prescription for a cholesterol-lowering diet. Characteristics of the subjects not specifically related to diet or diagnosis, such as age, sex, duration of stay, and level of care, had no significant relationship to diet prescription. These findings suggest that the practitioners in our sample were not convinced of the efficacy of modified diets to control disease for most nursing home residents. 
Thoracoscopic carbon dioxide laser treatment of bullous emphysema. A new technique of thoracoscopic laser ablation of pulmonary bullae suitable for patients with multiple bullae and diffuse emphysema was developed and assessed in 22 patients. 20 of 22 patients survived. Pre-operative and postoperative functional evaluation is available for the 11 patients followed up for more than a month; at 1 to 3 months postoperatively there were increases in FVC (mean 2.0 litres pre-operatively to 2.7 litres postoperatively, p less than 0.001), in FEV1 (0.74 to 1.06 litres, p = 0.01), and in maximum exercise treadmill times (5.4 min to 8.0 min, p less than 0.01). Postoperative air leaks lasted a mean of 13 days and usually resolved spontaneously. Other complications were bleeding (1 patient) and unilateral acute lung injury (1 patient). These results suggest that selected patients with diffuse emphysema and pulmonary bullae may benefit from thoracoscopic carbon dioxide laser ablation. 
Methotrexate and histologic hepatic abnormalities: a meta-analysis. STUDY OBJECTIVE: To determine the risk of liver toxicity from the long-term administration of methotrexate in patients with rheumatoid arthritis or psoriatic arthritis. DESIGN: A meta-analysis of 15 studies examining the relationship between long-term, low-dose methotrexate administration and biopsy evidence of liver fibrosis. PATIENTS: A total of 636 patients from 15 studies. RESULTS: The incidence of progression of liver disease (defined as worsening of at least one grade on the histologic classification of Roenigk) among 636 patients was 27.9% (95% confidence intervals 24.3 to 31.6). The rate of progression of liver disease in the 15 studies was associated with the cumulative dose of methotrexate (p = 0.01). Patients on average had a 6.7% (95% confidence intervals 2.1 to 11.4) chance of progressing at least one histologic grade on liver biopsy for each gram of methotrexate taken. The overall incidence of advanced pathologic changes on liver biopsy (grades IIIB or IV) among 636 patients was 5.0% (95% confidence intervals 3.5 to 7.0). The development of advanced histologic changes was not associated with the cumulative dose of methotrexate (p = 0.08). Patients who according to their history were heavy drinkers (at least 100 g of alcohol per week) were more likely to have advanced changes on liver biopsy (17.8% versus 4.5%, p = 0.0003) and to show histologic progression (73.3% versus 25.9%, p = 0.0002). Patients with psoriasis were more likely than patients with rheumatoid arthritis to have advanced changes (7.7% versus 2.7%, p = 0.003) and histologic progression (33.1% versus 24.3%, p = 0.02). CONCLUSIONS: The risk of liver toxicity in patients undergoing long-term, low-dose methotrexate therapy is substantial, and that risk increases with the total cumulative dose and with heavy consumption of alcohol. Heavy users of alcohol should not receive long-term methotrexate therapy. For most patients who are not heavy users of alcohol, liver biopsies should be done periodically to monitor for the occurrence of liver toxicity. 
A practical guide to nitrate use. Nitrate preparations are useful in the treatment of acute and chronic angina, acute and chronic congestive heart failure, and acute myocardial infarction. Development of tolerance is best managed by providing a nitrate-free interval, thus avoiding continuous drug levels. This interval probably should be 10 to 12 hours with use of a transdermal patch. Nitrate treatment of the elderly may require lower doses to avoid hypotension. 
Radial nerve paralysis and tumor. This paper presents ten cases of radial nerve paralysis because of tumor and reviews 38 previously reported cases. The tumor distribution was 35 lipomas, four neurofibromas, four ganglions, three neuromas, one fibroma, and one neurilemoma. Malignant tumors are not discussed in this review. Electromyography is of value if diagnostic problems occur. Postoperative results are normally good. 
Massive ST-segment elevation without myocardial injury in a patient with fulminant hepatic failure and cerebral edema. A 49-year-old woman presented in fulminant hepatic failure. The ECG showed dramatic ST-segment elevation, suggesting diffuse myocardial injury. However, echocardiography, creatine phosphokinase enzyme determinations, and examination of the heart at autopsy (six days later) failed to demonstrate any physiologic, anatomic, or histologic evidence of abnormality. The appearance of ST-segment elevation in this setting should not prompt treatment for cardiac disease or limit the candidacy for liver transplantation of such critically ill patients. 
Mononeuropathy in sickle cell anemia: anatomical and pathophysiological basis for its rarity. Peripheral neuropathy is a rare complication of sickle cell disease. We report a young black woman with sickle cell anemia who developed a proximal median mononeuropathy in the setting of sickle cell crisis. The clinical and electrodiagnostic features are consistent with an ischemic mechanism from the sickling process. The pathophysiological basis for the rarity of this complication may be related to the rich anastomotic microvasculature of peripheral nerve and the unique large size of the capillaries of this vascular network. 
Scleral buckling for rhegmatogenous retinal detachment associated with severe myopia. From Jan. 1, 1980, to Dec. 31, 1989, we performed scleral buckling surgery on 48 eyes of 46 patients for rhegmatogenous retinal detachments associated with severe myopia (greater than 5.00 diopters). Forty eyes of 38 patients were observed for at least six months, and the mean follow-up period was 46 months. Intraoperative complications occurred in four of 48 eyes (8%) and included retinal incarceration (two eyes), choroidal hemorrhage (one eye), and choroidal detachment (one eye). Three of the 40 eyes (7.5%) followed up for more than six months developed a recurrent retinal detachment and underwent a revision of the scleral buckle. At the last follow-up examination, the retinas of all 40 eyes were totally reattached. Final visual acuity of 20/40 or better was attained in 26 of 40 eyes (65%). Because of the low rate of intraoperative complications and the high rate of success, scleral buckling is recommended for most patients with rhegmatogenous retinal detachments associated with severe myopia. 
Cost-effectiveness analysis of mass screening for breast cancer in Japan. The official Japanese recommendation for breast cancer screening is physical examination by a physician, in contrast to US recommendations of mammography. In this analysis of breast cancer screening, the authors used Japanese data in a cost-effectiveness model to compare the following five strategies: (1) no screening (N); (2) physical examination alone (PE); (3) mammography (MG); (4) PE followed by MG if PE findings were abnormal (PE----MG); and (5) PE combined with MG for all screened women (PE + MG). None of these programs would save medical expenditures. The total discounted net costs per patient (in US dollars) were as follows: N, +54; PE, +412; MG, +517; PE----MG, +340; and PE + MG, +731. The number of years of life saved per cohort of 100,000 asymptomatic Japanese women would range from 708 (PE----MG) to 3724 (PG + MG). The additional cost of each strategy (compared with N) per additional year of life would be +49,700 for PE, +40,400 for PE----MG, +14,300 for MG, and +18,000 for PE + MG. The least costly screening option (PE----MG) does not have the lowest cost per additional year of life saved (MG does). MG would be preferable to the current Japanese recommendation of PE alone. 
C-erbB-2 oncogene protein in in situ and invasive lobular breast neoplasia. Lobular carcinoma in situ (LCIS) has uncertain malignant potential; biologic markers that will identify patients at risk for a poor clinical outcome have been sought actively. Amplification of the c-erbB-2 protooncogene has been correlated with poor prognosis in invasive mammary carcinoma, and immunohistochemical evaluation for expression of the oncogene protein has been correlated with gene amplification. The authors retrospectively evaluated 62 cases of lobular neoplasia for expression of the c-erbB-2 gene product on formalin-fixed, deparaffinized sections, using two monoclonal anti-erbB-2 (p185) antibodies (c-neu Ab3 and m-erb) and one polyclonal anti-erbB-2 antibody (pAb 1) by the avidin-biotin-peroxidase method. All 62 cases were negative with the pAb 1 antibody; one of 62 cases was weakly positive with the c-neu Ab3 in a membranous pattern. Expression of c-erbB-2 gene product was identified on adjacent invasive ductal carcinoma in one case and in adjacent ductal carcinoma in situ in another. None of 15 cases if infiltrating lobular carcinoma was positive with either of the two anti-c-erbB-2 antibodies. Strong positivity was found on benign epithelium in one case, demonstrating epitheliosis. In summary, evidence of expression of the c-erbB-2 gene product was found in one of 57 cases of LCIS and none of 15 cases of invasive lobular carcinoma. This suggests that, in contrast to reported data concerning intraductal and invasive ductal carcinoma, c-erbB-2 oncogene amplification and/or overexpression does not play a significant role in the progression of lobular breast neoplasia. 
Carcinoembryonic antigen and head and neck cancer. Carcinoembryonic antigen (CEA) concentrations were determined in the sera of 45 patients with a head and neck squamous cell carcinoma and of 13 controls. In 13 patients serial CEA measurements were made during the follow-up period. In 38% of the patients the serum CEA level was slightly elevated (greater than or equal to 2.5 ng/ml). Only 13% of the patients had clearly elevated CEA levels (greater than 5 ng/ml). CEA levels were significantly higher in patients with advanced, e.g. stage IV, disease but a correlation between serum CEA concentration and prognosis was not found. Patients who smoked had significantly higher serum CEA levels than non-smoking patients. In the serial determinations slight CEA elevations could be found in only 50% of patients with tumour recurrence. Combined with the data from the literature we conclude that serum CEA determination is not useful in predicting the outcome in patients with a head and neck squamous carcinoma. 
Spinal cord herniation associated with an intradural spinal arachnoid cyst diagnosed by magnetic resonance imaging. Two rare cases of spinal cord herniation associated with intradural spinal arachnoid cyst are reported. A preoperative magnetic resonance imaging scan demonstrated the presence of spinal cord herniation, identified as a protrusion continuous with the spinal cord. Surgery upon the intradural spinal arachnoid cyst improved progressive neurological dysfunction. The authors postulate that spinal cord herniation occurred for the following reason: The pressure of the intradural arachnoid cyst on the dorsal aspect of the spinal cord caused thinning of the dura, leading to a tear and, thus, the development of an extradural arachnoid cyst. Along with the enlargement of intradural arachnoid cyst, the spinal cord herniated through the tear in the dura into the extradural arachnoid cyst. 
Intraluminal pulsed Doppler evaluation of the pulmonary artery velocity time curve in a canine model of acute pulmonary hypertension. The velocity pattern of the blood flow in the pulmonary artery was investigated in an animal model of acute pulmonary hypertension. Nine anesthetized, open-chest dogs were embolized with polystyrene microspheres, and the velocity pattern of the blood flow in the pulmonary artery was studied with use of an invasive pulsed Doppler technique. Phasic intraluminal velocity was recorded with use of a miniature piezoelectric crystal activated by 20-MHz Doppler pulses and mounted on the tip of a needle probe introduced into the pulmonary artery. The recorded Doppler quadrature signals were processed by spectral analysis. Significant increases occurred in mean, systolic, and diastolic pulmonary arterial pressures (p less than 0.0002), in pulmonary vascular resistance (p less than 0.005), and in negative velocity time (duration in milliseconds that the mean velocity was directed toward the pulmonic valve) (p less than 0.002). Significant decreases occurred in right ventricular ejection time (p less than 0.006) and in positive velocity time (duration in milliseconds that the mean velocity was directed away from the pulmonic valve) (p less than 0.005). A significant shortening in the time to peak velocity (acceleration time) was found (p less than 0.005). Second-order regression analyses demonstrated an inverse correlation between the ratio of positive velocity time to negative velocity time and the mean pulmonary artery pressure in all animals (r = 0.71). These findings should be compared with the velocity patterns of the blood flow in the pulmonary artery obtained under pulmonary hypertensive conditions due to various causes to facilitate interpretation and understanding of clinical investigations. 
Energy state and vasomotor tone in hypoxic pig lungs. To evaluate the role of energy state in pulmonary vascular responses to hypoxia, we exposed isolated pig lungs to decreases in inspired PO2 or increases in perfusate NaCN concentration. Lung energy state was assessed by 31P nuclear magnetic resonance spectroscopy or measurement of adenine nucleotides by high-pressure liquid chromatography in freeze-clamped biopsies. In ventilated lungs, inspired PO2 of 200 (normoxia), 50 (hypoxia), and 0 Torr (anoxia) did not change adenine nucleotides but resulted in steady-state pulmonary arterial pressure (Ppa) values of 15.5 +/- 1.4, 30.3 +/- 1.8, and 17.2 +/- 1.9 mmHg, respectively, indicating vasoconstriction during hypoxia and reversal of vasoconstriction during anoxia. In degassed lungs, similar changes in Ppa were observed; however, energy state deteriorated during anoxia. An increase in perfusate NaCN concentration from 0 to 0.1 mM progressively increased Ppa and did not alter adenine nucleotides, whereas 1 mM reversed this vasoconstriction and caused deterioration of energy state. These results suggest that 1) pulmonary vasoconstrictor responses to hypoxia or cyanide occurred independently of whole lung energy state, 2) the inability of the pulmonary vasculature to sustain hypoxic vasoconstriction during anoxia might be associated with decreased energy state in some lung compartment, and 3) atelectasis was detrimental to whole lung energy state. 
Effect of early programmes of high and low intensity exercise on physical performance after transmural acute myocardial infarction. Does a programme of light exercise training after acute myocardial infarction produce the same improvement in treadmill performance as aerobic exercise training? Three hundred and eight men from a consecutive series of 479 men with transmural (Q wave) acute myocardial infarction, admitted to a single coronary care unit, were randomly allocated to eight weeks of group aerobic exercise training or group light exercise. Groups were well matched for all characteristics other than site of infarction, which did not significantly affect results. Mean (SD) physical working capacity (metabolic equivalents) determined by treadmill testing at the start of the study (in the third week after infarction) was 6.8 (2.2) v 6.7 (2.5) METs, at the end (in the eleventh week after infarction) 10.8 (2.3) v 9.9 (2.4) METs, and at 12 month review 10.8 (2.4) v 10.7 (1.9) METs for the exercise training group and the light exercise group respectively. The difference of 0.9 METs at the end of the study was the only significant difference between groups. There were no significant intergroup differences at any stage in resting and maximal heart rate, resting and maximal systolic blood pressure, or rate-pressure product. Apart from a small temporarily greater physical working capacity, the physical benefits of aerobic exercise training were equally well achieved by group light exercise. 
High nocturnal body temperature in premenstrual syndrome and late luteal phase dysphoric disorder. OBJECTIVE: Because women with late luteal phase dysphoric disorder (LLPDD) experience symptomatic affective states predictably, they can be studied to determine whether there are biological findings related solely to the clinically symptomatic state. The authors sought to answer the question, Does body temperature change with affective state? METHOD: The core body temperature and motor activity patterns of 10 women with premenstrual syndrome (PMS), six of whom also met criteria for LLPDD, and no other psychological or medical illness were compared to those of six women with chronic, noncyclic dysphoria and six asymptomatic comparison women at four phases of the menstrual cycle. RESULTS: The nocturnal temperatures of the women with PMS/LLPDD were significantly higher than those of the comparison subjects across the entire menstrual cycle, but there were no differences in nocturnal activity levels. The women with noncyclic dysphoria had a mean nocturnal temperature in the follicular phase as high as that of the women with PMS/LLPDD. The temperatures of all women were higher in the luteal phase than in the follicular phase. CONCLUSIONS: These findings suggest that in the future investigators should document menstrual cycle phase in all female subjects and, when studying body temperature, should carefully monitor symptomatic state in comparison subjects. 
Particular HLA-DQ alpha beta heterodimer associated with IDDM susceptibility in both DR4-DQw4 Japanese and DR4-DQw8/DRw8-DQw4 whites. Insulin-dependent diabetes mellitus (IDDM) susceptibility is associated with the DR4-DQw4 haplotype in Japanese and the DR4-DQw8/-Drw8-DQw4 genotype (among others) in whites. We investigated whether these Japanese and white individuals encode the same or a similar DQ alpha beta heterodimer, which may be an IDDM-susceptibility molecule in both populations. First, we carried out genomic DQA1 and DQB1 typing with sequence-specific oligonucleotide probes. The results revealed that Japanese DR4-DQw4 and white DR4-DQw8/DRw8-DQw4 IDDM patients carried the DQA1*0301 allele and the DQB1*0401 or DQB1*0402 allele, either in the cis (Japanese DR4-DQw4 individuals) or trans (white DR4-DQw8/DRw8-DQw4 individuals) position. Because the DQB1*0401 and DQB1*0402 alleles differ only at residue 23, these DQB1 genes are very similar. We next tested cells from these individuals with a particular DQ-specific T-lymphocyte clone, HH58. The clone was only restimulated with cells from Japanese individuals who carried the DQA1*0301 and DQB1*0401 alleles in the cis position or white individuals who carried the DQA1*0301 and DQB1*0402 alleles in the trans position. Thus, particular cis- or trans-encoded DQ alpha beta heterodimers, which in both cases are recognized by T lymphocytes, may confer susceptibility to IDDM in both ethnic groups. 
Endoscopic treatment by snare electrocoagulation prior to Nd:YAG laser photocoagulation in 85 voluminous colorectal villous adenomas. The association of endoscopic resection with Nd:YAG laser photocoagulation was used to treat benign colorectal villous adenomas. Eight-five patients were included: 49 with surgical contraindications, 35 for whom surgical resection appeared to be too hazardous, and 1 who refused surgery. Forty-five tumors had an axial extension between 1 and 3 cm, and 40 tumors had an axial extension of at least 4 cm. Diathermic snare resection was performed to remove large tumoral fragments prior to laser photocoagulation of the residual flat lesions. Treatments were repeated every 15 days until total tumor destruction was achieved. A carcinoma was detected in biopsy specimens obtained during endoscopic treatment of five patients. Two patients were lost to follow-up. Treatment results could be analyzed in 78 patients. Successful treatment was achieved in 67 patients. Tumor destruction was complete in 77 percent of patients who had lesions of at least 4 cm diameter and in 93 percent of patients with smaller lesions. The axial extension of the tumor was the main factor affecting the results of treatment. No major complications occurred. During the average 103-week follow-up period, 21 percent of the patients with total tumor destruction had a recurrence. The risk of recurrence was correlated with the number of initial treatment sessions and previous surgery treatment. It would appear that the treatment with endoscopic resection prior to Nd:YAG laser photocoagulation is a safe and effective method in the destruction of colorectal villous adenomas. 
Reference systems in echocardiographic quantitative wall motion analysis with registration of respiration. Registration of respiration allows analysis at the end-expiratory phase and may thus favor the use of the fixed-reference system versus the floating-reference system in echocardiographic quantitative wall motion analysis. Analysis is performed on two-dimensional echocardiograms of 44 normal subjects, 38 patients with anterior myocardial infarction, and 17 patients with posterior myocardial infarction. Two different models for wall motion analysis are applied, each using the fixed-reference system and the floating-reference system, respectively. In patients with anterior myocardial infarction, the fixed-reference system indicates severe wall motion abnormalities at the anterior, septal, and apical walls, whereas the floating-reference system indicates less severe wall motion abnormalities almost equally at every wall. In patients with posterior myocardial infarction, the fixed-reference system indicates severe wall motion abnormalities at the posterior wall, whereas the floating-reference system indicates less severe wall motion abnormalities almost equally at every wall. These findings indicate that the fixed-reference system is superior to the floating-reference system in quantification of wall motion of end-expiratory two-dimensional echocardiograms. 
Comparison of speed of onset of analgesic effect of diamorphine and morphine. In a random, double-blind crossover trial using an ischaemic limb pain model we have assessed the speed of onset of analgesia after an i.v. bolus of equipotent doses of diamorphine and morphine in 12 healthy male volunteers. Pain and its subsequent relief were assessed by means of a visual analogue scale. Two of the subjects found diamorphine acted quicker than morphine, one found no difference and nine found that morphine was quicker than diamorphine. The mean time to diamorphine effect was 53% greater than for morphine (P less than 0.005, Wilcoxon rank sum test). These findings suggest that, for rapid relief of pain, morphine is more suitable than diamorphine. 
New autonomic and sensory neuropathy with loss of adrenergic sympathetic function and sensory neuropeptides. A 30-year-old woman with longstanding dizziness was found to have a severe postural fall in blood pressure and a reduced skin axon-reflex flare response. Autonomic tests indicated selective impairment of adrenergic sympathetic function. Plasma noradrenaline, adrenaline, dopamine, and dopamine beta hydroxylase were undetectable. Skin biopsy specimens showed loss of tyrosine hydroxylase and neuropeptide Y (markers of adrenergic sympathetic fibres) and of substance P and calcitonin gene-related peptide (sensory neuropeptides). A sural nerve biopsy specimen showed severe depletion of unmyelinated fibres. The constellation of losses were compatible with nerve growth factor (NGF) deprivation, which was confirmed on assay. This new syndrome may be explained by loss of trophic action of NGF. 
Left ventricular hypertrophy in hypertension. Major advances in left ventricular hypertrophy (LVH) and hypertension have occurred in recent years. The ability to diagnose LVH has been improved by echocardiography, and with this technique it has been shown that evidence of LVH is an important independent risk factor for cardiovascular disease. The major cause of death in patients with hypertension and LVH is coronary artery disease. Therefore an understanding of the interrelationships between these two disorders is fundamental, and it is now clear that the hypertrophied ventricle is vulnerable to myocardial ischemia. Appreciation of the mechanisms of sudden death has also increased, although the exact situation in patients with LVH remains to be clarified. Regression of LVH is known to occur with the use of several different antihypertensive drugs. Recent studies indicate that the calcium blocking agent nicardipine, in addition to beta-blocking drugs and angiotensin-converting enzyme inhibitors, brings about LVH regression without any deterioration of left ventricular function. However, further studies are needed to assess the long-term benefits of this regression. 
Compartment syndrome of the thigh with osteogenesis imperfecta. A case report. Compartment syndrome of the thigh has been sporadically reported in the orthopedic literature. A 27-year-old man with osteogenesis imperfecta sustained a femoral fracture with relatively minor trauma and subsequently developed compartment syndrome of the thigh. Fat embolism syndrome and hyperplastic callus developed postoperatively. 
Regression of hepatic metastases from gastrointestinal leiomyosarcoma after hepatic arterial chemoembolization. Two patients with gastrointestinal leiomyosarcoma metastatic to the liver were treated by hepatic chemoembolization with cisplatin and polyvinyl sponge followed by hepatic arterial infusion of vinblastine. Effective palliation in terms of durable tumor regression was achieved in both patients after two chemoembolization-infusion procedures. These results suggest that regional therapy may offer new hope for the subset of sarcoma patients who have liver metastases resistant to combination systemic chemotherapy. 
The Damus-Fontan procedure. The Damus-Kaye-Stansel operation is a useful technique for the treatment of complex cyanotic congenital heart disease when there is obstruction between the systemic ventricle and the aorta. Modifications of the technique include transection of the aorta and the pulmonary artery, anastomosis of the contiguous aortic and pulmonary walls, and connection of the distal aorta to the perimeter of the new bivalved proximal great artery. In addition, the bidirectional cavopulmonary shunt technique can be used with or without the Fontan procedure. Six patients underwent a Damus-Fontan operation, and all survived. Two patients underwent the Damus-cavopulmonary shunt (hemi-Fontan) procedure, and 1 survived. The postoperative status of the 7 survivors is good to excellent. Follow-up ranges from 2 months to 7 1/2 years. 
Anastomotic obstruction after stapled enteroanastomosis. We have recently treated two cases of anastomotic obstruction after side-to-side stapled enteroanastomosis. Complete obstruction of a stapled small-bowel anastomosis has not been reported to our knowledge. The mechanism of the obstruction appears to be the healing together of the cut edges of viable bowel beyond the inverted stapled lines. An alternative method of constructing the functional end-to-end enteroanastomosis that is offered is intended to prevent the occurrence of postoperative anastomotic obstruction. 
Epidemiologic aspects of shigellosis and other causes of dysentery in Thailand. Nearly 20% of children seen in the outpatient department of Children's Hospital in Bangkok, Thailand, for diarrheal disease had bloody diarrhea. Shigella species and enteroinvasive Escherichia coli--isolated from 13% and 2% of children with diarrhea, respectively--were the most frequent causes of bloody diarrhea. Campylobacter species and nontyphoidal Salmonella species were also isolated frequently but were much less often associated with bloody diarrhea. Shigella species were rarely isolated from patients who did not have diarrhea, while Campylobacter and Salmonella species were isolated frequently from well children. None of the species isolated always caused bloody diarrhea. Studies on infection with Campylobacter suggest that natural immunity may prevent bloody diarrhea and in fact may eventually prevent all disease due to this organism. Studies of endemic Shigella flexneri and epidemic Shigella dysenteriae 1 in Thailand have shown that immunity may also explain an age-related decrease in rates of S. flexneri infection but not in rates of S. dysenteriae 1 isolation. 
Cerebrovascular disease in hypertensive blacks. There is convincing evidence that all grades of persistent diastolic hypertension, especially in blacks, should be treated in order to prevent stroke and other cardiovascular complications. Studies are now in progress to gather additional information concerning isolated systolic hypertension, especially in the aged. Inasmuch as at least one half or more of stroke deaths in blacks develop as the result of hypertension, lowering blood pressure offers the perfect opportunity to reduce considerably the frequency of this devastating illness. The recent dramatic fall in U.S. stroke mortality, greatest in the black female, is a commendable achievement, but the flattening of the declining mortality curve over the past several years should be a cause for alarm and intensive investigation. 
Gastrointestinal lipomas: a radiologic and pathologic review. Lipomas of the gastrointestinal tract are an infrequent finding on radiologic examination; however, they occur often enough to warrant consideration in the differential diagnosis of mass lesions of the gut. In many instances, their morphologic characteristics allow the specific diagnosis of a lipoma. In this report, we review gastrointestinal lipomas with an emphasis on their radiologic and pathologic correlation. 
Spectrum of orthostatic disorders: classification based on an analysis of the short-term circulatory response upon standing. 1. In 31 consecutively referred patients (20 females, 11 males) with overt or suspected orthostatic disorders, the changes in blood pressure and heart rate that occur in the first 2 min of standing were analysed. 2. Blood pressure was measured continuously by Finapres. The blood pressure and heart rate responses after 1-2 min of standing (early steady-state response) were used to classify the patients as follows: group I (n = 17, age 42 +/- 17 years), normal early steady-state blood pressure and heart rate responses; group II (n = 5, age 40 +/- 14 years), combination of normal early steady-state blood pressure and postural tachycardia; group III (n = 9, age 51 +/- 14 years), hypotensive orthostatic response with (4/9) or without (5/9) postural tachycardia. We examined whether additional information could be obtained by beat-to-beat analysis of the initial circulatory response (first 30 s). It was quantified by identifying the blood pressure trough and overshoot and the maximum heart rate and relative bradycardia. 3. The initial drop in systolic and diastolic blood pressures did not differ between the three groups. A recovery of blood pressure with a systolic and/or diastolic blood pressure overshoot was present in all group I and II patients, but was absent in all except two patients in group III. The initial maximum heart rate increase did not differ between the three groups. The relative bradycardia was less in groups II and III than in group I. 4. We conclude that analysis of the beat-to-beat blood pressure changes in the first 30 s after the onset of standing provides almost all the information that is necessary to determine abnormalities in orthostatic circulatory control. 
Does atrial appendectomy aggravate secretory function of atrial natriuretic polypeptide? The present study was designed to clarify how atrial appendectomy affects hemodynamics and secretory function of atrial natriuretic polypeptide in the failing heart. Eleven mongrel dogs were prepared for the experimental model of high-output heart failure by creation of arteriovenous fistulas between femoral arteries and veins. Two months after the first operation, effects of bilateral atrial appendectomies on basal and pacing-induced secretions of atrial natriuretic polypeptide were investigated in five dogs with simultaneous measurement of various hemodynamic indices. In the remaining six dogs, used as a control group, pacing-induced secretion of atrial natriuretic polypeptide was examined in the same way as in the appendectomy group. After excision of the atrial appendages, neither systolic blood pressure nor either atrial pressure changed, but plasma atrial natriuretic polypeptide level was decreased (292 +/- 54 to 188 +/- 47 pg/ml, p less than 0.01) and cardiac output fell (3.7 +/- 0.9 to 3.0 +/- 0.8 L/min, p less than 0.01). During pacing-induced tachycardia, the peak level of plasma atrial natriuretic polypeptide was lower in the appendectomy group than in the control groups (593 +/- 213 versus 1170 +/- 324 pg/ml, p less than 0.05), despite similar left atrial pressures in the two groups. The excised appendages contained approximately 30% of the total amount of atrial natriuretic polypeptide. These results demonstrate that atrial appendectomy decreases secretory function of atrial natriuretic polypeptide and reduces cardiac output in dogs with experimental high-output heart failure. 
Systemic contact dermatitis from pseudoephedrine. A patient with rhinitis developed systemic contact dermatitis when starting oral treatment with Rhinalair, containing pseudoephedrine hydrochloride. A few months later, another oral treatment Rinutan, containing norephedrine hydrochloride, provoked a more severe generalized eczema. Patch test reactions were strongly positive to ephedrine and pseudoephedrine, slightly positive to phenylephrine and negative to epinephrine. Norephedrine was not tested. 
Colorectal surgery: short-term prophylaxis with clindamycin plus aztreonam or gentamicin. A randomized study was conducted to compare the effectiveness of aztreonam plus clindamycin with that of gentamicin plus clindamycin for prophylaxis of infection following colorectal surgery. A total of 138 patients undergoing elective colorectal surgery were randomized to treatment with clindamycin (600 mg) plus either aztreonam (1 g) or gentamicin (80 mg) 30 minutes before and 8 and 16 hours after surgery. The study included 122 patients (88.4%) with colorectal carcinoma. Samples from the abdominal cavity and from the subcutaneous tissues were taken for bacteriologic study. All samples from the abdominal cavity yielded microorganisms; both aerobic and anaerobic bacteria were isolated. Wound infections occurred in eight patients (12.1%) in the aztreonam group and in 12 patients (16.7%) in the gentamicin group. Escherichia coli, Bacteroides species, enterococci, and staphylococci were isolated most frequently from wounds and were often isolated from bacteriologic samples from the abdominal cavity of the same patients. The incidence of septic complications reflected the extent of nutritional and immunologic impairment. No significant differences were found between groups in the rate of urinary tract or lower respiratory tract infections. Aztreonam/clindamycin appears to be a valid alternative to gentamicin/clindamycin for the prophylaxis of infections following colorectal surgery. 
Incidence and management of airway problems in the CHARGE Association. The airway problems associated with anaesthesia in patients with the CHARGE Association have been underreported. We undertook a retrospective review of 50 cases, of which anaesthetic records were available for 37 patients. Apart from choanal atresia and cleft lip and palate, 56% of patients has some other upper airway abnormality. There appeared to be greater difficulty in tracheal intubation with increase in age in four patients. The incidence and management of airway abnormalities are discussed. 
Report of a hidden case of overfeeding. Nutritional support is essential to the care of the critically ill patient, but complications of overfeeding can occur. Precise metabolic measurement by indirect calorimetry can detect problems of nutrition and allow adjustment in caloric intake. This case study illustrates the complications of carbon dioxide retention and inability to wean from mechanical ventilation with subsequent prevention of further complications. 
Failure of trimethoprim-sulfamethoxazole therapy in experimental enterococcal endocarditis. To assess the potential efficacy of trimethoprim-sulfamethoxazole (TMP-SMX) against serious enterococcal infections, we used a rat enterococcal endocarditis model comparing TMP-SMX therapy (500 mg of TMP plus 2,500 mg of SMX per kg of body weight per day given every 8 h by intragastric gavage) with intravenous ampicillin therapy (1,000 mg/kg per day). Despite concentrations of active drug in serum well in excess of the MIC and MBC, the mean residual vegetation bacterial titer in TMP-SMX-treated rats was similar to that in untreated controls (8.4 +/- 1.1 versus 8.6 +/- 1.3 log10 CFU/g) and significantly higher than that in the ampicillin-treated group (3.6 +/- 1.5 log10 CFU/g; P less than or equal to 0.001). This demonstrates discordance between in vitro activity and in vivo efficacy of TMP-SMX in serious enterococcal infection. 
Identification of a germ-line mutation in the p53 gene in a patient with an intracranial ependymoma. We detected a germ-line mutation of the p53 gene in a patient with a malignant ependymoma of the posterior fossa. This mutation, which was found at codon 242, resulted in an amino acid substitution in a highly conserved site of exon 7 of the p53 gene; the same mutation was found in both the germ-line and the tumor tissue. This is the most common region of previously described somatic p53 mutations in tumor specimens and of the germ-line p53 mutations in patients with the Li-Fraumeni cancer syndrome. Evaluation of the patient's family revealed several direct maternal and paternal relatives who had died at a young age from different types of cancer. The association of a germ-line p53 mutation with an intracranial malignancy and a strong family history of cancer suggests that p53 gene mutations predispose a person to malignancy and, like retinoblastoma mutations, may be inherited. 
Late potentials on signal-averaged electrocardiograms and patency of the infarct-related artery in survivors of acute myocardial infarction. This study evaluated the relation between patency of the infarct-related artery and the presence of late potentials on the signal-averaged electrocardiogram (ECG) in 124 consecutive patients (98 men, 26 women; mean age 59 years) with acute myocardial infarction receiving thrombolytic therapy, acute percutaneous transluminal coronary angioplasty or standard care. All patients were studied by coronary angiography, measurement of ejection fraction and signal-averaged ECG. The infarct-related artery was closed in 51 patients and open in 73. Among patients with no prior myocardial infarction undergoing early attempted reperfusion therapy, a patent artery was associated with a decreased incidence of late potentials (20% versus 71%; no significant difference in ejection fraction). In the 48 patients receiving thrombolytic agents within 4 h of symptom onset, the incidence of late potentials was 24% and 83% among patients with an open or closed artery, respectively (p less than 0.04). The most powerful predictors of late potentials were the presence of a closed infarct-related artery, followed by prior infarction and patient age. Among patients receiving thrombolytic agents within 4 h of symptom onset, the only variable that was predictive of the presence of late potentials was a closed infarct-related artery. These data imply that reperfusion of an infarct-related artery has a beneficial effect on the electrophysiologic substrate for serious ventricular arrhythmias that is independent of change in left ventricular ejection fraction as an index of infarct size. These findings might explain, in part, the low late mortality rate in survivors of myocardial infarction with documented reperfusion of the infarct-related artery. 
Serum inhibin levels in polycystic ovary syndrome: effect of insulin resistance and insulin secretion. Insulin resistance is common in women with the polycystic ovary syndrome. We investigated the relationship between insulin resistance and the serum inhibin concentration in a group of 19 women with polycystic ovary syndrome and eight control subjects at different phases of the menstrual cycle. Insulin resistance was measured by the frequently sampled intravenous glucose tolerance test, and inhibin was measured by a specific radioimmunoassay. Insulin sensitivity (mean +/- SE) was significantly reduced in the polycystic ovary syndrome group compared with controls: reduced insulin sensitivity 46.7 +/- 5.0 min-1/(nmol/mL), normally insulin-sensitive 106.6 +/- 11.7 min-1/(nmol/mL) (P less than .01). The women with polycystic ovary syndrome had inhibin levels (126 +/- 15.2 microLEq/mL) comparable to those found during the early follicular phase of the control group (117 +/- 22.1 microLEq/mL), but significantly lower than late follicular phase (259 +/- 25.6 microLEq/mL) or luteal phase (448 +/- 91.8 microLEq/mL) levels in the control group. No association was found between the degree of insulin resistance and the inhibin concentration, which remained unaltered over a 3-hour period despite maximal stimulation of endogenous insulin secretion. The inhibin concentrations in polycystic ovary syndrome may reflect impaired follicular maturation. Inhibin secretion is not acutely affected by insulin secretion in normal or in hyperandrogenic women. 
Absence of human papilloma virus in cervical adenocarcinoma determined by in situ hybridisation. A few studies using DNA technology have suggested that human papillomavirus (HPV) may be an aetiological factor for adenocarcinoma of the uterine cervix. Twenty one cases of cervical adenocarcinoma were studied by in situ hybridisation using biotinylated DNA probes for HPV types 6, 11, 16 and 18 and a streptavidin, biotinylated alkaline phosphatase detection system. Intranuclear HPV DNA was detected in none of the adenocarcinomas, while positive controls gave a clear intranuclear signal. Adjacent areas of normal, koilocytic, and dysplastic squamous epithelium also gave positive results. It may be that squamous epithelium contaminates adenocarcinomas reported as positive by Southern blotting. Our results showing absence of detectable HPV DNA within adenocarcinomas suggest that HPV infection may not have a major role in the aetiology of adenocarcinoma of the uterine cervix. 
Treatment with pulsatile luteinizing hormone-releasing hormone modulates folliculogenesis in response to ovarian stimulation with exogenous gonadotropins in patients with polycystic ovaries. Combined treatment with pulsatile LH-RH and hMG, given to eight patients who had anovulation associated with PCO and resistant to CC, significantly reduced the number of large follicles induced by hMG alone. A direct effect of pulsatile LH-RH on the ovary is postulated. This combined treatment eased the problems of multifollicular development, thereby increasing efficiency and reducing complications in patients with PCO stimulated by gonadotropins. 
First clinical study of the selective 5-HT3 antagonist, granisetron (BRL 43694), in the acute treatment of migraine headache. Granisetron (BRL 43694), a selective 5-HT3 receptor antagonist, was assessed as acute therapy for the first time in migraine patients. In an open pilot study 7 migraine attacks were treated in 6 patients. All but 1 patient experienced marked and rapid relief from the headache, and nausea and vomiting were rapidly resolved in the 6 cases where these symptoms accompanied the attack. No side effects were recorded. Development of granisetron for migraine was suspended during the study for extraneous reasons. 
Expression of Tn, sialosyl Tn, and T antigens in human pancreas. Carbohydrate antigens representing some of the initial steps in mucin O-linked glycosylation were examined in specimens of normal pancreas, chronic pancreatitis, and pancreatic adenocarcinoma. Tn antigen, recognized by Vicia villosa lectin, was expressed by all specimens of normal pancreas (acinar cells) and pancreatic cancers and all but one case of chronic pancreatitis. Sialosyl Tn antigen, recognized by monoclonal antibody TKH2, was expressed in a cancer-associated fashion, being completely absent in normal pancreas but expressed by 56% of chronic pancreatitis and 97% of pancreatic cancers. T antigen, recognized by monoclonal antibody AH9-16, was expressed in 68% of normal pancreas (acinar cells), 67% of chronic pancreatitis, and 48% of pancreatic cancer tissues. These results indicate that normal acinar cells of the pancreas are capable of expressing selected carbohydrate structures associated with the initial steps of mucin glycosylation. The marked expression of sialosyl Tn compared with T antigen in pancreatic cancers suggests that with malignant transformation there is selective usage of glycosyltransferase enzymes involved in mucin oligosaccharide synthesis. 
QTc prolongation measured by standard 12-lead electrocardiography is an independent risk factor for sudden death due to cardiac arrest. BACKGROUND. QTc prolongation has been implicated as a risk factor for sudden death; however, a controversy exists over its significance. METHODS AND RESULTS. In the Rotterdam QT Project, 6,693 consecutive patients who underwent 24-hour ambulatory electrocardiography were followed up for 2 years; of these, 245 patients died suddenly. A standard 12-lead electrocardiogram and clinical data at the time of 24-hour ambulatory electrocardiography were collected for all patients who died suddenly and for a random sample of 467 patients from the study cohort. In all patients without an intraventricular conduction defect (176 patients who died suddenly and 390 patients from the sample), QT interval duration was measured in leads I, II, and III and corrected for heart rate with Bazett's formula (QTc). In patients without evidence of cardiac dysfunction (history of symptoms of pump failure or an ejection fraction less than 40%), QTc of more than 440 msec was associated with a 2.3 times higher risk for sudden death compared with a QTc of 440 msec or less (95% confidence interval: 1.4, 3.9). In contrast, in patients with evidence of cardiac dysfunction, the relative risk of QTc prolongation was 1.0 (0.5, 1.9). Adjustment for age, gender, history of myocardial infarction, heart rate, and the use of drugs did not alter these relative risks. CONCLUSIONS. These data indicate that in patients without intraventricular conduction defects and cardiac dysfunction, QTc prolongation measured from the standard electrocardiogram is a risk factor for sudden death independent of age, history of myocardial infarction, heart rate, and drug use. In patients with cardiac dysfunction, QTc duration is not related to the risk for sudden death. 
Risk of adverse events in children completing treatment for acute lymphoblastic leukemia: St. Jude Total Therapy studies VIII, IX, and X. We studied the frequency, causes, and predictors of adverse events in 624 patients who had completed treatment for acute lymphoblastic leukemia (ALL) in three consecutive total therapy studies (VII, IX, and X, 1972 to 1983). Event-free survival in study X was significantly better overall than that in studies VIII and IX (P less than .0001 by the log-rank test). In study X, 75% of the patients were electively taken off therapy, compared with 54% in studies VIII and IX. However, the risks of having an adverse event during the first 5 years after completion of therapy were remarkably similar: 22% (95% confidence interval, 17% to 29%) in study X versus 24% (20% to 29%) in studies VIII and IX. Bone marrow, testicular, and CNS relapses accounted for the majority of failures in both groups (85% in study X and 92% in studies VIII and IX). Late adverse events consisted largely of hematologic relapses and the development of solid tumors. Black race (P = .001) and leukemia without an anterior mediastinal mass (P = .05) were associated with an increased risk of failure after completion of treatment in the two earlier clinical trials, whereas a lower leukemic cell DNA content (DNA index less than 1.16) was the only predictor of late treatment failure in the more recent trial (P = .019). None of the other presenting features that were examined (eg, age, leukocyte count, and sex) had value as predictors of late failure. Thus, improved treatment altered the impact of specific prognostic factors and the distribution of sites of relapse, but it did not significantly affect the risk of delayed failure. 
An educational device for Mohs micrographic surgery. A three-dimensional model of basal cell carcinoma. Mohs micrographic surgery for skin cancer (fresh-tissue technique) involves the processing of tissue in a complex fashion. The advantages of this method relate to the asymmetric three-dimensional growth of basal cell carcinoma (BCC). A device is described here based on published knowledge about the growth of BCC. The model demonstrates the precise way in which Mohs surgery varies from other surgical approaches to yield higher cure rates in specific circumstances. This device may be helpful in educating residents and medical students about Mohs surgery and in preparing patients for this procedure. 
Ischemic injury to the spinal cord or lumbosacral plexus after aorto-iliac reconstruction. Between January 1, 1980, and June 30, 1989, 9 patients (6 males and 3 females) developed ischemic injury to the spinal cord or lumbosacral plexus following 3,320 operations on the abdominal aorta (0.3%). The incidence of this complication was 0.1% (2 of 1,901) after elective and 1.4% (3 of 210) after emergency abdominal aortic aneurysm repair, and 0.3% (4 of 1,209) after repair for occlusive disease. Three of the latter had prior clinical evidence of distal embolization. Eight grafts were bifurcated (aorto-iliac:four, aorto-femoral: three, aorto-ilio-femoral:one). One patient underwent extra-anatomic revascularization. Only two patients had supraceliac aortic cross-clamping and one patient underwent exclusion of both internal iliac arteries. Four patients had hypotension. Early mortality was 22% (two of nine). Severe perioperative complications, mostly due to associated visceral and somatic ischemia and sepsis, were present in seven of the nine patients. The extent and type of the neurologic injury correlated with long-term outcome. Patients with ischemic injury of the lumbosacral roots or plexus had better recovery. Attention to the pelvic circulation and the collateral blood supply is important. Use of gentle technique to prevent embolization, avoidance of hypotension and prolonged supraceliac cross-clamping, revascularization of at least one internal iliac artery, and the use of heparin may decrease but not eliminate paraplegia. Once this unexpected complication occurs, careful neurologic evaluation should be done to localize the lesion and aid prognosis. 
Agrobacterium radiobacter peritonitis in two patients maintained on chronic peritoneal dialysis. We report two patients with end-stage renal disease maintained on chronic peritoneal dialysis who developed peritonitis in which the infecting organism was Agrobacterium radiobacter, normally a rare pathogen in humans. Both patients initially responded to antibiotics, but later relapsed and required catheter removal. Neither had been exposed to soil or plant material. A radiobacter is yet another of a growing list of unusual organisms that infect the peritoneal cavity of peritoneal dialysis patients. 
Modulating effects of calcium in animal models of colon carcinogenesis and short-term studies in subjects at increased risk for colon cancer. A substantive amount of evidence from animal models supports the hypothesis that dietary fat is an etiological factor in colon cancer. Although various theories account for possible mechanisms, it is clear that under the influence of a basic colonic pH, fatty acids and bile acids may become highly surfactant in the colon, causing cell loss and compensatory hyperproliferation. Calcium likely reduces lipid damage in the colon by complexing with fat to form mineral-fat complexes or soaps. It has been shown in an increasing number of animal experiments that calcium has the ability to inhibit colon cancer. In limited studies in man, the colonic hyperproliferation associated with increased risk for colon cancer has been reversed for short periods by administration of supplemental dietary calcium. Taken together the available evidence suggests that increases in the daily intake of calcium in the diet may provide a means of colorectal-cancer control. 
Cavernous malformations of the brain stem. Once they become symptomatic, cavernous malformations of the brain stem appear to cause progressive morbidity from repetitive hemorrhage, and can even be fatal. Twenty-four patients with long-tract and/or cranial nerve findings from their cavernous malformations of the brain stem were seen for initial evaluation or surgical consultation and thereafter received either surgical or continued conservative treatment. The decision to operate was based on the proximity of the cavernous malformation to the pial surface of the brain stem, the patient's neurological status, and the number of symptomatic episodes. Sixteen patients were treated by definitive surgery directed at excision of their malformation. In four patients, associated venous malformations influenced the surgical approach and their recognition avoided the risk of inappropriate excision of the venous malformation. Although some of the 16 patients had transient, immediate, postoperative worsening of their neurological deficits, the outcome of all except one was the same or improved. Only one patient developed recurrent symptoms: a new deficit 2 1/2 years after surgery required reoperation after regrowth of the cavernous malformation. She has been neurologically stable since the second surgery. One patient died 6 months postoperatively from a shunt infection and sepsis. The eight conservatively treated patients are followed with annual magnetic resonance imaging studies. One has a dramatic associated venous malformation. Seven patients have either minor intermittent or no symptoms, and the eighth died from a hemorrhage 1 year after his initial presentation. Based on these results, surgical extirpation of symptomatic cavernous malformations of the brain stem appears to be the treatment of choice when a patient is symptomatic, the lesion is located superficially, and an operative approach can spare eloquent tissue. When cavernous malformations of the brain stem are completely excised, cure appears permanent. 
A t(4;22) in a meningioma points to the localization of a putative tumor-suppressor gene. Cytogenetic analysis of meningioma cells from one particular patient (MN32) displayed the stem-line karyo-type 45, XY, -1, 4p+, 22q-, 22q+, which thus had rearrangements of both chromosomes 22. The 22q+ marker appeared as a dicentric: 22 pter----q11::1p11----qter. The reciprocal product of this translocation has presumably been lost because it lacked a centromere. The 22q- chromosome also appeared to have lost sequences distal to band q11. We assumed that this marker could have been the result of a reciprocal translocation between chromosomes 4 and 22. To investigate the 4p+ and 22q- chromosomes in more detail, human-hamster somatic cell hybrids were constructed that segregated the 22q- and 4p+ chromosomes. Southern blot analysis with DNA from these hybrids showed that sequences from 22q were indeed translocated to 4p+ and that reciprocally sequences from 4p were translocated to 22q-, demonstrating a balanced t(4;22)(p16;q11). On the basis of these results we presume that in this tumor a tumor-suppressor gene is deleted in the case of the 22q+ marker and that the t(4;22) disrupts the second allele of this gene. The latter translocation was mapped between D22S1 and D22S15, a distance of 1 cM on the linkage map of this chromosome. The area in which we have located the translocation is within the region where the gene predisposing to neurofibromatosis 2 has been mapped. 
The rapid and reversible activation of a calcium-independent plasmalogen-selective phospholipase A2 during myocardial ischemia. Recent studies have demonstrated the existence of two members of a novel family of calcium-independent plasmalogen-selective phospholipases A2 in mammalian myocardium (Wolf, R. A., and R. W. Gross. 1985. J. Biol. Chem. 260:7295-7303; and Hazen, S. L., D. A. Ford, and R. W. Gross. 1991. J. Biol. Chem. 266:5629-5633). To examine the potential role of these calcium-independent phospholipases A2 in mediating membrane dysfunction during early myocardial ischemia, the temporal course of alterations in phospholipase A2 activity during global ischemia in Langendorf perfused rabbit hearts was quantified and compared with traditionally accepted markers of myocytic ischemic injury and anaerobic metabolism. We now report that membrane-associated calcium-independent plasmalogen-selective phospholipase A2 activity increased over 400% during 2 min of global ischemia (P less than 0.01), was near maximally activated (greater than 10-fold) after only 5 min of ischemia, and remained activated throughout the entire ischemic interval examined (2-60 min). Activation of membrane-associated plasmalogen-selective phospholipase A2 after 5 min of myocardial ischemia was rapidly reversible during reperfusion of ischemic tissue. Both the activation of phospholipase A2 and its reversibility during reperfusion were temporally correlated to alterations in myocytic anaerobic metabolism. Furthermore, activation of membrane-associated phospholipase A2 was essentially complete before electron microscopic evidence of cellular damage. Collectively, these results identify dynamic alterations in calcium-independent plasmalogen-selective phospholipase A2 activity during myocardial ischemia which precede irreversible cellular injury and demonstrate that activation of plasmalogen-selective phospholipase A2 is amongst the earliest biochemical alterations in ischemic myocardium. 
Reproducibility of quantitative planar thallium-201 scintigraphy: quantitative criteria for reversibility of myocardial perfusion defects. Fifty-two paired stress/delayed planar 201TI studies (27 exercise studies, 25 dipyridamole studies) were processed twice by seven technologists to assess inter- and intraobserver variability. The reproducibility was inversely related to the size of 201TI perfusion abnormalities. Intraobserver variability was not different between exercise and dipyridamole studies for lesions of similar size. Based upon intraobserver variability, objective quantitative criteria for reversibility of perfusion abnormalities were defined. These objective criteria were tested prospectively in a separate group of 35 201TI studies and compared with the subjective interpretation of quantitative circumferential profiles. Overall, exact agreement existed in 78% of images (kappa statistic k = 0.66). We conclude that quantification of planar 201TI scans is highly reproducible, with acceptable inter- and intraobserver variability. Objective criteria for lesion reversibility correlated well with analysis by experienced observers. 
Delays in the treatment of acute myocardial infarction: an overview. Delays in treatment of acute myocardial infarction prevent a substantial portion of patients from receiving maximal benefit from reperfusion therapy. Median delay between onset of symptoms and arrival at the hospital is 2 to 4 hours. Average time between arrival at the hospital and initiation of thrombolytic therapy is 84 minutes. Approximately 50% of patients hospitalized for suspected acute myocardial infarction do not use the emergency medical service system. Delay before treatment can be divided into several components: patient delay, emergency medical service delay, and hospital delay. Factors contributing to delay in each component and possible approaches to decreasing these delays are discussed. The effects of treatment delay on prognosis and future care-seeking behavior of patients hospitalized with suspected acute myocardial infarction are also discussed. 
Na,K-ATPase in isolated nephron segments in rats with experimental heart failure. To characterize renal transport of Na+ in heart failure, urinary Na+ excretion (UNaV), aldosterone levels, and Na,K-ATPase activity in isolated nephron segments were determined in three groups: control rats, rats with heart failure and moderate sodium retention, and rats with heart failure and severe sodium retention. Heart failure was induced by a fistula between the aorta and vena cava. For the control group, UNaV was 0.66 +/- 0.04 (mean +/- SEM) mueq/min, and aldosterone was 18.4 +/- 3.5 ng%. Na,K-ATPase activity (in 10(-11) mol/mm/min) was 28.4 +/- 1.1 in the proximal convoluted tubule, 23.3 +/- 1.0 in the proximal straight tubule, 37.4 +/- 1.9 in the medullary thick ascending limb, 40.2 +/- 1.9 in the cortical thick ascending limb, 43.2 +/- 2.2 in the distal convoluted tubule, and 20.5 +/- 0.9 in the cortical collecting duct. For the group with moderate heart failure, UNaV was 0.35 +/- 0.02 (p less than 0.001 versus control), and aldosterone was 15.9 +/- 4.4 (p = NS versus control). Na,K-ATPase activity was unchanged in the proximal convoluted tubule, proximal straight tubule, medullary thick ascending limb, and cortical collecting duct, but it increased in the cortical thick ascending limb to 57.7 +/- 3.1 (p less than 0.001 versus control) and decreased in the distal convoluted tubule to 35.3 +/- 1.2 (p less than 0.005 versus control). For the group with severe heart failure, UNaV was 0.029 +/- 0.016 (p less than 0.001 versus control), and aldosterone was 186.0 +/- 14.8 (p less than 0.001 versus control). 
The prognosis of Hodgkin's disease in older adults. This investigation was undertaken to assess the apparent poor survival of older patients with Hodgkin's disease. The clinical course of Hodgkin's disease in 136 patients, 60 to 79 years of age, was compared with that of 223 patients, 40 to 59 years of age. The patients registered from November 1977 through December 1983 had not been previously treated, and were treated at eight cancer centers. When the prognosis of all patients was examined by age, a definite change in the pattern of survival first appeared in the 60- to 69-year-old cohort. The entire older group (60 to 79 years) experienced twice the risk of dying from Hodgkin's disease and four times the risk of dying from other causes than did the younger group. In both groups, stage of disease was the strongest factor in predicting adjusted survival. Delay in treatment and advanced stage at presentation were not characteristic of Hodgkin's disease in older patients as has been postulated. Older patients responded to therapy with a similar complete remission rate (84% v 88% in the younger group, P = .24). From this study, we conclude that (1) Hodgkin's disease in the older adult does not have a different natural history, its major risk factors are similar to those known in other age groups, and thus should be amenable to existing therapeutic approaches; and (2) the prognosis of older patients with Hodgkin's disease has been obscured in previous studies by the inclusion of deaths due to other causes in survival estimates. 
Somatostatin, gastrin-releasing peptide and gastrin in the stomach of rats with streptozotocin-induced diabetes and insulinoma. Somatostatin, gastrin-releasing peptide (GRP) and gastrin were measured in the stomach of rats with streptozotocin-induced diabetes, insulinoma-bearing rats and their respective controls. Rats injected with streptozotocin exhibited hyperphagia, insulinopenia and severe hyperglycemia. Stomach weights, and the concentrations and total amounts of GRP and gastrin in the stomach, were similar to nondiabetic control rats. The concentration of somatostatin in the stomach of diabetic rats was 25% greater, but the total stomach content of somatostatin was similar to that of control rats. Insulinoma-bearing rats exhibited hyperphagia, hyperinsulinemia and hypoglycemia. Concentrations of GRP and gastrin in the stomach were 72% and 19% lower, respectively, than in control rats. Despite 45% greater stomach weight, the total stomach content of GRP was 61% lower. Stomach concentrations of somatostatin, and total stomach contents of somatostatin and gastrin, were similar in insulinoma-bearing and control rats. The results demonstrate abnormalities in the stomach concentrations of regulatory peptides in rats with diabetes and insulinoma. These abnormalities are not attributable to changes in food intake alone, suggesting specific effects of these metabolic diseases on gastric regulatory peptides and gastric function. 
Periorbital hematoma secondary to sinusitis in a child. Periorbital abscess secondary to sinusitis is a well-recognized entity in children. However, subperiosteal hematoma is extremely rare and has been reported in only four adult patients. This article presents the case of a 4-year-old girl with sinusitis, proptosis, and decreased visual acuity. Surgical exploration of the orbit revealed the presence of a large organizing subperiosteal hematoma that was drained. The presence of a periorbital hematoma should be suspected in patients with acute onset of proptosis and findings of a periorbital mass and sinusitis on computed tomographic scan. 
Hypoxia-mediated in vivo release of dopamine in nucleus tractus solitarii of rabbits. A wide variety of neuroactive substances have been suggested to be involved in the respiratory depression observed in response to severe hypoxia. By use of the technique of microdialysis, the release of dopamine (DA) was measured in the nucleus tractus solitarii during severe hypoxic provocations (6% O2 in N2) in the adult pentobarbital-anesthetized rabbit. DA release was analyzed by high-performance liquid chromatography with electrochemical detection. Such hypoxic provocations caused pronounced phase of depression in the phrenic nerve activity and enhanced release of DA. After bilateral carotid sinus nerve denervation, acute severe hypoxia did not give rise to enhanced release of DA or to phrenic nerve depression. Mild hypoxic (9% or 12% O2 in N2) or hypercapnic (6% CO2) stimuli resulted in an increased phrenic nerve activity without any concomitant changes in DA release. Decerebration at the midcollicular level in rabbits prevented an enhanced release of DA in the nucleus tractus solitarii during severe hypoxia. The results suggest that 1) DA is involved in the central ventilatory response to severe hypoxia, 2) not only the initial excitatory but also the second depressive phase in response to severe hypoxia is mediated partially by the peripheral chemoreceptors, and 3) the depressive phase is dependent on intact connections from suprapontine structures. 
Gliomatosis peritonei with malignant transformation: a case report and review of the literature. Gliomatosis peritonei is the implantation of glial tissue within the peritoneal cavity associated with ovarian teratomas. Previous reports have emphasized improved outcomes when these implants are found to be mature, even if the ovarian component is immature. A 16-year-old female with grade 3 immature teratoma was found on two subsequent laparotomies to have extensive peritoneal implantation of mature glial tissue. More than 5 years after the original surgery she was found to have a malignant abdominal glial neoplasm. This case illustrates a rare finding of malignant transformation of previously mature gliomatosis peritonei. 
Glucagon-induced alteration of serum bile acid level in patients with liver cirrhosis. Percent changes in serum total bile acid level after IV administration of 1 mg glucagon were measured in 61 cirrhotics. Thirty-three of 38 cases with Child's grade A disease showed a reduction of total bile acid level at 15 minutes; this level was maintained in the majority of them until 120 minutes. A similar mode of serial changes in total bile acid level was also shown in the cases with Child's grade B disease. On the other hand, only 2 of 10 cases with Child's grade C showed a reduction of total bile acid level at 15 minutes. Reduction of total bile acid level at 15 minutes after glucagon administration was mimicked by infusion of dibutyryl cyclic adenosine monophosphate. However, in 3 of 6 cases with elevated total bile acid level at 15 minutes after glucagon administration, dibutyryl cyclic adenosine monophosphate induced a reduction of total bile acid level. Also, it was confirmed that glucagon enhances the uptake of taurocholate into freshly isolated rat hepatocytes by activating Na(+)-dependent, carrier-mediated membrane transport system and observed that its effect is associated with elevation of Vmax (0.6114 nmol.min-1 x 10(6) cells-1 without glucagon; 0.975 nmol.min-1 x 10(6) cells-1 in glucagon added) but not with affecting Km (13.58 mumol/L without glucagon; 13.71 mumol/L with glucagon) or protein synthesis which is inhibited by cycloheximide. These observations suggest that glucagon enhances Na(+)-coupled membrane transport of bile acids in the liver and causes the reduction of serum total bile acid level and that a lack of this response may be indicative of membrane dysfunction in the liver. 
Chimeric BCR-abl messenger RNA as a marker for minimal residual disease in patients transplanted for Philadelphia chromosome-positive acute lymphoblastic leukemia. We correlated polymerase chain reaction (PCR)-detectable BCR-abl fusion transcripts with cytogenetic status in 24 patients with acute lymphocytic leukemia (ALL). Of 10 Philadelphia chromosome negative (Ph-) patients, only one was found to exhibit a BCR-abl fusion transcript. Fourteen patients with Ph+ ALL, including eight in clinical remission, exhibited PCR-detectable BCR-abl rearrangements. A detectable Ph chromosome was present in only five of the eight patients in clinical remission. Of the three cytogenetically negative, BCR-abl-positive patients, two eventually succumbed to post-bone marrow transplantation (BMT) relapse. The third died of early transplant complications. Serial PCR analyses were performed on four Ph+ ALL patients in clinical remission who underwent allogeneic BMT. One patient who was PCR negative on post-BMT days 21 and 75 became PCR-positive on day 116 and died in relapse on day 154. One patient was weakly positive for BCR-abl on day 23, negative on day 56, but died of transplant complications on day 124. Two patients exhibited no post-BMT BCR-abl rearrangements and remain well on days 279 and 371. Our findings suggest that PCR analysis may be useful in the early identification of relapse in patients transplanted for Ph+ ALL. 
Bilateral internal mammary artery grafts in reoperative and primary coronary bypass surgery Bilateral internal mammary artery grafting is recognized as a preferred method of myocardial revascularization. However, its efficacy in coronary bypass reoperation has not been clearly established. From January 1982 through June 1989, 88 patients underwent coronary bypass reoperation with bilateral internal mammary artery grafts. Results were compared with those for a subset of 88 patients receiving primary revascularization with bilateral internal mammary artery grafts who were computer matched for sex, age, left ventricular function, anginal classification, and left main coronary artery disease. In each group, 62.5% (55 patients) had unstable angina, 43.2% (38 patients) had reduced ejection fraction, and 21.6% (19 patients) in the reoperation group and 20.5% (18 patients) in the reference group had left main coronary artery disease. Hospital mortality for the reoperation group was 6.8% (6 patients) and for the reference group, 3.4% (3 patients). No significant difference was found in the incidence of reoperation for bleeding, sternal infection, or stroke in the two groups. The incidence of respiratory insufficiency in the reoperation group was 13.6% (12 patients) and in the reference group, 3.4% (3 patients) (p less than 0.015). Recurrent angina occurred in 13.7% (10 patients) of patients in the reoperation group and 13.3% (10 patients) in the reference group. The long-term survival at 5 years for the reoperation group was 85.3% +/- 5.6% (+/- standard error of the mean) and for the reference group, 91.6% +/- 3.1%. No significant difference was found in the equality of survival distribution for the two groups. 
Occurrence of neoplasia in patients with rheumatoid arthritis enrolled in a DMARD Registry. Rheumatoid Arthritis Azathioprine Registry Steering Committee. The Rheumatoid Arthritis Azathioprine Registry (RAAR) was established in 1982 to examine the safety of azathioprine (AZA) and other disease modifying agents (DMARD) in the treatment of RA. In yearly followup over the past 7 years, 20 malignant conditions have been reported in 530 DMARD treated adult patients with RA. Incidence density ratios (IDR) and standardized morbidity ratios (SMR) were calculated to assess cancer risk. For all cancers the SMR was 1.52 (95% CI 0.90-2.60). For men the SMR was 1.71 (95% CI 0.84-3.52); for women the SMR was 1.52 (95% CI 0.89-2.60). Adjusted for age, the IDR was highest in the 70-79-year-old study population (3.41). The age and sex adjusted SMR for lymphoproliferative disorders and myeloma was 8.05 (95% CI 3.30-20.81). The SMR for lung cancer (n = 6) was also increased (3.37; 95% CI 1.58-7.34). Compared with the general population, patients with RA requiring DMARD therapy may be at increased risk of malignancy, particularly lymphoproliferative disorders. The RAAR is an important prospective technique which will ultimately permit assessment of neoplasia risk by type and duration of DMARD therapy. 
Adenosine in myocardial perfusion imaging using positron emission tomography. Because of its unique ability to demonstrate the metabolic consequences of myocardial ischemia, positron emission tomography (PET) is extremely valuable in assessing myocardial viability. PET imaging can identify the myocardial segments that are likely to improve after revascularization and may be more sensitive and specific for the detection of coronary artery disease compared with thallium perfusion imaging. Adenosine has several advantages over dipyridamole as a pharmacologic stress agent for use with PET. It produces maximal vasodilation in a significantly greater percentage of patients, is a more potent coronary vasodilator, and its very short half-life may be ideal for use with the very short half-life radioactive tracers used in PET. When combined with metabolic studies, adenosine may be useful for the assessment of patients who received thrombolytic therapy for an acute myocardial infarction. 
Colovesical fistula secondary to vesical gangrene in a diabetic patient. We present a case of colovesical fistula secondary to vesical gangrene. Precipitating factors were diabetes and vesical distension caused by the obstruction of an indwelling catheter. This complication is an exceptional outcome in gangrenous cystitis and it requires emergency surgical treatment. 
Beneficial effect of the atrial natriuretic factor analog A68828 in postischemic acute renal failure. Short-term administration of atrial peptides has been reported to improve renal function in several animal models of acute renal failure. We designed experiments that determined the effect of a 13-amino acid analog of atrial natriuretic factor (ANF), A68828, on renal function in the postischemic model of acute renal failure. Experiments were conducted using euvolemic, male Sprague-Dawley rats (200-250 g) under Inactin anesthesia. Acute renal failure was induced by complete occlusion of both renal arteries for 30 min. After release of the clamp, vehicle (0.1% bovine serum albumin in saline), A68828 (3, 10 or 30 micrograms/kg/min), dopamine (10 micrograms/kg/min), A68828 (10 micrograms/kg/min) plus dopamine (10 micrograms/kg/min) or ANF (1-28) (0.5 micrograms/kg/min) were infused i.v. for a 2-h period. A68828 at 10 micrograms/kg/min produced a significant increase in glomerular filtration rate (GFR) compared with vehicle controls (0.39 +/- 0.08 vs. 0.19 +/- 0.04 ml/min/100 g; P less than .05) despite a lower arterial pressure (87 +/- 5 vs. 101 +/- 5 mm Hg; P less than .05). A subpressor dose of dopamine had no effect on GFR during the postischemic period (0.25 +/- 0.11 ml/min/100 g). Dopamine in combination with A68828 prevented the decrease in arterial pressure seen with A68828 alone but did not potentiate the beneficial effects on GFR (0.28 +/- 0.05 ml/min/100 g). ANF (1-28) at 0.5 micrograms/kg/min increased GFR to levels nearly identical to those induced by A68828 (0.40 +/- 0.04 ml/min/100 g). These results indicate that infusion of a reduced-size analog of ANF improves renal function in the immediate postischemic period. Furthermore, prevention of the hypotensive effects of the analog with dopamine provides no additional beneficial effect. 
Clear cell cribriform hyperplasia of the prostate. Immunohistochemical and DNA flow cytometric study. Clear cell cribriform hyperplasia (CCCH) of the prostate is an unusual form of benign prostatic hyperplasia characterized by a nodular proliferation of clear cells with small, uniform nuclei. The authors studied 15 cases of CCCH by immunohistochemistry and 13 of them by DNA flow cytometry to establish the immunohistochemical and DNA profile of this lesion. Patients ranged in age from 58 to 88 years (mean, 68 years). Follow-up of a mean of 22 months showed all patients alive with no evidence of malignant prostatic disease. All 13 CCCHs showed diploid DNA content; in contrast, among 4 papillary/cribriform carcinomas of the prostate used for comparison, 3 were aneuploid and 1 was diploid. A basal cell layer was demonstrated in all 15 CCCHs by the use of the 34 beta E12 anti-high-molecular-weight keratin antibody (EAB-903) that reacts with the basal cells but not with the acinar cells of the prostate. A continuous basal cell layer was not evident in the carcinomas. The blandness of the epithelium, the well-defined nodular configuration, the presence of a basal cell layer demonstrable by immunocytochemistry, and the lack of aneuploidy as determined by DNA flow cytometry together lend support to the concept that CCCH is a benign lesion. 
Cramp-fasciculation syndrome: a treatable hyperexcitable peripheral nerve disorder. We report nine patients with muscle aching, cramps, stiffness, exercise intolerance, and peripheral nerve hyperexcitability. Neurologic examination showed calf fasciculations in seven, quadriceps myokymia in two, and deltoid myokymia in one patient. Two patients had mild increase in serum creatine kinase. Muscle biopsy showed either no abnormality (three patients) or mild neurogenic changes (four patients). Fasciculations were the only abnormality on routine electrodiagnostic studies. Supramaximal stimulation of the median, ulnar, peroneal, and posterior tibial nerves at frequencies of 0.5, 1, 2, and 5 Hz produced showers of electrical potentials following the M response in at least one nerve. In three patients, the fasciculations and evoked electrical potentials were abolished by regional application of curare but not nerve block. Carbamazepine therapy caused moderate-to-marked reduction of symptoms and nerve hyperexcitability. We designate this hyperexcitable peripheral nerve disorder as the "cramp-fasciculation syndrome.". 
Acid peptic disease in adolescents. How to avoid misdiagnosis and undertreatment. Acid peptic disease in adolescents may be more common than previously recognized. However, appropriate medical attention is often delayed because of misdiagnosis and undertreatment. Thorough questioning of adolescent patients is important to elicit a complete description of symptoms. Endoscopy or intraluminal pH monitoring may be necessary to establish a diagnosis of gastroesophageal reflux disease or peptic ulcer. Therapy with histamine receptor antagonists, especially ranitidine (Zantac), is recommended. Antireflux surgery may be needed to prevent potential long-term gastrointestinal damage. Patients with duodenal ulcer should also be advised to make life-style changes to avoid recurrence of disease later in life. 
Regimen compliance two years after myocardial infarction. Two-years postinfarction, the effect of a nursing intervention at 30 days postinfarction, and intentions, attitudes, and perceived beliefs of others on regimen compliance of myocardial infarction patients was investigated. The sample was comprised of 51 patients (E = 29, C = 22) who participated in a five-phase study over 2 years. No differences were found between experimental and control groups for regimen compliance to activity, stress, and medication prescriptions. The experimental group was significantly more compliant to the diet prescription than the control group. The control group was significantly more compliant than the experimental group with cessation from smoking. Perceived beliefs of others were predictive of compliance for all regimen prescriptions at 2 years. Attitude was also predictive of compliance with the diet, smoking, and stress regimens. 
Allergic reactions to long-term benzathine penicillin prophylaxis for rheumatic fever. International Rheumatic Fever Study Group. 1790 patients from 11 countries were enrolled in a prospective international study to determine the incidence of allergic reactions to monthly intramuscular benzathine penicillin (penicillin G benzathine) injections to prevent recurrences of rheumatic fever. After 32,430 injections during 2736 patient years of observation, 57 of the 1790 patients (3.2%) had an allergic reaction. 4 had anaphylaxis, an incidence of 0.2% (1.2/10,000 injections), all in patients over 12 years of age, and 1 patient died, a fatality incidence of 0.05% (0.31/10,000 injections). These rates are similar to those described for patients without rheumatic fever who receive short-term treatment with parenteral penicillin. Rheumatic fever recurred in 8 of 1790 patients (0.45%) who received benzathine penicillin prophylaxis compared with 11 of 96 (11.5%) who did not comply with treatment. Life-threatening allergic reactions are rare in patients on long-term parenteral benzathine penicillin to prevent recurrences of rheumatic fever; the long-term benefits of such prophylaxis by far outweigh the risk of a serious allergic reaction. 
Blood flow reactivity to hypercapnia in strictly unilateral carotid disease: preliminary results. To show relationship between degree of carotid arterial stenosis and cerebral blood flow reactivity (RES%) to induced hypercapnia, fluorine-18-fluoromethane and positron emission tomography (PET) was used to study 18 patients with carotid distribution transient ischaemic attacks (TIA), all free of stroke, who had angiographic-proven unilateral arterial disease. Non-involved carotid arteries were either normal or had non-stenotic plaque. Either normal arteries or nonstenotic ulcerations in the symptomatic carotid arteries were present in five of 18 (28%), ipsilateral carotid stenosis from 50-99% was present in eight of 18 (44%), and ipsilateral internal carotid occlusion was present in five of 18 (28%) patients. In comparison with 14 normal controls, all patients with symptomatic middle cerebral artery (MCA) flow territories had significantly lower mean (SEM) RES% [5.0' (0.2) vs 4.0 (0.9), p less than 0.04]. Symptomatic anterior borderzone (ABZ) RES% was also significantly lower [4.6 (0.4) vs 3.3 (0.9), p less than 0.04], than controls. In patient subgroup comparisons, the 50-99% stenosis subgroup clearly had the lowest MCA RES% [3.4 (0.2)] as well as the lowest ABZ RES% [2.8 (0.4)] on their symptomatic sides. Age, expired pCO2, mean arterial blood pressure, serum glucose, serum haematocrit and number, type and estimated duration of TIAs were not significantly different between subgroups. Linear regression showed a significant relationship between RES% and both measured percentage-stenosis (p = 0.04) and residual luminal diameter (p = 0.05) in symptomatic MCA territories. This approached significance in symptomatic ABZ regions. This preliminary data set suggests that unilateral carotid stenosis can and does result in impaired CO2 reactivity following hypercapnia. 
Protein kinase C is involved in PTH-induced homologous desensitization by directly affecting PTH receptor in the osteoblastic osteosarcoma cells. We have investigated mechanisms of PTH-induced homologous desensitization reflected in the refractoriness of cAMP response to the second exposure to PTH in the clonal rat osteosarcoma cell line, UMR-106. Preincubation with 10(-7) M rat (r) PTH-(1-34) for 6 h caused the desensitization, resulting in a 65% decrease in cAMP accumulation in response to further exposure to rPTH. This desensitization was apparent at 10(-10) M rPTH and maximal at 10(-7) M rPTH. UMR-106 cells treated with protein kinase C (PK-C) activating phorbol ester, phorbol 12-myristate 13-acetate (PMA, 10(-6) M) for 6 h also induced desensitization manifested by a loss of rPTH-stimulated cAMP accumulation to 50% of that in the control cells. On the other hand, 4 alpha-phorbol 12,13-didecanoate, incapable of activating PK-C, failed to induce desensitization. Fifty micromolar H-7 (PK-C inhibitor) significantly blocked both rPTH- and PMA-induced desensitization. Thus, PK-C seemed to play a major role in rPTH-induced desensitization. Pretreatment with neither rPTH nor PMA changed the cAMP responsiveness to 10 micrograms/ml cholera toxin or 100 microM forskolin. Islet activating protein failed to influence the desensitization in this cell line. PTH receptor binding, assessed by using 125I-labeled [Nle8,Nle18,Tyr34]PTH-(1-34) as a radioligand, was decreased along with PTH receptor numbers by pretreatment with rPTH or PMA. These data indicate that rPTH-induced homologous desensitization occurs at least in part through the activation of PK-C and that PK-C directly affects PTH receptor in UMR-106 cells. 
The benefit of the Hemonetics cell saver apparatus during cardiac surgery. This retrospective chart review of 155 patients having coronary artery bypass graft surgery (CABG) over a two-month period determined whether the use of a cell saver apparatus (CSA) (1) reduced or increased the requirements for homologous blood; (2) increased the incidence of post-surgical bleeding; (3) was cost-effective. Two groups of patients were identified. Group 1 (n = 99) received both CSA processed red blood cells and homologous blood components. Requirement for homologous blood products was reduced in the first 24 hr after surgery (0.5 +/- 1.0 vs 1.3 +/- 1.8 units; P less than 0.05) when compared with Group 2 (n = 56) in whom only homologous blood products were utilized. More patients in Group 1 had no transfusion requirements (45 vs 8; P less than 0.05) and there was no increased risk of major haemorrhage. When the capital costs are included, utilization of the CSA was not cost-effective. We conclude that utilisation of a CSA was safe, with no increased risk of bleeding, reduced requirements for homologous blood transfusions, but added to the cost of the procedure. 
Abnormal responses to orthostatic testing in children and adolescents with recurrent unexplained syncope. Syncope in the pediatric age group is a frequent event. Most often the cause is readily apparent--i.e., orthostatic hypotension or a vasovagal event. However, there are a large number of children with frequent recurrent unexplained syncope. Neither history, physical examination, nor standard testing reveals a cause. One hundred four consecutive patients were evaluated by orthostatic testing after standard methods found no cause for the recurrent syncope. Forty-seven (44%) of these 104 patients had syncope produced by orthostatic testing. Twenty-six of the 47 (55%) became syncopal within 5 minutes of testing initiation and 21 of the 47 (45%) after 5 to 11 minutes of testing. These patients had an average decrease of 81.5 mm Hg in blood pressure and a 25 beat/min decrease in heart rate. Of 12 control subjects, none lost consciousness with standing times as long as 14 minutes. Pacing was ineffective in preventing syncope, as two patients with a previously implanted normally functioning pacemaker had recurrent syncope clinically. Syncope was also induced by orthostatic testing, with the pacemaker showing a normal response with pacing as the patient became bradycardic. The syncopal event produced by orthostatic testing occurred with a downward blood pressure trend and a narrowing of the pulse pressure without a significant increase in heart rate. This was followed by a sudden drop in blood pressure and then by bradycardia. There is a group of children and adolescents with recurrent unexplained syncope due to abnormal orthostatic control mechanisms. Orthostatic testing appears helpful in identifying these patients. 
Lumbar epidural diamorphine following thoracic surgery. A comparison of infusion and bolus administration. Twenty-two patients received a single dose of diamorphine 5 mg through a lumbar epidural catheter before thoracic surgery. The patients were transferred after surgery to a high dependency unit where they were allocated randomly to receive either an infusion of epidural diamorphine at a rate of 1 mg/hour (group 1) or bolus doses of epidural diamorphine 5 mg on demand (group 2). There was no statistically significant difference between the groups in visual analogue pain scores in the first 18 postoperative hours. Arterial carbon dioxide tension was elevated in both groups and was consistently higher in group 1 than in group 2, with a statistically significant intergroup difference 12 hours after operation. Respiratory rate was not a useful index of respiratory depression. The commonest nonrespiratory side effect was urinary retention, but the incidences of this and other minor side effects were similar in the two groups. 
Carcinoma of the prostate: MR images obtained with body coils do not accurately reflect tumor volume. MR imaging with a body coil is unreliable in directly demonstrating tumor spread through the prostatic capsule. However, the likelihood of extracapsular spread of prostatic cancer rises with increasing tumor volume. The aim of our study was to assess the accuracy of MR with a body coil in diagnosing capsular penetration indirectly via an estimation of prostatic tumor volumes. Twenty-six patients with proved prostatic cancer that was clinically confined to the gland underwent MR imaging before radical prostatectomy and whole-mount pathologic sectioning of the specimen. Twenty of 31 lesions prospectively outlined on the MR images corresponded to cancers outlined on the pathology slides, and tumor volumes were calculated by using a voxel summation technique. On MR, tumor volume was underestimated in 11 of 20 cases and overestimated in nine of 20 cases. Only two of 20 size estimates based on MR findings were within 10% of actual tumor volume. Overlap in MR tumor volumes was significant between lesions with and without capsular penetration at microscopy. Factors contributing to inaccuracies in measurements of tumor volume on MR images included the variable histologic make-up of the tumors. Our results show that, although knowledge of the size of a prostatic lesion is important in predicting the behavior of the tumor, MR imaging with a body coil is not reliable for accurate estimation of tumor volume. 
Purification of parathyroid hypertensive factor from plasma of spontaneously hypertensive rats. Parathyroid hypertensive factor (PHF) is a newly described hypertensive factor that may be related to elevation of blood pressure in 30-40% of North American essential hypertensive patients. PHF is also found in several animal models of hypertension, including spontaneously hypertensive rats, and deoxycorticosterone acetate salt hypertensive rats. Plasma collected from spontaneously hypertensive rats (SHR) was used in the present study for purification of PHF. Plasma was dialyzed at a molecular mass cutoff of 1 kDa, and then ultrafiltered at a molecular mass cutoff of 5 kDa. PHF activity, as determined by bioassay (characteristic delayed hypertensive response in normotensive rat) was retained in the fraction that was greater than 1 kDa and less than 5 kDa. Dialyzed and ultrafiltered SHR plasma was fractionated by molecular-exclusion chromatography, either with Bio-Gel P-6 liquid chromatography, or TSK 2000 SW HPLC. The biological activity was detected in a discrete region corresponding to a molecular mass of 2.5-3 kDa. When the molecular-exclusion fraction was subsequently fractionated by reverse-phase HPLC, biological activity was located in a single discrete peak, which did not occur in plasma from normotensive rats prepared in a similar manner. The biologically active fraction of PHF was inactivated by trypsin; this and its UV spectrum indicate the presence of a peptide structure. 
Nasal schwannoma. A 36-year-old man with a nasal septal mass is presented. The diagnosis of a benign neoplasm arising from peripheral nerve Schwann cells was made by excisional biopsy. A benign nerve sheath tumor may be either a schwannoma or neurofibroma. Schwannomas may be distinguished from neurofibroma by clinical and histologic criteria. Malignant degeneration and intracranial extension may complicate the course of a nasal schwannoma. Complete excision is the preferred therapy. 
Essential fatty acid deficiency associated with the use of a medium-chain-triglyceride infant formula in pediatric hepatobiliary disease. Serum phospholipid fatty acid patterns were determined by gas chromatography in four infants with hepatobiliary disease receiving a formula with a high content of medium-chain-triglyceride (MCT) oil. All four infants demonstrated signs of essential fatty acid deficiency, characterized by decreased arachidonic acid and increased palmitoleic and oleic acids. All had substantial concentrations of the pathologic triene 5,8,11-eicosatrienoic acid. Three of four had decreased linoleic acid concentrations and abnormal ratios of triene to tetraene (5,8,11-eicosatrienoic acid: arachidonic acid), greater than 0.38. One patient may have experienced growth failure due to abnormal essential fatty acid status. Infants with the potential for fat malabsorption should only receive MCT-oil feedings with well above the generally recommended requirements for linoleic acid (3% of total caloric intake). 
Postoperative infusional continuous regional analgesia. A technique for relief of postoperative pain following major extremity surgery. A new technique using postoperative infusional continuous regional analgesia (PICRA) for postoperative pain relief was investigated in 23 surgical patients treated by amputation (12 patients) or by limb-salvage resection operations (11 patients). Bupivacaine was delivered into peripheral nerve sheaths via catheters placed therein at the time of surgery. Only patients in whom the nerves were easily accessible were treated. Catheters were placed in the axillary sheath, the lumbosacral trunk, and the femoral nerve sheaths of patients treated with shoulder girdle and pelvic procedures (resections and amputations), and within the sciatic nerve sheath of those treated with lower extremity procedures. The anesthetic agent was delivered at controllable rates. Regional analgesia was obtained in the operative site with minimal motor or sensory decrease. To assess the efficacy of this technique, the results of this study group were compared with those of a matched group of 11 patients treated with similar surgical procedures but who received epidural morphine. Eleven of the 23 patients on PICRA required no supplemental narcotic agents. The mean level of the narcotic agents required by the remaining 13 PICRA patients was approximately one third of that required by the matched group of 11 patients receiving epidural morphine. Overall, the patients on PICRA had an 80% reduction of narcotic requirements when compared to the historical controls. The technique is reliable and can be performed by the surgeon, requiring about a ten-minute increase in operating time. It has potentially wide application in orthopedics in procedures in which the major nerves are easily accessible (e.g., pelvic fractures and revision hip surgery) and for patients with intractable pain of the extremities. 
Extracellular binding sites of IgA anti-jejunal antibodies on normal small bowel detected by indirect immunoelectronmicroscopy. Patients with dermatitis herpetiformis (DH) have IgA deposition in the papillary dermis and in the lamina propria of the small bowel. In addition, most of DH patients' sera contain IgA class anti-reticulin antibodies, anti-endomysium antibodies (EMA), and anti-jejunal antibodies (JAB) during times of gluten intake. In previous studies, JAB and EMA seemed to be identical and related to the group of anti-reticulin antibodies. In the present study, pre-embedding en bloc immunoelectronmicroscopic methods were applied for analysis of the ultrastructural binding sites of JAB on monkey and rabbit small bowels. These substrates were incubated with sera from DH patients strongly positive for JAB. Simultaneous investigations with the PAP technique and with 5 nm gold-labeled protein A or second antibodies visualized the bound IgA identically: it was associated with collagen fibrils underlying the epithelial and cryptal basement membranes and with collagen fibrils around capillaries. Staining was also detected along the endomysial collagen fibrils of smooth muscle layers, around elastica and smooth muscle cells of blood vessel walls, and along collagen fibrils near smooth muscle cells in the lamina propria. Neither the peroxidase product nor gold deposition was detected directly on the fibers, but was associated with amorphous material surrounding collagen fibers of different diameters. The distribution of JAB-stained structures corresponded to the localization of reticulin network of the small bowel. Our data indicate that JAB recognize an antigen or antigens associated with an amorphous component of the reticulin-collagen structure of jejunum and may have identical binding sites, as anti-reticulin antibodies and EMA. 
Amenorrhoea in women with non-alcoholic chronic liver disease. Amenorrhoea is common in women with non-alcoholic chronic liver disease, but little is known about its causes or consequences. We investigated 12 young women with non-alcoholic chronic liver disease and amenorrhoea and compared them with 11 healthy age matched controls studied in the follicular phase of the menstrual cycle. None of the patients had raised serum concentrations of follicle stimulating hormone suggesting primary gonadal failure, but the variance in serum concentrations of testosterone, oestradiol, prolactin, and luteinising hormone were significantly greater in chronic liver disease patients than control subjects (p less than 0.01). Seven of the 12 chronic liver disease patients had low serum luteinising hormone concentrations, and compared with controls these patients also had significantly reduced median values of oestradiol (64 pmol/l), testosterone (1.1 nmol/l), and follicle stimulating hormone, and were significantly underweight as assessed by skinfold thickness measurements (all comparisons p less than 0.025). In the group with chronic liver disease skinfold thickness was significantly correlated with serum luteinising hormone (p less than 0.02). The five patients with normal serum luteinising hormone had higher median values of both oestradiol (237 pmol/l) and testosterone (3.0 nmol/l) than the control subjects (oestradiol: 113 pmol/l, testosterone: 1.9 nmol/l) but were not more obese or hirsute. Amenorrhoea was unrelated to the duration or severity of liver disease. The metacarpal cortical bone area (an index of bone density) was inversely related to the duration of amenorrhoea (p less than 0.02). We conclude that amenorrhoea in women with non-alcoholic chronic liver disease arises from hypothalamic-pituitary dysfunction and can occur at any stage. 
Computer-assisted superimposition of magnetic resonance and high-resolution technetium-99m-HMPAO and thallium-201 SPECT images of the brain. A method for registering three-dimensional CT, MR, and PET data sets that require no special patient immobilization or other precise positioning measures was adapted to high-resolution SPECT and MRI and was applied in 14 subjects (five normal volunteers, four patients with dementia (Alzheimer's disease), two patients with recurrent glioblastoma, and three patients with focal lesions (stroke, arachnoid cyst and head trauma]. T2-weighted axial magnetic resonance images and transaxial 99mTc-HMPAO and 201Tl images acquired with an annular gamma camera were merged using an objective registration (translation, rotation and rescaling) program. In the normal subjects and patients with dementia and focal lesions, focal areas of high uptake corresponded to gray matter structures. Focal lesions observed on MRI corresponded to perfusion defects on SPECT. In the patients who had undergone surgical resection of glioblastoma followed by interstitial brachytherapy, increased 201Tl corresponding to recurrent tumor could be localized from the superimposed images. The method was evaluated by measuring the residuals in all subjects and translational errors due to superimposition of deep structures in the 12 subjects with normal thalamic anatomy and 99mTc-HMPAO uptake. This method for superimposing magnetic resonance and high-resolution SPECT images of the brain is a useful technique for correlating regional function with brain anatomy. 
Survival of patients with dementia. The evidence on survival in dementia is summarized. There are no reliable data on survival after onset of dementia or after first contact with medical services. People with dementia in outpatient clinics and nursing homes have 2-year survival rates of 75% (range 60%-95%) and 50% (range 30%-65%), respectively. Differences in survival between patients with senile dementia of the Alzheimer's type (SDAT) and multi infarct dementia (MID) are small. Women in nursing homes have a better prognosis than men (2-year survival rates, 60% vs 40%). Dementia patients have a considerable excess mortality when compared to the vital statistics. There is no evidence for improvement of survival rates during recent decades. Recommendations for future studies are made. 
Percutaneous excimer laser coronary angioplasty of lesions not ideal for balloon angioplasty BACKGROUND. Excimer laser coronary angioplasty is a new, investigational technique for treating coronary artery stenoses. Initial reports have demonstrated acute efficacy and relative safety of this procedure, but have not addressed the effect of lesion type on acute success and complication rates. METHODS AND RESULTS. In the first 100 patients undergoing percutaneous excimer laser coronary angioplasty at our institution, acute laser success was obtained in 84% and procedural success was obtained in 94%. There were six acute closures during laser angioplasty and one myocardial infarction. Two patients required emergency coronary bypass surgery. Sixty-five percent of patients had lesions not ideal for balloon angioplasty because of lesion morphology (tubular, diffuse, or chronic total occlusion) or ostial location. There were 10 tubular stenoses, 29 diffuse lesions, 18 chronic total occlusions, and eight ostial lesions, including five aorto-ostial lesions. In this nonideal subgroup, the acute success rate with laser was 86% (72% of chronic total occlusions and 91% of non-totally occluded lesions), and the procedural success rate was 94%. There were three acute occlusions during laser angioplasty but no myocardial infarctions, emergency bypass surgeries, or deaths. One coronary artery perforation occurred without clinical sequelae. Laser angioplasty was successful in four of six lesions (67%) in which balloon angioplasty had failed. Laser success was obtained in 10 of 11 (91%) moderately or heavily calcified stenoses. Eight eccentric lesions and two lesions on bends were successfully treated without dissection or perforation. No side branch occlusions occurred in the 15 patients in whom one or more major branches originated within the lesion treated. Adjunctive balloon angioplasty was performed in 47% of cases, usually to obtain a larger final luminal diameter. Need for adjunctive balloon angioplasty decreased to 36% after a larger (2.0 mm) laser catheter became available. Twenty-eight percent of the 105 lesions treated were American College of Cardiology/American Heart Association classification type A, 47% were type B, and 25% were type C. Laser and procedural successes were obtained in 83% and 97% of type A, 88% and 96% of type B, and 85% and 88% of type C lesions, respectively. CONCLUSIONS. In our initial experience, excimer laser angioplasty was found to be acutely effective and safe therapy for lesions identified as not ideal for balloon angioplasty. This technique may provide a useful adjunct or alternative to balloon angioplasty in selected patients. 
The postmenopausal adnexal mass: correlation between ultrasonic and pathologic findings. One hundred two postmenopausal women underwent ultrasonographic evaluation of adnexal masses before surgery. Twenty-nine (28%) had malignant tumors and 73 (72%) had benign tumors. Two of 33 patients with a "simple cyst" smaller than 5 cm in diameter by ultrasound had malignant ovarian tumors. Twenty-two of the 52 women (42%) with "complex masses" by ultrasound and five of the 17 (29%) with solid tumors had ovarian cancer. For predicting malignancy in ovarian tumors, abdominal ultrasonography had a positive predictive value of 39% and a negative predictive value of 94%. If a negative sonogram had been relied upon, 6% of malignant ovarian tumors in postmenopausal women might have been missed. 
A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure BACKGROUND. To define better the efficacy of vasodilator therapy in the treatment of chronic congestive heart failure, we compared the effects of hydralazine and isosorbide dinitrate with those of enalapril in 804 men receiving digoxin and diuretic therapy for heart failure. The patients were randomly assigned in a double-blind manner to receive 20 mg of enalapril daily or 300 mg of hydralazine plus 160 mg of isosorbide dinitrate daily. The latter regimen was identical to that used with a similar patient population in the effective-treatment arm of our previous Vasodilator-Heart Failure Trial. RESULTS. Mortality after two years was significantly lower in the enalapril arm (18 percent) than in the hydralazine-isosorbide dinitrate arm (25 percent) (P = 0.016; reduction in mortality, 28.0 percent), and overall mortality tended to be lower (P = 0.08). The lower mortality in the enalapril arm was attributable to a reduction in the incidence of sudden death, and this beneficial effect was more prominent in patients with less severe symptoms (New York Heart Association class I or II). In contrast, body oxygen consumption at peak exercise was increased only by hydralazine-isosorbide dinitrate treatment (P less than 0.05), and left ventricular ejection fraction, which increased with both regimens during the 2 years after randomization, increased more (P less than 0.05) during the first 13 weeks in the hydralazine-isosorbide dinitrate group. CONCLUSIONS. The similar two-year mortality in the hydralazine-isosorbide dinitrate arms in our previous Vasodilator-Heart Failure Trial (26 percent) and in the present trial (25 percent), as compared with that in the placebo arm in the previous trial, (34 percent) and the further survival benefit with enalapril in the present trial (18 percent) strengthen the conclusion that vasodilator therapy should be included in the standard treatment for heart failure. The different effects of the two regimens (enalapril and hydralazine-isosorbide dinitrate) on mortality and physiologic end points suggest that the profile of effects might be enhanced if the regimens were used in combination. 
Pneumocystis carinii pneumonia after heart transplantation. Five patients with Pneumocystis carinii pneumonia after heart transplantation are reported. Four had severe clinical symptoms, whereas 1 was asymptomatic. Mechanical ventilatory support was necessary in 1 because of respiratory distress. Pneumocystis carinii infection developed in 4 patients within the first 4 postoperative months, and 1 patient had clinical disease 1 year after transplantation with a recurrence 9 months later. All were treated with trimethoprim-sulfamethoxazole either orally or intravenously (10 to 20 mg.kg-1.day-1 of trimethoprim). All patients recovered from infection and received the same drug prophylactically for 2 to 20 months after the infection. All patients are doing well after Pneumocystis carinii infection except 1 who died after an acute myocardial infarction 4 years after infection. We conclude that trimethoprim-sulfamethoxazole is an effective agent for the treatment of Pneumocystis carinii pneumonia after heart transplantation. 
Detection of single copies of Epstein-Barr virus in paraffin wax sections by non-radioactive in situ hybridisation. A highly sensitive non-isotopic in situ hybridisation technique was developed for the localisation of Epstein-Barr virus (EBV) in paraffin wax embedded tissue sections. The method uses a repeated sequence of the EBV genome as a probe, labelled with the novel reporter molecule, digoxigenin. The method can identify individual copies of EBV by detection of both EBV DNA and highly localised RNA transcripts. A combination of careful proteolytic digestion of tissue sections, high temperature denaturation of probe and target DNA, and sensitive immunocytochemical detection are used to attain single copy sensitivity. The technique is quicker and simpler to perform than some other methods used for the identification of EBV, and provides simultaneous morphological information which cannot be obtained by methods using tissue extracts. This method permits the investigation of the role of EBV in neoplastic conditions of lymphoid and epithelial cells, and may prove valuable in determining the sites of latent virus in healthy subjects. 
Intrathoracic meningocele associated with neurofibromatosis: case report. The authors present a case of intrathoracic meningocele associated with neurofibromatosis. Computed tomography with metrizamide myelography proved valuable in locating the lesion, thus facilitating surgical intervention. With the preoperative diagnosis established and the severity of the meningocele known, the surgeons safely employed a subpleural approach at thoracotomy. 
Mechanism of cyclosporine-induced hypertension. Cyclosporine is a common immunosuppressive agent used in solid organ and bone marrow transplants and the treatment of some immunological diseases. It has been established that treatment with cyclosporine can cause a patient to develop hypertension within a few weeks of treatment. This review will examine this effect and effective ways to treat it. 
Mucosal and systemic IgA anti-gliadin antibody in celiac disease. Contrasting patterns of response in serum, saliva, and intestinal secretions. Serum IgA anti-gliadin antibody estimation is a recognized screening method for celiac disease. However, celiac disease is primarily a small intestinal mucosal disorder, and so we have examined the possibility that secreted, mucosal IgA anti-gliadin antibody might provide a more relevant measure of gluten sensitivity than that obtained from serum tests. Serum IgA anti-gliadin antibody and serum, salivary, and small intestinal aspirate IgA anti-gliadin antibody were measured by enzyme-linked immunosorbent assay. Serum IgA and IgG anti-gliadin antibody were markedly increased in untreated celiacs (N = 31) as compared to normals (N = 20) or disease controls (N = 39) (P less than 0.0001). Levels were lower in treated (N = 30) than untreated celiacs (P less than 0.001). In intestinal aspirates both untreated and treated patients had similar levels of IgA anti-gliadin antibody (P = 0.48), but both were significantly higher than in controls (P less than 0.01). Salivary IgA anti-gliadin antibody, by contrast, was not increased in celiac patients as compared to controls. Serum IgA anti-gliadin antibody was the most sensitive (84%) and specific (95%) test for detecting untreated celiac disease. It was also the most useful in patient follow-up where it provides an early objective indicator of adherence to a gluten-free diet. Mucosal IgA responses to gliadin in celiac disease appear to be compartmentalized, with different portions of the gastrointestinal tract functioning as separate immunological organs. Our results also demonstrate that serum and secretory IgA production are under independent control. 
Intraaortic balloon pumping as the postangioplasty strategy in acute myocardial infarction. To assess the usefulness of intraaortic balloon pumping (IABP) in acute myocardial infarction (AMI), 114 patients with anterior AMI undergoing emergency percutaneous transluminal coronary angioplasty (PTCA) for total occlusion of the left anterior descending artery were studied. After successful PTCA 66 patients were treated with conventional therapy (group I), and 48 patients were treated with IABP for 25 +/- 8 hours (group II). The reocclusion rate was significantly lower in group II (2.4% vs 17.7% p less than 0.05). An increase in ejection fraction in group II compared with group I was marginally significant (4.5 +/- 12.2% vs 9.2 +/- 13.0%, p = 0.08). Vascular complications occurred in two patients, but there were no deaths from IABP. These results suggest that after successful PTCA for acute myocardial infarction, IABP prevents reocclusion and may add strength to reperfusion in the improvement of left ventricular function. 
IIB osteosarcoma. Current management and survival statistics in the USSR. Three hundred and ninety-three patients with IIB osteosarcoma were treated at the author's institution between 1955 and 1986. In the first stage of the study, 88 patients were treated with surgery only. The five-year disease-free survival rate was 7%. In the second stage of the study, the efficacy of preventive chemotherapy after radical surgery was studied in 55 patients. The five-year disease-free survival rate was 34.4%. In the third stage of the study, the efficacy of combination therapy consisting of preoperative treatment, limb-saving surgery, and preventive chemotherapy was studied in 66 patients. The five-year disease-free survival rate was 35.5%. The authors examined results in 21 patients with Grade IV responses to evaluate the relationship between prognosis and morphogenic changes after preoperative radiotherapy and chemotherapy. The five-year disease-free survival rate was 57.9%. In the fourth stage of the study (conducted in 1986), two regimens of preoperative chemotherapy were initiated. The first regimen consists of intraarterial platinum infusions to patients with lower extremity bone damage. The second regimen consists of high-dose methotrexate infusions. The preliminary conclusion is that primary tumor damage is significantly more marked after intraarterial cisplatin infusion. 
Single motor end-plates in myasthenia gravis and LEMS at different firing rates. The jitter and frequency of blocking was studied at single motor end-plates in 10 patients with myasthenia gravis (MG) and in a patient with Lambert-Eaton myasthenic syndrome (LEMS), using single fiber EMG (SFEMG) with axonal microstimulation at rates varying from 0.5 Hz to 20 Hz. While some myasthenic motor end-plates showed lowest degrees of transmission disturbance at the lowest rates and most pronounced abnormality at the highest rates of stimulation, over one-half were most abnormal at intermediate rates and improved at higher rates. In 1 patient, all end-plates behaved in this way. On the other hand, all end-plates in the LEMS patient showed the expected improvement of the abnormal jitter and blocking on increasing the stimulation rate. It is argued that improvement of jitter and blocking at higher rates, unless dramatic, does not necessarily suggest a presynaptic abnormality. 
Treatment of esophageal varices: low versus high dose of 5% ethanolamine oleate. Twenty-four patients, undergoing sclerotherapy for esophageal varices, were injected with 10-20 ml of ethanolamine oleate 5% in the first treatment session (group A). Fourteen patients were injected with 40 ml of the same sclerosant in the first session (group B). Retrospective analysis was carried out to evaluate the efficacy and safety of the two doses. Variceal eradication was achieved in group B in significantly fewer sclerotherapy sessions. Rebleeding occurred in 16% of patients in group A, compared with no rebleeding in group B. There was no significant difference in the incidence of various complications. We conclude that the use of 40 ml of 5% ethanolamine oleate in the first session is more effective and as safe as the use of 20 ml of the same sclerosant. 
Proarrhythmia, cardiac arrest and death in young patients receiving encainide and flecainide. The Pediatric Electrophysiology Group The potential for proarrhythmic responses to the class IC sodium channel-blocking drugs encainide and flecainide has not been well described in young patients. Therefore, data were retrospectively collected from 36 institutions regarding 579 young patients who were administered encainide or flecainide for treatment of supraventricular tachycardias (encainide 86 patients, flecainide 369 patients) or ventricular arrhythmias (encainide 21 patients, flecainide 103 patients) to assess the frequency of proarrhythmia, cardiac arrest and death during therapy (adverse events). The two drugs were similar in regard to efficacy (flecainide 71.4%, encainide 59.8%) and rate of proarrhythmic responses (flecainide 7.4%; encainide 7.5%). However, patients receiving encainide more frequently experienced cardiac arrest (encainide 7.5% vs. flecainide 2.3%, p less than 0.05) or died during treatment (encainide 7.5% vs. flecainide 2.1%, p less than 0.05). Detailed data were provided for 44 patients experiencing one or more adverse events. Patient age, previous drug trials, concomitant therapy and days of inpatient monitoring were similar for patients receiving encainide or flecainide. However, echocardiographic left ventricular shortening before treatment was lower among patients receiving encainide (0.23 +/- 0.09) than among those receiving flecainide (0.34 +/- 0.06, p less than 0.05). Plasma drug concentrations were rarely elevated. Cardiac arrest (12 patients) and deaths (13 patients) occurred predominantly among patients with underlying heart disease, particularly among patients receiving flecainide for supraventricular tachycardia (8.3% vs. 0.3%, p less than 0.001). Fifteen patients with an ostensibly normal heart and normal ventricular function experienced proarrhythmia during treatment for supraventricular tachycardia, but only 3 of the 15 had a cardiac arrest or died. The relatively high incidence of adverse events should be considered when contemplating treatment with encainide or flecainide, particularly among patients with underlying heart disease. 
Effect of plasma glucose on infarct size in focal cerebral ischemia-reperfusion. Although hyperglycemia has been shown to consistently exacerbate ischemia brain injury following global or diffuse cerebral ischemia, the effect of hyperglycemia in unilateral focal cerebral ischemia remains controversial. Recent advances in thrombolytic therapy have enhanced the clinical significance of postischemic reperfusion. We studied the effect of plasma glucose on ischemic brain injury in a newly developed focal cerebral ischemia-reperfusion model. Rats allowed free access to food until ischemic insult developed intra- and postischemic hyperglycemia and cortical infarction. Rats fasted for 24 hours had blunted hyperglycemic responses. Infarct volumes were correspondingly smaller. The protective effect of fasting was partially abolished by glucose loading during ischemia to induce intra-ischemic hyperglycemia. Glucose loading immediately or 3 hours after focal cerebral ischemia did not significantly alter the protective effect of fasting. Insulin treatment in fed rats before ischemia also reduced hyperglycemic responses and infarct volume. Timing of insulin treatment was also critical in the reduction of ischemic injury. These findings indicate that plasma glucose during the period of ischemia is an important determinant of brain injury in focal cerebral ischemia-reperfusion and there is a therapeutic window for normalization of plasma glucose to be efficacious. 
The role of albumin in human physiology and pathophysiology, Part III: Albumin and disease states. The serum albumin level is one of several clinical parameters of the status of general health. There is a marked correlation between low albumin levels and the incidence of morbidity and mortality in hospitalized patients. Therefore, it is not surprising to find that hypoalbuminemia is a common finding among hospitalized patients. This results from alterations in the catabolic or anabolic rates, losses of albumin, or redistribution between the various fluid compartments of the body. Somewhat less well defined than the role of albumin as a prognostic indicator is its role in compounding pathophysiology. Hypoalbuminemia is known to be associated with delayed wound healing. The hypoalbuminemic state interferes with the normal functioning of the gastrointestinal tract. Qualitative changes in the albumin molecule which occur in renal disease may damage the nephron. Low serum albumin levels may adversely affect the coagulation system. Further investigation into the role of albumin in pathophysiology is warranted. 
Blood pressure as a risk factor for cardiovascular disease. The Framingham Study--30 years of follow-up Data from 30 years of follow-up of the original Framingham Study cohort of 5,070 men and women aged 30-62 years who were first examined during the period 1948-1952 and who were free of cardiovascular disease reveal that blood pressure is a strong and consistent predictor of the development of coronary heart disease, stroke, transient ischemic attack, and congestive heart failure. Other factors related to blood pressure like obesity, left ventricular hypertrophy as demonstrated on electrocardiograms, and heart enlargement as shown by x-ray radiography made several selective additional independent contributions to risk; heart enlargement by x-ray radiography was the best predictor of congestive heart failure. 
Crohn's colitis complicated by superimposed invasive amebic colitis. The clinical characteristics and endoscopic appearance of inflammatory bowel disease (IBD) may be very similar to those of amebic colitis. Physicians, especially in areas in which amebiasis is endemic, are familiar with this difficulty. Moreover, in individual cases, it may even be impossible to distinguish between the two conditions, since stool specimens, bowel biopsies, and serological studies may be negative for Entamoeba histolytica, even in the presence of invasive amebic colitis. Invasive amebiasis may rarely be superimposed on IBD, which further complicates the issue. We report here a young patient with a 7-yr history of Crohn's colitis proven histologically who developed invasive amebic colitis during steroid and 6-mercaptopurine treatment for active disease. Stool specimens, mucosal biopsies, and serological studies were negative for E. histolytica, and the diagnosis was established on pathological examination of a surgically resected bowel. Anti-amebic therapy should be considered in endemic areas in cases of persistent IBD. 
Malignant melanoma occurring in those aged under 30 in the west of Scotland 1979-1986: a study of incidence, clinical features, pathological features and survival. The study population consisted of the 95 patients who presented with cutaneous malignant melanoma in the west of Scotland between 1979 and 1986 and who were aged under 30 at the time of diagnosis. Over this 7-year period, 1299 melanomas were diagnosed in all age groups in this geographical area, increasing in incidence by 82% from 135 in 1979 to 246 in 1986. The proportion of melanomas diagnosed before the patients' thirtieth birthday remained constant at 6%. None were diagnosed in the under-15 age-group, and none developed on giant congenital naevi. Forty-two of the 95 melanomas (44%) in the under-30 group developed on a small naevus present either from birth or early childhood. These melanomas were thicker than those apparently developing on normal skin, but once controlled for tumour thickness and sex the presence of a pre-existing naevus did not affect 5-year survival. The overall 5-year survival was 76% with poorer survival associated with thicker tumours and male sex. This study suggests that small early onset naevi may have a higher potential for post-pubertal malignant change than has been previously recognized. 
Haemodynamic changes during the apnoea test for diagnosis of brain death. Haemodynamic responses to the apnoea test for the diagnosis of brain death were investigated in nine patients with severe head injury or cerebrovascular disease. To prove apnoea, the ventilator was disconnected for ten minutes and oxygen was insufflated to avoid hypoxaemia. No respiratory movement was seen in any patient. Ten minutes after disconnecting the ventilator, PaCO2 was increased to 78 +/- 3 mmHg and pH was reduced to 7.17 +/- 0.02. Adequate oxygenation was maintained in all patients. Cardiac output increased from 4.8 +/- 0.7 to 5.7 +/- 0.8 L.min-1 (P less than 0.05), and mean pulmonary artery pressure increased from 11 +/- 1 to 17 +/- 2 mmHg (P less than 0.01). However, mean arterial pressure, heart rate, pulmonary artery wedge pressure and right atrial pressure did not change. Plasma catecholamines were measured in three patients. Plasma norepinephrine concentrations increased in all three patients but the changes in plasma epinephrine were minimal. These circulatory responses to acute hypercapnia were less than those reported in awake volunteers and in patients during general anaesthesia. However, since plasma norepinephrine concentration increased during the test, some sympathoadrenal response, probably of spinal origin, was present, and may have prevented the direct depressant circulatory effects of acute hypercapnia. In conclusion, the apnoea test did not produce haemodynamic disturbances when respiratory acidosis was limited to a pH 7.17 +/- 0.02 and PaCO2 60-80 mmHg. 
Traumatic facial injuries with steering wheel loading. This study was conducted to evaluate the biomechanics of facial fractures caused by steering wheel loading. Twelve intact fresh human cadaver heads were impacted onto standard or energy-absorbing steering wheels with a custom-designed and validated vertical-drop apparatus. Either zygoma was impacted once at a velocity of 2.0-6.9 m/s. The specimens were oriented to permit a direct comparison between pretest and posttest radiography, and two-dimensional and three-dimensional CT images. Bone mineral content was determined, and biomechanical forces, accelerations, and deformations were recorded. More severe fractures were associated with higher forces on the zygoma. With increasing velocities, fractures initiated at the zygomatic region propagated to other unilateral regions such as the mandible and orbit or to the contralateral side. Less facial trauma was observed with energy-absorbing steering wheels compared with standard wheels at similar impact velocities. Bone mineral content did not correlate well with specimen age or with fracture severity. Clinically significant fractures were identifiable on 3-D CT images. The flexibility of 3-D CT in evaluating the spatial extent of facial abnormalities in different orientations may have significant impact in planning surgical procedures. 
Erythropoietin concentrations in obstructive sleep apnoea. Eight patients with obstructive sleep apnoea and a normal haemoglobin concentration underwent nocturnal studies during which oxyhaemoglobin saturation was recorded continuously with an ear oximeter and serum erythropoietin concentration was measured hourly by means of a radioimmunoassay. Serum erythropoietin concentrations remained within the normal range throughout the study despite falls in oxyhaemaglobin saturation in individuals to 33-78%. There was no relation between the degree of nocturnal hypoxaemia and serum erythropoietin concentrations. The brief cyclical episodes of hypoxaemia typical of obstructive sleep apnoea may not be a sufficient stimulus for erythropoietin secretion. 
A frameless, armless navigational system for computer-assisted neurosurgery. Technical note. A computer-assisted neurosurgical navigational system has been developed which displays intraoperative manipulation on the preoperative computerized tomography (CT) scans or magnetic resonance (MR) images. The system consists of a three-dimensional digitizer, a personal computer, and an image-processing unit. Utilizing recently developed magnetic field modulation technology, the three-dimensional digitizer determines the spatial position and orientation angles of the resin probe, triangle-shaped pointer, or suction tube with a small attached magnetic field sensor. Four fiducial markers on the scalp were used to translate the spatial data of the probe onto the preoperative CT scans or MR images of the patient. With this frameless, armless navigational system, CT or MR-imaging stereotaxy can be applied to conventional open neurosurgery without limiting the operative field or interfering with the surgical procedures. 
Diclofenac delays healing of gastroduodenal mucosal lesions. Double-blind, placebo-controlled endoscopic study in healthy volunteers. The effects of the water-soluble and delayed-release formulations of a nonsteroidal antiinflammatory drug, diclofenac, on the healing of gastroduodenal mucosal lesions were compared in a double-blind, double cross-over, placebo-controlled endoscopic study conducted in 14 healthy volunteers. Severe endoscopic lesions (petechiae, erosions, ulcers, and esophageal candidiasis) were found only in the group taking the soluble formulation of diclofenac (P less than 0.05 vs placebo). The endoscopic healing of biopsies at one week was delayed by both preparations in comparison to placebo (P less than 0.05 vs placebo). Neither formulation produced significantly more histological inflammation or minor endoscopic lesions (erythema, red striae) than placebo. Both formulations were equally well tolerated and produced no more symptoms than placebo. This study suggests that soluble diclofenac acts topically to delay gastroduodenal healing and produce gastroduodenal injury; it thus provides a model for future studies of the production, perpetuation, and healing of peptic lesions. 
Progressive congestive heart failure. Ways to approach office management. Treatment of congestive heart failure depends on the cause, precipitating factors, and symptoms of the disease in each patient. Dr Kahn outlines the use of the three main types of pharmacologic agents given for heart failure--diuretics, vasodilators, and digoxin. He describes a stepwise regimen, whereby agents are added as needed to improve symptoms and prolong life. 
Combined evaluation of total and functional liver plasma flows and intrahepatic shunting A diagnostic protocol was studied, designed to evaluate the main parameters of liver circulation in man. A water solution of D-sorbitol (S) and indocyanine green (ICG) was infused intravenously in six controls and nine cirrhotics. Steady-state renal and hepatic S clearances as well as hepatic ICG clearance were calculated. In controls the values (mean +/- SD) of the independent measurements of S and ICG hepatic clearance were 978 +/- 107 and 519 +/- 142 ml/min, respectively, while in cirrhotic patients they were 554 +/- 238 and 231 +/- 90 ml/min. Owing to the kinetic properties of S, its hepatic clearance may be regarded as a measure of functional liver plasma flow (FLPF). The total liver plasma flow (TLPF) values (mean +/- SD), calculated according to Fick's principle, were 1091 +/- 157 ml/min (S method) and 1033 +/- 153 ml/min (ICG method) in controls, and 1251 +/- 554 and 1284 +/- 677 ml/min in cirrhotics. In controls, FLPF was found to be very close to TLPF. In cirrhotic patients the difference between TLPF and FLPF (ranging from 169 to 2093 ml/min when measured by S method) was considered as an approximate estimate of intrahepatic shunting. The procedure is safe and simple and may add a new dimension to the investigation of hepatic circulation. 
Treatment of superior vena cava thrombosis with recombinant tissue type plasminogen activator. Thrombotic occlusion of the superior vena cava is an uncommon but serious complication of chronic indwelling venous catheters. Several reports have shown thrombolytic therapy with intravenous streptokinase or urokinase to be effective in the treatment of this condition. We report a case of superior vena cava thrombosis in a 53-year-old woman receiving chemotherapy for breast carcinoma through a subcutaneously implanted venous access catheter who was successfully treated with peripheral infusion of recombinant tissue type plasminogen activator (rtPA). 
The aphasic isolate. A clinical-CT scan study of a particularly severe subgroup of global aphasics. This paper outlines the clinical and CT scan features of a subtype of global aphasia, characterized by an extreme loss of communicative abilities, verbal as well as nonverbal. Three to four weeks after a left hemisphere stroke, 17 patients were completely unable to communicate with people addressing them. Though there were differences in their willingness to interact with the environment, they were characterized by complete loss of speech output and by inaccessibility to any kind of message, whether given verbally or through gestures. Patients who survived were reassessed 6 and 12 mos later and half of them were still found in a state of complete communicative isolation. The remainder had somewhat improved, but remained globally aphasic. The attempt to find a CT scan basis for this picture was disappointing. Only 35% of patients had a lesional pattern in agreement with the traditional view that ascribes global aphasia to the involvement of Broca's and Wernicke's areas. The location of lesion in the other cases spanned from anterior cortical damage, to posterior cortical damage, to deep nuclei damage and none of the lesions that have been proposed to account for subcortical global aphasia was consistently observed. 
Clinical factors affecting the immediate outcome of PTCA in patients with unstable angina and poor candidates for surgery. Percutaneous Transluminal Coronary Angioplasty (PTCA) has been successfully applied in unstable angina to carefully selected patients. In this study, PTCA was performed in 277 consecutive patients suffering from unstable angina and for whom bypass surgery was not a valid alternative because either of inoperable conditions or of emergency, or because surgery was not the best option. All patients were admitted first to the intensive care unit where an attempt was made to control unstable angina under conventional medical therapy using at least iv nitroderivative, heparin, and calcium blockers. After a standardized preparation PTCA was performed either as an emergency procedure in medically refractory unstable angina (107 cases) or as an elective procedure in controlled situations after a 7 to 10 days symptom-free period. Three hundred fifty-three coronary vessels were attempted. Results of this group are compared with those of a control group made of 670 consecutive stable patients recruited during the same period, and clinical characteristics are envisaged as potential predictive factors. Unstable angina is undoubtedly associated with a higher overall complication rate, but the immediate outcome is strongly affected by the clinical context. As an example, respective success and mortality rates are: 93% and 0% when a full revascularization is attempted; 91% and 0% in elective procedures in patients under 60; 87% and 1.2% in elective PTCA for multiple vessel disease; 80% and 6.5% in emergency PTCA; 80% and 11% in the overall triple vessel disease; 84% and 16% in patients with deeply altered ejection fraction; and 58% and 26% in triple vessel disease with 2 previously occluded coronary arteries. 
Hemodynamic effects of octreotide in patients with autonomic neuropathy. BACKGROUND. The somatostatin analogue, ectrootide, is being used to treat postprandial hypotension in patients with autonomic neuropathy. Although the therapeutic effect of the drug is presumably secondary to a splanchnic vasoconstrictor action, its effect on splanchnic hemodynamics has never been characterized in patients with autonomic neuropathy. Moreover, it is unknown whether octreotide acts on other vascular beds in this group of patients or whether it affects cardiac output. We, therefore, measured splanchnic, forearm, and systemic vascular resistance and cardiac output before and after administering octreotide (0.4 microgram/kg s.c.) to patients with idiopathic autonomic neuropathy and diabetic autonomic neuropathy. METHODS AND RESULTS. Splanchnic blood flow was determined from the clearance of indocyanine green in seven patients. We observed that octreotide decreased splanchnic blood flow (from 850 +/- 77 to 664 +/- 48 ml/min, p less than 0.005), increased mean blood pressure (from 97 +/- 6 to 115 +/- 3 mm Hg, p less than 0.005), and increased splanchnic vascular resistance (from 0.118 +/- 0.012 to 0.18 +/- 0.018 mm Hg/ml/min, p less than 0.005). Forearm blood flow was measured by plethysmography in 13 patients. Octreotide increased forearm vascular resistance in patients with idiopathic autonomic neuropathy (n = 8) from 19.1 +/- 1.0 to 27.2 +/- 3.8 mm Hg/ml/min/100 ml forearm volume (p less than 0.01) and from 25.2 +/- 3.9 to 41.0 +/- 6.8 mm Hg/ml/min/100 ml (p less than 0.01) in patients with diabetic autonomic neuropathy (n = 5). Cardiac output was measured by two-dimensional echocardiography. Octreotide administration increased cardiac output in five of six patients with idiopathic autonomic neuropathy (from 4.4 +/- 0.4 to 5.0 +/- 0.5 l/min, p less than 0.02) and five of five patients with diabetic autonomic neuropathy (from 3.8 +/- 0.4 to 5.1 +/- 0.4 l/min, p less than 0.02). Systemic vascular resistance increased in patients with idiopathic autonomic neuropathy from 21.2 +/- 2 to 24.9 +/- 2.6 (p less than 0.05) but did not change in patients with diabetic autonomic neuropathy. CONCLUSION. The pressor effect of octreotide in patients with autonomic neuropathy is associated with increased splanchnic and forearm vascular resistance and with increased cardiac output. 
Medical aspects of delayed convalescence. Disease and illness are not synonymous. In most instances, disease is demonstrable by anatomic, physiologic, biochemical, microbiologic, or immunologic abnormalities. Disease is a pathologic process. Not all persons with a disease are sick or ill. Symptoms of illness associated with a disease may be manifest or persist after the disease has disappeared. The absence of demonstrable disease, however, does not necessarily mean that symptoms of illness are unreal. Recovery from disease and recovery from illness are not always equated. Many factors, including personal characteristics and social circumstances, can be responsible for recovery from disease and illness. Chronic fatigue syndrome or symptoms of illness can persist in some patients but not in others after many different diseases. 
How to identify psychogenic disorders of stance and gait. A video study in 37 patients. Thirty-seven patients with psychogenic disorders of stance and gait were clinically evaluated, recorded on video, and analysed with regard to clinical phenomenology. Characteristic, suggestive and unspecific features were identified. Six characteristic features proved most valuable for diagnosis of psychogenesis, as they occurred alone or in combination in 97% of patients: (1) momentary fluctuations of stance and gait, often in response to suggestion; (2) excessive slowness or hesitation of locomotion incompatible with neurological disease; (3) "psychogenic" Romberg test with a build-up of sway amplitudes after a silent latency or with improvement by distraction; (4) uneconomic postures with wastage of muscular energy; (5) the "walking on ice" gait pattern, which is characterized by small cautious steps with fixed ankle joints; (6) sudden buckling of the knees, usually without falls. Seventy-three percent of patients had additional suggestive features. Classification into characteristic subtypes was not found useful because predominant features varied from patient to patient and occurred in various combinations. Factitious impairment of stance and gait was studied in 13 healthy drama students. Simulated gait dysfunction appeared less conspicuous and more difficult to diagnose than the clinical psychogenic disorders. 
An analysis of thirty cases of orbital lymphangioma. Pathophysiologic considerations and management recommendations. Thirty cases of orbital lymphangioma were reviewed. Clinical, imaging, and microscopic findings were integrated to develop a pathophysiologic construct and management guidelines. The basic lesion might be considered an abortive vascular system which arborizes among normal structures. Intrinsic hemorrhage expands portions of the small-caliber network into large blood cysts, prompting clinical recognition. While major hemorrhage led to early surgery in 12 cases, long pretreatment intervals could be analyzed in 17 others. Twelve patients had second hemorrhages of varied magnitude, from 2 weeks to 15 years after initial recognition; five patients did not in an average of 6.8 years. Some blood cysts contracted spontaneously. Among 23 operated cases, 12 patients had major new bleeds from 4 days to 12 years after initial surgery; 11 patients did not in an average of 4.2 years. Poor final visual acuity was associated with multiple surgeries. The authors advocate conservatism in surgical case selection and in operative dissection. 
Percutaneous coronary excimer laser-assisted angioplasty: initial multicenter experience in 141 patients. Initial multicenter clinical experience with percutaneous coronary excimer laser-assisted angioplasty is described for 158 lesions in 141 patients. Using a xenon chloride (308 nm) excimer laser generator and 1.5 to 1.75 mm catheters, excimer laser angioplasty was attempted at 135 ns pulse width, 25 to 40 Hz repetition rate, 2 to 5 s laser delivery time and 30 to 60 mJ/mm2 energy fluence. Laser success (greater than 20% improvement in luminal diameter) was achieved in 138 (87%) of 158 lesions, with a reduction to less than 50% stenosis noted in 77 lesions (49%). Overall, laser-assisted balloon angioplasty success (less than 50% residual stenosis without major complication) was observed in 129 (91%) of 141 patients. Procedural complications (abrupt closure 1.3%, side branch occlusion 1.9%, intimal dissection 6.3%, embolization 1.3%, filling defect 1.3%, perforation 1.9% and spasm 1.3% and major complications (non-Q wave myocardial infarction 4.8%, emergency coronary bypass surgery 3.5% and death 0%) were infrequent and predominantly related to subsequent balloon angioplasty. In the early follow-up period (range 1 to 10 months, mean 7), 111 (79%) of the 141 patients remain asymptomatic, whereas symptoms have recurred in 27 (19%) and 3 patients (2.1%) have died. Thus, percutaneous coronary excimer laser angioplasty appears to be a feasible and safe procedure. Assessment of the impact of this technology on the acute complications of and restenosis rates after angioplasty awaits further follow-up analysis. 
Long-term nonsteroidal antiinflammatory drug use and Helicobacter pylori infection. This study investigates whether patients who take nonsteroidal antiinflammatory drugs are more likely to have Helicobacter pylori gastritis than age-matched individuals who do not take nonsteroidal antiinflammatory drugs, and whether patients who take nonsteroidal antiinflammatory drugs who are also infected with H. pylori are more likely to have dyspepsia, mucosal damage, or ulcers than those who are not infected. Two studies were performed, one serological and the other endoscopic, both in arthritis patients receiving nonsteroidal antiinflammatory drugs chronically. The presence of H. pylori was identified with a sensitive enzyme-linked immunosorbent assay test. One hundred eighty-three patients participated in the serological study and 75 patients in the endoscopic study. The frequency of H. pylori infection increased with age, independent of nonsteroidal antiinflammatory drug use; the age-adjusted frequency of H. pylori infection in arthritis patients paralleled that of 351 asymptomatic individuals without arthritis. The frequency of H. pylori infection increased from 30.7% in age group 21-30 years to 73.4% in age group 61-75 years. Nonsteroidal antiinflammatory drug-induced mucosal injury, either hemorrhages or erosions, was more frequent in those without H. pylori infection than with infection (61% vs. 32% for hemorrhages and 57% vs. 34% for erosions for those without and with H. pylori infection; only the difference in the frequency of hemorrhages was significant, P less than 0.05). No difference was observed in the presence of dyspeptic symptoms between those with and without H. pylori infection. These data suggest that nonsteroidal antiinflammatory drug-induced damage to the gastroduodenal mucosa does not increase the susceptibility to H. pylori infection. 
Effects of hypercapnia and hypocapnia on respiratory resistance in normal and asthmatic subjects. The effects of hypercapnia and hypocapnia on respiratory resistance were studied in 15 healthy subjects and 30 asthmatic subjects. Respiratory resistance (impedance) was measured with the pseudo-random noise forced oscillation technique while the subjects rebreathed from a wet spirometer in a closed respiratory circuit in which end tidal carbon dioxide tension (PCO2) could be controlled. Hypercapnia was induced by partially short circuiting the carbon dioxide absorber, and hypocapnia by voluntary hyperventilation. The circulating air was saturated with water vapour and kept at body temperature and ambient pressure. A rise of end tidal PCO2 of 1 kPa caused a significant fall in respiratory resistance in both normal and asthmatic subjects (15% and 9% respectively). A fall of PCO2 of 1 kPa did not cause any significant change in impedance in the control group. In the asthmatic patients resistance increased by 13%, reactance fell by 45%, and the frequency dependence of resistance rose 240%. These findings confirm that hypocapnia may contribute to airway obstruction in asthmatic patients, even when water and heat loss are prevented. 
Gliofibroma. Case report. The case history of an infant with a large gliofibroma is presented. Gliofibromas are rare mixed glialmesenchymal tumors that have been poorly characterized. The computerized tomography appearance and a detailed light and electron microscopic description are presented, along with immunoperoxidase studies of this tumor. This case is compared with gliofibromas described elsewhere in the literature. 
Midgut volvulus in infants: diagnosis with US. Work in progress. The authors present findings from ultrasound (US) studies that can alert sonologists to the possibility of midgut malrotation complicated by volvulus in neonates and infants. A fluid-filled, distended duodenum seen at US examination in infants is a nonspecific sign of duodenal obstruction, as well as one of the signs of midgut malrotation. In addition, dilated, thick-walled bowel loops, mainly to the right of the spine, and peritoneal fluid were found at abdominal US examinations of three infants with midgut malrotation complicated by volvulus. In one infant with uncomplicated midgut malrotation, only signs of duodenal obstruction were present. The findings at US of duodenal obstruction associated with thickened bowel loops to the right of the spine and peritoneal fluid should lead the sonologist to suspect midgut malrotation complicated by volvulus, a potentially fatal condition, and an upper gastrointestinal series should then be performed to confirm the diagnosis. 
Optimal dose of neuroleptic in acute schizophrenia. A controlled study of the neuroleptic threshold and higher haloperidol dose. After individual determination of neuroleptic threshold (NT) doses of haloperidol, 106 patients with schizophrenia or schizoaffective disorder (Research Diagnostic Criteria) were treated openly at such doses (mean, 3.7 +/- 2.3 mg/d) for 2 weeks. Ten responding patients were discharged and unavailable for follow-up or refused subsequent randomization, and one non-responding patient refused randomization. The remaining 95 responding or nonresponding patients were then randomly assigned, double-blind, to a dosage of haloperidol two to 10 times higher (mean, 11.6 +/- 4.7 mg/d) or to a continuing NT dosage (mean, 3.4 +/- 2.3 mg/d) for another 2 weeks. Of the 58 patients exposed only to NT dosages of haloperidol, 72% clinically recovered within the 5-week trial. Higher dosages given to 47 patients did not lead to greater improvement in measures of psychosis, but did produce slightly greater declines in measures of hostility. Higher dosages did regularly lead to significant increases in distressing extrapyramidal side effects. 
Physiology and pathophysiology of colonic motor activity (2). The basic motor function of the colon is to mix and knead its contents, propel them slowly in the caudad direction, hold them in the distal colon until defecation, and provide a strong propulsive force during defecation. Infrequently, it also produces mass movements in the proximal colon. These motor functions are achieved in most species by three different types of contractions: the individual phasic contractions that include the short- and long-duration contractions, organized groups of contractions that include the migrating and nonmigrating motor complexes, and special propulsive contractions (giant migrating contractions). The spatial and temporal patterns of all of these contractions are controlled by myogenic, neural, and chemical control mechanisms. The individual phasic contractions are highly disorganized in time and space in the colon. For this reason, they are effective in mixing and kneading and slow distal propulsion. The underlying cause of the disorganization of short duration contractions is the irregularity in the frequency and waveshape of colonic electrical control activity and its phase unlocking throughout the colon. The individual contractions in many species occur in cyclic bursts called contractile states. At least in some species, these contractile states exhibit mostly caudad and sometimes orad migration. However, there are also nonmigrating or randomly migrating contractile states in the colon. These two patterns of contractile states are called colonic migrating motor complexes and colonic nonmigrating motor complexes, respectively. The giant migrating contractions provide the strong propulsive force for defecation and mass movements. The neural control of colonic contractions is organized at three levels--enteric, autonomic, and central. The enteric nervous system contains cholinergic and peptidergic neurons and plays a major role in the control of colonic contractions. The autonomic nerves, the vagi, pelvic, lumbar colonic, hypogastric, and splanchnic nerves, seem to continuously monitor the state of the colon and provide a modulatory input when necessary. These nerves play a major role in the reflexive control of colonic motor function. The voluntary input from the central nervous system coordinates the motor activity of the colon, rectum, anal canal and sphincters for orderly evacuation of feces during defecation. The role of acetylcholine, nonadrenaline, and the yet to be completely identified nonadrenergic, noncholinergic neurotransmitter, possibly VIP, in the control of contractions is fairly well established. Besides these, there are several other peptides and chemicals that are localized in the colonic wall; their physiological roles remain unknown. Colonic motor activity has been studied in several disease states. The findings have not always been consistent.(ABSTRACT TRUNCATED AT 400 WORDS). 
Assessment of the role of the glucocorticoid system in aging processes and in the action of food restriction. The Glucocorticoid Cascade Hypothesis of Aging and the hypothesis that food restriction retards the aging processes by preventing the development with age of hyperadrenocorticism were investigated. A longitudinal life span study of the daily concentration pattern of plasma corticosterone was conducted in male Fischer 344 rats fed ad libitum or restricted to 60% of the mean food intake of ad libitum fed rats. In another group of ad libitum fed and food-restricted rats, the influence of age on the response of plasma corticosterone levels to restraint stress was measured as was the time course of the return of plasma corticosterone to basal levels following the stress. The findings do not support the hypothesis that food restriction retards the aging processes by preventing the development of hyperadrenocorticism with advancing age. They also indicate that the Glucocorticoid Cascade Hypothesis does not describe a major aspect of the aging processes. Rather, the results suggest the possibility that a lifetime of daily periods of mild hyperadrenocorticism may, if anything, retard the aging processes. 
Effects of calcium-free solution, calcium antagonists, and the calcium agonist BAY K 8644 on mechanical responses of skeletal muscle from patients susceptible to malignant hyperthermia. The purpose of this investigation was to determine if alteration in the function of the dihydropyridine receptor may in turn modify halothane-induced contractures in muscle bundles from patients susceptible to malignant hyperthermia (MH). The effects of Ca(2+)-free Krebs Ringer (KR) solution, 5 microM verapamil, 5 microM nifedipine, and 10 microM of the Ca2+ agonist BAY K 8644 on halothane-induced contracture were therefore investigated. The halothane-induced contracture was prevented in the absence of extracellular Ca2+ and significantly reduced in the presence of verapamil or nifedipine. BAY K 8644 significantly enhanced the 0.5-, 1.0-, and 1.5-vol % halothane-induced contracture in MH-susceptible muscle bundles. When BAY K 8644 was dissolved in Ca(2+)-free KR solution, no contracture was observed in MH-susceptible muscle bundles. These results on cut MH-susceptible human muscle bundles support the hypothesis that halothane-induced contracture in MH can be modified by the binding of Ca2+ agonists or antagonists to the dihydropyridine receptor. The role of Ca2+ entry phenomena remains unclear, but the results suggest that extracellular Ca2+ is required to reprime or to bind to some sites of the dihydropyridine receptors. 
Regulation of MHC class II antigen expression. Opposing effects of tumor necrosis factor-alpha on IFN-gamma-induced HLA-DR and Ia expression depends on the maturation and differentiation stage of the cell. MHC class II induction by cytokines has been suggested to play a major role in the initiation and propagation of immune and autoimmune processes. TNF-alpha has been found both to enhance and also to inhibit IFN-gamma-induced MHC class II expression. In the present studies, the effect of TNF-alpha on IFN-gamma induced MHC class II expression was tested in various cell lines. On the basis of the data, we propose that, depending on the stage of differentiation and maturation of the cells, TNF-alpha might synergize or antagonize the affects of IFN-gamma on the regulation of MHC class II expression. Thus, in immature cells such as HL-60 or THP-1, TNF-alpha enhances IFN-gamma-induced class II expression. However, when differentiation was induced in these cells by TPA or IFN-gamma, the additive effect of TNF-alpha on the IFN-gamma induced DR expression was eliminated. Furthermore, TNF-alpha down-regulates the IFN-gamma-induced class II expression in differentiated cells such as human skin fibroblasts or activated macrophages. In bone marrow cells induced to differentiate in vitro, TNF-alpha decreased the IFN-gamma-induced MHC class II expression in a maturation-dependent fashion. These results provide a rational explanation for the conflicting reports regarding the effect of TNF-alpha on IFN-gamma-induced class II expression. But more importantly they may be relevant to the biologic function of TNF-alpha. Thus, we show that TNF-alpha-treated mice have reduced level of Ia expression on peritoneal macrophages and in vivo treatment with TNF-alpha antagonizes the ability of IFN-gamma to induce class II expression on these macrophages. 
A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure BACKGROUND. To define better the efficacy of vasodilator therapy in the treatment of chronic congestive heart failure, we compared the effects of hydralazine and isosorbide dinitrate with those of enalapril in 804 men receiving digoxin and diuretic therapy for heart failure. The patients were randomly assigned in a double-blind manner to receive 20 mg of enalapril daily or 300 mg of hydralazine plus 160 mg of isosorbide dinitrate daily. The latter regimen was identical to that used with a similar patient population in the effective-treatment arm of our previous Vasodilator-Heart Failure Trial. RESULTS. Mortality after two years was significantly lower in the enalapril arm (18 percent) than in the hydralazine-isosorbide dinitrate arm (25 percent) (P = 0.016; reduction in mortality, 28.0 percent), and overall mortality tended to be lower (P = 0.08). The lower mortality in the enalapril arm was attributable to a reduction in the incidence of sudden death, and this beneficial effect was more prominent in patients with less severe symptoms (New York Heart Association class I or II). In contrast, body oxygen consumption at peak exercise was increased only by hydralazine-isosorbide dinitrate treatment (P less than 0.05), and left ventricular ejection fraction, which increased with both regimens during the 2 years after randomization, increased more (P less than 0.05) during the first 13 weeks in the hydralazine-isosorbide dinitrate group. CONCLUSIONS. The similar two-year mortality in the hydralazine-isosorbide dinitrate arms in our previous Vasodilator-Heart Failure Trial (26 percent) and in the present trial (25 percent), as compared with that in the placebo arm in the previous trial, (34 percent) and the further survival benefit with enalapril in the present trial (18 percent) strengthen the conclusion that vasodilator therapy should be included in the standard treatment for heart failure. The different effects of the two regimens (enalapril and hydralazine-isosorbide dinitrate) on mortality and physiologic end points suggest that the profile of effects might be enhanced if the regimens were used in combination. 
Endoscopic injection sclerotherapy versus conservative treatment for patients with unresectable hepatocellular carcinoma and bleeding esophageal varices. We performed endoscopic injection sclerotherapy (EIS) in the treatment of 37 patients with bleeding esophageal varices due to unresectable hepatocellular carcinoma (HCC). The results were compared with those in another 33 HCC patients treated only conservatively, without EIS, during the same period. A majority of both groups died within 3 weeks after treatment. Comparing the two groups, there was no significant difference in fatal bleeding (66% vs 75%), but significantly fewer of the EIS patients died of the index hemorrhage (43% vs. 83%; p less than 0.01). Also, in the absence of portal vein thrombosis, EIS significantly reduced the risk of fatal bleeding (31% vs. 73%; p less than 0.25). The mean days of survival were 32 +/- 15 (range, 2 to 320) in the EIS group and 10 +/- 14 (range, 2 to 270) in the compared group (p less than 0.001). We conclude that EIS provides temporary control of acute esophageal variceal bleeding in patients with unresectable HCC. The major factors contributing to EIS failure are the lethal propensity of the underlying disease and portal vein thrombosis. 
A relationship between proteinuria and acute tubulointerstitial disease in rats with experimental nephrotic syndrome. The relationship between tubulointerstitial nephritis and proteinuria was characterized in experimental nephrosis in rats. In one group, proteinuria induced by aminonucleoside of puromycin (PAN) was reduced by using an 8% protein diet and adding the angiotensin I-converting enzyme (ACE) inhibitor enalapril to the drinking water. Two control groups were injected with saline and PAN, respectively, and fed a 27% protein diet. The first group had significantly reduced albuminuria and a definite attenuation of tubular cell injury. There was a strong positive correlation between the number of interstitial macrophages and albuminuria. The beneficial effect was reproduced by dietary-protein restriction alone, whereas ACE inhibition alone had an insignificant effect on the degree of proteinuria. Depletion of circulating T lymphocytes in one group of nephrotic rats eliminated interstitial lymphocytes but did not affect interstitial macrophage influx. Inhibition of the in situ proliferation of resident interstitial macrophages by unilateral kidney irradiation failed to change the intensity of the macrophage infiltration. Treatment of rats with sodium maleate produced proximal tubular cell toxicity but interstitial inflammation did not develop, suggesting that the latter is not a nonspecific response to tubular injury. These studies demonstrate a strong relationship between tubulointerstitial nephritis and the severity of proteinuria in experimental nephrosis. 
The dizzy patient: etiologic treatment. The basis for the vestibular complaint in dizzy patients should be viewed as having an etiology rather than a description of its clinical presentation. Effective treatment of vestibular disorders is based on the stabilization of the vestibular abnormality, to allow for central vestibular compensation. While not all of the etiologies for dizziness have been described, there are effective etiologic treatments available. These fit into categories of neurotransmitters, blood sugar and blood fat control, hormones, minerals, and treatments for autoimmune dizziness. 
Contractile response of aorta to alpha 1-adrenergic stimulation in Ca(2+)-free medium is reduced in spontaneous hypertension. Vascular responses of aortic rings to alpha 1-adrenergic stimulation by phenylephrine (Phe) from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) were studied in Ca(2+)-containing medium and Ca(2+)-free medium plus 50 mumol/L EGTA. Although there was no difference in the sustained force development between SHR and WKY vessels in response to 100 mmol/L KCl or 10 mumol/L Phe in Ca(2+)-containing medium, the transient contractile response to 10 mumol/L Phe in Ca(2+)-free medium was substantially smaller in SHR compared to that in WKY. Subsequent addition of 2.5 mmol/L Ca2+ restored the sustained contractile response to a similar level in both SHR and WKY vessels. The transient contractile response to Phe in Ca(2+)-free medium containing EGTA, presumably due to the release of intracellular Ca2+, decreased progressively with preincubation time in Ca(2+)-free medium, indicating intracellular Ca2+ depletion. Such a temporal change of aortic response was more pronounced in SHR than in WKY. The subsequent response to Ca2+ repletion in the presence of Phe, on the other hand, increased progressively with Ca(2+)-depletion period and was higher in SHR than in WKY. The rate of relaxation after washout of Phe was slower in SHR aorta compared to WKY aorta. These results, together with our earlier findings, collectively suggest that the previous known deficiency in Ca2+ pumping mechanisms of vascular muscle microsomes leading to a reduced functional size of intracellular Ca2+ pool may account for the smaller contractile response of SHR aorta to alpha 1-adrenergic stimulation in Ca(2+)-free medium and the slower rate of relaxation. 
The occurrence of epilepsy and febrile seizures in Virginian and Norwegian twins. Twin studies provide an efficient method for examining the importance of genetic and environmental factors in the etiology of disorders such as epilepsy. Population-based twin registries are especially valuable for studies of this type since effects of reporting and self-selection biases on the resulting data are minimized. Among 14,352 twin pairs contained in the Virginia and Norwegian twin panels for whom questionnaire information was available, there was a history of epilepsy in one or both members of 286 pairs; febrile seizures were reported in 257 pairs. Analyses of questionnaire data revealed no significant differences in concordance rates between Virginian and Norwegian twins for either epilepsy or febrile seizures. Probandwise concordance rates for epilepsy were 0.19 in monozygotic twins and 0.07 in dizygotic twins. Analogous rates for febrile seizures were 0.33 (monozygotic) and 0.11 (dizygotic). These results provide further evidence that genetic factors do have a role in the expression of epilepsy and febrile seizures. 
Retinal migraine, chorea, and retinal artery thrombosis in a patient with primary antiphospholipid antibody syndrome. We report the case of a patient with the unusual combination of migraine, chorea, and retinal arterial thrombosis along with laboratory evidence of autoimmunity. In the absence of systemic lupus erythematosus, the clinical manifestations suggest the presence of the primary antiphospholipid antibody syndrome. 
Inability of coronary blood flow reserve measurements to assess the efficacy of coronary angioplasty in the first 24 hours in unselected patients. To determine functional and anatomic changes in the first 24 hours after coronary angioplasty, we studied at random 15 patients (9 men, mean age 60 years) who underwent coronary angioplasty of 16 coronary arteries. Quantitative coronary angiography and coronary flow reserve measurements from digitized coronary angiograms were performed before, immediately after, and 24 hours after coronary angioplasty. Calculated were the minimal luminal diameter, obstruction area, and percentage diameter stenosis from two preferably orthogonal projections. Prior myocardial infarction in the myocardial region of interest was present in four patients. Seven patients had multivessel disease. Collateral vessels supplying the compromised flow region were observed in three patients. Six patients had refractory unstable angina pectoris. After coronary angioplasty, angiographically visible dissection was noted in six patients, whereas side branch occlusion was observed in one. Minimal luminal diameter before, immediately after, and 24 hours after was 0.93 +/- 0.18 mm, 1.53 +/- 28 mm, and 1.53 +/- 0.21 mm, respectively; obstruction area was 0.70 +/- 0.26 mm2, 1.92 +/- 0.69 mm2, and 1.87 +/- 0.51 mm2, respectively; diameter stenosis was 60.4 +/- 8.0%, 36.8 +/- 11.4%, and 37.6 +/- 5.3%, respectively. The coronary flow reserve (lower limit of normal with this technique 3.4) was essentially the same before and immediately after coronary angioplasty (1.26 +/- 0.59 vs 1.30 +/- 0.42, p = NS) with a slight improvement to 1.78 +/- 0.90 (p less than 0.05) 1 day later. Coronary artery dimensions correlated poorly with coronary blood flow reserve before and after angioplasty. 
Posterior cortical dementia with alexia: neurobehavioural, MRI, and PET findings. A progressive disorder of relatively focal but asymmetric biposterior dysfunction is described in a 54 year old right handed male. Initial clinical features included letter-by-letter alexia, visual anomia, acalculia, mild agraphia, constructional apraxia, and visuospatial compromise. Serial testing demonstrated relentless deterioration with additional development of transcortical sensory aphasia, Gerstmann's tetrad, and severe visuoperceptual impairment. Amnesia was not an early clinical feature. Judgment, personality, insight, and awareness remained preserved throughout most of the clinical course. Extinction in the right visual field to bilateral stimulation was the sole neurological abnormality. Early CT was normal and late MRI showed asymmetrical bioccipitoparietal atrophy with greater involvement of the left hemisphere. Results from positron emission tomography (PET) showed bilaterally asymmetric (left greater than right) occipitotemporoparietal hypometabolism. The metabolic decrement was strikingly asymmetric with a 50% reduction in glucose consumption confined to the left occipital cortex. The picture of occipitotemporoparietal compromise verified by MRI, PET, and neurobehavioural testing would be unusual for such degenerative dementias as Alzheimer's (AD) and Pick's disease, although atypical AD with predominant occipital lobe involvement cannot be excluded. This case supports the concepts of posterior cortical dementia (PCD) as a clinically distinct entity and for the first time documents its corresponding metabolic deficit using PET. 
Evaluation of salvage surgery in heavily irradiated cancer of the buccal mucosa. This report describes the authors' experience with salvage surgery in 78 patients with carcinoma of the buccal mucosa who failed after high-dose radical radiation therapy at Regional Cancer Centre, Trivandrum, India. Forty-four patients (56%) required a hemimandibulectomy for adequate tumor clearance. Fifty-four patients (69%) required a primary reconstructive procedure for wound closure. Follow-up periods ranged from 28 months to 63 months (median follow-up, 41 months). Thirteen patients (17%) developed nonfatal postoperative complications. Thirty-one patients recurred after surgery, five of whom were again salvaged by further surgery. Overall, the recurrence rate was 36%. Most of the recurrences (26/31) were at the primary site. The overall 5-year actuarial disease-free survival after salvage surgery was 59.7%. T stage of the recurrent tumor and its skin infiltration emerged as factors which significantly influenced disease-free survival (P less than 0.05). 
Reactive astrogliosis is widespread in the subcortical white matter of amyotrophic lateral sclerosis brain. Widespread astrogliosis exists in the subcortical white matter in amyotrophic lateral sclerosis (ALS). As revealed by glial fibrillary acidic protein (GFAP) immunostaining, the gliosis has the morphological properties of an active process. It is present in the midfrontal, inferior parietal, temporal, cingulate, and occipital cortices, as well as in the motor cortex. Compared to matched regions from other neurological diseases, the gliosis in ALS does not appear to be the nonspecific result of a progressive, degenerative disease. In cell number and apparent cell size, the gliosis is comparable to that present in neurological diseases known to have white matter gliosis. Cytologically, the gliosis most closely resembles that present in cases of cerebral infarction. The basis for this similarity is unknown. 
Reversibility of cardiac abnormalities in human immunodeficiency virus (HIV)-infected individuals: a serial echocardiographic study. Seventy adults who tested positive for human immunodeficiency virus (HIV) were prospectively studied with serial echocardiography to better define the prevalence and progression of cardiac disease in such patients. Fifty outpatients (Group A), including 44 with acquired immunodeficiency syndrome (AIDS) and 6 with AIDS-related complex, and 20 additional patients (Group B) with asymptomatic HIV infection had baseline echocardiographic studies at a time when no patient had symptomatic heart disease. Follow-up studies were performed at 9 +/- 3 months in 52 patients (74%) and again at 15 +/- 3 months after baseline studies in 29 patients (41%). During the study, 22 patients (44%) in Group A and 1 patient (5%) in Group B died. Cardiac abnormalities were noted in 26 patients (52%) in Group A and 8 patients (40%) in Group B (p = NS) on initial or follow-up study. An abnormal left ventricular ejection fraction (less than 45%) or fractional shortening (less than 28%) was seen in seven patients in Group A; of these, three had normal left ventricular function on a later echocardiogram. One patient in Group B had persistent left ventricular dysfunction. All patients in Group A with left ventricular dysfunction on two serial studies died within 1 year after the initial echocardiogram. Ejection fraction did not change between baseline and two follow-up studies in either group (A: 52 +/- 9 vs. 56 +/- 9 vs. 55 +/- 5%, p = NS; B: 58 +/- 6 vs. 58 +/- 5 vs. 59 +/- 6%, p = NS). Right-sided cardiac enlargement resolved in 18 patients (44%), including 5 of 10 in Group A and 3 of 8 in Group B. 
Intestinal permeability after single dose gluten challenge in coeliac disease. The changes of intestinal permeability before and after a gluten load were studied. The study group comprised 27 patients with coeliac disease (mean age 12.3 years) and 19 healthy controls matched by sex and age. Intestinal permeability was studied by measuring the urinary excretion of two sugars, lactulose and L-rhamnose, before and six hours after the ingestion of five palatable biscuits made with 50 g of gluten powder. The patients with coeliac disease had been on a gluten free diet during the previous two years. After the gluten load lactulose and L-rhamnose urinary excretion changed significantly in patients, and a significant increase in the lactulose: L-rhamnose ratio was also observed. No significant changes were observed in the controls. In view of the modification of the three biopsies diagnostic protocol made by the European Society for Paediatric Gastroenterology and Nutrition, permeability tests associated with single gluten challenges may be an added contribution to the accuracy of the diagnosis in childhood. 
Clinical course and outcome in class IC antiarrhythmic overdose. 120 cases of class IC antiarrhythmic overdose, including propafenone, flecainide, ajmaline and prajmaline overdose, were evaluated with respect to clinical course, therapy and outcome. Whereas drug overdose in general has an overall mortality of less than 1%, intoxication with antiarrhythmic drugs of class IC was associated with a mean mortality of 22.5%. Nausea, which occurred within the first 30 minutes after ingestion, was the earliest symptom. Spontaneous vomiting probably led to self-detoxication in about half the patients. Cardiac symptoms including bradycardia and, less frequently, tachyrhythmia occurred after about 30 minutes to 2 hours. Therapeutic measures included administration of activated charcoal, gastric lavage and a saline laxative, catecholamines, and in some patients, hypertonic sodium bicarbonate, insertion of a transvenous pacemaker and hemoperfusion. Fatal outcome was mainly due to cardiac conduction disturbances progressing to electromechanical dissociation or asystolia. Resuscitation, which had to be performed in 29 patients, was successful in only two of them. No correlation was found between fatal outcome, the type of antiarrhythmic, and ingested dose. Since a specific treatment is not available and resuscitive procedures including sodium bicarbonate and insertion of a pacemaker are of limited therapeutic value, early diagnosis and primary detoxification are most important for prevention of fatal outcome. 
A pilot study of sphincter-sparing management of adenocarcinoma of the rectum. After analysis of 26 prospectively accrued patients with distal rectal adenocarcinomas who underwent sphincter preservation treatment, we have concluded that tumors that invade only the submucosa can safely be treated with surgery alone and that tumors that invade the muscularis or further can be safely treated with surgery combined with chemoradiotherapy. None of the patients had either local or distant recurrence, with a median follow-up of 21 months. All patients have been fully continent. The results, although preliminary, imply that resection of distal rectal adenocarcinoma with sphincter preservation, and adjuvant therapy when appropriate, have achieved local and distant control equal to the conventional Miles' abdominoperineal resection, but without the need for a permanent colostomy. 
Value of transesophageal echocardiography as an adjunct to transthoracic echocardiography in evaluation of native and prosthetic valve endocarditis. To determine if transesophageal echocardiography provides better visualization of valvular vegetations than transthoracic echocardiography, we used both methods to evaluate 24 consecutive patients (mean age, 54 years; 15 female patients and nine male patients) referred for symptoms suggestive of infectious endocarditis. Ten of the 24 patients had one or more valvular prostheses. Echocardiograms were classified as positive or negative based on visualization of valvular vegetations or abscesses. Of ten patients with a final diagnosis of infectious endocarditis on extended follow-up, transthoracic echocardiography was positive in five patients. Transesophageal echocardiography not only yielded abnormal findings in all ten of these patients, but also revealed additional information in four of the five patients with abnormal transthoracic echocardiographic examinations. Among the 14 patients who, on subsequent follow-up, were found not to have infectious endocarditis, transthoracic echocardiography was normal in 13 and falsely abnormal in one. Transesophageal echocardiography revealed no evidence of infectious endocarditis in any of these patients. The ten patients who were determined to have infectious endocarditis all had positive blood cultures and no alternative cause for their clinical presentation; in seven patients in this group who underwent operative or postmortem evaluation, infectious endocarditis was confirmed. All patients without infectious endocarditis were demonstrated to have other causes for their clinical presentation. We conclude that transesophageal echocardiography is a highly valuable test in the work-up of patients with suspected infectious endocarditis, especially those patients with inconclusive or normal transthoracic echocardiograms. In addition, transesophageal echocardiography may be of benefit to patients with previously documented infectious endocarditis and a complicated clinical course in whom additional cardiac lesions are suspected but not demonstrated by transthoracic echocardiography. 
C5a, cutaneous mast cells, and inflammation: in vitro and in vivo studies in a murine model. To evaluate further the interactions of C5a and mast cells in cutaneous inflammation, the ability of human native C5a (nC5a) (10 to 500 ng/ml) and human recombinant C5a (rC5a) (10 ng/ml to 100 ng/ml) to induce histamine release from purified BALB/c cutaneous mast cells (CMC) and peritoneal mast cells (PMC) was analyzed. It was found that nC5a induced histamine release from CMC but not from PMC, with a maximal net release at 250 ng/ml nC5a (22.8 +/- 2.6%). Kinetic experiments demonstrated that nC5a-induced maximal net histamine release occurred 5 min after the presentation of this stimulus (25.8 +/- 6.0%). Using rC5a and CMC, dose-response studies indicated a maximal net release of 7.0 +/- 1.7% at rC5a of 10 ng/ml, and kinetic studies showed a maximal net release at 5 min of incubation (12.9 +/- 1.6%). Release induced by rC5a was calcium-dependent, and peaked at 30 degrees C. These results indicate that functional heterogeneity exists between the CMC and the PMC of BALB/c mice, that C5a is a relevant stimulus for characterization of this heterogeneity, and that CMC from these animals can serve as a convenient in vitro model for the study of human C5a-mast cell interactions. In vivo, injections of nC5a (25-100 ng) and rC5a (25-100 ng) into the skin of BALB/c mice induced an increase in cutaneous vasopermeability, as assessed by the extravasation of intravenously injected 125I-bovine serum albumin. nC5a induced a dose-dependent increase in vasopermeability, whereas alterations induced by rC5a plateaued at 50 ng. The C5a-induced vasopermeability was markedly enhanced in animals that had been previously treated with an inhibitor of serum carboxypeptidase, which converts C5a to the less potent derivative, C5a des Arg. These findings suggest that carboxypeptidase plays an important role in vivo in the modulation of C5a-induced cutaneous inflammation in murine skin. 
Elevated intravesical pressure causes arterial hypoperfusion in canine colocystoplasty: a fluorometric assessment. Since 1988 there have been 15 reported cases of late, spontaneously ruptured intestinal cystoplasties at bowel sites remote from the anastomosis. Ischemic necrosis has been suggested as a possible etiology. We examined this hypothesis by quantifying the uptake of intravascular fluorescein in the augmented bowel of adult mongrel canines. There was a statistically significant decrease in fluorescein uptake at high intravesical pressures, which appeared to be most pronounced at the antimesenteric border. This laboratory study supports a recent clinical report of histological changes pathognomonic for chronic ischemia in the augmented bowel of patients with spontaneous rupture. 
Predictive value of ventricular arrhythmias for patency of the infarct-related coronary artery after thrombolytic therapy. In animal studies reperfusion of coronary arteries is commonly accompanied by ventricular arrhythmias. It is not certain, however, whether ventricular arrhythmias can be used as a reliable non-invasive marker of reperfusion in humans. Two-channel Holter recordings were obtained from the start of an intravenous infusion of streptokinase until coronary angiography (2.8 (2.7) hours (mean SD)) afterwards) in 57 patients with acute myocardial infarction of less than four hours who were generally not treated with antiarrhythmic drugs. Ventricular arrhythmias occurred in 21 (37%) of the 57 patients: accelerated idioventricular rhythm in 13 patients and non-sustained ventricular tachycardia in 15 patients. Seven patients had both accelerated idioventricular rhythm and non-sustained ventricular tachycardia. Coronary angiography showed a patent infarct-related vessel in 12 (92%) of the 13 patients with accelerated idioventricular rhythm (95% confidence interval 66 to 99%), in 22 (50%) of the 44 patients without accelerated idioventricular rhythm (95% CI 34 to 66%), in 11 (73%) of the 15 patients with non-sustained ventricular tachycardia (95% CI 45 to 92%), and in 23 (55%) (95% CI 39 to 71%) of the 42 patients who did not have non-sustained ventricular tachycardia. Seventeen (81%) of the 21 patients with accelerated idioventricular rhythm, or non-sustained ventricular tachycardia, or both, had a patent infarct-related vessel (95% CI 58 to 94%) as did 17 (47%) of the 36 patients with no ventricular arrhythmia (95% CI 29 to 65%). In patients with accelerated idioventricular rhythm after thrombolysis the infarct-related vessel is almost certain to be patent; but the infarct-related coronary artery can still be patent when no arrhythmia is seen. 
Atypical hyperplasia of the breast: mammographic appearance and histologic correlation. The mammograms and histologic slides of 58 cases of atypical hyperplasia (AH) of the breast were retrospectively reviewed to determine the geographic correlation (direct, near, or remote) between mammographic abnormalities (if present) and the histologic findings. A direct mammographic-histologic correlation was found in 24 of the 58 cases (41%), near correlation in 15 (26%), and remote correlation in 19 (33%). Clustered microcalcifications were the most common mammographic abnormality that was directly correlated with AH at histologic examination. Atypical ductal hyperplasia was much more frequently associated with a direct mammographic-histologic correlation than was atypical lobular hyperplasia (48% vs 9%). The authors conclude that, although no pathognomonic appearance of AH was discovered, mammographic abnormalities similar to those of small cancers could be directly correlated with histologic findings in 41% of cases. Since AH has been shown to be associated with a five- to tenfold increased risk of subsequent invasive carcinoma, frequent clinical and at least yearly mammographic follow-up is suggested once AH is discovered. 
A randomized study of closure of the peritoneum at cesarean delivery. This study was conducted to test the hypothesis that nonclosure of the visceral and parietal peritoneum during low transverse cervical cesarean delivery is not associated with increased intraoperative or immediate postoperative complications. One hundred thirteen patients scheduled for low transverse cervical cesarean were randomized to either closure of both the visceral and parietal peritoneum with absorbable suture (N = 59) or no peritoneal closure (N = 54). Patients were cared for in the usual postoperative manner without reference to treatment group. There were no demographic differences between the groups and no differences in method(s) of anesthesia, operative indication(s), or use of peripartum epidural narcotics. The incidence of fever, endometritis, or wound infection was similar between groups. There were no differences in the number of patients requiring parenteral narcotic analgesia or in the number of doses per patient. The number of oral analgesic doses was significantly greater with closure than without (P = .014). The frequency with which postoperative ileus was diagnosed in each group was similar, and there was no difference regarding the day on which patients were advanced to liquid or select diets. Bowel stimulants were administered more frequently to the closure than to non-closure patients (P = .03). The average operating time was shorter for the open group than for the closure group (P less than .005). We conclude that non-closure of the visceral and parietal peritoneum at low transverse cervical cesarean delivery appears to have no adverse effect on immediate postoperative recovery, may decrease postoperative narcotic requirements, allows less complicated return of bowel function, and provides a simplified and shorter surgical procedure. 
Experience with the first 250 endometrial resections for menorrhagia [published erratum appears in Lancet 1991 Jan 1;337(8753):1362] 234 patients with menorrhagia were treated hysteroscopically by transcervical resection of the endometrium (TCRE) instead of hysterectomy. 250 procedures were performed under general anaesthesia (63%) or under sedation plus local anaesthesia (38%). The endometrium was excised either totally (91%) or partially (9%) in all but one case, and 56 (22%) of the patients underwent simultaneous resection of submucous fibroids. Surgical time (range 10-100 min) varied with the gynaecologist's experience. 479 ml was the average volume of uterine irrigant absorbed by the patient. Blood loss was usually slight. Operative complications were uncommon, but 4 (2%) women sustained a uterine perforation (without serious sequelae), 7 (3%) absorbed more than 2 litres of fluid, and 1 required tamponade to control postoperative bleeding. Hospital stay was short and full recovery usual by 1-2 weeks. Menstrual symptoms improved in over 90% of the patients throughout the follow-up of up to 2 1/2 years; 27-42% of the women became amenorrhoeic at some time after total TCRE. Results were best in women greater than 35 years of age, but was not influenced by the presence of fibroids or pretreatment dysmenorrhoea. 10 (4%) women later underwent hysterectomy. Hysteroscopy 3 and 12 months after surgery revealed a small, fibrotic uterine cavity in the majority. 
Pathologic fibrosis and matrix connective tissue in the subaortic myocardium of patients with hypertrophic cardiomyopathy. To evaluate scar-type and matrix connective tissue and to assess their role in the diastolic dysfunction of hypertrophic cardiomyopathy, surgically resected subaortic myectomy specimens and several autopsy hearts from patients with hypertrophic cardiomyopathy were studied. Eighteen specimens were differentially stained by a newly developed method that precisely determines relative collagen content; these tissues were compared with postmortem hypertrophied and normal control subaortic specimens. Quantitation revealed a 72% higher level (36.5 vs. 22.1 micrograms collagen/mg protein) of stainable collagen in the hearts with hypertrophic cardiomyopathy than in hypertrophied control hearts. The endocardial plaque was quantitated morphometrically, and it constituted only 4.6 +/- 1.7% of the total increased collagen content in the cardiomyopathy specimens. For the matrix studies, the cardiomyopathy specimens were stained by a silver impregnation technique that identifies connective tissue elements not normally visible with routine histologic methods. There was a marked increase in content of all matrix components, both in areas of pathologic scarring and in "normal" zones. Whorls of matrix connective tissue were noted in regions of myocyte whorls, as well as independent of them. Thus, these studies revealed a striking increase of both scar-type and matrix connective tissue in hypertrophic cardiomyopathy. The extensive scarring and the pronounced interstitial and intercellular matrix connective tissue may contribute to the increased ventricular chamber stiffness and impaired relaxation in this disease. 
Erythropoietin concentrations in obstructive sleep apnoea. Eight patients with obstructive sleep apnoea and a normal haemoglobin concentration underwent nocturnal studies during which oxyhaemoglobin saturation was recorded continuously with an ear oximeter and serum erythropoietin concentration was measured hourly by means of a radioimmunoassay. Serum erythropoietin concentrations remained within the normal range throughout the study despite falls in oxyhaemaglobin saturation in individuals to 33-78%. There was no relation between the degree of nocturnal hypoxaemia and serum erythropoietin concentrations. The brief cyclical episodes of hypoxaemia typical of obstructive sleep apnoea may not be a sufficient stimulus for erythropoietin secretion. 
Growth of tracheal anastomoses: advantage of absorbable interrupted sutures [published erratum appears in Ann Thorac Surg 1991 Jul;52(1):176] Growth of the trachea after complete transection and anastomosis was studied in four groups of 1-month-old New Zealand white rabbits. The trachea was transected at the fifth cartilaginous ring and then anastomosed with continuous 6-0 polypropylene (Prolene) (group 1), interrupted 6-0 polypropylene (group 2), continuous 6-0 polydioxanone (PDS) (group 3), or interrupted 6-0 PDS (group 4). The animals were followed up for 90 to 103 days (mean follow-up, 95 days). At the time the animals were killed, body weight had increased 125% (1.2 to 2.7 +/- 0.18 kg). Growth of the trachea was assessed at the time of death. Results from this study suggest that growth of a tracheal anastomosis is retarded in a growing animal model. The degree of resultant stenosis was significantly less when an absorbable suture material (PDS) and an interrupted suturing technique were used. 
Impedance plethysmography: a new method for continuous muscle perfusion monitoring. Vigilant postoperative monitoring of the buried muscle flap is critical after free transfer because early diagnosis of vascular insufficiency is essential to allow prompt correction. We have identified a monitoring method utilizing needle electrodes and impedance plethysmography that gives a beat-to-beat representation of muscular perfusion. In 25 New Zealand White rabbits the gastrocnemius muscle was isolated on its vascular pedicle, and two intramuscular needle electrodes were placed. The instantaneous impedance changes of the muscle (corresponding to the pulsatile volume changes of perfusion) were measured and recorded. Using this representation of perfusion, an independent judge was able to correctly diagnose muscular ischemia 100 percent of the time (n = 25). Further, the judge was able to correctly distinguish the ischemia as arterial (n = 10) or venous (n = 10) in origin 100 percent of the time. Additionally, we monitored muscle perfusion transcutaneously in five free muscle flaps and demonstrated a reliable impedance signal that correlated with perfusion. 
Sclerosing vasculopathy of the central nervous system in nonelderly demented patients. Three nonelderly patients without hypertension whose clinical and radiologic features otherwise resembled Binswanger's subcortical arteriosclerotic encephalopathy underwent biopsy of the hyperintense periventricular lesions seen on magnetic resonance imaging. The pathologic findings of the periventricular lesions consisted of gliosis with mild rarefaction and edema of the white matter. All patients had a sclerosing vasculopathy of unknown cause, which involved numerous small vessels within the periventricular lesions. The vessels stained negatively for amyloid, amyloid precursors, desmin, vimentin, keratin, immunoglobulin, and complement. On electron microscopy, small arteries, arterioles, venules, and capillaries were characterized by swollen astrocytic foot processes surrounding the vessels; dense, perivascular collagen packing; crystalline arrays of filaments within basement membrane; giant lipid-laden lysosomes within perivascular cells; and narrowing of the vascular lumina. Similar changes were not seen in a control group of 19 patients. The pathologic features of the vessels in these cases are distinct from the vasculopathy associated with Binswanger's subcortical arteriosclerotic encephalopathy. We suggest that a spectrum of vasculopathies may be associated with dementia and periventricular hyperintense lesions on magnetic resonance imaging. 
Invasive treatment of pancreatic fluid collections with surgical and nonsurgical methods. Pancreatic fluid collections (PFC) can be drained surgically or nonsurgically with endoscopic or radiologic techniques. To define subgroups of patients with PFC who would benefit from the new modalities, we reviewed a period (1977 to 1990) during which both surgical and nonsurgical invasive techniques were available. Patients with phlegmon or necrosis at initial diagnosis were excluded. Sixty-five patients (35 male, 30 female) underwent 1 or more drainage procedures. A mean postprocedure follow-up of 10.2 months was available for 59 patients. Initial management was nonsurgical in 80% of patients. Procedures in patients with follow-up comprised invasive nonsurgical drainage (n = 25), invasive nonsurgical drainage plus surgery (n = 22), and surgery only (n = 12). Results for each group, respectively, were: morbidity, 20%, 20%, and 24%; mortality, 8%, 5%, and 0%; and successful drainage, 92%, 82%, and 83%. The choice of management appeared to be based on etiology and radiologic characteristics. Patients with nonalcohol- and nonbiliary-associated pancreatitis without a radiographically defined wall were more common in the invasive nonsurgical group and were successfully treated without surgery. Nonsurgical invasive techniques are efficacious in the treatment of PFC in this subgroup of patients. 
Seromuscular enterocystoplasty in rats. Enterocystoplasty is commonly used in clinical practice. Many of its undesirable effects, that is infections, stones, mucus production, absorption of urinary components into the blood stream and risk of cancer, result from the intestinal mucosa lining the urinary tract. We report on the feasibility of creating an enterocytoplasty with a seromuscular colonic segment that acquires a transitional epithelial lining. Augmentation enterocystoplasty was performed in 51 male, 500 gm., Sprague-Dawley rats with a 1.82 cm.2 patch of left colon from which the mucosa had been stripped. The serosal surface was used as lining for the enterocystoplasty. The intestinal patch and the bladder capacity at known pressure were measured at operation and at sacrifice. The histology of the enterocystoplasty was studied in detail following sacrifice. Of the animals 40 survived without significant complications and were sacrificed at a mean postoperative time of 30 days (range 5 to 80 days). In the remaining 11 rats a bladder stone developed but it did not seem to affect the outcome of the experiment. The size of the patch could be measured in 22 rats: it was 1.82 cm.2 (standard deviation +/- 0.86) at operation and 2.30 cm.2 (standard deviation +/- 1.1) at sacrifice. In none of the rats did the patch decrease in size. The bladder capacity at a known pressure (mean 17 cm. water) could be measured in 26 animals: it was 2.35 ml. (standard deviation +/- 0.65) at operation and 5.18 ml. (standard deviation +/- 1.19) at sacrifice. Histological analysis was done in 40 rats. In all cases the serosal surface was lined with transitional epithelium, there was no fibrosis or inflammation and the structure of the muscular layer of the bowel remained intact. The earliest growth of uroepithelium in the serosal surface of the bowel was noted at 5 days. This model suggests that the seromuscular enterocystoplasty can be constructed successfully in the rat model. The seromuscular intestinal patch does not shrink. The bladder capacity increases and histology shows a uroepithelial lining of the augmentation. 
Obesity: types and treatments. Causes of obesity include a low resting metabolic rate, environmental factors, family behavior patterns, a poorly developed satiety response and reactive eating due to stress or anxiety. Morbid obesity is characterized by an increased number of adipocytes and a degree of irreversibility. Overeating increases the size of adipocytes; however, once adipocytes achieve their maximal size, proliferation is induced and massive, irreversible obesity may result. A syndrome of restrained eating produced by chronic dieting leads to hunger, frustration and rebound overeating. Treatment may be unsuccessful because of the failure to address specific causes of obesity in individual patients and the use of reducing regimens that are not designed to maintain weight loss. Recognition of the diverse clinical forms of obesity and their different etiologies permits treatment regimens to be more specific, increasing the likelihood of success. Even with this approach, treatment failure is common. 
Transmembrane domain length variation in the evolution of major histocompatibility complex class I genes. The fifth exons of major histocompatibility complex (MHC) class I genes encode a transmembrane domain (TM) that is largely responsible for class I antigen cell-surface expression usually through conventional hydrophobic amino acid-membrane interactions or, less often, through phosphatidylinositol linkage. In this report we show that Peromyscus leucopus, a Cricetidae rodent, has MHC class I genes (Pele-A genes) encoding three distinct sizes of TMs. Increases in TM lengths were due to tandem duplications of sequences similar to human hypervariable minisatellite repeats and the lambda chi site. We discerned remnants of a similar duplication event in comparable rodent and primate MHC class I genes. Furthermore, several duplications and deletions appear to have occurred independently in H-2, RT1, Pele-A, and ChLA genes in near-identical positions. Accumulated data suggests that sequences in the fifth exon of MHC class I genes may, therefore, constitute a mutational or recombinational hot spot that is mediated by minisatellite- and chi-like sequences imbedded within the coding region. The MHC class I genes may thus have recruited "selfish" DNA in their evolution to encode cell surface proteins. Expression of Pele-A genes was examined by the polymerase chain reaction (PCR) using oligonucleotide primers specific for exon 4 and 5 sequences. The PCR product sizes indicated that genes encoding each TM domain length are ubiquitously transcribed. 
The use of FDG-PET in the detection and management of malignant lymphoma: correlation of uptake with prognosis. Twenty-one patients with untreated malignant lymphoma in the head and neck region were evaluated with positron emission tomography (PET) using fluorine-18-fluorodeoxyglucose (FDG) and gallium-67 SPECT imaging. Tumor-to-normal soft-tissue contrast ratios (TCRs) obtained 60 min after injection of FDG were higher than 2.6, and all malignant lymphomas were clearly visualized. In patients with poor prognosis, higher TCRs and glucose utilization rates (GURs) were observed, whereas low TCR and GUR were shown in a patient with low-grade malignancy. In comparison with 67Ga scintigraphy, patients with high TCRs and GURs were likely to show increased accumulation of gallium-67, but accumulation of gallium-67 was not increased as much as FDG in poor prognostic patients. FDG-PET may be useful in the detection and management of malignant lymphoma. 
Campylobacter enteritis--New Zealand, 1990. In August-September 1990, an outbreak of Campylobacter enteritis occurred at a camp near Christchurch, New Zealand. This report provides a preliminary summary of the investigation of this outbreak by the New Zealand Communicable Disease Centre and the Canterbury Area Health Board. 
Usefulness of transesophageal echocardiography in the diagnosis of conditions mimicking aortic dissection. Between September 1987 and April 1989, forty patients suspected to have aortic dissection were evaluated by transesophageal echocardiography. Aortic dissection was identified in 18 patients. This study evaluated the ability of transesophageal echocardiography in the assessment of the 22 patients in whom aortic dissection was not found. A range of pathologic conditions was diagnosed in these patients. Five patients had ischemic heart disease when they were initially seen. Among the remaining 17 only one patient had a normal aorta. Aortic disease was present in the other 16 patients with aortic dilatation in 10. Atheromas were detected in seven patients with concomitant aortic dilatation in five of them. An extrinsic aortic mass was present in two patients. Transesophageal echocardiography correctly identified an anastomotic leak at the site of left coronary artery implantation in a patient with a recent Bentall procedure, and a large mobile clot within the proximal descending aorta in a patient with blunt chest trauma. These findings obviated the need for other tests in 15 patients and led to surgery in four with no ancillary tests performed in three of them. Thus transesophageal echocardiography has an important role in assessing patients with suspected dissection. Aortic disease is common even in patients in whom aortic dissection is excluded, and some of the conditions can be just as life-threatening as dissection. Transesophageal echocardiography not only reliably identifies dissection but can also detect luminal and extraluminal diseases not adequately visualized by other modalities. 
Dispersion of refractoriness in canine ventricular myocardium. Effects of sympathetic stimulation. In 18 dogs on total cardiopulmonary bypass, the average interval between local activations during artificially induced ventricular fibrillation (VF interval) was measured from extracellular electrograms, simultaneously recorded from up to 32 ventricular sites. VF intervals were used as an index of local refractoriness, based on the assumption that during ventricular fibrillation, cells are reexcited as soon as they have recovered their excitability. In support of this, microelectrode recordings in two hearts during ventricular fibrillation did not show a diastolic interval between successive action potentials. Refractory periods determined at a basic cycle length of 300 msec with the extrastimulus method correlated well with VF intervals measured at the same sites. Thus, this technique allows assessment of spatial dispersion of refractoriness during brief interventions such as sympathetic stimulation. The responses to left, right, and combined stellate ganglion stimulation varied substantially among individual hearts. This was observed both in dogs with an intact (n = 12) and decentralized (n = 6) autonomic nervous system. Individual ventricular sites could show effects of both left and right stellate ganglion stimulation (42% of tested sites) or show effects of left-sided stimulation only (31%) or right-sided stimulation only (14%). In 13% of sites, no effects of stellate stimulation were observed. Apart from these regional effects, the responses could be qualitatively different; that is, within the same heart, the VF interval prolonged at one site but shortened at another in response to the same intervention, although shortening was the general effect and prolongation the exception. Whenever sites responded to stellate ganglion stimulation with a shortening of VF interval, this shortening was approximately 10% for left, right, or combined stimulation, whether the autonomic nervous system was intact or decentralized. In six of 12 hearts in the intact group, there was a distinct regional effect of left stellate ganglion stimulation; in the other six hearts, the effects were distributed homogeneously over the ventricles. In three hearts, the effect of left stellate ganglion stimulation was strongest in the posterior wall, and in the other three hearts, in the anterior wall. The effects of right stellate ganglion stimulation were restricted to the anterior or lateral part of the left ventricle. Dispersion of VF intervals increased after left and combined stellate ganglion stimulation in the intact group and after right stellate ganglion stimulation in the decentralized group, but not significantly in every heart. This points to a marked individual variation with regard to the effects of sympathetic stimulation on electrophysiological properties of the heart. 
Depressed contractile function due to canine mitral regurgitation improves after correction of the volume overload [published erratum appears in J Clin Invest 1991 Aug;88(2):723] It is known that long-standing volume overload on the left ventricle due to mitral regurgitation eventually leads to contractile dysfunction. However, it is unknown whether or not correction of the volume overload can lead to recovery of contractility. In this study we tested the hypothesis that depressed contractile function due to volume overload in mitral regurgitation could return toward normal after mitral valve replacement. Using a canine model of mitral regurgitation which is known to produce contractile dysfunction, we examined contractile function longitudinally in seven dogs at baseline, after 3 mo of mitral regurgitation, 1 mo after mitral valve replacement, and 3 mo after mitral valve replacement. After 3 mo of mitral regurgitation (regurgitant fraction 0.62 +/- 0.04), end-diastolic volume had nearly doubled from 68 +/- 6.8 to 123 +/- 12.1 ml (P less than 0.05). All five indices of contractile function which we examined were depressed. For instance, maximum fiber elastance (EmaxF) obtained by assessment of time-varying elastance decreased from 5.95 +/- 0.71 to 2.25 +/- 0.18 (P less than 0.05). The end-systolic stiffness constant (k) was also depressed from 4.2 +/- 0.4 to 2.1 +/- 0.3. 3 mo after mitral valve replacement all indexes of contractile function had returned to or toward normal (e.g., EmaxF 3.65 +/- 0.21 and k 4.2 +/- 0.3). We conclude that previously depressed contractile function due to volume overload can improve after correction of the overload. 
Septic shock. Septic shock (SS) is the most common type of shock encountered by internists, and its prevalence appears to be increasing. SS complicates all types of infections. The hemodynamic characteristics of SS include a low systemic vascular resistance and an elevated, but relatively inadequate, cardiac output. A cardiomyopathy frequently occurs. The major endogenous mediator of SS is tumor necrosis factor, and interleukins-1 and -2 may also contribute. Important secondary phenomena include release of platelet activating factor, vasodilator prostaglandins, and upregulation of adhesion molecules on polymorphonuclear leukocytes and endothelial cells. Current therapy is often ineffectual, and potentially promising new therapeutic approaches are reviewed. 
Clinical indications for cervical spine radiographs in alert trauma patients. Cervical spine fracture/dislocation is a potentially devastating injury that may be clinically difficult to diagnose. Therefore, a vast majority of trauma patients undergo cervical spine X rays when only a relatively small number of them will actually have a cervical spine injury. Because of the costly overuse of radiography, studies have been undertaken to define high yield criteria for evaluation of patients. This study examined the characteristics of acute cervical spine fracture/dislocation in alert trauma patients. Of 79 patients with this discharge diagnosis at St. Elizabeth Hospital Medical Center between 1982 and 1987, 47 met the criteria of Class I level of consciousness. All 47 patients complained of neck pain or demonstrated cervical tenderness to palpation. Other parameters (such as loss of consciousness, paresthesias, decreased sensation, weakness, cervical muscle spasm, decreased anal tone, and associated injuries) did not, individually or in combination with each other, consistently predict cervical spine injury. Although occult or painless cervical spine injuries have been reported in the literature, a careful review of these cases revealed that these injuries were not truly asymptomatic. Our study suggests that selected patients can be excluded from radiologic evaluation of the cervical spine. However, large prospective studies are needed to validate this finding. 
Pacemaker failure on induction of anaesthesia. A patient with a permanent pacemaker presented for repair of a strangulated hernia. During induction of anaesthesia, the pacemaker generator stopped discharging, thus causing cardiac arrest. The likely cause of the generator failure was inhibition by suxamethonium-induced muscle fasciculations. Following defibrillation, and increase in stimulation threshold necessitated urgent insertion of a transvenous pacing system. It is suggested that, when suxamethonium is to be used in a patient with a permanent pacemaker, consideration should be given to reprogramming the pacemaker to asynchronous mode before induction of anaesthesia. If a patient with a pacemaker requires defibrillation, an acute increase in stimulation threshold may result and cause loss of capture. Rapid insertion of a transvenous pacing system may be necessary. 
Shock wave-induced pancreatic trauma. A case is described of the appearance of a pancreatic or peripancreatic lesion after left renal calculus fragmentation by extracorporeal shock wave lithotripsy (ESWL). Its anatomical location and subsequent disappearance suggest it was related to trauma caused by the shock waves. The brief literature on pancreatic injury after ESWL is reviewed, and the role of the patient's underlying liver disease in the genesis of this complication is discussed. 
Different types of skew deviation. Although all manifest skew deviations appear the same for the clinician, skew deviation can result from different combinations of dysconjugate vertical ocular deviations. Evidence is presented for three different types of skew deviation when it occurs as a feature of an ocular tilt reaction. In type 1 (utricle) there is upward deviation of both eyes with different amplitudes, as described for otolith Tullio phenomenon in humans. In Type 2 (dorsolateral medulla oblongata) hypertropia of one eye occurs while the other eye remains in the primary position, the hypothetical mechanism of skew deviation in Wallenberg's syndrome. In Type 3 (midbrain tegmentum) there is simultaneous hypertropia of one eye and hypotropia of the other eye, as described for electrical stimulation of midbrain tegmentum in monkeys and observed in clinical cases with a paroxysmal ocular tilt reaction. 
Effect of P6 acupressure on postoperative vomiting in children undergoing outpatient strabismus correction. A prospective, double-blind study was conducted to compare the effect of pressure at the P6 (Neikuan) point with placebo as an antiemetic in children. Sixty-six patients, ages 3-12 yr, undergoing outpatient surgery for correction of strabismus, were allocated randomly to receive either bilateral P6 acupressure or placebo during the perioperative period. The study was designed to detect a 50% difference in the incidence of postoperative vomiting between the two groups, with a 90% power of achieving a statistically significant result at the 5% level (two-tailed). The incidence of postoperative vomiting for the placebo group was 58% before discharge from hospital, 73% at home and 82% in the first 24 h after surgery. The corresponding results for the acupressure group were 58% before discharge, 71% at home and 94% in the first 24 h. These differences were not significant; P6 acupressure did not reduce the incidence of postoperative vomiting in children undergoing strabismus surgery. 
Prognosis for recovery from prolonged posttraumatic unawareness: logistic analysis. This study reviews the course and outcome of 130 patients who remained in a state of prolonged unawareness 30 days after severe cranio-cerebral trauma. Prognostic indicators and outcome were fitted by a logistic model. The significant prognostic factors observable in the first week after trauma were found to be ventilatory status, motor reactivity and significant extraneural trauma. The significant prognostic factors after the first month of unawareness were early ventilatory status, early motor reactivity, late epilepsy and hydrocephalus. The estimated probability of recovery of awareness (that is, consciousness) ranged from 0.94 in patients with early decorticate posturing in the absence of both extraneural trauma and ventilatory disturbance to 0.06 in patients with flaccidity, extraneural trauma and ventilatory disturbance in the first week after injury. 
Coronary artery thrombolysis: comparison of approved agents. Three agents approved for the lysis of thrombi in coronary arteries--alteplase, anistreplase and streptokinase--have undergone critical clinical experimental trials in Europe and the United States. Global comparison of their efficacy shows that alteplase is slightly more effective (71 percent) in restoring patency than anistreplase (60 percent) and streptokinase (58 percent). Streptokinase and anistreplase are allergenic, and repeat administration is not feasible in the short-term, a distinct advantage for alteplase. More accurate dosing of thrombolytic agents and skillful use of aspirin and heparin improve the efficacy of thrombolytic therapy but can also increase the risk of bleeding. A recanalization rate of 90 percent or more could be achieved if the thrombolytic agent is administered within the first hour after thrombosis. Administration this soon after the development of thrombosis may be possible if the agent is given outside the hospital by practicing physicians or, perhaps, paramedics. 
Preoperative prediction of pathological tumor volume and stage in clinically localized prostate cancer: comparison of digital rectal examination, transrectal ultrasonography and magnetic resonance imaging. Accurate preoperative staging is important for proper selection of patients for radical retropubic prostatectomy. Preoperative staging by digital rectal examination, transrectal ultrasound, magnetic resonance imaging (MRI), Gleason grade and prostate specific antigen was compared to pathological stage for 25 patients who underwent radical retropubic prostatectomy. The predictive value for tumor confinement was 36% by rectal examination, 37% by ultrasound and 30% by MRI. The predictive value for extracapsular disease was 100% by rectal examination, 83% by ultrasound and 66% by MRI. Preoperative determinations of tumor volume by any modality did not correlate with pathological tumor volume. Digital rectal examination, ultrasound and MRI clinically understage the disease in most patients but they may be reliable to predict extracapsular disease. 
Sublaminar fixation in lumbosacral fusions. Sublaminar fixation to stainless steel rectangles was employed in an effort to improve the fusion rate in lumbar and lumbosacral arthrodesis. Thirty-seven patients had spondylolisthesis, and 26 had other causes of pain secondary to lumbar mechanical instability. Of the 63 patients, 53 achieved fusion and 52 had relief of pain. No infections or neurologic complications were encountered. This fusion rate of 84% does not significantly differ from rates obtained with noninstrumented methods, and this construct is no longer used for lumbar fusions. 
Leber's hereditary optic neuropathy and Kearns-Sayre syndrome: mitochondrial DNA mutations. Mitochondrial DNA (mt DNA) supplies extranuclear (cytoplasmic) genes which program the manufacture of 13 of the 67 peptides of the mitochondrial respiratory enzymes. The remaining 54 are coded by nuclear DNA. All human children and adults, male and female, are entirely dependent on the cytoplasm of the ovum for their complement of mt DNA; the sperm contributes none. Accordingly, mutations in the mt DNA in a mother's ova will be passed on to all her children, although not all are clinically affected. Leber's hereditary optic neuropathy is in most cases due to a mutation that leads to the replacement of guanine by adenine at position 11778 in mt DNA. This causes histidine to be inserted instead of the normal arginine at the site of the 340th amino acid in the respiratory enzyme NADH subunit 4, hence its defective function. Other point mutations in the mt DNA coding for polypeptides of the respiratory chain complex or controlling sequences coded by mt DNA have been found in other families with Leber's hereditary optic neuropathy. Mitochondrial DNA is the site of other mutations as well. For ophthalmologists, the most important of these is the rare Kearns-Sayre syndrome (pigmentary retinopathy plus muscular dystrophies, especially of the extraocular muscles). Kearns-Sayre syndrome is due to deletions in the mt DNA, which vary in size and so affect a number of different respiratory enzymes, hence the variable manifestations. Cases are usually sporadic because the disease is often so severe that affected individuals do not reproduce if they survive, but in some cases inheritance from the mother has been reported. 
Treatment of uterine leiomyomata with a luteinizing hormone-releasing hormone agonist: the possibility of nonsurgical management in selected perimenopausal women. OBJECTIVE: To evaluate the efficacy of luteinizing hormone-releasing hormone agonist (LH-RH-a) in the treatment of leiomyomata. DESIGN: A retrospective randomized trial. SETTING: Hospital department of obstetrics and gynecology. PATIENTS: Twenty-five women, ages 36 to 54 years with symptomatic uterine leiomyomata, were divided into two groups according to the responsiveness to LH-RH-a: group A patients reached menopause after LH-RH-a, whereas resumption of menstruation occurred within 12 weeks after cessation of therapy in group B. INTERVENTIONS: Luteinizing hormone-releasing hormone agonist was administered intranasally three times a day with 150 micrograms insufflation of one spray in each nostril (total dose: 900 micrograms/d). MAIN OUTCOME MEASURES: Efficacies of treatment were assessed in terms of uterine volume, hemoglobin concentrations, serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), and bone density during and after treatment. RESULTS: In both groups, hemoglobin concentrations increased significantly after 16 weeks of treatment. A significant reduction in uterine volume was observed in both groups. After completing therapy, there was no further significant change in uterine volume in group A, whereas uterine volume in group B returned to pretreatment values. Serum LH and FSH concentrations were suppressed during treatment, but those gonadotropins in group A increased significantly up to the menopausal levels after treatment. Serum E2 concentrations in both groups showed consistent suppression by the end of the first treatment cycle. After cessation of therapy, serum E2 levels on group A remained in the castrate range, whereas E2 in group B returned to pretreatment levels, concomitant with the return of normal ovulation. CONCLUSIONS: Intranasal administration of LH-RH-a was successful in significantly decreasing uterine volume and increasing hemoglobin concentration in premenopausal women with leiomyomata. 
Expression of Tn, sialosyl Tn, and T antigens in human pancreas. Carbohydrate antigens representing some of the initial steps in mucin O-linked glycosylation were examined in specimens of normal pancreas, chronic pancreatitis, and pancreatic adenocarcinoma. Tn antigen, recognized by Vicia villosa lectin, was expressed by all specimens of normal pancreas (acinar cells) and pancreatic cancers and all but one case of chronic pancreatitis. Sialosyl Tn antigen, recognized by monoclonal antibody TKH2, was expressed in a cancer-associated fashion, being completely absent in normal pancreas but expressed by 56% of chronic pancreatitis and 97% of pancreatic cancers. T antigen, recognized by monoclonal antibody AH9-16, was expressed in 68% of normal pancreas (acinar cells), 67% of chronic pancreatitis, and 48% of pancreatic cancer tissues. These results indicate that normal acinar cells of the pancreas are capable of expressing selected carbohydrate structures associated with the initial steps of mucin glycosylation. The marked expression of sialosyl Tn compared with T antigen in pancreatic cancers suggests that with malignant transformation there is selective usage of glycosyltransferase enzymes involved in mucin oligosaccharide synthesis. 
Patterns of epithelial migration in the unaffected ear in patients with a history of unilateral cholesteatoma. Epithelial migration in a centrifugal manner is an established phenomenon in the normal human tympanic membrane. This pattern of migration is symmetrical in both ears of any one individual. We present a prospective study on the pattern of tympanic ink dot migration on the normal drum, in patients with a history of cholesteatoma in one ear. It was demonstrated that patients who develop cholesteatoma have a normal migratory pattern and rate in the unaffected ear. The conclusion from this study is that defective migration is not the initiating factor in the development of acquired cholesteatoma. 
The use of CT scanning to triage patients requiring admission following minimal head injury. Recent data have suggested that patients with both a normal cranial CT scan and normal neurologic examination following minimal head injury (MHI) have no risk of neurologic deterioration. This study prospectively examined the safety of discharging patients from the emergency department (ED) after MHI whether or not there was a responsible observer at home. MHI was defined as a history of loss of consciousness (LOC), a Glasgow Coma Scale (GCS) score of 14 or 15, and no focal neurologic findings. In a 4-month period 111 patients with MHI were evaluated. Fifteen (14%) patients had a CT scan which revealed an intracerebral injury; 96 patients had a normal CT scan; five patients with normal CT scans were admitted because of persistent lethargy; and one patient was admitted after his CT that demonstrated an old infarct; the remaining 90 patients were discharged. There were 71 men and 19 women with a mean age of 29 years. The mechanism of injury was assault in 55, MVA in 30, and falls in five. The initial GCS in was 15 in 79 and 14 in 11. Fifty-eight per cent of patients were intoxicated. Fifty-seven (63%) patients were successfully contacted by telephone; none had developed any neurologic symptoms. Thirty-one patients who could not be followed up gave fictitious phone numbers. These data suggest that CT can reliably triage patients who can be discharged from the ED following MHI, even in the absence of a responsible observer. Hospital admission can be avoided in more than 80% of patients sustaining MHI, better utilizing scarce hospital resources. 
Collateral circulation as a marker of the presence of viable myocardium in patients with recent myocardial infarction. The relationship between the presence of viable myocardium and the extent of coronary collateral circulation to the infarct area was evaluated in 20 patients with a recent anterior myocardial infarction who had complete obstruction of the left anterior descending coronary artery. The viability of myocardial tissue was assessed by exercise thallium-201 myocardial scintigraphy, and the collateral circulation was angiographically evaluated by means of a collateral index ranging from 0 to 3. Patients were divided into two groups according to the presence (group 1, n = 10) or absence (group 2, n = 10) of viable myocardium in the perfusion territory of the infarct-related artery. The collateral index in group 1 was 2.5 +/- 0.5 (SD), which was significantly higher than the 0.7 +/- 0.8 in group 2. These findings indicate that the presence of ischemic but viable myocardium is intimately related to the development of collateral circulation in patients with myocardial infarction, and the existence of well-developed collateral channels predicts the presence of viable myocardium in the infarct area. 
Patient dose and associated risk due to radiological investigation of the internal auditory meatus. The radiation doses and associated somatic risks due to four radiological examinations for acoustic neuromata (AN) have been investigated. These examinations were (1) plain film radiography of the internal auditory meatus (IAM), (2) computed tomography (CT) of the IAM, (3) CT of the posterior fossa and (4) CT of the IAM with air contrast. Organ dose measurements were performed using lithium fluoride thermoluminescent dosemeters loaded in a patient equivalent phantom. Dose equivalents to various organs are presented, together with the effective dose equivalent and collective effective dose equivalent for each examination. Hypothetical fatal somatic risks for each examination studied here have been estimated from the effective dose equivalents. The estimated number of hypothetical fatal cancers induced by radiological examinations for AN is between approximately 110 and 820 times lower than the number of detected AN, depending on the method of assessing the radiation dose to the remainder organs. It is concluded that in this particular study the radiological examinations are of net benefit to this group of patients. 
Hydatidiform mole and fetus with normal karyotype: support of a separate entity. Repetitive hydatidiform mole was observed in four pregnancies. The pregnancies presented with heavy bleeding and vomiting, but the post-evacuation courses were uncomplicated, with rapid regression of serum hCG levels. Cytogenetic investigations, analyses of restriction fragment length polymorphisms, and flow cytometry in three pregnancies were consistent with diploid, biparental conception as the origin of fetal tissue and molar and nonmolar villi. In one pregnancy, the analyses of cytogenetic markers suggested the coexistence of two different cell lines of dizygotic, biparental origin, whereas DNA analysis was consistent with a single conception. With incomplete genetic information, a hydatidiform mole with coexistent normal fetus is generally considered to result from dizygous twinning comprising an androgenetic complete mole and a normal conception. In the present gestations, the results based on several techniques applied on numerous samples from different tissues render this possibility unlikely. Some of the contradictions between histologic and cytogenetic classifications of hydatidiform mole may be explained by diploid, biparental partial mole, which seems to constitute a separate subgroup within hydatidiform mole. Following chorionic villus sampling or amniocentesis, continued pregnancy may be considered, depending on prenatal diagnosis including genetic marker analysis. 
Phenothiazine-associated apnea in two siblings. A two-month-old white girl presented to our facility with increasing lethargy and new onset apnea and bradycardia following a week of upper respiratory tract infection symptoms. The patient had been receiving a cough syrup containing promethazine hydrochloride during the previous five days, which was temporally correlated with the onset of lethargy and apneic episodes. Upon further investigation, it was discovered that the patient's older sibling also may have experienced phenothiazine-associated apnea after receiving a combination of meperidine hydrochloride, promethazine hydrochloride, and chlorpromazine as a premedication prior to an endoscopic examination. In addition to the presentation of these cases, the literature pertaining to phenothiazine-associated apnea is reviewed. 
Confirmation of endotracheal tube placement: a miniaturized infrared qualitative CO2 detector. STUDY OBJECTIVES: A miniaturized, infrared, solid-state, end-tidal CO2 detector was used to confirm emergency endotracheal tube (ETT) placement. DESIGN: This prospective, clinical study used a miniature, infrared, solid-state end-tidal CO2 detector to confirm ETT placement in an acute setting. SETTING: The ICU, emergency department, and hospital floor. TYPE OF PARTICIPANTS: There were 88 consecutive adult patients requiring 100 emergency intubations. MEASUREMENTS AND MAIN RESULTS: The indication for airway intervention was considered urgent in 79% and under arrest conditions in 21%. The mean number of intubation attempts was 1.83 (range, one to five) with difficulty of intubation of 6.48 and confirmation of 7.75, on a linear scale from 0 (lowest) to 10 (highest). Determination of ETT position revealed intratracheal intubation in 96% and esophageal intubation in 4%. Placement was confirmed by direct visualization or radiography in all cases. Sensitivity and specificity for ETT localization was 100% (P less than .0001). CONCLUSION: This hand-held infrared capnometer reliably confirms ETT placement under emergency conditions. 
Lateral rhachotomy for thoracic spinal lesions. Capener's "Lateral Rhachotomy" was modified by additional excision of the pedicle, articular facets, part of the lamina, and a posterior half of the vertebral bodies on one side through a transpleural approach to the thoracic spine, and a retroperitoneal approach to the lumbar spine. The aim was to excise a space-occupying lesion, which exists in front of the thoracic or lumbar spinal cord, safely. This modification enable the authors to expose more than 50% of the spinal canal, and decompress it from its anterior, lateral, and posterior compressing mass. The utmost important point of this procedure is the excision of the lesion under the direct visualization of the dura. In ossification of the posterior longitudinal ligament (OPLL), the dura is usually indented by the thick bony mass, and the lesion extends over a few segment with adhesion. Using "Modified Lateral Rhachotomy," it was possible to explore three or four vertebral levels in continuity through the same skin incision. In the present report, the authors described their "Modified Lateral Rhachotomy" procedure, and reviewed the case material. 
Factor XIII subunits in relation to some other hemostatic parameters in ulcerative colitis. The hemostatic parameters, particularly with respect to F.XIII subunits, were examined in 48 untreated UC patients (22 at active and 26 at quiescent stage). UC active patients showed a significant decrease of F.XIII subunit "a," compared with healthy subjects, as well as in UC patients in remission. In contrast, the level of F.XIII subunit "b" in each group was similar. Compared with normal subjects, UC active patients revealed a significant decrease in AT III concentration, prolonged ELT, and elevated fibrinogen level. In addition, the elevated titer of SDPS test for SFMC appeared in approximately 40% of those patients. However, no strict relationship was found between the presence of positive SDPS and diminution of AT III, as well as of F.XIIII subunit "a" in active UC state. In patients in remission, AT III level and ELT were similar to those as in the control group, but fibrinogen concentration was elevated. Such constellation of hemostatic parameters may indicate a tendency to blood hypercoagulability in UC active patients, whereas, in general, these changes are not associated with the stage of remission. The present data may also suggest that F.XIII behavior pattern should be taken into account in the clinical management of UC. 
The prevalence of carcinoma in palpable vs impalpable, mammographically detected lesions. Concern over excessive numbers of false-positive mammograms, leading to unnecessary investigations and surgical interventions, has been cited as a barrier to mammographic screening for breast cancer. We compared the biopsy results from palpable vs impalpable, mammographically detected lesions from one experienced breast surgeon's practice from July 1980 through July 1989. Overall, there were 372 biopsies in 346 women. Of 143 biopsies for palpable abnormalities, 48 (34%) yielded a primary malignant lesion. The length of the palpable cancers averaged 3.7 cm (median, 2.8 cm). Sixteen (33%) of the 48 biopsies were in patients who had positive axillary lymph nodes, and five (10%) were in patients who had distant metastases at the time of biopsy. Of 229 biopsies for impalpable, mammographically detected lesions, 72 (31%) yielded a primary breast carcinoma. Excluding 34 carcinomas that had only calcifications, the length of the mammographically detected tumors averaged 2.0 cm (median, 1.5 cm). Eleven (15%) of the 72 biopsies were in patients who had positive axillary nodes, and none were in patients who had distant metastases at the time of biopsy. The positive predictive values (number of cancers detected divided by the number of biopsies recommended) were not significantly different when comparing biopsies indicated for palpable, clinically detected (34%) vs impalpable, mammographically detected (31%) abnormalities (p = .669). However, the mammographically detected cancers were smaller, more often noninvasive (32% vs 4%), less often associated with axillary metastases (15% vs 33%), and without distant metastases (0% vs 10%). 
The role of fiberoptic endoscopy in the management of corrosive ingestion and modified endoscopic classification of burns. We prospectively evaluated the role of fiberoptic esophagogastroduodenoscopy in the management of 81 patients with corrosive ingestion. A total of 381 endoscopic examinations were performed: 88 within 96 hours following corrosive ingestion, 108 between the third and ninth week, and 185 during the period of follow-up after bougie dilation of esophageal strictures. The customary endoscopic classification of burns (grades 0 to 3) was modified by subdividing grade 2 burns into 2a and 2b, and grade 3 burns into 3a and 3b for prognostic and therapeutic implications. There was no significant correlation between oropharyngeal and upper gastrointestinal tract injury. Early major complications and deaths were confined to patients with grade 3 burns. All patients with grade 0, 1, and 2a burns recovered without sequelae. The majority of patients (71.4%) with grade 2b injury and all survivors with grade 3 injury developed esophageal or gastric cicatrization, or both, which needed endoscopic or surgical treatment. There were no complications related to endoscopy. We conclude that early endoscopy is not only a safe, reliable, and accurate diagnostic tool in such patients, but also is of crucial importance in management and prognosis. 
The effect of corneal hypesthesia on the duration of proparacaine anesthetic eyedrops. The duration of action of proparacaine is known in the normal cornea but not in the hypesthetic cornea. To determine this, we examined both eyes in seven patients with documented unilateral corneal hypesthesia associated with inactive herpetic disease. Cochet-Bonnet measurements were made in both eyes before and at two- to five-minute intervals after the instillation of one drop of 0.5% proparacaine until baseline corneal sensitivity levels were again achieved. Mean recovery time was 34.86 minutes in eyes with normal corneal sensitivity, compared to 45.43 minutes in hypesthetic corneas. In all patients, the recovery time was remarkably longer in the hypesthetic eye than it was in the normal fellow eye. These data demonstrate the need to wait up to one hour after the instillation of proparacaine in eyes suspected of having corneal hypesthesia if corneal sensitivity is to be determined accurately. Additionally, the duration of action of topically instilled anesthetic may be a useful method of discovering subtle differences in corneal sensitivity. 
Absence of synergistic effects of CNS treatments on neuropsychologic test performance among children. Three hypotheses are proposed to account for neurobehavioral impairments following treatment with cranial radiation therapy (CRT) and intrathecal (IT) chemotherapy: CNS treatments exert a synergistic effect (A x B), an additive effect (A + B), or a single-agent effect (A or B). Eighty-five long-term survivors of non-CNS cancers aged 6 to 16 years were classified into groups on the basis of CNS treatments: CRT-IT (n = 25), CRT-No IT (n = 11), No CRT-IT (n = 24), and No CRT-No IT (n = 25). Study I findings did not provide support for synergistic mechanisms; nonorthogonal analysis of variance showed interaction effects (CRT x IT) restricted to tactile-perceptual speed. However, main effects were significant for a single agent (CRT) across a wide range of measures. General intelligence, academic achievement, verbal knowledge and reasoning, and perceptual-motor abilities were found to be significantly lower among CRT-treated groups. Study II findings provided additional support for the role of CRT; Pearson correlations within the CRT-No IT group indicated significant negative associations between CRT dose estimates for cortical regions and perceptual-motor abilities. 
Renal vascular lesions as a marker of poor prognosis in patients with lupus nephritis. Gruppo Italiano per lo Studio della Nefrite Lupica (GISNEL). The frequency of renal vascular lesions (RVL) and their relevance in the progression of renal damage were evaluated by the Pathology Group of the "Gruppo Italiano per lo Studio della Nefrite Lupica" (GISNEL). Of 285 patients with lupus nephritis collected from 20 nephrology centers in Italy and classified according to World Health Organization (WHO) criteria, 79 cases (27.7%) with RVL were identified and classified as follows: (1) lupus vasculopathy (n = 27); (2) hemolytic-uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP) malignant hypertension-like lesions (n = 24); (3) vasculitis (n = 8); (4) arterio-arteriosclerosis (n = 20). At the time of renal biopsy, patients with RVL had mean serum creatinine levels significantly higher than patients without RVL (201.8 +/- 195.9 mumol/L [2.2 +/- 2.2 mg/dL] v 108.1 +/- 108.0 mumol/L [1.2 +/- 1.2 mg/dL]; P less than 0.01). Hypertension was more frequent in patients with RVL than in those without (68.4% v 30.5%; P less than 0.01). The probability of kidney survival assessed according to the Kaplan-Meier method at 5 and 10 years was, respectively, 74.3% +/- 5.9% and 58.0% +/- 8.9% in patients with RVL, compared with 89.6% +/- 2.7% and 85.9% +/- 3.7% in patients without RVL. However, the two groups did not differ significantly as regards overall survival, the probability of survival at 5 and 10 years being 86.5% +/- 4.5% and 78.8% +/- 6.6% in patients with RVL and 92.2% +/- 2.2% and 83.3% +/- 4.4% in patients without RVL. 
Perfusion imaging with 99mTc-sestamibi for the assessment of myocardial area at risk and the efficacy of acute treatment in myocardial infarction. There is a clear need to develop better measurement tools for assessment of the effect of acute therapy in myocardial infarction. Such tools must permit accurate measurement of the amount of myocardium that is initially at risk. 99mTc-sestamibi is a new radiopharmaceutical with unique properties that are well suited to the measurement of myocardium at risk without any delay in acute therapy. Tomographic imaging with this agent has been shown to provide accurate quantitative estimates of the myocardium at risk, which varies widely, even for patients with a similar coronary occlusion. For example, there is more than a threefold range in myocardium at risk for patients with a nonproximal occlusion of the left anterior descending coronary artery. The determination of the myocardium at risk before intervention and the change in this region after intervention constitute a promising measurement tool for the assessment of the effect of acute therapy. Initial studies with tomographic imaging have shown a significant improvement in a group of patients treated with thrombolysis, although the magnitude of improvement is highly variable in individual patients. Qualitatively similar results have been reported with planar imaging. Although it has a number of technical limitations, sequential imaging with 99mTc-sestamibi seems to have a clear advantage over those end points that have previously been used to assess acute therapy. This new measurement tool should facilitate future clinical trials of different treatments in acute myocardial infarction. 
Soft tissue sarcoma of the pleural cavity. Seventeen cases of soft tissue sarcoma (STS) developing in the pleural cavity were collected from Japanese hospitals, and their clinical and pathologic findings summarized. Eight of the 17 patients had a 15-year to 50-year (mean, 28.8) history of chronic pleural inflammatory disease (pleuritis, pyothorax, and pulmonary tuberculosis) before the onset of the pleural sarcoma. Histologically, malignant fibrous histiocytoma was the most common tumor type (11 cases), followed by angiosarcoma (four). The age at diagnosis of the sarcoma ranged from 15 to 74 years (mean, 58); the male-to-female ratio was 3.3:1. In the eight cases of sarcoma associated with chronic pleural inflammatory disease, male preponderance was more marked (7:1). The commonest presenting symptom was chest pain. A mass could be detected by chest roentgenograms in 13 patients and computed tomographic scans in 15 patients. No patient had distant metastases at first admission. Thirteen patients were treated by surgery, chemotherapy, and/or radiation therapy. Thirteen of the 17 patients died 1 to 87 months (mean, 14.2) after therapy for STS. The actuarial 1-year survival rate was 38.5%. These findings suggest that long-standing pleural inflammation might be an etiologic factor for development of pleural STS. 
Endoscopic assessment of mucosal hemodynamic changes in a canine model of gastric ulcer. In studying the side effects of sclerosants injected into the gastric submucosa in dogs (N = 7), we noted that 3 ml of absolute ethanol induced a large gastric ulceration. We describe the time course of change in the ulcer size, and suggest that such ulceration can be used for the endoscopic assessment of factors important in ulcer genesis and healing. Endoscopic reflectance spectrophotometric measurement of indices of mucosal hemoglobin concentration (IHB) and oxygen saturation (ISO2) were performed in a separate group of dogs (N = 4) with ethanol-induced gastric ulceration. We found a significant difference (p less than 0.05) in IHB and ISO2 immediately before (97 +/- 8 and 37 +/- 3, respectively) and after (138 +/- 7 and 21 +/- 5, respectively) the ethanol injection. At 24 hours after the ethanol injection, the IHB at the lesion margin (141 +/- 14) was significantly higher (p less than 0.05) than that at the adjacent mucosa (101 +/- 4), whereas the ISO2 measurements were not significantly different in these two locations, 34 +/- 2 and 31 +/- 2, respectively. We conclude that (1) injection of 3 mol of absolute ethanol into the submucosa of the canine stomach provides an animal model of gastric ulceration in which the ulcer can be examined repeatedly with the aid of the endoscope; (2) in this ulcer model, ischemia with congestion (increases IHB, decreases ISO2) precedes the development of gross mucosal ulcerations; and (3) the margin of the established ulceration in this model exhibits hyperemia (increases IHB, normal ISO2) which mimics that of a healing gastric ulcer. 
Orbital lesions with granulomatous inflammation. Orbital lesions characterized by granulomatous inflammation are a heterogeneous group of diseases of various causes with a common histopathological substrate involving aggregates of epithelioid cells. Forty-one patients (27 females and 14 males) with biopsy-proven granulomatous inflammation were seen at an orbital clinic between 1978 and 1989. The mean age at presentation was 40.2 (extremes 6 and 77) years. Two main clinical presentations were noted: painless, subacute or chronic mass effect, and tender, subacute inflammatory process. Six patients had secondary features that were infiltrative in character. The lesions were primarily located in the anterior superior orbit. In nearly half the patients the granulomatous reaction was confined to the orbit (predominantly ruptured dermoid and localized orbital sarcoid), and the remainder had either regional involvement (Wegener's granulomatosis or fibro-osseous process) or systemic involvement (sarcoidosis). 
Felbamate: a clinical trial for complex partial seizures. We performed a randomized, double-blind, three-period cross-over study of felbamate (FBM, 2-phenyl-1,3-propanediol dicarbamate: Carter-Wallace 554) in patients with complex partial seizures. Patients continued carbamazepine (CBZ) throughout the study and were observed in the hospital for the entire trial period. The entry criteria required at least six seizures in a 3-week baseline period (and no more than 1 week with a single seizure) with CBZ alone. Thirty subjects were randomized. Two left the study after randomization, 1 owing to seizure exacerbation, and 1 owing to hyponatremia, which may have been related to CBZ therapy. The daily dosage of 50 mg/kg (maximum 3,000 mg) FBM per day was well tolerated by all 28 patients who completed the study. Only mild adverse experience were observed during the trial. FBM reduced CBZ level (p less than 0.0001; 95% confidence interval -28%, -20%). There was no significant difference in seizure frequency between placebo and FBM periods (one-sided p = 0.172), but when a correction was made for the lower CBZ level noted during FBM periods, the data suggested a strong antiseizure effect of FBM. 
Cytokine-endothelial interactions in inflammation, immunity, and vascular injury. This paper reviews the evidence that cytokines induce a variety of functional and structural alterations in endothelium and that cytokine-endothelial interactions play important roles in the evolution of inflammatory and immune responses. The effect of cytokines, particularly interleukin-1 and tumor necrosis factor, on leukocyte-endothelial adhesion has led to the discovery of several endothelial adhesion molecules, and the molecular and biological characteristics of these are described. Finally, the review discusses the possible contribution of cytokine-induced activation to vascular injury in such pathological processes as septic shock, the Shwartzman reaction, delayed hypersensitivity, and immune-mediated vasculitis. 
Pontine myelinolysis after correction of hyponatremia during burn resuscitation. Central pontine myelinolysis is a neurologic disease produced by the rapid correction of hyponatremia. This report describes the occurrence of central pontine myelinolysis in a patient with burns. The natural history of this paralyzing condition and suggestions for its prevention are discussed. Severely burned and hyponatremic patients are at risk for this disorder because a large amount of sodium ion is typically required for the treatment of burn shock. Awareness of this phenomenon and avoidance of rapid correction of hyponatremia are essential to its prevention. 
Endoscopic palliation of tracheobronchial malignancies. The prognosis for tracheobronchial tumours remains poor. Most patients can be offered only palliation. When the main symptom is breathlessness or refractory haemoptysis from a large airway tumour endoscopic treatment may be very effective. Over the last decade most attention has focused on the neodymium YAG laser. This often produces dramatic effects but has some important limitations. In the last few years better techniques for stenting and intrabronchial radiotherapy (brachytherapy) have also been developed. This article discusses the range of techniques now available and aims to help clinicians decide which patients may benefit from referral to centres providing these techniques. 
Detection of Epstein-Barr virus sequences in primary brain lymphoma without immunodeficiency. We searched for Epstein-Barr virus (EBV) sequences by enzymatic DNA amplification in nine primary brain lymphomas from patients without immunodeficiency. We used seven nonlymphoma brain tumors as negative controls, and the Raji cell line as a positive control. We detected EBV DNA, using ethidium bromide-stained-agarose minigel electrophoresis and dot blot hybridization, in the positive control and in only one brain lymphoma tumor; we did not detect EBV DNA in the other tumors. The EBV-positive patient had a second B-cell monoclonal population in the peripheral blood without detectable EBV DNA, suggesting a direct role for EBV in the development of the brain lymphoma. 
Treatment-seeking behavior among those with signs and symptoms of acute myocardial infarction. Significant delays in seeking definitive treatment for the signs and symptoms of acute myocardial infarction increase morbidity and mortality. In most studies, delay times average more than 4 hours. The following variables are associated with increased delay: a medical history of angina, diabetes mellitus, or hypertension; older age; black race; seeking advice from a family member or a physician; symptom onset on a weekday; and attempts at self-treatment. Variables associated with reduced delay times are the following: pain recognized as cardiac in origin, hemodynamic instability, severe chest pain, younger age, and consultation with a coworker. Surprisingly, patients who have already experienced a myocardial infarction are just as likely to delay as patients who have not had this experience. These findings provide direction for developing and testing patient and family interventions, establishing community education programs, and reducing patient delay in response to the signs and symptoms of acute myocardial infarction. 
Cardiac tumors and the nevoid basal cell carcinoma syndrome. Nevoid basal cell carcinoma syndrome is a multisystem disease with a wide range of initial symptoms that can be seen at any age. The most characteristic features are vertebral or rib anomalies, intracranial falx calcification, multiple basal cell carcinomas, odontogenic keratocysts of the jaw, and palmar and/or plantar pits. Pediatricians need to be aware that if any one of these major anomalies is seen, this diagnosis should be considered. There now appears to be an established association between cardiac tumors and nevoid basal cell carcinoma syndrome. Primary cardiac tumors have been associated with cerebral tuberous sclerosis and neurofibromatosis, and evaluation of cardiac status is recommended when these genetically determined syndromes are diagnosed. This communication should serve to alert pediatricians to the need for complete cardiac evaluation and genetic counseling when a diagnosis of nevoid basal cell carcinoma is made. 
The surgical pathology of gastrointestinal Hodgkin's disease. The files of the National Cancer Institute were searched for all surgical specimens from the gastrointestinal (GI) tract with the diagnosis of Hodgkin's disease (HD) that were accessioned during the years 1953-1990; six patients with a histologically reconfirmed diagnosis were identified. Of these patients, four presented with GI HD and two had recurrent HD. Primary HD appeared in the stomach (three patients) and the duodenum (one patient); recurrent HD after diagnosis in a conventional nodal site appeared in the stomach (one patient) and the colon (one patient). One of the cases of primary gastric disease was a composite lymphoma consisting of HD and diffuse large cell lymphoma. In view of the rarity of GI tract involvement by HD, a diagnosis of primary GI HD should be viewed with skepticism; support for such a diagnosis may be provided by both classic histopathologic features of HD and immunostaining, but no single feature can be regarded as pathognomonic. 
Dislodgement of a vein graft thrombus by angiographic injection of native coronary artery. A case of retrograde dislodgement of thrombus in a saphenous vein graft during injection of the native right coronary artery is presented. Attention to this previously undescribed complication may allow for timely treatment with emergency surgery or thrombolysis. 
Compartment syndrome of the foot after intraarticular calcaneal fracture. Seventeen patients with a total of 21 intraarticular calcaneal fractures were examined at up to 30 days after trauma for the development of tissue pressure in the central plantar muscle compartment. Twelve patients had a significant increase in tissue pressure with values greater than 30 mmHg because of primary fracture hematoma or interstitial fluid accumulation. This increase in pressure persisted for three to five days after trauma, so that ischemic damage to the short plantar foot muscles had to be suspected. Plantar muscle scarring and claw-toe formation were observed in seven patients with a total of 11 fractures during a mean observation period of 18 months. The plantar aponeurosis, which forms the constricting fascial envelope of the plantar muscles, is the anatomic structure responsible for the compartment syndrome that may develop after calcaneal fracture. Therefore, to avoid functional deficit, plantar compartmental pressures should be regularly measured after calcaneal fracture. Significantly increased plantar tissue pressure greater than 30 mmHg should be relieved by longitudinal incision of the plantar aponeurosis, preferably by a plantar incision as soon as the diagnosis is made. 
IgM antibody to hepatitis C virus in acute and chronic hepatitis C. To assess possible role of testing for IgM-specific antibody in the diagnosis and monitoring of patients with hepatitis C, we tested sera from 14 patients with acute and 97 patients with chronic non-A, non-B hepatitis for IgG and IgM antibody to hepatitis C virus. IgG antibody to hepatitis C virus was detected in 93% of acute cases and 91% of chronic cases. Of the 101 patients with IgG antibody to hepatitis C virus, 57% had IgM antibody to hepatitis C virus. None of the 20 healthy subjects or 40 patients with acute or chronic hepatitis A or hepatitis B had IgM antibody to hepatitis C virus. At the onset of clinical symptoms in acute hepatitis C, IgG antibody to hepatitis C virus was detected in 8 (57%) and IgM antibody to hepatitis C virus in 9 of 14 patients (64%). Eventually, both IgG and IgM antibody to hepatitis C virus became detectable in 13 of 14 patients with acute hepatitis C. Seven patients with antibody to hepatitis C virus resolved the acute infection within 6 mo and all seven cleared IgM antibody to hepatitis C virus, whereas two cleared IgG antibody to hepatitis C virus. Six patients had a chronic outcome of the acute infection and IgM antibody to hepatitis C virus persisted in detectable amounts for more than 6 mo in all (mean = 15.5 mo). Among 88 patients with chronic non-A, non-B hepatitis with IgG antibody to hepatitis C virus, IgM antibody to hepatitis C virus was detected in 45 (51%). 
Emergency treatment of headache. Headache is a frequent presenting complaint in the emergency department. Once a diagnosis is established, and significant organic disease can be ruled out, relief of pain must be addressed. Referral for follow-up care and narcotic habituation is a recurrent problem for the emergency physician. This article discusses the differential diagnosis of headache, evaluation of the emergency room patient, and treatment of the patient with headache. 
Efficacy of desipramine in painful diabetic neuropathy: a placebo-controlled trial. Although amitriptyline relieves pain in many patients with painful diabetic neuropathy, side effects often preclude effective treatment. Desipramine has the least anticholinergic and sedative effects of the first generation tricyclic antidepressants. We compared a 6 week course of desipramine (mean dose, 201 mg/day) to active placebo in 20 patients with painful diabetic neuropathy in a double-blind crossover trial. Pain relief with desipramine was statistically significant in weeks 5 and 6. Eleven patients reported at least moderate relief with desipramine, compared to 2 with placebo. Pain relief tended to be greater in depressed patients, but relief was also observed in patients who did not show an antidepressant effect. We conclude that desipramine relieves pain in many patients with painful diabetic neuropathy, offering an alternative for patients unable to tolerate amitriptyline. Blockade of norepinephrine reuptake, an action shared by desipramine, amitriptyline, and other antidepressants proven effective in neuropathic pain, may mediate this analgesic effect. 
Cystoid macular edema secondary to juxtafoveolar telangiectasis in Coats' disease. A 28-year-old man with unilateral Coats' disease and cystoid macular edema secondary to juxtafoveolar telangiectasis underwent successful juxtafoveolar argon green laser photocoagulation therapy with resolution of the edema and improvement in metamorphopsia and visual acuity. Despite this success, the effect of laser therapy in these patients remains uncertain. It should be considered only after detailed discussion with the patient about the possibility of posttreatment paracentral scotomata and the alternative of a reasonable period of observation for possible spontaneous resolution of the edema. 
Hypertonic saline resuscitation: efficacy in a community-based burn unit. Many have discussed hypertonic saline for resuscitation in burned patients only to discourage its use or to emphasize it only as a research tool and not as standard resuscitation. We reviewed the records of 47 adults with burns over 20% or more of the total body surface area (TBSA) in whom hypertonic saline was used as standard resuscitation fluid in a large community burn unit. The solution consisted of sodium, 300 mEq/L, acetate, 200 mEq/L, and chloride, 100 mEq/L, with an osmolality of 600 mOsm/L. The mean TBSA burned was 37% and the mean patient age was 44.8 years. Eighteen patients (mean age 39.7 years, mean TBSA burned 27%) received hypertonic saline alone. They required an average of 75% of the Parkland calculated volume to achieve a urinary output of 1 mL/kg/hr. The mean hematocrit value over the first 48 hours was 44.2% and the mean serum sodium level was 141.6 mEq/L. Twenty-nine patients (mean age 51.8 years, mean TBSA burned 47.8%) received hypertonic saline plus colloid (albumin or fresh frozen plasma). Colloid was used in older patients with more serious burns. This group required 57% of the Parkland calculated volume to achieve a urinary output of 1 mL/kg/hr. The mean hematocrit value was 45.1% and mean sodium level was 143.8 mEq/L. The mean weight gain for both groups was 7.3% of the admission weight. None of the patients had changes in pH or renal function. All patients survived the resuscitation phase of their injury; the overall death rate was 49%. We conclude that hypertonic saline is a safe, effective means of resuscitation even in a community-based unit. It allows less fluid to be delivered for adequate resuscitation. The usual hyponatremia, hemoconcentration, and significant weight gain associated with administration of isotonic solutions was avoided. Colloid may further improve the resuscitation capabilities of hypertonic saline. 
Immediate versus deferred beta-blockade following thrombolytic therapy in patients with acute myocardial infarction. Results of the Thrombolysis in Myocardial Infarction (TIMI) II-B Study In the Thrombolysis in Myocardial Infarction (TIMI) Phase II trial, patients received intravenous recombinant tissue-type plasminogen activator (rt-PA) and were randomized to either a conservative or an invasive strategy. Within this study, the effects of immediate versus deferred beta-blocker therapy were also assessed in patients eligible for beta-blocker therapy, a group of 1,434 patients of which 720 were randomized to the immediate intravenous group and 714 to the deferred group. In the immediate intravenous group, within 2 hours of initiating rt-PA metoprolol was given (5 mg intravenously at 2-minute intervals over 6 minutes, for a total intravenous dose of 15 mg, followed by 50 mg orally every 12 hours in the first 24 hours and 100 mg orally every 12 hours thereafter). The patients assigned to the deferred group received metoprolol, 50 mg orally twice on day 6, followed by 100 mg orally twice a day thereafter. The therapy was tolerated well in both groups and the primary end point, resting global ejection fraction at hospital discharge, averaged 50.5% and was virtually identical in the two groups. The regional ventricular function was also similar in the two groups. Overall, there was no difference in mortality between the immediate intravenous and deferred groups, but in the subgroup defined as low risk there were no deaths at 6 weeks among those receiving immediate beta-blocker therapy in contrast to seven deaths among those in whom beta-blocker therapy was deferred. These findings for a secondary end point in a subgroup were not considered sufficient to warrant a recommendation regarding clinical use. There was a lower incidence of reinfarction (2.7% versus 5.1%, p = 0.02) and recurrent chest pain (18.8% versus 24.1%, p less than 0.02) at 6 days in the immediate intravenous group. Thus, in appropriate postinfarction patients, beta-blockers are safe when given early after thrombolytic therapy and are associated with decreased myocardial ischemia and reinfarction in the first week but offer no benefit over late administration in improving ventricular function or reducing mortality. 
Thoracic epidural analgesia in a patient with bilateral phaeochromocytoma undergoing coronary artery bypass grafting. A patient suffering from phaeochromocytoma and coronary artery stenoses needed coronary artery bypass grafting before adrenalectomy. High thoracic epidural analgesia (T1-T2) with bupivacaine and sufentanil in combination with general anaesthesia was used. Plasma adrenaline and noradrenaline concentrations decreased during the period before bypass grafting compared to the baseline value and no important haemodynamic changes were seen during this period. Thoracic epidural analgesia failed to suppress the release of catecholamine during the bypass period. After the operation, the plasma catecholamine concentrations returned to the baseline value. Excellent analgesia (visual analogue scale = 1-2) was achieved with a postoperative epidural, but the plasma catecholamine concentration increased considerably. 
The significance of antibody to hepatitis C virus in patients with chronic hepatitis B. We assessed the prevalence and clinical significance of antibodies to hepatitis C virus among a cohort of 148 patients with chronic hepatitis B virus infection. Sixteen patients (11%) had anti-hepatitis C virus detectable by enzyme-linked immunoassay. The results from eight of these patients were positive by recombinant immunoblot assay. The results of recombinant immunoblot assay testing were not consistent; therefore the analysis of the patients' data was based on anti-hepatitis C virus enzyme-linked immunoassay results. Patients with chronic hepatitis B with anti-hepatitis C virus were more likely to be cirrhotic (44% vs. 21%) and to have decompensated liver disease (24% vs. 6%). Hepatitis B virus replication appeared to be suppressed in patients with both infections as measured by hepatitis B virus-associated DNA polymerase activity (mean = 2,055 vs. 2,555 cpm). Human immunodeficiency virus infection was more common in the anti-hepatitis C virus positive group (36% vs. 11%). Thus hepatitis C virus appears to suppress hepatitis B virus replication and to cause more severe liver disease in patients with chronic hepatitis B infection. 
Amiodarone inhibits the mitochondrial beta-oxidation of fatty acids and produces microvesicular steatosis of the liver in mice. Amiodarone has been shown to produce microvesicular steatosis of the liver in some recipients. We have determined the effects of amiodarone on the mitochondrial oxidation of fatty acids in mice. In vitro, the formation of 14C-acid-soluble beta-oxidation products from [U-14C]palmitic acid by mouse liver mitochondria was decreased by 92% in the presence of 125 microM amiodarone and by 94% in the presence of 125 microM N-desethylamiodarone. Inhibition due to 100 or 150 microM amiodarone persisted in the presence of 5 mM acetoacetate, whereas acetoacetate totally relieved inhibition due to 15 microM rotenone. In vivo, exhalation of [14C]CO2 from [U-14C]palmitic acid was decreased by 31, 40, 58 and 78%, respectively, in mice receiving 19, 25, 50 and 100 mg.kg-1 of amiodarone hydrochloride 1 hr before the administration of [U-14C]palmitic acid. One hour after 100 mg.kg-1, the exhalation of [14C]CO2 from [1-14C]palmitic acid, [1-14C]octanoic acid or [1-14C]butyric acid was decreased by 78, 72 and 53%, respectively. Exhalation of [14C]CO2 from [1-14C]palmitic acid was normal between 6 and 9 hr after administration of 100 mg.kg-1 of amiodarone hydrochloride, but was still inhibited by 71 and 37%, 24 and 48 hr after 600 mg.kg-1. Twenty four hours after the latter dose of amiodarone, hepatic triglycerides were increased by 150%, and there was microvesicular steatosis of the liver. We conclude that amiodarone inhibits the mitochondrial beta-oxidation of fatty acids and produces microvesicular steatosis of the liver in mice. 
DNA analysis of atrial myxomas. The atrial myxoma is a primary tumor of the heart which may have an uncertain clinical course. In this study, we performed flow cytometric DNA analysis of 15 paraffin-embedded atrial myxomas and correlated DNA ploidy status and proliferative fraction with clinical findings. Twelve of 15 cases (80 percent) were diploid and the remaining three cases (20 percent) were aneuploid. Two patients with aneuploid histograms were free of tumor at the time follow-up; the third patient experienced local tumor recurrence and metastases. Five patients with diploid myxomas demonstrated an elevated (greater than or equal to 17 percent) proliferative cell cycle fraction; four of these patients experienced embolic phenomenon or tumor recurrence. This pilot study suggests that an atrial myxoma with either aneuploid DNA content or elevated proliferative fraction may be associated with aggressive biologic behavior. 
Assessment of the psychological impact of a breast screening programme. In order to assess the psychological effect of mammographic screening, questionnaires (which included psychometric tests) were sent to 750 women at invitation and, 6 weeks after screening, to 420 women normal after the first mammograph, to 240 women normal after special assessment, and to 68 women normal after open biopsy. Increasing degree of the investigation was associated both with increasing frequency of breast self examination (10% were practising breast self-examination at least once a week before screening compared with 24% for women after special assessment and 35% of women who had had an open biopsy (p less than 0.001)), and with greater confidence that any malignancy in the breast would have been found. Psychometric scores showed no increase of general levels of anxiety or depression in the screened groups. For anxiety, percentages abnormal were 5, 4, 2 and 6 for the four groups, respectively, and for depression the percentages abnormal were 5, 4, 4 and 6, respectively; 10% of screened women were more anxious about having breast cancer as a result of the screening. At least 10% of women proceeding to open biopsy of benign lesions require professional counselling and support. Psychological ill effects were not detected by the psychometric test among women who did not proceed to this final investigation. Behavioural changes did suggest a raised awareness or fear of potential cancer among the screened population. 
Neurologic outcome after electroencephalographically proven neonatal seizures. Infants in whom neonatal seizures were confirmed by randomly recorded ictal electroencephalographic (EEG) tracings were retrospectively examined to determine their global neurologic outcome and the specific frequency of epilepsy, development delay, and cerebral palsy. Perinatal and postnatal clinical and EEG variables were also examined for their relevance to the neurologic outcome. Forty infants with EEG documented seizures of diverse etiologies were studied. The 27 survivors were followed up at a mean of 31 months. The outcome was unfavorable in 70%. The rate of epilepsy was 56%, of developmental delay 67%, and of cerebral palsy 63%. The etiology of seizures was an important factor influencing the outcome. Other clinical factors that showed a significant relationship with global or specific aspects of the neurologic outcome included the age at the onset of seizures, birth weight, and neurologic examination results. The EEG parameters that significantly predicted the neurologic outcome were interictal EEG background, increased seizure frequency, and decreased seizure duration. 
Sudden cardiac death: management of high-risk patients Sudden cardiac death remains a leading cause of death in the United States, accounting for more than 350,000 deaths each year, and the survival rate of victims remains low. Most survivors face a significant risk for recurrence. The typical substrate is chronic--abnormal myocardium with fibrosis (often from previous myocardial infarction) and left ventricular dysfunction. Acute triggers for sudden cardiac death are primarily electrical, ischemic, metabolic, neurohormonal, and pharmacologic. In most electrocardiographically documented cases of sudden cardiac death, the trigger-substrate interaction appears to result in ventricular tachycardia and fibrillation. After initial resuscitation, survivors need a thorough cardiovascular evaluation, including definition of coronary anatomy, left ventricular function, and wall-motion abnormalities, as well as an electrophysiologic evaluation. An attempt must be made to determine what each survivor's correctable triggers are. Management should address all reversible triggers, such as acute ischemia and electrolyte abnormalities, and should include modifying or correcting the arrhythmogenic substrate. Empiric antiarrhythmic therapy offers no advantage in such modification. Pharmacologic therapy with antiarrhythmic drugs should be guided by an objective therapeutic endpoint, which is best accomplished through the use of programmed ventricular stimulation and serial electrophysiologic studies. Other therapeutic options include surgical suppression of ventricular tachycardia and implantation of a cardioverter defibrillator. 
Serum aminoterminal propeptide of type III procollagen in psoriasis and psoriatic arthritis: relation to liver fibrosis and arthritis. Levels of serum aminoterminal propeptide of type III procollagen were measured in 170 patients with psoriasis (49% with coexistent psoriatic arthritis) who had liver biopsies performed during or before treatment with methotrexate or, in some cases, with retinoids. Psoriasis patients with fibrosis or cirrhosis in their liver biopsy specimens had a significantly higher mean serum aminoterminal propeptide of type III procollagen than did patients without fibrosis and without arthritis. Only 4% of patients without cirrhosis or fibrosis and no arthritis had an elevated serum aminoterminal propeptide of type III procollagen. In contrast, 38% of patients with psoriatic arthritis had an increased aminoterminal propeptide of type III procollagen in the absence of detectable liver fibrosis. It is concluded that the number of liver biopsies performed on methotrexate-treated psoriasis patients with or without arthritis may be reduced to a minimum as long as serum aminoterminal propeptide of type III procollagen is normal. Increased serum aminoterminal propeptide of type III procollagen in the absence of arthritis is a strong indicator of liver fibrogenesis and suggests the need for liver biopsy to monitor possible methotrexate-induced toxicity. In patients with psoriatic arthritis an increased aminoterminal propeptide of type III procollagen may be related to the joint disease. Patients with psoriatic arthritis and increased levels of aminoterminal propeptide of type III procollagen should therefore follow the established guidelines for the use of methotrexate in psoriasis. 
Delayed sleep phase syndrome response to melatonin. The actions of melatonin on the sleep-wake cycle were investigated by means of a randomised, double-blind, placebo-controlled trial in 8 subjects with a delayed sleep phase syndrome attending a sleep disorders clinic. In randomised order the subjects received placebo or melatonin 5 mg daily for 4 weeks with a 1 week washout period between the treatments. Drug or placebo was given at 2200 h, 5 h before the mean time of sleep onset determined by pretrial sleep logs. In all 8 subjects sleep onset time (mean advance 82 [range 19-124] min; p less than 0.01) and wake time (117 [10-187] min; p less than 0.01) were significantly earlier during melatonin treatment than during placebo. Mean total sleep time was slightly less on melatonin (8 h 12 min) than on placebo (8 h 46 min). Alertness acrophase calculated from the subjects' ratings of alertness made every 2 h while awake was unaltered. Melatonin may act as a phase-setter for sleep-wake cycles in subjects with a delayed sleep phase syndrome. 
Overseas fatalities of United States citizen travelers: an analysis of deaths related to international travel. STUDY OBJECTIVE: Studies of travel-related mortality and morbidity have been limited to nonfatal events. Causes of travel-related mortality may differ significantly from morbidity and thus have different prevention strategies. DESIGN: We examined the overseas fatalities of US citizen travelers for the years 1975 and 1984. The death certificates were abstracted; all deaths under age 60 and a 20% sample of deaths 60 and older were examined. SETTING AND TYPE OF PARTICIPANTS: All overseas travel fatalities of US citizens were examined excluding those occurring in Canada. INTERVENTIONS: None. RESULTS: Cardiovascular events (including myocardial infarctions and cerebrovascular accidents) and injuries accounted for 49% and 25% of the overseas deaths of US citizen travelers, respectively. Infectious diseases other than pneumonia accounted for only 1% of the deaths. Eighty percent of injury deaths occurred outside of hospitals. Injury death rates for male travelers were greater than US age-specific death rates. CONCLUSIONS: Greater emphasis on the prevention of fatal events, especially those resulting from injury, must be given by physicians and other individuals and organizations who advise travelers. Further studies are needed to explore the issues of preventable injury deaths, emergency medical services, and overseas travel. 
Twenty-four-hour blood pressure control with isradipine in mild essential hypertension. The hypotensive effect of isradipine was assessed in 26 male patients, aged 40 to 64 years, with hypertension. After withdrawal of previous antihypertensive treatment and a four-week placebo period, patients were randomized into a double-blind active-treatment period of eight weeks to receive either placebo or 1.25 to 2.5 mg isradipine twice daily. Twenty-four-hour ambulatory blood pressure was measured by Accutracker (Suntech, Oxford, England) after the placebo period and at the end of the active-treatment period. In the isradipine group n = 13), both systolic and diastolic blood pressure and number of blood pressure spikes decreased significantly (P less than .0001), whereas there was a significant increase of these variables in the placebo control group (n = 13). The results of this study indicate that, in these subjects, blood pressure control was achieved throughout the 24-h period by monotherapy with isradipine. 
Damage to tissue defenses by EMLA cream. EMLA is a new topical agent that safely anesthetizes intact skin. The purpose of this study was to determine if this cream could be safely used for anesthetizing wounds. This investigation evaluated the potential toxicity of EMLA cream in wounds by measuring its effect on host defenses and on the biology of wound repair. In contaminated wounds, EMLA cream elicited an exaggerated inflammatory response that damaged host defenses, inviting the development of infection. As a result of these investigations, we do not recommend the use of EMLA cream in wounds. 
Carotid cavernous fistula after minimal facial trauma. Report of a case. The carotid cavernous fistula has historically been associated with extensive facial trauma as a result of direct or indirect forces. Most fistulas of traumatic origin develop as a result of a fracture through the base of the skull, which produces a force causing laceration of the internal carotid artery in the region where it approximates the cavernous sinus. We report a case in which apparently minimal head trauma resulted in the development of a carotid cavernous fistula. The rather innocuous presentation of this complication requires particular attention by the caregiver in assessing the patient sustaining maxillofacial trauma. 
Ethnic differences in mortality from ischaemic heart disease and cerebrovascular disease in England and Wales. OBJECTIVE--To examine mortality from ischaemic heart disease and cerebrovascular disease in England and Wales by country of birth of the deceased. DESIGN--Standardised mortality ratios were computed by country of birth groups for ischaemic heart disease and cerebrovascular disease for 1979-83 and 1970-2 by using the five year age-sex specific rates for England and Wales for 1979-83 as standard. SETTING--England and Wales 1970-2 and 1979-83. RESULTS--In 1979-83 mortality from ischaemic heart disease was highest in men and women born in the Indian subcontinent (standardised mortality ratio 136 and 146 respectively). Young Indian men suffered the greatest excess (313 at ages 20-29). Other groups with raised mortality included Irish, Scottish, and Polish born immigrants. Those born in the Caribbean, the old Commonwealth, west Europe, and the United States had low death rates. In England and Wales mortality from ischaemic heart disease declined by 5% in men and 1% in women between 1970-2 and 1979-83, with greatest percentage declines in immigrants born in the United States, South Africa, the old Commonwealth, the Caribbean, and France. immigrant groups with raised mortality in the earlier period showed little improvement, and mortality from ischaemic heart disease increased among Indians (6% in men and 13% in women). In 1979-83 mortality from cerebrovascular disease was highest in Caribbeans (standardised mortality ratios 176 in men and 210 in women), followed by Africans, Indians, and Irish. Rates were low in west Europeans. Mortality from stroke declined by 28% overall in this period, a rate of decline shared by most groups. Men from the Indian subcontinent showed a decline of only 3%. CONCLUSION--In the 1980s mortality from ischaemic heart disease and cerebrovascular disease differed significantly between ethnic groups in England and Wales. In general, ethnic groups that experienced lower mortality from ischaemic heart disease in the 1970s showed the greatest improvement over the following decade. 
Effect of exercise supplementation on dipyridamole thallium-201 image quality To determine the effect of different types of exercise supplementation on dipyridamole thallium image quality, 78 patients were prospectively randomized to one of three protocols: dipyridamole infusion alone, dipyridamole supplemented with isometric handgrip, and dipyridamole with low-level treadmill exercise. Heart-to-lung, heart-to-liver, and heart-to-adjacent infradiaphragmatic activity ratios were generated from anterior images acquired immediately following the test. Additionally, heart-to-total infradiaphragmatic activity was graded semiquantitatively. Results showed a significantly higher ratio of heart to subdiaphragmatic activity in the treadmill group as compared with dipyridamole alone (p less than 0.001) and dipyridamole supplemented with isometric handgrip exercise (p less than 0.001). No significant difference was observed between patients receiving the dipyridamole infusion, and dipyridamole supplemented with isometric handgrip exercise. We conclude that low-level treadmill exercise supplementation of dipyridamole infusion is an effective means of improving image quality. Supplementation with isometric handgrip does not improve image quality over dipyridamole alone. 
Creutzfeldt-Jakob disease in a patient with a cadaveric dural graft. We report a 26-year-old woman with Creutzfeldt-Jakob disease (CJD) who had received cadaveric dural material 33 months before the onset of neurologic symptoms. This is the fourth case in which a dural graft was the putative source of the CJD agent. All four cases had the grafting before changes in the sterilization procedure adopted in 1987 to inactivate the CJD agent. 
Mammographic follow-up of nonpalpable low-suspicion breast abnormalities: one versus two views. A retrospective study involving 498 women with a total of 666 breast lesions was undertaken to determine the relative efficacy of one- and two-view mammography in the follow-up evaluation of "low-suspicion" abnormal mammographic findings. These abnormalities consisted of well-defined masses (47.1%), well-defined punctate microcalcifications (20.9%), and parenchymal asymmetry (32.0%). Confidence in the adequacy of the single-view follow-up was high in 91% of cases. The addition of the second mammographic view changed the one-view interpretation in approximately 1% of all cases. Two cancers were detected during the initial follow-up period. Both cancers were detected with single-view and standard two-view follow-up examinations, with high confidence. In this controlled retrospective study, the single-view follow-up examination was adequate for follow-up of most low-suspicion mammographic abnormalities. Monitoring by physicians, however, would be necessary to prevent an unacceptable number of patient recalls, which could make the one-view follow-up study impractical to use in some practices. 
The "two week syndrome" associated with injection treatment for chronic pain--fact or fiction? Many patients attending the pain clinic for regular injections of local anaesthetic state that the pain returned "two weeks" ago. This study demonstrates that 85% of these patients have a "return of pain" interval which coincides with the proximity of their next clinic appointment. 
Choledochal cyst and biliary atresia in the neonate: imaging findings in five cases. The radiologic findings in five neonates with choledochal cyst associated with extra-hepatic biliary atresia are described. All five patients (age range, 13-72 days) presented with jaundice and acholic stools. In all four patients who underwent sonographic examination, a cystic structure separate from the gallbladder representing the choledochal cyst was shown. The diagnosis of atresia of the distal common bile duct was made preoperatively in all cases by hepatobiliary scintigraphy. Diagnosis was confirmed by surgical findings and was demonstrated by intraoperative cholangiography in four cases. All patients were successfully treated with surgical intervention within 1 month from the time of diagnosis. Early detection of this rare disorder, which may be distinct from choledochal cyst found in children and adults, is important to prevent fatal complications of biliary obstruction. The combined use of sonography and hepatobiliary scintigraphy can correctly identify this subset of patients with persistent neonatal jaundice and provide valuable information for prompt surgical management. 
Regional changes in hemodynamics and cardiac myocyte size in rats with aortocaval fistulas. 1. Developing and established hypertrophy. The effects of a large arteriovenous fistula on left and right ventricular hemodynamics and cardiac myocyte size were examined in adult rats at 1 week and 1 month after surgery. Cardiac output, left ventricular function, and right ventricular function were evaluated before obtaining isolated myocytes for cell size measurements. Average heart weight increased 35% at 1 week and 86% at 1 month in rats with fistulas. In general, myocyte hypertrophy was due to a proportional increase in length and width (length/width ratio remained constant). This change was more evident in the large hearts from rats with 1-month fistulas. At both the 1-week and 1-month intervals, the hypertrophic response of right ventricular myocytes was slightly greater than that observed in the left ventricle or interventricular septum. Left ventricular systolic pressure and dP/dtmax were significantly reduced at 1 week but returned to normal after 1 month of overloading. Left ventricular end-diastolic pressure was increased approximately fivefold and twofold at 1 week and 1 month, respectively. Right ventricular systolic pressure and dP/dtmax were increased at both intervals examined. We conclude that severe volume overloading from a large aortocaval fistula in the rat is characterized by 1) depressed left ventricular function at 1 week followed by a large compensatory hypertrophy and near normal function at 1 month, 2) right ventricular pressure overload, and 3) changes in myocyte shape that resemble normal physiological growth. 
Initial clinical trial of EXOSURF, a protein-free synthetic surfactant, for the prophylaxis and early treatment of hyaline membrane disease. EXOSURF is a protein-free surfactant composed of 85% dipalmitoylphosphatidylcholine, 9% hexadecanol, and 6% tyloxapol by weight. A single dose of 5 mL of EXOSURF per kilogram body weight, which gave 67 mg of dipalmitoylphosphatidylcholine per kilogram body weight, or 5 mL/kg air was given intratracheally in each of two controlled trials: at birth to neonates 700 through 1350 g (the prophylactic trial, n = 74) or at 4 to 24 hours after birth to neonates greater than 650 g who had hyaline membrane disease severe enough to require mechanical ventilation (the rescue trial, n = 104). In both studies, time-averaged inspired oxygen concentrations and mean airway pressures during the 72 hours after entry decreased significantly (P less than .05) in the treated neonates when compared with control neonates. Thirty-six percent of the treated neonates in the rescue study had an incomplete response to treatment or relapsed within 24 hours, suggesting the need for retreatment in some neonates. In the rescue trial, risk-adjusted survival increased significantly in the treated group. There were no significant differences in intracranial hemorrhages, chronic lung disease, or symptomatic patent ductus arteriosus between control and treated infants in either trial. 
"Heartstart Scotland"--initial experience of a national scheme for out of hospital defibrillation. OBJECTIVE--To determine the outcome of out of hospital defibrillation in Scotland during the year after the introduction of automated external defibrillators in October 1988. DESIGN--Retrospective analysis of ambulance service reports and hospital records. SETTING--Scottish Ambulance Service and acute receiving hospitals throughout Scotland. MAIN OUTCOME MEASURES--Delay from cardiac arrest to first defibrillator shock; vital state on arrival at hospital accident and emergency department; survival to hospital discharge. RESULTS--During the study period 268 defibrillators were purchased by public subscription and 96% of the 2000 ambulance crew underwent an eight hour training programme in cardiopulmonary resuscitation and defibrillation. A total of 1111 cardiac arrests were recorded, and defibrillation was indicated and undertaken in 602 (54%) patients, mean age 63 (range 14-92) years. A spontaneous pulse was present on arrival at hospital in 180 (30%) of the defibrillated patients, and 75 (12.5%) were subsequently discharged alive. As expected, the likelihood of survival was inversely related to the delay from the onset of cardiac arrest to the time of the first shock and was greater in the case of witnessed arrest. If ventricular fibrillation occurred after the arrival of the ambulance, survival to discharge was 33%. CONCLUSIONS--An effective scheme for out of hospital defibrillation can be introduced rapidly, and with limited training implications and costs, by the use of automated external defibrillators in ambulances. 
Colonic ischemia complicating immunotherapy with interleukin-2 and interferon-alpha. Colonic ischemia (CI) is a rare complication of high-dose interleukin-2 (IL-2) immunotherapy. This complication occurred in three of 141 patients (2.1%) with metastatic cancer treated with high-dose IL-2 therapy; CI only developed in patients receiving interferon-alpha (IFN) with IL-2 (three of 21, 14%) compared with none of 120 in those patients receiving IL-2 alone (P equals 0.0009). Severe diarrhea (greater than or equal to 7 bowel movements/day) also was significantly more common in patients receiving IFN with IL-2 (six of 21, 29%) than in those receiving IL-2 alone (three of 120, 2.5%, P equals 0.001) and preceded the clinical diagnosis of CI in all three patients. Three of nine patients with severe diarrhea had CI. Hematochezia occurred in four patients, all of whom received IFN with IL-2; three had CI, and the other patient had nonspecific colitis. Differences in vasopressor use did not explain the increased risk of CI in patients receiving IFN; those receiving IFN with IL-2 required phenylephrine less often than patients receiving IL-2 alone (P equals 0.01). The administration of lymphokine-activated killer (LAK) cells had no significant effect on the incidence of CI, severe diarrhea, peritonitis, or vasopressor use; two of three patients with CI, however, had their ischemic episode within 24 hours after the last of three LAK cell infusions. In conclusion, CI is an unusual complication of high-dose IL-2 and IFN immunotherapy. In patients receiving such combination therapy, severe diarrhea is a risk factor for the subsequent occurrence of CI. 
Carcinoma of the pancreas: a personal experience with 100 cases. One hundred patients with pancreatic cancer were evaluated between March 1981 and December 1989. This study showed that 61 were not candidates for definitive surgery because of nonoperability (28 patients) or nonresectability (33 patients). An additional 25 patients had cancers that were unresectable because of metastases (13 patients) or local spread of disease (12 patients) discovered at laparotomy. Fourteen patients had resectable cancers. Ten were treated by total pancreatectomy, three by distal pancreatectomy and one by pancreatoduodenectomy (Whipple). There were two operative mortalities. The median patient survival time was 20.5 months. Two patients survived 5 years. Five patients are alive at 3, 14, 18, and 47 months. Palliative surgical procedures performed in 18 patients included 10 biliary bypasses, 9 gastrojejunostomies, and 6 T-tube placements. This was associated with an operative mortality rate of 11%. The median survival time was 5 months. Other palliative measures included endoscopic placement of biliary and pancreatic stents (47 patients, 2.7% mortality rate), endoluminal radiation therapy, interstitial radiation therapy and external beam radiation therapy. The median survival time of patients so treated was 4.5 months. 
Successful medical treatment of presumed Candida endocarditis in critically ill infants. Few infants have been reported who survived fungal endocarditis; all have required both surgical and intensive antifungal therapy. We describe three infants, two weighing less than 1000 gm, who survived Candida endocarditis without surgery. Two had Candida parapsilosis, an agent not previously reported as a cause of neonatal endocarditis. All three infants were treated with amphotericin B and 5-flucytosine. Despite administration of 44, 38, and 48 mg/kg amphotericin B, respectively, no nephrotoxicity was noted; 5-flucytosine therapy was stopped in one infant because of thrombocytopenia. One infant died of an unrelated cause 6 months later; there was no evidence of Candida or endocarditis at autopsy. The other two infants are thriving 2 and 3 years after the completion of antifungal therapy; no remaining evidence of endocarditis is present on echocardiography. We conclude that antifungal therapy without surgery is an option for Candida endocarditis in critically ill infants. 
Clinical correlates of abnormal sensitivity to intraesophageal balloon distension. Sixty-five patients with esophageal complaints were studied to determine clinical associations with abnormal sensitivity to intraesophageal balloon distension (esophageal sensory dysfunction). Associations were examined in four categories: motility, esophageal symptoms, recent psychological symptoms, and general clinical features. A positive response to balloon distension (pain with less than or equal to 8 ml volume) was found in 29 (45%) of the subjects. This response was associated with specific findings in each category except recent psychological symptoms. A multiple logistic regression analysis indicated that an increased frequency of multipeaked waves on motility testing, presence of dysphagia, and shorter height of the subject each had an independent association with positive response to balloon distension (P less than or equal to 0.05 for each). Further comparison of subjects with sensory dysfunction, motor dysfunction, or both (sensorimotor dysfunction) indicated that subjects with the combined disorder appeared more symptomatic than those with either finding alone. These observations indicate that: (1) esophageal motor and sensory dysfunction are partially associated, but both contribute to the symptomatic state; (2) dysphagia may be representative of sensory dysfunction in some cases; and (3) subject height should be taken into consideration when interpreting balloon distension results. 
Smoking, the oral contraceptive pill, and Crohn's disease. Both cigarette smoking and the oral contraceptive pill have been implicated as aggravating factors in Crohn's disease. Based upon the recent demonstration of multifocal gastrointestinal infarction in Crohn's disease, a possible pathogenic mechanism for this condition, we propose how smoking and the oral contraceptive pill may potentiate a tendency for focal thrombosis and hence exacerbate the activity of Crohn's disease. 
Long-term therapy of HIV-associated Kaposi's sarcoma with recombinant interferon alpha-2a. Five young male patients with HIV-associated Kaposi's sarcoma (KS) were treated with recombinant interferon alpha 2a (rIFN-alpha-2a) over a period of 2-2.5 years. An IFN dose of 18 x 10(6) IU was given subcutaneously every day during the first 3 months of treatment and then on alternate days. Additional treatment with radiotherapy and laser therapy was given and, in some cases, isolated skin nodules were excised. Within 7 months of initiation of therapy one patient had a complete remission of his tumours, however, tumour progression recurred after the patient discontinued treatment. In another patient the tumour cleared within 9 months of rIFN therapy, and after 52 months he is still free of KS. The condition of a third patient tended to become stabilized during the first 6 months of therapy, but after 60 months there has been a slow progression. The fourth and fifth patients died 25 and 28 months, respectively, after the histological diagnosis of KS and the initiation of treatment. While on therapy with rIFN-alpha-2a, no life-threatening opportunistic infections occurred. The side-effects were mostly well tolerated, and no severe changes in haematological parameters were caused by the therapy. 
Value of dual-energy CT in differentiating focal fatty infiltration of the liver from low-density masses. Focal (irregular, partial) fatty infiltration of the liver may simulate neoplastic or other hypodense masses on CT. On the basis of previous observations of the phenomenon that differences in X-ray attenuation diminish with increasing energy of X-rays used, we performed a preliminary study to determine if dual-energy CT could be used to discriminate between fatty infiltration and hypodense liver masses. Dual-energy CT at 140 and 80 kVp was performed in 14 patients undergoing liver biopsy and in seven control subjects with presumedly normal liver. Attenuation measurements were taken, and the changes in attenuation between 140 and 80 kVp were calculated. The mean changes in attenuation were 3.5 H for normal liver (n = 7), 2.5 H for hypodense liver masses (n = 6), 13 H for fatty liver (n = 5), 0.3 H for fatty liver combined with hemochromatosis or hemosiderosis (n = 3), and 2 H for the spleen (n = 18). The change in attenuation increased as the fat content in the liver increased. Analysis of variance showed a statistically significant difference (p less than .001) between fatty liver and the other groups. A difference greater than 10 H was unique to fatty infiltration. These results suggest that dual-energy CT may help to differentiate focal fatty infiltration of the liver from low-density neoplastic or other lesions, but only if the iron content of the liver is not increased. 
Abnormal expression of histocompatibility and mitochondrial antigens by cardiac tissue from patients with myocarditis and dilated cardiomyopathy. Autoantibodies against the adenine nucleotide translocator (ANT), the branched chain alpha-ketoacid dehydrogenase (BCKD) complex proteins, and myosin have been implicated in the pathogenesis of human dilated cardiomyopathy (DCM). Cardiac tissue from patients with DCM and, for control purposes, cardiac tissue from patients with other forms of cardiomyopathy and from patients with no history of cardiac disease were stained with heterologous and ANT-, BCKD-, and myosin-specific affinity-purified sera from DCM patients. Data demonstrate that although anti-myosin stains tissues from both patients and normal controls, the ANT- and BCKD-specific heterologous and affinity-purified sera from DCM patients stain only cardiac tissues from DCM patients. Intense staining in patchy areas of cardiac tissue suggests that abnormal increased expression of these putative autoantigens occurs in discrete areas of cardiac myocytes. The reactivity of the antisera was organ specific and only seen in tissues from DCM patients. The organ and disease specificity of these findings suggests that such expression may play an important role in the pathogenesis of human DCM. 
Nifedipine reduces the incidence of myocardial infarction and transient ischemia in patients undergoing coronary bypass grafting. A randomized study was performed on 104 patients undergoing elective coronary artery bypass grafting to examine whether the infusion of nifedipine (n = 53) reduces the incidence of perioperative myocardial ischemia and necrosis in the early postoperative period. Continuous hemodynamic and three-channel Holter monitoring was performed for 24 hours and serial assessment of serum enzymes and 12-lead electrocardiography were performed for 36 hours postoperatively. Nifedipine (minimum dose, 10 micrograms/kg/hr for 24 hours) was applied from the onset of extracorporal circulation. The control group (n = 51) received nitroglycerin (minimum dose, 1 micrograms/kg/min for 24 hours). Using the combined analyses of electrocardiography and Holter recordings, myocardial ischemia was defined as being either a transient ischemic event (TIE), transient coronary spasm (TCS), or myocardial infarction (MI). The two groups did not differ with respect to preoperative New York Heart Association classification, age, history of myocardial infarction, extracorporal circulation and aortic cross-clamp time, number of distal anastomoses, or systemic and pulmonary hemodynamics. The incidence of perioperative myocardial ischemia was substantially lower in the nifedipine than in the nitroglycerin group [TIE: three of 53 patients (6%) versus nine of 50 patients (18%), p less than 0.001; MI: two of 53 patients (4%) versus six of 50 patients (12%), p less than 0.001; and TCS: none of 53 patients (0%) versus two of 50 patients (4%), p = NS]. 
Prevention of stroke and brain damage with calcium antagonists in animals. In a rat model of embolic stroke (permanent occlusion of the left middle cerebral artery [MCAO]), various 1,4-dihydropyridine calcium antagonists have been shown to attenuate brain damage and the resultant functional impairment when administered after MCAO. Dose-response curves reveal that isradipine is one of the most potent and efficacious representatives of this class of compounds, reducing the infarct size by more than 60%. These results suggest that isradipine, when administered shortly after stroke onset, may have beneficial effects in patients suffering from brain ischemia. When isradipine is used to normalize the high blood pressure in spontaneously hypertensive rats, it will, in addition, also protect the brain from damage engendered by a subsequent stroke. This is not the case if blood pressure is controlled with a calcium antagonist which does not cross the blood-brain barrier, suggesting that the brain protection seen with isradipine is not due to blood pressure normalization. Isradipine, when used as an antihypertensive, appears to have an additional beneficial effect within the brain itself. As high blood pressure is a major risk factor for stroke, such an additional benefit with isradipine would be particularly valuable in antihypertensive therapy. 
The relationship between large airway inflammation and airway metaplasia. To assess the role of acute inflammatory cells in large airways in the pathogenesis of metaplasia, we performed BAL (divided into aliquots) and mucosal biopsies on asbestos workers. They had evidence of asbestos-related lung injury. We found that acute inflammatory cells were significantly increased in the first aliquot. Ex-smokers had a greater percentage of PMN compared with nonsmokers and current smokers. The subjects were subgrouped with respect to biopsy-detected metaplasia. There was no difference between these groups for percentage or total number of PMN in the first aliquot. However, subjects with metaplasia had significant reduction in FEV1/FVC compared with those without. We conclude that there are significant differences in cells between the first and subsequent aliquots. Although inflammatory stimuli may be important in the pathogenesis of metaplasia, PMN present in the first aliquot could not be related to the severity of the metaplastic changes in these workers. 
Risks of leaving the gallbladder in situ after endoscopic sphincterotomy for bile duct stones. There is controversy concerning the subsequent clinical course of patients whose gallbladder is left in situ following successful endoscopic removal of stones from their common bile ducts. A total of 191 patients (median age 76 years) were reviewed between 12 and 100 months (mean 38 months) after endoscopic sphincterotomy. Ten patients (5.2 per cent) had symptoms requiring cholecystectomy which was uneventful, nine in the first year. Cholangitis at presentation or failure to fill the gallbladder by endoscopic retrograde cholangiography were not helpful in identifying these patients. Forty-nine (25.6 per cent) patients died during the review period from non-biliary pathology (usually cardiovascular). Elective cholecystectomy is not required in elderly patients with symptomatic bile duct stones if the common bile duct can be cleared of stones after endoscopic sphincterotomy. 
Carcinoma of the cervix treated with radiation therapy. I. A multi-variate analysis of prognostic variables in the Gynecologic Oncology Group. Between 1977 and 1985, the Gynecologic Oncology Group (GOG) conducted three clinical trials in locally advanced carcinoma of the cervix, clinical Stages I to IVA as classified by the International Federation of Gynecology and Obstetrics (FIGO). All 626 patients had primary carcinoma of the cervix and underwent operative assessment of the para-aortic (PA) lymph nodes. Patients received standardized external radiation therapy to the pelvis or to the pelvis and PA lymph nodes followed by one or two brachytherapy applications. To date, no statistically significant differences in progression-free interval (PFI) or survival time have been identified between the randomization treatment arms on any of these studies. Basic similarities among these studies led us to pool these data to identify patient characteristics and tumor characteristics associated with an increased risk of treatment failure. Multi-variate analysis showed patient age, performance status (PS), PA lymph node status, tumor size, and pelvic node status to be significantly associated with PFI. When modeling for survival, all these factors and clinical stage and bilateral extension were significant. 
Intrahepatic spontaneous arterioportal fistula: duplex ultrasound diagnosis and angiographic treatment. A 54-yr-old male with portal hypertension received ineffective medical therapy for the diagnosis of portal hepatic cirrhosis. Duplex ultrasound (US) revealed pulsatile arterial flow in the right main portal vein. The correct diagnosis of intrahepatic arterioportal fistula was established and confirmed by angiography. Right hepatic artery embolization with three coils was performed. The patient is alive for 16 months after the embolization, and his complaints have disappeared. There has been full resorption of ascites and absence of varices. Nine previously reported similar cases are reviewed. 
Transvaginal sonographic follow-up on the formation of fetal cephalocele at 13-19 weeks' gestation. An occipital meningocele was detected by transvaginal sonography in a fetus of 13 weeks' gestation. This changed at 14 weeks to a cephalocele, which disappeared at 15-16 weeks and was detected again at 19 weeks. It is possible that sliding backward and forward of the herniated brain tissue caused this sequence of events. 
Respiratory problems in emergence from anesthesia. In conclusion, anesthesia and mechanical ventilation have major effects on respiratory function, both intraoperatively and postoperatively. Recognition that mechanical ventilation represents a major departure from spontaneous ventilation should enable anesthesiologists to compensate for the increases in dead space ventilation and the propensity for alveolar collapse that accompany low volume mechanical ventilation. The use of postoperative regional analgesic techniques to alleviate respiratory compromise constitutes both current clinical practice and an area of active, ongoing investigation. Gone are the days when the anesthesiologist's responsibility stopped at the recovery room door. Today, anesthesiologists with expertise in postoperative pain management, cardiovascular physiology, and intensive ventilatory care are able to provide patients an improved likelihood of avoiding postoperative respiratory complications. 
Red cell deformability is an early indicator of infection. Red blood cells (RBC) have been shown to become less deformable during infection. The RBC deformability index (DI) was measured within 24 hours of admission in 37 patients who had suffered trauma and every 48 to 72 hours thereafter while they were in the surgical intensive care unit to assess whether DI could be used as an early indicator of infection after injury. Infection was defined as a temperature of 101 degrees F or more and a white blood cell count of more than 12,000/cm3 associated with a positive culture. Eighteen patients developed an infection, and 19 patients did not. On day 1, both groups showed a significant decrease in DI, compared to controls (0.33 +/- 0.18 and 0.34 +/- 0.25 for patients with infection and patients with no infection vs 1.52 +/- 0.12 for control volunteers; p less than 0.05). In the group with no infection, the DI improved in 16 of 19 patients after injury; the DI in patients with infection continued to decrease in 17 of 18 patients. The decrease in DI occurred 4 +/- 2 days (range, 2 to 8 days) before the diagnosis of infection. No significant differences were apparent in the absolute white blood cell count between the group with infection and the group with no infection at any time after injury. Differences in maximal temperature were noted on day 3 and beyond; however, 30% of patients with no infection had a temperature of more than 101 degrees F for 7 days. These data show that trauma results in a significant decrease in RBC deformability and that serial changes in DI appeared to predict which patients would develop an infection and which patients would recover uneventfully. RBC deformability may be helpful in early detection of infection in patients who have suffered trauma. 
Sensitivity of the gastric mucosa to acid and duodenal contents in patients with nonulcer dyspepsia. Nonulcer dyspepsia is a common clinical syndrome whose etiology is unknown. The sensitivity of the gastric mucosa to acid and duodenal contents in 18 patients with nonulcer dyspepsia was studied. The patients had a normal upper gastrointestinal endoscopy and biopsy specimens were obtained for determination of Helicobacter pylori status. Fifteen of the 18 patients were infected with H. pylori. All patients underwent intubation with double-lumen tube and collection of cholecystokinin-stimulated pancretico-biliary secretions. Subsequently, normal saline, 0.1N hydrochloric acid, and autologous duodenal secretions were infused into the stomach in a randomized blinded fashion. A positive response was defined as the production of epigastric pain by acid and/or bile but not by saline. By this definition, only 6 patients (33%) had a positive response and none had reproduction of their usual symptoms. In patients with a negative response, only 4 remained asymptomatic during all infusions. The remaining 8 had symptoms during infusion of saline, 7 of whom also had symptoms during infusion of acid and/or duodenal secretions. Two of these patients had reproduction of their usual symptoms. In conclusion, the gastric mucosa in patients with nonulcer dyspepsia is not abnormally sensitive to acid or duodenal contents. 
Fever response in elderly nursing home residents: are the older truly colder? OBJECTIVE: To test the hypothesis that many nursing home residents with an apparently blunted fever response (maximum temperature less than 101 degrees F) may actually have a significant change in temperature (delta T greater than or equal to 2.4 degrees F) which is not recognized because of a low baseline temperature. DESIGN: Retrospective chart review for cases of infection that met specific criteria and for chart-recorded baseline and infection temperatures. Chart-recorded baseline temperatures were prospectively compared with re-measurement of morning temperatures. SETTING: Nursing Home Care Unit of the VAMC West Los Angeles. PATIENTS: Random review of 40 residents' charts resulted in the detection of 69 infections among 26 residents over a 20-month period. Fifty randomly selected residents prospectively underwent comparison of chart-determined and actual re-measurement of baseline temperatures. RESULTS: In 50 randomly selected residents, the mean oral baseline temperature of 97.4 +/- 0.2 (degrees F +/- SEM) closely approximated the mean nurse-recorded measures in the charts (97.6 +/- 0.1). Chart review detected 69 infections among 26 residents, with 53 episodes having a temperature recorded during the infection. The mean maximum temperature (Tmax) during an infection was 101.3 +/- 0.3 (degrees F +/- SEM) but 47% (25/53) of the episodes had a "blunted" fever response (Tmax less than 101 degrees F). Of the 25 "blunted" fevers (Tmax less than 101 degrees F), about one-fourth demonstrated an adequate change in temperature from baseline (delta T greater than or equal to 2.4 degrees F) but failed to reach 101 degrees F because of a low baseline. Most infections (89%) had a Tmax greater than 99 degrees F. CONCLUSION: Establishing a nursing home patient's basal temperature and monitoring for changes in temperature (delta T greater than 2.4 degrees F) and/or lowering the threshold for recognition of fevers (to 99 degrees or 100 degrees F) in nursing home residents with a change in function should assist in early recognition of infections. 
Primary tumors of the facial (extracranial) nerve. Nearly 25% of all primary neurogenous tumors arise from peripheral nerves in the head and neck. The extracranial parts of the facial nerve, however, rank low as potential sites. Their tumors nonetheless pose diagnostic and management problems. In the intraparotid location the neurogenous tumors most often present as mass lesions, accompanied, in one third of patients, by various degrees of facial weakness. With the exception of a peculiar predilection of childhood plexiform neurofibromas to afflict the facial nerve, the majority of the tumors are neurilemomas. Recurrences are unusual after surgical removal of either neurilemomas or neurofibromas. The rare facial nerve sarcoma is a high-grade malignancy. 
Mucinous pancreatic tumors: ERCP findings Mucin-producing tumors of the pancreas are rare and difficult to diagnose neoplasms. To further characterize the nature of these lesions, four such cases are described here in which the diagnosis was suspected at endoscopic retrograde cholangiopancreatography by the presence of ampullary or intraductal mucus. In one patient, pancreatoscopy directly visualized the tumor. Ultrasound and computed tomography failed to suggest the presence of a neoplasm in the majority of these cases, but endoscopic ultrasound was performed in one and correctly identified the multi-cystic tumor. A high incidence of acute pancreatitis was seen in these cases and was felt to be secondary to intermittent ductal obstruction by mucus. The characteristic appearance of intra-ductal mucus provides an important clue to the presence of this type of pancreatic neoplasia. 
Antibody to hepatitis C virus and liver disease in volunteer blood donors. OBJECTIVE: To evaluate the specificity of antibodies to hepatitis C virus (anti-HCV) and their relation to liver disease in blood donors. DESIGN: Case series of consecutive blood donors found positive for anti-HCV by enzyme-linked immunosorbent assay (ELISA). Patients were evaluated for antibody specificity using a recombinant immunoblotting assay (RIBA) and were evaluated for biochemical evidence of liver disease. Patients showing increased alanine aminotransferase (ALT) levels had a liver biopsy. SETTING: University hospital. PARTICIPANTS: Fifty consecutive blood donors found to be anti-HCV positive on both an initial and repeat ELISA. Inclusion criteria were as follows: an absence of hepatitis B surface antigens and non-organ-specific autoantibodies; a daily alcohol intake of less than 50 g; no history of recent hepatotoxic drug use; and normal serum levels of alpha 1 antitrypsin, ceruloplasmin, and copper. MAIN RESULTS: Anti-HCV positivity was confirmed by RIBA in only 13 of 50 donors (26%) who had positive ELISA results. These 13 donors had an elevated ALT level and histologic evidence of chronic hepatitis, which was active in 8 patients (62%) and had already produced cirrhosis in 2 patients (15%). In contrast, the 17 donors with an intermediate RIBA pattern had only mild and often nonspecific histologic liver abnormalities. The 20 patients with a negative RIBA result had normal ALT levels. CONCLUSION: In blood donors, the anti-HCV RIBA is not only more specific than the anti-HCV ELISA, but is also useful in identifying patients who have an underlying chronic liver disease. 
Carcinoma of the uterus: use of gadopentetate dimeglumine in MR imaging. This prospective study assessed the role of gadopentetate dimeglumine-enhanced magnetic resonance imaging in the detection and staging of carcinomas of the endometrium and cervix. Surgical-pathologic findings were used as the standard of reference. In the evaluation of endometrial carcinoma, contrast-enhanced imaging improved tumor detection and differentiation between viable tumor and retained debris. Use of contrast material significantly improved the staging accuracy. The ability to assess the depth of myometrial invasion was also improved. In the evaluation of cervical carcinoma, assessment of tumor location and size did not improve following contrast enhancement. Use of gadopentetate dimeglumine resulted in overestimation of stromal, parametrial, vaginal, and/or bladder wall invasion in eight patients. However, evaluation of intratumoral architecture and large lesions was easier with contrast-enhanced imaging. When only stage II and higher disease was analyzed, use of contrast material improved the evaluation of disease extent. The authors conclude that gadolinium enhancement adds to the accuracy of evaluation of endometrial carcinoma but is useful in only advanced cases of cervical carcinoma. 
Osteogenic sarcoma arising adjacent to a long-standing ameloblastoma. A case report. Ameloblastoma is an uncommon odontogenic tumor usually occurring in the mandible. Rarely do other primary tumors occur with or arise from ameloblastoma. We describe a patient with simultaneous osteogenic sarcoma of the maxilla and recurrent ameloblastoma. 
Postradiation lower motor neuron syndrome presenting as monomelic amyotrophy. Monomelic amyotrophy developed 16 months, nine and 12 years after irradiation of the lumbosacral spinal cord for seminoma in one patient and for Hodgkin's disease in two others. In two patients, involvement was clinically limited to one leg, with a subacute course followed by plateau in the first case and with progressive worsening in the second one. In the third patient, the course was progressive with involvement of the other lower limb occurring five years later. From clinical and electrophysiological data, it seems probable that the disease process was a result of a selective injury to the lower motor neuron in the lower spinal cord. 
Right-to-left shunt across a patent foramen ovale caused by cardiac tamponade: diagnosis by transesophageal echocardiography. Cardiac tamponade can manifest as profound hypoxemia from intracardiac shunting across a patent foramen ovale. As a consequence, pulmonary embolus can be erroneously diagnosed. As demonstrated in the case described herein, transesophageal echocardiography can be useful in determining the correct diagnosis, especially if transthoracic echocardiography is technically limited. In our patient, the findings on transesophageal echocardiography also helped determine the appropriate treatment. The relative inaccessibility of the pericardial effusion to needle drainage prompted open surgical drainage. 
EMG activity in pericranial muscles during postural variation and mental activity in healthy volunteers and patients with chronic tension type headache. EMG activity was recorded over frontalis, temporalis and trapezius muscles in a supine position, a standing position and during a mental task in 32 female patients suffering from chronic tension-type headache and in 20 healthy volunteers. Measurements in patients were made before and after biofeedback therapy. All EMG levels were on average significantly higher in patients than in controls. 62.5% of patients had at least one abnormal EMG level, but only 34% were beyond the normal range, if 1 muscle and 1 recording condition was considered. EMG levels were not correlated with headache severity, anxiety or response to biofeedback treatment. It is therefore suggested that pericranial EMG activity is not pathogenetic in chronic tension type headache, but merely one of several pathophysiologic changes, that are produced by a central dysfunction. 
Anterior uveitis and hypopyon. We undertook a study to determine the incidence of hypopyon, as well as the most common anterior uveitis entities with which hypopyon is associated. A total of 216 patients with anterior uveitis were studied. The uveitis was acute in 155. Of the 155 patients, 11 (7.1%) had hypopyon. Nine of the 11 patients with hypopyon were positive for HLA B27. Of these nine, two had Reiter's syndrome and one had ankylosing spondylitis; the other six had no confirmed systemic disease. Of the two patients with hypopyon who were HLA B27-negative, one had mixed connective-tissue vascular disease, and one had idiopathic anterior uveitis. Of the 155 patients with acute anterior uveitis, 62 were HLA B27-positive. Thus, the incidence of hypopyon uveitis among HLA B27-positive patients was 14.5% (nine of 62 patients), whereas the incidence among HLA B27-negative patients was only 2.2% (two of 93 patients). These results suggest that HLA B27-related anterior uveitis is the most common cause of hypopyon uveitis, and that most patients with anterior uveitis associated with hypopyon will test positive for HLA B27. Although these results reflect a referral population, they should be of benefit in the treatment of patients with anterior uveitis. 
Concurrent eosinophilic fasciitis and cutaneous T-cell lymphoma. Eosinophilic fasciitis as a paraneoplastic syndrome of T-cell malignant neoplasms? Eosinophilic fasciitis has been reported to precede hematologic malignant neoplasms such as myelomonocytic leukemia, lymphocytic leukemia, and Hodgkin's lymphoma. In this case study, eosinophilic fasciitis occurred concurrently with cutaneous T-cell lymphoma (mycosis fungoides). The clinical diagnosis of eosinophilic fasciitis was based on painful sclerodermatous lesions on the extremities and trunk without acrosclerosis. There was histologic confirmation with edema and lymphocytic inflammation in the superficial muscular fascia and dermis. Deposition of immune reactants was found in the fascia and dermis. In addition, peripheral eosinophilia and circulating immune complexes were detected. The diagnosis of cutaneous T-cell lymphoma (mycosis fungoides) was based on extensive erythematous cutaneous plaques, dermal and epidermal lymphocytic atypia, loss of pan-T-cell immunologic markers, and a cutaneous lesional T-cell receptor beta-chain rearrangement by Southern blot analysis. Eosinophilic fasciitis may occur as a paraneoplastic syndrome associated with hematologic malignant neoplasms, including mycosis fungoides. Cytokines or lymphokines released by activated immunocytes, either malignant leukocytes or normal leukocytes reacting to malignant cells, may be responsible for the eosinophilia and sclerosis seen in these associated hematologic malignant neoplasms. 
Adhesion formation after ovarian electrocauterization on patients with polycystic ovarian syndrome. The rate of adhesion formation after ovarian electrocauterization has been described in two selective and unselective groups of patients with PCOS. The rate of this complication in the selective group was 0 from 16 ovaries and in the unselective group (5/25). However, the rate of major adnexal adhesion in the unselective group was 1 from 25 ovaries. 
Asperger's syndrome: who is being abused? Six case histories of children referred and admitted to a psychiatric inpatient unit at a tertiary referral centre because of concerns about poor functioning and possible emotional abuse are presented. On initial assessment the children appeared to be well functioning and the impression was confirmed that their emotional needs were not being met by their parents. After detailed inpatient appraisal the diagnosis of Asperger's syndrome was made in all six cases, exemplified mainly by a formal concrete way of thinking and an inability to identify and understand human emotions and relationships. The impact of the diagnosis on the parents and their consequent relationships with their child and their willingness to work with professionals is discussed. 
Large molecular form of serum HBeAg in chronic hepatitis B virus infection: relation to liver cell damage. We have separated circulating HBeAg into small and large molecular forms by agarose gel electrophoresis and analyzed the relationship between the two forms and other clinical features of chronic hepatitis B, especially in regard to liver cell damage. The large HBeAg accounted for 7.3% +/- 3.4% of serum HBeAg in 9 subjects with normal liver histological findings or nonspecific reactive hepatitis, 38.0% +/- 27.8% in 32 patients with chronic persistent hepatitis and 65.6% +/- 23.3% in 21 patients with chronic active hepatitis (p less than 0.01). A positive correlation was seen between the height of aminotransferase elevations and the percentage of large HBeAg. Three patients who progressed from histologically normal liver or nonspecific reactive hepatitis to chronic active hepatitis had dramatic increases in the percentage of large HBeAg. The finding that the presence of large HBeAg in serum correlated with the severity of hepatitis suggests that HBeAg may play an important role in determining the degree of liver injury in chronic hepatitis B. 
Ischaemic myelopathy secondary to disseminated intravascular coagulation in AIDS. A 39-year-old patient with AIDS presented with a rapidly progressive myelopathy with a partial Brown-Sequard syndrome. He died, 9 weeks after onset of the first neurological signs, from diffuse encephalopathy. Neuropathological examination revealed multiple, usually small, frequently haemorrhagic, infarcts or various ages and numerous fibrin thrombi in medium and small penetrating vessels and capillaries of the brain and spinal cord, characteristic of disseminated intravascular coagulation. There were no inflammatory changes. Immunohistochemical studies for human immunodeficiency virus, cytomegalovirus, varicella zoster virus, herpes simplex virus type 1 and type 2 were negative. Ischaemic spinal cord lesions due to disseminated intravascular coagulation may represent an unusual cause of focal, non-inflammatory, non-tumoral, myelopathic syndrome in AIDS. 
Infection by mink cell focus-forming viruses confers interleukin 2 (IL-2) independence to an IL-2-dependent rat T-cell lymphoma line. The development of T-cell lymphomas in rodents infected with type C retroviruses has been linked to the generation of a class of envelope (env) recombinant viruses called mink cell focus-forming viruses (MCF viruses) in the preleukemic thymus. To determine whether infection by MCF viruses altered the growth phenotype of retrovirus-induced T-cell lymphomas, a Moloney murine leukemia virus-induced interleukin-2 (IL-2)-dependent rat T-cell lymphoma line (4437A) was infected with MCF-247, modified MCF-V33 (mMCF-V33), or NZB-xenotropic (NZB-X) virus. The effects of virus infection on the IL-2 dependence of these cells was examined by cultivating them in the absence of IL-2. After IL-2 withdrawal, the uninfected and NZB-X-infected cells went through a crisis period characterized by massive death. All the independently maintained cultures of MCF- and mMCF-V33-infected cells, on the other hand, became IL-2 independent without a crisis. All the polytropic virus-infected IL-2-independent cultures contained a population of cells that was polyclonal with regard to polytropic provirus integration. Over this polyclonal background each culture produced multiple clones of cells that were selected rapidly after IL-2 withdrawal. Furthermore, the resulting MCF- or mMCF-V33-infected IL-2-independent cells retained the expression of IL-2 receptor. These data show that MCF and mMCF-V33 viruses may alter the growth phenotype of a T-cell lymphoma line and suggest that their effect on cell growth may be due to the direct interaction of the MCF envelope glycoprotein with cellular components, perhaps the IL-2 receptor. 
Pulmonary angiitis and granulomatosis. The presentation of a patient with multiple pulmonary nodules with or without cavitation and often with signs of a multisystemic vasculitis should suggest one of the pulmonary angiitis and granulomatosis syndromes. The five conditions traditionally considered together in the category of pulmonary angiitis and granulomatosis differ widely in their cause and pathogenesis and are more appropriately considered as variants or relatives of other processes. The radiologic features of this group of diseases, however, are similar, and it is useful to still consider them together. Table 1 summarizes the radiologic features of these conditions. 
Acanthoma fissuratum. Acanthoma fissuratum secondary to the use of spectacles is a rare clinical finding associated with an ill-fitting frame. An interesting case is presented to highlight such a problem. Surgical excision of such lesions is recommended with advice to the patient regarding the suitable fitting of spectacles. 
Electrophysiologic and anatomic characteristics of ventricular tachycardia induced at the right ventricular outflow tract but not at the apex. The site of ventricular stimulation is an important variable in the initiation of ventricular tachycardia (VT) by programmed ventricular stimulation. Among 169 patients studied consecutively, 17 (10%) had ventricular tachycardia induced by programmed electrical stimulation from the right ventricular outflow tract but not from the apex. Fourteen of these 17 patients had had prior myocardial infarction (12 had inferior, and two had both inferior and anterior myocardial infarction), two had a dilated cardiomyopathy, and one had a localized cardiomyopathy. Fourteen patients had echocardiograms suitable for analysis. Of these, 12 had posterior/inferior ventricular wall motion abnormalities located at the base of the heart. The ventricular effective refractory periods from the right ventricular outflow tract and right ventricular apex were 237 +/- 4 and 244 +/- 5 msec, respectively (p less than 0.05, mean +/- SEM). Induced VT had a cycle length of 229 +/- 4 msec and had the morphology of right bundle branch block in 12 patients, of left bundle branch block in three patients, and had both morphologies in two patients. In 14 patients the axis was superior. VT was initiated with two extrastimuli in 15 patients and with burst right ventricular pacing in two patients. Similar pacing techniques with identical pacing intervals did not induce VT at the right ventricular apex in 14 of these 17 patients. Further, among the 15 patients whose VT was induced at the right ventricular outflow tract with two extrastimuli, neither burst pacing (n = 13) nor two extrastimuli introduced at faster paced rates (n = 12) induced VT at the right ventricular apex. 
Effect of bile diversion and sphincterotomy on gallbladder muscle contractility and gallstone formation. Feeding prairie dogs a diet rich in cholesterol induces gallstone formation that is preceded by a sustained decrease in gallbladder smooth muscle contractility. Sphincterotomy is known to prevent gallstone formation in cholesterol-fed prairie dogs. Experiments were designed to determine whether the effect of sphincterotomy is a consequence of hepatic bile diversion, and whether bile diversion prevents the altered contractility. Following sham operation, surgical biliary enteric bypass, or sphincterotomy, prairie dogs were fed a high-cholesterol or a regular diet. Gallbladder muscle contractility and the presence of crystals and stones were determined. In sham-operated animals, the cholesterol diet induced a decrease in gallbladder muscle contractility and caused the formation of cholesterol gallstones. In animals with bile diversion and sphincterotomy, the effects of cholesterol feeding were reduced or prevented. Thus, these procedures may prevent stone formation by preventing a reduction in gallbladder contractility. Contractility was depressed in animals with bile diversion fed a regular diet, compared with animals with a sham operation fed a regular diet. The mechanism for this depression may differ from that induced by the cholesterol diet. Diversion, and perhaps sphincterotomy, impairs gallbladder filling. Thus, gallbladder muscle is not stretched and does not contract against a load. This could result in a "disuse atrophy." If the results from our study apply to humans, sphincterotomy may reduce stone formation by preventing the effects of lithogenic bile on gallbladder muscle contractility and by enhancing the ability of the muscle to empty the lithogenic bile. 
Antibody to hepatitis C is common among patients with alcoholic liver disease with and without risk factors. Thirty-seven patients with clinically suspected alcoholic liver disease were retrospectively studied for the prevalence of antibody to hepatitis C virus (HCV) by enzyme-linked immunosorbent assay (ELISA) and immunoblot assay. Twenty-four had biopsy-proven cirrhosis. Nineteen had identifiable risk factors for non-A, non-B viral hepatitis, and 18 did not. Five of 19 high-risk (26%) and 6 of 18 low-risk (33%) patients had positive antibody, compared with two of 179 healthy blood donors (p less than 0.01 for either group of alcoholics compared with blood donors). Nine of 11 ELISA-positive patients were also either positive or indeterminable by immunoblot testing. Histologic scores for parameters commonly associated with chronic viral hepatitis were numerically worse among anti-HCV-positive patients, but none reached statistical significance. Clinically, seven of 11 (64%) of anti-HCV-positive patients versus 14 of 26 (54%) anti-HCV-negative patients were Child's class C. Among the 21 Child's class C patients, seven (33%) were anti-HCV-positive versus four of 16 (25%) of Child's class A/B patients. A weak correlation between IgG and ELISA optical density was observed (r = 0.52). We conclude that antibody to hepatitis C by ELISA and immunoblot is common among alcoholics with liver disease even in the absence of known or suspected risk factors for viral hepatitis. Although hepatitis C-positive patients tended to have more severe histologic disease, neither histologic parameters nor clinical findings were adequate to predict antibody seropositivity. 
Site-directed mutagenesis of the region around Cys-241 of complement component C2. Evidence for a C4b binding site. We probed the functional significance of the region around Cys-241 in human C2 by testing the hemolytic activity of a series of mutant rC2. Mutant C2 cDNA were constructed by oligonucleotide-directed site-specific mutagenesis and expressed transiently in COS cells. Wild-type rC2 had threefold higher specific hemolytic activity than native serum C2. Substitution of Gly, Ala, or Ser for Cys-241 resulted in a slightly, but significantly, increased activity. In addition, I2 had no effect on the activity of these mutant C2. Substitution of Lys for Gln-243 increased the hemolytic activity by more than two-fold. Increased activity in all cases was due to slower decay rates of the C3 convertase. Finally, substitution of Leu or Ala for Asp-240 or Ser-244, respectively, resulted in more than 100-fold decrease of hemolytic activity. The results suggest that residues 240 to 244 of human C2 represent an important structural determinant of the C4b binding site of C2a. They also confirm that Cys-241 is the residue responsible for the increased activity of C2 reacted with I2. 
Psychiatric disorders in 36 families with Wolfram syndrome. OBJECTIVE: The purpose of this study was to test the hypothesis that heterozygous carriers of the gene for the Wolfram syndrome, who constitute about 1% of the population, are predisposed to significant psychiatric illness. The Wolfram syndrome is an autosomal recessive neurodegenerative syndrome in which 25% of the individuals who are homozygous for the condition have severe psychiatric symptoms that lead to suicide attempts or psychiatric hospitalizations. METHOD: The authors collected questionnaires, death certificates, and hospital records for blood relatives and their spouses in 36 families of individuals with the Wolfram syndrome and compared the proportion of blood relatives who had had psychiatric hospitalizations, had committed suicide, or had self-reported mental illness to the proportion of spouses with the same manifestations. RESULTS: The proportion of blood relatives who had had psychiatric hospitalizations, had committed suicide, or had self-reported mental illness significantly exceeded the proportion of spouses with the same manifestations. CONCLUSIONS: Since heterozygous carriers of the gene for the Wolfram syndrome are 50-fold more common among the blood relatives than among the spouses, the larger proportion among blood relatives is evidence that heterozygous carriers of the gene for the Wolfram syndrome are predisposed to significant psychiatric illness. 
Value of sonography in monitoring the therapeutic response of mediastinal lymphoma: comparison with chest radiography and CT. The aim of this retrospective study was to assess the diagnostic value of mediastinal sonography, compared with that of chest radiographs and CT, in the follow-up of patients with mediastinal lymphomas and in the prediction of clinical outcome. The sonograms, chest radiographs, and CT scans of 40 consecutive patients with Hodgkin (n = 29) and non-Hodgkin (n = 11) lymphoma obtained before and after completion of therapy were analyzed blindly and independently by three radiologists and compared with clinical outcome. Nine patients were treated with radiotherapy, 12 with chemotherapy, and 19 with combined therapy. Therapeutic response was assessed from all available clinical and biochemical findings as well as from the combined results of all imaging studies performed on further follow-up. The sonograms showed obvious changes in the size and echogenicity of the mediastinal lymphomas that corresponded closely with the response to therapy. Sonography showed complete regression of the lymphomas in 30 patients who had complete remission. In five patients with incomplete remission, sonographic diagnoses were correct. All lymph nodes, irrespective of size, detected with sonography after a phase of complete remission indicated recurrence (five patients). Sonographic findings corresponded with those of CT in 25 (81%) of 31 cases. Clinical outcome suggested that the sonographic findings were more reliable in the five cases in which CT and sonographic findings conflicted. Chest radiographs were inadequate for monitoring the response of mediastinal lymphomas to therapy; in 17 (43%) of 40 cases, a false impression was obtained of the extent and therapeutic response of mediastinal lymphomas. The results of this study indicate that sonography is clearly superior to chest radiographs and comparable to CT for monitoring patients with mediastinal lymphomas. 
Pyruvate kinase activity and isozyme composition in normal fibrous tissue and fibroblastic proliferations. Pyruvate kinase (PK) was studied in 57 fibroblastic and fibrohistiocytic proliferations and normal fibrous tissue (n = 10). The specific activity was significantly increased in malignant tumors (1.67 +/- 0.25) compared with normal tissue (0.26 +/- 0.04; P less than 0.001) and benign proliferations (0.52 +/- 0.05; P less than 0.005). Although an overlap exists between aggressive fibromatosis and the benign group, high values of PK activity are indicative of Grade 2 and 3 malignancy. Significant shifts in isozyme pattern, favoring the expression of K-type subunits were found in tumors with a metastasizing potential and aggressive fibromatosis. These changes in the isozyme pattern of PK in aggressive fibromatosis may act as another argument to place them in the category of malignant fibroblastic tumors. 
Evaluation of mixed chimerism by in vitro amplification of dinucleotide repeat sequences using the polymerase chain reaction. The influence of mixed hematopoietic chimerism (MC) after allogeneic bone marrow transplantation remains unknown. Increasingly sensitive detection methods have shown that MC occurs frequently. We report a highly sensitive novel method to assess MC based on the polymerase chain reaction (PCR). Simple dinucleotide repeat sequences called microsatellites have been found to vary in their repeat number between individuals. We use this variation to type donor-recipient pairs following allogeneic BMT. A panel of seven microsatellites was used to distinguish between donor and recipient cells of 32 transplants. Informative microsatellites were subsequently used to assess MC after BMT in this group of patients. Seventeen of the 32 transplants involved a donor of opposite sex; hence, cytogenetics and Y chromosome-specific PCR were also used as an index of chimerism in these patients. MC was detected in bone marrow aspirates and peripheral blood in 18 of 32 patients (56%) by PCR. In several cases, only stored slide material was available for analysis but PCR of microsatellites or Y chromosomal material could be used successfully to assess the origin of cells in this archival material. Cytogenetic analysis was possible in 17 patients and MC was detected in three patients. Twelve patients received T-cell-depleted marrow and showed a high incidence of MC as revealed by PCR (greater than 80%). Twenty patients received unmanipulated marrow, and while the incidence of MC was lower (44%), this was a high percentage when compared with other studies. Once MC was detected, the percentages of recipient cells tended to increase. However, in patients exhibiting MC who subsequently relapsed, this increase was relatively sudden. The overall level of recipient cells in the group of MC patients who subsequently relapsed was higher than in those who exhibited stable MC. Thus, while the occurrence of MC was not indicative of a poor prognosis per se, sudden increases in the proportions of recipient cells may be a prelude to graft rejection or relapse. 
Let sleeping dogs lie: role of the omentum in the ileal pouch-anal anastomosis procedure. A surgical aphorism has long held that the omentum is the "watchdog of the abdomen." However, detractors believe that leaving the omentum behind after colectomy precipitates later small bowel obstruction. A retrospective comparison was made between a group of 406 patients (Group I) having omentectomy with proctocolectomy and ileoanal anastomosis and a group of 239 patients (Group II) having a similar procedure without omentectomy. Follow-up in this series of 645 patients was 4.3 +/- 2.1 years (mean +/- SEM). No difference was present in the rate of partial small bowel obstruction or complete small bowel obstruction between Group I patients (32 percent partial, 12 percent complete) and Group II patients (29 percent partial, 12 percent complete; P greater than 0.1). However, a better outcome with regard to postoperative sepsis and sepsis requiring operation was apparent in Group II patients retaining the omentum (4 percent and 3 percent, respectively) than in Group I patients (10 percent and 8 percent, respectively), in whom the omentum was removed (P less than 0.01). As this experience would support, we urge surgeons to "let sleeping dogs lie" and, when possible, retain the omentum when performing colectomy or proctocolectomy. 
Hepatosplenic candidiasis: successful treatment with fluconazole. PURPOSE: To determine if fluconazole is effective treatment for hepatosplenic candidiasis that has not resolved with amphotericin B and flucytosine treatment. PATIENTS AND METHODS: Six patients (ages 3 to 44) with acute leukemia and hepatosplenic candidiasis who did not respond to prior antifungal therapy were treated with fluconazole. RESULTS: All six patients had fever and three had nausea and vomiting; computed tomographic (CT) scan showed lucencies in the liver in six, lucencies in the spleen in five, and lucencies in the kidneys in three. Prior therapy with 1.6 to 4 g of amphotericin B in the five adults and 526 mg of amphotericin B in the child (with the addition of flucytosine in four) failed to improve clinical symptoms or lucencies in the liver, spleen, and kidneys seen on CT scan. Fluconazole was given at a dose of 200 to 400 mg daily (70 to 100 mg in the child) for 2 to 14 months. All patients had resolution of fever and other symptoms in 2 to 8 weeks. Improvement of the lesions noted on CT scan was seen in 4 to 8 weeks in all patients. Total resolution of lesions noted on CT scan occurred by 4 weeks in two patients, but took 4 to 5 months for three patients and 13 months for one patient. Three patients had relapse of their acute leukemia and two died, presumably cured of their candidiasis. Two patients underwent successful bone marrow transplantation without relapse of their candidiasis. CONCLUSION: Fluconazole appears to be useful in the treatment of hepatosplenic candidiasis that has not resolved with amphotericin B and flucytosine therapy. 
Moderate protection of renal function and reduction of fibrosis by colchicine in a model of anti-GBM disease in the rabbit. A rabbit model of renal glomerulosclerosis induced by anti-glomerular basement membrane antibody was used to determine whether colchicine would protect renal function and reduce fibrosis. Initial studies established the time course of renal function changes and fibrosis. Colchicine at a dose of 0.02 to 0.04 mg/kg per day injected ip was begun at day 4 when injury had been initiated, and the experiment was ended at day 21 when fibrotic changes were established. Colchicine significantly reduced the rise in serum creatinine (serum creatinine = 2.7 +/- 0.3 mg% in vehicle-treated animals versus 1.8 +/- 0.1 mg% in colchicine-treated animals) and interstitial fibrosis (fibrosis score = 2.6 +/- 0.2 in vehicle-treated versus 1.5 +/- 0.2 in colchicine-treated animals). Colchicine treatment did not significantly affect weight, anti-guinea pig immunoglobulin level, % fibrocellular crescents formed, hydroxyproline per gram (dry weight) in tissue, or urine protein: creatine ratio. Regression analysis was performed to examine the interrelationships between variables for all animals and the effect of colchicine on pairs of variables. No clear-cut site of colchicine action could be identified. These data show that colchicine, in doses that could be used in humans, protected renal function by about 25% and reduced interstitial fibrosis in a model of severe crescentic nephritis. 
Diarrheal deaths in the United States, 1979 through 1987. A special problem for the elderly. OBJECTIVE.--Diarrhea is an important cause of death among young children in both developing and developed countries, but little is known about diarrheal death among adults. In this study, we examined trends in diarrheal deaths among all age groups in the United States. DESIGN/SETTING/PARTICIPANTS.--We reviewed national mortality data complied by the National Center for Health Statistics, Hyattsville, Md, which consists of information from all death certificates filed in the United States for the period 1979 through 1987. A death for which diarrhea was listed as an immediate or underlying cause was considered a "diarrheal death" and included in the analysis. RESULTS.--We found that 28,538 persons died of diarrhea cited as either an immediate or the underlying cause of death during the 9-year period. A majority of diarrheal deaths occurred among the elderly (older than 74 years of age, 51%), followed by adults 55 to 74 years of age (27%), and young children (younger than 5 years of age, 11%). For the elderly, adjusted risk factors for dying of diarrhea included being white, female, and residing in a long-term care facility. Only the elderly and young children had clear, distinct winter peaks of diarrheal deaths, suggesting that the diarrhea may, in part, be infectious in origin. CONCLUSION.--For the elderly, more directed studies of those at risk, such as nursing home residents, are needed to determine if oral rehydration therapy, vaccines, or other preventive measures might benefit this population. 
Acute and chronic hemodynamic effects of xamoterol in mild to moderate congestive heart failure. Xamoterol, a new beta 1 partial agonist, has the potential to modulate cardiac response to variations in sympathetic tone in patients with heart failure. Its properties should result in beta-receptor stimulatory effects at low levels of sympathetic tone and beta-receptor protective effects at higher levels of sympathetic tone. The acute effects of intravenous (i.v.) xamoterol on hemodynamics at rest and during exercise were studied in 30 patients with mild to moderate heart failure (13 patients in New York Heart Association class II; 17 in class III) due to ischemic (n = 24) or cardiomyopathic (n = 6) heart disease. Cardiac index, stroke volume and stroke work index at rest were significantly improved after i.v. administration of xamoterol and consistent with net agonist effects. During exercise, heart rate and double product were significantly reduced (net antagonist effects), but with preservation of the expected increases in cardiac index and systolic blood pressure. These hemodynamic findings confirm the ability of xamoterol to modulate cardiac response to variations in sympathetic tone. Tachyphylaxis and arrhythmogenicity limit the chronic use of drugs with full beta-agonist properties as positive inotropes in heart failure. The patients were therefore entered into a 6-month double-blind, placebo-controlled, crossover study of chronic oral xamoterol therapy, 200 mg twice daily, and the hemodynamic responses to i.v. xamoterol were repeated at the end of the trial. No impairment in either resting or exercise effects was observed, indicative of a maintained response and absence of tachyphylaxis after chronic therapy. Furthermore, 24-hour ambulatory electrocardiographic monitoring showed no change in ventricular arrhythmias during oral treatment. 
Trisomy 12 in chronic lymphocytic leukemia: an interphase cytogenetic study. Interphase cytogenetics by means of in situ hybridization with the chromosome 12-specific biotinylated alpha satellite DNA probe pSP 12-1 was used for the study of trisomy 12, the most common chromosomal abnormality in chronic lymphocytic leukemia. In situ hybridization was performed on methanol/acetic acid fixed cells of conventional cytogenetic preparations from eight patients and on morphologically and immunologically classified cells of cytospin preparations from seven patients. The results show that trisomy 12 is more common than assumed on the basis of karyotype analysis of metaphase chromosomes: 2 of 13 patients with a normal karyotype in G-banding analysis were shown to have trisomy 12 by interphase cytogenetics. Immunophenotyping of the cells of one patient showed that the trisomy was restricted to cells with Ig light chain clonality. For the evaluation of the prognostic, therapeutic, and biologic significance of trisomy 12, in situ hybridization should be used in parallel with karyotype analysis because it allows the study of all cell populations of both interphase and mitotic cells, whether neoplastic or normal. 
Multiple endocrine neoplasia type 1: a 10-year prospective screening study in four kindreds. A total of 80 individuals in 4 kindreds with multiple endocrine neoplasia type 1 (MEN 1) have been subjected to repeated biochemical screening during a 10-yr period with the principal aim being to analyze characteristics of the developing pancreatic lesion. Age at presentation of the MEN 1 trait averaged 18 yr in 7 previously unaffected individuals, and this effect of the screening procedure represented a lowering by almost 2 decades. Pancreatic endocrine involvement was recognized at a mean age of 25 yr and constituted the presenting lesion in a majority of the patients. A standardized meal test and basal values of serum pancreatic polypeptide, insulin, proinsulin, and gastrin were the most efficient markers for the pancreatic lesion and preceded signs of pancreatic tumors upon radiological examinations by a mean of 3.5 yr. A 75% penetrance of the islet cell disease and 90% for primary hyperparathyroidism within the affected individuals equalled the prevalences reported in autopsy studies. Two of the kindreds showed signs of intrafamilial homogeneity with respect to the profile of peptide excess (P less than 0.05) and considerable discrepancy in the malignant potential of the pancreatic lesions. The results of early detection and surgical intervention of the pancreatic tumors in MEN 1 suggested an impact on morbidity, while any effect on the mortality of these individuals remains to be clarified. 
Surgical risk of hemorrhage in cerebral amyloid angiopathy. Cerebral amyloid angiopathy is increasingly recognized as a cause of lobar cerebral hemorrhage in normotensive elderly individuals. Isolated reports have suggested that neurosurgical intervention entails a high risk of precipitated hemorrhage. We identified 16 pathologically confirmed cases of cerebral amyloid angiopathy. Fourteen of these patients presented with lobar cerebral hemorrhage. Fifteen neurosurgical procedures in eight patients included eight clot evacuations, three abscess drainage procedures, two ventriculoperitoneal shunts, one biopsy, and one lobectomy. Recurrent postoperative cerebral hemorrhage was seen in four patients at 2 days, 9 days, 6 weeks, and 10 months, but surgery was thought to have precipitated the cerebral hemorrhage in only one patient. Recurrent cerebral hemorrhage also was seen in two of the eight nonoperated cases. Recurrent cerebral hemorrhage is characteristic of cerebral amyloid angiopathy, but we conclude that neurosurgical intervention, particularly evacuation of hematomas, is not associated with major risk of precipitated hemorrhage. 
Ventricular fibrillation complicating endomyocardial biopsy of a cardiac allograft. Transvenous endomyocardial biopsy remains the most useful diagnostic aid in assessing rejection in the transplanted heart. Although invasive, the complications associated with endomyocardial biopsy are few, and the procedure is generally regarded as safe. We report a case of apparent ventricular fibrillation complicating transvenous endomyocardial biopsy. Histologic section revealed evidence of moderate acute rejection. This case represents the first report of a life threatening ventricular dysrhythmia following routine endomyocardial biopsy in a cardiac transplant recipient. 
Catheter-less suprapubic cystolithotomy in children. Bladder stones in children are common in developing countries and the procedure of choice for their removal is suprapubic cystolithotomy. It is standard practice to drain the bladder for a few days post-operatively to prevent urinary leakage. We have observed that, if the bladder is closed meticulously in 2 layers, bladder drainage by means of a catheter is not required. We have analysed 86 children treated by suprapubic cystolithotomy without a catheter. Size of the stones and intra-operative findings were noted and it was found that 85% of the patients had an excellent result; 10% had a satisfactory result and 4.7% were unsatisfactory. The advantages of the procedure and selection of the patients are discussed. 
Deleted HTLV-I provirus in blood and cutaneous lesions of patients with mycosis fungoides. Mycosis fungoides, a rare form of cutaneous T cell leukemia/lymphoma, is suspected of having a viral etiology on the basis of certain similarities to adult T cell leukemia, which is associated with human T cell leukemia/lymphoma virus type I (HTLV-I) infection. Cell lines were established from peripheral blood mononuclear cells (PBMC) of an HTLV-I-seronegative patient with mycosis fungoides. DNA hybridization analysis revealed the presence of HTLV-I-related sequences with unusual restriction endonuclease sites. Sequence analysis of subcloned fragments demonstrated the presence of a monoclonally integrated provirus with a 5.5-kilobase deletion involving large regions of gag and env and all of pol. Additional evidence for the presence of deleted proviruses was found by polymerase chain reaction (PCR) amplification of DNA from cutaneous lesions of five other HTLV-I-seronegative patients. The findings suggest that HTLV-I infection may be involved in the etiology of at least certain cases of mycosis fungoides. 
Prostate specific antigen in the management of patients with localized adenocarcinoma of the prostate treated with primary radiation therapy. The records of 143 patients treated at 5 institutions with external beam megavoltage irradiation for localized prostatic cancer were reviewed to evaluate post-treatment changes in prostate specific antigen (PSA) in the context of subsequent events. Complete responders were defined as patients clinically well with normal PSA, clinical failures were patients with documented local tumor recurrence or distant metastases and chemical failures were patients clinically well but with a PSA level above the upper limits of normal. Correlations with pre-treatment PSA values were also made for the 50 of 143 patients for whom pre-treatment PSA data were available. Median patient followup was 27 months (range 18 to 91 months). The data were analyzed with parametric and nonparametric univariate and multivariate statistical procedures. Pre-treatment PSA levels increased with increasing tumor stage (p = 0.004) but not with increasing summed Gleason pattern scores (p = 0.15). The probability of remaining a complete responder decreased with increasing stage (p = 0.008) but not with increasing Gleason score (p = 0.14). Increasing pre-treatment PSA correlated with clinical failure (p = 0.01) and chemical failure (p = 0.006). Of the patients with a pre-treatment PSA level of less than 4 times the upper limits of normal 83% remained as complete responders compared to 30% of those with a higher pre-treatment PSA (p = 0.0002). The return of PSA levels to the normal range within 6 months after treatment was strongly correlated with a favorable outcome when analyzed by multivariate logistic regression. The status at last followup of patients who had a normal PSA level at 6 months versus those with an elevated PSA level 6 months after treatment is 94% versus 8% for complete responders (p = 0.0001), 0% versus 60% for clinical failures (p = 0.002) and 6% versus 32% for chemical failures (p = 0.14). Similar results occurred when analyzing outcomes in relationship to PSA normalization within 12 months after treatment (p = 0.001 for clinical failures, p = 0.02 for chemical failures and p = 0.001 for complete responders). We conclude that the pre-treatment level of PSA is an independent prognostic factor for prostate cancer patients treated with primary radiation therapy, and that the failure of PSA to return to the normal range within 1 year after completion of treatment identifies a group of patients at high risk for tumor recurrence. 
Hemodynamic effects of direct angiotensin II blockade compared to converting enzyme inhibition in rat model of heart failure. The purpose of this investigation was to compare the chronic effects of converting enzyme inhibition with captopril to direct blockade of angiotensin II (AII) with DuP 753 in the rat model of heart failure. Rats with chronic heart failure postinfarction were treated for 2 weeks with either captopril (2 g/L, N = 9) in their drinking water or with DuP 753 (40 mg/kg/day for two weeks by gastric gavage, N = 10), or placebo (N = 9). At this dose, DuP 753 shifted the log dose-pressor response curve to AII parallel to the right by two orders of magnitude in both chronically treated normal and heart failure rats. In rats with heart failure, DuP 753 and captopril reduced left ventricular end-diastolic pressure from 26.7 +/- 1.5 to 14.2 +/- 3.0 (P less than .01) and 15.8 +/- 2.2 mm Hg (P less than .05), respectively, left ventricular end-diastolic volume index from 2.71 +/- 0.10 to 2.03 +/- 0.17 (P less than .05) and 2.18 +/- 0.15 (P less than .05), respectively; venous compliance increased from 2.27 +/- 0.06 to 2.80 +/- 0.18 (P less than .05) and 3.02 +/- 0.21 mL/mm Hg/kg (P less than .01), respectively. There were no significant changes in left ventricular weight/body weight ratio, mean aortic pressure, heart rate, or right atrial pressure. There was a trend, but not significant, for a reduction in total blood volume from 65.8 +/- 1.1 to 59.4 +/- 3.0 and 64.9 +/- 3.9 mL/kg, respectively. Thus, direct blockade of AII with DuP 753 or with converting enzyme inhibition with captopril produces similar hemodynamic changes in rats with heart failure after myocardial infarction. 
Preventive maintenance of the aging heart. Coronary heart disease (CHD) is the major cause of mortality in the elderly. Important risk factors include hypercholesterolemia, systolic and diastolic hypertension, cigarette smoking, hyperglycemia, and obesity. Elderly patients with existing CHD should be treated aggressively to control these risk factors, along with other medical therapies to treat myocardial ischemia. For elderly patients without recognized CHD, however, a more conservative approach is recommended and includes behavioral interventions when appropriate and pharmacologic therapy for higher risk patients with persistent, uncontrolled risk factors. 
Screening in ovarian cancer. Ovarian cancer will affect 20,000 American women this year and some 13,500 will die of the disease. Most patients will have stage III or IV disease at the time of diagnosis. Because ovarian cancer may be initially without symptoms, attempts have been made to develop screening tests that would lead to an early diagnosis. Two tests, serum CA 125 and pelvic ultrasonography, have been suggested by some to be accurate enough to be included in yearly screening for ovarian cancer. Although further testing of these techniques is encouraged, data to date do not justify yearly screening with CA 125 or pelvic ultrasonography in all women. 
Indicators of prognosis after hepatic resection for colorectal secondaries. From 1960 to 1988, 266 patients underwent resection of colorectal secondaries to the liver with curative intent. All patients were followed until April 1, 1990, or death, with a median follow-up time of 52 months. Nine patients with minimal macroscopic residual disease and 38 patients with all gross tumor removed but positive margins showed a poor prognosis with a median survival time of 13.3 months, the longest being 42 months. Of the 219 patients having potentially curative resection, 12 patients died postoperatively (5.5%). Actuarial 5, 10 and 20-year survival for the remaining 207 patients was 39%, 28%, and 18%, respectively. At April 1, 1990, 77 patients were alive with no evidence of disease for up to 24 years, and 12 patients had died without recurrence. The following factors were associated with less favorable crude survival: presence and extent of mesenteric lymph node involvement (p = 0.0003), grade III/IV primary tumor (p = 0.035), synchronous diagnosis of metastases (p = 0.017), satellite metastases (p = 0.0003), limited resection margins (p = 0.019), and nonanatomic procedures (p = 0.013). With respect to disease-free survival, grading of the primary (p = 0.055) and the extent of clear margins (p = 0.019) failed to achieve statistical significance. Two other criteria are commonly recommended as absolute contraindications to hepatic resection: extrahepatic disease and the presence of four or more independent metastases. A radical excision of all detectable disease may rarely be possible in these circumstances. Nevertheless, within the curative settings, no significant predictive value regarding either overall or disease-free survival was found in this series. Three corresponding "high risk" patients are alive without disease at 5 to 11 years from hepatic resection. These patients with more advanced intrahepatic or concomitant limited extrahepatic disease require a particularly thorough diagnostic work up. As no superior therapeutic alternative is currently available, an aggressive surgical approach may occasionally be justified, and may, in a small portion, result in definite tumor control. 
The effect of palliative radiation therapy on epidural compression due to metastatic malignant melanoma. The efficacy of palliative radiation therapy in the treatment of spinal cord and cauda equina compression due to metastatic malignant melanoma was evaluated in 38 sites in 35 patients treated between 1970 and 1990. All patients had radiographic documentation of epidural compression. The median dose of radiation therapy was 2850 cGy (range, 500 to 4000 cGy), with daily fractions ranging from 200 to 800 cGy. Twenty-eight sites in 26 patients were evaluable 1 month after completion of radiation therapy, and symptoms responded completely in 11 of 28 (39%) sites. Fourteen sites (46%) showed a partial response of symptoms. Response lasting until death was documented in 21 of 26 patients (81%). Patients receiving a total dose of 3000 cGy or greater were more likely to achieve a complete response than those receiving less than 3000 cGy (62% versus 20%) by univariate (P = 0.025) and multivariate (P = 0.048) analyses. A treatment program of radiation therapy and corticosteroids is effective in palliating the symptoms of epidural compression due to metastatic malignant melanoma. It is recommended to deliver an accelerated course of radiation therapy to a dose of 3000 cGy or greater without exceeding spinal cord tolerance (e.g., 3000 cGy in ten fractions at 300 cGy per fraction). 
Management of adipsia by a behavioural modification technique. Adipsia combined with diabetes insipidus after hypothalamic damage may produce major difficulties in clinical management. If there is an associated memory impairment it may be impossible to teach self-regulation of fluid balance, necessitating long-term hospital supervision. The successful use of a behaviour modification technique to achieve independent drinking and allow discharge from hospital into the community is described in a patient with adipsia, diabetes insipidus and memory impairment resulting from the removal of a craniopharyngioma. 
Thermal ablation of the gallbladder. Gallbladder ablation by means of injection of hot contrast medium was attempted in 13 dogs. Room temperature contrast medium was injected into the gallbladders of two additional dogs (controls). After midline laparotomy was performed to expose the gallbladder, temperature probes were placed in the liver adjacent to the gallbladder, and on the surface and in the lumen of the gallbladder. A 7-F catheter with multiple side holes was placed into the gallbladder. The cystic duct was clamped during the procedure. After injection of boiling contrast medium, the mean temperature in the gallbladder lumen was 80 degrees C; in the adjacent liver, 43.5 degrees C; and on the gallbladder surface, 45.8 degrees C. After the procedure, the cystic duct was unclamped, temperature probes and catheter were removed, and the laparotomy was closed in standard fashion. In the hot contrast medium group, one dog each was sacrificed at 2, 4, 8, and 12 weeks, and at 6 months. Six animals were sacrificed at 1 year. The gallbladder was completely ablated in 11 of 13 animals in the hot contrast medium group. One dog was sacrificed at 8 days because of bile leakage, and another was sacrificed at 17 days because of gallbladder rupture. The two control animals were sacrificed at 12 and 13 weeks, and their gallbladders were normal at that time. 
A study guided by the Health Belief Model of the predictors of breast cancer screening of women ages 40 and older. In late 1987, a total of 852 Rhode Island women ages 40 and older were interviewed by telephone (78 percent response rate) to measure their use of breast cancer screening and to investigate potential predictors of use. Predictors included the women's socioeconomic status, use of medical care, a provider's reported recommendations for screening, and the women's health beliefs about breast cancer and mammography. The Health Belief Model guided the construction of the interview questions and data analysis. Logistic regression was used to identify leading independent predictors of breast cancer screening according to contemporary recommendations: reporting that a medical provider had ever recommended a screening mammogram (odds ratio [OR] = 18.77), having received gynecological care in the previous year (OR = 4.92), having a regular source of gynecological care (OR = 2.63), having ever had a diagnostic mammogram (OR = 2.32), and perceiving mammography as safe enough to have annually (OR = 1.93). The findings suggest that programs intended to increase the use of breast cancer screening should include "inreach" and "outreach" elements; inreach to patients with established patient-provider relationships, by assuring that physicians recommend screening to all eligible patients, and outreach to all eligible women, by helping them overcome barriers to effective primary care, and by promoting mammography, emphasizing its effectiveness and safety. The findings also suggest that socioeconomically disadvantaged women, who are less likely to be screened than other women, should become special targets of inreach and outreach interventions. 
Percutaneous drainage of traumatic pancreatic pseudocysts in children. To determine the effectiveness of percutaneous drainage of traumatic pancreatic pseudocysts, we reviewed the courses of 13 children. Six pseudocysts resolved on complete bowel rest and total parenteral nutrition. Seven required further therapy. Two pseudocysts were treated operatively; five were drained percutaneously with fluoroscopic guidance. These five ranged from 5 to 15 cm in diameter and were present for 10 to 42 days (mean, 26 days). In all cases, the cyst fluid was clear, had an amylase level of greater than 40,000 IU/L, and grew no organisms. The pigtail catheters left in place in four of the five children were removed when drainage stopped. Patients were followed by ultrasound while still in the hospital and 1 month after discharge. There were no complications nor any pseudocyst recurrence. Percutaneous drainage of traumatic pancreatic pseudocysts in children is an effective alternative to the standard operative therapy of pseudocystenteric anastomosis. 
A placebo-controlled trial of continuous intravenous diltiazem infusion for 24-hour heart rate control during atrial fibrillation and atrial flutter: a multicenter study. The safety and efficacy of a 10- to 15-mg/h continuous infusion of intravenous diltiazem were evaluated in 47 patients with atrial fibrillation or flutter who first responded to 20 mg or 20 mg followed by one or more 25-mg bolus doses of open label intravenous diltiazem. Of the 47 patients, 44 responded to the bolus injection and were randomized under double-blind conditions to receive either a continuous infusion of intravenous diltiazem (10 to 15 mg/h) (23 patients) or placebo (21 patients) for up to 24 h. Seventeen (74%) of the 23 patients receiving diltiazem infusion and none of the 21 with placebo infusion maintained a therapeutic response for 24 h (p less than 0.001). Over 24 h, patients receiving diltiazem infusion lost response significantly more slowly than did those receiving placebo infusion (p less than 0.001). Nonresponders to the double-blind infusion were given an additional bolus injection of open label intravenous diltiazem and administered an open label 24-h intravenous diltiazem infusion. The overall proportion of patients maintaining a response to a 24-h infusion of intravenous diltiazem under double-blind or open label conditions combined was 83% (34 of 41). Efficacy of the 24-h infusion of intravenous diltiazem was similar in elderly versus young patients, those who did versus those who did not receive digoxin and those weighing less than 84 versus greater than or equal to 84 kg. However, intravenous diltiazem appeared to be more effective in atrial fibrillation than in atrial flutter. No significant untoward effects were noted. 
Histamine H2-receptor antagonists. In summary, histamine initiates acid secretion by stimulating the H2 subtype histamine receptor on parietal cells. Cimetidine, rantidine, famotidine, and nizantidine are histamine H2-receptor antagonists that block this action of histamine, reducing gastric acid output and concentration under both basal and stimulated conditions. These agents are used for treatment and prevention of peptic and stress ulcers as well as for hypersecretory states. Because of their effectiveness and low incidence of side effects, H2-antagonists have largely replaced more traditional antiulcer regimens. 
Seizures caused by nontraumatic parenchymal brain hemorrhages. Seizures occurred in 15% of patients with parenchymal brain hemorrhage (early in 12% and delayed in 3%). Seizures were most frequent with lobar hemorrhages and uncommon with deep subcortical hemorrhages. Lobar hemorrhages in the frontal, parietal, or temporal region were more commonly associated with seizures, whereas occipital hemorrhages were not. Seizures were most common if the hemorrhage was due to an aneurysm, angioma, or neoplasm and less common if hypertensive or spontaneous. If the patient had recurrent seizures or developed delayed seizures, CT showed that the hemorrhage evolved to a hypodense appearance; if the seizure did not recur, CT showed that the hemorrhage evolved to an isodense appearance. 
Patent ductus arteriosus in an infant with atrioventricular septal defect and pulmonary hypertension: diagnosis by transesophageal color flow echocardiography. An infant with complete atrioventricular septal defect (atrioventricular canal) was examined by standard transthoracic two-dimensional pulsed Doppler and color Doppler echocardiography. No evidence of ductus arteriosus was present. Preoperative transesophageal echocardiography identified a patent ductus: the left-to-right shunt seen by color Doppler echocardiography was enhanced by pharmacologic maneuvers aimed at decreasing pulmonary vascular resistance and increasing systemic vascular resistance. Transesophageal echocardiography was found to be more sensitive than transthoracic echocardiography even in a small infant. 
Using ADLs to establish eligibility for long-term care among the cognitively impaired. Using a database from the Oregon Medicaid program, we examined the differences in the potential insurance coverage of demented persons by using different formulations of ADL (activities of daily living) dependencies in which the definition of dependency did or did not include the need for supervision. For those with clear dementia, 81-88% of the persons with significant behavioral problems were correctly identified when a cut score of three or more ADLs was used; this percentage was even higher for two or more ADLs. This approach was not as effective in correctly discriminating those who had no behavioral problems. 
Neuropathy, myopathy and destructive arthropathy in primary hypothyroidism. A 75-year-old woman with untreated primary hypothyroidism was found with peripheral neuropathy (including carpal tunnel syndrome), severe myopathy (high levels of creatine phosphokinase) and destructive arthropathy, affecting fingers, toes and the left knee. Radiographs of her knee showed destructive lesions of the tibial plateau similar to a pathologic compression fracture, while the joints of the fingers and toes showed all signs of severe erosive osteoarthritis (OA), radiographically documented over a period of 7 years. It is suggested that hypothyroidism is causally related to the development of erosive OA. 
Autoimmune aetiology for acquired neuromyotonia (Isaacs' syndrome). Neuromyotonia is a rare disorder of unknown cause in which hyperexcitability of peripheral motor nerves leads to incapacitating muscle twitching, cramps, and weakness. We investigated an antibody-mediated mechanism for neuromyotonia in a 24-year-old man with a 7-year history of severe disease unresponsive to pharmacological treatment. Two periods of plasma exchange each produced almost complete disappearance of symptoms for 2-3 weeks, and a highly significant decrease in recorded neuromyotonic discharges. Injection of the patient's plasma or purified IgG into mice significantly enhanced in-vitro resistance to d-tubocurarine at the neuromuscular junction of phrenic nerve-diaphragm preparations. This finding suggests that an increase in neurotransmitter release might result from an antibody-mediated reduction in the number of functional potassium channels that normally regulate nerve excitability. The demonstration of pathogenic IgG autoantibodies in acquired neuromyotonia suggests that immunosuppressive treatment may be helpful in severe cases. 
Use of a marshmallow bolus for evaluating lower esophageal mucosal rings. Sixty-three patients (35 women, 28 men; mean age 55 yr) with lower esophageal mucosal ring shown radiographically were examined with a semi-solid bolus consisting of a portion of a standard marshmallow. The most common symptom was dysphagia, present in 46 (73%) patients. Impaction of the marshmallow bolus by the ring occurred in 40 (63%) of the 63 patients, and produced symptoms in 27 (68%) of these 40 patients. Nine (14%) rings were detected radiographically only with a solid bolus; eight of these patients had dysphagia and seven rings were 20 mm or less in caliber. Impaction related to ring caliber, and was found in all 17 (100%) rings that were 13 mm or less in diameter, in 17/24 (71%) 14- to 19-mm rings, and in 6/22 (27%) rings 20 mm or more in caliber. Endoscopy in 23 patients detected 16 (70%) rings, and also depended on ring caliber: less than or equal to 13 mm, 6/6 (100%); 14-19 mm, 5/9 (56%); greater than or equal to 20 mm, 5/8 (63%). Marshmallow impaction occurred in 17 (74%) of 23 patients who had endoscopy; three of the 23 patients had normal endoscopy. In conclusion, radiographic examination supplemented by the use of a marshmallow bolus best detects lower esophageal mucosal ring. 
Blindness as an ictal phenomenon: investigations with EEG and SPECT in two patients suffering from epilepsy. Blindness is a rare ictal phenomenon in epileptic seizures. It can occur as an aura, as the seizure itself, or postictally. We investigated two such patients, in one of whom blindness manifested as an aura prior to tonic clonic seizures; the interictal EEG exhibited a spike-wave focus bioccipitally. In the second patient blindness occurred postictally. An ictal SPECT, carried out at the onset of the seizure demonstrated marked hyperperfusion in both occipital regions. 
Malignant pleural mesothelioma: CT manifestations in 50 cases. Malignant pleural mesothelioma, a rare and usually fatal neoplasm that is associated with asbestos exposure, is being encountered with increasing frequency. Pretreatment CT findings from 50 patients with malignant pleural mesothelioma are illustrated. Pleural thickening was found in 46 (92%) of the 50 patients, thickening of the pleural surfaces of the interlobar fissures in 43 (86%), pleural calcifications in 10 (20%), and pleural effusions in 37 (74%). The volume of the involved hemithorax varied appreciably. Contractions of the involved hemithorax was noted in 21 (42%) of 50 patients and contralateral mediastinal shift in seven (14%). Disease beyond the parietal pleura was found in the chest wall (nine patients), mediastinum, lymph nodes, and diaphragm. 
Pseudosarcomatous fibromyxoid tumor of the prostate. A case report with immunohistochemical, electron microscopic, and DNA flow cytometric analysis. A 22-year-old man presented with symptoms of urinary obstruction and was found to have a 5-cm mass protruding from the left side of the prostate into the prostatic urethra. The lesion was partially removed by transurethral resection (TURP). The patient's symptoms recurred, so he required another TURP four months later; at latest follow-up (four years later), there waas no evidence of disease. Light microscopy revealed a myxoid lesion characterized by an atypical fibroblastic proliferation associated with a prominent inflammatory component and granulation tissue-type vasculature. The lesion nearly replaced the prostatic parenchyma and invaded the bladder wall. Immunohistochemistry and electron microscopy showed a predominance of fibroblasts with occasional myofibroblasts. DNA flow cytometric analysis showed that the tumor cells had a diploid DNA content. Given these findings and the indolent clinical course, the authors think that this lesion represents a benign, reactive process consistent with a pseudosarcomatous fibromyxoid tumor, a recently described rare lesion of the genitourinary tract. 
Characterization of macrophage colony-stimulating factor in body fluids by immunoblot analysis. We characterized the molecular species of human macrophage colony-stimulating factor (hM-CSF) found in serum and urine, using immunoblot analysis after partial purification on an antibody-bound affinity column. Although antibodies were prepared using the recombinant product of the large form of hM-CSF with a molecular weight (MW) of 85 Kd as the antigen, this immunoblot system was also capable of detecting the small form of hM-CSF with a MW of 40 to 60 Kd. A single band with a MW of 43 Kd, which reacted with anti-recombinant hM-CSF IgG but not with control IgG, was found when serum and urine from normal adults underwent electrophoresis on reduced sodium dodecyl sulfate-polyacrylamide gel and subsequent immunoblotting. This band represented a subunit of the large form of hM-CSF, because the large form of hM-CSF is a homodimer of a subunit with a MW of 43 Kd and the small form of hM-CSF is a homodimer of a subunit with a MW of 20 to 30 Kd. Analysis of serum and urine from leukemic patients and pregnant women, who had higher serum levels of hM-CSF than normal adults, showed only a single band with a MW of 43 Kd as a hM-CSF-specific molecule. These results suggest that the large form of hM-CSF is the major species in human body fluids. 
Positive direct antiglobulin tests in myeloma patients. Occurrence, characterization, and significance. Review of direct antiglobulin testing (DAT) in 88 patients with multiple myeloma (MM) and five with Waldenstrom's macroglobulinemia revealed 26 cases with a positive DAT. Twenty-two of these had immunoglobulin G-M protein, three had light chain MM, and one had immunoglobulin A-MM protein. None of the immunoglobulin GD-MM (n = 2), nonsecretory MM (n = 5), or Waldenstrom's macroglobulinemia patients (n = 5) were positive. None of the patients had hemolysis attributable to the adsorption of the M protein. The serum concentration of M protein was higher in DAT-positive patients (57.6 +/- 3.8 g/L, mean +/- SEM) than in the negative ones (35.7 +/- 6.4 g/L; probability value of the difference was less than 0.01). The erythrocyte eluates from DAT-positive patients contained a single immunoglobulin, of the same class as the M protein, and did not react with a panel of ABO-compatible erythrocytes. Addition of melphalan during incubation did not affect the results. The M protein of DAT-positive patients was of immunoglobulin G-3 subclass in 7 of 10 patients. A positive direct antiglobulin test frequently is seen in patients with multiple myeloma, the reaction is due to passive adsorption of the M protein onto the erythrocytes, is most frequently observed with immunoglobulin G3-MM, and usually does not produce hemolysis. 
The importance of surface immunoglobulin, mouse rosettes, and CD5 in the immunophenotyping of chronic lymphocytic leukemia and reactive lymphocytosis. Peripheral blood from 167 B-chronic lymphocytic leukemia (B-CLL) and 119 reactive lymphocytosis (RLC) patients were analyzed to evaluate the immunophenotypic diagnostic value of mouse rosettes (M-rosette), and weak expression of monoclonal surface immunoglobulin (SIg). In B-CLL, 145 cases were M-rosette+ (86.83%), 135 surface immunoglobulin (SIg)+ (80.84%), and 117 M-rosette+ SIg+ (70.06%). Of 32 SIg- cases, 28 were M-rosette+; and of 22 M-rosette-cases, 18 were SIg+. By combining results of the two assays and accepting positivity of either one or both as sufficient for diagnosis, B-CLL was diagnosed in 163 cases (97.60%). CD5 was performed in 49 cases of the 167 with paired data for SIg and M-rosettes. By combining the results of the three assays and accepting positivity of any two or all three as sufficient for diagnosis, all 49 cases (100%) were diagnosed. Correlation analysis showed no significant association between M-rosette, SIg, and CD5 expression. The results demonstrate the independent expression of the three markers, and their complementary role in immunophenotyping B-CLL. In RLC, all 119 cases were T-lineage and SIg-, and 115 were M-rosette-, indicating the role of the two markers in differentiating B-CLL from RLC. Three of the four M-rosette+ T-RLC were subsequently diagnosed as B-CLL, suggesting the necessity of follow-up of such cases. 
Class II-restricted presentation of an endogenously derived immunodominant T-cell determinant of hen egg lysozyme. An in vitro model was used to investigate the potential for different structural forms of endogenous antigen to be processed and presented by major histocompatibility complex class II molecules. For this purpose the class II-restricted presentation of an immunodominant epitope of hen egg lysozyme [HEL-(46-61)] was studied in class II-positive B-lymphoma cells (M12.C3) transfected with genes encoding HEL molecules either (i) secreted in high (hi) or low (lo) amounts as soluble antigen [sHEL(hi/lo)], (ii) localized within the endoplasmic reticulum (ER)/salvage compartment (ER-HEL), or (iii) anchored on the cell surface as an integral membrane protein (mHEL). The corresponding sHEL, ER-HEL, and mHEL gene products were expressed as predicted except that HEL determinants accumulated in the culture supernatant as well as on the cell membrane of mHEL-transfected cells. Class II-positive cells endogenously expressing all three forms of HEL antigen constitutively presented the immunodominant HEL-(46-61) determinant with differential efficiency (mHEL, sHEL greater than ERHEL) to a class II-restricted T hybridoma. A second T hybridoma recognized endogenous HEL-(46-61) determinants constitutively presented on sHEL(hi) and mHEL transfectants but not on sHEL(lo) or ERHEL transfectants. The formation of HEL-(46-61)/I-Ak complexes in the ERHEL and sHEL(lo) transfectants was therefore limiting. Mixing experiments with different antigen-presenting cells indicated that the HEL-(46-61) determinant was derived from endogenous antigen rather than by reuptake of shed or secreted HEL determinants. We conclude that MHC class II molecules can present some antigenic determinants derived from endogenous proteins that are sequestered in the ER/salvage compartment as well as distally transported in the form of secretory or membrane antigens. 
Thoracoscopic diagnosis and treatment of chylothorax after pneumonectomy. Chylothorax after pneumonectomy was treated successfully by selective application of fibrin glue through a thoracoscope. Conservative therapy for 18 days failed to close the fistula. The site of leakage was identified during thoracoscopy, and fibrin glue was applied under direct vision. Leakage decreased immediately and eventually stopped completely. This technique is less invasive than standard surgical treatment and should be considered in all patients with postoperative chylothorax. 
Strategy for management of distal ileal Crohn's disease. We have determined the outcome of a defined policy for the management of distal ileal Crohn's disease using a prospective computer-based analysis of 139 patients diagnosed between 1970 and 1988 with a mean follow-up of 10 years. The policy in outline consists of conservative treatment for acute obstructive episodes, resection or strictureplasty for recurrent obstructive episodes, surgical treatment for abscess and fistula formation and specific medical treatment (corticosteroids, immunosuppressive therapy or metronidazole) for symptomatic non-obstructive disease. Twenty-nine patients had a benign course without resection. The remainder were treated surgically at some time but only 28 of these patients had specific treatment before operation. Thirty-three needed more than one resection and five needed more than three surgical procedures. Immediate, early or delayed surgical treatment did not affect the reoperation rates or the long-term outcome. Eleven patients died, ten of causes unrelated to Crohn's disease. Of the 128 living patients, 114 are fit and well, and only two are currently taking specific medication. Fourteen are unwell of whom six either need or have refused further surgery which could restore them to good health. This management policy has achieved excellent long-term results in nearly all patients, and our findings suggest that the timing of surgery and its nature are more important in determining outcome than specific medical therapy. 
The modified buccal musculomucosal flap method for cleft palate surgery. We have reported previously on a palatoplasty method, called the T-shaped musculomucosal buccal flap method, for the primary repair of a cleft palate. This method has been used on more than 90 patients, and satisfactory outcomes have resulted in terms of maxillar development, the prevention of fistulation, and verbal functions. However, 14.3 percent of these patients exhibited a velopharyngeal incompetence that showed no potential improvement through training. In the majority of these patients, the entire raw surface of the oral cavity side could not be covered with a buccal musculomucosal flap, and as a result, postoperative contraction of the soft palate occurred. Thus a new surgical method has proven effective in which both buccal musculomucosal flaps are used as an oral lining, the nasal mucosa having been extended by Z-plasty. We have performed 25 operations using this new method and have observed no postoperative contractions of the soft palate, notwithstanding two cases (8.0 percent) of postoperative fistulation. 
Comparative studies of extracorporeal shock wave lithotripsy by Dornier HM3, EDAP LT 01 and Sonolith 2000 devices. During a 2-year period extracorporeal shock wave lithotripsy (ESWL) was done at our institution in 70 patients with the Dornier HM3, 113 with the EDAP LT 01 and 104 with the Sonolith 2000 lithotriptors. The size and location of stones were comparable in all 3 series, and all treatments were done by the same team of urologists. Complete fragmentation occurred in 79% of the patients treated by the Dornier, 82% treated by the EDAP and 79% treated by the Sonolith devices, with 3-month stone-free rates of 66, 67 and 58%, respectively. Auxiliary procedures were needed in 12% of the patients in the Dornier, 13% in the EDAP and 9% in the Sonolith groups. Repeat treatment was necessary in 4% of the Dornier group, 42% of the EDAP group and 26% of the Sonolith group. Therefore, all 3 lithotriptors are effective in stone disintegration and produce satisfactory results when selection criteria for ESWL are observed. The most significant difference among the 3 lithotriptors is the number of repeat treatments, which reflects the power and energy output of the lithotriptors. In conclusion, the Dornier HM3 device has the advantage of low repeat treatment rate and easier stone localization. The EDAP LT 01 unit has the advantage of lower treatment costs and anesthesia-free treatment with no irradiation. The Sonolith 2000 device has features of the other 2 lithotriptors with a superior ultrasound image. 
A systematic consideration of the neoplastic spectrum of AIDS: registry linkage in Illinois. To examine unexplored aspects of the association between AIDS and neoplasia, the Illinois AIDS and Cancer Registries were linked. The method integrated use of a personal computer to find exact matches on names and dates of birth with manual review to assure satisfaction of a match definition. Of the factors examined, white race and homosexuality predicted Kaposi's sarcoma (KS) among people with AIDS (PWAs), and white race predicted non-Hodgkin's lymphoma (NHL). Earlier reports of a declining proportion of PWAs with KS were confirmed. Lymphoma (mixed lymphocytic/histiocytic type), while not currently diagnostic of AIDS, occurred more frequently among PWAs than in the Illinois population. For the first time, rates of cancers other than KS and NHL were demonstrated to be significantly increased among PWAs compared with general populations. In the light of these findings, reconsideration of current neoplastic definitions may be useful. 
Chronic inflammatory demyelinating polyradiculoneuropathy of childhood: treatment with high-dose intravenous immunoglobulin. We treated four children with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) with high-dose intravenous immunoglobulin (IVIG). All patients received 400 mg/kg of IVIG a day for 5 days during relapses, and one patient received additional periodic infusions of 400 mg/kg. All patients showed excellent recovery of motor strength following each relapse that was treated with IVIG. Compared with plasmapheresis (which was used to treat relapses earlier), recovery of function with IVIG treatments was similar, and in two patients it was superior, to plasmapheresis. There were no side effects with IVIG treatments as compared with plasmapheresis with which two children had infection of central lines with Staphylococcus epidermidis, one had profuse bleeding from accidental extrusion of a central line, and one had multiple episodes of major venous thromboses. High-dose IVIG was a safe and effective adjunctive therapy for childhood CIDP in these four patients. 
Experience with laser-assisted balloon angioplasty and a rotary angioplasty instrument: lessons learned. Favorable early results with mechanical angioplasty devices and laser-assisted balloon angioplasty have resulted in aggressive marketing and a rapid increase in the use of these devices for the treatment of femoropopliteal occlusive disease. Recent reports, however, have questioned the durability of these less invasive procedures. Since 1986 we have been involved in the clinical investigation of the Kensey dynamic angioplasty instrument and laser-assisted balloon angioplasty. One hundred two balloon angioplasty procedures assisted by the Nd:YAG laser (n = 56) and the Kensey dynamic angioplasty instrument (n = 46) were performed for the treatment of femoropopliteal occlusive lesions. Both Kensey dynamic angioplasty instrument and laser-assisted balloon angioplasty groups were similar with regard to age, operative indication, preoperative ankle-brachial index, lesion length, and distal runoff. Mean follow-up was 19 months in the Kensey dynamic angioplasty instrument group and 15 months in the laser-assisted balloon angioplasty group. Technically successful recanalization was achieved in 67% of Kensey dynamic angioplasty instrument-assisted balloon angioplasty procedures and 82% of laser-assisted balloon angioplasty procedures. Early hemodynamic and clinical improvement was obtained in 59% of Kensey dynamic angioplasty instrument-assisted balloon angioplasty procedures and 57% of laser-assisted balloon angioplasty procedures. Two-year clinical success by life-table analysis was 37% in the Kensey dynamic angioplasty instrument group and 19% in the laser-assisted balloon angioplasty group. The level of subsequent surgical revascularization was not altered in any patient by Kensey dynamic angioplasty instrument-assisted balloon angioplasty or laser-assisted balloon angioplasty. 
Passive immunoprophylaxis after liver transplantation in HBsAg-positive patients. 110 HBsAg-positive patients underwent orthotopic liver transplantation and received long-term anti-hepatitis B virus (HBV) passive immunoprophylaxis with anti-HBs immunoglobulin. During a mean follow-up period of 20 months, all patients became HBsAg negative after transplantation but circulating HBsAg reappeared in 25 (22.7%). Overall 1-year survival was 83.6% and overall 2 year actuarial recurrence of HBsAg was 29% (59% after posthepatitis B cirrhosis, 13% after posthepatitis B-delta cirrhosis, and 0% after fulminant hepatitis B). Patients with HBV cirrhosis who were HBV-DNA positive had a much greater risk of HBsAg recurrence than patients who were HBV-DNA negative (96% vs 29% at 2 years). Reappearance of HBsAg was associated with evidence of HBV replication and abnormal histological findings in the graft. Long-term passive anti-HBV immunoprophylaxis significantly reduced HBV reinfection and improved survival in patients without evidence of active HBV replication before orthotopic liver transplantation. 
Differential activation within costal diaphragm during rapid-eye-movement sleep in cats. Simultaneous recordings of the diaphragmatic electromyogram (EMG) were made from two separate regions of the costal diaphragm in six normal cats. The diaphragmatic activities were always synchronous and the amplitudes and rates of rise were similar during slow-wave sleep. In contrast, during natural rapid-eye-movement (REM) sleep, different activity was often present in the two leads. These differences were in the time of onset and offset, as well as in the amplitude and spike patterns, and occurred in approximately 5-20% of the diaphragmatic bursts averaged over the entire REM sleep period. With respect to eye movement density, the rate of differential activation was higher during periods of high density (26%) than in the absence of eye movements (1%) in the four animals for which these data were available. Differential activation of portions of the costal diaphragm is apparently a normal event of REM sleep. This could result from descending state-specific phasic neuronal activity that bypasses the medullary respiratory generator. Differential activation of portions of the diaphragm could contribute to disordered ventilation during REM sleep. 
Posttraumatic headache and the postconcussion syndrome. Although headache is the most common sequelae of head injury, the posttraumatic headache is associated frequently with dizziness, irritability, lack of concentration, and intolerance to alcohol ingestion as a part of a symptom complex known as the postconcussion syndrome. This article clarifies the definitions of acute traumatic headache, posttraumatic headache, and the postconcussion syndrome and improves diagnostic ability, making the assessment and treatment of patients with these three conditions more accurate and effective. 
Characterization of interactions of enteropathogenic Escherichia coli O127:H6 with mammalian cells in vitro. Previous studies have identified two bacterial factors involved in enteropathogenic Escherichia coli (EPEC) infection. A plasmid-mediated EPEC adherence factor (EAF) is responsible for initial and localized adherence. A chromosomally encoded E. coli attachment and effacement factor (eae) is involved in effacement of the eukaryotic cell surface and characteristic "pedestal" formation. By using isogenic strains deficient in either EAF, eae, or both, the process of EPEC adherence and entry in vitro was examined. While EAF proved necessary and sufficient for efficient bacterial association with HEp-2 cells, both EAF and eae were required for efficient effacement of and entry into these cells and other cultured cell lines. Invasion mediated by eae was markedly inhibited by cytochalasin D and colchicine. Afimbrial adhesion or type I pili from uropathogenic strains of E. coli substituted for EAF in EAF-Eae+ strains to provide initial adherence to HEp-2 cells and to facilitate actin condensation. 
Who will operate on Africa's 3 million curably blind people? About half the 6 million blind people in sub-Saharan Africa have surgically curable cataract. The available manpower and resources can only provide services for less than 10% of the new blind cataract patients each year, and little is being done for the estimated 3 million "cataract backlog". A serious limiting factor to the development of prevention of blindness programmes is lack of trained manpower. Despite an increase in the number of ophthalmologists trained in cataract surgery (which varies greatly from country to country), this number is not keeping pace with increased demand for eye-care services, especially in large rural populations. Initiatives that will help to overcome this dilemma are specific post-graduate courses in community ophthalmology in Africa, plans to develop a one-year diploma in ophthalmology course for English-speaking West African countries, and a proposal to upgrade a similar course in Zimbabwe. Additionally there is a need for the training of more ophthalmic assistants, cataract surgeons, and nurses in the diagnosis and management of common ophthalmic disorders. Experienced expatriate ophthalmologists also have an important role in the teaching of doctors and ophthalmic assistants how to select patients and carry out successful inexpensive cataract surgery with appropriate technology and limited facilities. 
Ectopic pituitary adenoma in the suprasellar cistern: case report. The case of a 56-year-old man with an ectopic pituitary adenoma is reported. Neurological examinations, neurodiagnostic imaging, surgical observation, endocrinological evaluation, histological examination, and immunohistological study demonstrated evidence of ectopic prolactinoma in the suprasellar cistern and the presence of a normal pituitary in the sella turcica. The patient underwent total removal of the suprasellar mass by a pterional approach, leading to a surgical and endocrinological cure. 
Two cases of neoplastic angioendotheliomatosis presenting with myelopathy. We describe two patients with autopsy-proven neoplastic angioendotheliomatosis (NAE) presenting only as a transverse myelopathy for 10 to 12 months, followed by disseminated intracranial manifestations. Postmortem examination disclosed a vasculocentric distribution of neoplastic cells in various organs that stained positively with B-lymphocyte-specific monoclonal antibody. These cases were unusual because they manifested as an isolated myelopathy for many months. 
Treatment of esophageal varices: low versus high dose of 5% ethanolamine oleate. Twenty-four patients, undergoing sclerotherapy for esophageal varices, were injected with 10-20 ml of ethanolamine oleate 5% in the first treatment session (group A). Fourteen patients were injected with 40 ml of the same sclerosant in the first session (group B). Retrospective analysis was carried out to evaluate the efficacy and safety of the two doses. Variceal eradication was achieved in group B in significantly fewer sclerotherapy sessions. Rebleeding occurred in 16% of patients in group A, compared with no rebleeding in group B. There was no significant difference in the incidence of various complications. We conclude that the use of 40 ml of 5% ethanolamine oleate in the first session is more effective and as safe as the use of 20 ml of the same sclerosant. 
Endothelium-dependent responses of cerebral blood vessels during chronic hypertension. Acetylcholine produces less dilatation of pial arterioles in stroke-prone spontaneously hypertensive rats (SHRSP) than in normotensive (WKY) rats. Responses of cerebral vessels to acetylcholine and bradykinin appear to involve different mechanisms. Our first goal was to determine whether responses of pial arterioles to bradykinin are impaired in SHRSP. Diameter of pial arterioles (20-60 microns) was measured using intravital microscopy in WKY rats and SHRSP (9-12 months old). Superfusion of bradykinin (3 x 10(-7) M) dilated pial arterioles by 35 +/- 6% (mean +/- SEM) in WKY rats, but only 21 +/- 3% in SHRSP (p less than 0.05 versus WKY rats). Both nitric oxide (5 x 10(-7) M) and nitroglycerin (10(-5) M) produced similar vasodilatation in WKY rats and SHRSP. Our second goal was to determine whether alteration of postreceptor mechanisms contributes to impairment of endothelium-dependent cerebral vasodilatation in SHRSP. Calcium ionophore A23187 (10(-5) M) produced more vasodilatation in WKY rats than in SHRSP (32 +/- 8% versus 9 +/- 4%, p less than 0.05). Responses to A23187 (10(-5) M) were inhibited by indomethacin (46 +/- 13% versus 15 +/- 5%, p less than 0.05) in WKY rats, whereas responses to A23187 (10(-6) M) were potentiated modestly by indomethacin (-3 +/- 2% versus 4 +/- 2%, p less than 0.05) in SHRSP. 
Primary malignant melanoma of the gasserian ganglion associated with neurofibromatosis. A case of primary intracranial malignant melanoma of the left gasserian ganglion associated with temporal lobe gliosis in a patient suffering from von Recklinghausen's disease is reported. The association of primary malignant melanoma of the trigeminal nerve and neurofibromatosis is discussed. 
Lymph node counts in the upper abdomen: anatomical basis for lymphadenectomy in gastric cancer. The number of regional lymph nodes was determined in sites relevant to lymphadenectomy in gastric cancer in 30 cadavers. Tissue was cleared by dissolving fatty tissue, thus making lymph nodes with a diameter of at least 1 mm visible. All lymph node stations indicated by the Japanese Research Society for Gastric Cancer were studied. In stations 1-11 (corresponding with R2 resection) an average of 27 nodes (range 17-44 nodes) was found, whereas stations 1-16 (corresponding with R3 resection) showed an average of 43 nodes (range 25-64 nodes). These values are higher than those usually obtained from lymphadenectomy for gastric cancer. Striking individual differences in the total number of lymph nodes and the number of single stations was observed. The number of lymph nodes in these investigations are the normal anatomical values and serve as quality control of lymph node dissection in gastric carcinoma. 
Gamma-interferon promotes proliferation of adult human astrocytes in vitro and reactive gliosis in the adult mouse brain in vivo. Reactive gliosis is a characteristic response of astrocytes to inflammation and trauma of the central nervous system. To investigate whether soluble factors (cytokines) from inflammatory mononuclear cells that accumulate at lesion sites can provide the cellular signals to initiate gliosis and to identify such cytokines, we have tested and found that supernatants derived from subsets of activated human T lymphocytes (CD8+ or CD4+) are potent mitogens for cultured human adult astrocytes. This effect is blocked by a neutralizing antibody to gamma-interferon (IFN). Recombinant IFN alone can induce proliferation of human adult astrocytes in vitro and increase the extent of trauma-initiated gliosis in the adult mouse brain. The astrocyte proliferation-inducing activity of supernatants of glial cultures treated with IFN can be completely blocked with IFN-neutralizing antibody, suggesting that the proliferative effect does not require intermediary cytokines or cells. These results implicate IFN as an important mediator of the gliosis observed in pathologic conditions of the adult central nervous system associated with infiltrating lymphocytes. 
Clinically significant pneumatosis intestinalis with postoperative enteral feedings by needle catheter jejunostomy: an unusual complication. We evaluated the incidence of clinically significant pneumatosis intestinalis and intestinal necrosis with the use of needle catheter jejunostomy in 217 consecutive patients who had undergone complicated abdominal operations or selected bariatric procedures. The needle catheter jejunostomy was used to deliver immediate postoperative nutrition, maintenance, and replacement fluids, and selected medications. In this group, no serious complications requiring surgical intervention were related to the use of needle catheter jejunostomies. Clinically significant pneumatosis intestinalis was encountered in two of 217 patients (1%). With the needle catheter jejunostomy in place, both patients improved rapidly when enteral feedings were discontinued and parenteral antibiotics were administered. None of the 217 patients developed ischemic intestinal necrosis. We conclude that 1) clinically significant pneumatosis is a rare complication of enteric feeding via needle catheter jejunostomy when the intrajejunal feeding is begun with a diluted, hypoosmolar solution with stepwise increases in osmolality, and 2) patients who do develop clinically significant pneumatosis (n = 2) seem to respond rapidly to a temporary stoppage of enteral feedings and administration of parenteral antibiotics. 
Facial nerve and medially invasive petrous bone cholesteatomas. Eight patients with extensive petrous bone cholesteatomas that invaded the labyrinth and fallopian canal are presented. The eight cases are added to a tabulation of prior literature reports to elucidate concepts of routes of extension of medially invasive temporal bone cholesteatoma. Medially invasive petrous bone cholesteatoma develops insidiously, often without symptoms other than facial palsy and/or unilateral deafness. Typically, a history of chronic ear disease can be obtained. While hearing is unlikely to be preserved in this group of patients, facial nerve function can usually be preserved, and a facial nerve graft was not necessary in our series. Acute facial nerve palsy or facial nerve paresis progressing to palsy in patients with a history of chronic ear disease should be studied radiographically for petrous bone cholesteatoma, even if there is no physical evidence of cholesteatoma. 
Controlled trial of 2, 4, and 6 months of pyrazinamide in 6-month, three-times-weekly regimens for smear-positive pulmonary tuberculosis, including an assessment of a combined preparation of isoniazid, rifampin, and pyrazinamide. Results at 30 months. Hong Kong Chest Service/British Medical Research Council In a study in Hong Kong 1,386 Chinese patients with sputum smear-positive pulmonary tuberculosis were allocated at random to four 6-month regimens of chemotherapy, all given three times weekly from the start and all containing isoniazid (H) and rifampin (R) throughout. Three contained streptomycin (S) for the first 4 months and pyrazinamide (Z) for 2 months (Z2), 4 months (Z4), or 6 months (Z6); the fourth contained pyrazinamide for 6 months but no streptomycin (Z6noS). Every dose of all four regimens was given under the direct supervision of clinic staff on a predominantly outpatient basis. During the later part of the intake patients were allocated at random to be given their HRZ either as a combined formulation (Rifater), each tablet containing 125 mg isoniazid, 100 mg rifampin, and 375 mg pyrazinamide, or as the three drugs separately. Among 892 assessable patients with drug-susceptible strains of tubercle bacilli pretreatment, bacteriologic failure during chemotherapy occurred in 4, all Z6noS (2% of 224; p less than 0.005 for the comparison with the S-containing regimens). During 30 months of follow-up after the end of chemotherapy, bacteriologic relapse occurred in 2 (3%) of 71 Z2, 2 (3%) of 72 Z4, 4 (6%) of 66 Z6, and 6 (9%) of 64 Z6noS patients allocated to Rifater, and in 4 (3%) of 149 Z2, 8 (6%) of 133 Z4, 2 (1%) of 142 Z6, and 6 (4%) of 135 Z6noS patients allocated to separate drugs. In the relapse rates there were no significant differences between the Rifater and separate drug regimens, the different durations of pyrazinamide, or the regimens with and without streptomycin. 
Failure of initial 24-hour esophageal pH monitoring to predict refractoriness and intractability in reflux esophagitis. Prolonged esophageal pH monitoring is considered to be the most sensitive and specific test for the diagnosis of gastroesophageal reflux disease (GERD). However, the role of pH monitoring in predicting the clinical and endoscopic response of reflux esophagitis is not well defined. In this study, 106 patients with moderate to severe symptoms of GERD and esophagitis (grades 0-IV) by endoscopy were initially studied by ambulatory esophageal pH monitoring, and their clinical response to standard H2 antagonist therapy was monitored at 8 wk. Refractory patients were defined as those who failed to heal and/or had intractable reflux symptoms after 8 wk of H2 antagonist therapy, and who required continuous therapy with higher doses of H2 antagonists, addition of prokinetic agents, or omeprazole. There was a positive correlation (r = 0.89) between endoscopic severity of esophagitis upon entry into the study and refractoriness to standard medical therapy. However, there were no differences in the various pH parameters analyzed between the 58 patients who responded and the 48 patients who were refractory to medical therapy, regardless of the endoscopic grading of their esophagitis. We conclude that 24-h ambulatory esophageal pH monitoring does not predict refractoriness of reflux esophagitis to standard therapy. The decision for more aggressive methods of treatment probably requires assessment of symptomatic and endoscopic response after 8 week standard H2 antagonist therapy. 
Ultrastructural morphometry of gastric endocrine cells before and after omeprazole. A study in the oxyntic mucosa of duodenal ulcer patients. Long-term toxicological experiments with inhibitors of acid secretion were found to induce hyperplasia and eventually carcinoid tumors of the enterochromaffin-like cells of the oxyntic mucosa. To evaluate the effects of 6 months' treatment with omeprazole in humans, the oxyntic endocrine cells were morphometrically investigated at the ultrastructural level in five patients with active duodenal ulcer. No omeprazole-induced changes were found in the volume density of the total endocrine cell population and specific cell types (including the enterochromaffin-like cell) as well as in the other cytological parameters investigated (number of cell profiles per unit area, mean cross-sectional area of cell profiles, nuclear-cytoplasmic ratio, and density of cytoplasmic secretory granules). Both pretreatment and post-treatment values in our patients with duodenal ulcer significantly differed from those of a previous investigation of healthy volunteers with regard to the volume density of enterochromaffin-like cells and non-granulated cells, which increased, and of D cells, which markedly decreased. The latter result may provide a cellular basis for impairment in the paracrine release of fundic somatostatin in peptic ulcer disease. Finally, morphometric data on endocrine cell volume density provided by electron microscopy were found to correlate with those obtained in the same patients using light microscopy techniques (Grimelius silver impregnation and chromogranin A immunostaining). It is concluded that 6 months' treatment with pharmacological doses of omeprazole is devoid of appreciable trophic effect on endocrine cells of human oxyntic mucosa. 
Fate of patients with acute myocardial infarction with patency of the infarct-related vessel achieved with successful thrombolysis versus rescue angioplasty. Patients with failure of infarct-related artery recanalization after thrombolytic therapy have a poor clinical outcome. These patients have been considered for rescue angioplasty 90 min after thrombolytic therapy at the time of emergency catheterization in the course of five Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) trials. The outcome of 776 patients with patent infarct-related vessels after emergency catheterization was analyzed--607 with thrombolysis-mediated patency of the infarct-related vessel and 169 with patency achieved by angioplasty. Baseline characteristics of the thrombolysis and angioplasty patency groups were similar except for a higher acute left ventricular ejection fraction (51.3% versus 48.2%) in the thrombolysis group (p = 0.003). Seven to 10 day left ventricular ejection fraction was higher (52.3% versus 48.1%), infarct zone functional recovery was greater (0.44 versus 0.21 standard deviation/chord, or 18% versus 7%, p = 0.001) and reocclusion was less (11% versus 21%) in the thrombolysis compared with the angioplasty group. Despite these differences, angioplasty patency was associated with the same low in-hospital mortality rate (5.9% versus 4.6%) and long-term mortality rate (3% versus 2%) as thrombolysis patency. Reocclusion adversely affected the mortality rate and ventricular functional recovery. Technical failure of rescue angioplasty was associated with a much higher mortality rate than was technical success (39.1% versus 5.9%). Thrombolysis patency was preferable to angioplasty patency after thrombolytic therapy in acute myocardial infarction, but both were associated with the same low in-hospital and long-term mortality rates, suggesting that rescue angioplasty is beneficial in some patients with failure of infarct-related artery recanalization after thrombolytic therapy. 
Exploring the molecular basis for variability among patients with Becker muscular dystrophy: dystrophin gene and protein studies. Becker muscular dystrophy (BMD) often results from in-frame mutations of the dystrophin gene that allow production of an altered but partially functional protein. To address potential structure-function relationships for the various domains of dystrophin, we examined both the dystrophin gene and protein in 68 patients with abnormal dystrophin. Eighty-six percent of BMD patients with dystrophin of altered size have deletions or duplications, and the observed sizes of dystrophin fit well with predictions based on DNA data. Deletions within the amino-terminal domain I tended to result in low levels of dystrophin and a more severe phenotype. The phenotypes of patients with deletions or duplications in the central rod domain were more variable. This region can be divided into three portions based on differences in clinical presentations of patients. Deletions around exons 4553 were most common and generally caused typical BMD; however, phenotypic variability among patients with similar mutations suggests that epigenetic and/or environmental factors play an important role in determining the clinical progression. In contrast, deletions or duplications in the proximal portion of this domain tended to cause severe cramps and myalgia. Finally, loss of the middle of this region probably causes a very mild phenotype, as only one such patient was found and his only symptom was elevated serum creatine phosphokinase levels. 
Anterior urethral polyp associated with hematuria in six-year-old child. Anterior urethral polyps are rare, occur only in male patients, and have been associated with obstruction, terminal hematuria, and enuresis. We believe this is the fifth reported case of anterior urethral polyp associated with terminal hematuria. The radiographic findings, treatment, and pathology are reviewed. 
Percutaneous stimulation of the cauda equina. A new diagnostic method in spinal stenosis. A study to determine the feasibility of measurement of conduction velocities through the lumbosacral nerve roots by direct percutaneous stimulation of the cauda equina is reported. The technique was applied to a series of normal volunteers and its reliability and reproducibility confirmed. An electrophysiologic defect was demonstrated in most patients with surgically proven lateral recess stenosis. Electrophysiologic recovery was shown in patients examined after surgery. Although the technique can be refined, these early results are encouraging. 
Reducing the risk of stroke: identifying patients to refer for carotid endarterectomy. The most common causes of stroke are two diseases of aging: hypertension and atherosclerosis. Therefore, although stroke may occur at any age, the incidence is highest among the elderly population. Noninvasive efforts to reduce the risk of stroke in the elderly include control of hypertension and diabetes, smoking cessation, low-cholesterol dietary habits, and moderate exercise. Routine low-dose aspirin also provides some protective effect. High-risk patients (with asymptomatic high-grade stenosis, TIAs, or prior stroke) should be considered candidates for carotid endarterectomy in the absence of contraindications to surgery. 
Comparison of 1 or 3 MU of interferon alfa-2b and placebo in patients with chronic non-A, non-B hepatitis. Ninety patients with histologically documented chronic non-A, non-B hepatitis were randomly allocated to receive SC injections of placebo or of 1 or 3 MU of recombinant interferon alfa-2b three times weekly for 24 weeks. Complete normalization of alanine aminotransferase levels occurred posttreatment in 43.3% of patients receiving 3 MU, in 20% of those receiving 1 MU, and in 6.7% of untreated patients (P less than 0.0005 vs. those treated with 3 MU). Alanine aminotransferase normalization was sustained for 6 months after therapy in 13.3% of the patients treated with 3 MU and in 3.3% of those given 1 MU or placebo. The decline of alanine aminotransferase levels following interferon therapy showed independent, positive correlations with female sex (P less than 0.03) and younger age (P less than 0.05). The Knodell's fibrosis score was strongly positively correlated with age (P less than 0.0001). It is concluded that 3 MU of interferon is a more effective dose than 1 MU for controlling disease activity in non-A, non-B chronic hepatitis patients. Women and younger and noncirrhotic patients are more likely to respond. 
Angiographic management of retroperitoneal hemorrhage from renal angiomyolipoma in polycystic kidney disease. Angiographic management of bilateral angiomyolipomas complicated by hemorrhage in autosomal dominant polycystic kidney disease is presented. The patient had mild stigmata of tuberous sclerosis, and a family history of tuberous sclerosis and autosomal dominant polycystic kidney disease. The radiographic features at diagnosis, and those present during and after embolization are described. Radiological criteria for diagnosis and successful control of bleeding with intra-arterial selective embolization are discussed. Radiographic features before, during and after embolization are exhibited. 
Paraplegia in a pregnant thalassemic woman due to extramedullary hematopoiesis: successful management with transfusions. The investigation and treatment of a pregnant thalassemic woman who developed severe paraplegia is presented. Magnetic resonance imaging showed a paravertebral mass infiltrating the epidural space, resulting from extramedullary hematopoiesis (marrow heterotopia). The patient was treated successfully with repeated blood transfusions and made a complete recovery. The literature (36 cases) is reviewed and the magnetic resonance imaging features of spinal extramedullary hematopoiesis are presented. The efficacy of transfusions in the management of spinal cord compression due to marrow heterotopia in thalassemic patients is discussed. 
Hypertension following erythropoietin therapy in anemic hemodialysis patients. Recombinant human erythropoietin (rHuEpo) corrects the anemia of end-stage renal disease. However, hypertension has been observed as an adverse effect of increasing red cell mass. In our study, 44 of 63 patients (70%) treated with rHuEpo had an increase in mean arterial pressure greater than 10 mm Hg or required new or additional hypertensive medications. Retrospective analysis disclosed that increasing blood pressure was associated with pretreatment hematocrit level less than or equal to 0.20 (P = .05) and dependency on red cell transfusions (P less than .01). Factors not associated with hypertension included the rate of rise of the hematocrit, the net rise in hematocrit, age, sex, the number of years on dialysis, the presence or absence of kidneys, smoking, or the presence of pretreatment hypertension. Noninvasive hemodynamic studies in eight normotensive patients before and after improvement of the anemia demonstrated a normalization of the decreased peripheral vascular resistance and a reduction toward normal in the elevated cardiac output. In three of these patients, clinical hypertension subsequently evolved. Follow-up hemodynamic studies in nine other patients receiving new or additional antihypertensive medications were difficult to interpret. Although the hypertension can be controlled with routine medication, hypertensive encephalopathy may occur if the blood pressure increases rapidly when the hematocrit increases with rHuEpo therapy. 
Is craniospinal irradiation required to cure children with malignant (anaplastic) intracranial ependymomas? Between 1970 and 1989, 17 children with histologically malignant intracranial ependymomas received treatment at the University of Pennsylvania (Philadelphia, PA). Eleven were treated with prophylactic cranial or craniospinal irradiation plus a local boost (CS-XRT), five with local (L-XRT) irradiation only, and one was treated without (NRT) irradiation. With a median survival of 2 years and a median follow-up time for long-term survivors of 6.0 years, five of 11 patients who received CS-XRT are alive compared with none treated with L-XRT and none treated with NRT. Two-year actuarial survival rates are 40% (L-XRT) and 52% (CS-XRT). When examined for other factors, age and local radiation dose remain the most significant prognostic indicators of survival. The 2-year actuarial survival for children younger than 4 years at diagnosis is 20% compared with 83% for their older counterparts. Likewise, the 2-year survival for patients treated with local radiation doses over 4500 cGy was 55% compared with 0% for patients treated with lesser doses. To date there are a total of 28 recurrences. All have occurred with local components except for six (unknown) who died before the exact site(s) could be determined. There is no significant difference in the failure rates outside the original tumor bed in the three groups. These data suggest that local relapse remains the most significant component of failure. Because intrinsic and extrinsic factors such as age and radiation dose seem to be interrelated and at least as important as the use of craniospinal irradiation, the need for prophylactic treatment for children with anaplastic ependymoma could neither be substantiated nor refuted. The use of local radiation alone, however, should be restricted to carefully designed clinical trials in which meticulous pretreatment evaluation is performed, and vigilant posttreatment evaluation of the spine and brain is mandatory. 
Increased free light chains in the urine from patients with multiple sclerosis. We quantitated free kappa (kappa) and lambda light (L) chains in coded urine specimens from subjects with clinically definite multiple sclerosis (MS) (N = 56), other neurologic diseases (OND) (N = 30), and age-matched normal controls (N = 28). Urine from MS patients showed statistically significant increases in free L chains compared with the other groups, although there was overlap between MS patients and OND patients. The ratio of kappa/creatinine was significantly greater in the relapsing-remitting MS group than in patients with clinically stable MS, OND, and normal controls. Elevated free L chains were usually independent of urinary albumin and beta 2-microglobulin levels. Serial studies showed that urinary free kappa/creatinine ratios were elevated during periods of clinical worsening in seven of eight MS patients and subsequently decreased during clinical recovery. The measurement of free L chains in urine obtained at intervals from MS patients may be useful as a marker to monitor disease activity. 
The interaction of plasminogen activator inhibitor 1 with plasminogen activators (tissue-type and urokinase-type) and fibrin: localization of interaction sites and physiologic relevance. Plasminogen activator inhibitor 1 (PAI-1), an essential regulatory protein of the fibrinolytic system, harbors interaction sites for plasminogen activators (tissue-type [t-PA] and urokinase-type [u-PA]) and for fibrin. In this study, anti-PAI-1 monoclonal antibodies (MoAbs) were used to identify interaction sites of PAI-1 with these components. The binding sites of 18 different MoAbs were established and are located on five distinct "linear" areas of PAI-1. MoAbs, binding to two distinct areas of PAI-1, are able to prevent the inhibition of t-PA by PAI-1. In addition, two interaction sites for fibrin were identified on PAI-1. The area located between amino acids 110 and 145 of PAI-1 contains a binding site for both components and its significance is discussed in the context of the t-PA inhibition by fibrin-bound PAI-1. Subsequently, the MoAbs were used to assess the role of platelet-PAI-1 in clot-lysis. An in vitro clot-lysis system was used to demonstrate that clot-lysis resistance is dependent on the presence of activated platelets and that PAI-1 is a major determinant for lysis-resistance. We propose that, upon activation of platelets, PAI-1 is fixed within the clot by binding to fibrin and retains its full capacity to inhibit t-PA and u-PA. 
Granulomatous pulmonary zygomycosis in a patient without underlying illness. Computed tomographic appearances and treatment by pneumonectomy. Pulmonary zygomycosis rarely occurs in the absence of underlying disease. We report a patient with granulomatous pulmonary zygomycosis without underlying disease who presented with a pulmonary mass. We present the computed tomographic findings that we believe have not been described previously. We also report the successful treatment by pneumonectomy. 
Mucosal dysplasia and DNA content in ulcerative colitis patients with ileorectal anastomosis. Follow-up study in a defined patient group. In a follow-up study of an epidemiologically defined patient group comprising 1,274 patients with ulcerative colitis diagnosed in Stockholm County during 1955-1979, 55 patients had undergone colectomy with ileorectal anastomosis (IRA). Nine of these were found to have Crohn's disease after histopathologic review of the colectomy specimens. Of the 46 patients with ulcerative colitis remaining for evaluation, two died postoperatively. Twenty-five patients were subsequently reoperated with rectal excision owing to intractable inflammatory activity (n = 22, one postoperative death) or owing to dysplasia (n = 3). Of 19 patients with their IRA still intact at time of follow-up, 15 patients (median disease duration 23 years) had a flexible sigmoidoscopy with multiple biopsies performed. The average length of the remaining rectum and sigmoid colon was 26 cm. No patient had findings of dysplasia, carcinoma, or DNA aneuploidy. None of the four remaining patients had developed dysplasia or carcinoma at the time of the latest regular rigid sigmoidoscopy. The risk of malignant transformation in this selected group of patients with ulcerative colitis operated upon with colectomy and IRA derived from an epidemiologically defined population seems to be low. 
Is erythrokeratoderma one disorder? A clinical and ultrastructural study of two siblings. Two sisters with erythrokeratoderma are described. In the younger sister the clinical appearance corresponded to erythrokeratoderma variabilis (EKV), whereas in the older sister it corresponded to progressive symmetrical erythrokeratoderma (PSEK). Ultrastructural findings in both cases were identical. We suggest that EKV and PSEK are different manifestations of a single condition. 
Oral contraceptives increase insulin-like growth factor binding protein-1 concentration in women with polycystic ovarian disease. Insulin-like growth factor-I (IGF-I) stimulates ovarian androgen production. Insulin-like growth factor binding protein-1 (IGFBP-1) inhibits IGF actions in vitro. OBJECTIVE: To investigate the effect of oral contraceptive (OC) pills, given for 3 months, on serum gonadotropin, androgen, IGF-I, and IGFBP-1 concentrations, and glucose tolerance in seven women with polycystic ovarian disease (PCOD) and in five healthy control subjects. PATIENTS: Seven women with PCOD and five healthy control subjects. INTERVENTIONS: An oral glucose tolerance test (OGTT) was performed before and after treatment with OC. RESULTS: After treatment with OC, serum luteinizing hormone, androstenedione, and free testosterone levels decreased, and sex hormone-binding globulin concentration increased in the women with PCOD as well as in the control subjects. The cumulative response of serum insulin to OGTT was larger in the women with PCOD than in the control subjects both before and after treatment. Serum IGF-I concentration, which was unchanged during OGTT, decreased from basal level of 326 +/- 70 micrograms/L to 199 +/- 28 micrograms/L after treatment with OC in the women with PCOD, whereas no change was found in the control subjects (from 235 +/- 11 micrograms/L to 226 +/- 11 micrograms/L). Treatment with OC caused an increase of the mean basal IGFBP-1 concentration from 24 +/- 7 micrograms/L to 73 +/- 14 micrograms/L in the women with PCOD. This increase was constant during the OGTT. In the control subjects, treatment with OC did not result in any significant change in IGFBP-1 concentrations (from 44 +/- 11 micrograms/L to 61 +/- 9 micrograms/L). CONCLUSION: The combination of decreased total IGF-I concentration and increased IGFBP-1 concentration induced by OC may decrease ovarian androgen production in PCOD. 
Immunohistochemical demonstration of CD23 expression on lymphocytes in rheumatoid synovitis. The leucocyte antigen CD23 is expressed by B lymphocytes following activation by a number of stimuli and functions as an IgE receptor, and in its soluble form, as a putative B cell growth factor. The expression of CD23 on the surface of lymphocytes in paraffin wax sections of synovial biopsy specimens was studied using a novel mouse monoclonal antibody, BU38. Specimens were investigated from nine cases of rheumatoid arthritis, six cases of osteoarthritis, and eight cases of chronic inflammation in articular and non-articular tissues. CD23 was expressed on a high proportion of lymphocytes in all forms of chronic inflammation and was not specific for rheumatoid arthritis. It may be a characteristic feature of any chronic inflammatory response. As CD23 was found on the surface of lymphocytes in many cases of these arthritides, sCD23 in serum or synovial fluid may yet prove a useful marker for the severity of the inflammatory infiltrate. 
Ulcerative colitis in the autotransplanted neovagina. A 33-year-old woman had undergone a radical surgical excision for carcinoma of the vagina at age 11. Vaginal reconstruction using a pedicled transplant of the sigmoid colon was successfully accomplished at age 19. Fourteen years later she developed vaginal bleeding, and a biopsy of the neovagina revealed changes consistent with ulcerative colitis. Within 2 weeks the patient developed bleeding per ano, and a rectal biopsy also revealed changes consistent with ulcerative colitis. Symptoms responded to sulfasalazine. This is believed to be the first case report of ulcerative colitis developing in colonic tissue used for a neovagina. The etiology, natural history, and surveillance of ulcerative colitis in relation to this unique case are reviewed. This case argues against the hypothesis that chronic ulcerative colitis is causally related to direct exposure to alimentary antigens. 
An atrial natriuretic factor analogue at low doses attenuates forearm reflex vasoconstriction to cardiopulmonary receptor deactivation in patients with hypertension. Contrasting data exist about a possible modulation of the autonomic function by atrial natriuretic factor (ANF) in human beings, particularly at low, biologically, significant concentrations. We have evaluated that possibility by increasing plasma ANF levels through the infusion of a synthetic analogue (WY-47,663, anaritide) in five male patients with mild to moderate uncomplicated hypertension. Nonhypotensive lower body negative pressure (-10 mm Hg x 5 min) was used to selectively deactivate cardiopulmonary receptors and to stimulate sympathetic efferent tone reflexogenically. ANF was given at either a low rate (0.005 micrograms/kg/min x 60 min, which was previously shown to increase plasma ANF in a range compatible with physiologic stimuli) or at a high rate (0.05 micrograms/kg/min x 60 min, each). Administration of ANF was preceded and followed by vehicle infusion (Haemacell x 30 min). Forearm blood flow (venous plethysmography), intraarterial blood pressure, and heart rate were monitored continuously, and venous immunoreactive ANF, plasma renin activity, aldosterone level, and venous hematocrit were measured at the end of both control and infusion periods. Arterial norepinephrine values, an indirect index of sympathetic discharge, were measured at rest and during lower body negative pressure conditions. Graded systemic ANF infusion increased immunoreactive ANF and venous hematocrit, decreased aldosterone level and plasma renin activity, whereas resting norepinephrine levels, blood pressure, and heart rate did not change. Lower body negative pressure decreased forearm blood flow during vehicle infusion, but it lost its vasoconstrictor effect during infusion of ANF. To identify the site of that inhibitory action, ANF was also infused into the brachial artery at rates that raised local but not systemic levels of immunoreactive ANF. 
Immunological evidence for the co-existence of the Lambert-Eaton myasthenic syndrome and myasthenia gravis in two patients. Two patients are described in whom a clinical and electromyographic diagnosis of the Lambert-Eaton myasthenic syndrome (LEMS) was made. Serum antibodies to voltage-gated calcium channels (VGCCs), the antigenic target in LEMS and to acetylcholine receptors (AChRs), the antigen in myasthenia gravis, were detected at raised titres in both cases, using radioimmunoassays based on 125I-omega-Conotoxin labelled VGCCs and 125I-alpha-Bungarotoxin labelled AChRs. These data provide immunological evidence for the coexistence of the two disorders in these patients. 
Fine-needle aspiration biopsy: application to pediatric head and neck masses. Fine-needle aspiration biopsy cytology is widely used to screen masses in adults. The authors present a series of 89 fine-needle aspiration biopsies performed between January 1973 and December 1988 on 86 pediatric patients with clinically significant head and neck masses. All fine-needle aspiration diagnoses were confirmed by subsequent surgical biopsy, autopsy, or clinical follow-up for a minimum of 18 months. Of 21 tumors identified, 19 were malignant. Of the 89 aspirations performed, 67 required no subsequent surgical biopsy. In 11 of these cases, metastatic or recurrent tumor was diagnosed and appropriate therapy instituted. Fifteen of the 89 aspirates revealed previously undiagnosed tumors requiring surgical intervention. One false-negative and two false-positive results were obtained. No radical treatment resulted from the false-positive diagnoses, and no patient delay in treatment occurred because of the false-negative result. The sensitivity was 94.4%, and the specificity was 97.1%. The usefulness and cost-effectiveness of fine-needle aspiration is stressed. 
Orthotopic cardiac transplantation in two patients with previous malignancy. This report presents 2 patients with previous malignancy in whom congestive cardiomyopathy developed secondary to doxorubicin toxicity. Both patients underwent orthotopic cardiac transplantation 3 and 5 years ago and are now in functional class I with no evidence of malignant recurrence. 
Priapism as a manifestation of isolated genital vasculitis. Vasculitis may affect virtually any organ system in the body. We describe a patient who presented with priapism due to isolated genital vasculitis. This responded promptly to oral corticosteroids. In patients presenting with priapism, a possible underlying vasculitis should be considered in the differential diagnosis; the treatment for this may be nonsurgical. 
Acute and chronic symptoms of mononucleosis. BACKGROUND. The clinical symptoms and durations of illness of patients with infectious mononucleosis (IM) are variable and are poorly documented in the scientific literature. METHODS. Patients who presented for care at the Student Health Service of a Canadian university between September 1985 and May 1988 and had been diagnosed as having IM were surveyed. Health experience during the acute and convalescent phases of IM was compared with that of a group of patients matched for age, sex, date of diagnosis, and year of study, who had suffered acute upper respiratory tract infections (URI), other than Epstein-Barr virus (EBV)-induced, during the same period. RESULTS. Students were sicker for longer after IM than after non-EBV-induced URI. During the acute phase of illness, the symptoms of fatigue (P = less than .000001), night sweats (P = .000001), and painful neck swelling (P = .00003) were seen significantly more often in the IM group. The severity and duration of these symptoms were also significantly worse in IM patients. Getting tired easily (P = .002), diurnal somnolence (P = .002), and depression (P = .002) were significantly more common postacute symptoms. Eleven percent of IM patients reported persistence of symptoms longer than 100 days, and in 6% of patients the symptoms had persisted after 1 year. Convalescent cases showed a trend toward reduced alcohol intake and, perhaps, reduced alcohol tolerance. CONCLUSIONS. IM involves excessive morbidity in a student community compared with URI that was other than EBV-induced, during both the acute and the postacute phases of infection. 
Dynamic exercise-induced elevation in plasma levels of atrial natriuretic peptide in patients with effort angina pectoris. We investigated the relationship between plasma atrial natriuretic polypeptide (ANP) levels and hemodynamic indices during dynamic exercise testing in 15 patients with effort angina pectoris. Patients exercised on an angina-limited, supine, multistage bicycle ergometer, and plasma ANP levels and hemodynamic indices were measured at rest, at peak exercise, and 6 minutes after exercise. Plasma ANP levels increased significantly at peak exercise. Pulmonary artery wedge pressure (PAWP) and coronary sinus blood flow (CSBF) were significantly correlated with plasma ANP levels before and at peak exercise (PAWP: r = 0.69, p less than 0.001; CSBF; r = 0.45, p less than 0.05). In six of eight patients whose PAWP exceeded 20 mm Hg at peak exercise, plasma ANP levels were increased at 6 minutes after exercise, whereas PAWP had decreased relative to the values obtained at peak exercise. Plasma ANP concentrations at 6 minutes after exercise were not correlated with PAWP at the same time. However, PAWP at peak exercise was correlated with the plasma ANP levels at 6 minutes after exercise (r = 0.80, p less than 0.001). These results suggest that in patients with effort angina pectoris left ventricular dysfunction resulting from exercise-induced myocardial ischemia may increase preload excessively and may contribute to the excess secretion of ANP after dynamic exercise. 
Acute appendicitis in patients with AIDS/HIV infection. Nine patients known to have acquired immunodeficiency syndrome (AIDS) and/or human immunodeficiency virus (HIV) infection and operated on for acute appendicitis are presented. Six of the nine patients did not have an elevation in the white blood cell count preoperatively. Two patients underwent diagnostic laparoscopy prior to exploration. In four cases, a perforated appendix was removed. Seven patients had persistent postoperative fever, while all nine had a significant lack of leukocytosis after surgery. Other than the absence of a preoperative increase in white blood cell count, the presenting characteristics of this group were similar to those expected in immunocompetent patients. However, concern for a possible opportunistic infection etiology and a desire to avoid operating on these patients resulted in an undue delay prior to exploration. The use of diagnostic laparoscopy aided in earlier and more accurate diagnosis. Despite persistent postoperative fever, appendectomy was performed in patients with AIDS/HIV infection without significant increase in morbidity and mortality. 
Changes in hypertension treatment and in congestive heart failure mortality in the United States. The use of antihypertensive agents has increased in recent years and has been more marked among individuals in older age groups (65-74 years) than in middle-aged groups (45-54 years). Because hypertension is a strong risk factor for the development of congestive heart failure, more common use of antihypertensive agents would be expected to reduce the incidence of congestive heart failure. Examination of the national death statistics reveals decreases in congestive heart failure mortality at younger ages with mortality increases at older ages. The reasons for these divergent trends in congestive heart failure mortality in different ages and the apparent inconsistency with respect to the changes in the use of antihypertensive drugs are explored. We speculate that antihypertensive treatment does not completely prevent congestive heart failure but merely postpones its development by several decades. 
Causes of death in patients with tuberous sclerosis. Of the 355 patients with tuberous sclerosis complex (TSC) examined at the Mayo Clinic, 49 had died (9 of causes other than TSC). We attempted to determine what pattern of organ involvement occurred most often in the 40 patients who died of TSC. One baby died of cardiac failure due to cardiac rhabdomyomas, and one child died of rupture of an aneurysm of the thoracic aorta. Eleven patients died of renal disease, which was the commonest cause of death. Ten patients died as a result of brain tumors, and four patients (who were 40 years of age or older) died of lymphangiomyomatosis of the lung. Thirteen patients with severe mental handicaps died of either status epilepticus or bronchopneumonia; in all but one of these patients, the only source of information was the death certificate. Survival curves show a decreased survival for patients with TSC in comparison with that for the general population. Patients with TSC need lifelong follow-up for early detection of potentially life-threatening complications. 
Sigmoid sinus thrombosis diagnosis by contrasted MRI scanning. Septic thrombosis of the transverse-sigmoid sinuses and the jugular bulb is a highly lethal condition. The presenting signs and symptoms of this disease entity are subtle and not in proportion to the magnitude of the problem. Later in the disease course, sudden fulminant findings appear. A high index of suspicion, combined with scanning techniques of either enhanced MRI or CT, allows prompt diagnosis and treatment. MRI enhanced with gadolinium-DTPA (Gd) is a valuable adjunct that confirms the diagnosis and delineates the extent of suspected pathology. 
Coarctation and hypoplasia of the aortic arch: will the arch grow? Hypoplasia of the transverse aortic arch of various degrees of severity is commonly seen in infants who have coarctation of the aorta. It is more often present when the coarctation is associated with intracardiac lesions that diminish or limit forward flow in the ascending aorta and promote right to left flow through an arterial duct. The increased frequency of surgical treatment of infants with complex coarctation, which is in part related to the ability to stabilize their condition with prostaglandin E1, has posed the question of the potential for growth and development of the originally hypoplastic aortic arch after conventional repair of aortic coarctation. Review of our experience with transverse aortic arch hypoplasia, found in 33 (32%) of 102 infants undergoing coarctation repair by subclavian flap aortoplasty or classic resection and end-to-end anastomosis, revealed excellent growth of the transverse arch after repair in all patients available for linear follow-up. The currently proposed extended arch repair should be reserved for the small group of infants with transverse aortic arch to ascending aorta diameter ratios (arch indices) of less than 0.25. 
Mechanism of augmented left atrial pump function in myocardial infarction and essential hypertension evaluated by left atrial pressure-dimension relation. To analyze left atrial (LA) pump function in normal subjects, in patients with essential hypertension and in patients with a healed myocardial infarction, LA dimension (aortic-root echogram) and pressure (catheter-tip manometer) were simultaneously recorded in 25 patients (8 normal subjects, 7 with hypertension and 10 with myocardial infarction). The pressure-dimension relation of the left atrium was composed of 2 loops: the A loop (expressing the pump function of the left atrium) and the V loop. LA dimension at the beginning of active LA shortening was significantly greater in hypertensive subjects (33 +/- 3 mm) and in those with myocardial infarction (32 +/- 4 mm) than in normal subjects (28 +/- 3 mm) (p less than 0.01, p less than 0.05, respectively). The area of the A loop significantly increased in subjects with hypertension (48 +/- 3 mm Hg.mm, p less than 0.01) and in subjects with myocardial infarction (29 +/- 10 mm Hg.mm, p less than 0.05), compared with normal subjects (20 +/- 8 mm Hg.mm). The mean fractional shortening velocity of the left atrium significantly increased in subjects with hypertension, compared with normal subjects and those with myocardial infarction (p less than 0.05 for both). LA peak wall tension during the LA active contraction period significantly increased with hypertension and with myocardial infarction, compared with normal subjects (p less than 0.01, p less than 0.05, respectively). The area of the A loop was directly proportional to the LA dimension at the beginning of active LA shortening (r = 0.53), p less than 0.01). 
Observation of spinal canal and cisternae with the newly developed small-diameter, flexible fiberscopes. Small-diameter (0.5-, 0.9-, and 1.4-mm) flexible fiberscopes were developed for visual diagnosis of spinal canal diseases. The fiberscopes were introduced via a Tuohy needle into the subarachnoid and epidural spaces of ten patients with various pain syndromes. Clear visualization of the subarachnoid space was achieved using the fiberscopes. The epidural space could be visualized only during withdrawal of the fiberscope. In five cases, the fiberscope could be advanced up to the level of the cisternae without causing the patient any discomfort. A slight headache and transient fever were noted after the examination in five and two cases, respectively, but no other complications occurred. Interestingly, preexisting pain diminished (two cases) or disappeared (one case) after the myeloscopy in three of five cases in which the myeloscopy revealed aseptic adhesive arachnoiditis. Further studies should be carried out to evaluate the usefulness of this technique. 
Thickening at the root of the superior mesenteric artery on sonography: evidence of vascular involvement in patients with cancer of the pancreas. Thickening of the root of the superior mesenteric artery (SMA) was studied by using preoperative sonography in 23 patients with pancreatic cancer and in 10 healthy control subjects. Of the 23 with cancer, 11 had neoplastic involvement of the SMA and 12 did not. Prominent thickening of the area around the SMA with (six patients) or without (five patients) decreased echogenicity compared with the adjacent retropancreatic connective tissue was observed in patients with involvement of the SMA, a finding called the "cuff sign." Mean thickness of the periarterial area in the cancer patients with and without involvement of the SMA and in control subjects were 8.5 mm, 4.0 mm, and 2.9 mm, respectively. With an upper limit of normal of 7.0 mm for the thickness of the SMA, the sensitivity, specificity, and overall accuracy of this sign in the evaluation of involvement of the SMA were 91%, 100%, and 96%, respectively. Decreased echogenicity of the periarterial area was not observed in patients without involvement of the SMA or in control subjects. Our results show that sonographic evidence of periarterial thickening of the root of the SMA (cuff sign), especially with decreased echogenicity, is a reliable finding of tumor infiltration of the SMA in patients with pancreatic carcinoma. 
Masseter muscle spasm in children: implications of continuing the triggering anesthetic. This retrospective study was undertaken to examine the management and outcome of children who developed isolated masseter muscle spasm (MMS) after the administration of intravenous succinylcholine during anesthetic induction. The inhalation anesthetics used for induction were continued in all of these cases. The medical records of 68 patients (male/female ratio, 1.7:1), identified from approximately 42,000 anesthetics given during the period 1980-1989, were reviewed. Fifty-seven children (2.3-12 yr old) were diagnosed as having isolated MMS, i.e., MMS without spasm of other muscles; 11 experienced generalized rigidity in combination with MMS. Anesthetic and postoperative management of these two groups differed. The overall incidence of MMS was 0.3% of inhalation anesthetics during which succinylcholine was given. Intraoperative arrhythmias occurred in 33% of the patients who developed isolated MMS and more frequently in older children. Most children experienced some degree of hypercarbia and/or metabolic acidosis, but the significance of these abnormalities in the spontaneously ventilating, fasting child is unknown. Serum creatine kinase levels when measured 18-24 h postoperatively were elevated in all but one child (n = 45). There was no long-term morbidity and no mortality. We conclude that failure of the masseter muscles to relax after succinylcholine is not uncommon in children. Based on our experience, and accepting that MMS may be part of the clinical spectrum of malignant hyperthermia, we believe that anesthesia can be continued safely in cases of isolated MMS when careful monitoring accompanies diagnostic evaluation. This differs from the current practice of discontinuing the anesthetic or switching to a nontriggering anesthetic technique. 
Hemisphere asymmetry in decision making abilities. An experimental study in unilateral brain damage. Thirty control subjects and 60 unilateral brain-damaged patients, 30 with left hemisphere (LH) damage and 30 with right hemisphere (RH) disease, underwent a disjunctive 4-choice reaction time study. Speed of reaction (as defined by the reciprocal of reaction time (RT), movement time (MT) and total response time (TRT] and accuracy of response (as represented by the sum of errors in selecting the correct response key) were investigated comparatively as a function of side of lesion and of performance on Raven's Coloured Progressive Matrices (PM47). In contrast to movement speed (1/MT), reaction speed (1/RT) as well as total response speed (1/TRT) showed a lesion effect independent of side of damage. Conversely, accuracy was differentially impaired, LH damage being associated with a significantly higher number of errors. Speed and accuracy had different relationships with the performance on the PM47 in the two hemisphere groups. Speed was affected in parallel with changes in PM47 performance both in the LH and in RH groups, whereas accuracy was altered only in LH patients. It was concluded that speed of motor reaction is affected by unilateral brain lesions irrespective of their side, whereas decision making processes, as expressed by accuracy of response, seem to be specifically impaired by LH damage. 
Cisplatin and etoposide as first-line chemotherapy for metastatic breast carcinoma: a prospective randomized trial of the Italian Oncology Group for Clinical Research. In this prospective randomized study, first-line treatment with the combination of cisplatin (P) and etoposide (E) was compared with the standard cyclophosphamide, methotrexate, and fluorouracil (CMF) combination in 140 patients. Complete remissions were obtained in 11% of 65 assessable patients on CMF and in 12% of 65 assessable patients on PE. Complete plus partial remission rates were 48% on CMF and 63% on PE (P = .08). Time to progression (median, 32 v 31 weeks), duration of response (48 v 39 weeks), and survival (75 v 76 weeks) were not different. Hematologic toxicity was significantly higher with PE, and gastrointestinal side effects were frequent with this treatment. This study demonstrated that the PE combination is effective as front-line chemotherapy. As far as response rate is concerned, a trend of superiority over CMF was observed, which was of borderline significance. Due to the lack of survival advantage and to toxicity, this combination is not recommended for routine clinical use. However, its high level of activity should be taken into account for further research. 
Idiopathic colonic perforation in the neonate. We describe a premature infant in whom spontaneous perforation of the colon was initially detected on routine abdominal films. There was no clinical evidence of necrotizing enterocolitis, peritonitis, or bowel obstruction. Surgical and pathologic findings confirmed the diagnosis of idiopathic bowel perforation. Since spontaneous gastrointestinal perforation in the neonate is often difficult to diagnose clinically, radiographic evaluation may allow earlier diagnosis and prompt surgical treatment of this life-threatening condition. 
Prognostic factors and complication rates for cervical cerclage: a review of 482 cases. Charts from 482 singleton pregnancies undergoing cerclage placement in patients over a 6-year period were reviewed. Cervical dilatation at time of surgery, number of previous spontaneous losses, and gestational age at placement were key determinants of outcome. The most frequent complication, premature rupture of the membranes, ultimately occurred in 38% of patients. The 6.6% infection rate was increased in patients undergoing emergent versus elective surgery (12.7% vs 4.7%, p less than 0.005) and in patients at increased dilatation at time of surgery (5.7% for less than or equal to 2 cm vs 41.7% for greater than 2 cm, p less than 0.005). McDonald and Shirodkar procedures had similar obstetric outcomes in patients undergoing their first cerclage. The subgroup of patients with prior cerclage surgery showed improved birth weight when the Shirodkar procedure was performed instead of the McDonald cerclage (mean birth weight 3020 vs 2470 gm, p less than 0.005). An increased rate of primary cesarean section was found in the Shirodkar group (31% vs 17%, p less than 0.005). Complication rates and pregnancy outcome appear to reflect cervical dilatation more than gestational age at time of surgery. 
Extraspinal causes of lumbosacral radiculopathy. Twelve of 12,125 patients who had been referred during a seven-year period to a specialist in spinal disorders were found to have an extraspinal cause of radiculopathy or neuropathy of the lower extremity. The records of these twelve patients were reviewed retrospectively. The average age of the twelve patients was sixty-five years (range, forty-two to seventy-seven years). The cause of the symptoms was an occult malignant tumor in nine patients and a hematoma, an aneurysm of the obturator artery, or a neurilemoma of the sciatic nerve in the others. The average time from the onset of symptoms to the final diagnosis was eight months (range, one month to two years). The most useful test for determination of the correct diagnosis was computed tomography or magnetic resonance imaging of the abdomen and pelvis. Computed tomography or magnetic resonance imaging of the spine and bone-scanning of the whole body were of little help in localizing the disease. In four of the twelve patients, an operation was performed on the basis of an incorrect diagnosis. In dealing with elderly patients who have radiculopathy, one should be suspicious that the cause is outside the spine. 
Hepatotoxicity of rifampin and isoniazid. Is it all drug-induced hepatitis? Serologic markers for hepatitis viruses were studied in 40 children who developed acute hepatitis during antituberculosis therapy with rifampin and isoniazid, with the aim of assessing the contributory role of these viruses toward producing hepatic injury. Hepatitis A and B were confirmed in 7.5 and 35% patients, respectively, by IgM antibodies. Epidemiologic evidence suggested the possibility of non-A, non-B hepatitis in at least a few of the remaining 23 children. Hepatitis B was seen more often in children with severe tubercular disease (72%) and was largely (92.8%) parenterally transmitted. The study highlights that the endemicity of viral hepatitis in developing countries, among other factors, could also be responsible for the reported higher incidence of hepatotoxicity from developing countries and also for the increased risk of hepatotoxicity seen in severe tubercular disease. 
Hyperemesis gravidarum. A comparison of single and multiple admissions. Recurrent hyperemesis gravidarum is a frustrating and poorly studied complication of early pregnancy. Between 1979 and 1987, 140 women with emesis severe enough to require parenteral fluid and electrolyte replacement were admitted to the Medical University of South Carolina Hospital, Charleston, on 220 occasions. Thirty-nine of the 140 women were admitted on multiple occasions. A comparison of clinical characteristics of women with single and multiple admissions revealed no significant differences except that women admitted repeatedly for hyperemesis gravidarum were more likely to be nulliparous (P less than .05). Ptyalism (59% vs. 9%) and persistent vomiting for greater than 24 hours after admission (69% vs. 23%) were significantly more common among women who were admitted repeatedly (P less than .05). Despite published reports that hyperemesis gravidarum has no impact on ultimate perinatal outcome, this study indicated that women admitted repeatedly have a more severe nutritional disturbance, associated with significantly reduced maternal weight gain and neonatal birth weight. These risks argue for more aggressive antenatal treatment and increased fetal surveillance in pregnancies complicated by recurrent hyperemesis gravidarum. 
Vancomycin added to empirical combination antibiotic therapy for fever in granulocytopenic cancer patients. European Organization for Research and Treatment of Cancer (EORTC) International Antimicrobial Therapy Cooperative Group and the National Cancer Institute of Canada-Clinical Trials Group [published erratum appears in J Infect Dis 1991 Oct;164(4):832] A total of 747 febrile granulocytopenic patients with cancer were randomized to receive ceftazidime plus amikacin (CA) with or without vancomycin (V) as initial empirical therapy. Single gram-positive bacteremias responded in 29 (43%) of 68 patients treated with CA and in 48 (72%) of 67 treated with CAV (P = .001). For single gram-negative bacteremias and clinically documented and possible infections the response rates of CA and CAV were 80% and 63% (P = .17), 55% and 75% (P = .009), and 74% and 81% (P = .16), respectively. However, for patients with gram-positive bacteremia and for all other patients, there were no differences by treatment regimens in the proportion of febrile patients on each trial day (P = .85, P = .82, respectively) or in the duration of fever (P = .22, P = .93, respectively). Moreover, no patient with gram-positive bacteremia died during the first 3 days of true empirical therapy. Antibiotic-associated nephrotoxicity was more frequent in patients treated with vancomycin (6% vs. 2%, P = .02). These results do not support the empirical addition of vancomycin to initial antibiotic therapy in cancer patients with fever and granulocytopenia. 
The conversion of primaquine into primaquine-aldehyde, primaquine-alcohol, and carboxyprimaquine, a major plasma metabolite. Although efficacy and toxicity of primaquine (PQ) depend on bioconversion, the process is poorly understood, even for carboxyprimaquine (CPQ), the major plasma metabolite. Earlier work to clarify drug metabolism showed that PQ could be converted quantitatively into CPQ, in vitro, with human erythroleukemic K562 cells or nonleukemic bone marrow supplemented with calf serum. We have now found--using systems with serum only, as well as with K562, bone marrow, and adult or embryonic liver cells--that the bioconversion of the side chain of PQ involves a branched pathway with at least three separate enzymes and two derivatives other than CPQ. An oxidase activity in serum converted PQ first into a novel side chain aldehyde (Y). Aldehyde dehydrogenase transformed PQ-aldehyde into CPQ in cell-free systems and in K562, bone marrow, and adult liver cells. Embryonic hepatocytes or bone marrow treated with 1,3-bis(2-chloroethyl)-1-nitrosourea did not produce CPQ; instead, they made a metabolite (Xc) that we could synthetize via PQ-aldehyde and identify as PQ-alcohol. PQ-alcohol replaced CPQ as the final product whenever alcohol-dehydrogenase prevailed over aldehyde dehydrogenase. These enzymes operated in intact cells and controlled the biotransformation of PQ absolutely. Unless both dehydrogenase were absent, inhibited, or deprived of coenzyme, potentially cytotoxic PQ-aldehyde intermediate did not accumulate. Some of the unique tissues schizonticidal and gametocidal effects of PQ may depend on the distribution pattern and relative activities of PQ oxidase, aldehyde dehydrogenase, and alcohol dehydrogenase in human subjects and in parasites. 
Inflammatory pseudotumor of the liver causing biliary obstruction. Treatment by biliary stenting with 5-year follow-up. Inflammatory pseudotumors of the liver are rare lesions that are becoming increasingly recognized, possibly because of frequent use of abdominal computed tomography (CT) and ultrasonography. Most previously reported cases have been treated by hepatic resection. For this reason, we describe a patient with obstructive jaundice secondary to an inflammatory hepatic pseudotumor in the porta hepatis. Bilateral internal biliary stents were inserted, and the patient remains well 5 years later. The clinicopathologic features of inflammatory pseudotumors of the liver are described, as are the implications of accurate diagnosis. There have been no previous reports of biliary stenting in management of inflammatory hepatic pseudotumors. 
Syncope and orthostatic hypotension. PURPOSE: The purpose of this study was to determine the postural blood pressure response over time, the prevalence of orthostatic hypotension in patients with syncope, and the relationship of orthostatic hypotension to recurrence of symptoms. PATIENTS AND METHODS: We prospectively evaluated 223 patients with syncope in a standardized manner. Orthostatic responses were measured in a standardized fashion at 0, 1, 2, 3, 5, and 10 minutes or until symptoms occurred. Follow-up was obtained at 3-month intervals. Causes of syncope were assigned by predetermined criteria. RESULTS: Orthostatic hypotension (20 mm Hg or greater systolic blood pressure decline) was found in 69 patients (31%). The median time to reach minimal standing systolic blood pressure was 1 minute for all subjects. In patients with orthostatic hypotension (20 mm Hg or greater), mean time to reach minimum blood pressure was 2.4 minutes. The vast majority of patients with significant orthostatic hypotension had this finding within 2 minutes of standing. Orthostatic hypotension was common in patients for whom other probable causes of syncope were assigned. The recurrence of syncope was not related to the degree of orthostatic hypotension; however, the recurrence of dizziness and syncope as end-points was lower in patients with 20 mm Hg or greater systolic blood pressure reductions as compared with patients with lesser degrees of orthostatic blood pressure declines. CONCLUSION: Orthostatic hypotension is common in patients with syncope and is detected in the vast majority of patients by 2 minutes. Although symptom recurrence on follow-up was lower in patients with more severe orthostatic hypotension, the clinical significance of this finding needs to be further defined by future studies. 
A meta-analysis of prophylactic antibiotics in head and neck surgery. Although it is generally agreed that prophylactic antibiotics are necessary for the prevention of postoperative wound infection, the choice of antibiotic regimen is controversial. In an attempt to determine the most effective antibiotic regimen, a meta-analysis of published clinical trials of prophylactic antibiotics for head and neck surgery was undertaken. The meta-analysis revealed a relative difference in infection rates of 43.7 percent in favor of the use of antibiotics versus placebo, of 8.3 percent in favor of multiple antibiotics versus a single antibiotic, of 13.7 percent in favor of multiple antibiotics versus cefazolin, and of 4.1 percent in favor of multiple-day prophylaxis versus single-day prophylaxis. This meta-analysis suggests that a 1-day course of clindamycin may be the most effective prophylactic antibiotic regimen for head and neck surgery. 
Ossifying fibromyxoid tumor of soft parts. Additional observations of a distinctive soft tissue tumor. The author studied four subcutaneous soft tissue tumors, similar to those recently described by Enzinger and associates (Am J Surg Pathol 1989;13:817) by the name "ossifying fibromyxoid tumor," by immunohistochemistry and electron microscopy to further understand the cellular nature of this lesion. The four tumors were composed of uniform round cells often surrounded by a lacunar space. The tumors often contained a peripheral zone of metaplastic bone. The cellularity was high, but the mitotic rate was low, suggesting a benign or borderline nature of the lesion. Longer follow-up was available for three cases, showing recurrence-free survival times of 11, 8, and 3 years. Immunohistochemistry studies revealed that all tumors were strongly positive for S-100 protein and focally positive for Leu-7, whereas melanoma-specific marker HMB45 was negative. Vimentin was the main type of intermediate filament protein, and one case also contained scattered glial fibrillary acidic protein-positive cells. Epithelial markers (keratins, epithelial membrane antigen), desmin, and muscle actins were negative. Electron microscopic examination showed partial, sometimes reduplicated, basal lamina surrounding many cells. Complex cell processes were also present. No myofilaments were found. The immunohistochemical and electron microscopic results may suggest that this tumor has Schwann's cell differentiation. 
Mucosal vascular stasis precedes loss of viability of endothelial cells in rat acetic acid colitis. The hypothesis that a significant reduction in colonic mucosal perfusion, and hence ischemic injury, precedes the development of mucosal ulceration and inflammation is tested in this report. The microcirculatory changes in the rat colonic mucosa within 1 hr of topical exposure to 10% acetic acid were assessed. Colonic mucosal blood flow signals measured by laser Doppler flowmetry were significantly reduced to 61 +/- 8, 52 +/- 10, and 37 +/- 13% (mean +/- SEM) of baseline values at 1 min, 4 min, and 10 min after the colonic mucosa was exposed to 10% acetic acid, respectively, but not in controls exposed to saline. After the start of application of 10% acetic acid (for 4 min), in vivo microscopy studies demonstrated that colonic mucosal ischemia (stasis of the red blood cells in the mucosal capillaries) occurred at 9 +/- 5 min (mean +/- SEM). Evidence of endothelial cell death (failure to exclude a fluorescent dye, propidium iodide, by endothelial cells) developed at 25 +/- 10 min (mean +/- SEM). These findings indicate that within minutes after contact of the colonic mucosa with 10% acetic acid, colonic mucosal ischemia develops, followed shortly by death of endothelial cells. The data do not establish a cause-and-effect relationship between the reductions in mucosal blood flow and loss of endothelial cell viability in response to acetic acid. Nevertheless, because these events occur at such an early time point, they may play a pathogenetic role in the development of the subsequent inflammatory and ulcerative changes in this animal model of colitis. Further studies to define the potential causal relationships between these parameters are warranted. 
Sufentanil citrate and morphine/bupivacaine as alternative agents in chronic epidural infusions for intractable non-cancer pain. Intraspinal narcotic (usually intrathecal morphine) infusions with implanted pumps are increasingly used in patients with intractable chronic pain not caused by cancer. In some patients, pain control is difficult with infusions of morphine. Seven patients with diagnoses of arachnoiditis, epidural scarring, and/or vertebral body compression fracture were treated with alternative solutions in an epidural route. For maximal flexibility, Medtronic implanted programmable infusion pumps with catheters to T6-T10 were used, and pain was monitored by verbal pain scales. In three patients, epidural infusions of morphine in 0.5% bupivacaine (MS-MARC) resulted in little or no pain relief without significant side effects (e.g., headache, nausea, or vomiting). In these same patients, epidural infusions of sufentanil citrate resulted in pain scale reductions of 92%, 82%, and 40%, respectively, with no side effects. Four other patients found more effective pain relief when switched from initial sufentanil citrate infusions to MS-MARC. Pain scale reductions (with no side effects) were 92%, 76%, 59%, and 47% in these patients. Pain relief and minimal side effects with sufentanil citrate is theorized to result from its higher lipophilicity promoting local transdural diffusion to spinal cord and limiting upward diffusion to the brain stem. Sufentanil citrate is also advantageous for programmable pumps because it is 100 times more potent than morphine and therefore allows longer pump refill times and higher infusion doses. Although this study was done on a limited number of patients, sufentanil citrate and MS-MARC in epidural infusions using programmable infusion pumps for non-cancer patients provide significant alternative drug combinations and routes. 
Processing of the precursor of NF-kappa B by the HIV-1 protease during acute infection. Transcription of the human immunodeficiency virus type-1 (HIV-1) genome is regulated in part by cellular factors and is stimulated by activation of latently infected T cells. T-cell activation also correlates with the induction of the factor NF-kappa B which binds to two adjacent sites in the HIV-1 long terminal repeat. This factor consists of two DNA-binding subunits of relative molecular mass 50,000 (50K) associated with two 65K subunits. It is located in the nucleus in mature B cells, but is present in other cell types as an inactive cytoplasmic complex. External stimuli, including those that activate T cells, result in nuclear translocation of active NF-kappa B. The cloning of the complementary DNA for the 50K subunit helped to identify an exclusively cytoplasmic 105K precursor (p105) (V.B., P.K. and A.I., manuscript submitted). The expression of active NF-kappa B might therefore also be regulated by the extent of processing of p105. Because HIV-1 requires active NF-kappa B for efficient transcription, we tested the effect of HIV-1 infection on the processing of the human 105K precursor. We show here that the HIV-1 protease can process p105 and increases levels of active nuclear NF-kappa B complex. 
Trichinella spiralis infection alters small bowel motor activity in the fed state. The effect of Trichinella spiralis infection on small intestinal transit and motor activity in the fed state during the intestinal phase of infection was studied. Contractions were recorded by strain gauge transducers, and mean transit time was measured by marker dilution technique. The mean amplitude and area of individual phasic contractions decreased, but no change occurred in their mean duration during trichinosis. The total amplitude and area of phasic contractions also decreased; this was caused by a decrease in the frequency of contractions as well as a decrease in the mean parameters. The reduction in the total duration was entirely caused by the decrease in frequency. The reduction in the total parameters of all contractions was the result of a reduction in the same parameters for both propagating and nonpropagating contractions. However, the decrease in the parameters of propagating contractions was much greater. Also, there was a decrease in the distance of propagation of phasic contractions. The transit time as a result of phasic contractions increased during T. spiralis infection. Additionally, T. spiralis infection induced giant migrating contractions in the fed state that were never observed during control. Chyme was propelled very rapidly and effectively by giant migrating contractions. The findings of the present study suggest that during diarrhea induced by T. spiralis infection, the phasic contractions may act to decrease transit and, hence, allow more contact time for absorption of water and nutrients. However, this response may be counter-balanced by giant migrating contractions that rapidly propel chyme into the colon and compound the diarrhea associated with T. spiralis infection. 
Identification of stromal cell precursors in human bone marrow by a novel monoclonal antibody, STRO-1. Murine IgM monoclonal antibody STRO-1 identifies a cell surface antigen expressed by stromal elements in human bone marrow (BM). STRO-1 binds to approximately 10% of BM mononuclear cells, greater than 95% of which are nucleated erythroid precursors, but does not react with committed progenitor cells (colony-forming unit granulocyte-macrophage [CFU-GM], erythroid bursts [BFU-E], and mixed colonies [CFU-Mix]). Fibroblast colony-forming cells (CFU-F) are present exclusively in the STRO-1+ population. Dual-color cell sorting using STRO-1 in combination with antibody to glycophorin A yields a population approximately 100-fold enriched in CFU-F in the STRO-1+/glycophorin A+ population. When plated under long-term BM culture (LTBMC) conditions, STRO-1+ cells generate adherent cell layers containing multiple stromal cell types, including adipocytes, smooth muscle cells, and fibroblastic elements. STRO-1+ cells isolated from LTBMC at later times retain the capacity to generate adherent layers with a cellular composition identical to that of the parent cultures. The STRO-1-selected adherent layers are able to support the generation of clonogenic cells and mature hematopoietic cells from a population of CD34+ cells highly enriched in so-called long-term culture-initiating cells. We conclude that antibody STRO-1 binds to BM stromal elements with the capacity to transfer the hematopoietic microenvironment in vitro. 
Percutaneous posterolateral lumbar discectomy and decompression with a 6.9-millimeter cannula. Analysis of operative failures and complications. The operative failures and complications of percutaneous posterolateral lumbar discectomy were analyzed in 100 patients who had a herniated nucleus pulposus and were prospectively studied and treated with use of a 6.9-millimeter outer-diameter (4.9-millimeter inner-diameter) sheath and manual insertion of the instruments. Twelve operations were considered to have failed, regardless of the length of postoperative follow-up or the incidence of reinjury; eleven patients had a repeat operation at the index level, and one patient was a chronic drug-abuser. In eight of the eleven patients, subsequent laminectomy was successful. Two patients had a psoas hematoma and one had a transitory sensory and distal motor deficit; all of these complications resolved without sequelae. There were no major complications, including superficial or deep infection, and no patient had neurovascular compromise. 
Obesity in minority populations: policy implications of research. Obesity is a major health problem for many Americans, with an overall prevalence for adults of approximately 25% and a range for specific subgroups of 24-75%. This range is striking and reflects many factors shown to influence the development and maintenance of obesity, including physical activity, diet, ethnicity, income, education, and genetic susceptibility. Many minority populations have higher prevalences of obesity and, thus, experience its adverse health consequences disproportionately. Research in diverse populations indicates that the relative importance of risk factors for cardiovascular disease varies in many populations. Data characterizing the profile of risk factors, including obesity and physical activity, for various special populations are limited and some, such as obesity, are based on standards developed in the general population. For public health policy and interventions to succeed, they must address the needs of special populations and of the overall population. This paper discusses some of the relevant broader social and research issues. 
Bioelectrical impedance assay (BIA) of total body composition in alcohol-induced migraine patients. Preliminary report. "Whole body composition" was investigated in 30 people subject to alcohol-induced migraine. The control group was 30 people matched for age, sex, height and weight, who were not subject to migraine and who consumed moderate amounts of alcohol. The following were evaluated: anthropometric data, alcohol intake in grams per day, total body water, fat-free mass, fat mass, and body mass index (kg/m2). Two methods of measurement were used: skin fold thickness evaluation, and bioelectric impedance assay (BIA). BIA is a non-invasive method based on the principle that lean tissues conduct a low frequency alternating current of electricity better than do fatty tissues. Body mass index was increased in the alcohol-induced migraine patients (p less than 0.04), as was fat mass, (p less than 0.03) as evaluated by skin fold measurements. Bioelectric impedance assay demonstrated a slight total body water increase in alcohol-induced migraine patients (p less than 0.07). Possibly, if this total body water increase was reflected at the neuronal level, the bioelectric properties of the migrainous brain may be altered, thus creating a hypothetical link with the phenomenon of spreading depression. 
Detection of alcoholism in hospitalized children and their families The study sought to measure provider recognition of family alcohol-related problems among hospitalized children and to identify characteristics distinguishing "positive" families. The study sample (N = 147) was drawn from admissions to the general pediatric medical service of a metropolitan teaching hospital. Positivity was assessed through parent and patient interviews that included standard alcohol abuse screening instruments. Provider recognition was assessed through record review and physician interview. Of the 22 families screened positive, only one was so identified by the child's attending or resident physician. Positive and "negative" families were similar in most respects, although parents in positive families were more likely to report stress and sleeping problems and adolescents were more likely to report being troubled by a parent's drinking. The similarity of positive and negative families and the low pediatrician recognition rate suggest that alcohol problems are likely to go unnoticed without a conscious screening effort. 
Neonatal detection of generalized resistance to thyroid hormone [published erratum appears in JAMA 1991 Feb 20;265(7):869] Generalized resistance to thyroid hormone (GRTH) is an inherited disease that is usually suspected when elevated serum thyroid hormone levels are associated with nonsuppressed thyrotropin. Often these test results are obtained because of short stature, decreased intelligence, and/or hyperactivity with learning disability noted in childhood and adolescence, or because of goiter in adulthood. We detected GRTH at birth by analysis of blood obtained during routine neonatal screening. The proposita, born to a mother with GRTH, had a thyrotropin level of 26 mU/L and a corresponding thyroxine concentration of 656 nmol/L (normal, 84 to 232 nmol/L). Administration of thyroid hormone in doses eightfold to 10-fold above replacement levels (liothyronine sodium, 21 micrograms/kg per day, and levothyroxine sodium, 44 micrograms/kg per day) were required to reduce serum thyrotropin to normal levels without induction of hypermetabolism. This case, and the retrospective finding of high thyroxine levels in five newborns subsequently diagnosed as having GRTH, suggest that measurement of thyroxine at birth, in conjunction with thyrotropin, could allow the early detection of GRTH. 
Total hip replacement with cemented, uncemented, and hybrid prostheses. A comparison of clinical and radiographic results at two to four years. One hundred and thirty-one patients who had 144 cemented or uncemented hip prostheses were followed prospectively for two to four years. A cemented or a hybrid prosthesis (consisting of a cemented femoral component and an uncemented acetabular component) was used in men older than seventy years, in women older than sixty years, and in younger patients in whom adequate initial fixation could not be obtained without cement. Uncemented, porous-surfaced implants were used in all other patients. The over-all clinical results were similar for the three groups. For the fifty-two hips that had a cemented prosthesis, the mean total Harris hip rating was 91 points and the score for pain, 42 points; for the twenty-seven hips that had a hybrid prosthesis, 90 and 43 points; and for the sixty-five hips that had an implant allowing ingrowth of bone in both the acetabulum and the femur, 95 and 43 points. Two prosthetic stems that were designed to allow ingrowth of bone had aseptic loosening; one was revised. Pain in the thigh, usually slight and not disabling, occurred at one year in 24 per cent of the patients in whom a femoral component allowing ingrowth had been used; the prevalence of pain then declined. The incidences of migration of the components and of radiolucent lines were greater in the acetabula that had a cemented component than in those that had a cup allowing ingrowth of bone. 
The effect of oral nitroglycerin on portal blood velocity as measured by ultrasonic Doppler. A double blind, placebo controlled study. We studied the effect of oral nitroglycerin on portal blood velocity (PBV) in 20 cirrhotic patients by a double blind, placebo controlled method using noninvasive Doppler sonography. After we obtained baseline Doppler in the fasting state, 0.6 mg nitroglycerin or placebo was given orally and the mean of 3 s averaged mean PBVs was repeated at 5 min intervals for 60 min. Ten patients each received nitroglycerin or placebo. Portal vein flows were antegrade in all. Of the 10 patients receiving nitroglycerin, seven (P = 0.002) showed a greater than 10% fall in the mean PBVs for at least 15 min. Of these seven "responders," five patients had a 10% decrease in mean systemic blood pressure for at least 15 min. None of the "nonresponders" had systemic hypotension. Our study suggests that the PBV-reducing effect of nitroglycerin in cirrhotics may be explained in part by systemic hypotension. 
Twin delivery: influence of the presentation and method of delivery on the second twin. To ascertain the perinatal mortality and morbidity in the second twin as related to its presentation and method of delivery, we reviewed the data on 578 sets of twins delivered from 1980 to 1987 and included 397 sets in whom both twins were greater than or equal to 1000 gm, without lethal anomalies, and in whom the first twin presented as a vertex. The perinatal outcome comparing twin A (all vertex) with twin B (vertex or nonvertex) with cesarean section or vaginal delivery was analyzed. No statistically significant difference in perinatal mortality or morbidity was found in comparing the nonvertex second twin delivered vaginally or by cesarean section. The one perinatal death and significant perinatal morbidity occurred in infants weighing less than 1500 gm or at less than 32 weeks' gestational age. It is concluded that vaginal delivery, irrespective of the position of the second twin, is valid in selected cases as long as fetal weight is greater than 1500 gm and the gestational age is greater than or equal to 32 weeks. 
A phase II evaluation of menogaril in cisplatin-refractory advanced ovarian carcinoma. A collaborative trial of the North Central Cancer Treatment Group and the Mayo Clinic. Forty-one women with advanced, recurrent epithelial ovarian carcinoma (in whom prior chemotherapy with a platinum-based regimen failed) were treated with menogaril 200 mg/m2 intravenously every 4 weeks in a Phase II trial. Partial responses were seen in two of 19 (10.5%) measurable disease patients and three of 12 (25%) nonmeasurable but evaluable patients, an overall objective response rate of 16.1% (95% confidence interval, 5% to 34%). Median time to progression for all patients was 2 months and median survival, 5 months. Toxicities were acceptable and consisted primarily of leukopenia and gastrointestinal toxicity. Twenty-nine percent of the patients had venous irritation or painful phlebitis at the intravenous injection site. Menogaril, as administered in this protocol, had modest antineoplastic activity in previously treated ovarian carcinoma patients. The responses were of short duration, and there appeared to be no survival advantage with menogaril treatment. 
The binding and functional properties of voltage dependent calcium channel receptors in pediatric normal and myelodysplastic bladders. The present study was designed to compare the binding and functional properties of calcium channel receptors in normal and myelodysplastic bladders. Normal bladders were obtained from children with vesicoureteral reflux undergoing ureteral reimplantation. Myelodysplastic bladder specimens were obtained from patients undergoing bladder augmentation. The functional studies included agonist (calcium chloride) dose response experiments and the determination of apparent antagonist dissociation constants for various calcium channel antagonists. The receptor binding studies were performed using the ligand (+)-3H-PN200-110 (specific activity 86.6 Ci./mmol.). The mean maximal response of myelodysplastic bladders to calcium ions was 31% less than normal bladders (p greater than 0.05). The mean EC50 for calcium mediated isometric tension and the mean -log antagonist dissociation constant values of nifedipine, diltiazem and verapamil were similar in normal and myelodysplastic bladders. The radioligand receptor binding studies demonstrated that the equilibrium dissociation constant of (+)-3H-PN200-110 in myelodysplastic bladders was 4-fold greater than in normal bladders. The density of dihydropyridine binding sites in myelodysplastic and normal bladders was similar. Our study demonstrated that the pathophysiology of the poorly compliant hyperreflexic bladder is not related to up regulation of dihydropyridine calcium channel receptors or alterations in the response of detrusor muscle to calcium ions. The relative abundance of calcium channel receptors in the normal and myelodysplastic bladders, and the regulation of detrusor contraction by calcium ions suggest that calcium channel receptors have a meaningful role in detrusor function. 
IgA nephropathy in blacks: studies of IgA2 allotypes and clinical course. The prevalence of IgA nephropathy (IgAN) varies among racial groups, being most common among Caucasians and Orientals and rare in Blacks. Other investigators have hypothesized that the risk for IgAN may be influenced by the IgA2 allotype. It has been suggested that the rare Black patients with IgAN may be homozygous for the A2m(1) allele which predominates in Whites, but is less common in Blacks. In a multicenter study, 27 Black IgAN patients were enrolled to investigate this hypothesis and analyze the clinical course of disease in Blacks. The IgA2 allotypes of 18 Black patients and 14 controls were determined using restriction fragment length polymorphism analysis. Three patients were homozygous for the A2m(1) allele, four were homozygous for A2m(2) and 11 were heterozygous. The respective allelic frequencies of A2m(1) and A2m(2) were 0.47 and 0.53 and did not differ significantly from Black controls. Most clinical manifestations of disease did not significantly differ with respect to distribution of the two alleles, although the gender ratio differed between the homozygous A2m(1) and heterozygous patients. The presence of the A2m(1) allele did not increase the risk for IgAN, and the presence of the A2m(2) allele or homozygosity for this allele did not protect Blacks from the development of IgAN. 
Coronary artery vasoregulation and left ventricular function in patients with angina pectoris-like pain and normal coronary angiograms. Twenty patients with angina pectoris-like pain, normal coronary angiography and abnormal exercise 201Tl scans were investigated by means of haemodynamic, coronary sinus blood flow and lactate determinations before and after cold provocation, pacing and dipyridamole infusion. Radionuclide angiography, a new exercise 201Tl scan and noninvasive hyperventilation and ergonovine tests were performed. Intracoronary infusions of acetylcholine were given in increasing doses and a second coronary angiogram in combination with a 201Tl scintigram was performed. Despite a previously pathological 201Tl scintigram, with reversible perfusion defects, only ten of the patients had reversible perfusion defects at the second investigation. Hyperventilation and ergonovine tests did not result in ECG signs indicative of coronary spasm. Intracoronary infusion of acetylcholine resulted in a diffuse coronary constriction in 3 of 14 patients, and in one patient a perfusion defect was observed on thallium scintigram. In conclusion, although most of the common methods for inducing coronary vasospasm were used, no consistent pattern of reaction was found to explain the chest pains experienced in this group of patients. 
Erdheim-Chester disease. Case report with autopsy findings. Erdheim-Chester disease is a rare pathologic entity characterized by symmetrical radiodensities in the metaphyseal and the diaphyseal portions of the long bones. Fibrosis, osteoblastic cortical bone deposition, and fibroxanthomatous granulomas with lipid-laden macrophages and multinucleated giant cells, which have a particular tropism for connective and adipose tissues, are the pathologic hallmarks. To our knowledge, 27 cases have been reported in the literature since the entity was first described in 1930. Protean clinical features range from a focal and asymptomatic process to a multisystemic infiltrative disease. We describe the clinical course of a new case and review the extensive pathologic findings at autopsy, including those demonstrated by light and electron microscopy and cytochemical and immunocytochemical studies. 
Comparison of direct insertion of disposable and standard reusable laparoscopic trocars and previous pneumoperitoneum with Veress needle. A randomized prospective study was conducted to evaluate the ease of use and safety of direct insertion of laparoscopic trocars. Comparison of previous pneumoperitoneum by Veress needle insertion with direct insertion of the reusable conventional laparoscopic trocar and direct insertion of the disposable shielded trocar revealed minor complication rates of 22, 6 and 0%, respectively. No major complications occurred in this series of 200 patients. 
Conservative treatment of patients with acoustic tumors. Seventy of 178 patients with acoustic tumors initially were treated conservatively and have been followed up for an average of 26 +/- 2 months. The tumor size was determined by the mean maximum anteroposterior and mediolateral diameters, using computed tomographic or magnetic resonance imaging scans obtained sequentially throughout the follow-up period. The average tumor growth was 1.6 +/- 0.4 mm the 1st year, and 1.9 +/- 1.0 mm the 2nd year (range, -2 to 17 mm/y): 4 tumors showed apparent regression, 28 (40%) had no detectable growth, and 37 (53%) exhibited growth (average, 3.8 +/- 1.2 mm/y). Within individual patients, the tumor growth rate determined during the 1st year of follow-up was predictive of tumor growth rate determined during the following year. Rapid tumor growth or clinical deterioration in 9 of the 70 patients (13%) who initially were treated conservatively necessitated subsequent surgery an average of 14 +/- 5 months after the patient was initially seen. This group had a larger initial tumor size (27.0 +/- 3.4 mm vs. 21.3 +/- 0.9 mm, P less than 0.05), and a faster 1-year growth rate (7.9 +/- 2.3 mm/y vs. 1.3 +/- 0.3 mm/y, P less than 0.05) than the 61 patients who did not require surgery. Two patients, however, experienced neurological deterioration that required surgery, even though there was no tumor growth. The high incidence of acoustic tumors with no detectable growth or apparent spontaneous regression must be taken into account when evaluating the indications for surgery and the efficacy of radiotherapy. 
Superior vena cava syndrome caused by an intrathoracic plasmacytoma. A case of an extramedullary intrathoracic plasmacytoma causing superior vena cava syndrome is described. Review of the literature on intrathoracic plasmacytomas and superior vena cava syndrome revealed that no similar cases have been described to date. The initial presentation, management, and response to treatment are described. 
Effects of left atrial pressure on the pulmonary vascular response to hypoxic ventilation. We investigated the effects of hypoxic ventilation on the pulmonary arterial pressure- (P) flow (Q) relationship in an intact canine preparation. Mean pulmonary P-Q coordinates were obtained during hypoxic ventilation and during ventilation with 100% O2 at normal and at increased left atrial pressure. Specifically, we tested the hypothesis that, over a wide range, changes in left atrial pressure would alter the effects of hypoxic ventilation on pulmonary P-Q characteristics. Seven dogs were studied. When left atrial pressure was normal (5 mmHg), the mean value of the extrapolated intercept (PI) of the linear P-Q relationship was 10.9 mmHg and the slope (incremental vascular resistance, IR) of the P-Q relationship was 2.2 mmHg.l-1.min. Hypoxic ventilation increased PI to 18 mmHg (P less than 0.01) but did not affect IR. Subsequently, during ventilation with 100% O2, when left atrial pressure was increased to 14 mmHg by inflation of left atrial balloon, PI increased to 18 mmHg. IR was 1.6 mmHg.l-1.min. Again, hypoxic ventilation caused an isolated change in PI. Hypoxia increased PI from 18 to 28 mmHg (P less than 0.01). As in the condition of normal left atrial pressure, hypoxic ventilation did not affect IR. We conclude that, in an anesthetized intact canine preparation, hypoxic ventilation causes an isolated increase in the extrapolated pressure intercept of the pulmonary P-Q relationship. Furthermore the effects of hypoxic ventilation on pulmonary P-Q characteristics are not affected by the resting left atrial pressure. 
Detection of autoantibodies against myeloid lysosomal enzymes: a useful adjunct to classification of patients with biopsy-proven necrotizing arteritis. PURPOSE: Assessment of the value of determination of antineutrophil cytoplasmic antibodies (ANCA) and its specificities for classification of patients with biopsy-proven necrotizing arteritis. PATIENTS AND METHODS: The serum samples of 28 consecutive patients with biopsy-proven vasculitis involving medium- and/or small-sized arteries were tested for ANCA by an indirect immunofluorescence technique, by neutrophil extract enzyme-linked immunosorbent assay (ELISA), and by catching ELISA. RESULTS: Eight patients had Churg-Strauss syndrome; six had myeloperoxidase (MPO) antibodies, and in the other two patients, ANCA were not detected. Six patients had polyarteritis nodosa (PAN) limited to the skin and the musculoskeletal system; ANCA were not detected in these patients. Two patients had systemic PAN and both had MPO antibodies. The remaining 12 patients had overlapping clinical features of the different forms of vasculitis. Five patients had polyarteritis in combination with chronic nasal inflammation and glomerulonephritis compatible with Wegener's granulomatosis (WG) but without granulomas in the respiratory tract. All five patients had 29-kd serine protease antibodies. Two patients had polyarteritis in combination with nasal polyposis and asthma compatible with Churg-Strauss syndrome, but eosinophilia was not detected. Both patients had MPO antibodies. Three patients with unclassified granulomatous arteritis had either elastase antibodies or ANCA of unknown specificity. One patient with unclassified systemic vasculitis had 29-kd serine protease antibodies, and one patient with necrotizing arteritis of the bowel in combination with Schonlein-Henoch purpura was negative for ANCA. CONCLUSION: Determination of ANCA and its specificities is a useful adjunct to the classification of patients with biopsy-proven necrotizing arteritis. Within the spectrum of idiopathic vasculitides, 29-kd serine protease antibodies are associated with WG, MPO antibodies are associated with Churg-Strauss syndrome and systemic PAN, and PAN limited to the skin and the musculoskeletal system is not associated with ANCA. 
Current status of lung transplantation. Techniques and indications for single and bilateral lung transplantation have evolved significantly in the past several years. Lung transplantation has entered a new era in which transplantation can be achieved with the same degree of success as that achieved with other major organ transplants. Many problems, common to organ transplantation remain to be solved including availability of suitable donor organs, improved immunosuppressive regimens, and the ability to properly diagnose and effectively treat organ rejection. 
Five-year vascular audit from a district hospital. Vascular patients under the care of one surgeon over a 5-year period have been reviewed, from computer-based discharge records, with regard to in-hospital measures of outcome to determine whether or not surgery was being performed to an acceptable standard. Out of 466 procedures, 30 per cent of patients had at least one complication, 14 per cent had further surgery and 9 per cent died. Outcome was examined within the following treatment groups: aorto/iliac aneurysm, aortofemoral bypass, femoroproximal popliteal bypass, femorodistal popliteal bypass, femorocrural bypass, embolectomy and percutaneous transluminal angioplasty. Patients having below-knee bypass surgery were found to have an unacceptably high rate of complications, reoperations and amputations. An overall rate of reoperation for postoperative bleeding of 5 per cent was also considered to be high. With these exceptions, it was concluded that the surgery was being performed to an acceptable standard, but that comparative audit of this type remained difficult while there was a deficiency of national statistics against which the work of individual surgeons could be judged. 
Clinical characteristics of patients in the persistent vegetative state Little is known concerning the specific clinical characteristics of patients in persistent vegetative states (PVS). Fifty-one patients from four nursing homes, approximately 3% of the total patients, were identified as being in a PVS. The mean age of the patients was 64.8 +/- 3.2 years (range, 19 to 96 years) and the mean duration of the PVS was 3.3 +/- 5.0 years (range, 1 to 16.8 years), with 13 patients' PVS being longer than 5 years. Cerebrovascular accidents and dementia were the most common causes of the PVS, accounting for 32 of the cases (63%). In the younger patients cerebral trauma secondary to motor vehicle accidents was the most common cause. All 51 patients were fed via tube feeding and 35 patients had urinary catheters (75%). All patients were receiving daily medications, with greater than 50% taking daily vitamins. Over 30% were taking digitalis and/or diuretics and over 32% were taking H2 blockers. Transfer of patients to an acute care hospital was not uncommon, with 31 patients (61%) requiring 63 acute care hospitalizations during their stay in the nursing home. As expected, infections were the most common reason for acute care hospitalization, although 15 of the patients were hospitalized for surgical procedures. Another common problem encountered by the patients was pressure sores, with 78% of patients requiring specific therapy for at least one pressure sore. Surprisingly, only 27 (53%) of 51 patients had a specific resuscitation status designation in the medical chart, and neither presence of a chart designation nor specific resuscitation order was related to the patient's age or the cause or duration of PVS. From these data it would appear that clinical characteristics of patients in PVS are variable. Some patients are young, others are old. The cause varies from cerebrovascular accidents to cerebral trauma. Survival may be prolonged; complications are not uncommon, with some patients requiring acute care hospitalization. 
Attenuation of circadian variation by combined antianginal therapy with suppression of morning and evening increases in transient myocardial ischemia. The circadian variation of total ischemic activity was examined during 3289 hours of ambulatory ECG monitoring in 101 patients with stable angina pectoris and proved coronary artery disease, who were not receiving any prophylactic antianginal therapy. The 101 patients displayed 411 episodes of ischemia, 312 (76%) of which were silent; a circadian rhythm was noted for the occurrence of total and silent ischemia. Thirty-eight percent of the ischemic episodes occurred between 6 AM and 12 noon, and total and silent ischemia were significantly more frequent during this period compared with the other three 6-hour periods (p less than 0.01); a lesser peak was noted in the evening. The effects of metoprolol and combined therapy with metoprolol and nifedipine on the circadian variation of ischemic activity were studied in two subgroups of patients in a random, double-blind study design (31 patients receiving metoprolol and 42 receiving combined therapy). During therapy with metoprolol the morning increase in ischemic activity was attenuated, and the highest frequency of ischemia was then noted in the evening (6 AM to 12 noon compared with 6 PM to 12 midnight; p less than 0.05). Combined therapy abolished the morning peak as did metoprolol monotherapy, but even the evening increase in ischemic activity was attenuated (p less than 0.05). The diurnal distribution of the mean heart rate at the onset of ischemia, when patients were off therapy, showed a morning increase similar to the increase in ischemic activity but no second peak in the evening. 
Hereditary lymphedema and distichiasis. Two patients with lymphedema-distichiasis syndrome illustrate that both Milroy's disease and late-onset hereditary lymphedema are sometimes associated with distichiasis. It is important for ophthalmologists to be aware of the lymphedema-distichiasis syndrome because of its ophthalmic manifestations and the associated systemic abnormalities that can be potentially life threatening. 
Management of hypertensive emergencies: changing therapeutic options. Rapid lowering of severe hypertension is essential to prevent irreversible damage to vital organs. The patient's clinical status should be evaluated, noting particularly cardiac, neurologic, and renal functions. Choice of treatment should be based on speed and efficacy of action and on hemodynamic, vascular, and renal consequences. It is also important to preserve circulatory homeostasis and vital organ function. Sodium nitroprusside, labetalol, diazoxide, and hydralazine have been used parenterally for rapid control of severe hypertension, but they do not always produce optimal, balanced hemodynamic effects. Calcium antagonists have been advocated because of their beneficial circulatory effects. Nicardipine, a new dihydropyridine calcium antagonist, produces significant antihypertensive effects, and when given intravenously, results in a rapid fall in blood pressure. Studies have confirmed that nicardipine is effective and safe in the management of severe hypertension and hypertensive crises. Because the aim of rapidly controlling severe hypertension is to prevent target organ dysfunction, nicardipine therapy offers a useful additional option in the clinical management of severe hypertension and hypertensive crises. 
Preparing children for venous blood sampling. A convenience sample of 100 children, aged 6-12 years, attending Kuwait government hospital laboratories for venous blood sampling was studied. A picture book was used to prepare half of the children for the procedure. Preparation was carried out just prior to sampling and took less than 5 min. The story provided a simple description of venous blood sampling, and why it is carried out; it stressed that the pain is noticeable but not unbearable, and that children will experience less pain if they relax their arm and cooperate with the technician. Prepared children reported significantly less pain, and radial pulse rates confirmed that they were less distressed by the procedure. Observers' and parents' evaluations also indicated that prepared children coped better. Various explanations for the benefits observed are discussed, together with requirements for managing the pain, fear and stress experienced by children during medical treatment. 
Relationship between outlet obstruction constipation and obstructed urinary flow. Ten women with symptoms and radiological features of outlet obstruction constipation underwent urodynamic bladder studies. The results were compared with ten age- and sex-matched controls. The mean (s.e.m.) peak flow rate for patients was 19.4 (6.4) ml/s compared with 32.1 (7.2) ml/s for controls (P less than 0.05). The mean (s.e.m.) voiding time for patients was 62.9 (23.7) s against a corresponding value of 15.6 (6) for controls (P less than 0.05). The mean (s.e.m.) bladder volume in patients was 482 (80) ml compared with a control value of 254 (112) ml (P less than 0.03). The mean (s.e.m.) detrusor pressure during the voiding phase was 53.3 (12) cmH2O. These results demonstrate that patients with outlet obstruction constipation have a generalized pelvic floor disorder resulting in obstructed urinary flow. 
Cystic mesothelioma of the peritoneum. A report of three cases. Three cases of peritoneal cystic mesothelioma are reported. All patients were women who had undergone previous abdominal surgery for unrelated conditions. Tumors consisted of solitary and multiple cystic masses involving the abdominal and pelvic peritoneum. The cysts focally infiltrated the muscularis externa of the small intestine in case 1, the outer muscular layer of the uterus in case 2, and the omental tissue in case 3. These findings give morphologic support to the borderline clinical behavior of this tumor that often recurs and support the hypothesis that previous surgery may play a role in its pathogenesis. 
Surgery for chronic ear disease in a non-university hospital: open cavity, obliteration and intact canal wall techniques. The long-term results of surgery for chronic suppurative middle ear disease at a non-university ENT-clinic (Vasa Central Hospital, Finland) are reported. The material consisted of 273 ears, 65 of which had been operated on by open cavity techniques, 178 by the original Palva obliteration method, and 30 by the intact canal wall method. Post-operative cholesteatoma occurred equally frequently with the two canal wall down methods (7.7 and 7.3%, respectively) but was more frequent after intact canal wall surgery (23.3%). Hearing was better and the infection rate lower with obliteration than with open cavity techniques. Post-operative infection was the least frequent and the hearing result best in the intact canal wall ears, but compared to the other two groups the extent of disease found at surgery was considerably less in this group. The obliteration operation proved to be a safe method in the hands of a practising otologist outside university clinics. 
Establishment and characterization of a new human prostatic carcinoma cell line (DuPro-1). A new human prostate adenocarcinoma cell line (DuPro-1) has been established from the athymic nude mouse supported xenograft DU5683. This was accomplished by embedding dispersed xenograft cells in 0.1 by 5.0 cm. spaghetti-like strands of Basement Membrane MATRIGEL [BMM (Collaborative Research, Inc.)], a unique technique facilitating the transition to tissue culture. Now passed over 30 times, the cells display anchorage and serum concentration independent growth with a doubling time of 22 to 24 hours. Cells exhibit pronounced morphological differences when grown on BMM coated culture dishes, assuming a pseudoglandular configuration, in contrast to typical homogeneous monolayer growth on plastic culture dishes. Light and electron microscopy show cohesive sheets of anaplastic epithelial cells, consistent with prostate carcinoma. Karyotypic analysis revealed all human chromosomes, near tetraploidy, 10 to 12 markers, and 3 to 4 X chromosomes, without a Y chromosome. Cells injected s.c. or embedded in BMM and implanted in the subrenal capsule space are equally tumorigenic in male and female athymic mice, suggesting that DuPro-1 cells are hormonally insensitive. Embedding cells in BMM may be useful in developing other tissue culture cell lines from neoplasms difficult to initiate in vitro. DuPro-1 should provide a valuable means to study the biology, immunology, and chemosensitivity of human prostate cancer. 
Induced hypertension during restoration of flow after temporary middle cerebral artery occlusion in the rat: effect on neuronal injury and edema. The effect of hypertension instituted during restoration of flow after focal ischemia was studied. After the middle cerebral artery (MCA) of 12 rats was occluded for 2 hours, the ligatures were released and flow was restored for a period of 2 hours. In the control group, mean arterial pressure (MAP) was not manipulated. In the hypertensive group, the MAP was elevated by 25-30 mm Hg immediately after reestablishment of MCA patency. The area of neuronal injury, determined by 2,3,5-triphenyltetrazolium staining, was significantly smaller in the hypertensive group. Specific gravity, determined by microgravimetry, did not differ between groups. The data demonstrate that modest hypertension, when induced during reperfusion after 2 hours of MCA occlusion, reduces neuronal injury and does not exacerbate edema formation. 
The early management of flap necrosis in breast reconstruction. Flap necrosis is a potential complication of any type of breast reconstruction. Of 302 breast reconstructions performed by the author at the University of Texas M.D. Anderson Cancer Center, some degree of flap necrosis occurred in 59 (19.5 percent). Small areas of flap necrosis can be managed with simple observation, but secondary healing may not be complete for months. Early and aggressive excision of the ischemic tissue with immediate primary closure often can achieve rapid primary healing. In addition, early revision and reshaping of the breast may, in selected patients, permit achievement of a significantly better final result. This is true not only for TRAM and latissimus dorsi flaps, but also for the mastectomy flap necrosis sometimes encountered in immediate reconstruction with simple implants or tissue expanders. 
Monthly pulses of vincristine and prednisone prevent bone marrow and testicular relapse in low-risk childhood acute lymphoblastic leukemia: a report of the CCG-161 study by the Childrens Cancer Study Group. On study CCG-161 of the Childrens Cancer Study Group (CCSG), 631 children with acute lymphoblastic leukemia (ALL) at low risk for relapse were randomized to receive monthly pulses of vincristine-prednisone (VCR-PDN ) during maintenance therapy in addition to standard therapy with mercaptopurine (6MP) and methotrexate (MTX), and either cranial irradiation during consolidation or intrathecal (IT) MTX every 3 months during maintenance. All patients received six doses of IT MTX during induction and consolidation. With a minimum follow-up time of 4.25 years, 76.7% receiving VCR-PDN were in continuous complete remission at 5 years, in contrast to 63.9% receiving GMP-MTX alone (P = .002). The difference in relapse-free survival was due primarily to bone marrow relapse (P = .0008), and in boys also to testicular relapse (P = .003). Among the nonirradiated patients, the 5-year disease-free survival (DFS) was 79.4% for patients randomized to the VCR-PDN pulses, in contrast to 61.2% for the patients randomized to receive 6MP-MTX alone (P = .0002). Among the irradiated patients, the DFS was not significantly different. Of the four combinations of maintenance and CNS therapy studied, the highest DFS was achieved with VCR-PDN pulses and maintenance IT MTX. 
Expression of the insulin like growth factor-binding protein 3 (IGFBP-3) gene is increased in human renal carcinomas. After we had established that the IGFBP-3 gene is expressed in normal human kidney we examined renal adenocarcinoma tissue for alterations of the expression of this gene. For this purpose we prepared poly(A)+ RNA from normal kidney tissue and adjacent renal adenocarcinoma of 18 adult patients and compared the levels of IGFBP-3 mRNA by Northern analysis in both samples. The mean content by densitometry was markedly increased in the carcinoma tissues; in 17 of 18 patients the carcinoma contained significantly more IGFBP-3 mRNA than the normal kidney sample. The highest mRNA levels were found in patients with N2 and N3 lymph node extensions. Comparative Southern analysis of paired samples of four of these patients did not reveal amplification of the gene as the cause of these increased mRNA levels. In one patient, however, we identified a restriction fragment length polymorphism (RFLP) present in normal and malignant cellular DNA. This suggests a participation of the IGFBP-3 gene in the development of human renal cell cancer. 
A difference in mortality between two strains of jaundiced rats. Homozygous Gunn rats lack bilirubin glucuronyltransferase, become jaundiced, and often develop kernicterus, thus providing a model for neonatal hyperbilirubinemia. Two new, inbred rat strains that carry the Gunn mutation are described. These were developed by breeding the mutant Gunn gene (j) into the RHA/N and ACI/N strains, producing the new lines, which were designated RHA/N-j and ACI/N-j. Liver assay confirmed the absence of transferase activity in jaundiced rats from both of the new strains, but marked differences in mortality between the strains were observed. The mortality of jaundiced RHA/N-j rats through 8 weeks was the same as that of their nonjaundiced littermates (20%). In contrast, mortality of jaundiced ACI/N-j rats was distinctly greater than that of their nonjaundiced littermates (81% vs 34%, P less than .001). Signs of kernicterus such as ataxia were much more frequent in jaundiced ACI/N-j rats than in jaundiced RHA/N-j rats (73% vs 11%, P less than .001). Both strains had comparable albumin concentrations through 8 weeks of age. Serum bilirubin concentrations were also comparable, except for a small but significant difference at 20 days of age (ACI/N-j = 294 mumols/L, RHA/N-j = 248 mumols/L, P less than .01). Similarly, the bilirubin-to-albumin ratios were comparable except for a significantly higher ratio at 20 days of age in the ACI/N-j rats (ACI/N-j = 0.70, RHA/N-j = 0.51, P less than .01). Thus, the RHA/N-j strain is unusual in that the jaundiced animals remain healthy. Conversely, the ACI/N-j animals demonstrate a high incidence of kernicterus with mortality. 
Asymptomatic bacterascites: is it spontaneous bacterial peritonitis? Asymptomatic bacterascites is defined as the presence of bacteria in ascitic fluid without clinical features of peritonitis or increased ascitic fluid polymorphonuclear cells. Asymptomatic bacterascites is a controversial entity, and little information is available regarding its spontaneous evolution. Clinical features, bacteriological data and outcome in 22 cirrhotic patients with asymptomatic bacterascites are reported and are compared with those of a group of 36 cirrhotic patients with spontaneous bacterial peritonitis. Eleven patients had gram-negative bacteria and 11 had one gram-positive bacteria. Only in three patients (13.6%) did peritonitis develop. Twelve patients received no antibiotic therapy, and in none did peritonitis develop. At 1 month, 27% of patients with asymptomatic bacterascites had died. Patients with asymptomatic bacterascites had less-severe liver disease; they more frequently had gram-positive bacteria in ascitic fluid and had a lower 1-mo mortality rate than did patients with spontaneous bacterial peritonitis. We conclude that asymptomatic bacterascites is usually the transient residence of bacteria in ascitic fluid. Peritonitis rarely develops in patients with asymptomatic bacterascites and, in most of them, antibiotic therapy is not required. 
Fetal hypertension induced by norepinephrine infusion and umbilical artery flow velocity waveforms in fetal sheep. This study was designed to examine the effects of fetal hypertension on the umbilical artery pulsatility index. Fetal arterial blood pressure and umbilical venous pressure were measured in eight sheep, 3 to 5 days after surgery. Umbilical blood flow was measured with an electromagnetic flowmeter around the common umbilical vein. Umbilical artery flow velocity waveforms were obtained either by an indwelling 5 MHz pulsed Doppler device (n = 4) or transcutaneously by a 4 MHz continuous-wave Doppler device (n = 4). Fetal blood pressure was raised by intravenous infusion of norepinephrine 10 micrograms/min during 5 minutes. Norepinephrine infusion resulted in elevated arterial and umbilical venous pressures, accompanied by a bradycardia during the first 3 minutes. Umbilical blood flow, calculated placental vascular resistance, and umbilical artery pulsatility index did not change. After atropine administration, the norepinephrine-induced elevated arterial and umbilical venous pressures were accompanied by tachycardia, increased umbilical blood flow, and no change in placental vascular resistance and umbilical artery pulsatility index. It is concluded that fetal arterial hypertension provoked by norepinephrine infusion has no effect on placental vascular resistance, umbilical blood flow, and umbilical artery pulsatility index. 
Prolactin-producing pituitary carcinoma with pulmonary metastases. Pituitary adenomas rarely are metastatic. Extracranial visceral metastases of prolactinomas were not previously reported. The authors report a case of a 34-year-old man with a prolactin-producing pituitary carcinoma and histologically proven lung metastases. Pathologic examination of the pulmonary spread included electron microscopy and immunohistochemistry; these confirmed prolactin production by the tumor. The patient's presentation at initial diagnosis, disease recurrence, clinical course, management, and response to therapy (with its theoretic basis) are detailed. Despite the use of dopamine analogues (to tolerance and in combination), there was documented intracranial and extracranial disease progression. Possible future therapeutic maneuvers are discussed. 
Renal pelvic explosion during conservative management of upper tract urothelial cancer. Ureteroscopic fulguration of a renal pelvic papillary transitional cell carcinoma is a relatively new and limited procedure. We present a case of intrarenal explosion during ureteroscopic fulguration. 
Cutaneous vasomotor sensitivity to ethanol and acetaldehyde: subtypes of alcohol-flushing response among Chinese. A cutaneous test has been applied in examination of the flushing response to ethanol and acetaldehyde in 402 Chinese of Han ethnicity. Using this noninvasive method, five response subtypes have been observed: (A) fast flushing to both ethanol and acetaldehyde; (B) fast flushing only to ethanol but not to acetaldehyde; (C) slow flushing to ethanol only; (D) no response either to ethanol or to acetaldehyde; (E) vasoconstriction to ethanol, or to both ethanol and acetaldehyde. A total of 94% in subtype (A) are reported to be flushers, while only 25% was reported in subtype (D). Other physiological responses, such as tachycardia, dizziness, headache, drowsiness, and nausea are less frequent after alcohol ingestion. The recent history of consumption of alcohol of the subjects in different subtypes was also obtained. Although alcohol-induced flushing is thought to be a deterrent factor to heavy consumption of alcohol, the frequency of drinking of alcoholic beverages was not found to be different between flushers and nonflushers. 
Parental occupations of children with leukaemia in west Cumbria, north Humberside, and Gateshead OBJECTIVE--To determine whether parental occupations and chemical and other specific exposures are risk factors for childhood leukaemia. DESIGN--Case-control study. Information on parents was obtained by home interview. SETTING--Three areas in north England: Copeland and South Lakeland (west Cumbria); Kingston upon Hull, Beverley, East Yorkshire, and Holderness (north Humberside), and Gateshead. SUBJECTS--109 children aged 0-14 born and diagnosed as having leukaemia or non-Hodgkin's lymphoma in study areas during 1974-88. Two controls matched for sex and date and district of birth were obtained for each child. MAIN OUTCOME MEASURES--Occupations of parents and specific exposure of parents before the children's conception, during gestation, and after birth. Other adults living with the children were included in the postnatal analysis. RESULTS--Few risk factors were identified for mothers, although preconceptional association with the food industry was significantly increased in case mothers (odds ratio 2.56; 95% confidence interval 1.32 to 5.00). Significant associations were found between childhood leukaemia and reported preconceptional exposure of fathers to wood dust (2.73, 1.44 to 5.16), radiation (3.23, 1.36 to 7.72), and benzene (5.81, 1.67 to 26.44); ionising radiation alone gave an odds ratio of 2.35 (0.92 to 6.22). Raised odds ratios were found for paternal exposure during gestation, but no independent postnatal effect was evident. CONCLUSION--These results should be interpreted cautiously because of the small numbers, overlap with another study, and multiple exposure of some parents. It is important to distinguish periods of parental exposures; identified risk factors were almost exclusively restricted to the time before the child's birth. 
L-tryptophan-induced eosinophilia-myalgia syndrome. This report describes three Belgian cases of the eosinophilia-myalgia syndrome associated with the use of L-tryptophan-containing products. Three women, aged 51, 53 and 73 years, were taking L-tryptophan for 2 months to 2 years, at 500, 1500, and 2250 mg d-1, respectively. All developed disabling myalgias, fatigue, and a variable skin rash, in association with marked eosinophilia. In one patient, symptoms and eosinophilia reappeared after rechallenge with L-tryptophan. Discontinuation of the drug resulted in gradual disappearance of the symptoms, signs and laboratory abnormalities in two patients. One patient was treated with corticosteroids because of persisting myalgias. Because of the non-specific clinical manifestations, clinicians from all subspecialties of internal medicine might be confronted with such patients and should be aware of this new entity. 
Mitral valve prolapse, panic disorder, and chest pain. Mitral valve prolapse is a common cardiac disorder that can readily be diagnosed by characteristic auscultatory and echocardiographic criteria. Although many diseases have been associated with mitral valve prolapse, most affected individuals have the primary form of the disorder. Mitral valve prolapse is an inherited condition commonly associated with myxomatous degeneration of the mitral valve and its support structures. Complications of mitral valve prolapse, including cardiac arrhythmias, sudden death, infective endocarditis, severe mitral regurgitation (with or without chordae tendineae rupture), and cerebral ischemic events, occur infrequently considering the wide prevalence of the disorder. Panic disorder is a specific type of anxiety disorder characterized by at least three panic attacks within a 3-week period or one panic attack followed by fear of subsequent panic attacks for at least 1 month. It too is a common condition with a prevalence and age and gender distribution similar to that of mitral valve prolapse. Panic disorder and mitral valve prolapse share many nonspecific symptoms, including chest pain or discomfort, palpitations, dyspnea, effort intolerance, and pre-syncope. Chest pain is the symptom in both conditions that most commonly brings the patient to medical attention. The clinical description of chest pain in patients with mitral valve prolapse is highly variable, possibly reflecting multiple etiologies. Chest pain in panic disorder is usually characterized as atypical angina pectoris and as such bears resemblance to the chest pain commonly described by patients with mitral valve prolapse. Multiple investigative attempts to elucidate the mechanism of chest pain in both conditions have failed to identify a unifying cause. Review of the literature leaves little doubt that mitral valve prolapse and panic disorder frequently co-occur. Given the similarities in their symptomatology, a high rate of co-occurrence is, in fact, entirely predictable. There is, however, no convincing evidence of a cause-effect relationship between the two disorders, nor has a single pathophysiologic or biochemical mechanism been identified that unites these two common conditions. Until specific biologic markers for these disorders are identified, it may be impossible to do so. The lack of a proven cause-and-effect relationship between mitral valve prolapse and panic disorder and the absence of a unifying mechanism do not diminish the clinical significance of the high rate of co-occurrence between the two conditions. Primary care physicians and cardiologists frequently encounter patients with mitral valve prolapse and nonspecific symptoms with no discernible objective cause who fail to respond to beta-blockade. Panic disorder should be considered as a possible explanation for symptoms in such patients.(ABSTRACT TRUNCATED AT 400 WORDS). 
Induction of the protooncogene c-fos and recovery of cytosolic adenosine triphosphate in reperfused liver after transient warm ischemia: effect of nitrone free-radical spin-trap agents. Ischemia and reperfusion stimulate several adenosine triphosphate (ATP)-dependent processes involving release of substances including free radicals. This cellular response is mediated through receptors responsive to transcriptional products of gene expression; c-fos acts as a transcriptional factor involved in the regulation of genes associated with cellular proliferation and differentiation. We hypothesized that nitrone free-radical spin traps promote restoration of cytosolic ATP during reperfusion and prevent c-fos induction. Four control rats had no ischemia. Global hepatic ischemia was induced in 19 rats in four groups: saline solution, phenyl-N-tert-butyl nitrone (PBN), alpha 1-pyridyl-N-oxide N-tert-butyl nitrone (POBN), and 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). ATP and intracellular pH were measured at intervals before, during, and after ischemia. At 90 minutes of reperfusion, liver c-fos mRNA was measured. A fourfold elevation of c-fos occurred in the saline-treated group (p less than 0.001). PBN and POBN groups did not differ from the saline group. DMPO resulted in significantly less induction of c-fos than did NS. ATP depletion and recovery in all treatment groups was similar to that of the saline group. We conclude that (1) nitrone spin traps do not prevent c-fos induction or alter the pattern of ATP recovery after hepatic ischemia and reperfusion and (2) c-fos induction is not necessary for restoration of ATP, but the rate of ATP restoration is inversely related to c-fos induction. 
Localization of the translocation breakpoint in a female with Menkes syndrome to Xq13.2-q13.3 proximal to PGK-1. Menkes syndrome is a rare X-linked recessive disorder characterized by an inability to metabolize copper. A female patient with both this disease and an X; autosome translocation with karyotype 46,X,t(X;2)(q13;q32.2) has previously been described. The translocation breakpoint in Xq13 coincides with a previous assignment of the Menkes gene at Xq13 by linkage data in humans and by analogy to the mottled mutations which are models for Menkes disease in the mouse. Therefore, this translocation probably interrupts the gene for Menkes syndrome in band Xq13. We describe here experiments to precisely map the translocation breakpoint within this chromosomal band. We have established a lymphoblastoid cell line from this patient and have used it to isolate the der(2) translocation chromosome (2pter----2q32::Xq13----Xqter) in human/hamster somatic cell hybrids. Southern blot analyses using a number of probes specific for chromosomes X and 2 have been studied to define precisely the location of the translocation breakpoint. Our results show that the breakpoint in this patient--and, therefore, likely the Menkes gene--maps to a small subregion of band Xq13.2-q13.3 proximal to the PGK1 locus and distal to all other Xq13 loci tested. 
Solitary extradural cavernous hemangiomas in the spinal canal. Report of five cases. Five cases of solitary extrathecal cavernous hemangioma in the spinal canal are reported. In one case, two coexistent massive cerebral venous medullary malformations were found. The symptomatology and prognosis of extrathecal spinal cavernous hemangiomas are discussed, as is the significance of various diagnostic measures. The patient material further permitted a rough calculation of the incidence of symptomatic extrathecal cavernous hemangiomas in the spinal canal. 
Transesophageal echocardiography: a simple method for monitoring the patency of ventriculoatrial shunts. Technical note. A new method for evaluating the patency of a ventriculoatrial shunt is described, and early experience with it is reported. Transesophageal echocardiography can demonstrate a cerebrospinal fluid leak in the right atrium through the atrial tip of a shunting device. This capability was an incidental discovery, and since then the accuracy of the technique in evaluating the patency of a ventriculoatrial shunt has been prospectively studied in 20 observations of 16 patients. The method proved to be accurate in 90% to 100% of cases. It is concluded that transesophageal echocardiography offers a rapid and accurate assessment of ventriculoatrial shunt function, is well tolerated, and is easy to perform. 
Heterotopic ossification and peripheral nerve entrapment: early diagnosis and excision. Heterotopic ossification can occur in neurologic disorders, burns, musculoskeletal trauma, and metabolic disorders. In addition to producing the complications of contracture, skin breakdown, and pain, it can cause peripheral nerve entrapment. Nerve entrapment due to heterotopic ossification may be misdiagnosed, and it is difficult to evaluate and treat without recurrence. Computed tomography is especially useful in localization before surgical release of the entrapped nerve. Resection of heterotopic ossification can be successful using disodium etidronate to decrease the risk of recurrence, and resection can improve range of motion and nerve function. Two case studies of nerve entrapment due to heterotopic ossification are presented with the results of computed tomography localization, successful resection, and long-term follow-up. Clinicians should be aware of this complication and the potential for rapid nerve injury. If heterotopic ossification is causing clinically significant peripheral nerve entrapment, early surgical treatment may be indicated, and may be successful. 
The effect of chronic orthopedic infection on quality of life. The patient with chronic orthopedic infection presents a unique challenge to the orthopedic surgeon. The orthopedic surgeon must not only possess an expertise in constantly evolving diagnostic and treatment techniques but also be able to identify numerous related problems and direct the patient in receiving the most appropriate treatment. This demands a commitment of time by the treating surgeon to the individual patient to properly assess the need for support, the extent of psychologic distress, the intensity of pain, and the requirement for medication management. The effective utilization of a multidisciplinary team of health care providers (e.g., specialists in infectious disease, physical medicine and rehabilitation, psychiatry, nursing, pharmacology) can provide an optimal treatment program for this multifaceted problem and maximize the potential for a favorable outcome. 
Cellular energy metabolism during hypoxia. Tissue hypoxia is frequently seen in critically ill patients and it perhaps predisposes these patients to development of multiple system organ failure. In cellular terms, hypoxia is characterized by decreases in the intracellular concentration of oxygen, leading to a decline in aerobically produced adenosine triphosphate (ATP). The deficit arising from unequal levels of cellular ATP requirements and aerobic ATP production is partially satisfied by anaerobic sources of ATP, including glycolysis, the creatine kinase reaction, and the adenylate kinase reaction. These reactions can set in motion cellular mechanisms that ultimately may lead to cellular dysfunction and death. A clear understanding of the relative importance of these reactions is impossible to acquire from global measures of oxygen delivery and oxygen consumption; therefore, the clinical monitoring of tissue oxygenation also should include the measurement of metabolically relevant, organ-specific variables. 
Acoustic neuroma (schwannoma) surgery 1978-1990. A series of 151 patients with 154 acoustic schwannomas have been operated upon in Manchester Royal Infirmary by a joint Otological and Neurosurgical team, employing either the translabyrinthine or the suboccipital approach. The perioperative mortality rate was 3 per cent. Anatomical preservation of the facial nerve was achieved in 89 per cent of tumour removals and a good to normal functional result in 79 per cent of cases. Attempts at hearing preservation have been unsuccessful, largely because of the small number of patients in the series in whom useful hearing was present preoperatively. Complications included major brain stem ischaemia (1.2 per cent), CSF fistula (5 per cent) and facial dysaesthesia (7 per cent). The incidence of mortality and morbidity is directly related to tumour size and to the experience of the surgeons. A number of patients experienced an unusual type of post-operative dreamlike state which appeared to be a form of hypnagogic hallucination, and the possible neurophysiological mechanism responsible for this phenomenon is discussed. The continuing failure to attain the ideal of early diagnosis is lamented, and the importance of a flexible bidisciplinary surgical approach emphasized. 
Mitochondrial encephalomyopathies in childhood. II. Clinical manifestations and syndromes. During a 4-year period 1984 to 1988, 20 children referred with manifestations of central nervous system or neuromuscular disease combined with hyperlactatemia were found to have a mitochondrial disease. Each diagnosis was based on the results of thorough biochemical and morphologic investigations. The patients were separated into one series with mainly encephalopathy (n = 14) and another with mainly myopathy (n = 6). The patients with encephalopathy had the following syndromes: Kearns-Sayre (n = 2), MERRF (myoclonus epilepsy and ragged red fibers; n = 2), MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes; n = 3), Alpers (n = 3), Leigh (n = 1), and other variants (n = 3). In patients with myopathy, three had hypertrophic nonobstructive cardiomyopathy. Ultrastructural abnormalities of mitochondria were the most common morphologic changes in the muscle biopsies. Complex I deficiency was most common in the patients with encephalopathy. All of the patients with myopathy had complex IV deficiency. Mutations of mitochondrial DNA were found in six patients with encephalopathy. We conclude that identification of defects at the DNA level and determination of the phenotypic expression with clinical, morphologic, and biochemical methods are fundamental for future rational classification of mitochondrial disorders. 
Cervicomedullary junction decompression in a case of Marshall-Smith syndrome. Case report. The case is reported of a 2-year-old boy born with Marshall-Smith syndrome who had difficulty in swallowing and who exhibited spasticity and quadriparesis due to compression of the medulla and cervical spine. This is the first child with this rare condition reported to have brain-stem compression from bone abnormalities at the craniovertebral junction and who has required surgery. 
Histological and morphometrical indicators for a biopsy diagnosis of well-differentiated hepatocellular carcinoma. Among 597 patients with nodular hepatic lesions who underwent ultrasonically guided needle biopsy, 305 were histologically confirmed as having hepatocellular carcinoma, and 37 patients had borderline lesions. Histological reexamination was correlated with morphometrical analysis on selected cases of well-differentiated, microtrabecular hepatocellular carcinomas (n = 29), borderline lesion (n = 10), typical (mid-sized and macrotrabecular) hepatocellular carcinomas (n = 15) and cirrhotic liver tissue obtained from extranodular hepatic parenchyma of hepatocellular carcinoma patients (n = 47). Morphometrical analyses revealed that the mean cell size and nucleocytoplasmic ratio were most useful for distinguishing well-differentiated, microtrabecular hepatocellular carcinoma from cirrhosis. These two parameters were well correlated with nuclear density. The grade of nuclear density, therefore, seemed to be a convenient semiquantitative indicator for diagnosing well-differentiated hepatocellular carcinoma. A comparison between intranodular and extranodular hepatic tissues was particularly important for its assessment. It is concluded from the results that hepatic nodules presenting a nuclear density larger than two times that of controls could be classified into the overt hepatocellular carcinoma group. From the statistical aspect, the possibility of microtrabecular hepatocellular carcinoma should be considered when a nodule has a nuclear density exceeding 1.3 times that of the extranodular tissue. 
Pure akinesia: an atypical manifestation of progressive supranuclear palsy. Two patients with "pure akinesia" who showed the characteristic changes of progressive supranuclear palsy (PSP) at necropsy are described. They had akinesia but no rigidity or tremor, and ophthalmoplegia was not observed during the course of illness. The symptoms of "pure akinesia" was not improved by levodopa therapy but was considerably improved by L-threo-3,4-dihydroxy-phenylserine. At necropsy, pathological findings were not different from those reported for PSP. It is suggested that "pure akinesia" is an atypical manifestation of PSP, and that norepinephrinergic neurons may be involved in some types of PSP. 
Catalase-negative listeria monocytogenes causing meningitis in an adult. Clinical and laboratory features. A 63-year-old previously healthy woman presented with acute meningitis. Cultures of the cerebrospinal fluid yielded a serotype 1/2a isolate of Listeria monocytogenes that was biochemically typical in all respects, other than the reproducible lack of catalase production. During therapy, the patient developed oculomotor dysfunction that was attributed to an abscess in the internal capsule. This case report documents the existence of catalase-negative L. monocytogenes indicating that catalase production should not be a strict criterion for identification of Listeria. Furthermore, this clinical experience extends in vitro and experimental animal studies indicating that catalase production is not a necessary virulence factor for invasion by Listeria. 
Intra-arterial thrombolytic therapy in the management of acute and chronic limb ischaemia. A group of 54 patients with acute or chronic limb ischaemia were initially treated with low dose intra-arterial thrombolytic therapy using streptokinase (10,000 units h-1) or plasminogen activator (0.5 mg h-1). Complete thrombolysis was obtained in 90 per cent of patients with symptoms of less than 1 week duration, and in 50 per cent with symptoms of greater than 1 week (P less than 0.05). Successful lysis in 36 patients was followed by successful bypass surgery in seven, percutaneous angioplasty in 13, no further treatment in 13, repeat thrombolysis in two and amputation in one. Failed therapy was associated with major amputation in 40 per cent. One patient died of haemorrhage and another of stroke as a direct result of thrombolytic treatment. The most common complication was haematoma at the site of cannulation of the vessel. Intra-arterial thrombolytic therapy can be very useful for the management of acute and chronic limb ischaemia, but complications do occur and patients should be carefully selected. 
Limited hepatic resection for selected cirrhotic patients with hepatocellular or cholangiocellular carcinoma: a prospective study. From 1 January 1983 to 1 January 1989 123 cirrhotic patients with hepatocellular cancer (n = 122) or cholangiocarcinoma (n = 1) were screened using liver function tests, alpha-fetoprotein determination, ultrasonography with biopsy (and in selected cases computed tomography or nuclear magnetic resonance), laparoscopy and angiography, Child-Pugh classification and urea-nitrogen synthesis rate. Twenty-three patients were selected for surgical resection because the tumour was smaller than 5 cm, not centrally located and at least 1 cm away from main structures; there was no evidence of multicentricity or metastatic disease; and the Child-Pugh classification was A or B and the urea-nitrogen synthesis rate at least 6 g/day. Upper gastrointestinal endoscopy was used routinely to identify oesophageal varices which were present in 17 cases; ten patients with a history of variceal haemorrhage (43 per cent) had preoperative endoscopic sclerotherapy. In cases with recurrent haemorrhage, surgery was used to prevent intraoperative and postoperative bleeding. Tumour resection was carried out using controlled hypotension and hepatoduodenal ligament clamping. Twelve bisegmentectomies, ten segmentectomies and one atypical resection were performed. The operative mortality rate was 13 per cent with liver failure and sepsis as the causes of death. The 'recurrence rate' was 26 per cent and the late mortality rate for the whole group up to 1 January 1990 was 30 per cent; 13 patients were still alive. The 12-month survival rate was 77 per cent and after 5 years it was 49 per cent. Thus, surgical resection of small liver tumours is the treatment of choice in this selected group of patients. 
Clinical and biologic features of childhood T-cell leukemia with the t(11;14). Cytogenetic analysis of cells from 622 consecutive patients with newly diagnosed acute lymphoblastic leukemia (ALL) and successful G-banding chromosome studies disclosed seven cases with the t(11;14)(p13;q11) and one with the t(11;14)(p15;q11). Leukemia cells in all eight cases had a T-cell immunophenotype. The t(11;14)(p13;q11) occurred in 6.8% and the t(11;14)(p15;q11) in 1% of T-cell ALL cases (n = 103). The t(11;14) was associated with presenting clinical features typical of T-cell ALL: male predominance (n = 6), age greater than 10 years (n = 3), hyperleukocytosis (white blood cells greater than 100 x 10(9)/L, n = 5), relatively high hemoglobin level (median, 10.8 g/dL), high serum lactic dehydrogenase level (median, 3248 U/L), presence of mediastinal mass (n = 6), and central nervous system leukemia (n = 2). While there were no significant differences in presenting features between T-cell ALL cases with or without the t(11;14), leukemic cells from patients with the translocations were more likely to coexpress CD4 and CD8 antigens (6 of 6 v 35 of 86 cases tested, P less than .05). Adverse events have occurred in six patients: three central nervous system relapses [including the one with t(11;14)(p15;q11)], two secondary acute myeloid leukemia, and one hematologic relapse. Our results indicate that the t(11;14)(p13;q11) occurs exclusively in T-cell malignancies of intermediate- or late-stage thymocyte differentiation. Additional studies are needed to determine the prognostic implications of these translocations. 
Spinal leptomeningeal metastasis from cerebral glioblastoma. Appearance on magnetic resonance imaging. A case of circumferential leptomeningeal metastasis to the spinal cord from an intracranial glioblastoma multiforme (spinal meningeal gliomatosis) is presented. The clinical, radiographic, and pathological features are described. Spinal magnetic resonance imaging with gadolinium-diethylenetriaminepentaacetic acid accurately demonstrated the spread of disease when compared with autopsy findings. The value of spinal magnetic resonance imaging in patients with symptoms attributable to cerebrospinal fluid metastases is discussed. 
Supravalvar aortic stenosis: a 29-year review of surgical experience Between February 1960 and August 1989, 73 consecutive patients underwent surgical correction for supravalvar aortic stenosis (SVAS) at the Texas Heart Institute. There were 43 male (59%) and 30 female patients (41%) ranging in age from 5 days to 27 years (mean age, 12 years). Preoperatively, 8 patients were in New York Heart Association functional class I, 43 in class II, 18 in class III, and 4 in class IV. Of the 73 patients, 62 had localized SVAS and 11 (15%), diffuse SVAS. For all procedures, patients were placed on cardiopulmonary bypass. Those with localized SVAS were successfully treated with patch aortoplasty, whereas those with diffuse SVAS required either an apicoaortic conduit or extensive end-arterectomy with extended patch aortoplasty. There were eight early deaths (less than or equal to 30 days postoperatively) (11%) and four late deaths (greater than 30 days postoperatively) (6%) in a follow-up period ranging from 2 months to 28 years. Sixteen patients (25%) underwent one or more additional operations in the follow-up period. Postoperatively, there were 44 patients in New York Heart Association functional class I and 17 in class II. Preoperative functional class III and class IV (p less than 0.0005), diffuse SVAS (p = 0.05), and the presence of associated congenital defects (p less than 0.01) were important determinants of death. 
Visual evoked potentials and visual acuity after transurethral resection of the prostate. Changes in visual evoked potentials, visual acuity, blood ammonia levels and serum electrolytes (Na+ and K+) after transurethral resection of the prostate using glycine as an irrigating fluid performed under subarachnoid block were studied in 12 patients, in the pre-operative and immediate postoperative periods. Visual evoked potentials (p100 latency), recorded by shift of a checkerboard pattern, increased significantly from a pre-operative value of mean (SEM) 101.18 (1.63) msec in the right eye, and 102.5 (1.47) msec in the left eye to 108.91 (1.8) msec (p less than 0.01) and 108.08 (2.53) msec (p less than 0.01) respectively in the postoperative phase. There were no changes in visual acuity as assessed by a Snellen's chart, blood ammonia levels and serum electrolyte concentrations. The amount of glycine used intra-operatively for irrigation ranged from 3 to 31 litres. 
Alzheimer's disease with delusions and hallucinations: neuropsychological and electroencephalographic correlates. We longitudinally evaluated the neuropsychological functions, rate of progression, and waking EEG findings in 17 patients with probable Alzheimer's disease (AD) with delusions and hallucinations, and compared them with those of matched AD patients without delusions and hallucinations. AD patients with delusions and hallucinations had a more rapid rate of decline, as measured by the Mini-Mental State Examination, a specific defect in receptive language, and a greater frequency of aggression and hostility. Visual EEG analysis showed that these patients had a significantly greater proportion of moderately abnormal EEGs, and spectral analysis confirmed the increased amount of delta and theta activity. These data demonstrate that AD patients with delusions and hallucinations have a greater degree of cerebral dysfunction and a relatively focal neuropsychological defect, which may indicate a localized pathologic abnormality. 
Williams syndrome: masseter spasm during anaesthesia. A 4-year-old boy with Williams syndrome developed masseter spasm after halothane and suxamethonium. He did not develop malignant hyperthermia; the surgery was accomplished with a nontriggering anaesthetic and no further problems. 
Inappropriate use of transillumination for breast cancer screening--Wisconsin, 1990. The overall effectiveness of early breast cancer detection efforts requires the appropriate use and maintenance of dedicated radiographic mammography systems. However, the effectiveness of early detection efforts can be compromised if proven technology is improperly used and/or maintained or if ineffective technology is successfully marketed as an equivalent or superior alternative to mammography. This report summarizes state and federal responses to the inappropriate use of a nonradiographic imaging technique in a breast cancer screening service advertised and used in Wisconsin in 1990. 
Thallium stress testing does not predict cardiovascular risk in diabetic patients with end-stage renal disease undergoing cadaveric renal transplantation. PURPOSE: This study assessed the usefulness of thallium stress testing as a predictor of perioperative cardiovascular risk in diabetic patients with end-stage renal disease undergoing cadaveric renal transplantation. Demographic factors influencing the exercise performance in these patients were also examined. PATIENTS AND METHODS: The medical records of 189 consecutive patients with diabetic nephropathy who were evaluated for cadaveric renal transplantation were reviewed. Thallium stress testing was the initial examination of cardiovascular status in 141 patients. An adequate examination was one in which at least 70% of maximum heart rate was achieved. A thallium stress test was normal if there were no ST segment depressions on the electrocardiogram and no perfusion abnormalities on the thallium scan. Forty-four patients underwent cardiac catheterization as the initial evaluation (Group C) and four patients underwent transplantation without a formal cardiovascular evaluation (Group D). RESULTS: Sixty-four of the 141 patients undergoing thallium stress testing had an adequate and normal examination (Group A). The incidence of perioperative cardiac events in this group was 2%. Seventy-seven patients (Group B) had an abnormal (n = 41) or an inadequate (n = 36) thallium stress test and most (n = 61) then underwent coronary angiography. The use of beta-blockers was the only predictor of an abnormal or inadequate thallium stress test (10 of 64 versus 27 of 77, chi 2 = 6.66, p less than or equal to 0.025). Forty-three percent (26 of 61 in Group B) of patients with inadequate or abnormal thallium stress tests had significant coronary artery disease on cardiac catheterization. The perioperative risk of cardiac events was not different in Group A versus Groups B, C, and D combined. Survival of Group A and B patients was not different but was significantly longer than that of Group C patients (p less than 0.001). Thallium stress testing was less expensive than cardiac catheterization ($1,000 versus $4,000 to $5,000). CONCLUSIONS: Thallium stress testing allowed 45% of patients to avoid cardiac catheterization before renal transplantation. Discontinuing beta-blockers before thallium stress tests may improve exercise performance. The risk of perioperative cardiac events after transplantation was low and not different among patient groups. The relatively low predictive value of thallium stress testing for significant coronary artery disease and perioperative cardiac events in diabetic patients with end-stage renal disease suggests the need for the development of a more cost-effective, noninvasive screening test for this patient population. 
Diagnosis of portal vein thrombosis: value of color Doppler imaging. This study was undertaken to determine the accuracy of color Doppler imaging in the diagnosis of portal vein thrombosis. Two hundred fifteen patients were studied with color Doppler imaging to determine patency of the main portal vein. Sonographic findings were confirmed in 75 patients, aged 19 to 66 years. Correlation with angiography was obtained in 13 patients, and surgical correlation was obtained in the remaining 62. Nine patients had portal vein thrombosis on the basis of these gold standards. Sonograms were classified as showing either patency or thrombosis, depending on the ability to show color flow within the main portal vein. Agreement between sonography and angiography or surgery was found in 69 patients (61 patent, eight thrombosed). One patient with a patent portal vein at sonography was found to have a thrombosed vessel at surgery, whereas five patients without portal venous flow at sonography had patent vessels at angiography (one patient) or surgery (four patients). Overall sensitivity and specificity for detection of portal vein thrombosis were 89% and 92%, with an accuracy of 92%, a false-negative rate of 0.11, a negative predictive value of 0.98, and a positive predictive value of 0.62. We postulate that the majority of errors in our study occurred in vessels that, although patent, had only sluggish flow, which could not be resolved because of technical limitations. We conclude that color Doppler imaging is a valuable screening procedure for the assessment of portal vein patency. If the sonogram shows a patent portal vein, no further studies are required. However, a lack of demonstrable flow does not always indicate thrombosis, and other imaging studies should be performed for confirmation. 
Local control and survival from the Cooperative Osteosarcoma Study Group studies of the German Society of Pediatric Oncology and the Vienna Bone Tumor Registry. The use of aggressive chemotherapy undoubtedly has brought about a dramatic increase in the cure rate of osteosarcoma. The authors' investigations have increased the authors' knowledge of chemotherapy for osteosarcoma, the differential efficacy of currently used agents, and the pronounced schedule dependency and relative route independency of their efficiency. The authors were able to confirm the prognostic significance of tumor response after preoperative chemotherapy. Preoperative chemotherapy in itself has facilitated and promoted limb-salvage surgery. Also, more patients can be cured today by use of aggressive thoracic surgery in case of primary or secondary pulmonary metastases. The authors' efforts to steadily increase metastasis-free survival rates by intensifying chemotherapy in this series of studies, however, have been only moderately successful. Still, chemotherapy-related acute toxicity is considerable and increases with aggressiveness of treatment, and the manifestations of late toxicity may continue to increase with follow-up time. Future trials should be targeted toward exploration of the minimum indispensable amount of toxic treatment yielding comparable or even better results than those currently attainable. 
Rupture of the posterior wall of the left ventricle after mitral valve replacement. During a 20 year period from 1970 to 1989, 1100 patients underwent mitral valve replacement. Rupture of the posterior wall of the left ventricle occurred in seven patients (0.6%); four in the operating room and three in the postoperative room. It was possible to institute CP bypass in six patients and in all of them bleeding was controlled successfully, with repair by an external approach. Only one patient survived. We believe that institution of CP bypass and reinfusion of cardioplegic solution is a major determinant of the outcome. 
Heterogeneity of immunotypes of heat-labile enterotoxins of enterotoxigenic Escherichia coli of human origin. A new technique, checkerboard immunoblotting (CBIB), has been applied to detect and to differentiate heat-labile enterotoxins, (LTs), from enterotoxigenic strains of Escherichia coli of human origin using polyclonal and monoclonal antibodies. Optimal conditions of production and release of LTs were defined using CBIB. LT release was enhanced when E. coli cells were treated with 8 M urea. LT production was highest when E. coli strains were incubated with shaking (200 rpm) at 37 degrees C for 12 h in CAYE-2 medium. Two hundred and five strains of E. coli, isolated from patients with diarrhea in Japan, Thailand, the United States, Mexico, and Brazil, were examined for LT. Of 133 LT-positive strains, 4 (3%) produced an LT that reacted like H-LT-1 (originally isolated from E. coli strain H-74-114) while 126 strains (94.7%) produced LT that reacted like H-LT-2 (originally isolated from strain H-10407) or H-LT-3 (from strain H-240-3). Three strains of human origin (2.3%) produced an LT that reacted like P-LT (produced by E. coli strains of porcine origin). This study shows that CBIB, a simple, efficient, and practical assay, might be useful for epidemiologic surveys and for evaluation of serologic responses to LTs and antitoxic vaccines. 
Role of von Willebrand factor in arterial thrombosis. Studies in normal and von Willebrand disease pigs. With normal and von Willebrand disease (vWD) pigs, we studied the role of von Willebrand factor (vWF) in platelet-vessel wall interactions and occlusive arterial thrombosis. Two methods of arterial injury have been used to determine the thrombotic response of flowing blood in vivo. The first involves balloon catheter injury. After superficial denudation of endothelium from coronary intima, platelets adhere to the subendothelium in a monolayer. Similar numbers of adherent platelets are found in both phenotypes, but platelets in vWD pigs have impaired pseudopod formation and are less well spread morphological indexes of limited platelet activation. Deeper injury, which involves the media, produces nonocclusive platelet-fibrin microthrombi. The second injury method involves pinching the artery at a site of superimposed stenosis, a procedure that almost always exposes media. This procedure induces platelet-fibrin microthrombi in normal and vWD pigs, but only normal pigs develop occlusive thrombosis. Both methods of arterial injury have also been performed in normal and vWD pigs with diet-induced hypercholesterolemia and atherosclerosis. Atherosclerosis promotes platelet spread in vWD pigs but does not abolish the protection from stenosis and injury-induced occlusive thrombosis. In addition, neutralization of vWF activity in normal pigs by a monoclonal antibody prevents the induction of occlusive thrombosis by the stenosis and pinch-injury procedure. This monoclonal antibody also causes performed platelet aggregates to break up. These experimental models of inducing arterial thrombosis have been used in normal and vWD pigs to demonstrate interactions between normal and atherosclerotic vessel wall constituents, circulating platelets and vWF that are fundamental in the process of arterial thrombosis. 
Serum zinc, copper, and selenium levels in inflammatory bowel disease: effect of total enteral nutrition on trace element status. Serum levels of zinc, copper, and selenium, and alkaline phosphatase activity were prospectively studied in 29 patients with inflammatory bowel disease. Fifteen patients had extensive active colitis (active colitis group). Seven patients had active, and seven cases inactive small bowel or ileocecal Crohn's disease (small bowel disease group). Ninety-three healthy subjects acted as controls. Serum trace element levels were considered in relation to vitamin A and E levels, nutritional parameters, the activity of the disease, and the recent intake of steroids. The effect of total enteral nutrition on serum trace elements was studied in seven cases. Serum zinc levels were lower and serum copper levels higher in the active colitis group than in controls (p = 0.0007, and p = 0.02, respectively). More than 50% of patients with active colonic or small bowel disease showed zinc levels below the 15th percentile of the control group. Serum zinc levels correlated with plasma vitamin A in acute colitis (r = 0.67; p = 0.006), and with both serum albumin concentration (r = 0.76; p = 0.002) and disease activity score (r = -0.67, p = 0.009) in patients with small bowel disease. The copper:zinc ratio was higher in the active colitis group than in controls (p = 0.002). In spite of the increase in serum albumin levels and the decrease in disease activity, serum zinc levels remained low after total enteral nutrition. The implications of the abnormal trace element status in patients with inflammatory bowel disease are discussed. 
Tranexamic acid treatment of hemothorax in two patients with malignant mesothelioma. Patients with malignant mesothelioma may present with hemothorax. We used a combination of oral and intrapleural tranexamic acid to treat two patients with this severe complication. Initiation of treatment with this potent anti-fibrinolytic drug resulted in rapid reduction of bleeding and of transfusion requirements. 
Peripheral nerve lesions in hemophilia. Between 1962 and 1986, eighty-one of the 1351 admissions of patients who had hemophilia to the Nuffield Orthopaedic Centre were for peripheral nerve lesions. Eighty-eight such lesions were identified in fifty-four patients, and thirty-nine of these patients (sixty-one lesions) had adequate follow-up (mean, 8.4 years; range, four months to eighteen years). The femoral nerve was most commonly involved, but involvement of other peripheral nerves also occurred. In thirty (49 per cent) of the sixty-one lesions, the nerve had full motor and sensory recovery; in twenty-one (34 per cent), a residual sensory deficit; and in ten (16 per cent), both a persistent motor and sensory deficit. Patients who had antibodies to factor VIII were significantly less likely to recover full motor or sensory function than were those who did not have such antibodies, and the time to full motor recovery in these patients was significantly longer. 
Mammography in the management of patients with small breast cancers. Findings on mammography resulted in a change of treatment policy in 17 of 200 patients with small breast cancers (T1/T2 less than 4 cm, N0/N1, M0). Twelve patients were considered unsuitable for conservation therapy because of mammographic evidence of either extensive in situ carcinoma or more than one focus of invasive carcinoma. These patients were treated by mastectomy and histology confirmed widespread in situ carcinoma or multifocal/multicentric invasive carcinoma. Seven patients were found to have unsuspected contralateral lesions on mammography, of which five were subsequently shown to be malignant. Routine preoperative mammography is essential in the management of patients with small breast cancers. 
Treating insulin resistance in hypertension with metformin reduces both blood pressure and metabolic risk factors. Insulin resistance and hyperinsulinaemia may play an important role in both the development of hypertension and its accompanying metabolic aberrations. In order to investigate this possibility, nine non-obese, non-diabetic, non-smoking, middle-aged men with untreated hypertension were treated with metformin 850 mg b.i.d. for 6 weeks as a pilot study and within-patient comparison. Metformin decreased total and LDL-cholesterol (P less than 0.01), triglyceride (P less than 0.01), fasting plasma insulin (P less than 0.01) and C-peptide levels (P less than 0.02). Glucose disposal, an indicator of insulin action measured by means of the euglycaemic clamp technique, increased (P less than 0.001). Tissue plasminogen activator (t-PA) activity increased (P less than 0.02), and t-PA antigen decreased (P less than 0.01), whereas plasminogen activator inhibitor (PAI-1) and fibrinogen were unaffected by metformin treatment. Body weight remained unchanged. Withdrawal of metformin was associated with the return of both blood pressure and metabolism towards the initial levels. In conclusion, metformin treatment increased insulin action, lowered blood pressure, improved the metabolic risk factor profile and tended to increase the fibrinolytic activity in these mildly hypertensive subjects. These results support the view that insulin resistance plays a role in hypertension, and may open up a new field for the alleviation of abnormalities associated with cardiovascular disease. 
Generalized cortical dysplasia. Clinical and pathologic aspects. Three children with profound mental retardation and intractable seizures died at ages 10 months, 3 years, and 7 years, respectively. Complete examination of their brains showed generalized cortical dysplasia, without any major malformation of the external gyral pattern. The neuropathologic features of cortical dysplasia include abnormally thickened cortex with indistinct demarcation of the gray-white matter junction. In many areas, the cortex contained increased numbers of large neurons with disordered cortical lamination. Heterotopic neurons were scattered throughout the white matter with decreased myelination of the underlying white matter. To our knowledge, these cases represent the first fully detailed neuropathologic study of diffuse cortical dysplasia--a newly recognized entity of abnormal neuronal migration. 
Alcohol induction of ferritin expression in a human hepatoblastoma cell line (HEP G2). Hyperferritinemia, an unclear mechanism, is frequently observed in chronic alcoholics. The aim of this work was to study the effect of alcohol on ferritin expression in a human hepatoblastoma cell line, HepG2. This cell line proved to be sensitive to alcohol, since alcohol increased gamma-GT activity both in cells and media. The most striking result was the increase of ferritin in cells and media by alcohol. Moreover, this effect was specific, since it contrasted with a decrease in total protein synthesis and secretion, a decrease in transferrin excretion and a lack of effect on orosomucoid. In our model, alcohol was able to induce, in a specific manner, ferritin expression. 
Comparison of the findings on preoperative dipyridamole perfusion scintigraphy and intraoperative transesophageal echocardiography: implications regarding the identification of myocardium at ischemic risk. The evidence of myocardium at potential ischemic risk on preoperative dipyridamole perfusion scintigraphy was compared with that of manifest ischemia on intraoperative transesophageal echocardiography in 26 patients at high risk of a coronary event undergoing noncardiac surgery. The clinical outcome was also assessed. Induced intraoperative wall motion abnormalities were more common in patients and myocardial segments with, than in those without, a preoperative reversible perfusion defect (both p less than 0.05). Conversely, a preoperative reversible perfusion defect was more common in patients and segments with, than in those without, a new intraoperative wall motion abnormality (both p less than 0.05). Six patients, five with a reversible scintigraphic defect but only three with a new wall motion abnormality, had a hard perioperative ischemic event. Events occurred more often among patients with, than in those without, a reversible perioperative scintigraphic defect (5 [33%] of 15 vs. 1 [9%] of 11) but this difference did not reach significance (p = 0.14), probably owing to the sample size. Intraoperative wall motion abnormalities were all reversible and did not differentiate between risk groups; these findings were possibly influenced by treatment. These preliminary data support the known relation between reversible scintigraphic defects and perioperative events and identify another manifestation of ischemic risk in the relation between reversible scintigraphic defects and induced intraoperative wall motion abnormalities. The value of intraoperative echocardiography in identifying ischemia and guiding therapy in patients with a reversible scintigraphic abnormality should be further assessed. 
Recognition, management, and prevention of Clostridium septicum abscess in immunosuppressed patients. Spontaneous gas gangrene due to Clostridium septicum is a rapidly progressing disease that usually ends in fatal toxemia. We report three cases of asymptomatic C septicum abscesses to document the clinical course of this entity and to establish guidelines for its prevention and treatment. In contrast to previously reported data, C septicum infections can produce abscesses in solid organs, the retroperitoneum, and the extremities. These lesions often occur in patients with cancer, producing liver abscesses without gas formation that may be misinterpreted as metastatic carcinoma. Symptoms may be minimal or nonspecific before fulminant toxemia. Asymptomatic bacteremia should prompt a search for unsuspected cancer and an abscess. Computed tomography is the diagnostic modality of choice. The treatment consists of surgical debridement of necrotic tissue in concert with an appropriate course of antibiotics. We have found recurrences after adequate debridement and short-term antibiotic therapy, suggesting that prolonged and even lifelong prophylactic oral penicillin G potassium may be necessary to prevent further recurrences. 
Time course of hypoxic pulmonary vasoconstriction after endotoxin infusion in unanesthetized sheep. Endotoxin [lipopolysaccharide (LPS)] has been reported to reduce hypoxic pulmonary vasoconstriction and thus increases venous admixture. The time course of this failure of pulmonary blood flow regulation was investigated in six chronically instrumented unanesthetized sheep after infusion of Escherichia coli LPS (1 microgram/kg). The change in left pulmonary arterial blood flow (LPBF, ultrasonic transit time) in response to unilateral lung hypoxia (10 min of N2 alternately to the left and right lungs) was compared before and at various time intervals after the administration of LPS. During baseline conditions, LPBF was 33% of total cardiac output and decreased to 15% when the left lung was ventilated with a hypoxic gas mixture. One hour after endotoxin infusion, LPBF remained at 33% of total cardiac output yet only decreased to 28% during the hypoxic challenge. The response to one-lung hypoxia was still significantly depressed 10 h post-LPS administration. It is concluded that hypoxic pulmonary vasoconstriction is almost completely abolished for a prolonged time period after a small dose of LPS. 
Anterograde amnesia with fornix damage following removal of IIIrd ventricle colloid cyst. Two patients developed anterograde amnesia following the apparently uncomplicated transcallosal-transventricular removal of a colloid cyst. Damage to the fornical columns was demonstrated on CT and MRI scans, whilst other memory related structures were entirely normal. Longitudinal neuropsychological evaluation, over 12-24 months, has revealed a very similar pattern of deficit in the two cases: verbal memory has remained persistently impaired whilst nonverbal anterograde memory has improved to some degree. Formal tests of remote public (famous faces and events) and personal autobiographical memory have supported the clinical impression that neither patient has a temporally extensive retrograde amnesia. These findings address the role of the fornix, and the dissociation of memory processes in humans. 
Changes in upper airway resistance during progressive normocapnic hypoxia in normal men. The effects of normocapnic progressive hypoxia on nasal and pharyngeal resistances were evaluated in nine normal men. To calculate resistances, upper airway pressures were measured with two low-bias flow catheters; one was placed at the tip of the epiglottis and the other in the posterior nasopharynx, and we measured flow with a Fleish no. 3 pneumotachograph connected to a tightly fitting mask. Both resistances were obtained during a baseline period and during progressive normocapnic hypoxia achieved by a rebreathing method. We collected the breath-by-breath values of upper airway resistances, minute ventilation, O2 and CO2 fractions, arterial O2 saturation (SaO2), and changes in functional residual capacity (inductance vest). The central respiratory drive was evaluated by the mouth occlusion pressure 0.1 s after the onset of inspiration (P0.1), and breath-by-breath P0.1 values were estimated by intrapolation from the linear relationship between P0.1 and SaO2. In each subject both resistances decreased during the hypoxic test. The slope of the decrease in resistance with decreasing SaO2 (%baseline/%SaO2) was steeper for pharyngeal resistance than for nasal resistance [2.67 +/- 0.29 and 1.61 +/- 0.25 (SE), respectively; P less than 0.05]. The slope of the decrease in resistance with increasing P0.1 (%baseline/cmH2O) was -0.24 +/- 0.05 for nasal resistance and -0.39 +/- 0.07 for pharyngeal resistance (P less than 0.05). Functional residual capacity progressively increased during the test, but the decrease in resistance was greater than expected from an isolated increase in lung volume. We conclude that nasal and pharyngeal resistances decrease during progressive normocapnic hypoxia. 
Long-term angiographic follow-up after angioplasty of venous coronary bypass grafts. From April 1981 to June 1987, 57 patients underwent venous coronary bypass graft percutaneous angioplasty and had a minimal follow-up of 18 months. The procedure was elective for 28 patients, urgent for 19, and was considered as an emergency for 10. A total of 64 grafts were dilated that had been bypassed 58 +/- 48 months previously (range 2 to 184 months); lesions were located on the aortic anastomosis in 12 grafts, on the body in 38, and on the coronary anastomosis in 14. Technical success was 95.3% (61 of 64) per lesion; clinical success was 84.4% (54 of 64) per lesion and 82.5% (47 of 57) per patient. Thrombotic complications with images of a lacunar defect occurred in 11 grafts (17.2%). Predictive factors for these complications were: age of grafts 38.5% for greater than 60 month grafts versus 2.6% for less than 60 month grafts (p less than 0.01); site of lesion, body lesion 28.9% versus anastomosis none (p less than 0.01); type of lesion, concentric and short 6% versus other 29% (p less than 0.05); and recent fibrinolysis in 66% versus 10.6% (p less than 0.05). Long-term follow-up is available in the 47 successful patients and the three limited non-Q wave myocardial infarction patients. Two patients died at 13 and 17 months. Long-term angiographic follow-up is available in 45 of 48 patients or 94%. At the end of the study, 35 of 57 (61.4%) venous bypass grafts in 32 patients (64%) were patent after one or more percutaneous transluminal angioplasties. 
Differences in "primary response" gene expression in renal compensatory hypertrophy and hyperplasia. The induction of a family of primary response genes (ie, genes whose transcription is not dependent on new protein synthesis) occurs within minutes after stimulation of quiescent 3T3 cells by phorbol esters and growth factors. A similar pattern of gene expression is seen in PC-12 pheochromocytoma cells induced to differentiate by nerve growth factor (NGF), suggesting that a common set of activating signals occur in different forms of cell growth. To determine whether the same "activation" process occurs in renal hypertrophy, we measured mRNA levels in mice subjected to uninephrectomy (UNX) or sham operation. Regenerative renal hyperplasia was induced by intraperitoneal folic acid (FA) injection with vehicle as control. Northern blots showed induction of these genes by FA with elevated mRNA levels persisting for up to 24 to 48 hours. UNX and sham operation demonstrated a slight and transient elevation of mRNA levels, with a prompt return to basal levels by 60 minutes. 
Long-term psychologic implications of congenital heart disease: a 25-year follow-up. Patients with various types of congenital heart disease were contacted 25 years after their original examination at the Mayo Clinic. In addition to providing their current health status, level of education achieved, and current occupation, they were asked to complete a detailed standardized questionnaire to assess their degree of psychologic stress. Of the original 463 patients, 168 completed and returned the psychologic questionnaires. These patients had evidence of psychologic stress in excess of that expected on the basis of normative data. Furthermore, the degree of stress was unrelated to the clinical severity of the original cardiac defect. In addition, the psychologic stress occurred despite "success" as defined by educational achievement and occupational level. One can speculate that as children these patients were exposed to environmental stresses that may well have been colored by parental attitudes and perceptions. 
Spinal epidural hematoma causing cord compression after tissue plasminogen activator and heparin therapy. Bleeding is the most serious complication of thrombolytic therapy and limits its usefulness. We have reported a case of epidural hematoma, a rare occurrence after combined therapy with tissue plasminogen activator (TPA) and heparin. We emphasize that in patients treated with thrombolytic agents, any trauma may increase the risk of bleeding. The sudden onset of back pain and neurologic deficits should alert the clinician to the possibility of spinal hematoma with cord compression. 
Cerebral edema causing death in children with maple syrup urine disease. Four children with the classic form of maple syrup urine disease (MSUD) died of cerebral edema during an intercurrent infection that caused severe dehydration and acidosis. The diagnosis of MSUD had been established during the neonatal period in all four patients, on day 1 of life in three of them. All were in satisfactory control before the intercurrent illness. Two patients underwent peritoneal dialysis. Signs of brain-stem compression occurred after treatment, when biochemical abnormalities were improving. Computed tomography of the head, which was done in two patients, revealed cerebral edema; one of these patients also had subarachnoid hemorrhage. Autopsy in one case revealed cerebral edema with herniation. Our experience documents that cerebral edema may occur in the older child with MSUD as well as in the neonate. The pathogenesis of cerebral edema in MSUD remains unclear. Early treatment of dehydration and acidosis may prevent the catastrophic consequences that we have observed. 
The association of frequent headaches with personality and life events. The associations between personality traits, life events and frequent headaches were studied in a sample of 5766 adult subjects between 20 and 65 years of age from the general population. Subjects with at least weekly headaches had more life events and higher inadequacy, social inadequacy, rigidity and injuredness than subjects with less frequent headaches. These relationships were not observed in subjects of 50 years of age and older, with the exception of the association with inadequacy. From the traits measured, inadequacy had the highest odds ratios for frequent headaches and showed a modest interaction with the presence of a life event. These findings are in agreement with Sarason's interactional model. 
Inflammation at the neuromuscular junction in myasthenia gravis. To better define the pathogenic mechanisms in the antibody-mediated autoimmune disease myasthenia gravis (MG), we analyzed the morphology and electrophysiology of the neuromuscular junction in anconeus muscle biopsy specimens from eight patients with MG and seven control subjects. There were inflammatory cells at the neuromuscular junction in seven of the eight biopsies from MG patients. The endplate index (length of the postsynaptic membrane divided by the length of the apposed presynaptic membrane) was abnormally reduced in all the MG patients, and fiber type grouping, suggestive of reinnervation, was present in six of the eight MG patients. Intracellular recording revealed diminished amplitude of miniature endplate potentials and miniature endplate currents in the MG patients compared with the controls. The time constant of decay of miniature endplate currents did not differ from that of controls, suggesting no change in mean channel open time of the acetylcholine receptor. The endplate receptor sensitivity to iontophoretically applied acetylcholine was also decreased in MG patients compared with controls. The quantal content of neurally evoked endplate potentials was reduced in six of the eight MG patients, demonstrating abnormal presynaptic function as well. The presence of inflammatory cells at the neuromuscular junctions of limb muscles in MG reconciles an apparent disparity between the animal model of MG, experimental autoimmune myasthenia gravis, and the human disease. This study also demonstrates a frequent presynaptic component to the abnormal neuromuscular transmission in MG. 
On lowering lipids in the post-infarction patient. In patients with coronary heart disease (CHD) elevated serum cholesterol levels, like other classical risk factors, remain predictive of further coronary events. The excess risk attributable to raised cholesterol levels is considerable, and greater than that in subjects without CHD. A recent meta-analysis of all eight qualifying trials of secondary prevention of CHD by cholesterol lowering is reviewed. There were significant reductions in recurrent non-fatal and fatal CHD, with a downward trend in total mortality. Mechanisms underlying the relationship between cholesterol lowering and secondary prevention are reviewed. The implication of this analysis of trials for clinical practice is that hypercholesterolaemia should be sought and effectively treated in patients with CHD, unless contraindications are present. 
Glutathione peroxidase deficiency and childhood seizures. 4 children with intractable seizures, repeated infections, and intolerance to anticonvulsants had evidence of glutathione peroxidase deficiency. 2 had low intracellular enzyme activity but normal blood selenium and high plasma glutathione peroxidase concentrations. The other 2 had low intracellular glutathione peroxidase activity with low circulating glutathione peroxidase and selenium concentrations. The clinical state of the children improved after discontinuation of anticonvulsant medication and selenium substitution. 
Polysialic acid of the neural cell adhesion molecule distinguishes small cell lung carcinoma from carcinoids. The neural cell adhesion molecule (NCAM) exists in various types of neuroendocrine cells and their tumors. A typical feature of NCAM is polysialic acid, of which the chain length is developmentally regulated. The authors have performed a comparative immunohistochemical study on small cell lung carcinomas and bronchial as well as gastrointestinal carcinoids with the monoclonal antibody (MAb) 735 reactive with the long-chain form of polysialic acid. The small cell lung carcinomas, irrespective of their histological type, were positive for polysialic acid. Metastatic tumor cell complexes also exhibited immunostaining. The tumor cell-surface-associated immunostaining for polysialic acid was sensitive to endoneuraminidase. The mature and atypical bronchial and gastrointestinal carcinoids were not immunoreactive for polysialic acid. Cytoplasmic staining in groups of cells of carcinoids (2 of 28 cases) was due to nonspecific antibody binding, which could be prevented by increased ion strength. These data indicate that neuroendocrine tumors of the lung can be distinguished by their content of highly sialylated NCAM. 
Malignant tumors of the eye in geriatric patients. The ocular tissues can be the site of a number of malignant tumors in adults and geriatric patients. In addition to posing a threat to the patient's life, these tumors can cause severe visual loss or blindness. Therefore, the primary care clinician should be capable of prompt diagnosis of the various malignant ocular tumors and be prepared to refer the patient for appropriate management. This article provides a photographic guide to the most common primary and secondary malignancies that can affect the eyelid, conjunctiva, intraocular structures, and orbit in the geriatric patient. 
Restenosis after coronary angioplasty: a multivariate statistical model to relate lesion and procedure variables to restenosis. The M-HEART Investigators. The Multi-Hospital Eastern Atlantic Restenosis Trial group obtained follow-up angiography in 510 patients with 598 successfully dilated coronary lesions who were enrolled in a controlled trial of the effects of a single dose of 1 g of methylprednisolone on restenosis after coronary angioplasty. The overall restenosis rate was 39.6%. The strongest univariate relations to the restenosis rate were found for lesion location (saphenous vein graft, 68%; left anterior descending artery, 45%; left circumflex artery and right coronary artery, 32%; p = 0.002); lesion length (less than or equal to 4.6 mm, 33%; greater than 4.6 mm, 45%; p = 0.001); percent stenosis before angioplasty (less than or equal to 73%, 25%; greater than 73%, 43%; p = 0.005), percent stenosis after angioplasty (less than or equal to 21%, 33%; greater than 21%, 46%; p = 0.017) and arterial diameter (less than 2.9 mm, 44%; greater than or equal to 2.9 mm, 34%; p = 0.036). Two multivariate models to predict restenosis probability were developed with use of stepwise logistic regression. The preprocedural model, which included only variables whose values were known before angioplasty, entered lesion length, vein graft location, left anterior descending artery location, percent stenosis before angioplasty, eccentric lesion and arterial diameter. The postprocedural model, which also included variables whose values were known after angioplasty was performed, was similar to the preangioplasty model except that it also entered postangioplasty percent stenosis and "optimal" balloon sizing but did not enter eccentric lesion. These data indicate that the probability of restenosis after angioplasty is determined predominantly by the characteristics of the lesion being dilated. They are consistent with the known intimal proliferative mechanism of restenosis, offer a means of identifying lesions at unusually high or low risk of restenosis, and of predicting the likelihood that a particular lesion will restenose after angioplasty and provide a rationale for stratification by restenosis probability in the design of future studies of restenosis. 
Prenatal diagnosis of fetal left ventricular aneurysm: a case report and review. Fetal echocardiography in a 30-year-old black woman, gravida 4, para 3, demonstrated left ventricular aneurysm. This was confirmed by color flow pulsed Doppler techniques. After delivery, neonatal echocardiography and magnetic resonance imaging further confirmed the diagnosis. The infant was followed closely and underwent surgical correction at 8.5 months of age. Before surgery, cardiac catheterization demonstrated normal hemodynamic function. A review of the literature revealed a paucity of information. Issues of prenatal diagnosis, antenatal surveillance, method of delivery, and neonatal follow-up are not well defined in either the obstetric or pediatric cardiology literature. A rationale for our approach to this complex problem is presented. 
Community obstetric care in West Berkshire OBJECTIVE--To assess the effects of a revised obstetric booking policy whereby all low risk pregnant women received their antenatal care entirely in the community. DESIGN--Comparison of the distribution of antenatal clinic attendances, transfers, and perinatal mortality rates for 1987 and 1989, before and after introduction of the revised policy. SETTING--West Berkshire Health District. SUBJECTS--All women who delivered with a registrable birth in the district in 1987 (5817 women) and 1989 (5372). MAIN OUTCOME MEASURES--Attendances at community and consultant antenatal clinics; bookings transferred from community care to consultant care; perinatal mortality rates. RESULTS--Of 5372 women delivering in West Berkshire in 1989, 3185 (58.3%) were originally booked for general practitioner-midwife care, of whom 1567 (49.2% of general practitioner-midwife bookings) were transferred to consultant care. 1618 women (30.1% of all women delivered) received their entire obstetric care from general practitioners and midwives. Attendance at hospital antenatal clinics was reduced by 16%. In 1989 the perinatal mortality rates (1987 values) for the district were 6.3 (7.6) per 1000 births overall; 8.2 (8.3) per 1000 consultant bookings; 5.0 (4.7) per 1000 for community bookings; and 10.2 (14.4) per 1000 for women transferred to consultant care. CONCLUSION--Antenatal care of low risk pregnant women may safely be provided by their general practitioner and midwife. 
Outcome of psychogenic seizures in children and adolescents compared with adults. We compared outcome of psychogenic seizures documented by video-EEG in 18 nonepileptic children and adolescents (ages 8 to 18; median, 14.5 years old) and 20 adults (ages 25 to 56; median, 34.0 years old). Outcome was significantly better for the younger patients at 1 year, 2 years, and 3 years after diagnosis. At these follow-up times, the percentages of children and adolescents free of psychogenic attacks were 73%, 75%, and 81%; at the same follow-up times, the percentages of adults free of psychogenic attacks were only 25%, 25%, and 40%. Factors leading to better outcome for younger patients may have been different psychological mechanisms at different ages of onset and greater effectiveness with earlier intervention. 
Criteria for the diagnosis of migraine in clinical practice. Criteria for the diagnosis of migraine have evolved from generalized descriptions to specific rules designed to ensure the selection of homogenous groups of patients for research studies. For clinical practice, the former are insufficiently specific and the latter are too complex. For care of headache patients by primary care physicians, we propose that the diagnosis of migraine without aura (common migraine) is warranted if any two of the following symptoms are present: unilateral site, throbbing quality, nausea, photophobia or phonophobia. These criteria are derived from a study comparing the features of 100 patients with migraine without aura and 100 patients with chronic daily headache. The proposed criteria for the diagnosis of migraine without aura were highly sensitive and adequately specific in discriminating groups. These simple criteria should facilitate the diagnosis of migraine by primary care physicians. 
Use of secondary prophylaxis against myocardial infarction in the north of England OBJECTIVE--To record the use of secondary prophylactic drugs in patients discharged from hospital having had a myocardial infarction. DESIGN--Prospective postal questionnaire survey of a random one in two sample of general practitioners in the region. SETTING--The nine family practitioner committee areas within the Northern Regional Health Authority. PATIENTS--Patients who had had a myocardial infarction and were discharged to their general practitioner. MAIN OUTCOME MEASURE--Whether beta blockers or aspirin, or both, were given on discharge. RESULTS--Of 267 patients, 158 (59%) were treated suboptimally in that they did not receive a secondary prophylactic drug to which they had no contraindication. For most patients this entailed underuse of one drug, but 17 (6%) of patients received no treatment. beta Blockers were 2.5 times less likely to be used than aspirin. Treatment was not associated with the age or sex of the patient, risk of further infarction, or hospital of discharge. CONCLUSIONS--Secondary prophylaxis after myocardial infarction is practised haphazardly. It should be offered to all patients who can tolerate it, after a trial period to assess any side effects of the drugs if necessary. 
Impairment of mitochondrial transcription termination by a point mutation associated with the MELAS subgroup of mitochondrial encephalomyopathies. Defects in mitochondrial DNA (mtDNA) are associated with several different human diseases, including the mitochondrial encephalomyopathies. The mutations include deletions but also duplications and point mutations. Individuals with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) carry a common A-to-G substitution in a highly conserved portion of the gene for transfer RNA(Leu(UUR)). Although the MELAS mutation may be comparable to the defect in the tRNA(Lys) gene associated with MERRF (myoclonus epilepsy associated with ragged-red fibres), it is also embedded in the middle of a tridecamer sequence necessary for the formation of the 3' ends of 16S ribosomal RNA in vitro. We found that the MELAS mutation results in severe impairment of 16S rRNA transcription termination, which correlates with a reduced affinity of the partially purified termination protein for the MELAS template. This suggests that the molecular defect in MELAS is the inability to produce the correct type and quantity of rRNA relative to other mitochondrial gene products. 
Differential effects of thromboxane A2 synthase inhibition, singly or combined with thromboxane A2/prostaglandin endoperoxide receptor antagonism, on occlusive thrombosis elicited by endothelial cell injury or by deep vascular damage in canine coronary arteries. In open-chest dogs, cyclic flow reductions (CFRs, 5.1-6.6/hr in controls; n = 24) caused by platelet deposition/dislodgment at sites of endothelial cell injury in critically stenosed left anterior descending coronary arteries (59% flow reduction) were attenuated to the same extent either by single thromboxane A2 (TXA2) synthase inhibition (0.31 mg/kg i.v. ridogrel; CFR, 0.16 +/- 0.16/hr; n = 6; p less than 0.05) or by a comparatively modest degree of TXA2/prostaglandin endoperoxide receptor antagonism on top of TXA2 synthase inhibition (5 mg/kg i.v. ridogrel; CFR, 0.22 +/- 0.1/hr; n = 10; p less than 0.05). By contrast, occlusive thrombosis on deep vascular damage elicited by intraluminal stimulation (150-microA anodal constant current) in nonpreconstricted canine coronary arteries (time to occlusion, 237.1 +/- 13.9 minutes; n = 7; incidence of occlusion within 300 minutes, six of seven experiments) was not affected by platelet cyclooxygenase inhibition (5 mg/kg i.v. acetylsalicylic acid; n = 7), single TXA2 synthase inhibition (1.25 mg/kg i.v. ridogrel; n = 7), or single TXA2/prostaglandin endoperoxide receptor antagonism (10 mg/kg + 10 mg/kg/hr i.v. sulotroban for 300 minutes; n = 5). However, such an occlusive thrombus formation was significantly reduced by combined TXA2 synthase/prostaglandin endoperoxide receptor inhibition (5 mg/kg i.v. ridogrel; time to occlusion greater than 300 minutes, n = 7; incidence of occlusion within 300 minutes, one of seven experiments; p less than 0.05). This study reveals 1) a differential efficacy of TXA2 synthase inhibition, singly or combined with TXA2/prostaglandin endoperoxide receptor antagonism, depending on the extent of the vessel wall lesion triggering thrombosis and the size of the thrombus required to obstruct the vascular lumen and 2) a significant synergism in preventing occlusive thrombosis of extensively damaged coronary arteries between strong TXA2 synthase inhibition and comparatively modest TXA2/prostaglandin endoperoxide receptor antagonism with ridogrel. 
Double blind crossover comparison of the effects of dual chamber pacing (DDD) and ventricular rate adaptive (VVIR) pacing on neuroendocrine variables, exercise performance, and symptoms in complete heart block. OBJECTIVE--To compare the effects of dual chamber pacing (DDD) and ventricular rate adaptive pacing (activity sensing) (VVIR) in patients with complete heart block. DESIGN--Double blind crossover comparison with one month in each pacing mode. PATIENTS--10 consecutive patients aged 23-74 presenting with complete anterograde atrioventricular block at rest and on exercise and with an intact atrial rate response received Synergyst I (Medtronic) pacemakers. MAIN OUTCOME MEASURES--Symptom scores, maximal exercise performance on a treadmill, and the plasma concentrations of atrial natriuretic peptide, adrenaline, and noradrenaline. RESULTS--No significant differences were identified between pacing modes in symptom scores for dyspnoea, fatigue, and mood disturbance; exercise time; and maximal oxygen consumption. One patient with intact ventriculoatrial conduction developed pacemaker syndrome during VVIR pacing. Resting plasma concentrations of atrial natriuretic peptide were raised in complete heart block and were restored to normal by DDD pacing but not by VVIR pacing. Resting plasma catecholamine concentrations were normal in complete heart block and in both pacing modes. During exercise the increase in the concentrations of all three hormones was similar in both pacing modes. CONCLUSIONS--In patients with complete anterograde and retrograde atrioventricular block, symptoms and maximal exercise performance were no better during DDD than during VVIR pacing. 
Epstein-Barr virus and persistent graft dysfunction after liver transplantation. Epstein-Barr virus infection has been associated with a broad spectrum of clinical manifestations, depending on the immune status of the host. In this report, we describe two liver transplant patients who received hepatic allografts from donors serologically positive for Epstein-Barr virus and who experienced primary infection with Epstein-Barr virus associated with prolonged liver graft dysfunction. In both patients, Epstein-Barr serologies converted within 3 mo of liver transplantation, and hepatic histological study revealed mononuclear infiltration of the sinusoids evolving to pronounced immunoblastic features suggestive of evolving lymphoma. In both cases, in situ hybridization studies confirmed the presence of Epstein-Barr virus genome in the liver. Furthermore, polymerase chain reaction analysis suggested that high levels of Epstein-Barr virus DNA were present in biopsy specimens obtained during the episode of acute hepatitis that followed Epstein-Barr virus seroconversion. The degree of Epstein-Barr virus DNA estimated by polymerase chain reaction appeared to increase in parallel with the progression of parenchymal lymphocytic infiltrates. In one patient, a biopsy sample from a cervical node also revealed high levels of Epstein-Barr virus DNA estimated using the polymerase chain reaction technique. Furthermore, in these patients, Epstein-Barr virus DNA levels appeared to decrease dramatically after discontinuing azathioprine administration and beginning treatment with acyclovir. These two cases illustrate the dynamics of Epstein-Barr virus immune regulation and confirm chronic hepatic allograft dysfunction related to Epstein-Barr viral infection. 
Pseudarthrosis of the scaphoid treated by the Matti-Russe operation. A long-term review of 77 cases. We report the long-term results of the Matti-Russe operation for pseudarthrosis of the scaphoid in 100 cases, reported previously by Mulder in 1968. Clinical results for 77 patients and radiographic data for 74 were reviewed at 22 to 34.8 years after surgery. In general, there was satisfactory relief of pain and stiffness but some patients had limitation of motion and reduced grip-strength, with usually slight osteoarthritic changes. There was poor correlation between subjective, objective, and radiographic results but 88% of the patients were satisfied with their results. 
Hydroureteronephrosis secondary to perforated Meckel's diverticulum. Complications related to Meckel's diverticulum are not unusual. However, involvement of the urinary tract is extremely rare. To our knowledge this is the first reported case of ureteral obstruction due to perforation of Meckel's diverticulum. 
Pathogenesis of respiratory infections due to influenza virus: implications for developing countries. The influenza viruses have an important and distinctive place among respiratory viruses: they change antigenic character at irregular intervals, infect individuals of all ages, cause illnesses characterized by constitutional symptoms and tracheobronchitis, produce yearly epidemics associated frequently with excess morbidity and mortality, and predispose the host to bacterial superinfections. Much is known about influenza viruses, but their role in respiratory infections among children in developing countries is poorly understood, and the risk factors that lead to the excess morbidity and mortality have not been identified clearly. Among the many risk factors that may be important are alterations in host immunity, malnutrition, prior or coincident infections with other microorganisms, inhaled pollutants, and lack of access to medical care. There is a great need for research that can establish more precisely the role these and other unidentified factors play in the pathogenesis of influenza infections in children in the developing world. 
Expression of atrial natriuretic factor in the human ventricle is independent of chamber dilation This study investigated the presence of atrial natriuretic factor in ventricular tissue obtained from humans with dilated or restrictive heart disease. In 17 patients with ventricular dilation and impaired systolic function and in 8 patients with restrictive heart disease and preserved systolic function, the presence of ventricular atrial natriuretic factor was investigated in tissue obtained by ventricular endomyocardial biopsy. The objective of the study was to determine if the ventricular presence of atrial natriuretic factor is dependent on ventricular dilation. Left ventricular end-diastolic volume index was greater in the group with dilated cardiomyopathy than in the group with restrictive cardiomyopathy (134 +/- 13 versus 78 +/- 5 ml/m2, p less than 0.05); end-diastolic pressure was elevated in the two groups (20 +/- 2 versus 25 +/- 4 mm Hg, p = NS). With the use of immunohistochemical techniques, ventricular atrial natriuretic factor was clearly detected in 15 of the 17 patients with dilated cardiomyopathy and in 6 of the 8 patients with restrictive cardiomyopathy. This study demonstrates the high prevalence of ventricular atrial natriuretic factor in living patients with either systolic or diastolic dysfunction. Whereas in the atria, stretch or dilation may be an important stimulus, atrial natriuretic factor in the ventricular chamber occurs independent of dilation. 
Knowledge-based computer system to aid in the histopathological diagnosis of breast disease. A knowledge-based computer system, designed to assist pathologists in the histological diagnosis of breast disease, is described. This system represents knowledge in the form of "disease profiles" and uses a novel inference model based on the mathematical technique of hypergraphs. Its design overcomes many of the limitations of existing expert system technologies when applied to breast disease. In particular, the system can quickly focus on a differential problem and thus reduce the amount of data necessary to reach a conclusion. The system was tested on two sets of samples, consisting of 14 retrospective cases and five hypothetical cases of breast disease. Its recommendations were judged "correct" by the evaluating pathologist in 15 cases. This study shows the feasibility of providing "decision support" in histopathology. 
Diurnal variations of neurocardiac rhythms in acute myocardial infarction. To determine the diurnal pattern of cardiac autonomic tone in acute myocardial infarction (AMI), this study examined the power spectrum of heart rate (HR) variability in 24 patients during a single 24-hour segment within 4 days of AMI. Patients were nonrandomly allocated to a group (n = 14) without autonomic drugs and to a group (n = 10) already receiving beta blockers at the time of AMI. With use of autoregressive modeling, the power spectrum of HR variability was computed from continuous 1-hour electrocardiographic segments recorded at equally spaced intervals; 7 to 8 A.M., 3 to 4 P.M., and 11 to 12 P.M. All patients were supine, awake and pain free during recordings. There were no differences in HR, HR variance or the low-frequency peak power (0.06 to 0.1 Hz) from one temporal sequence to another. For the patients not taking beta blockers, the high-frequency peak power (0.2 to 0.36 Hz) or vagal component increased significantly from 3 P.M. to 11 P.M. (28 +/- 11 to 45 +/- 20 beats/min2.Hz-1, p less than 0.01). There was a significant decrease in the low- to high-frequency peak power and area ratios from 3 P.M. to 11 P.M. All power spectral parameters in the patients taking beta blockers remained unchanged over 24 hours. There was significantly heightened vagal modulation of sinus node activity in those receiving beta blockers, especially at 7 A.M. and 3 P.M. The data suggest that under steady-state wakeful conditions in the early recovery phase after an AMI, vagal tone is more pronounced during the late evening hours with a possible shift to relative sympathetic dominance during early morning and midafternoon hours. 
Argyrophilic nucleolar organizer regions and alpha-fetoprotein in adenomatous hyperplasia in human cirrhotic livers. Recently, adenomatous hyperplasia (AH) of the liver has been suspected as a precancerous lesion in human hepatocarcinogenesis. The authors examined 75 cases of AH from 42 cirrhotic livers, using staining of argyrophilic nucleolar organizer regions (AgNORs). These reflect proliferative cell activity. Findings in AH were compared with those seen in hepatocellular carcinoma (HCC) and other chronic liver diseases. Expression of alpha-fetoprotein (AFP) was also examined immunohistochemically. The authors classified AH into three types: ordinary (OAH), atypical (AAH), and AH with focal malignancy (FM). OAH implies a lack of atypia; AAH represents AH with structural and cellular atypia but without the features of overt carcinoma; and FM denotes AH with foci of overt HCC. Forty of the 75 cases of AH were categorized as OAH, 19 as AAH, and 16 as FM. The noncancerous areas of FM had features of AAH. The mean number of AgNORs in AH was intermediate between that seen in cirrhosis (2.93) and HCC (6.18) and showed a step-wise increase in the following order: OAH (2.95), AAH (3.89), noncancerous areas in FM (4.58), and malignant foci in FM (5.71). There was no significant difference in AgNOR counts between OAH and cirrhosis. AgNOR counts in AAH and FM were significantly higher than those of OAH, and lower than those of HCC. AFP was positive in 12 of 25 HCCs and in malignant foci of 3 FM lesions, but it was absent in OAH and AAH. These data suggest that OAH has a limited capacity for proliferation but that AAH and FM are much more replicative. The latter two conditions are probably preneoplastic lesions or early forms of HCC. 
Explicit memory and repetition priming in depression. Preliminary findings. Explicit memory and repetition priming, a form of implicit memory, were examined in depressed patients and controls. Explicit memory of depressed patients was severely impaired, whereas repetition priming was intact. These results are consistent with the hypothesis that the impairment of memory in depression is linked to a failure of effort-demanding cognitive processes. Repetition priming might be useful in differentiating between depression and dementia. 
Lupron retards proliferation of ovarian epithelial tumor cells cultured in serum-free medium. Some patients with recurrent ovarian epithelial cancer respond favorably to treatment with GnRH agonists. This effect was proposed to be mediated by suppression of pituitary gonadotropin release. The present in vitro study investigated effects of human gonadotropin (Pergonal LH/FSH, 1:1) and Lupron, a GnRH agonist, on proliferation of an ovarian cancer cell line, 2774, which is estrogen receptor negative and grows well in serum-free, defined medium. Pergonal, 10 IU/mL or 30 IU/mL, did not enhance cell proliferation, which argues against stabilization of ovarian tumors in vivo due to decreased serum gonadotropin. Lupron, 1.4 micrograms/mL and 140 micrograms/mL, retarded cell division by day 6-8 of culture, in a dose-dependent manner. Flow cytometric cell cycle phase DNA analysis demonstrated Lupron caused a reversible 5-6% increase in the portion of cells in rest phase, G0/G1, compared to controls during log growth, and a corresponding decrease in the portion of cells in DNA synthesis, S phase. However, long-term culture, 3 weeks, with Lupron failed to arrest cells in G0/G1, and experimental cultures plateaued at cell number similar to control cultures. We conclude Lupron's effect on ovarian cancer cell proliferation is independent of gonadotropin and steroid, involves a cell cycle regulatory event, and duration of benefit observed in vivo for some patients may be related to total tumor volume at the time of treatment. 
Early-initiated zidovudine therapy prevents disease but not low levels of persistent retrovirus in mice. An F1 hybrid mouse strain containing the Rfv-3r/s genotype was inoculated with Friend virus complex (FV) and treated with zidovudine (ZDV) intraperitoneally three times daily for 20 days beginning as early as 10 min after initial viral exposure. This strain of mice develops FV-specific neutralizing antibodies that aid in reducing viremia and splenic virus titers but do not prevent splenomegaly and eventual FV-associated death. The virally exposed mice treated with ZDV did not develop splenomegaly or have detectable viremia after the last drug treatment. On day 21, a single animal had demonstrable virus in the spleen as determined by a focal immunoenzyme assay; 57% had detectable virus at 5 weeks, but non displayed splenic virus after 35 weeks. None of the animals died after the 35-week holding period, compared to 38% dying in placebo-treated mice. To detect low levels of the virus, or potentially latent virus, splenocytes were cocultivated with a cell line known to readily propagate FV, and the cells were subsequently passaged four times to amplify replication of the virus. After amplification, a significant increase was seen in the number of mice testing positive for virus. Thus, ZDV treatment initiated early after virus exposure was effective in preventing FV-induced splenomegaly and death, but did not prevent low levels of persistent retrovirus in the mice. 
Minute lesions of the rectum and sigmoid colon in patients with Crohn's disease. Sigmoidoscopy with a spray of 0.1% indigocarmine was performed on 20 patients with Crohn's disease whose main lesions were located proximal to the transverse colon and on 10 age-matched healthy volunteers. Minute lesions such as apthoid lesions, areas of erythema, and small ulcers were found in 90% of patients with Crohn's disease and in 0% of healthy volunteers (p less than 0.001). Among the minute lesions, aphthoid lesions were found in the highest incidence (85%). It was difficult to determine the presence of aphthoid lesions without the spray of indigocarmine, which facilitated detection. Histologically, granulomas were found in 15% of patients with Crohn's disease. Aphthoid lesions were not associated with superficial erosions and lymphoid follicles. The presence of aphthoid lesions in the rectum and sigmoid colon would be a strong indication of the presence of Crohn's disease. 
Regional changes in hemodynamics and cardiac myocyte size in rats with aortocaval fistulas. 2. Long-term effects. Regional changes in hemodynamics and cardiac myocyte size were examined in adult rats 5 months after creating a large aortocaval fistula. At that time, cardiac output, left and right ventricular pressures, and left and right ventricular dP/dtmax were measured. Subsequently, isolated cardiac myocytes were collected from the left ventricle, right ventricle, and septum for cell size measurements. Compared with sham-operated controls, percent dry weight was reduced in the liver and kidney but was unchanged in the lung. Heart rate, left ventricular systolic pressure, left ventricular dP/dtmax, and systolic aortic pressure were not changed in rats with fistulas. However, cardiac output, stroke volume, left ventricular end-diastolic pressure, and all measured parameters in the right ventricle were significantly increased. Mean cell volume and the ratio of heart weight to body weight were both elevated 92%. Cell volume, cell length, and cross-sectional area increased significantly in each heart region examined. Hypertrophy was more pronounced in cells from the right ventricle and the endomyocardium of the left ventricle. The percentage of cells with mononucleation or binucleation was not changed in any heart region of rats with fistulas. In summary, despite evidence of renal and hepatic congestion, most indexes of cardiac function were normal or elevated 5 months after creation of a large volume-overload-induced hypertrophy. Data from isolated cardiac myocytes suggested that cellular hypertrophy, rather than hyperplasia, was responsible for the increased cardiac mass. 
Somatosensory function following dorsal root entry zone lesions in patients with neurogenic pain or spasticity. The goal of this study was to assess the effects of the dorsal root entry zone (DREZ) lesioning procedure, microsurgical DREZ-otomy (MDT), on spinal cord somatosensory function based on peri- and intraoperative clinical and electrophysiological data. The study was performed prospectively on a series of 20 patients suffering from either chronic neurogenic pain or spasticity. Physiological observations were made of the intraoperative evoked electrospinographic recordings as collected from the surface of the spinal cord. The MDT procedure produced analgesia or severe hypalgesia, moderate hypesthesia, and only slight deficits in proprioception and cutaneous spatial discrimination on the body segments operated on. These clinical data correlated well with evoked electrospinographic recordings, which showed a moderate effect of MDT on presynaptic compound action potentials recorded from the spinal cord (N11 and N21), a partial or even reversible effect on the cortical postcentral N20 wave, a more marked effect on the postsynaptic dorsal horn waves N13 and N24 related to large primary afferent fibers, and a disappearance of dorsal horn waves related to finer afferents (N2 and possibly N3). These data provide evidence for an acceptably selective action of MDT on spinal cord nociceptive mechanisms, and for a partial, often slight, involvement of the other somatosensory domains. The presence of abnormal evoked electrospinographic waves is discussed in relation to the mechanisms of neurogenic pain and spasticity. The hypothesis of a "retuning" of the dorsal horn as the mode of action of MDT is presented. 
Control of local blood flow in pulmonary inflammation: role for neutrophils, PAF, and thromboxane. The intrapulmonary instillation of C5a results in a local inflammatory response that, in this site, is accompanied by a decrease in local blood flow. Reversal of this decrease by vasodilators or the thromboxane synthesis inhibitor dazmegral has been shown to result in enhanced lung inflammation. In the present study the mechanisms underlying the decrease in flow in pulmonary inflammation were investigated in the rabbit in vivo and in the isolated blood-perfused rabbit lung. In vivo, the decrease in local blood flow was shown to be dependent on circulating neutrophils. In the isolated blood-perfused lung, inflammation induced by airway instillation of C5a was similar histologically to that seen in vivo and was also accompanied by a decrease in local blood flow. The decrease in blood flow appeared to require circulating neutrophils and was prevented by dazmegral and the platelet-activating factor (PAF) antagonists WEB 2086 and L-659,989. Furthermore, no decrease occurred in aspirin-treated lungs perfused with normal blood, suggesting that the source of thromboxane was lung rather than circulating cells. The decrease in blood flow in inflammation did not appear to be a consequence of hypoxic vasoconstriction. Inflammation in the guinea pig lung was also accompanied by a decrease in local blood flow and was also prevented by dazmegral and PAF antagonists. We conclude that local inflammation in the lung is accompanied by a decrease in blood flow that involves neutrophils and the lipid mediators PAF and thromboxane. We suggest that this form of negative feedback by the neutrophil serves to control the inflammatory response. 
Role of echocardiography in the diagnosis and evaluation of severity of mitral and tricuspid stenosis. The presence, severity, and hemodynamic consequences of mitral and tricuspid stenosis can be determined by echocardiographic techniques. In mitral stenosis two-dimensional echocardiographic imaging allows definition of leaflet anatomy and dynamics, subvalvular disease, ventricular function, and involvement of other valves. Spectral and color Doppler echocardiographic techniques permit accurate measurement of transvalvular gradient, determination of functional orifice area, evaluation of associated valvular regurgitation, and assessment of pulmonary artery pressures. These approaches are of recognized clinical value, and they provide additional diagnostic information that is unavailable from clinical assessment alone in a significant number of patients. Compared with available invasive diagnostic standards of reference, echocardiographic data have been found to be comparable in accuracy. In tricuspid stenosis echocardiographic imaging and Doppler techniques provide an assessment of valve morphology and function that should be similarly useful in clinical management decisions, although rigorous comparative studies have not been performed. Currently, carefully done echocardiographic studies are a definitive means of establishing the presence and significance of mitral stenosis and tricuspid stenosis, thereby obviating the need for invasive evaluation in many patients, reducing risk, and potentially decreasing the cost of diagnostic assessment. 
Lack of diameter effect on short-term patency of size-matched Dacron aortobifemoral grafts. This study examined the relationship between graft diameter and subsequent patency in 79 patients who received Dacron aortobifemoral bypass grafts for aortoiliac occlusive disease between 1985 and 1989. Sixty-five percent of these patients were men, 25% were diabetic, and 94% were smokers, with an average age of 62 years. Patients were followed for a mean interval of 24 months. Life-table survival was 92% at 3 years. All surviving patients showed "significant" postoperative improvement by use of Society for Vascular Surgery/International Society for Cardiovascular Surgery combined clinical and vascular laboratory criteria. There were three early and five late graft thromboses. Primary and secondary life-table patencies were 85% and 92%, respectively, at 3 years. Dacron bifurcation grafts were selected to match the size of native arteries. Patients receiving small diameter grafts, defined as 12 mm (n = 9) and 14 mm (n = 39), were compared with patients receiving large diameter grafts of 16 mm (n = 26) and 18 mm (n = 5). Small diameter grafts were more likely to be used in women (p less than 0.01), but patient groups were otherwise comparable with respect to age, smoking history, diabetes, outflow status, operative indications, type of proximal anastomosis (end-to-end or end-to-side), location of distal anastomosis (common femoral vs deep femoral), type of graft construction (knitted vs woven), and functional result. Graft diameter did not influence life-table patency, which was 84% for small and 87% for large diameter grafts at 3 years (p = 0.74). Furthermore, none of the other variables listed above influenced graft patency. 
Amnesia following damage to the left fornix and to other sites. A comparative study. Two memory-impaired patients, who had suffered damage to the left or both fornix columns during removal of a ventricular cyst, were compared with 3 others having left-sided hippocampal or thalamic lesions, and with normal controls. The tests used were nonverbal--scene recognition, delayed matching-to-sample and concurrent pattern and object discrimination learning. The last two are differentially sensitive to fornix transection and to hippocampal or thalamic ablations in monkeys; however, the patients with fornix damage did not show a distinctive pattern of impairment. The reasons for this discrepancy are discussed. The study adds to the evidence that fornix transection can cause wide-ranging memory disturbances in man. 
DNA ploidy analysis of effectiveness of radiation therapy for cervical carcinoma. Cellular DNA content from 30 patients with cervical carcinoma was determined using flow cytometry before and after radiation therapy (RT). The authors attempted to correlate changes in DNA content, tumor response to RT, and post-RT pathologic findings. Before RT, tumors from eight of 30 patients (26.7%) were diploid or near-diploid; tumors from 22 patients (73.3%) were aneuploid. After RT, diploid or near-diploid tumors were found in 23 patients (76.7%), and aneuploid tumors were observed in seven patients (23.3%). Aneuploidy disappeared in 15 of the patient tumors, and complete tumor response (CR) was observed in 13 of these 15 patients (86.7%). Pathologic examinations were negative in 12 of 15 cases and suspicious in one of 15 cases. Of the seven patients whose tumor aneuploidy did not change after RT, CR was observed in only two (28.7%). Pathologic examinations were positive in five of seven cases and suspicious in one of seven cases. The CR for the 22 patients with pre-RT aneuploid tumors was 15 of 22 (68.2%); the CR for the eight patients with pre-RT diploid tumors was two of eight (25%, P less than 0.01). From these data the authors conclude there is a direct correlation between DNA content and radiosensitivity in cervical carcinoma. Aneuploid tumors from these patients were more radiosensitive than diploid tumors, and they patients had a better clinical tumor response and improved pathologic findings. 
Enhanced GABAergic inhibition preserves hippocampal structure and function in a model of epilepsy. Extensive electrical stimulation of the perforant pathway input to the hippocampus results in a characteristic pattern of neuronal death, which is accompanied by an impairment of cognitive functions similar to that seen in human temporal lobe epilepsy. The excitotoxic hypothesis of epileptic cell death [Olney, J. W. (1978) in Kainic Acid as a Tool in Neurobiology, eds. McGeer, E., Olney, J. W. & McGeer, P. (Raven, New York), pp. 95-121; Olney, J. W. (1983) in Excitotoxins, eds. Fuxe, K., Roberts, P. J. & Schwartch, R. (Wenner-Gren International Symposium Series, Macmillan, London), Vol. 39, pp. 82-96; and Rothman, S. M. & Olney, J. W. (1986) Ann. Neurol. 19, 105-111] predicts an imbalance between excitation and inhibition, which occurs probably as a result of hyperactivity in afferent pathways or impaired inhibition. In the present study, we investigated whether the enhancement of gamma-aminobutyric acid (GABA)-mediated (GABAergic) inhibition of neurotransmission by blocking the GABA-metabolizing enzyme, GABA transaminase, could influence the histopathological and/or the behavioral outcome in this epilepsy model. We demonstrate that the loss of pyramidal cells and hilar somatostatin-containing neurons can be abolished by enhancing the level of synaptically released GABA, and that the preservation of hippocampal structure is accompanied by a significant sparing of spatial memory as compared with placebo-treated controls. These results suggest that enhanced GABAergic inhibition can effectively block the pathophysiological processes that lead to excitotoxic cell death and, as a result, protect the brain from seizure-induced cognitive impairment. 
Cortical blindness in children: a study of etiology and prognosis. Thirty-four children (20 boys, 14 girls) with congenital and acquired cortical blindness were analyzed for visual outcome in relation to etiology, visual evoked potentials, electroencephalography, and cranial computed tomography. All 7 children with congenital cortical blindness remained blind on subsequent examination. Of the 27 children with acquired blindness, 16 (59%) had poor visual outcome. Poor visual outcome occurred in those with cardiac arrest, hypoxia, status epilepticus, intracranial hemorrhage, cerebral thrombosis, and head trauma. Good visual outcome occurred in children with hypotensive episodes after cardiac surgery. Of the 12 children with recovery of vision, the interval from acute loss of vision to partial or total recovery was 2 weeks to 5 months. Seven children had complete recovery of vision with no residual visual field defect. The majority of children (87%) had focal or multifocal spike-and-waves and slow sharp-wave discharges on electroencephalography. None had photic recruitment response or occipital spike-and-wave discharges. Flash visual evoked potential studies performed during acute episodes of cortical blindness documented 11 with absent response, 10 with bilateral increases in latency, and 6 with normal responses. There was no correlation between normal visual evoked potentials and a good visual outcome. Only 2 of 6 children with normal responses had normal vision. Abnormal or absent responses are more predictive of a poor recovery of vision because only 3 of 21 (14%) had normal vision on subsequent examination. Abnormal electroencephalographic findings with focal or multifocal spike-and-wave discharges or cerebral atrophy on cranial computed tomography are also poor prognostic signs. 
Factors affecting ability to resume oral nutrition in the oropharyngeal dysphagic individual. Successful oral intake of nutrition depends not only on the patient's ability to swallow efficiently and safely but also a number of cognitive, neurolinguistic, and behavioral variables. This paper reviews these competencies as they are integrated into the act of oral feeding and describes the types of disorders that affect these abilities. Methods of evaluating and treating the abilities needed for successful oral intake are described. 
Recurrent abortion and the diagnosis of Wilson disease. We describe the first patient with Wilson disease and recurrent abortion who was effectively treated with oral zinc for both conditions. Between the ages of 21-26, this patient experienced seven successive unexplained abortions. At age 27, neurologic signs and liver function disturbances appeared. Wilson disease was diagnosed when Kayser-Fleischer rings were detected in the cornea. Decoppering therapy was instituted with zinc sulfate per os. By the age of 31, hepatic and neurologic signs had vanished. The patient conceived, and after an uncomplicated eighth pregnancy she delivered her first healthy child. Two years later, a ninth pregnancy was equally successful. The chance that Wilson disease may be the cause of recurrent abortion is small. However, because the disease is fatal if left untreated and because it is an underdiagnosed disease, we recommend screening for Wilson disease in cases of unexplained recurrent abortion when family history demonstrates consanguinity or neurologic, psychiatric, and/or liver disorders. A strategy to this end is proposed. 
Ki-67 immunostaining in node-negative stage I/II breast carcinoma. Significant correlation with prognosis. Prognostic predictors for node-negative breast carcinoma have not been clearly established. Immunostaining with Ki-67 antibody was performed on frozen sections of histologically proved node-negative breast carcinomas from 42 patients to examine its prognostic value and its association with other clinicopathologic and biochemical parameters, i.e., patient age and tumor size, histologic type, nuclear grade, mitotic rate, presence of vascular or lymphatic invasion, DNA ploidy, percentage of cells in S-phase, estrogen content, and c-erbB-2 amplification. Thirty-seven of the 42 tumors showed immunoreactivity with Ki-67 antibody in 1% to 55% of the tumor cells. A strongly significant correlation was observed between Ki-67 staining percentage and, respectively, nuclear grade, age, and mitotic rate. Nuclear grade 1 (the most anaplastic) tumors showed a significantly higher median percentage of cells stained (median, 14; range, 3 to 40) compared with nuclear grade 3 tumors (median, 0.5; range, 0 to 8). Thirteen patients developed recurrence; six of them died of disease. On univariate analysis, both 5-year disease-free and overall survivals were strongly associated with percentage of cells stained with Ki-67 antibody. Our results suggest that Ki-67 immunostaining correlates well with nuclear grade and clinical outcome in node-negative breast carcinoma. Because of small sample size analyzed in this study we were unable to do multivariate analysis. Therefore, further studies with larger number of cases are needed to determine whether tumor proliferative activity determined by Ki-67 immunostaining is an independent prognostic parameter or it merely reflects histopathologic features such as nuclear grade or mitotic activity. 
A forensic application of DNA typing. Paternity determination in a putrefied fetus. Using minisatellite DNA probes that hybridize to a variable number of tandemly repeated loci, an individual-specific DNA fingerprint can be determined. In the case reported here, we succeeded in extracting high-molecular-weight DNA from a 3-month-old fetus discovered during the autopsy of a murdered 28-year-old pregnant woman reported missing 10 days earlier. The results of analysis of restriction-fragment-length polymorphisms showed that all bands present in the fetus's pattern, but absent in the mother's, matched only those of the putative father. Thus, the paternity of the victim's husband was ruled out. 
Chemotherapy dose intensity correlates strongly with response, median survival, and median progression-free survival in metastatic neuroblastoma We examined the efficacy of five commonly used drugs, teniposide (VM26), cisplatin (CDDP), cyclophosphamide (CPM), doxorubicin (DOXO), and vincristine (VCR) in a retrospective analysis of 44 clinical trials of induction chemotherapy for stage IV neuroblastoma patients newly diagnosed at older than 1 year of age. Dose intensity (DI) of each drug was calculated as milligrams per square meter per week. Linear regression analyses showed that the Dls of VM26 and CDDP had the greatest influence on clinical outcomes (ie, proportion of major response, median survival, and median progression-free survival [PFS]), while those of CPM and DOXO were less significant. VCR had no influence on the three clinical end points. Although many protocols extended treatment to more than 1 year, none of these end points correlated positively with the duration of therapy. Twenty-one weeks appeared adequate for achieving superior response, median survival, and median PFS. These results suggest that maximal dose intensification of selective drugs over a short duration may improve the outcome of patients with poor-risk neuroblastoma. 
Major amputations done with palliative intent in the treatment of local bony complications associated with advanced cancer. Palliative amputations were performed on 11 patients (7 men, 4 women) with disseminated disease to control local bony complications. The average patient age was 54 years (range 14-78 years). The primary diseases were melanoma/sarcoma (seven patients) and carcinoma (four patients). All had pain; eight had intractable pain that could not be controlled by analgesics. All 11 patients had additional severe local complications, which included recurrent pathological fracture (4), sepsis (2), hemorrhage (2), radiation necrosis (2), and iliofemoral thrombosis secondary to tumor (1). Previous attempts of palliation had been made in all 11 patients, and 8 had undergone previous operative procedures (5 had undergone two or more) prior to amputation. Three anterior hemipelvectomies, five posterior hemipelvectomies, two hip disarticulations, and one forequarter amputation were performed. All patients survived the surgery, and there were no intraoperative complications. All patients received dramatic relief of pain. Postoperative complications included two cases of flap necrosis and two infections; all resolved satisfactorily. The six patients who were nonambulatory before surgery ambulated postoperatively, and two eventually ambulated with a prosthesis. Six of 11 patients survived 1 year or longer, with a median postoperative survival period of 13 months (average 16 months). Although major amputations are viewed at times as offering little to already-compromised patients, they can improve dramatically the quality of life in selected patients. 
Confirming the theoretical structure of the McGill Pain Questionnaire in acute clinical pain. Based upon a tripartite theoretical model of pain, the Pain Rating Index (PRI) of the McGill Pain Questionnaire (MPQ) continues to be one of the most frequently used instruments to measure clinical pain. Although a number of exploratory factor analytic studies have failed to consistently support the theoretical structure of the instrument, one previous confirmatory factor analytic study of chronic pain did statistically support the a priori model. Because it has been suggested that acute pain may not involve the same dimensions as chronic pain, this study provided a direct test of the theoretical structure of the MPQ through multi-sample confirmatory factor analysis (CFA) using data provided by women experiencing pain during labor (n = 185) and women experiencing acute postoperative pain (n = 192). Results of the LISREL CFA analysis indicated that the a priori, 3-factor, oblique model originally proposed by Melzack provided the most parsimonious representation of the data across the 2 samples of acute pain. 
The physician's responsibilities: residua and sequelae. Cardiologists assuming responsibility for adults with congenital heart disease must have knowledge of electrophysiologic, valvular (native valves), prosthetic (valves, patches and conduits), ventricular (especially chamber function), vascular (especially elevated pulmonary vascular resistance) and noncardiovascular residua and sequelae. Acquired cardiac and noncardiac diseases coexist in older adults with postoperative congenital heart disease and add to the physician's responsibilities. 
The mini-grommet and tympanosclerosis. One hundred and sixteen children with otitis media with effusion underwent myringotomy and insertion of a conventional pattern of Shah grommet in one ear and the much smaller Mini Shah grommet in the other. Close observation post-operatively determined the comparative rate of extrusion, recurrence of effusion, and of onset and degree of tympanosclerosis. At one year review, the Mini Shah shows a significantly earlier extrusion and a greater tendency to recurrence of otitis media with effusion. However, this is compensated by a decreased incidence of tympanosclerosis and reduced severity in those affected. This tends to support the view that shear forces produced by heavier patterns of ventilation tube promote tympanosclerosis. 
Hemobilia due to vasculitis of the gall bladder in a patient with mixed connective tissue disease. A 30-year-old woman with mixed connective tissue disease presented with acute abdominal pain and signs of blood loss. At cholecystectomy she appeared to have lost a considerable amount of blood into the biliary tract due to bleeding of the gall bladder. Microscopic examination showed vasculitis of the gall bladder wall. Hemobilia has not been described before as a complication in mixed connective tissue disease. 
A world record marathon runner with silent ischemia without coronary atherosclerosis. A 62-year-old world record marathon runner was found to have silent ischemia manifested by a very abnormal stress test, whereas at autopsy nine months later, there was virtually no coronary atherosclerosis nor other disease of the coronary microvasculature. However, there was focal fibrosis of the papillary muscles consistent with remote ischemia secondary to possible CV. It is postulated that endurance-related high catecholamine levels might have been responsible. 
Lack of ciprofloxacin ototoxicity after repeated ototopical application. The possible side effects of ototopically applied ciprofloxacin on inner ear function were investigated. The hearing function of pigmented guinea pigs was evaluated by daily frequency-specific evoked response audiometry after repeated application of the drug to both ears. Ciprofloxacin appeared to have no statistically significant effect on the hearing thresholds of the experimental animals. 
Risk factors for tunnel infections in continuous peritoneal dialysis. Little data are available about risk factors for peritoneal catheter subcutaneous tunnel infection. Therefore, we analyzed tunnel infections occurring in our program over a 10.5-year period. One hundred twenty-nine tunnel infections occurred in 92 of 411 patients (22%) on peritoneal dialysis for a mean of 19 +/- 19 months. Tunnel infection rate was 0.19 per year. By 1 year, 15% of patients had a tunnel infection, and by 2 years, 23%. Tunnel infection rates decreased with increasing time on peritoneal dialysis: 2.4 per year for patients on peritoneal dialysis less than 1 year, 0.8 per year for patients on dialysis 1 to 2 years, and 0.4 per year for patients on dialysis greater than 2 years (all different at P less than 0.01). Organisms were cultured in 109 tunnel infections: gram-positive cocci in 77 episodes (71%) [Staphylococcus aureus 57, 52%], and gram-negative bacilli in 24 episodes (22%). Tunnel infection rates were higher in diabetics than in nondiabetics (0.27 per year v 0.16 per year, respectively; P less than 0.001 by life-table analysis of time to first infection) and also higher in women than in men (0.23 per year v 0.17 per year, P less than 0.001). Tunnel infection rates were 0.35 per year for diabetic women, 0.20 per year for diabetic men, 0.18 per year for nondiabetic women, and 0.15 per year for nondiabetic men (groups different, P less than 0.001). Race and age were similar in patients with and without tunnel infections. Catheter loss was 80% when tunnel infection was associated with peritonitis and 40% when tunnel infection alone was present (P less than 0.001). We conclude that the risk of tunnel infection is highest early in the course of peritoneal dialysis and that diabetic women, for unclear reasons, are at the highest risk. 
Assessment of normal and abnormal erectile function: color Doppler flow sonography versus conventional techniques. The penile arteries were studied with color Doppler flow sonography in 10 subjects with normal and 39 patients with abnormal erectile function. The relationships of systolic and diastolic velocities to spectral waveform changes in the penile arteries in response to tumescence were studied before and after intracorporal injection of vasoactive medications that induce erection. In normal subjects, a characteristic spectral waveform pattern corresponded to increasing intracorporal pressure. Patients with abnormal arterial inflow and/or abnormal venous sinusoidal leakage demonstrated deviation from the patterns noted in normal subjects. Patients with abnormal arterial inflow had lower mean peak systolic velocities than normal subjects. Patients with severe venous sinusoidal incompetence had an arrest of waveform progression with evolution to but not beyond phases 1 or 2 (diastolic flow remained positive). Patients with abnormal arterial inflow and abnormal venous sinusoidal outflow had waveform changes that reflected both processes. Systolic/diastolic velocity and waveform relationships can be used to define the integrity of both the cavernosal artery inflow and venous sinusoidal outflow occlusion mechanisms. 
Breast cancer metastatic to the eye is a common entity. Breast cancer metastatic to the eye is a common entity occurring in up to 30% of women with metastatic disease. The prevalence of this lesion is not appreciated because of the dominant clinical picture of metastases occurring in other organs. The diagnosis should be suspected in any women with a history of breast cancer and any visual symptoms, particularly metamorphopsia and scotomata. A thorough ophthalmologic evaluation, aided by ultrasonography, computed tomography, or magnetic resonance scanning, usually confirms the diagnosis. Early treatment with radiation therapy can alleviate symptoms and control local disease. The recognition and treatment of this disorder is important in maximizing the quality of life in patients with metastatic breast cancer, especially because newer treatment regimens prolong survival and thereby increase the chances for ocular metastasis. 
Incidental detection of a microcystic adenoma of the pancreas. Cystic neoplasms of the pancreas are uncommon. The two major types of cystic pancreatic neoplasms are microcystic (serous) cystadenoma and mucinous cystic lesions (mucinous cystadenoma and mucinous cystadenocarcinoma). The two types differ substantially in the long-term mortality. Symptoms and signs do not distinguish between the two types, and small lesions are often asymptomatic. The neoplasms may be discovered during imaging procedures for unrelated complaints. Computerized tomography may suggest the diagnosis of microcystic adenoma or mucinous cystic neoplasm when the features are typical, but the final diagnosis must be established by surgical biopsy. Characteristic gross findings, light microscopic findings, and immunohistochemical staining patterns distinguish between the two types. When preliminary open biopsy confirms microcystic adenoma, extensive unnecessary surgery can be avoided. 
Effects of beta-adrenergic stimulation with dobutamine on isovolumic relaxation in the normal and failing human left ventricle. BACKGROUND. We tested the hypothesis that beta-adrenergic receptor-stimulated acceleration of left ventricular (LV) isovolumic relaxation (i.e., positive lusitropic response) is attenuated in patients with severe congestive heart failure (CHF) compared with patients without LV dysfunction or CHF. METHODS AND RESULTS. The beta-adrenergic agonist dobutamine was infused by the intracoronary route in 14 subjects (normal group, six; CHF patients, eight) and by the intravenous route in a second group of 14 subjects (normal group, four; CHF patients, 10). The positive inotropic response to intracoronary or intravenous dobutamine was substantially and significantly reduced in the patients with CHF. LV isovolumic relaxation rate was determined by the methods of Weiss (TL), Mirsky (T1/2), and by a nonlinear regression technique (TNL). LV isovolumic relaxation assessed by all three methods was significantly prolonged in CHF patients compared with normal subjects. Intracoronary and intravenous infusions of dobutamine caused significant acceleration of LV isovolumic relaxation in both normal subjects and patients with CHF. The magnitude of the dobutamine-stimulated acceleration of isovolumic relaxation in patients with CHF was comparable with that in normal subjects. CONCLUSIONS. These data demonstrate that beta-adrenergic receptor stimulation causes significant acceleration of LV isovolumic relaxation in both normal subjects and patients with severe CHF. Coronary to our hypothesis, the lusitropic response to beta-adrenergic stimulation is well preserved in patients with severe CHF despite substantial attenuation of the beta-adrenergic positive inotropic response. These findings have potentially important implications regarding the physiology and pharmacology of adrenergically mediated LV relaxation in humans. 
Dystrophin expression and somatic reversion in prednisone-treated and untreated Duchenne dystrophy. CIDD Study Group. The mechanism by which prednisone improves muscle strength and function in Duchenne muscular dystrophy (DMD) is unknown. We addressed the possibility that clinical improvement was related to prednisone-induced alterations in skeletal muscle dystrophin. We performed muscle biopsies on patients at the conclusion of a randomized, double-blind, 6-month trial of prednisone and analyzed dystrophin content using Western blots and antibody staining of tissue sections. These studies demonstrated no significant differences in dystrophin content between treatment (prednisone 1.5 mg/kg/d, n = 12; prednisone 0.75 mg/kg/d, n = 9) and placebo (n = 12) groups. Of interest, however, was the presence of varying numbers of dystrophin-positive fibers (revertants) occurring individually or in clusters in antibody-stained tissue sections of more than one-half of the Duchenne patients. Mutation analysis revealed that revertants occurred in DMD patients with identifiable deletions half of the Duchenne patients. Mutation analysis revealed that revertants occurred in DMD patients with identifiable deletions or duplications, and in nondeletion patients. Prednisone treatment did not influence the prevalence of revertants. Revertants are most likely due to a second-site mutation occurring in a somatic cell allowing for restoration of the translational reading frame of the dystrophin transcript. 
Dimethylformamide-induced liver damage among synthetic leather workers. Prevalence of liver injury associated with dimethylformamide (DMF) exposure was determined. Medical examinations, liver function tests, and creatine phosphokinase (CPK) determinations were performed on 183 of 204 (76%) employees of a synthetic leather factory. Air concentrations of solvents were measured with personal samplers and gas chromatography. The concentration of DMF in air to which each worker was exposed was categorized. High exposure concentrations of DMF (i.e., 25-60 ppm) were significantly associated with elevated alanine aminotransferase (ALT) levels (ALT greater than or equal to 35 IU/l), a result that did not change even after stratification by hepatitis B carrier status. Modeling by logistic regression demonstrated that exposure to high concentrations of DMF was associated with an elevated ALT (p = .01), whereas hepatitis B surface antigen (HBsAg) was slightly but independently associated with an elevated ALT (p = .07). In those workers who had normal ALT values, there occurred still significantly higher mean ALT and aspartate aminotransferase (AST) activities, especially among those who were not HBsAg carriers. A significant association existed between elevated CPK levels and exposure to DMF. However, an analysis of the CPK isoenzyme among 143 workers did not reveal any specific damage to muscles. This outbreak of liver injury among synthetic leather workers is ascribed to DMF. It is recommended that the occupational standard for DMF and its toxicity among HBsAg carriers be evaluated further. 
Parathyroid hypertensive factor, a circulating factor in animal and human hypertension. A new circulating hypertensive factor (parathyroid hypertensive factor; PHF) was shown to exist in the plasma of spontaneously hypertensive rats (SHR) but not in that of normotensive rats. PHF produced a delayed increase in blood pressure with a peak response at 45 min (bolus injection) or 60 to 90 min (continuous infusion). This increase in blood pressure was coupled with an in vitro increase in calcium uptake in rat tail artery with a similar time course. The involvement of calcium in the mechanism of action was supported by the inhibitory effect of calcium antagonists on the vascular action of PHF. Furthermore, PHF increased the intracellular free calcium concentration in cultured smooth muscle cells from rat tail artery. Parathyroidectomy and parathyroid transplant experiments indicated the parathyroid origin of PHF. A culture of parathyroid glands from SHR, but not from normotensive rats, produced in the medium a factor which has the same biological property and HPLC retention time as plasma PHF. A novel cell type was described in the parathyroid gland of SHR, but not normotensive rats, and the percent of these cells correlated significantly with plasma PHF level and blood pressure. In some hyperparathyroid patients, plasma PHF and hypertension were found, both of which disappeared after surgical removal of the parathyroid gland. In both animal models and human studies, PHF seems to be associated with low or normal plasma renin and salt-sensitive type of hypertension. 
How well can radiographers triage x ray films in accident and emergency departments? [published erratum appears in BMJ 1991 Mar 23;302(6778):696] OBJECTIVE--To assess the ability of radiographers to identify abnormal radiographs of patients attending accident and emergency departments. DESIGN--Prospective study over six weeks. SETTING--Teaching hospital casualty x ray department. PATIENTS--3394 consecutive patients referred for radiography. INTERVENTIONS--Radiographs were assessed by radiographers who were offered a four point triage scheme: normal, abnormal, insignificantly abnormal, or further advice required. MAIN OUTCOME MEASURES--Comparison of radiographers' assessments with an assessment made independently by the reporting radiologists. RESULTS--Overall disagreement between the radiographers and radiologists was 9.4%. There were 7% false positives and 14% false negatives. Most errors occurred in assessing radiographs of the skull, facial bones, chest, abdomen, and soft tissues. CONCLUSION--Unselected radiographers can offer useful advice on radiographs to casualty officers, but their high rate of false positive diagnoses indicates that they cannot triage casualty radiographs sufficiently accurately to allow them to extend their current reporting role. 
Early treatment of ischemic stroke with a calcium antagonist. We performed a feasibility and safety study (phase II) of nicardipine, a calcium antagonist, in 57 patients. The objectives of the study were to begin therapy as early as possible (less than or equal to 12 hours) after the onset of ischemic stroke and to administer as high a dose as possible. All patients received an intravenous infusion of nicardipine for 72 hours, starting with a dose of 3 mg/hr and increasing to a maximum dose of 7 mg/hr. Upward titration of the dose was limited by a 10% decrease in blood pressure or a 20 beats/min increase in pulse. Intravenous therapy was followed by 30 days of oral therapy. The mean +/- SD interval from onset of stroke to commencement of therapy was 9.1 +/- 5.4 hours. Adverse reactions consisted primarily of hypotension requiring discontinuation of therapy in four patients. Score on a graded neurologic examination increased from 41/100 at baseline to 64/100 at 3 months for the 41 patients completing follow-up. There was no correlation between the dose of nicardipine administered and outcome, but the 11 patients starting therapy less than or equal to 6 hours after onset did better than those starting therapy 6-12 hours after onset. Further study of very early therapy with nicardipine is justified. 
Should intravenous immunoglobulin G be first-line treatment for acute thrombotic thrombocytopenic purpura? Case report and review of the literature. Acute thrombotic thrombocytopenic purpura (TTP) is a rare and serious disease. Treatment with prednisone, anticoagulation, antiplatelet drugs, splenectomy, exchange transfusions, vincristine, and plasmapheresis may be effective in some patients, but the response to these therapies is inconsistent and all carry the potential for serious side effects. We, and others, have recently seen dramatic responses to intravenous (IV) immunoglobulin G (IgG) when other treatments have failed. Although IV IgG is expensive, its costs are low compared with those extended plasmapheresis regimens. Since the response to treatment can usually be evaluated within a few days and the side effects appear less than with other treatments, we believe a strong case can be made for the use of IV IgG as first-line therapy for acute TTP. Continued multicenter studies are necessary to finally solve the problem of competing and confusing treatment attempts and synergism of treatment in acute TTP. 
The prognostic value of deoxyribonucleic acid flow cytometric analysis in stage D2 prostatic carcinoma. This study was designed to compare the prognostic potential of tumor grade and ploidy status in patients with stage D2 prostate cancer. Two outcome groups were selected on the basis of survival after orchiectomy: a bad outcome group consisting of 66 patients who died of the disease within 12 months and a good outcome group comprising 37 patients who survived beyond 5 years. Tumors were classified histologically as well (17%), moderately (17%) or poorly (66%) differentiated. Tumor grade was a significant predictor of outcome, with 76% of poorly differentiated tumors in the bad outcome group and 65% of well differentiated tumors in the good outcome group (p less than 0.005). Deoxyribonucleic acid (DNA) ploidy analysis was performed on formalin fixed, paraffin embedded samples of the primary tumor to yield 97 final tracings that were classified using set criteria for DNA ploidy status. Over-all, 54% of the tumors were nondiploid (33% aneuploid and 21% tetraploid) and the remaining 46% were diploid. DNA ploidy status was a significant indicator of outcome (p less than 0.001), with 64% of diploid tumors in the good outcome group and 88% of the nondiploid tumors in the poor outcome group. Tetraploid tumors behaved no differently from other nondiploid tumors. We conclude that DNA ploidy status and tumor grading are significant independent predictors of outcome after orchiectomy and when combined yield important additional prognostic information. 
Effects of milrinone on left ventricular remodeling after acute myocardial infarction. BACKGROUND. Left ventricular remodeling after an acute myocardial infarction may result in progressive left ventricular dilation that may be associated with increased mortality. We studied the effects of the phosphodiesterase inhibitor milrinone on left ventricular remodeling after acute myocardial infarction. METHODS AND RESULTS. Rats (n = 90) were randomized to undergo either left coronary artery ligation or sham operation. Three weeks after surgery, rats received either no treatment or milrinone, which was continued until 2 days before the rats were killed. Ninety days after the initial surgery, hemodynamic measurements were made before and after volume loading. The rats were killed, the hearts were removed, and passive pressure-volume curves were obtained. The hearts were fixed at a constant pressure and analyzed morphometrically. Compared with untreated infarcted rats, milrinone-treated infarcted rats had a lower left ventricular end-diastolic pressure (1.7 +/- 0.4 versus 4.3 +/- 1.4 mm Hg, p less than 0.05), a lower left ventricular volume (1.25 +/- 0.20 versus 2.37 +/- 0.30 ml/kg, p less than 0.001) and a lower left ventricular wall stress index (1.3 +/- 0.2 versus 1.7 +/- 0.1, p less than 0.05). Left ventricular chamber stiffness was higher in milrinone-treated infarcted rats than in untreated infarcted rats. Milrinone had no cardiac effect on uninfarcted animals. CONCLUSION. Chronic milrinone therapy after acute myocardial infarction improves cardiac hemodynamic indexes and attenuates progressive left ventricular dilation. 
Nongynecologic somatic pathology in women with chronic pelvic pain and negative laparoscopy. One hundred eighty-three women with chronic pelvic pain were referred to a multidisciplinary chronic pelvic pain clinic after negative laparoscopy. One hundred twenty-two of them completed a thorough medical and psychologic evaluation and were followed for a minimum of six months after completion of therapy. Occult somatic pathology was diagnosed in 57 women (47%), including 19 in whom coexistent psychopathology was diagnosed. Myofascial pain was the most common somatic diagnosis, followed by atypical cyclic pain (dysmenorrhea or mittelschmerz); gastroenterologic, urologic and infectious diseases; and pelvic vascular congestion. No plausible somatic etiology was apparent in the remaining 65 (53%) of the 122 referrals. Nongynecologic somatic pathology accounted for 34 (29%) and gynecologic pathology for 23 (19%) of the referrals, only 6 (5%) of whom ultimately required hysterectomy. Women with a somatic diagnosis were found to be significantly older than the remainder of the referral population. Long-term symptomatic improvement or resolution of pain was obtained in 43 (75%) of the 57 patients with somatic diagnoses. Coexistent psychopathology was found to correlate with a poorer long-term prognosis. Our findings underscore the importance of a multidisciplinary approach to evaluating and treating chronic pelvic pain in women and confirm that hysterectomy is indicated in this setting only rarely. 
Treatment of bone, joint, and vascular-access-associated gram-positive bacterial infections with teicoplanin. Teicoplanin, a glycopeptide antibiotic, was evaluated for safety and efficacy in the treatment of vascular-access-associated bacteremias and of bone and joint infections due to susceptible gram-positive organisms. Of 35 patients enrolled, 26 had osteomyelitis, 8 had vascular-access-associated bacteremias, and 1 had a joint infection. A total of 38 gram-positive isolates were identified: 23 Staphylococcus aureus and 6 coagulase-negative staphylococcus and 9 streptococcus isolates. After at least 6 months of follow-up, 17 patients were evaluable for efficacy: 10 of 14 (71%) with osteomyelitis and 3 of 3 with vascular-access-associated bacteremias had full resolution of their infections. Inadequate debridement, the presence of metal, and inadequate dosing were likely causes of two failures and two relapses in patients with osteomyelitis. For all but two organisms, teicoplanin MICs were less than or equal to 2 micrograms/ml. Patients who responded had median peak and trough serum bactericidal levels at serum dilutions of 1:64 and 1:16; trough levels of teicoplanin in serum were greater than 30 micrograms/ml. Patients did not respond as expected to daily doses of 4 mg/kg of body weight, which consequently were increased to greater than or equal to 15 mg/kg. Audiology testing of 20 patients found 2 with a mild loss of high-frequency hearing; 1 patient complained of tinnitus. Patients tolerated peak levels in serum as high as 127 micrograms/ml and trough levels of 49 micrograms/ml. However, 5 of 18 patients (28%) whose daily dose was greater than or equal to 12 mg/kg developed drug fever and rash and had teicoplanin discontinued. Further study of the antibiotic at such higher doses is needed. 
Effect of the calcium antagonist nicardipine hydrochloride on glucose tolerance and insulin secretion. The calcium antagonist nicardipine was administered to 42 patients at a dose of 60 or 120 mg/day for an average of 7.8 weeks to determine its effects on glucose tolerance and insulin secretion. Glucose tolerance and immunoreactive insulin levels were essentially unchanged by nicardipine regardless of the preexisting level of glucose tolerance. Mean systolic and diastolic blood pressures decreased in all patients. Concentrations of triglycerides decreased and high-density lipoprotein cholesterol levels increased significantly (p less than 0.05) in association with nicardipine administration. Therefore it is concluded that, regardless of the preexisting level of glucose tolerance, nicardipine exerted hypotensive effects without significant adverse effects on glucose tolerance or insulin secretion. 
Monitoring of somatosensory evoked potentials during surgery for middle cerebral artery aneurysms. Somatosensory evoked potentials (SEPs) were monitored during 53 procedures for aneurysms of the middle cerebral artery (MCA). "Significant" changes were reported to the surgeon, who took corrective action when possible. Changes in the SEPs were categorized as follows: Type I, no change; Type II, significant change with complete return to baseline; Type III, significant change with incomplete return to baseline; Type IV, complete loss with no return; and Type V, no response at baseline. Only 1 of 37 patients with a Type I SEP had a new neurological deficit, and this was a patient who could not be examined for several days after surgery because he was in a pentobarbital coma. All 4 patients with Type III and IV changes had new postoperative neurological deficits. Perhaps of greater importance, 4 of 5 patients with Type II changes had no new deficit. These patients all had changes in SEPs that were completely reversible by clip adjustment (2), prompt removal of temporary clips (1), and inducing hypertension after aneurysm trapping (1). These cases may, therefore, represent instances in which SEP monitoring allowed the clinicians to prevent a neurological deficit. The MCA supplies the area of the somatosensory cortex that controls the hand. Median nerve SEPs are, therefore, a theoretically ideal monitor during surgery for MCA aneurysms. This study suggests that the results of MCA aneurysm surgery may be accurately predicted and improved with SEP monitoring. 
Clinical diagnosis for metastatic adenocarcinoma of spine of unknown origin. A comparative study. The diagnostic values of the presence of Virchow's node (VN) or rectal shelf (RS) in spinal metastasis from adenocarcinoma of unknown origin were studied prospectively in 60 patients during 1986-1988. These were compared with 14 cases with other malignancies of the spine and 37 controls with nonneoplastic spinal lesions. The diagnosis was confirmed by histologic study in all malignant cases. The results were analyzed by diagnostic test analysis and McNemar chi 2 testing. This yields 18.3-21.6%, 97.2-100%, and 92.8-100% sensitivity, specificity, and predictive value, respectively, for a positive test for VN and RS to differentiate significantly adenocarcinoma from other malignancies and control patients (P less than 0.005). These findings may thus be considered as a simple and economic guide for physicians to determine the proper approach to patients with a spinal lesion suspected to be malignant. 
Indirect laryngoscopic approach for injection of botulinum toxin in spasmodic dysphonia. Spasmodic dysphonia is a focal dystonia that causes a loss of the fine control of intrinsic laryngeal muscles and produces a strained staccato voice. Temporary relief from symptoms has been reported in patients treated with botulinum toxin percutaneously injected into the thyroarytenoid muscle. A newly developed method of treatment differs from reported methods by increasing the accuracy of botulinum toxin placement, reducing soft tissue trauma, and applying basic scientific information about the functional histology of intrinsic laryngeal musculature. Sixteen patients with primarily adductor spasmodic dysphonia were treated. Initial assessment included laryngeal examination by indirect laryngoscopy, videoendoscopy, and stroboscopy, neurology examination (including laryngeal EMG), and vocal function studies with acoustic analysis and aerodynamic studies. A device originally designed for collagen injection allowed the precise microdelivery of toxin to the thyroarytenoid muscle. Indirect laryngoscopy was used to direct the needle, in an attempt to cover a broad area of motor end plates. The minimally effective dose was titrated for each patient, to avoid paralysis and preserve laryngeal function. All patients showed improved voices after treatment. There were no major complications. The basic technique can be performed in the otolaryngologist's office and does not require electromyography equipment or expertise. 
A new approach to the differential diagnosis of a regular tachycardia with a wide QRS complex. BACKGROUND. In the differential diagnosis of a tachycardia with a wide QRS complex (greater than or equal to 0.12 second) diagnostic mistakes are frequent. Therefore, we investigated the reasons for failure of presently available criteria, and we identified new, simpler criteria and incorporated them in a stepwise approach that provides better sensitivity and specificity for making a correct diagnosis. METHODS AND RESULTS. A prospective analysis revealed that current criteria had a poor specificity for the differential diagnosis. The value of four new criteria incorporated in a stepwise approach was prospectively analyzed in a total of 554 tachycardias with a widened QRS complex (384 ventricular and 170 supraventricular). The sensitivity of the four consecutive steps was 0.987, and the specificity was 0.965. CONCLUSIONS. Current criteria for the differential diagnosis between supraventricular tachycardia with aberrant conduction and ventricular tachycardia are frequently absent or suggest the wrong diagnosis. The absence of an RS complex in all precordial leads is easily recognizable and highly specific for the diagnosis of ventricular tachycardia. When an RS complex is present in one or more precordial leads, an RS interval of more than 100 msec is highly specific for ventricular tachycardia. This new stepwise approach may prevent diagnostic mistakes. 
The infectious and hematologic otolaryngic complications of myelosuppressive cancer chemotherapy. The otolaryngologist-head and neck surgeon is frequently consulted to evaluate patients before the administration of myelosuppressive cancer chemotherapy. Fifty consecutive patients treated at the University of Pennsylvania Oncology Center were studied before and during chemotherapy for adult leukemia or bone marrow transplantation. Otolaryngic history, physical examination, radiographic studies, and hematologic surveys were analyzed for the duration of therapy in an attempt to identify risk factors for infectious and hematologic otolaryngic complications. Two-thirds of the patient studied experienced untoward effects that required the further attention of an otolaryngologist-head and neck surgeon. The various complications and associated correlations with the study parameters before and during chemotherapy are discussed. 
Results of long-term rice bran treatment on stone recurrence in hypercalciuric patients. A series of 182 calcium stone formers with idiopathic hypercalciuria underwent treatment with rice bran for 1 to 94 months. Urinary calcium excretion was considerably reduced, but there was some increase in urinary phosphate and oxalate. Urinary excretion of magnesium and uric acid, serum calcium, magnesium, phosphate, uric acid, parathyroid hormone (PTH) and ALP was unaffected. There were no obvious changes in serum iron, zinc and copper even when patients were treated for long periods. Rice bran was well tolerated in almost all cases and there were no serious side effects; 49 patients have undergone treatment for more than 3 years (average duration of administration 5.09 years). The frequency of new stone formation was drastically reduced (individual stone formation rate (no./year) from 0.720 +/- 0.533 to 0.125 +/- 0.204; group stone formation rate (no./patient-year) from 0.721 to 0.120) compared with the 3-year period before treatment. During treatment, 61.2% of patients remained in remission. Although rice bran therapy should be effective in correcting absorptive hypercalciuria, there may be limits to the overall ability of rice bran monotherapy to prevent recurrence. 
Phase II trial of weekly or biweekly intraperitoneal mitoxantrone in epithelial ovarian cancer. Previous experimental and clinical evaluation has suggested that ovarian cancer is sensitive to the cytotoxic effects of mitoxantrone at concentrations achievable within the peritoneal cavity after intraperitoneal (IP) administration. Unfortunately, the use of the drug delivered IP at high doses (20 mg/m2 in 2 L normal saline [NS]) on a monthly schedule is compromised by severe local effects secondary to the irritant properties of the drug. To reduce toxicity and take advantage of minimal systemic drug exposure following IP administration, we treated 28 patients with a lower drug concentration of mitoxantrone (10 mg/m2 in 2 L NS), but on a weekly or every other week schedule (total, 12 courses). Compared with the monthly program, this regimen caused less pain, allowed for a higher cumulative dose of mitoxantrone to be delivered, and resulted in less serious treatment-related morbidity. Four of 13 assessable patients (31%) whose largest tumor was less than or equal to 1 cm in diameter demonstrated a surgically defined response. All responding patients had failed previously or exhibited a minimal response to cisplatin. Despite the improved toxicity profile of this regimen, the overall response rate was similar to the monthly program, probably secondary to inadequate IP drug distribution in many patients. Future investigative efforts using IP mitoxantrone as therapy for ovarian cancer might focus on developing methods to improve drug delivery to all sites of tumor within the peritoneal cavity (eg, intraoperative therapy, increased treatment volumes, and antiinflammatory agents to reduce adhesion formation). 
The influence of the renin gene on alcohol consumption in Dahl rats. A rat renin allele (the S-allele) has been identified in Dahl rats which cosegregates with increases in blood pressure. Rats with a double dose of the allele--the salt-sensitive hypertensive rats--have low renin activity compared with the salt-resistant hypertensive rat that does not have this S-allele. Alcohol consumption in rats has also been shown to vary with renin activity, and the possible involvement of renin activity in the genetics of alcohol consumption was suggested by previous work showing that the alcohol-preferring P line of selected rats had low renin levels. In the present study we examined alcohol consumption in a group of inbred Dahl rats, which have a double dose of the S renin allele, and in a group of selected Dahl rats, which have only a single dose of this S-allele. After an initial acclimation period, these two groups were first given daily 1-hr access to ascending concentrations of alcohol (3%, 6%, 8% w/v) over a 34-day period followed by continuous access to alcohol for a further 10 days. Water and food were always available. Regardless of whether alcohol was rationed or continuously available, the rats with the double dose of the S-allele drank significantly more alcohol than the rats that had only a single dose of this allele. These findings suggest that genetically mediated alterations in the renin gene may exert a significant influence on alcohol consumption and may be a component in the etiology of alcoholism. 
Electrothrombosis of saccular aneurysms via endovascular approach. Part 2: Preliminary clinical experience. Fifteen patients with high-risk intracranial saccular aneurysms were treated using electrolytically detachable coils introduced via an endovascular approach. The patients ranged in age from 21 to 69 years. The most frequent clinical presentation was subarachnoid hemorrhage (eight cases). Considerable thrombosis of the aneurysm (70% to 100%) was achieved in all 15 patients, and preservation of the parent artery was obtained in 14. Although temporary neurological deterioration due to the technique was recorded in one patient, no permanent neurological deficit was observed in this series and there were no deaths. It is believed that this new technology is a viable alternative in the management of patients with high-risk intracranial saccular aneurysms. It may also play an important role in the occlusion of aneurysms in the acute phase of subarachnoid hemorrhage. 
The impact of National Health Service Corps physicians in the lowering perinatal mortality rate in Dade County, Florida. In some parts of Dade County, Florida, perinatal mortality rates have revealed serious problems in the delivery of health care to poor pregnant women. From 1982-1985, the reported perinatal mortality rates varied from 32-36 per 1000 live births, more than double the national average. Under the leadership of the Primary Health Care Consortium of Dade County (a federation of community health centers and other primary care providers), National Health Service Corps obstetricians and pediatricians served inner-city, medically needy patients as part of a coordinated perinatal plan from 1987-1989. Data on fetal and neonatal deaths, collected from census tracts adjacent to the community health centers, were used to study the impact of Corps obstetrician and pediatrician placement. The respective perinatal mortality rates were compared with those of 1986 as historic controls. Within a year, the overall perinatal mortality rate was reduced by 45%. As a result, an estimated 320 lives were saved between 1987-1989. This public health achievement represents a measurable impact due to assignment of National Health Service Corps physicians and can be used as a working model to reduce perinatal mortality in medically underserved communities in the United States. 
Elevation of ambulatory systolic blood pressure in hypertensive smokers. A case-control study. Although smoking raises blood pressure, the office blood pressure measurements of smokers are the same as, or lower than, those of nonsmokers. To resolve this paradox, we compared the office and 24-hour ambulatory blood pressures of 59 untreated hypertensive smokers with 118 nonsmoking hypertensives matched for age, sex, and race. The office blood pressures of the smoking and nonsmoking groups were 141/93 and 142/93 mm Hg, respectively. The awake ambulatory systolic blood pressure was significantly higher in the smokers (145 vs 140 mm Hg). This difference was greater among patients over the age of 50 years (153 vs 142 mmHg), and absent among patients under 50 years (140 vs 139 mm Hg). Blood pressures during sleep did not differ between the two groups (121/76 vs 123/77 mm Hg). We conclude that, among white hypertensives above the age of 50 years, smokers maintain a higher daytime ambulatory systolic blood pressure than nonsmokers even though blood pressure measured in the office is similar. 
Bilateral central retinal vein occlusion as an initial manifestation of pseudotumor cerebri. Pseudotumor cerebri, or benign intracranial hypertension, is known to produce visual symptoms. Central retinal vein occlusion has been linked with pseudotumor cerebri but rarely as an initial manifestation. We describe a 46-year-old patient--who was obese and mildly hypertensive with bilateral central retinal vein occlusions--who was subsequently diagnosed as having pseudotumor cerebri. In patients with simultaneous bilateral central retinal vein occlusions, unusual underlying systemic conditions such as pseudotumor cerebri should be considered in the diagnostic evaluation. 
Laser laparoscopic management of large endometriomas. Forty-seven patients underwent laser laparoscopic management of endometriomas from 3 to 12 cm in diameter. Eighteen patients had infertility, 15 had pelvic pain, and 14 had both. The types of laser used were the carbon dioxide, argon, and potassium-titanyl-phosphate. There were no surgical complications. Twelve of 32 patients with infertility achieved pregnancy after the initial procedure. Subsequently, 2 patients conceived after a second-look procedure. Twenty-three of 30 patients with pelvic pain reported improvement or resolution. We confirm the efficacy of operative laparoscopy using lasers in the management of large ovarian endometriomas. 
Serum cholesterol: attitudes and behavior of family practice residents BACKGROUND. Given the current health promotion efforts regarding coronary artery disease, more information is needed about residents' attitudes and behaviors that relate to identification and management of patients with elevated serum cholesterol levels. METHODS. Family practice residents from eight US programs (N = 128) were surveyed in 1989 to assess their attitudes and reported practice patterns. Resident survey data were compared, when feasible, to published data from 1986 and 1990 surveys of practicing physicians performed by the National Heart, Lung, and Blood Institute. RESULTS. The use of faculty "key contacts" resulted in a 90% response rate (N = 115). Both residents and practicing physicians attributed a high degree of importance to cholesterol as a risk factor. Residents reported more frequent routine screening of middle-aged men than the routine screening rate of practicing physicians in 1986 (P less than .01). Residents reported less frequent screening of younger and older adults than of middle-aged men (P less than .001). Residents' threshold for the use of cholesterol-lowering medication was lower than that of practicing physicians surveyed in 1986, but higher than that of physicians surveyed in 1990. Compared with practicing physicians, residents did not believe they were as well prepared to counsel patients about dietary change or as successful when they tried to help patients make changes; residents reported a significantly higher rate of referral to dietitians (P less than .01). CONCLUSIONS. Residents may need more education regarding screening guidelines for children and young adults. A health promotion skills gap may exist that explains reported discrepancies between self-report and actual behavior and indicates that residency educators may need to pay more attention to fostering dietary assessment and counseling skills in their residents. 
Normal serum levels of calcitonin gene-related peptide (CGRP) in mild to moderate essential hypertension. Calcitonin gene-related peptide (CGRP), a highly potent vasodilator, is expressed from the calcitonin-gene and has been localized to nerve fibers of the cardiovascular system, suggesting involvement in the physiologic regulation of vascular tone. In this investigation serum concentrations of CGRP were measured in patients with untreated mild to moderate essential hypertension (WHO I-II) and compared with concentrations in sex- and age-matched normal controls to assess a possible relationship between changes in concentrations of CGRP and this condition. The study showed no significant difference in concentrations of CGRP between patients and the normotensive controls. However, a weak but significant positive correlation was found between systolic (SBP), diastolic (DBP), mean blood pressures (MBP), and circulating concentrations of CGRP when calculated for all individuals included in the study. No correlation was found between heart rates (HR) and concentrations of CGRP. In the normotensive control group, but not in patients with hypertension, a significant positive correlation was present between body weights and concentrations of CGRP. These findings do not support the hypothesis that low expression of CGRP plays a causal role in essential hypertension, but the results do not exclude a potential receptor defect for CGRP to be involved in the disease. 
Constitutive expression and role in growth regulation of interleukin-1 and multiple cytokine receptors in a biphenotypic leukemic cell line. A cell line (B1) was established from the bone marrow of a patient with a relapse of acute leukemia characterized by a 4;11 chromosomal translocation and biphenotypic features of early B and myeloid lineages. Analysis of the growth requirements of this cell line showed density-dependent growth and secretion of an autostimulatory growth factor, suggesting an autocrine mechanism. Several lines of evidence implicate the participation of interleukin-1 (IL-1) in the autocrine growth regulation of B1 cells. These cells constitutively express the messenger RNA (mRNA) for IL-1 and IL-1 receptor and secrete IL-1; recombinant IL-1 stimulated the growth of colonies when cells were seeded at low density, and anti-IL-1 antibodies inhibited the growth of colonies with cells seeded at higher density. B1 cells do not express detectable levels of mRNA for any of the other cytokines tested, and other cytokines failed to support the growth of B1 cells at low density. In addition, B1 cells express multiple cytokine receptor genes, including the receptors for IL-6, IL-7, tumor necrosis factor and gamma-interferon. Addition of the respective cytokines to the B1 cells resulted in inhibition of the growth of leukemic cells in vitro. The multiplicity of growth-inhibitory cytokine receptors on this leukemic cell line might be due to its biphenotypic lineage and may suggest new therapeutic possibilities in controlling leukemic cell proliferation. 
Cephalometric measurements in snorers, non-snorers, and patients with sleep apnoea. Cephalometry is often used to assess patients with sleep apnoea but whether these measurements differ from those in non-apnoeic snorers and how they are influenced by age is not clear. Cephalometric radiographs of patients with sleep apnoea were compared with those of snorers without sleep apnoea and those of non-snorers. Fifty two snorers with suspected sleep apnoea had a conventional sleep study and were divided into two groups: those with an apnoea-hypopnoea index greater than 10/h (n = 40, sleep apnoea group) and those whose apnoea-hypopnoea index was 10/h or less (n = 12, snorer group). The cephalometric measurements in these patients were compared with those of 34 non-snoring control subjects. Controls were subdivided into two groups: control group 1 included 17 subjects similar in age to the sleep apnoea and snorer groups (mean (SD) age 50.0 (10.9), 50.7 (9.4), and 50.6 (9.7) years); control group 2 included 15 young men (25.4 (2.6) years). The distance from the mandibular plane to the hyoid bone (MP-H) and the length of the soft palate were greater in the patients with sleep apnoea (28.7 (7.8) and 43.6 (5.0) mm) than in the snorers (23.7 (4.2) and 40.3 (4.9 mm). The MP-H was similar in snorers and age matched control subjects, but was significantly greater in the older than in the younger control subjects (22.1 (6.1) vs 17.0 (6.8]. The soft palate was longer in subjects who snored (both sleep apnoea patients and snorers) than in control subjects. The MP-H distance significantly correlated with age for all subjects (snorers and controls) and for the control subjects alone. This study shows that non-apnoeic snorers have cephalometric abnormalities that differ from those of patients with sleep apnoea and that cephalometric values are influenced by the subject's age. 
Unexpected immunoreactivities of intermediate filament antibodies in human brain and brain tumors. Immunoreactivities of 35 different monoclonal antibodies (MAbs) that detect intermediate filaments were studied systematically on serial cryostat sections of 14 well-defined human gliomas (five astrocytomas, three oligodendrogliomas, six glioblastomas) and on normal brain. Glial fibrillary acidic protein (GFAP), vimentin, desmin, neurofilaments, and broad-specificity keratin MAbs, as well as MAbs that recognize several or only single keratin polypeptides, were used. Unexpected reactivities were surprisingly frequent. As these may lead to diagnostic confusion and misinterpretation on this material, the authors investigated these phenomena more thoroughly. Four major sources of artifactual staining were found: 1) positive staining attributable to the rabbit gamma G immunoglobulins used in the alkaline phosphatase anti-alkaline phosphatase technique; 2) certain desmin and keratin MAbs cross-reacted with astrocytic glia and with other brain-specific epitopes; 3) technical difficulties; 4) some MAbs directed against neurofilaments and keratins showed unexpected reactivities only on individual anaplastic gliomas. The implications of these findings for intermediate filament typing of neuropathologic material are discussed. 
A novel behavioral model of neuropathic pain disorders produced in rats by partial sciatic nerve injury. Partial nerve injury is the main cause of causalgiform pain disorders in humans. We present here a novel animal model of this condition. In rats we unilaterally ligated about half of the sciatic nerve high in the thigh. Within a few hours after the operation, and for several months thereafter, the rats developed guarding behavior of the ipsilateral hind paw and licked it often, suggesting the possibility of spontaneous pain. The plantar surface of the foot was evenly hyperesthetic to non-noxious and noxious stimuli. None of the rats autotomized. There was a sharp decrease in the withdrawal thresholds bilaterally in response to repetitive Von Frey hair stimulation at the plantar side. After a series of such stimuli in the operated side, light touch elicited aversive responses, suggesting allodynia to touch. The withdrawal thresholds to CO2 laser heat pulses were markedly lowered bilaterally. Suprathreshold noxious heat pulses elicited exaggerated responses unilaterally, suggesting thermal hyperalgesia. Pin-prick evoked such exaggerated responses bilaterally (mechanical hyperalgesia). In a companion report, we show that these abnormalities critically depend on the sympathetic outflow. Based on the immediate onset and long-lasting perpetuation of similar symptoms, such as touch-evoked allodynia and hyperalgesia, and the resemblance of the contralateral phenomena to 'mirror image' pains in some humans with causalgia, we suggest that this preparation may serve as a model for syndromes of the causalgiform variety that are triggered by partial nerve injury and maintained by sympathetic activity. 
Susceptibility of normal human joint tissue to viruses. A model system has been developed to investigate the comparative ability of different viruses to replicate and persist intraarticularly. The viruses chosen for study were rubella, mumps, Coxsackie B4, adenovirus and varicella zoster, a selection of viruses with different degrees of association with joint symptoms in clinical studies. Our results showed that these viruses demonstrated a range of abilities to infect and persist in human joint tissue cultured in vitro. The most arthritogenic viruses, rubella, and to a lesser extent mumps, replicated and penetrated deeply into the synovial membrane. In contrast, the other 3 viruses were much less arthrotropic, and may only induce arthritis by immunopathological mechanisms. 
Intermittent claudication as a manifestation of silent myocardial ischemia: a pilot study. One hundred consecutive patients with intermittent claudication were screened noninvasively with electrocardiography chest wall mapping stress test and transcutaneous aortovelography during bicycle ergometry. Electrocardiographic chest wall stress testing indicated three-vessel coronary disease in 25 patients and left anterior descending plus circumflex (left main stem equivalent) disease in seven. In these 32 patients transcutaneous aortovelography demonstrated a decrease in stroke distance (an index of cardiac stroke volume) (median, -28%; 90% range, +5% to -48%), and coronary angiography confirmed the presence and severity of the disease. The claudication distance ranged between 50 and 250 meters. After myocardial revascularization or medical therapy a significant increase occurred in the stroke distance after exercise (median, +20; 90% range, +40% to -25%); also a significant increase in the postexercise pressure index and a reduction in the recovery time (p less than 0.01). No change occurred in the ankle/pressure index at rest. Twelve patients were able to walk without being limited by claudication; 15 reported improvement with a two to tenfold increase in claudication distance. No change occurred in three. The results indicate that silent myocardial ischemia is a common finding in patients with intermittent claudication. It produces left ventricular dysfunction and a decrease in stroke volume leading to a large fall in ankle pressure and early onset of claudication during exercise. Niltrates and myocardial revascularization tend to reverse this. 
Intractable ulcerating enterocolitis of infancy. Five children (three boys, two girls) presenting in the first year of life with intractable diarrhoea had a number of features in common. All had ulcerating stomatitis, four had partial villous atrophy on small intestinal biopsy, all had colitis characterised by large ulcers with overhanging edges, and four had severe perianal disease; no stool pathogens were detected. Treatment with steroids, sulphasalazine, and azathioprine was unsuccessful. All five required subtotal colectomy. Four were children of consanguinous marriages, two were siblings of Pakistani origin, two were cousins of Arab origin, and the fifth was Portuguese. Although the diagnoses of Behcet's disease and Crohn's disease were considered, it appears that these children represent a distinct inherited condition affecting the whole gastrointestinal tract, particularly the colon. 
Improving survival in gastric cancer: review of operative mortality in English language publications from 1970. In this review of English language publications from 1970, operative mortality following surgery for gastric cancer has been analysed. Operative mortality has declined in series reporting operations in successive decades to 1970, 1980 and 1990. Series reporting patients having surgery for gastric cancer in the decade to 1990 show a mean operative mortality rate of 7.8 per cent (median 4.6 per cent). This improvement may have contributed to the declining mortality rates for gastric cancer in the face of unchanging surgical workload. Results of operations for gastric cancer should be reported in a standard manner. 
Aetiological parallel between anal cancer and cervical cancer. It has been postulated that an infectious agent and/or specific sexual behaviour is involved in the aetiology of anal cancer, in analogy with the aetiology established for cancer of the cervix. A case-control study of 29,648 women with cancers registered in the Danish Cancer Registry during 1968-87 tested the hypothesis that anal cancer patients were more likely than patients with colon, stomach, or vulva cancer to have had a previous diagnosis of cervical intraepithelial neoplasia (CIN) or invasive cervical cancer. The odds ratio of CIN, adjusted for age and year of diagnosis, for anal vs colon cancer was 5.2 (95% confidence interval [CI] 3.3-8.3), that for anal vs stomach cancer 3.6 (2.1-6.0), and that for anal vs vulva cancer 1.6 (0.9-2.9). The median time from diagnosis of CIN to diagnosis of the registered cancer was 151 months for anal, 112 months for vulva, 114 months for colon, and 126 months for stomach cancer. The association with previous invasive cervical cancer was also investigated; no patient with cervical cancer in this second analysis had been included in the CIN analysis. The odds ratios were similar. In addition, anal cancer patients were significantly more likely to have had cervical cancer than were patients with vulva cancer (odds ratio 1.8 [1.0-3.9]). The strong association between anal cancer and CIN/invasive cervical cancer suggests that these cancers share common risk factors. The association is at least as strong as that between cervical and vulva cancer. 
Reversible tricuspid stenosis. Demonstration with two-dimensional echocardiography and continuous-wave Doppler. We report a case of pseudo-tricuspid stenosis as a result of extrinsic compression of the tricuspid valve by a large right-sided pericardial effusion. Two-dimensional echocardiography and continuous-wave Doppler enabled accurate noninvasive diagnosis and hemodynamic assessment. 
Positive serum antibody and negative tissue staining for Helicobacter pylori in subjects with atrophic body gastritis. Helicobacter pylori is rarely found in gastric biopsy specimens from individuals with atrophic gastritis of the body mucosa. To determine if subjects with atrophic body gastritis have evidence of previous infection with H. pylori, immunoglobulin G antibody to H. pylori was measured by enzyme-linked immunosorbent assay in sera of 399 Finnish subjects. In 124 subjects, multiple biopsy specimens from body and antrum had been evaluated for the presence of H. pylori by Giemsa staining. Antibody correlated well with H. pylori staining except in the subgroup with atrophic body gastritis, in whom the prevalence of seropositivity (86%) was significantly greater than the prevalence of positive staining (33%) (P less than 0.001). Twenty-five subjects had positive antibody and negative staining. This group had a significantly higher prevalence of atrophic body gastritis (80%), lower maximal acid output, lower serum pepsinogen I levels, and higher serum gastrin concentrations than did seropositive subjects with H. pylori. These data suggest that most patients with atrophic body gastritis, despite having a low incidence of current overt infection, have been infected with H. pylori at some point in their lives. 
Superoxide production by Crohn's disease neutrophils. Neutrophil superoxide anion production was measured in healthy subjects and in patients with quiescent and active Crohn's disease using superoxide dismutase inhibitable cytochrome C reduction. Three stimuli were used: phorbol 12-myristate 13-acetate (PMA1), phorbol 20-oxo-20-deoxy 12-myristate 13-acetate (PMA2), and Candida albicans in serum. Normal neutrophils produced significantly more superoxide anion than Crohn's disease neutrophils with both PMA1 (mean (SD) 9.6 (2.2) v 8.6 (1.8) nmol/10(6) cells/5 minutes, p = 0.04) and PMA2 (1.8 (0.8) v 0.8 (0.77) nmol/10(6) cells/5 minutes, p = 0.00004). With C albicans in serum, normal and Crohn's disease neutrophils produced similar amounts of superoxide anion (4.4 (1.5) v 4.3 (1.7) nmol/10(6) cells/30 minutes, not significant). Results were independent of disease activity. Superoxide anion production by PMA-stimulated Crohn's disease neutrophils is significantly lower than by normal neutrophils. 
Increased circulating concentration of the N-terminus of the atrial natriuretic factor prohormone in persons with pheochromocytomas. To investigate the possible relationship of hypertension and the N-terminus of the atrial natriuretic factor (ANF) prohormone which contains two peptides [i.e. pro ANF-(1-30) and pro-ANF-(31-67)] with blood pressure-lowering effects, we examined the circulating levels of the N-terminus of the ANF prohormone in three patients with pheochromocytomas before surgery, during an increase in their blood pressure with surgical manipulation of their tumors, and after surgery when their blood pressures returned to normal. The circulating levels of the whole N-terminus [amino acids 1-98; pro-ANF-(1-98)] and pro-ANF-(31-67) from the midportion of the N-terminus of the ANF prohormone were increased 2-fold in patients with both extraadrenal and intraadrenal pheochromocytomas. In both the intraadrenal and extraadrenal patients N-terminus [pro-ANF-(1-98)] and pro-ANF-(31-67) circulating levels increased further during surgical manipulation and returned to normal after surgical removal of their respective tumors. Each of these pheochromocytomas was found to have pro-ANF-(1-30) and -(31-67)-binding sites that were functional, since they could enhance the guanylate cyclase-cGMP system 2-fold in these pheochromocytomas. The entire 126 amino acids of the prohormone were present within each of the pheochromocytomas, since both the whole N-terminus and C-terminus (i.e. ANF) of the prohormone were present. Examination of the pheochromocytomas by electron microscopy revealed electron-dense granules similar to those in the heart, which have been associated with the synthesis and storage of the ANF prohormone. We conclude that 1) the whole N-terminus [pro-ANF-(1-98)] and pro-ANF-(31-67) of the ANF prohormone circulate at higher concentrations in persons with pheochromocytomas and return to normal with removal of the tumors; 2) pheochromocytomas contain specific binding sites for pro-ANF-(1-30) and -(31-67); 3) these binding sites are functional, since pro-ANF-(1-30) and -(31-67) could enhance the enzyme guanylate cyclase within these tumors; and 4) the entire 126 amino acids of the ANF prohormone are present within these tumors, which have electron-dense granules associated with polypeptide hormone synthesis, suggesting that the ANF prohormone is being synthesized within the pheochromocytomas. 
Use of human recombinant erythropoietin to correct severe preoperative anemia. The risks of homologous blood transfusion are well known. Herein, we describe the successful preoperative use of human recombinant erythropoietin to correct severe anemia in a patient refusing transfusion. This case report emphasizes the important perioperative role human recombinant erythropoietin may play in the future. 
Cancer staging may have different meanings in academic and community hospitals. We investigated differences in lung cancer care and outcome between academic and community settings for all lung cancer patients diagnosed during 1973-1976 in New Hampshire and Vermont. Trained abstracters reviewed hospital charts to record personal, diagnostic, and clinical information, and survival was determined for all patients through the end of 1979. Patients diagnosed in university hospital cancer centers underwent more staging procedures and tended to be assigned to a higher stage than similar patients diagnosed in community hospitals. When tumor stage was considered as a covariable in a survival analysis, these patients appeared to have a lower mortality rate both for non-small cell tumors (mortality rate ratio, 95% confidence interval = 0.81, 0.71-0.91) and for small cell tumors (0.71, 0.55-0.91). When functional status rather than tumor stage was used to adjust for disease severity, there was no apparent survival advantage for university patients with non-small cell cancer (0.96, 0.85-1.09) and the lower mortality for small cell cancers (0.76, 0.59-0.97) was attenuated, although still statistically significant. We conclude that inconsistently-collected data on clinical stage can complicate comparisons of prognosis between cancer patients from different types of hospitals and that measures of performance status may be more useful indicators of disease severity in population based studies. 
Changes in intracranial CSF volume after lumbar puncture and their relationship to post-LP headache. Post-lumbar puncture (LP) headache may be due to "low CSF pressure", leading to stretching of pain sensitive intracranial structures. The low intracranial pressure is secondary to net loss of intracranial CSF. It has, however, not been possible to measure intracranial CSF volume accurately during life until recently. Intracranial CSF volume can now be measured non-invasively by a MRI technique. The changes in intracranial CSF volume were studied in 20 patients who had LP. Total intracranial CSF volume was reduced in 19 of the 20 patients 24 hours after LP (range -1.8 mls to -158.6 mls). Most of the CSF was lost from the cortical sulci. Very large reductions in intracranial CSF volume were frequently related to post-LP headache but some patients developed headache with relatively little alteration in the intracranial CSF volume. There was not a measurable change in position of the intracranial structures following LP. 
Prognostic value of proliferating cell nuclear antigen in gastric carcinoma. A new monoclonal antibody to proliferating cell nuclear antigen (PCNA), PC10, which can be used on routinely processed tissue, was applied to 93 cases of gastric carcinoma. Significant intra-tumoural variation in staining occurred. In addition to a PCNA index (percentage of positive cells per 1000 tumour cells), a semiquantitative PCNA grading system was devised, based on estimates of less than or more than 50% of positive tumour cells in whole sections. Neither PCNA index nor PCNA grade showed any correlation with established histological variables, tumour stage, or the presence of lymph node metastases. No significant correlation was observed between PCNA index and S + G2M phase fraction measured by flow cytometric analysis. To analyse survival tumours with PCNA indices above and below the median level (41%) were compared. Those with a higher index tended to have a worse prognosis, but when PCNA grade was considered, it was found to have definite independent prognostic value, tumours of low grade surviving better than those of high grade. The ability of semiquantitative PCNA grading to allow for intra-tumoural variation suggests it may have advantages over absolute counting, which is prone to sampling error when tumour heterogeneity is a major factor. The prognostic value of PC10 staining in gastric carcinoma is therefore promising. 
Renal oncocytomas--an Australian experience. A review was made of 24 cases of renal oncocytoma seen between 1978 and 1989. There was considerable overlap between the clinical presentation of renal oncocytomas and renal carcinomas. Although pre-operative radiological, cytological and pathological investigations may suggest the presence of an oncocytoma, these studies cannot make a definitive diagnosis. We recommend that these tumours be treated as potential renal carcinomas until post-operative microscopic evaluation proves otherwise. 
Transient myocardial ischemia during daily life in rest and exertional angina pectoris and comparison of effectiveness of metoprolol versus nifedipine. The clinical characteristics of 65 patients with mixed angina were classified by means of (1) a questionnaire investigating the proportion of symptoms occurring at rest and on effort, (2) an exercise stress test, (3) 24-hour ambulatory Holter monitoring, and (4) coronary arteriography. According to the questionnaire, the proportion of effort-induced anginal episodes ranged from 1 to 99%. The ischemic threshold during exercise testing ranged from 110 x 10(2) to 350 x 10(2) mm Hg x beats/min. At least 1 episode of ST-segment depression was observed in 29 of the 65 patients during Holter monitoring. Ischemic episodes during Holter monitoring were more frequent (p less than 0.05) in patients reporting greater than or equal to 50% of anginal attacks on effort, with moderate to severe limitation of exercise capacity and with multivessel coronary artery disease. The effect on ambulatory ischemia of a 6-week treatment with a beta blocker (metoprolol CR, 200 mg once daily) or a dihydropyridine calcium antagonist (nifedipine retard 20 mg twice daily) were then compared according to a double-blind, parallel group design. Metoprolol significantly reduced the number and duration of the ischemic episodes during daily life (p less than 0.05) irrespective of the patients' clinical characteristics. Nifedipine was ineffective, particularly in patients with angina predominantly on effort and with a moderate to severe reduction in exercise tolerance. It is concluded that in patients with mixed angina, ischemic episodes during daily life are more likely to occur in patients with a clinical presentation suggesting poor coronary reserve. 
Liver transplantation for alcoholic liver disease, viral hepatitis, and hepatic neoplasms. In closing, it is important to note that the indications for liver transplantation are not static but rather are remarkably dynamic and capable of change over time. Thus yesterday's major indications can become relative contraindications, while yesterday's absolute contraindications have become today's nuisances. The goal for physicians who care for individuals with problems such as alcoholic liver disease, viral hepatitis, and hepatic cancer should be to develop new strategies of care that will ultimately eliminate these diseases as problems, rather than eliminating individuals with such health problems from currently available health options. In other words, physicians who accept the responsibility for a patient's life should be searching for the best form of therapy available for their patient rather than examining the reasons that exist for limiting one's choice in health care. 
The value of class IC antiarrhythmic drugs for acute conversion of paroxysmal atrial fibrillation or flutter to sinus rhythm. In a single-blind randomized study, the efficacy and safety of intravenous propafenone (2 mg/kg body weight per 10 min) versus flecainide (2 mg/kg per 10 min) were assessed in 50 patients with atrial fibrillation or flutter. Treatment was considered successful if sinus rhythm occurred within 1 h. Conversion to sinus was achieved in 11 (55%) of 20 patients with atrial fibrillation treated with propafenone and in 18 (90%) of 20 with atrial fibrillation treated with flecainide (p less than 0.02). If atrial fibrillation was present less than or equal to 24 h, conversion to sinus rhythm was achieved in 8 (57%) of 14 patients in the propafenone group and 13 (93%) of 14 in the flecainide group (p less than 0.05). Atrial flutter was converted in two (40%) of five patients treated with propafenone and in one (20%) of five with flecainide (p = NS). Mean time to conversion was 16 +/- 10 min in the propafenone group versus 18 +/- 13 min in the flecainide group (p = NS). QRS lengthening (83 +/- 15 to 99 +/- 20 ms) was observed only in the patients treated with flecainide (p less than 0.001). Patients successfully treated with propafenone showed significantly higher plasma levels than those whose arrhythmia did not convert to sinus rhythm. Transient adverse effects were more frequent in the flecainide group (40%) than in the propafenone group (8%) (p less than 0.01). In conclusion, at a dose of 2 mg/kg in 10 min, flecainide is more effective than propafenone for conversion of paroxysmal atrial fibrillation to sinus rhythm. However, considering the propafenone plasma levels and very few adverse effects, the dose or infusion rate, or both, used in the propafenone group may not have been sufficient to achieve an optimal effect. Neither drug seems very effective in patients with atrial flutter. 
Intracerebral hemorrhage related to cerebral amyloid angiopathy and t-PA treatment. Tissue plasminogen activator (t-PA) has been approved as thrombolytic therapy for the treatment of acute myocardial infarction, but this agent can cause serious bleeding complications including intracerebral hemorrhages. Mechanisms underlying the development of these hemorrhages have not been clarified. We report a patient who developed two intracerebral hemorrhages shortly after receiving t-PA for the treatment of an acute myocardial infarction, and who was found to have cerebral amyloid angiopathy at autopsy. Staining of cortical sections with Congo red and an antibody directed against beta amyloid protein (A4 peptide) disclosed specific involvement of most of the subarachnoid and superficial cortical vessels in the region of the two hemorrhages. Based on the findings in this patient and in 6 additional patients reported recently, it is likely that cerebral amyloid angiopathy plays a pathogenic role in some intracerebral hemorrhages associated with the administration of t-PA. The cautious use of t-PA with heparin in patients who are elderly or demented may be advisable. 
The initiation of failure in cemented femoral components of hip arthroplasties. We studied 16 femora retrieved at post-mortem from symptomless patients who had a satisfactory cemented total hip arthroplasty from two weeks to 17 years earlier, with the aim of delineating the initial mechanisms involved in loosening. Only one specimen showed radiographic evidence of loosening; the other 15 were stable to mechanical testing at 17.0 Nm of torque. In all 16 specimens, the cement-bone interface was intact with little fibrous tissue formation. By contrast, separation at the cement-prosthesis interface and fractures in the cement mantle were frequent. The most common early feature was debonding of the cement from the metal, seen at the proximal and distal ends of the prosthesis. Specimens which had been in place for longer also showed circumferential fractures in the cement, near the cement-metal interface, and radial fractures extending from this interface into the cement and sometimes to the bony interface. The most extensive cement fractures appeared to have started at or near sharp corners in the metal, or where the cement mantle was thin or incomplete. Fractures were also related to voids in the cement. The time relationship in this series suggested that long-term failure of the fixation of cemented femoral components was primarily mechanical, starting with debonding at the interface between the cement and the prosthesis, and continuing as slowly developing fractures in the cement mantle. 
Epicardial coronary artery tone and reactivity in patients with normal coronary arteriograms and reduced coronary flow reserve (syndrome X) The vasomotor response of proximal and distal angiographically normal coronary artery segments was studied in 12 patients with syndrome X, 17 age- and gender-matched patients with chronic stable angina and 10 control subjects with atypical chest pain and a normal coronary arteriogram. Ergonovine (300 micrograms by intravenous injection) and isosorbide dinitrate (1 mg by intracoronary injection) were administered to all patients. Computerized coronary artery diameter measurement (angiographically normal segments only) was carried out before and after the administration of ergonovine and nitrate. Baseline intraluminal diameters (mean +/- SEM) of proximal and distal coronary segments were not significantly different in control subjects and patients with syndrome X or coronary artery disease (proximal 2.88 +/- 0.19, 3.01 +/- 0.13 and 2.86 +/- 0.13 mm; distal 1.57 +/- 0.09, 1.70 +/- 0.10 and 1.61 +/- 0.06 mm, respectively). With ergonovine, proximal segments constricted by 10 +/- 2%, 7 +/- 2% and 11 +/- 3% and distal segments by 12 +/- 3%, 14 +/- 3% and 14 +/- 2% in control subjects and patients with syndrome X or coronary artery disease, respectively (p = NS). With isosorbide dinitrate, proximal coronary segments dilated by 11 +/- 2%, 10 +/- 2% and 8 +/- 2% (p = NS) and distal segments by 15 +/- 2%, 11 +/- 3% and 13 +/- 2% (p = NS) in control subjects and patients with syndrome X or coronary artery disease, respectively. Within groups, constriction in response to ergonovine and dilation in response to nitrate were not significantly different in proximal and distal segments. 
Surgical evaluation of Henoch-Schonlein purpura. Experience with 110 children. Henoch-Schonlein purpura is a disorder of unknown origin that is probably related to an autoimmune phenomenon. This report concerns 110 children (mean age, 6.2 years; range, 6 months to 14 years) with Henoch-Schonlein purpura. Seventy-two (65%) had abdominal pain associated with nausea and vomiting, bloody stool, and upper gastrointestinal bleeding. Sixty patients with abdominal pain were evaluated and treated conservatively. However, 12 patients underwent laparotomy. Six underwent unnecessary appendectomy for wrongly diagnosed appendicitis. Bowel resection was performed in one patient for an obstructive ileal lesion. Six additional patients had intussusception; surgery was required in three, while barium enema reduction was successfully accomplished in three others. Massive gastric hemorrhage required ligation, vagotomy, and pyloroplasty in two instances. One child with severe scrotal pain, hemorrhage, and swelling underwent unnecessary scrotal exploration. Four additional patients with similar symptoms avoided operation after a testicular scintiscan demonstrated good blood flow. A high index of suspicion and early diagnosis of Henoch-Schonlein purpura based on clinical, roentgenographic, and laboratory findings may avoid unnecessary operations in most cases. However, life-threatening complications (hemorrhage, obstruction, and intussusception) may occur and require operative intervention. All of the patients survived. 
Surgically induced endometriosis does not alter peritoneal factors in the rabbit model. OBJECTIVE: It was the purpose of this study to examine the cause and effect relationship between alterations in peritoneal factors and the presence of ectopic endometrium in the rabbit model. DESIGN: Forty rabbits had autologous endometrial or omental (control) tissue surgically implanted. Peritoneal fluid (PF) volume, macrophage number, and macrophage activation, as well as the number of implants with adhesions, were compared with values obtained during the initial surgery. The effect of hormonal treatment on these factors was evaluated at a third laparotomy. RESULTS: There was a significant increase (P less than 0.05) of adhesions in animals with endometrial implants. Peritoneal fluid volume, macrophage number, or macrophage activation were not increased in rabbits with endometrial implants as compared with controls, nor was there a response to hormonal manipulation. CONCLUSIONS: These results demonstrate that PF volume, macrophage number, and macrophage activation are not altered by endometrial implants in the rabbit model. This suggests that the increase in these peritoneal factors in women with endometriosis may not be caused exclusively by the presence of ectopic endometrial tissue. 
Jugular venous 'a' wave in dilated cardiomyopathy: sign of abbreviated right ventricular filling time. OBJECTIVE--To study the mechanisms underlying the high venous pressure often seen in patients with dilated cardiomyopathy. DESIGN--Retrospective and prospective examination of the pattern of flow in the superior vena cava, cardiac echo-Doppler studies, and recordings of the jugular venous pulse. SETTING--A tertiary referral cardiac centre. PATIENTS PARTICIPANTS--23 patients with dilated cardiomyopathy, all with functional mitral and tricuspid regurgitation. RESULTS--Two patterns of venous pulse were seen: a dominant 'a' wave and 'x' descent, with systolic flow in the superior vena cava (group 1, n = 11), and a dominant 'v' wave with 'y' descent and diastolic flow in the superior vena cava (group 2, n = 12). A comparison of group 1 and group 2 showed: age (mean (SD] 58 (12) v 61 (6) years, left ventricular end diastolic dimension 7.0 (0.7) cm in both groups, right ventricular short axis 3.3 (0.6) v 3.6 (0.5) cm and long axis 7.3 (0.5) v 7.1 (0.7) cm, and duration of tricuspid regurgitation 350 (65) v 370 (50) ms. The RR interval (550 (100) v 680 (80) ms) and right ventricular filling time (150 (30) v 290 (50) ms) were significantly shorter in group 1. In all patients in group 2 right ventricular filling time was more than 200 ms with separate E and A waves on the tricuspid Doppler echocardiogram, while in all group 1 patients it was less than 200 ms with a single summation peak. In nine patients in group 1, the right ventricular filling time was limited by prolonged tricuspid regurgitation and in the remaining two by prolonged isovolumic relaxation time (215 (80) ms), so that it was consistently significantly less than that of the left ventricle. CONCLUSION--In patients with dilated cardiomyopathy, right ventricular filling time may be so short that it limits stroke volume. Such patients can be recognised by a dominant 'a' wave on the jugular venous pulse. Patients in whom the right ventricular filling time was longer showed a dominant 'v' wave. Both groups can present as "congestive heart failure". 
Impaired response of atrial natriuretic factor to blood volume expansion in acute right ventricular infarction. To assess the role of atrial natriuretic factor (ANF) in right ventricular (RV) infarction, 30 patients with inferior wall acute myocardial infarction (15 with RV involvement) and normal left heart filling pressures were studied 39 +/- 12 hours after the onset of symptoms. Serial measurements of cardiac output, right atrial, pulmonary artery and pulmonary wedge pressures, as well as plasma ANF, plasma renin activity, plasma aldosterone and vasopressin were obtained before and 30 minutes after acute volume expansion to raise wedge pressure greater than or equal to 20 mm Hg. Baseline mean right atrial pressure and plasma ANF levels were greater in patients with than without RV infarction (8 +/- 3 vs 5 +/- 2 mm Hg; p less than 0.0001, and 4.6 +/- 2.9 vs 2.7 +/- 1.5 fmol/ml; p less than 0.05, respectively). There were no differences in other baseline hemodynamic or humoral parameters between both groups. After volume expansion, pulmonary wedge pressure was similar in both groups, but right atrial pressure increased to higher levels in patients with RV infarction (19 +/- 2 vs 14 +/- 2 mm Hg; p less than 0.0001). Despite this greater stimulus for ANF secretion, the increase in plasma ANF was less pronounced in patients with RV infarction (63 +/- 81 vs 455 +/- 417%; p less than 0.002), especially among those with paroxysmal supraventricular tachyarrhythmias. Thus, despite higher baseline plasma levels of ANF, response to volume loading is markedly attenuated in patients with RV infarction complicating an inferior wall acute myocardial infarction. 
Relative importance of eight virulence characteristics of pyelonephritogenic Escherichia coli strains assessed by multivariate statistical analysis. We have previously reported univariate statistical analysis of the prevalences of putative virulence determinants in Escherichia coli isolated from children and adults with acute pyelonephritis. The expression of P-fimbriae, cell surface hydrophobicity, mannose resistant haemagglutination, haemolysin synthesis, cytotoxic necrotizing factor production and aerobactin mediated iron uptake occurred more often in a collection of 115 Escherichia coli strains isolated from children and women with acute non-obstructive pyelonephritis compared to 96 strains isolated from the commensal fecal flora. With the aim to study which of these virulence markers were independently associated with strains causing infection we performed a multivariate statistical analysis with the data from these strains. The previously proposed virulence factors, expression of type 1 fimbriae and adhesion to HeLa cells were also included in the analysis. P-fimbriae, mannose resistant haemagglutination and the production of haemolysin were, in the multivariate analysis, associated with strains isolated from patients with acute pyelonephritis. 
Sensitivity, specificity and predictive value of the sensation of warmth as a method of detecting inadvertent subarachnoid injection of local anaesthetic when performing extradural blocks. In order to test if the rate of onset of sensation of warmth in the legs after the injection of 0.5% bupivacaine might discriminate between subarachnoid and extradural injection, 150 urological patients were allocated randomly to receive either spinal anaesthesia with isobaric (IS) or hyperbaric (HS) 0.5% bupivacaine, or extradural anaesthesia with isobaric 0.5% bupivacaine. The volume of the local anaesthetic for spinal anaesthesia and for the extradural test dose was 3-4 ml. The patients were asked to report at once if they had a sensation of warmth in the legs during or after injection of local anaesthetic. The mean time to the sensation of warmth was significantly shorter in the spinal groups (80 (SEM 10) s in IS and 76 (8.0) s in HS) than in the extradural group (558 (38) s). However, six patients in the IS and two in the HS group had no sensation of warmth. 
Recommendations for preventing transmission of human immunodeficiency virus and hepatitis B virus to patients during exposure-prone invasive procedures. This document has been developed by the Centers for Disease Control (CDC) to update recommendations for prevention of transmission of human immunodeficiency virus (HIV) and hepatitis B virus (HBV) in the health-care setting. Current data suggest that the risk for such transmission from a health-care worker (HCW) to a patient during an invasive procedure is small; a precise assessment of the risk is not yet available. This document contains recommendations to provide guidance for prevention of HIV and HBV transmission during those invasive procedures that are considered exposure-prone. 
The value of pancreatic pseudocyst amylase concentration in the detection of pseudocyst communication with the pancreatic duct. The aims of the study were to compare the results of endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous cystopancreatography (PCP) in the detection of the communication between the pancreatic pseudocyst and the pancreatic duct, and to assess the reliability of the increased amylase concentration in the pseudocyst content as an indicator of the existence of communication between the pancreatic pseudocyst and the pancreatic duct system. Forty-three patients were included in the study. Pseudocystic fluid content was obtained by percutaneous aspiration. Twenty-four patients had pseudocyst amylase concentrations above 64 Wolgemuth units (WU), and 19 patients had less than 64 WU. The communication between pseudocyst and the pancreatic duct was determined in 22 patients by ERCP and in 13 patients by PCP, all in the group with increased pseudocyst amylase concentration. Due to high sensitivity and specificity of pseudocyst amylase concentration for the existence of pseudocyst communication with the pancreatic duct, we conclude that guided percutaneous aspiration of the pancreatic pseudocyst with the determination of amylase concentration in the fluid can replace ERCP as a method of choice for the detection of pseudocyst communication with the pancreatic duct. 
Intestinal injury after lumbar discectomy. In a review of 5,200 lumbar discectomies performed from 1974 to 1989, two patients sustained a ventral perforation of the disc space followed by isolated small intestinal injury. Both patients underwent lumbar discectomy at the lumbosacral junction and presented with signs and symptoms of acute abdominal distress within three days after the operation. At surgical laparotomy, small tears were noted in the ileum, which were closed primarily. The patients had an uneventful recovery. The results of a review of 11 instances reported in the literature suggest that isolated intestinal injuries usually occur postoperatively at the lumbosacral junction and involve the small intestine. Factors, such as body habitus, surgical experience, patient positioning and types of instruments, as well as the use of a surgical microscope, do not appear to modify the risk of intestinal injury. After discectomy, patients may present with acute abdominal signs and symptoms or chronic wound infections. Work-up studies include evaluation of vascular structures and ureters either roentgenographically or at abdominal exploration. A high index of suspicion and adequate disc space visualization during discectomy may reduce the incidence of this complication. 
Salvage of nonunion following ankle arthrodesis for failed total ankle arthroplasty. Revision operations for nonunion following total ankle arthrodesis for total ankle arthroplasty (TAA) were reviewed in ten patients. Operations averaged 2.0 years after prior arthrodesis attempts and featured external fixation in seven, internal fixation in one, percutaneous pin fixation in one, and cast immobilization only in one. Bone graft was used in seven. Union was achieved in 78%. The one complication was an infection in a patient with prior sepsis. The results were considered excellent in three, good in one, fair in three, and poor in two of the nine patients with adequate follow-up evaluation (average, 7 years). Despite successful arthrodesis, residual symptoms were common because of factors such as hindfoot degenerative arthritis and malalignment. 
Serum vitamin D metabolites and bone mineralization in young children with chronic low to moderate lead exposure. One hundred five children (49 male, 99 black) with known lead exposure indices from birth and adequate nutrient intake of calcium, phosphorus, and vitamin D were studied at 1 of 3 ages (21, 27, or 33 months) to determine the effects of chronic low to moderate lead exposure on circulating concentrations of vitamin D metabolites and bone mineral content as determined by photon absorptiometry. Univariate multiple regression analyses showed no direct relationship of blood lead levels to vitamin D metabolites or bone mineral content. Structural equation analyses which took into account potential covariates of age, season, race, and sex showed estimated declines in serum concentrations of total calcium (from 9.72 to 9.61 mg/dL), phosphorus (from 5.4 to 4.67 mg/dL), and 25-hydroxyvitamin D (from 27.24 to 25.8 ng/mL) and estimated increases in concentrations of parathyroid hormones (from 73.03 to 83.14 microL Eq/mL), 1,25-dihydroxyvitamin D (from 62.39 to 62.69 pg/mL), and bone mineral content (from 222.66 to 234.91 mg/cm) over the observed range of average lifetime blood lead concentrations (4.76 to 23.61 micrograms/dL, geometric mean 9.74 micrograms/dL). However, the only statistically significant effect of average lifetime blood lead concentration was that for phosphorus, and the multivariate test of the combined effects of lead on these six outcomes was not statistically significant (P = .2). It is concluded that significant alterations in vitamin D metabolism, calcium and phosphorus homeostasis, and bone mineral content are not present in children whose nutritional status is adequate and who experience low to moderate lead exposure. 
A weekly cisplatin-based induction regimen for extensive non-small cell lung cancer. A Southwest Oncology Group study. The purpose of this Phase II pilot study was to determine whether a dose-intensive regimen of weekly cisplatin combined with other active non-cross-resistant agents would improve the response rate and survival time of patients with extensive non-small cell lung cancer. Patients received cisplatin (50 mg/m2/wk) on days 1, 8, 15, 22, 36, 43, 50, and 57 combined with mitomycin C (8 mg/m2) on days 1 and 36, vinblastine (3 mg/m2) on days 8 and 43, and 5-fluorouracil (5-FU) (1 g/m2) by continuous infusion over 24 hours on days 15 and 50. Responding patients received consolidation therapy with cisplatin and etoposide (VP-16). Of 82 registered patients, 80 were eligible and 77 were evaluable for response. The overall response rate was 23% with 1 patient achieving a complete response (CR) and 17 patients achieving a partial response (PR). The median survival time was 4.6 months. The toxicity profile was not different from that described for standard-dose regimens. Although this regimen does not offer any benefit over standard-dose cisplatin regimens for patients with extensive non-small lung cancer, the weekly schedule permits a dose-intensive regimen with acceptable toxicity for tumors that may benefit from this approach. 
Increased expression of intercellular adhesion molecule 1 on bile ducts in primary biliary cirrhosis and primary sclerosing cholangitis. It has been suggested that immunological mechanisms involving lymphocyte-mediated damage are important in the characteristic bile-duct damage that occurs in primary biliary cirrhosis and primary sclerosing cholangitis. Because adhesion is necessary for the interaction of lymphocytes with their target structures, we have studied the expression of intercellular adhesion molecule 1, a ligand for the leukocyte adhesion receptor lymphocyte function-associated antigen 1 in the liver of patients with primary biliary cirrhosis and primary sclerosing cholangitis. Strong expression of intercellular adhesion molecule 1 was seen on interlobular bile ducts and proliferating bile ductules in both conditions. In primary biliary cirrhosis, medium-sized ducts, which are spared by the disease, were negative. Minimal bile-duct staining was seen in conditions in which bile-duct damage is not a major feature, such as nonbiliary cirrhosis and acute liver diseases. In patients with cirrhosis from any cause, strong expression of intercellular adhesion molecule 1 was detected on the periseptal hepatocytes adjacent to new connective tissue. The intensity of immunohistochemical staining was recorded using a semiquantitative visual scoring system that was subsequently validated quantitatively by confocal laser scanning microscopy. The expression/induction of intercellular adhesion molecule 1 on bile ducts may be important in the pathogenesis of bile-duct damage in primary biliary cirrhosis and primary sclerosing cholangitis and is further evidence to support an immune pathogenesis in these two conditions. Furthermore, the induction of intercellular adhesion molecule 1 on hepatocytes may be an important factor in the liver-cell damage and fibrosis that occur during the development of cirrhosis. 
Salvage of thrombosed forearm polytetrafluoroethylene vascular access grafts by reversal of flow direction and venous bypass grafting. A technique is described for salvage of looped forearm polytetrafluoroethylene (PTFE) vascular access grafts that fail because of thrombosis due to cephalic vein outflow obstruction. It entails reversal of blood flow direction through the graft and construction of a new venous outflow in the medial upper arm. This procedure was performed in nine patients and, at the present time, has increased the graft life by an average of 6.2 months (range: 2 to 14 months) in eight. We conclude that this is a useful alternative to abandoning failed looped forearm PTFE grafts that have cephalic vein outflow obstruction. 
A comparison of dopexamine and dopamine to prevent renal impairment in patients undergoing orthotopic liver transplantation. The efficacy of low-dose dopamine as a renal protective agent was compared with that of dopexamine in patients who underwent orthotopic liver transplantation. Twelve patients who received a continuous infusion of dopexamine (1-3 micrograms/kg/minute) were matched for age, diagnosis, pre-operative creatinine clearance and blood loss with 12 patients who received a low-dose infusion of dopamine (2 micrograms/kg/minute). The catecholamine infusion was started after induction of anaesthesia and continued for 48 hours after surgery. Patients in the dopexamine group had less evidence of renal impairment and failure than those in the dopamine group during 7 days after the operation, although the differences between groups did not achieve statistical significance. Similarly there were no significant differences between the two groups in peri-operative urine output, urine/plasma osmolality ratio or creatine clearance. Dopexamine is at least as effective as dopamine for renal protection in patients who undergo liver transplantation. 
Alteration of urinary carnitine profile induced by benzoate administration. To study the effect of sodium benzoate on carnitine metabolism, the acylcarnitine profile in the urine of five normal volunteers and two patients with urea cycle disorders was examined with fast atom bombardment-mass spectrometry. The volunteer subjects were given 5 g of sodium benzoate orally and the two patients with urea cycle disorders (carbamyl phosphate synthetase deficiency type I and ornithine transcarbamylase deficiency) were already undergoing treatment with sodium benzoate and L-carnitine. The amount of benzoylcarnitine excretion depended on the dose of both sodium benzoate and L-carnitine in a reciprocal relation. Increased excretions of acetylcarnitine and propionylcarnitine were also noted after sodium benzoate administration. The alteration of the urinary aclycarnitine profile was consistent with the change of mitochondrial CoA profile predicted by in vitro studies of an animal model. It is suggested that urinary acylcarnitine analysis is important to assess the effect of benzoate administration on mitochondrial function in vivo. Supplementation with carnitine may be necessary to minimise the adverse effects of sodium benzoate treatment in hyperammonaemia. 
Magnetic resonance imaging of spinal trauma. A retrospective series of 118 magnetic resonance examinations of 110 patients who had sustained previous spinal trauma is reported. Examinations performed within 3 weeks of trauma showed extraspinal soft tissue (including ligamentous) injury in 48% and intraspinal lesions in 61% (mostly consisting of extradural haematoma and spinal cord contusion). In examinations performed more than 3 weeks after injury intraspinal abnormalities were shown in 51% and these represented spinal cord compression, atrophy, myelomalacia and syringohydromyelia. Magnetic resonance imaging has the unique capability of displaying non-invasively the late sequelae of spinal trauma permitting simultaneous evaluation of the extra-spinal soft tissues, vertebral column and spinal cord. It is therefore recommended as the technique of choice in the investigation of patients who have sustained previous spinal injury, particularly those with neurological deficit. In the acute phase potentially remediable causes of neurological impairment such as disc herniation or extradural haematoma can be identified. Signal changes in the cord may allow the prognosis for neurological recovery to be established. In the later stages sequelae such as cord atrophy, myelomalacia and syringohydromyelia are accurately identified and surgical therapy may be guided, where appropriate. 
Altered density of glomerular binding sites for atrial natriuretic factor in bile duct-ligated rats with ascites. The renal response to atrial natriuretic factor is blunted in cirrhosis with ascites. This might be due to alterations of renal receptors for atrial natriuretic factor. Therefore density and affinity of glomerular atrial natriuretic factor binding sites of bile duct-ligated rats with ascites (n = 10) and of sham-operated controls (n = 10) were determined. Glomerular atrial natriuretic factor binding sites were identified to be of the B-("biologically active") and C-("clearance") receptor type. Discrimination and quantitative determination of B and C receptors for atrial natriuretic factor were achieved by displacement experiments with atrial natriuretic factor(99-126) or des(18-22)atrial natriuretic factor(4-23), an analogue binding to C receptors only. Density of total glomerular atrial natriuretic factor binding sites was significantly increased in bile duct-ligated rats (3,518 +/- 864 vs. 1,648 +/- 358 fmol/mg protein; p less than 0.05). This was due to a significant increase of C-receptor density (3,460 +/- 866 vs. 1,486 +/- 363 fmol/mg protein; p less than 0.05), whereas density of B receptors was not significantly different in bile duct-ligated rats (58 +/- 11 vs. 162 +/- 63 fmol/mg protein). Affinity of atrial natriuretic factor to its glomerular binding sites did not differ significantly between both groups. These data suggest that an altered glomerular atrial natriuretic factor receptor density could be involved in the renal resistance to atrial natriuretic factor in cirrhosis with ascites. 
The change in patterns of relapse in medulloblastoma. The authors reviewed 89 patients treated for cerebellar medulloblastoma between 1970 and 1989 to determine the impact of changing treatment (high-dose posterior fossa radiation therapy and chemotherapy) on the pattern of failure in medulloblastoma. Between 1970 and 1983, 50 patients (median follow-up, 110 months) were treated with surgery and postoperative craniospinal irradiation (CSI). Nineteen of the 50 (38%) recurred in the central nervous system (CNS). Isolated systemic (bone) metastases occurred in six. The median time to the development of bone metastases was 12 months. Since 1984, 39 patients (median follow-up, 27 months) were treated with preradiation chemotherapy consisting of cisplatin and vincristine for 9 weeks before initiation of CSI. Nine of the 39 (23%) patients recurred in the CNS. There were no systemic failures in this cohort. The actuarial 5-year disease-free survival was 55 +/- 7% for the earlier cohort and 72 +/- 8% for the later cohort (P equals 0.3). Posterior fossa recurrence was associated with radiation therapy to this area. The cumulative incidence of posterior fossa relapse was 50 +/- 13% in patients who received less than 5300 cGy and 18 +/- 7% in those who received 5300 cGy or more (P equals 0.005). All six bone relapses were in patients treated with CSI alone and 5300 cGy or more to the posterior fossa for a 5-year cumulative incidence of bone metastases of 18 +/- 7% compared with 0% for patients treated with 5300 cGy or more and chemotherapy (P equals 0.03). The authors concluded that high-dose radiation therapy has altered the pattern of relapse with an increase in systemic recurrence after radiation therapy alone that is now equivalent to the risk of recurrence in the posterior fossa. Chemotherapy may be indicated in an attempt to decrease this high risk of systemic metastases. 
Long-term follow-up after prosthetic replacement of the superior vena cava combined with resection of mediastinal-pulmonary malignant tumors. The contraindication to curative excision of mediastinal and pulmonary cancers because of invasion of the superior vena cava is now challenged by the existence of vascular prostheses that are suitable for venous replacement. Between 1979 and 1990 22 patients underwent resection of lung cancer (n = 6) or malignant mediastinal tumors (n = 16) involving the superior vena cava. Resection was done with concomitant venous reconstruction, and polytetrafluorethylene grafts were used. All bronchogenic carcinomas necessitated right pneumonectomy, whereas the excision of mediastinal tumors had to include pulmonary resections in nine patients (five lobectomies and four sublobar resections) and the right phrenic nerve in 12 patients. Venous reconstruction was performed by interposition of a large polytetrafluoroethylene graft between the proximal and cardiac ends of the superior vena cava (n = 8), or between one (n = 10) or both brachiocephalic veins (n = 4) and the right atrium. One patient died postoperatively (4.5%), and another had mediastinitis that was successfully treated by omentopexy. Chemotherapy was administered preoperatively to five patients and postoperatively to seven patients; radiotherapy was administered to two and 10 patients, respectively. The overall actuarial survival rate is 48% at 5 years, with 11 patients presently alive. The survival rate of patients with mediastinal tumors is 60% at 5 years. Among the patients with lung cancer, two with N1 disease are alive at 16 and 51 months, and one died at 38 months; the two patients with N2 disease died at 6 and 8 months. Only one graft occlusion occurred in the postoperative period; another occurred 14 months after operation and was precipitated by insertion of a central venous catheter. The patency of all remaining grafts was demonstrated after an average time of 23 (1 to 98) months. On the basis of these results, polytetrafluoroethylene graft replacement of the superior vena cava should be part of the planning and execution of radical excision with curative intent of mediastinal and right pulmonary malignant tumors that are not present with other contraindications, such as pleural or distant metastasis and severe systemic disease. 
Tolerance of gastric mucosal flap to postoperative irradiation. When malignant lesions of the oral cavity, base of tongue, and oropharynx are treated with radical resection, adequate reconstruction is required. The free gastric mucosal flap with microvascular transfer is being used with increasing frequency at Washington University Medical Center. Because of the advanced nature of the primary lesions, most patients also require postoperative radiation therapy. In this paper the tolerance of the gastric mucosal flap to postoperative radiation therapy is reviewed. The changes resulting from radiation therapy in the mucosal flap were found to be acceptable, and no major complications were encountered. 
Intravenous heme-albumin in acute intermittent porphyria: evidence for repletion of hepatic hemoproteins and regulatory heme pools. The purpose of this study was to assess effects of heme administered intravenously, complexed to human serum albumin, on activities of the hepatic hemoproteins, cytochrome(s) P-450, and tryptophan pyrrolase, and on the size of the heme pool that regulates activity of 5-aminolevulinate synthase. Effects were compared in six normal women and four women with acute intermittent porphyria. All porphyric subjects over-excreted heme precursors and had histories of acute neurovisceral porphyric attacks. All subjects were placed on a constant daily diet that included at least 3 g carbohydrate/kg body weight and sufficient total intake to provide 1.4 times the estimated resting energy expenditure. Urinary excretions of 5-aminolevulinate, porphobilinogen, porphyrins, and metabolites of tryptophan were measured daily before, during, and after infusions of heme-albumin. In the porphyric subjects, intravenous heme [4 mg (6.1 mumol)/kg body weight (BWt) with equimolar albumin], given daily for 4 days, markedly reduced overexcretion of 5-aminolevulinate, porphobilinogen, and porphyrins, indicating repletion of the regulatory heme pool. The heme infusions also decreased mean urinary excretion of 5-hydroxyindoleacetic acid from 4.9 to 2.9 mg/g creatinine per day, suggesting increased activity of hepatic tryptophan pyrrolase, the rate-controlling enzyme for metabolism of tryptophan to products not in the serotonin-5-hydroxyindoleacetic acid pathway. Heme-albumin infusions were without detectable effects on excretions of heme precursors or tryptophan metabolites in normal subjects. In contrast, in both normals and porphyrics, heme-albumin infusions significantly increased rates of antipyrine metabolism (by 159% and 330%, respectively), suggesting increased activities of cytochrome(s) P-450 were produced by the infusions. The infusions were well tolerated; no subject developed thrombophlebitis or bleeding. We conclude that such infusions are safe and effective in repleting deficient heme pools and hemoproteins in patients with acute porphyria, and that activities of cytochrome(s) P-450 in normal subjects may also be increased by heme administration. The therapeutic effect of heme in acute porphyria probably relates to its ability to decrease overproduction of precursors of heme or serotonin, as the result of its increasing critical cellular heme pools. 
Anti-V region antibodies as "almost clonotypic" reagents for the study of cutaneous T cell lymphomas and leukemias. Despite recent advances in the understanding of normal T lymphocyte immunobiology, there has been little progress in characterizing the non-HTLV cutaneous T-cell lymphomas and leukemias (CTCL) Mycosis Fungoides and Sezary syndrome. The two major impediments to in vitro studies of these malignancies have been the contamination of CTCL cells with normal T cells and the inability to induce a vigorous proliferative response or establish long-term cultures with standard T-cell mitogens. The ideal reagent for identifying CTCL cells in a given patient would be tumor specific. Although a monoclonal antibody to the clonotypic antigen receptor on CTCL cells would approach this ideal, it is not currently feasible to generate such antibodies for each CTCL patient. As a compromise, we chose to test an "almost clonotypic" reagent by examining whether monoclonal antibodies directed at the variable (V) region of the T-cell antigen receptor could be applied to CTCL. We identified three Sezary patients, who by standard T-cell phenotype and Southern blot analysis for clonality had a virtually pure peripheral blood population of leukemic cells (PBL). We then screened the PBL of these patients with a panel of seven commercially available monoclonal anti-V region antibodies and found one patients' cells reacted greater than 99% with alpha V beta 5. The other patients' cells were non-reactive. In addition, we utilized a solid-phase system to cross-link V beta 5 on the one CTCL patients' PBL cells, and found that they proliferated vigorously in the presence of 10 units of IL-2 and IL-4. Parallel cultures have been maintained for one month by restimulation twice a week. These findings suggest that anti-V region antibodies should prove useful for investigating the immunobiology of CTCL. 
Double-blind, placebo-controlled study of the therapeutic use of recombinant human erythropoietin for anemia associated with chronic renal failure in predialysis patients. The US Recombinant Human Erythropoietin Predialysis Study Group [published erratum appears in Am J Kidney Dis 1991 Sep;18(3):420] One hundred seventeen patients with anemia related to chronic renal failure not severe enough to require maintenance dialysis were randomly assigned to receive recombinant human erythropoietin (rHuEPO; 50, 100, or 150 U/kg body weight) or placebo intravenously (IV) three times a week for 8 weeks or until their anemia was corrected. Correction of anemia (hematocrit of 40% for males, 35% for females) occurred in 87% of those given 150 U/kg, 64% of those given 100 U/kg, 46% of those given 50 U/kg rHuEPO and in 3% of the placebo group. Energy levels and work capacity improved significantly in the group with corrected anemia compared with the group with uncorrected anemia. rHuEPO appeared to be well tolerated. There was no evidence that rHuEPO therapy accelerated the deterioration of renal function as measured by serum creatinine and reciprocal of serum creatinine compared with placebo treatment. However, it is essential that blood pressure and hematocrit be carefully monitored, particularly in hypertensive patients, to prevent the development of complications associated with hypertension. 
Preeclampsia as the great impostor. In contrast with a generation ago when preeclampsia was misdiagnosed as medical or surgical disease unrelated to pregnancy, today's diagnostic errors are those that consider surgical and medical problems as either pregnancy-induced hypertension or as the hemolysis, elevated liver enzymes, and low platelet count syndrome. Eleven case histories are presented of significant medical or surgical problems that were initially diagnosed as hemolysis, elevated liver enzymes, and low platelet count syndrome or pregnancy-induced hypertension. The incorrect diagnosis of medical-surgical cases during pregnancy often meant that appropriate therapy was delayed and that the rate of iatrogenic prematurity was increased. 
IgA nephropathy in non-cirrhotic portal hypertension. Renal glomerular changes are a well recognised complication of cirrhosis and are frequently characterised by mesangial IgA deposition. We report a patient with non-cirrhotic portal hypertension who developed IgA nephropathy and a nephrotic syndrome with renal histological changes classically associated with cirrhosis. Splenectomy with resection of a splenic artery aneurysm resulted in remission of the nephrotic syndrome. This case illustrates the factors which contribute to the pathogenesis of IgA nephropathy in liver disease. 
Folk terminology for diarrhea in rural Bangladesh. Diarrhea, a descriptive term used in medical science for a variety of clinical diseases, denotes an illness that is categorized differently and known by numerous terms in various cultures. These diversified classifications and terminologies are based on the symptoms of diarrheal disorders, their perceived etiology, and their treatment. In Bangladesh, four types of illnesses with names derived from folk terminology have been identified for which the clinical symptoms resemble those of diarrhea. These include dud haga, which is due to ingestion of breast milk by infants; ajirno, which is due to overeating; amasha, a mucoid diarrhea; and daeria, which is severe watery diarrhea or cholera. Use of the word diarrhea in epidemiologic evaluations was discovered to be problematic; people confused this term with daeria, which accounted for only 5% of all episodes of diarrhea. The implications of such epidemiologic information for a large-scale program of oral rehydration therapy are also discussed. 
31P localized magnetic resonance spectroscopy of head and neck tumors--preliminary findings. Magnetic resonance imaging (MRI) is a powerful tool for accurate assessment of the anatomic extent of head and neck neoplasms. The development of methods for spatial localization by use of multiply tuned radio frequency coils that permit the measurement of multiple nuclear MR spectra (1H and 31P) from precisely defined volumes of interest has provided a basis for integrating spectroscopy into the clinical MRI examination. This offers a means for noninvasive monitoring of relative concentrations of mobile metabolites within a tumor. With the use of imaging to determine proper coil placement, a test-retest variance of about 17% is seen on MR spectroscopy. Data are presented from MRI/MRS studies for four head and neck lesions: (1) a squamous cell carcinoma of the lip; (2) a juvenile angiofibroma extending into the nasal cavity; (3) a massive chondrosarcoma of the nasal septum; and (4) a cervical nodal metastasis of a squamous cell carcinoma of the pharynx. Spectra are evaluated by comparison of relative concentrations of phosphorus compounds. The concentrations of phosphomonoesters and phosphodiesters are significantly higher in the neoplasms studied than in normal skeletal muscle. The developing role of integrated MRI/MRS to monitor the response of malignant neoplasm to radiation therapy is discussed. 
Metabolic responses to swimming exercise in Streptococcus pneumoniae infected rats. The present study was performed to determine whether alterations in fuel reserves or energy substrate utilization might explain the performance decrements that occur in bacterial infections. Male Fisher-Dunning rats were studied at 24, 48, and 72 h after inoculation with Streptococcus pneumoniae. Rats were either sedentary or subjected to a 2-h swimming session at these three time points (N = 10 in each group). A more than 60% reduction (P less than 0.01) in performance capacity was observed on day 3 of infection compared with that in noninfected controls. This infection in the rat is characterized by fever (P less than 0.01), depression of plasma zinc (P less than 0.01) and free fatty acid (FFA) levels (P less than 0.01), inhibition of the two- to threefold increase in fasting ketonemia, and a decreased (NS) insulin:glucagon ratio, indicating a catabolic state. Glycogen stores were reduced in the heart (47%), liver (43%), and skeletal muscles (39%) but not in the carcass. Superimposed exercise resulted in a further reduction but not depletion of liver, muscle, and carcass glycogen stores, a less pronounced lactic acid accumulation, and a lower oxygen debt. However, plasma FFA and ketone body levels were still maintained or even elevated, suggesting that fat is supplied as fuel during swimming exercise in this infection. Thus, results indicate that unavailability of energy substrates or lactacidosis is not limiting for performance capacity during this severe infection. 
Congestive heart failure. New frontiers. Congestive heart failure is a common syndrome with high mortality in its advanced stages. Current therapy includes the use of vasodilator drugs, which have been shown to prolong life. Despite current therapy, mortality remains high in patients with severe heart failure. Potent new inotropic vasodilators have improved ventricular performance but have not prolonged life in patients with end-stage heart failure. Serious arrhythmias are implicated in the sudden deaths of 30% to 40% of patients with severe heart failure, but the benefits of antiarrhythmic therapy have not been established. Upcoming trials will address this question. Ventricular remodeling and progressive dilatation after myocardial infarction commonly lead to congestive heart failure; early unloading of the ventricle with an angiotensin-converting enzyme inhibitor may attenuate these events. These findings support the concept that angiotensin-converting enzyme inhibitors may be useful in managing heart failure of all degrees of severity, including left ventricular dysfunction and end-stage heart failure. Part of the damage that may occur with acute myocardial infarction, particularly in this era of thrombolysis therapy, is reperfusion injury, which may be mediated by oxygen-derived free radicals. Better knowledge of the mechanisms and treatment of myocardial infarction, the leading cause of congestive heart failure, may help prevent or attenuate the development of this syndrome. 
Management of severe fibrocystic disease of the breast with leuprolide acetate. Symptoms of severe fibrocystic disease of the breast were successfully ameliorated in two patients as a result of treatment with daily subcutaneous LA without adverse effects. A state of drug-induced hypogonadotropic hypogonadism appears to be responsible for the clinical effect and is further suggestive of the hormonal dependence of this common disorder. 
Safety of surgical procedures performed by residents. The outcome of surgical procedures on the gallbladder performed by surgical residents in a university hospital was compared with the outcome of those performed by the attending staff. More than 60% of the operations (643/1084) were done by residents under the direct supervision of the attending surgeon. We found no differences in the rate of technical complications, postoperative morbidity and mortality, or length of hospitalization between the two groups. Thus, resident surgery under appropriate guidance is safe and does not compromise the quality of patient care or operative outcome. 
Chickenpox pneumonia, its complications and management. A report of three cases, including the use of extracorporeal membrane oxygenation. We report three cases of chickenpox pneumonia in adults, all of whom required intermittent positive pressure ventilation. One patient developed a variety of complications, and another, a pregnant woman, required extracorporeal membrane oxygenation. 
Acetylcholine regulates pancreastatin secretion from the human pancreastatin-producing cell line (QGP-1N). Studies were made of pancreastatin (PST) secretion from a human PST-producing cell line (QGP-1N) in response to various secretagogues. Cells with immunoreactivity for PST were observed in monolayer cultures of QGP-1N cells. Carbachol stimulated PST secretion and the intracellular Ca2+ mobilization concentration dependently in the range of 10(-6)-10(-4) M. The PST secretion and Ca2+ mobilization induced by carbachol were inhibited by atropine. The calcium ionophore (A23187) stimulated PST secretion. However, cholecystokinin and gastrin-releasing peptide did not stimulate either PST secretion or Ca2+ mobilization. Secretin also did not stimulate PST secretion. The glucose concentration in the culture medium had no effect on PST secretion. These results suggest that PST secretion is mainly regulated by acetylcholine through a muscarinic receptor, and that an increase in intracellular Ca2+ plays an important role in stimulus-secretion coupling in QGP-1N cells. 
Delayed visual loss due to trauma of the internal carotid artery. The group of six patients in this study experienced delayed visual loss following head trauma. Visual loss occurred from 1 day to 13 years after the initial injury. All patients suffered indirect trauma to the internal carotid artery resulting in formation of either an aneurysm or pseudoaneurysm or a carotid-cavernous fistula. Review of the radiologic and clinical findings was performed in six patients. The diagnosis was established by computed tomography, magnetic resonance imaging, and angiography. All patients had follow-up clinical evaluation and imaging studies. Treatment by neurosurgical or interventional neuroradiologic procedures resulted in significant visual improvement in five patients. Different pathophysiologic mechanisms could be correlated with the delayed visual loss produced by the two types of lesions. The pathologic changes associated with the aneurysms/pseudoaneurysms included direct compression of optic nerves and/or chiasm and intracranial hematoma. A carotid-cavernous fistula caused delayed visual loss by either hematoma at the orbital apex or compression of the chiasm and/or optic nerves by saccular dilatation of the cavernous sinus. The delayed onset of decreased vision following head trauma should alert the physician to the possibility of a traumatic aneurysm/pseudoaneurysm or a carotid-cavernous fistula. Different neuro-ophthalmologic symptoms can usually be correlated with the pathologic changes demonstrated by neuroimaging procedures. 
Clinical and angiographic observations on resuscitated victims of exercise-related sudden ischemic death. The clinical and angiographic findings of 17 resuscitated victims of exercise-related sudden ischemic death are reported in an attempt to elucidate the mechanism(s) of these deaths. Ten survivors developed cardiac arrest during or after sporting activities (group A) and 7 others during or after an exercise stress test (group B). There were 15 men and 2 women. The mean age of group A was 46 years and of group B 55 years. Coronary risk factors, as well as previous angina and myocardial infarction, were more frequent in group B. Only 3 of the 17 survivors had anginal symptoms before sudden death. Sudden death in group A was associated with acute myocardial infarction in 8 and unstable angina in 2 and was associated in group B with acute myocardial infarction in 2, unstable angina in 3 and silent ischemia in 2. Coronary angiography was acutely performed in 15 patients. In most patients the ischemia-related coronary artery was totally or subtotally occluded. Clinical and angiographic findings indicate that exercise-related sudden ischemic death was due to an acute coronary event--in most cases unexpected and unpredictable. It is suggested that exercise-induced intracoronary changes were probably responsible for the development of acute coronary (sub)occlusion and sudden death. 
Establishment from Shope carcinoma induced in an inbred rabbit of culture cell lines with various potentials for differentiation and tumorigenicity. Shope papillomas induced by cottontail rabbit papilloma-virus (CRPV) in domestic rabbits frequently regress spontaneously or, failing to do so, convert into squamous cell carcinomas at a high rate. This papilloma-carcinoma complex in rabbits provides an experimental model for human papillo-mavirus-associated malignancies. The aim of this study was to prepare an experimental system in inbred rabbits by establishing culture cell lines of the tumor. Squamous cell carcinoma developed from a Shope papilloma that had been induced 6 months previously by inoculating CRPV into an inbred B/J rabbit. By in vitro culturing of the tumor cells, cell lines with potentials for terminal differentiation and tumorigenicity were established. Cloning yielded sublines that varied in these potentials and possessed episomal and integrated CRPV genomes as revealed by Southern hybridization in both one- and two-dimensional electrophoresis. Major CRPV-specific transcripts were similarly observed both in well-differentiated and in poorly differentiated sublines. Immunofluorescence with syngeneic rabbit antibody against tumor-specific antigens localized such antigens mainly in the nuclei of the cells of these sublines. This experimental system allows experiments that were not feasible in randomly bred rabbits. 
Access to neurological care for minorities. Minority groups comprise a major segment of the estimated more than 34 million Americans without insurance coverage and also the underinsured. Neurologic disease and neurologic complications of the major causes of morbidity and mortality affect minorities protracted by limited access to health care. Hypertension, a major cause of stroke in the black population, is just one example of the impact of accessibility to intervention in central nervous system disease. Health statistics note the persisting gap between minority groups and the nation's norms for life expectancy. Aging America and particularly black elderly women, combined with the lagging infant mortality among minority groups, demonstrate limited access issues beyond economics, reflecting inner city mores, cultural barriers, and communication delay limiting contact with the practicing neurologist. Awareness of such access limitations to neurological care for minorities demands the attention of the practicing neurologist and the neurological societies. 
Neurological disease in xeroderma pigmentosum. Documentation of a late onset type of the juvenile onset form. Xeroderma pigmentosum (XP) is an autosomal recessive, neurocutaneous disorder characterized by sunlight-induced skin cancers and defective DNA repair. Many XP children develop a primary neuronal degeneration. We describe 2 unusual XP patients who had a delayed onset of XP neurological disease. Somatic cell genetic studies indicated that they have the same defective DNA repair gene and are both in XP complementation group A. These 2 patients, together with a group A patient previously reported from London, establish as a distinct clinical entity the late onset type of the juvenile onset form of XP neurological disease. The functional capacity of these patients' cultured fibroblast strains to survive after treatment with ultraviolet radiation indicates that their DNA repair defect is less severe than that of typical group A patients who have a more severe neurodegeneration with an earlier symptomatic onset. The premature death of nerve cells in XP patients (which is presumably due to their inherited defects in DNA repair mechanisms) suggests that normal repair of damaged DNA in neurons is required to maintain integrity of the human nervous system. 
Brain stem atrophy in Joseph disease: a morphometric study using two-dimensional (area) measurement by computed tomography. Eight Japanese patients with Joseph disease were studied using computed tomography (CT). Morphometric analysis using the two-dimensional (area) measurement by CT was performed in the infratentorial region. The brain-stem index, an index of brain-stem atrophy or pontine atrophy, revealed a significant decrease (P less than 0.01), with a mean of 66.7% when compared with 16 control subjects. The patients showed a significant increase (P less than 0.01), with a mean of three times that of the controls in the fourth ventricular index, an index of fourth ventricular dilatation. There were no differences in the cerebellar index, an index of cerebellar atrophy, between these patients and the controls, although the patients had an increased number of visible cerebellar vermian (2.0, SD 0.7) and hemispheric sulci (2.6 SD 0.6) as compared with the controls (vermian sulci: 0.4, SD 0.7: hemispheric sulci: 0). These data indicate severe pontine atrophy, fourth ventricular dilatation with mild involvement of the cerebellum and correlate well with the common pathological features of Joseph disease. The present morphometric evaluation by CT may be useful in the clinical diagnosis of Joseph disease. 
The incidence of postoperative nausea and vomiting in women undergoing laparoscopy is influenced by the day of menstrual cycle. Postoperative nausea and vomiting is a major cause of postoperative morbidity. It can lead to increased recovery time, delaying patient discharge and an increase in hospital costs. Past studies have shown that postoperative nausea and vomiting is more frequent in women than men, appears to elevate around the time of menarche and is reduced around the time of menopause. This retrospective review of a one-year experience of laparoscopic tubal ligation at our institute examined the effect of menstrual cycle on postoperative nausea and vomiting. The anaesthetic and surgical techniques were consistent for all patients. Patient data included age, weight, last day of menstrual cycle, the length of anaesthetic, the dose of inhalational agent, the dose of narcotic, emesis on emergence and whether or not droperidol was used. Of the the 235 patients in the study, the incidence of nausea and vomiting was 28%. One hundred fifty-eight had had no preoperative antiemetic and 77 had received droperidol. These two groups were analyzed separately. The incidence in the group not receiving droperidol was 33.5% and in the droperidol group, 16.9% (P less than 0.01). The incidence of nausea and vomiting was higher on the first eight menstrual days (51.6 vs 21.6, P less than 0.001), was highest on day five of the menstrual cycle and lowest on days 18, 19, and 20 where there was no nausea and vomiting. Droperidol reduced the incidence of postoperative nausea and vomiting but the variation in postoperative nausea and vomiting during the cycle persisted. 
Bio-medicus ventricular assist device for salvage of cardiac surgical patients Over a 5-year period, 41 (1%) of 4,193 patients undergoing cardiac operations underwent intraoperative or early postoperative insertion of a Bio-Medicus ventricular assist device when it became apparent that the patient could not otherwise survive. Fourteen patients were in cardiogenic shock and 7 were in cardiac arrest at the time of initiation of their primary cardiac surgical procedure, and in no instance was the device planned as a bridge to cardiac transplantation. Bleeding, sepsis, and thromboembolism were frequent postoperative complications. Central nervous system deficits were observed in 16 patients during their postoperative course. Eight patients (19.5%) were long-term survivors. Of the preoperative risk factors evaluated only age was significantly associated with survival, with 7 (33%) of the 21 younger (39 to 63 years) patients surviving. Blood product usage and hospital cost were analyzed in an attempt to assess cost/effectiveness of use of this device for attempted salvage of such desperately ill patients. 
The applications of PET in clinical oncology. With the advent of a new generation of PET scanners that have introduced whole-body PET to the clinical setting, there is now more interest in developing protocols for the evaluation of both intracranial and somatic cancers. The value of PET in clinical oncology has been demonstrated with studies in a variety of cancers including colorectal carcinomas, lung tumors, head and neck tumors, primary and metastatic brain tumors, breast carcinoma, lymphoma, melanoma, bone cancers, and other soft-tissue cancers. A summary of current clinical applications of PET in oncology is presented with special attention to colorectal, lung, and intracranial neoplasms since the majority of clinical trials have focused on these cancers. A variety of radiopharmaceuticals are described that are currently included in clinical tumor-imaging protocols, including metabolic substrates such as fluorine-18-fluorodeoxyglucose and carbon-11-methionine, and analogs of chemotherapeutic agents such as fluorine-18-fluorouracil and fluoroestradiol. An attempt is also made to include examples of clinical trials that demonstrate response to therapeutic intervention. The increasing number of oncologic PET studies reflects the growing interest in functional imaging in oncology. 
Cardiopulmonary hemodynamics in systemic sclerosis and response to nifedipine and captopril. PURPOSE: This prospective study was performed to evaluate the response of the cardiopulmonary vasculature to two vasodilators in patients with systemic sclerosis and either minimal or no central hemodynamic abnormalities. PATIENTS AND METHODS: Twenty patients with systemic sclerosis, Raynaud's phenomenon (19 of 20 patients), and clinically normal cardiac function underwent right heart catheterization. Rest and exercise hemodynamic measurements, including cardiac output by thermodilution, were performed before and after oral administration of nifedipine 20 mg and captopril 25 mg. RESULTS: Half of the patients had normal hemodynamics (Group A); the other half (Group B) had abnormal baseline elevations in pulmonary vascular resistance and four of them showed "borderline" pulmonary arterial hypertension. Group A, with significantly shorter disease duration compared with Group B, responded poorly to nifedipine and captopril. However, Group B had significant decreases in pulmonary vascular resistance (from 148 +/- 20 to normal levels of 94 +/- 21 dynes.second.cm-5) and pulmonary mean pressure in response to nifedipine treatment but not to captopril. CONCLUSION: These observations show a short-term beneficial effect of nifedipine in the cardiopulmonary vasculature of patients with systemic sclerosis and suggest that a potentially reversible vasoconstrictive element is included in the vascular lesion of this disorder. 
Suppression of experimental autoimmune encephalomyelitis by oral administration of myelin antigens: IV. Suppression of chronic relapsing disease in the Lewis rat and strain 13 guinea pig. Oral administration of proteins is a long-recognized method of inducing antigen-specific peripheral immune tolerance. We previously showed that oral administration of myelin basic protein suppresses monophasic experimental autoimmune encephalomyelitis in the Lewis rat when it is given in association with immunization and prior to disease onset. As a potential therapy for human autoimmune disease, it is crucial to determine whether oral tolerance can ameliorate an ongoing immune response. We therefore asked whether oral administration of myelin antigens, after sensitization and disease expression has occurred, could affect immunological, clinical, or pathological features of experimental autoimmune encephalomyelitis. Chronic relapsing experimental autoimmune encephalomyelitis was induced in the Lewis rat and strain 13 guinea pig by immunization with whole guinea pig cord homogenate, complete Freund's adjuvant, and Mycobacterium tuberculosis. Following recovery from the first attack, animals were orally given bovine myelin, guinea pig myelin, or guinea pig myelin basic protein three times per week for up to 3 months. Animals receiving myelin products orally had decreased severity and frequency of clinical relapses, decreased delayed-type hypersensitivity responses to myelin antigens, diminished inflammation in the central nervous system (CNS), and decreased areas of CNS demyelination. In the rat, guinea pig myelin basic protein was as effective as guinea pig myelin in ameliorating the disease and also resulted in decreased serum anti-myelin basic protein antibody levels. No exacerbation of disease or worsening of pathological findings occurred in the animals given myelin products. These results demonstrate that oral administration of myelin antigens can suppress chronic relapsing experimental autoimmune encephalomyelitis and have direct relevance to therapy of human demyelinating disorders such as multiple sclerosis. 
Intrahepatic spontaneous arterioportal fistula: duplex ultrasound diagnosis and angiographic treatment. A 54-yr-old male with portal hypertension received ineffective medical therapy for the diagnosis of portal hepatic cirrhosis. Duplex ultrasound (US) revealed pulsatile arterial flow in the right main portal vein. The correct diagnosis of intrahepatic arterioportal fistula was established and confirmed by angiography. Right hepatic artery embolization with three coils was performed. The patient is alive for 16 months after the embolization, and his complaints have disappeared. There has been full resorption of ascites and absence of varices. Nine previously reported similar cases are reviewed. 
Focal hepatic lesions: differentiation with MR imaging at 0.5 T. Magnetic resonance (MR) examinations of 43 patients with 95 focal hepatic lesions (diameter, greater than 1 cm) were analyzed for lesion shape, homogeneity, and relative signal intensity compared with normal liver parenchyma, spleen, and skeletal muscle. On T1-weighted, balanced, and T2-weighted images, most metastases (74%), cavernous hemangiomas (76%), and cysts (82%) were smooth and round or oval, while the hepatocellular carcinomas all had irregular borders (40%) or were lobulated (60%). All lesions with irregular borders were malignant. Seventy percent of metastatic lesions, 85% of cavernous hemangiomas, and 100% of simple hepatic cysts were of homogeneous signal intensity, while 60% of hepatocellular carcinomas were inhomogeneous. Logistic regression analysis of multiple lesion characteristics showed that inhomogeneous lesions had a high likelihood of malignancy, while markedly hyperintense lesions had a very low probability of being malignant, regardless of other traits. Homogeneous lesions that were isointense or hyperintense compared with spleen on balanced images but were not markedly hyperintense on T2-weighted images also had a high likelihood of malignancy. 
Staging relationships and outcome in early stage testicular cancer: a report from the Testicular Cancer Intergroup Study. The Testicular Cancer Center Intergroup Study entered surgically staged patients with nonseminomatous tumor and metastases limited to the regional lymph nodes into a previously reported cooperative trial of immediate versus delayed therapy for positive retroperitoneal node disease. Patients with negative nodes (stage I) were placed in an observation registry with specified treatment strategy upon relapse. Of 264 stage I cancer patients 27 (10.2%) had recurrence: 5 of these 27 patients died after recurrence of the testicular malignancies, while 4 other nontumor-related deaths have occurred. Pre-lymphadenectomy staging characteristics observed to predict significantly node positivity are the results of radiological examinations, presence of tumor invasion, vascular invasion and tumor histology. In a multiple logistic regression analysis with these variables, misclassification still occurs in more than a fourth of the patients. Future refinements in diagnosis may allow for better prediction of these patients at risk to have positive lymph nodes and ultimately recurrence. Presently, if assessment of nodal involvement is the objective, noninvasive procedures are not an adequate substitute for surgical staging with modified lymphadenectomy. 
Crackles in patients with fibrosing alveolitis, bronchiectasis, COPD, and heart failure. We have studied the crackling lung sounds of ten patients with cryptogenic fibrosing alveolitis, ten with bronchiectasis, ten with chronic obstructive pulmonary disease, and ten with heart failure by analyzing frequency, waveform, and timing of crackles. The upper frequency limit of inspiratory sounds was higher in CFA than in COPD or in HF. The period of crackling was shorter in COPD than in CFA or BE. Inspiratory crackling terminated significantly earlier in COPD than in CFA, BE, or HF. The initial deflection width and the two-cycle duration of the expanded waveforms of crackles were smaller in CFA than in BE, COPD, or HF. The largest deflection width was smaller in CFA than in BE, HF, or COPD and smaller in BE than in HF. The results indicate that crackling lung sounds in different diseases have distinctive features and that their analysis can be of diagnostic value. 
Parkinson's disease: new treatment strategies. Recent interest has focused on two novel approaches to the treatment of Parkinson's disease-medications to slow or arrest disease progression, and cerebral transplantation. Two recent studies have demonstrated that selegiline can slow, although not halt, the progression of recent-onset Parkinson's disease. The data are sufficiently compelling to justify the use of this drug in most new patients. It also seems reasonable to extrapolate from the data and offer this medication to all patients but those with the most advanced Parkinson's disease. The current focus on excessive oxidative stress as a causative factor has led some investigators to recommended treating patients with the antioxidant tocopherol (vitamin E). There is no clinical evidence demonstrating its effectiveness, but a current multicenter study is being conducted, with the results expected within the next 2 years. High-dose vitamin E (such as 800 to 2000 U/d), taken for a number of months, is probably harmless. It is probably reasonable, therefore, to allow patients to take this over-the-counter compound until more definitive evidence is available. Another antioxidant, vitamin C, has also been advocated as a means of slowing the progression of Parkinson's disease. There are no studies that demonstrate any clinical effectiveness, and there are also no ongoing studies investigating this issue in patients with Parkinson's disease. The excitement surrounding the initially favorable results of adrenal-brain transplantation has waned with the failure of numerous institutions to replicate the original dramatic success. While mild or occasionally moderate improvement has been noted in subsequent patients undergoing adrenal-brain transplantation, the improvement has not been sufficient to justify the risk and expense of this surgery. 
Obstructive sleep apnea complicating negative-pressure ventilatory support in patients with chronic paralytic/restrictive ventilatory dysfunction. The purpose of this study was to determine the incidence and severity of obstructive events and oxyhemoglobin desaturation (dSaO2) in 37 patients with paralytic/restrictive ventilatory insufficiency during use of nocturnal ventilatory assistance provided by means of negative-pressure body ventilators (BVs). Thirteen of the 37 patients had mean oxyhemoglobin saturation (SaO2) less than 95 percent and a mean of ten or more episodes per hour when the dSaO2 was greater than or equal to 4 percent (4%dSaO2/h). In all, 26 of the 37 patients had evidence of significant multiple episodes of dSaO2 while asleep on BVs. Polysomnography performed on three of these patients substantiated the obstructive nature of the dSaO2. Twenty-two of the 37 patients who had a mean SaO2 of 90.6 +/- 7.2 percent and a mean of 17.7 +/- 16.1 4%dSaO2/h on BVs were switched to noninvasive ventilatory assistance by intermittent positive airway pressure (NV-PAP). Their mean SaO2 improved to 96.0 +/- 2.2 percent, and the 4%dSaO2/h decreased to 1.2 +/- 1.8 per hour. All symptoms similar to those of obstructive sleep apnea were relieved. We conclude that BV use is associated with significant dSaO2 in over 50 percent of patients. The dSaO2 is predominantly obstructive in nature but may be due to chronic underventilation in patients using less effective BVs. Patients with a mean SaO2 less than 95 percent or 10 or more 4%dSaO2/h may benefit from conversion to NV-PAP via the nose, the mouth, or an oral-nasal interface. 
Rehabilitation in rheumatic diseases. What's new. In the past decade, considerable change has occurred in concepts of rehabilitation in patients with rheumatic diseases. This includes approaches to functional assessment and outcome, new concepts in exercise, and new orthotics. 
Family history of myocardial infarction and hemodynamic responses to exercise in young black boys. The influence of family history of coronary artery disease on children's hemodynamic responses to exercise was examined with 25 black boys aged 7 to 10 years. Blood pressure, heart rate, cardiac output, stroke volume, and total peripheral resistance were evaluated during preexercise, peak exercise, and recovery stages. Children with a family history of CAD exhibited greater systolic blood pressure and total peripheral resistance during preexercise and peak exercise stages than did those without a family history of coronary artery disease. After controlling for preexercise differences, the group with a family history of coronary artery disease exhibited greater increases in systolic blood pressure and less attenuation of total peripheral resistance to peak exercise than the group without a family history of coronary artery disease. Cardiac output indexed by body surface area and stroke volumes were higher at all times in the group without a family history compared with the group with a family history of coronary artery disease. Findings are compared with those of adult studies in terms of influence of family history of coronary artery disease on cardiovascular reactivity to stress. 
Emergence of a B-cell lymphoblastic lymphoma in a patient with B-cell chronic lymphocytic leukemia: evidence for the single-cell origin of the two tumors. A patient is described who presented with a chronic lymphocytic leukemia (CLL) and later developed a lymphoblastic lymphoma. The cells from the CLL were typical mature B lymphocytes as could be assessed by morphologic, cytochemical, and surface marker analyses. The cells from the lymphoblastic lymphoma were immature B cells that expressed CD10, CD20, and HLA-DR markers, but not surface Ig or cytoplasmic mu chains, and were negative for terminal deoxynucleotidyl transferase (TdT). The cells of two continuous cell lines, obtained from the bone marrow and the peripheral blood of the patient, had the same phenotype as the lymphoblastic lymphoma cells, did not contain the Epstein-Barr virus genome, and displayed malignant features in vitro, including the capacity to form colonies in agar. The two cell lines also shared identical chromosomal abnormalities, a finding which suggests that they derived from the same malignant cell already present in vivo. Such chromosomal abnormalities were not seen in the karyotype of the peripheral blood cells at the onset of the disease. Analysis of the Ig heavy chain genes using a DJ-specific probe showed the very same monoclonal rearrangement in the cells from the B-CLL, the lymphoblastic lymphoma and the two cell lines, thus demonstrating their common clonal origin. By contrast, a monoclonal rearrangement of the lambda chain gene locus was found in the B-CLL cells only, a finding consistent with their exclusive capacity to express surface IgM lambda. This patient represents a rare case in whom a chronic lymphoproliferative disorder with mature malignant cells transforms into a lymphoblastic lymphoma characterized by cells frozen at a very early maturational stage. The possible mechanisms leading to such transformation within the same cell clone are discussed. 
Psychological changes accompanying non-pharmacological treatment of chronic headache: the effects of outcome. Several prior studies suggest that non-drug treatment for chronic headache is accompanied by concomitant reductions in patients' anxiety, depression and somatization. It is currently unclear, however, whether such beneficial side effects are a function of degree of headache relief or are due simply to receiving treatment. Most work to date in this area has treated outcome as a dichotomous variable. The present report employed a regression approach which treats outcome (degree of headache relief) as a continuous variable in the study of 149 chronic headache patients and their accompanying psychological changes. Anxiety and depression were significantly reduced for headache patients regardless of degree of headache relief. With somatization, however, degree of headache relief had a significant effect; the greater the reduction in headache, the fewer somatic concerns were expressed, especially for mixed headache. 
Exocrine pancreatic function in children with coeliac disease before and after a gluten free diet. This study was designed to determine the extent of pancreatic insufficiency in untreated coeliac disease and whether pancreatic secretion is impaired after a prolonged gluten free period. Three groups of patients were studied: group A comprised 44 patients, mean (SD) age 4.0 (3.1) years, with coeliac disease and total or subtotal atrophy of the intestinal mucosa; group B comprised 67 patients, mean age 4.4 (3.0) years, with coeliac disease but with normal morphology of the intestinal villi (after 12.9 months of a gluten free diet); group C comprised 49 control subjects, mean age 3.2 (3.0) years, with normal jejunal histology. In all subjects exocrine pancreatic function was determined by the secretin-caerulein test; bicarbonate concentration and lipase, phospholipase, and chymotrypsin activity were measured after an intravenous injection of secretin 1 clinical unit (CU) + caerulein 75 ng/kg body weight. Faecal chymotrypsin concentration was also assayed. No significant difference was found between values of the duodenal output of pancreatic enzymes and bicarbonate obtained in the three groups; however, 10 of 44 untreated coeliac patients showed tryptic or lipolytic activity, or both, below the normal limit for our laboratory. The mean value of the faecal chymotrypsin concentration was significantly lower in untreated than in treated coeliac patients (p less than 0.0001) or in control subjects (p less than 0.0001). It is concluded that untreated coeliac patients may have pancreatic deficiency independent of a decrease in enterohormone release. No primary or secondary pancreatic insufficiency was found in coeliac patients where the intestinal mucosa had returned to normal. 
Left atrial spontaneous echo contrast: a clinical and echocardiographic analysis. The clinical and echocardiographic variables related to left atrial spontaneous echo contrast were prospectively evaluated in a consecutive series of 400 patients undergoing transesophageal echocardiography with a 5-MHz single plane transducer. Left atrial spontaneous echo contrast was found in 75 patients (19%) and was significantly associated with atrial fibrillation, mitral stenosis, absence of mitral regurgitation, increased left atrial dimension and a history of suspected embolism. Seventy-one (95%) of the patients with spontaneous echo contrast had atrial fibrillation or mitral stenosis. Anticoagulant therapy had no significant association with spontaneous echo contrast. Multivariate analysis in 89 patients with mitral stenosis or mitral valve replacement showed that spontaneous echo contrast was the only independent predictor (p = 0.03) of left atrial thrombus or suspected embolism, or both. In 60 patients with atrial fibrillation of nonvalvular origin, spontaneous echo contrast (p = 0.01) and age (p = 0.03) were the only independent predictors of left atrial thrombus or suspected embolism, or both. It is concluded that left atrial spontaneous echo contrast is 1) a common finding in patients undergoing transesophageal echocardiography, 2) associated with conditions favoring stasis of left atrial blood, and 3) a marker of previous thromboembolism in patients with nonvalvular atrial fibrillation and those with mitral stenosis or mitral valve replacement. 
Resting energy expenditure in patients with newly detected gastric and colorectal cancers. Resting energy expenditure (REE) was measured in 104 patients with newly detected gastric or colorectal (GCR) cancer and was compared with two groups of control subjects without cancer: healthy subjects (H control subjects) and patients with nonmalignant diseases of the gastrointestinal tract (GI patients). REE in GCR-cancer patients was not significantly different from REE in GI patients or H control subjects. Comparison of measured REE with predicted REE obtained from prediction equations may erroneously suggest that increased REE is a contributing factor in the development of cancer cachexia. No significant differences in REE were found when patients with liver metastases were compared with patients without metastases. There were no differences in REE between gastric and colorectal cancer patients. The decrease in energy expenditure, which normally occurs during starvation and weight loss in healthy men and women, could not be demonstrated in weight-losing, GCR-cancer patients. In conclusion, elevation of REE contributes little to the pathogenesis of cancer cachexia in GCR-cancer patients. 
Comparative efficacy of short-term versus long-term cefoxitin prophylaxis against postoperative infection after radical hysterectomy: a prospective study. We report the results of a randomized, double-blind comparison of short-term versus long-term cefoxitin prophylaxis against infections after radical abdominal hysterectomy with pelvic and para-aortic lymphadenectomy. Of 113 evaluable patients, 54 (47.8%) received short-term (three doses) and 59 (52.2%) long-term (12 doses) prophylaxis with intravenous cefoxitin (2 g per dose). No significant differences in demographics, preoperative risk factors, or clinical course were detected between the two groups; nor did we detect significant differences in the incidence of surgical-site-related infections (7.4 versus 5.1%, respectively, P = .61), postoperative urinary tract infection, or other febrile morbidity. We conclude that short-term and long-term cefoxitin prophylaxis are equally effective for the prevention of post-operative surgical-site-related infections after radical hysterectomy. 
Intravenous carboplatin for recurrent malignant glioma: a phase II study. Thirty patients with recurrent malignant glioma were treated with intravenous (IV) carboplatin (CBDCA) every 4 weeks at a starting dose of 400 mg/m2 escalating to 450 mg/m2. All patients had documented recurrent tumor after prior radiotherapy but had not received prior chemotherapy. Of 29 assessable patients, four (14%) responded to the treatment for 44, 51+, 72, and 91 weeks; 10 (34%) achieved stable disease (S); while 15 (52%) had progressive disease (P). The total response (responses plus S) rate was 48%, with a median time to progression (MTP) of 26 weeks in these patients; the MTP for all 29 patients was 11 weeks. The toxic effects were mainly hematologic, with thrombocytopenia and granulocytopenia being mild at 400 mg/m2 and 450 mg/m2 doses. NO neurotoxicity or renal toxicity was encountered. These results suggest that CBCDA given at 400 mg/m2 or 450 mg/m2 every 4 weeks is marginally active in patients with recurrent malignant gliomas. Since hematologic toxicity is mild, a higher dose could possibly be given, and may increase the response rate. 
Autologous fibrin gel: bactericidal properties in contaminated hepatic injury. Fibrin glue is an effective hemostatic agent in a variety of clinical situations; its utility is limited by potential transmission of viral infection. We studied the bactericidal properties of fibrin gel (FG) in a murine contaminated hepatic injury model and in vitro by agar plate culture method. Intra-abdominal abscess formation and adhesion rate were assessed following controlled liver injury in association with abdominal contamination with 10(7) Bacteroides fragilis and hepatorrhaphy (H, n = 15) or FG (n = 12). Animals treated by hepatorrhaphy had a significantly greater intra-abdominal abscess rate (15/15 vs. 4/12, p less than 0.05) and adhesion rate (14/15 vs. 6/12, p less than 0.05) than animals treated with FG. Fibrin gel is bactericidal to Bacteroides fragilis, Enterobacter faecium, Escherichia coli, and Staphylococcus aureus but has no effect against Klebsiella pneumoniae or Pseudomonas aeruginosa; the plasma component appears active. Fibrin gel demonstrates significant improvement in adhesion formation and intra-abdominal abscess rate when compared with suture hepatorrhaphy. Fibrin gel appears protective in contaminated hepatic injury. 
Blindness as an ictal phenomenon: investigations with EEG and SPECT in two patients suffering from epilepsy. Blindness is a rare ictal phenomenon in epileptic seizures. It can occur as an aura, as the seizure itself, or postictally. We investigated two such patients, in one of whom blindness manifested as an aura prior to tonic clonic seizures; the interictal EEG exhibited a spike-wave focus bioccipitally. In the second patient blindness occurred postictally. An ictal SPECT, carried out at the onset of the seizure demonstrated marked hyperperfusion in both occipital regions. 
Acute hemiplegia associated with HIV infection. An acute hemiplegia secondary to a large cerebral infarct is described in a 16-month-old infant with congenitally-acquired human immunodeficiency virus infection. Serial imaging studies during the next year documented improvement in his hemiplegia and a static underlying human immunodeficiency virus encephalopathy. Acquired immunodeficiency syndrome should be included in the differential diagnosis of children with acute hemiplegia. 
Moricizine: a new agent for the treatment of ventricular arrhythmias. Over the last several years, a number of new antiarrhythmic agents have come into use. One of these promising new drugs, moricizine hydrochloride (Ethmozine), is now available for use in this country. Although similar in some aspects to both quinidine and lidocaine, Moricizine hydrochloride is in many ways unique. The purpose of this review is to summarize the pharmacologic and physiologic effects of moricizine and to outline its clinical use. 
Success and failure with neonatal tracheo-oesophageal anomalies. In seven and a half years, one surgical team treated 67 consecutive neonates with oesophageal atresia and/or tracheo-oesophageal fistula. According to Waterston's classification, 28 were in group A, 12 in group B and 27 in group C. The mortality rate during the initial admission was 10 per cent, all seven deaths being unavoidable in infants in group C with multiple anomalies. Birthweight alone had no bearing upon the chances of survival. Primary oesophageal repair, including one suture-fistula procedure and one delayed primary repair, was attempted in 54 (84 per cent) of the 64 patients with atresia and was successful in 46 (85 per cent). All three H-type tracheo-oesophageal fistulae were successfully divided in infants in group A. Recurrent tracheo-oesophageal fistula developed in four (7 per cent) infants, one of whom (group A) underwent successful repair. One disrupted anastomosis was successfully resutured (group A), so an intact oesophagus was finally achieved in 51 patients, of whom six (12 per cent) developed anastomotic strictures and 21 (41 per cent) underwent surgery for gastro-oesophageal reflux. Of the 60 early survivors, 10 (17 per cent) underwent aortopexy for tracheomalacia. Whenever possible, primary repair is advocated in all infants. Even for those in group C with multiple, severe associated anomalies, the combined early and late mortality was no greater following primary repair (7 died of 12 operated) than after staged repair (4 died of 7 operated), but major anastomotic complications were more common in infants in group C (5 out of 19) than in those in groups A and B (3 out of 38). 
Assessment of quality of life by patient and spouse during antihypertensive therapy with atenolol and nifedipine gastrointestinal therapeutic system. To evaluate differences in efficacy, safety, and quality of life, 394 male patients with mild-to-moderate hypertension were randomized to receive 20 weeks of either atenolol or nifedipine gastrointestinal therapeutic system (GITS) in a multicenter double-blind trial. A four-week placebo washout was followed by 8 weeks of titration and 12 weeks of maintenance therapy. Quality-of-life evaluation included clinical assessments by the patient and parallel take-home assessments by patient and spouse. Blood pressure was controlled equally in both groups. The total incidence of adverse reactions was similar in both groups, but a greater percentage of nifedipine GITS patients withdrew due to peripheral edema. Patients completing 20 weeks of therapy demonstrated a more favorable quality-of-life profile (P less than .05) for nifedipine GITS over atenolol in psychosocial (P less than .01), well-being (P less than .05), general affect (P less than .05), emotional ties (P less than .01), emotional control (P less than .05), vitality (P less than .05), and leisure (P less than .05) scores. Treatment differences were particularly pronounced for patients over 50 years of age and were not fully detectable until after 14 weeks of therapy. Deterioration in quality of life was associated with withdrawal. Spouses of younger patients receiving atenolol reported deterioration in sexual satisfaction as compared to spouses of patients taking nifedipine GITS (P less than .02). Thus age, length of trial, and third-party observation are important factors in quality-of-life assessment. Comparison of adverse reactions provides an incomplete measure of how well a drug is tolerated. In contrast, findings indicate that even subtle CNS-mediated effects on mood and well-being can be detected by quality-of-life evaluation. 
Esophagobronchial fistula and mediastinal tuberculosis. A 59-year-old man was seen with what preoperatively was thought to be an acquired esophagobronchial fistula secondary to an old burned-out infection with tuberculosis. At operation the gross and microscopic findings were most compatible with a congenital H-shaped esophagobronchial fistula. However, cultures of calcified lymph nodes grew Mycobacterium tuberculosis. The need for culturing calcified tissue to assure proper treatment is emphasized. 
Acute appendicitis in patients with AIDS/HIV infection. Nine patients known to have acquired immunodeficiency syndrome (AIDS) and/or human immunodeficiency virus (HIV) infection and operated on for acute appendicitis are presented. Six of the nine patients did not have an elevation in the white blood cell count preoperatively. Two patients underwent diagnostic laparoscopy prior to exploration. In four cases, a perforated appendix was removed. Seven patients had persistent postoperative fever, while all nine had a significant lack of leukocytosis after surgery. Other than the absence of a preoperative increase in white blood cell count, the presenting characteristics of this group were similar to those expected in immunocompetent patients. However, concern for a possible opportunistic infection etiology and a desire to avoid operating on these patients resulted in an undue delay prior to exploration. The use of diagnostic laparoscopy aided in earlier and more accurate diagnosis. Despite persistent postoperative fever, appendectomy was performed in patients with AIDS/HIV infection without significant increase in morbidity and mortality. 
Reduction in defibrillator shocks with an implantable device combining antitachycardia pacing and shock therapy. Implantable defibrillators reduce the risk of sudden death in patients with malignant ventricular arrhythmias, but significant restriction in quality of life can occur as a result of frequent device activation. To determine if a device that provides both antitachycardia pacing and shock therapy can safely reduce the frequency of shocks after implantation, 46 consecutive patients undergoing initial implantation of a defibrillator were studied. In all patients, the implanted device provided antitachycardia pacing and shock therapy. Detected tachycardia characteristics and the results of therapy were stored in the device's memory. There were 42 men and 4 women, aged 26 to 71 years (mean 58.7 +/- 13.5). Left ventricular ejection fraction ranged from 13% to 67% (mean 32.2 +/- 13.4%) and 31 patients had experienced one or more episodes of cardiac arrest. Induced arrhythmias included sustained monomorphic ventricular tachycardia in 38 patients, nonsustained polymorphic ventricular tachycardia in 2 and ventricular fibrillation in 4. Over a total follow-up period of 255 patient-months (range 1 to 13, mean 6.1), 25 patients experienced spontaneous arrhythmic events. In 22 patients, 909 episodes of tachycardia were treated by antitachycardia pacing, which was successful on 840 occasions (92.4%). Acceleration of ventricular tachycardia by pacing therapy was estimated to have occurred 39 times. Syncope occurred once during pacing-induced acceleration of ventricular tachycardia. Forty-four episodes of tachycardia in seven patients were treated directly by shocks because of short tachycardia cycle length; 88% of all detected tachycardias were treated without the need for shocks. Four patients died from cardiorespiratory failure and one patient died suddenly without any detected tachyarrhythmia. 
Bleeding esophagogastric varices. Ways to treat active episodes and prevent recurrence. Bleeding from esophagogastric varices carries a high mortality rate. Active variceal bleeding can usually be temporarily controlled medically with a combination of intravenous vasopressin and nitroglycerin, with balloon tamponade, or with endoscopic sclerotherapy. Because of the high likelihood of recurrence, long-term treatment, such as repeated sclerotherapy, propranolol therapy, or shunt surgery, is necessary. The proper selection of such measures requires consideration of the site of variceal bleeding, local availability of specialized techniques, and patient factors. Only liver transplantation reverses the liver damage and offers hope of improved long-term survival. As success at identifying high-risk patients by endoscopic features improves, propranolol or other pharmacologic prophylaxis may become an acceptable treatment. 
Reorientation of the left ventricular long-axis on myocardial transaxial tomograms by a linear fitting method. A method is described for reorientating the left ventricular (LV) long-axis from myocardial transaxial tomographic data. On a midventricular transverse slice and on a midventricular sagittal slice, the apical and basal limits are selected successively by the operator. The linear activity profiles between these two limits are plotted line by line. In each profile, the two points with the maximum counts in the septal and lateral walls on the transverse slice, or in the anterior and inferior walls on the sagittal slice, are detected. The intermediate point with the minimum counts is then determined. The set of points with minimum counts are fitted by a straight line using the least squares method. This line is taken as the LV long-axis. In a series of 15 cases with stress-delayed 201Tl SPECT, the reproducibility of the reorientation with this semi-automatic method was compared with manual selection of the LV long-axis. In all patients, a successful reorientation was obtained with the present method. The reproducibility was significantly better with the semi-automatic method than with the manual selection of the LV long-axis. 
Nocturnal airflow obstruction, histamine, and the autonomic central nervous system in children with allergic asthma. A study was carried out to investigate whether an imbalance in the autonomic nervous system or release of histamine, or both, is responsible for the nocturnal increase in airflow obstruction in asthmatic children. The study comprised 18 children with allergic asthma, nine with (group 1) and nine without (group 2) nocturnal airflow obstruction, and an age matched control group. All drugs were withheld for three days before and during the study. On day 4 each child was admitted to hospital and a series of measurements was made every four hours for 24 hours. These included measurements of the forced expiratory volume in one second (FEV1), heart rate and sinus arrhythmia gap from an electrocardiogram (an indirect measure of parasympathetic activity) and urine sampling for determination of catecholamine and N'-methylhistamine concentrations (measures of sympathetic activity and histamine release respectively). Urinary N'-methylhistamine excretion was significantly higher over the 24 hours in children in group 1 than in children in group 2, and overnight values were also significantly higher in children in group 1 than those in group 2. Mean (SEM) values (mumol/mol creatinine) were 154.6 (11.2) in group 1 and 110 (11.2) in group 2 for 2400-0400 hours samples and 139.2 (13.1) and 101.2 (10.6) 0400-0800 hours samples. There was no evidence of decreased sympathetic or increased parasympathetic activity in association with the nocturnal airflow obstruction; noradrenaline concentrations were increased in group 1. These observations indicate that nocturnal airflow obstruction is associated with increased release of histamine overnight. 
Regional cerebral blood flow after human cardiac arrest. A hexamethylpropyleneamine oxime single photon emission computed tomographic study. We studied 30 patients 24 hours after out-of-hospital cardiac arrest and 13 age-matched normal controls with the use of technetium Tc 99m-hexamethylpropyleneamine oxime single photon emission computed tomography. All patients were followed up for 12 months or until death. Frontal hypoperfusion (anteroposterior perfusion ratio, less than 0.90) was observed in 23 patients (77%). In eight patients who remained comatose and died, the total size of perfusion defects was larger (38% +/- 20%) than in the 21 patients who recovered consciousness (24% +/- 14%), but the anteroposterior ratio was similar in both of these patient groups (0.83 +/- 0.09) and significantly lower than in the controls (0.96 +/- 0.03). During follow-up, both the anteroposterior perfusion ratio and the relative defect size improved, but frontal hypoperfusion was still observed in seven of 13 patients. After cardiac arrest, regional cerebral blood flow is characterized by frontal hypoperfusion that tends to improve over time but that persists in most patients. 
Decrease in the size of tetanic responses produced by nitrendipine or by extracellular calcium ion removal without blocking twitches or action potentials in skeletal muscle. The effects of removing extracellular Ca++ ions or of adding the organic calcium channel antagonist, nitrendipine, were tested on twitches and tetani (100 Hz for 2 sec) in frog toe muscles. Under conditions that did not reduce or that potentiated twitches, both procedures reduced the size of the tetanic responses. This depression was seen as an inability to maintain the maximum tetanic tension for more than 0.5 sec. Intracellular microelectrode recordings showed that the muscle fibers were depolarized (mean about 23 mV) during the stimulus train and the fiber only slowly repolarized after the train. The latter effect is the "late negative afterpotential" and it is produced by the accumulation of K+ ions in the t-tubules during the action potential train. Neither the depolarization nor the late negative afterpotentials were decreased in amplitude by nitrendipine. These results indicate that the voltage-sensitive, slow Ca++ channels are opened by the accumulation of K+ ions in the t-tubules during the tetanus and that the Ca++ ions entering via these channels are required to maintain the full strength of the tetanic contraction. It is suggested that this is a function of these Ca++ channels concentrated in the t-tubules of skeletal muscle fibers. 
Sonography of focal lesions of the spleen. The sonographic appearances of benign and malignant splenic lesions in 154 patients are illustrated. Sixty-six of the 154 patients had malignant splenic lesions; 55 of these had malignant lymphoma and 11 had splenic metastatic lesions. The lesions were hypoechoic in 64 cases (97%), including all cases of malignant lymphoma, and were hyperechoic in two. Eighty-eight patients had benign splenic lesions; findings included cysts, infarcts, abscesses, hemangiomas, and calcifications. 
Rebound tenderness test. The usefulness of the rebound tenderness test in indicating peritonitis was prospectively assessed in 142 unselected patients admitted as emergencies with abdominal pain and tenderness. It was found to be of no predictive value. 
Localized depigmentation after steroid injection of a ganglion cyst on the hand. Presented is the case of a man who had localized depigmentation after local injection of triamcinolone diacetate. Search of the literature indicates that this is a rare complication of such therapy. Localized depigmentation may have important cultural implications for dark-skinned patients. There is some experimental evidence that less-potent and shorter-acting steroid preparations have a lower likelihood for depigmenting side effects, and such agents may be more appropriate when injecting subcutaneous structures to prevent this complication. 
Enterobius egg granuloma of the vulva and peritoneum: review of the literature. Two cases of Enterobius granuloma containing eggs only are reported. The first case involved the vulva, where no such granuloma has been reported previously. The coexistence of peritoneal granuloma and rectal adenocarcinoma in the second case suggests the possibility of direct penetration of the damaged colonic wall by the parasite, as emphasized by several previous reports of neoplastic involvement and perforation of the intestinal wall in cases of ectopic infections. The diagnostic criteria of Enterobius eggs granuloma, which might be a diagnostic dilemma for pathologists who are not familiar with such criteria, are described herein. 
Acute encephalopathy due to thiamine deficiency (Wernicke's encephalopathy) in a chronic hemodialyzed patient: a case report. We report the case of a patient with terminal renal disease on chronic hemodialysis who developed acute thiamine deficiency as confirmed by erythrocyte transketolase determinations. The patient presented with a confusional state and severe memory disturbances, but other classical features of Wernicke's encephalopathy were absent. Almost all central nervous system symptoms rapidly disappeared after thiamine therapy. Therefore the possibility of thiamine deficiency must be considered in patients on chronic dialysis who present with central nervous system disturbances, even if all of the classical features of Wernicke's encephalopathy are not present. 
Percutaneous transjugular portosystemic shunt. OBJECTIVE.--To determine the effectiveness of the Palmaz balloon expandable stent for the creation of a transjugular intrahepatic portosystemic shunt. The device is designed to achieve portal decompression in patients with variceal hemorrhage secondary to portal hypertension. DESIGN.--Transjugular intrahepatic portosystemic shunting was performed in eight patients during a 9-month period. Mean follow-up was 5 months. PATIENTS.--All patients had cirrhosis with portal hypertension and varices. Bleeding occurred in seven patients from esophageal varices and in one patient from hemorrhoids. MAIN OUTCOME MEASURES.--Shunt patency and recurrent variceal hemorrhage. RESULTS.--Shunts created from a transjugular approach between a hepatic and a portal vein (diameters of 8 to 12 mm) lowered the average portosystemic pressure gradient from 36 to 11 mm Hg. Mean postoperative hospital stay was 7.7 days. Complete variceal decompression after transjugular intrahepatic portosystemic shunt placement was identified endoscopically in all eight patients. The patient treated for hemorrhoids rebled and was treated successfully by transfemoral balloon expansion of the shunt diameter from 8 to 12 mm. All shunts were patent at 1 to 9 months (mean, 5 months) of follow-up. CONCLUSION.--Initial results suggest that transjugular intrahepatic portosystemic shunt is a safe and effective method of portal decompression for the treatment of variceal hemorrhage. 
Histiocytic neoplasias: immunohistochemical evaluation of their frequencies among malignant lymphoma and related conditions in Japan. Through histologic review of 1,766 cases with malignant lymphoma and related conditions, 35 cases (2%) were selected as probable histiocytic neoplasias. Proliferating cells in these cases had voluminous, granulated cytoplasm, and round to irregularly shaped nuclei often with bi- or multinucleated forms showing monomorphous or polymorphous proliferation accompanying small lymphocytes, plasma cells, and, less frequently, eosinophils. Cases showing proliferation of convoluted cells with numerous benign-appearing histiocytes or large cells with clear cytoplasm were excluded under a diagnosis of T-cell lymphoma. To evaluate the immunologic character of proliferating cells, immunohistochemistry using antibodies Mx-Pan B, MB-1, MT-1, UCHL-1, lysozyme, alpha 1-antitrypsin, alpha 1-antichymotrypsin, S-100 alpha, S-100 beta, Leu M1, epithelial membrane antigen, and Ki-1 were carried out in 23 cases. Naphthol-ASD-chloracetate reaction and toluidine blue stain were also performed. These procedures revealed that 12 cases (52%) were B-cell type, three cases (13%) T-cell type, six cases (26%) true histiocytic type, and two cases null type. Therefore, the frequency of cases with true histiocytic neoplasias among cases with malignant lymphoma and related conditions in Japan may be 0.5%. 
Childhood predictors of future blood pressure. Blood pressure in infants and children is much lower than that in adults. It is suspected that children whose blood pressures are greatest for their age or body size may be destined for future hypertension. However, it is apparent that some children with lower blood pressures are also destined for hypertension as adults. Children with a family history of hypertension demonstrate greater blood pressure and heart rate responses to mental challenge. These responses are enhanced when a high salt diet is consumed. Increased maximal exercise systolic blood pressure and increased left ventricular wall mass in childhood add significantly to the prediction of future high blood pressure. In addition, the acquisition of excess weight for height from childhood to young adult life adds to the prediction of future blood pressure elevations. Both children and adults who are obese have significantly higher blood pressures than those who are lean. Approximately 34% of the variability in body mass index is explained by genotype differences at a single recessive locus, 41% by genotype differences at polygenic loci, and 25% by nongenetic factors. Thus, the genetic influence of obesity may be an important factor responsible for elevated blood pressure in both children and adults. 
Anemia and postoperative apnea in former preterm infants. To examine the association between anemia and postoperative apnea in former preterm infants, 24 former preterm infants of less than 60 weeks postconceptual age undergoing inguinal hernia repair were studied. A hematocrit of at least 25% was required for study participation. General endotracheal inhalational anesthesia, supplemented with neuromuscular blockade and controlled ventilation, was used. No barbiturates or opioids were administered. Respiratory pattern and heart rate were recorded for at least 12 h postoperatively using an impedance pneumograph. Tracings were analyzed for evidence of apnea, periodic breathing, and/or bradycardia by a pulmonologist unaware of the hematologic profile of the infant. Nineteen patients had a hematocrit of 30% or greater (group 1). Their mean (+/- standard deviation [SD]) gestational age was 33.5 +/- 2.7 weeks and postconceptual age 45.5 +/- 4.6 weeks. Five infants had a hematocrit less than 30% (group 2). Their mean gestational age (+/- SD) was 32.4 +/- 3.2 weeks and postconceptual age 43.6 +/- 5.5 weeks. Anemic infants had an 80% incidence of postoperative apnea versus 21% in infants with a normal hematocrit (P less than .03). In the infants who developed postoperative prolonged apnea and/or bradycardia, a prior history of apnea was equally present in both groups (21% in group 1 and 20% in group 2). This study shows that anemia in former preterm infants can be associated with an increased incidence of postoperative apnea. 
Haemangioma of the urinary tract: review of the literature. General features. Haemangiomas are benign vascular tumours. They can regress spontaneously as a result of fibrosclerosis, suggesting a conservative approach wherever possible. Asymptomatic haemangiomas do not require treatment. Renal haemangioma. In all, 198 cases have been reported. The lesion is usually solitary and unilateral and occurs most often in the pyramid, and in the mucosa or subepithelial tissue of the pelvis. In some cases a tentative diagnosis of haemangioma has been made by means of selective renal angiography and pre- or per-operative renoscopy. Partial nephrectomy is recommended in cases of minor haemangioma. Ureteric haemangioma. Six cases have been described. When haemangioma is suspected a conservative operation is recommended. Bladder haemangioma. A total of 106 cases have been reported. Many of the tumours had the characteristics of an iceberg, with considerable extravesical extension making endoscopic management less suitable because of the possibility of massive haemorrhage or recurrence. Consequently, many authors prefer local excision. In the case of endoscopic treatment the patient should be prepared for open surgery. Urethral haemangioma. Twenty cases have been described. The lesions often extend further than is immediately apparent. Endoscopic management is recommended for small lesions and, in the case of more extensive lesions, open exploration is advised followed by appropriate urethral reconstruction. 
Gastrointestinal complications in 4473 patients who underwent cardiopulmonary bypass surgery. Thirty-nine gastrointestinal complications occurred in 35 of 4473 patients (0.78 per cent) who underwent surgery involving cardiopulmonary bypass during an 8-year period. The mortality rate when one of these complications occurred was 22 (63 per cent) representing 11.5 per cent of the 191 deaths from all causes in the series. The relative risk of developing a gastrointestinal complication was 1:249 when the heart was not opened, 1:66 when it was and 1:5 after cardiac transplantation. Gastrointestinal bleeding (n = 20) was the most common complication of whom nine (45 per cent) died, followed by intestinal infarction (n = 12) with eight (67 per cent) deaths and acute pancreatitis (n = 6) all of whom died. There was one death after surgery for gastrointestinal bleeding (n = 7). No patient survived bowel infarction without operation but resection was possible in five of the eight who underwent surgery, four of whom survived. The results demonstrate that surgical intervention is not associated with undue mortality but inappropriate conservative therapy is poorly tolerated in this high-risk group. 
Familial enteric neuropathy with pseudoobstruction. We report a case of autosomal dominant chronic intestinal pseudoobstruction secondary to a familial enteric neuropathy. Esophagogastrointestinal manometry studies in the index case showed decreased postprandial contractile frequency with normal amplitude of pressure activity in the stomach and small bowel. Pupillary function and autonomic reflexes were all normal, excluding an extrinsic autonomic neuropathy of the viscera. Histologic examination of the small intestine by hematoxylin and eosin stains revealed normal smooth muscles but a reduced number of neurons in the myenteric plexus without inflammatory cells or neuroNal intranuclear inclusions. Histologic examination of the myenteric plexus using the sections taken along the longitudinal axis of the intestine, stained with silver by the Smith technique, disclosed decreased numbers of argyrophilic neurons and degeneration of neurons and axons; however, there was no reactive increase in the number of glial cell nuclei. The patient's mother had suffered from chronic intestinal pseudoobstruction, which did not abate following extensive small bowel resection. This is the third family reported with an autosomal dominant enteric neuropathy unassociated with evidence of extrinsic autonomic or peripheral neuropathy. Subtotal resection of the small bowel was followed by recurrence of the pseudoobstruction syndrome in both affected members of the family. 
Does the retrocecal position of the vermiform appendix alter the clinical course of acute appendicitis? A prospective analysis. Ninety-four adult patients undergoing appendectomy for acute appendicitis were prospectively studied during a 2-year period. Patients were divided into retrocecal (group 1; n = 27 [29%]) and anterior (group 2; n = 67 [71%]) groups according to the position of the appendix. There was no statistical difference between the two groups in duration of symptoms, presenting signs and symptoms, and initial white blood cell count. Furthermore, retrocecal appendicitis was not associated with a higher rate of perforation or increased morbidity. We conclude that the retrocecal position of the appendix does not alter the presentation of appendicitis. 
Transmetatarsal amputation: the role of adjunctive revascularization. Over a 12-year period, 160 transmetatarsal amputations were performed in patients with peripheral vascular occlusive disease. The following groups were defined: group 1 - nonreconstructable disease (n = 40); group 2 - transmetatarsal amputation in conjunction with distal revascularization (n = 99); group 3 - reconstructable disease but transmetatarsal amputation performed without simultaneous revascularization (n = 21). There were nine early deaths in the entire series, for an operative mortality rate of 5.6%. The lowest rate of transmetatarsal amputation healing (24%) occurred in group 1. An 86% healing rate was achieved in group 3, but in seven cases (33%) some type of revascularization was required within 3 months of the amputation. In group 2 the healing rate was 62% but reached 83% where the bypass remained patent for at least 3 months after the amputation. Long-term patency rates also affected healing. Healing was not influenced by the number of local procedures (single vs multiple). The presence of severe infection or extensive necrosis necessitated open transmetatarsal amputation in 89 cases; the remaining 71 amputations involved primary closure. Since many patients were treated at a time when diagnostic modalities as well as the operative indications and techniques differed somewhat from the current practice, much of the information regarding group I patients in particular should be considered as a negative historical control and any conclusion from our data should be adjusted accordingly. Healing after amputation at the transmetatarsal level can be expected in the majority of instances in which revascularization can be performed with predictable patency, even when the standard criteria for performing such amputations are liberalized. 
Idiopathic gastroparesis in patients with unexplained nausea and vomiting. Nausea and vomiting are symptoms sometimes associated with motor dysfunction. We compared a group of young patients suffering from chronic nausea and/or vomiting and normal upper gastrointestinal x-ray series with a control group. The members of both groups underwent isotopic examinations of their stomachs. The aim of the study was to find a simple method of checking the stomach and proving a motor dysfunction in a group of patients with chronic, inexplicable nausea and vomiting. Patients and controls fasted for at least 6 hr were given 0.5 mCI of [99mTc] diethylene triaminopentaacetic acid orally in 150 cc milk with 50 g cornflakes. A time-activity curve was obtained and radioactivity over the stomach was recorded exponentially. The parameter of the T1/2 emptying time was used. In normal controls T1/2 emptying time ranged from 18 to 26 min. Twenty-five symptomatic patients were examined, three of whom achieved normal values, but 22 patients showed pathologic results ranging from 36 to 184 min. In patients with chronic nausea and/or vomiting an isotopic examination of the stomach may provide a simple and rapid diagnostic method of evaluation. 
Correction of a human beta S-globin gene by gene targeting. As a step toward using gene targeting for gene therapy, we have corrected a human beta S-globin gene to the normal beta A allele by homologous recombination in the mouse-human hybrid cell line BSM. BSM is derived from a mouse erythroleukemia cell line and carries a single human chromosome 11 with the beta S-globin allele. A beta A-globin targeting construct containing a unique oligomer and a neomycin-resistance gene was electroporated into the BSM cells, which were then placed under G418 selection. Then 126 resulting pools containing a total of approximately 29,000 G418-resistant clones were screened by PCR for the presence of a targeted recombinant: 3 positive pools were identified. A targeted clone was isolated by replating one of the positive pools into smaller pools and rescreening by PCR, followed by dilution cloning. Southern blot analysis demonstrated that the isolated clone had been targeted as planned. The correction of the beta S allele to beta A was confirmed both by allele-specific PCR and by allele-specific antibodies. Expression studies comparing the uninduced and induced RNA levels in unmodified BSM cells and in the targeted clone showed no significant alteration in the ability of the targeted clone to undergo induction, despite the potentially disrupting presence of a transcriptionally active neomycin gene 5' to the human beta A-globin gene. Thus gene targeting can correct a beta S allele to beta A, and the use of a selectable helper gene need not significantly interfere with the induction of the corrected gene. 
N-myc genomic content and DNA ploidy in stage IVS neuroblastoma. DNA ploidy and N-myc genomic content were analyzed in a series of stage IVS neuroblastomas by flow cytometry and Southern blot hybridization, respectively. Of the 12 stage IVS neuroblastomas studied, nine were aneuploid (DNA index [DI] greater than 1), two were diploid (DI = 1), and one was not assessable for DNA content due to insufficient tumor material. N-myc gene amplification was present in two of 12 tumors. None of the aneuploid tumors exhibited N-myc amplification. Among the aneuploid neuroblastomas, the DIs were between 1.27 and 1.60, ie, in the near-triploid range. The follow-up from diagnosis ranged from 1 to 41 months (mean, 20 months). The nine neuroblastomas with near-triploid DNA content were free of disease at the end of the follow-up period. In contrast, a rapid and fatal tumor progression was observed for the three neuroblastomas with N-myc amplification and/or diploidy. Although involving only a limited series, these results strongly suggest that the combined analysis of DNA ploidy and N-myc genomic content could predict clinical outcome in stage IVS neuroblastoma and should help to identify patients for whom a more aggressive therapy is required. 
Long-term results after lateral cranial base surgery. The surgical management of patients with slow-growing benign temporal bone neoplasms has been criticized because of its significant morbidity and mortality compared with results after radiation therapy, but long-term control by irradiation remains unproved. Long-term surgical results have not been studied previously. One hundred twenty-nine skull base operations were performed in 126 patients at the Otology Group, Nashville, Tenn., from January 1970 through May 1987. Fifty-eight patients responded to questionnaires focusing on recovery from loss of cranial nerves. All patients regained some degree of facial function (class V or better), no alimentary tubes or tracheotomies were in use, and no patients had debilitating aspiration. Long-term compensation from the cranial nerve deficits of lateral skull base surgery can be expected in most patients and should not be used as an argument for irradiation in patients with a long life expectancy at time of diagnosis. 
Intracerebral temperature in neurosurgical patients. Recent laboratory results have indicated that the ischemic brain is very sensitive to minor variations in temperature. This has created new interest in hypothermia and brain temperature. There is, however, very little information available regarding human intracerebral temperature and its relation to body core temperature during normal and pathological circumstances. We therefore made continuous measurements of the temperature of the lateral ventricle in 15 neurosurgical patients utilizing a newly developed technique with copper-constantan thermocouples introduced through a plastic catheter also used for monitoring intracranial pressure. The intraventricular temperature was higher than the rectal temperature during approximately 90% of all measurements. The largest temperature gradient measured was 2.3 degrees C. Usually the difference between the temperature of the rectum and the brain was much smaller, the mean value being 0.33 degrees C. For the patients in the most severe condition, the rectal temperature was sufficiently close to the brain temperature to afford a reliable basis for adequate clinical judgment. 
The potential roles of leukotrienes in bronchial asthma. Leukotrienes (LTs), in particular LTC4, LTD4, and LTE4, have been shown to be capable of participating in the induction of three related processes observed during the immediate reaction in bronchial asthma: edema formation, mucus secretion, and muscle contraction. Despite impressive evidence potentially implicating the LTs, the role of LTs in asthma is still unproved, and a positive answer to their critical actions in causing airflow obstruction will require studies with specific antagonists. 
Functional recovery of hibernating myocardium after coronary bypass surgery: does it coincide with improvement in perfusion? To determine the relationship between functional recovery and improvement in perfusion after coronary artery bypass graft surgery (CABG), 49 patients were studied. Radionuclide angiography was performed before, 1 month after, and 6 to 12 months after CABG to evaluate regional wall motion. Exercise thallium-201 myocardial perfusion imaging was done before and 1 month after CABG to assess regional perfusion. Preoperative asynergy was observed in 108 segments, and 74 of them showed an improvement in wall motion 1 month after CABG (segment A). Sixty-six of these segments (89%) were associated with an improvement in perfusion. Eight segments that had not improved 1 month after CABG demonstrated a delayed recovery of wall motion 6 to 12 months after CABG (segment B). However, seven of eight segments (88%) already showed an improvement in perfusion 1 month after CABG. A total of 82 segments exhibited functional recovery after CABG and were considered hibernating segments. In the preoperative study segment B more frequently had areas of akinesis or dyskinesis than segment A (75% vs 34%, p less than 0.05). The mean percent thallium-201 uptake in segment B was lower than that in segment A (74% +/- 9% vs 83% +/- 8%, p less than 0.05). Functional recovery of hibernating myocardium usually coincided with an improvement in perfusion. However, delayed functional recovery after reperfusion was observed in some instances. Severe asynergy and severe thallium-201 defects were more frequently observed in these segments with delayed recovery. Hibernating myocardium might remain stunned during those recovery periods. 
Human immunodeficiency virus infection and diffuse polyneuropathy. Implications for rehabilitation medicine. Patients at various stages of human immunodeficiency virus (HIV) infection require rehabilitation services. These patients present problems for each of the disciplines in a rehabilitation team, and all team members must confront the psychosocial and ethical issues involved with the disease. Patients with HIV infection may have polyneuropathy with multisystem involvement, including dysphagia, autonomic dysfunction, respiratory failure, bowel and bladder dysfunction, generalized weakness, a painful sensory neuropathy, and depression. Guidelines are presented for determining if inpatient rehabilitation or other settings are appropriate. Case management is a valuable strategy for the rehabilitation of patients with this complicated disorder. 
Intestinal absorption of cholecalciferol and 25-hydroxycholecalciferol in patients with both Crohn's disease and intestinal resection. We compared the intestinal absorption of cholecalciferol and 25-hydroxycholecalciferol in patients with Crohn's disease and resections of the small bowel. Patients were subgrouped into those with small (less than 100 cm), intermediate (100-300 cm), and large (greater than 300 cm) resections. [3H]cholecalciferol or [3H]25-hydroxycholecalciferol were given orally and serial blood samples were taken for measurement of plasma radiolabeled vitamin. Absorption of both forms of the vitamin decreased with extent of resection but 25-hydroxycholecalciferol absorption was always greater than that of cholecalciferol. When compared with normal control subjects, 25-hydroxycholecalciferol absorption in these patients was better maintained than that of cholecalciferol. These data indicate that vitamin D malabsorption reflects the extent of distal small-bowel resection in Crohn's disease. Treatment with oral cholecalciferol is sufficient in those with small or moderate resections but oral 25-hydroxycholecalciferol supplementation may be preferred in those with a severe short-bowel syndrome. 
Zinc sulphate therapy for Wilson's disease after acute deterioration during treatment with low-dose D-penicillamine. A 30-year-old woman with Wilson's disease was treated with low-dose D-penicillamine. After 12 days, treatment was changed to zinc sulphate because of severe neurological deterioration. The patient subsequently improved within a few days. During a follow-up period of 20 months, the effectiveness of therapy was evaluated by measuring copper and zinc levels in plasma and urine, and by 64Cu-loading tests. We conclude that sulphate therapy may be a satisfactory alternative, even when rapid deterioration occurs in the early stages of D-penicillamine treatment. 
Cardiovascular risk factors in primary hyperparathyroidism: a 15-year follow-up of operated and unoperated cases. The need for treatment of mild and apparently asymptomatic primary hyperparathyroidism (HPT) is questioned, but a raised incidence of cardiovascular disease has been regarded as evidence in favour of surgery. While it is well known that several risk factors for cardiovascular disease (hypertension, hyperlipidaemia and diabetes mellitus/impaired glucose tolerance) are overrepresented in HPT, it is not known whether surgery provides long-term normalization in these respects and reduces the risk of premature death. In a 15-year follow-up of a cohort of 172 subjects in whom mild hypercalcaemia was initially detected during a health screening, it was found that 56 subjects had died. 17 individuals had been operated on for HPT, 47 individuals were persistently hypercalcaemic, while 45 subjects had serum calcium within the normal range (seven individuals were lost to follow-up). There had been no significant differences in blood pressure between these groups of mildly hypercalcaemic patients and age- and sex-matched controls at the initial screening, but at follow-up blood pressure was significantly higher not only in subjects with persistent hypercalcaemia, but also in those who had been successfully operated on for HPT. Neither of the hypercalcaemic groups showed any significant deviations from the controls with regard to indices of lipid or glucose metabolism. These findings suggest that there is no simple cause-and-effect relationship to account for the propensity toward high blood pressure in primary HPT. Consequently it cannot be assumed that surgery for HPT will eliminate the increased risk of cardiovascular disease in patients with mild HPT. 
Maturation of respiratory reflex responses in the piglet. Stimulation of chemo-, irritant, and pulmonary C-fiber receptors reflexly constricts airway smooth muscle and alters ventilation in mature animals. These reflex responses of airway smooth muscle have, however, not been clearly characterized during early development. In this study we compared the maturation of reflex pathways regulating airway smooth muscle tone and ventilation in anesthetized, paralyzed, and artificially ventilated 2- to 3- and 10-wk-old piglets. Tracheal smooth muscle tension was measured from an open tracheal segment by use of a force transducer, and phrenic nerve activity was measured from a proximal cut end of the phrenic nerve. Inhalation of 7% CO2 caused a transient increase in tracheal tension in both age groups, whereas hypoxia caused no airway smooth muscle response in either group. The phrenic responses to 7% CO2 and 12% O2 were comparable in both age groups. Lung deflation and capsaicin (20 micrograms/kg iv) administration did not alter tracheal tension in the younger piglets but caused tracheal tension to increase by 87 +/- 28 and 31 +/- 10%, respectively, in the older animals (both P less than 0.05). In contrast, phrenic response to both stimuli was comparable between ages: deflation increased phrenic activity while capsaicin induced neural apnea. Laryngeal stimulation did not increase tracheal tension but induced neural apnea in both age groups. These data demonstrate that between 2 and 10 wk of life, piglets exhibit developmental changes in the reflex responses of airway smooth muscle situated in the larger airways in response to irritant and C-fiber but not chemoreceptor stimulation. 
Abrupt vessel closure following platelet transfusion post-PTCA. A successful PTCA was complicated by abrupt closure following a platelet transfusion which was given for control of local bleeding. Possible mechanisms of abrupt closure are discussed. Recommendation is made to avoid giving platelet transfusion following PTCA. 
Porencephalic cyst: a complication of fetal intravascular transfusion. A case of unilateral porencephalic cyst as a result of intravascular intrauterine transfusion is reported. Although other factors may have contributed, fetal bradycardia and relative hyperviscosity as a result of increased fetal hematocrit value were considered to be related to this event. Because some authors recommend direct intravascular transfusion to supraphysiologic hematocrits to prolong the interval between procedures, we would caution the use of this approach on the basis of theoretic considerations and the occurrence of this complication. 
Infrapopliteal bypass for severe ischemia: comparison of autogenous vein, composite, and prosthetic grafts. Results of 253 consecutive bypass grafts to infrapopliteal arteries were reviewed. Most (92%) were placed for rest pain (103) or tissue loss (130). Autogenous veins were used in 175 (69%) cases, composite vein-prosthetic grafts were used in 45 (18%), and prosthetic grafts alone were used in 33 (13%). Follow-up ranged from 0 to 101 months (mean, 19 months); 37 grafts (15%) were lost to follow-up. The operative mortality rate was 4%, and 5-year patient survival rate was 44%. Limb salvage was 82% at 5 years. The 5-year patency of vein grafts (63%) exceeded that of both composite (28%) and prosthetic (7%) grafts (p = 0.005 and p = 0.00007, respectively); but the patency of composite and prosthetic grafts did not differ significantly (p = 0.29). The patency of reversed vein (59%) and in situ vein grafts (74%) was not significantly different at 5 years (p = 0.34). Patency was also not affected by the site of the proximal or distal anastomoses or diabetes. The major determinant of long-term patency in infrapopliteal reconstructions continues to be graft material. Composite grafts offered no clear advantage over prosthetic grafts, and both should be used only when there is no other alternative to amputation. 
Experience with rehabilitation in the acquired immunodeficiency syndrome. Patients with the acquired immunodeficiency syndrome (AIDS) represent a novel referral population for rehabilitation services. Limited information about the rehabilitation needs of individuals with human immunodeficiency virus infection is available. We reviewed 51 consecutive patients with AIDS referred to a rehabilitation consult service. Common problems encountered included generalized deconditioning (27%) and neurologic dysfunction (45%). Neurologic presentations were diverse and included hemiparesis, diffuse cognitive dysfunction and dementia, myelopathy, myopathy and peripheral neuropathy. Other patients were referred for wound care as well as the management of the local effects of Kaposi's sarcoma, various musculoskeletal syndromes and new onset blindness. Problems identified included impaired mobility (76%), difficulty with self-care (57%), impaired cognition (29%) and uncontrolled pain (37%). Among the rehabilitation interventions utilized were therapeutic exercise (73%), gait aids (45%), bathroom and safety equipment (45%), orthotics (29%), vocational counseling (4%), pain management (29%) and whirlpool treatments (10%). Five patients were too ill or refused treatment. We conclude that AIDS patients referred for rehabilitation have a wide variety of physical deficits, demonstrate a considerable degree of functional impairment and may require multiple rehabilitation interventions. 
Adnexal torsion. An unusual cause of abdominal pain in postmenopausal women. Adnexal torsion is a rare cause of abdominal pain in older women. Because the presenting symptoms and signs are vague, the diagnosis is not often considered. Lower abdominal pain with nausea and vomiting are usual in patients with torsion. Ultrasonography or computed tomography are useful diagnostic tests. Two case reports of older patients with adnexal torsion are presented to emphasize the diagnostic features of this entity, including lower abdominal pain, nausea and vomiting, and abdominal mass. Although the condition is uncommon, adnexal torsion should be considered in the differential diagnosis of acute abdominal pain. 
Genetic analysis of autoimmune type 1 diabetes mellitus in mice Two genes, Idd-3 and Idd-4, that influence the onset of autoimmune type 1 diabetes in the nonobese diabetic mouse have been located on chromosomes 3 and 11, outside the chromosome 17 major histocompatibility complex. A genetic map of the mouse genome, analysed using the polymerase chain reaction, has been assembled specifically for the study. On the basis of comparative maps of the mouse and human genomes, the homologue of Idd-3 may reside on human chromosomes 1 or 4 and Idd-4 on chromosome 17. 
Effect of Helicobacter pylori infection on the severity of gastroduodenal mucosal injury after the acute administration of naproxen or aspirin to normal volunteers. This study asked whether Helicobactor pylori infection accentuated the severity of NSAID-induced mucosal injury of the stomach or duodenum. We evaluated the severity of acute mucosal injury and H. pylori status in 61 normal volunteers (ages 22-43 yr) receiving naproxen (1000 mg, n = 30) or aspirin (3900 mg, n = 31) daily for 7 days. NSAID-induced gastric and duodenal mucosa each were endoscopically graded separately for hemorrhages and erosions-ulcers on a scale of 0 to 4. H. pylori infection was identified by a sensitive and specific ELISA. Nine of the 30 subjects in the naproxen group and 12 of the 31 subjects in the aspirin group were H. pylori positive (p = NS). There was no statistically significant difference between the frequency of mucosal hemorrhage in those with and those without H. pylori infection (44% compared with 33% for those receiving naproxen and 90% of those receiving ASA, p = NS for each). There were also no differences in the frequency or severity of erosive mucosal injury seen, e.g., acute ulcers were found in 16.5% and 17.5% of infected and uninfected subjects, respectively. We conclude that the presence of H. pylori infection does not influence the degree or type of mucosal damage associated with the acute administration of naproxen or aspirin. 
Down syndrome due to de novo Robertsonian translocation t(14q;21q): DNA polymorphism analysis suggests that the origin of the extra 21q is maternal. Down syndrome is rarely due to a de novo Robertsonian translocation t(14q;21q). DNA polymorphisms in eight families with Down syndrome due to de novo t(14q;21q) demonstrated maternal origin of the extra chromosome 21q in all cases. In seven nonmosaic cases the DNA markers showed crossing-over between two maternal chromosomes 21, and in one mosaic case no crossing-over was observed (this case was probably due to an early postzygotic nondisjunction). In the majority of cases (five of six informative families) the proximal marker D21S120 was reduced to homozygosity in the offspring with trisomy 21. The data can be best explained by chromatid translocation in meiosis I and by normal crossover and segregation in meiosis I and meiosis II. 
Oxygen transport in cardiogenic and septic shock. OBJECTIVE: To review clinical studies of oxygen transport in cardiogenic and septic shock. DESIGN: Descriptive and prospective studies. SETTING: University hospital multi disciplinary ICU. PATIENTS: Critically ill cardiogenic and septic shock patients greater than 18 and less than 80 yrs of age. INTERVENTIONS: The responses to volume loading with colloid or crystalloid and infusion of catecholamines are documented with baseline hemodynamic and oxygen transport measurements before and after administration of catecholamines. MEASUREMENTS AND MAIN RESULTS: Nineteen patients in cardiogenic shock were studied. In three patients, invasive systemic mean arterial pressure was greater than 80 mm Hg and cardiac index was greater than 2.0 L/min.m2. In all patients, there were increases in oxygen extraction ratio that averaged 48 +/- 18 (SD) %. However, in 30 septic shock patients, extraction ratio was 24 +/- 2%. In both groups, the response to therapy was an increase in mixed venous oxygen saturation from 54 +/- 16% to 69 +/- 8% in cardiogenic patients (p less than .001) and from 75 +/- 2% to 80 +/- 1% in septic shock (p less than .01). CONCLUSIONS: There are widely differing oxygen transport patterns in cardiogenic and septic shock that may have implications for therapy. 
Repair of a cerebrospinal fluid perilymph fistula primarily through the middle ear and secondarily by occluding the cochlear aqueduct. A 35-year-old man had a 5-year history of fluctuating hearing loss in his only hearing ear. History and diagnostic tests indicated a perilymph fistula, a diagnosis subsequently confirmed by exploration. Primary and secondary repairs temporarily ameliorated symptoms. A spinal fluid to middle ear fluid pathway was identified by radioactive tracer. A patent cochlear aqueduct indicated on computed tomography scan was found and repaired through a posterior cranial fossa approach. Hearing was preserved, remaining relatively stable during the 2-year follow-up period. 
New trends in gallstone management. Many new therapies for the management of gallstone disease have been pioneered in the past decade. The object of this review is to equip the surgeon with the answers to all of the questions a patient will ask about gallstone therapy; the review is therefore didactic as well as comprehensive. 
Cardiac performance indices during hypervolemic therapy for cerebral vasospasm. The effect of hypervolemic preload enhancement on cardiac performance was systematically analyzed in nine patients following aneurysmal subarachnoid hemorrhage. The patients ranged in age from 34 to 63 years, and none had a history of cardiac disease. Each patient underwent placement of a flow-directed balloon-tipped catheter and the following measurements were taken during hypervolemic therapy: pulmonary artery wedge pressure (PAWP), central venous pressure (CVP), cardiac index (CI), stroke volume index (SVI), and left ventricular stroke work index (LVSWI). After baseline measurements were recorded, hetastarch or plasmanate was infused intravenously at 300 cc/hr. Thermal output determination and pressures were measured every 15 minutes. The PAWP did not correlate in a statistically significant fashion with the CVP in the ranges recorded; however, a statistically significant correlation did exist between PAWP increases and increases in CI, SVI, and LVSWI (p less than 0.01). There was no statistical correlation between PAWP increases above 14 mm Hg and improvement in cardiac performance as evidenced by CI, SVI, and LVSWI measurements. It is concluded that CVP is an unreliable index of cardiac performance during hypervolemic therapy and that, in previously healthy individuals, a PAWP of 14 mm Hg is associated with maximum cardiac performance. 
Histologic and ultrastructural findings of tissue ingrowth. The Leeds-Keio prosthetic anterior cruciate ligament. A light and electron microscopy investigation was performed on a Leeds-Keio ligament removed because of rupture 18 months after implantation to repair an anterior cruciate ligament. The investigation showed fibrous connective tissue on the plane of the main stress force. There was elastin and adequate vascularization interspersed with Type I collagen fibrils in the area most distant from the ligament. The tissue near the Dacron fibers was highly cellular with a matrix of infrequent, thin collagen fibrils and abundant fine granular material. The growth of the host tissue occurred in and around a Leeds-Keio ligament in response to tensile stresses. 
Surgical method for treatment of syndactyly with osseous fusion of the distal phalanges. For the interdigital space plasty to correct a syndactyly with fusion of the distal phalanges, we adopted a new operative procedure, covering the exposed distal bone with local rectangular flaps designed transversely on both dorsal and volar surfaces. A full-thickness skin graft from the groin region covers the remaining raw surface. The procedure was performed in six patients, and the flaps measured 6 mm (width) x 12 to 16 mm (length) in four patients, 5 x 15 mm in one patient, and 5 x 18 mm in one patient. Partial necrosis was observed in only one patient, in whom a narrow flap of 5 x 18 mm was used. In the other five patients, however, the results were satisfactory on both external appearance and function during the follow-up period of 3 to 6 years. 
Flexible cystoscopy compared with ultrasound in the detection of recurrent bladder tumours. A combination of transrectal and transabdominal ultrasound was compared with flexible cystoscopy as a means of detecting recurrent bladder tumours. The study group comprised 50 patients who had previously had rigid cystoscopy. They underwent combination ultrasound in the out-patient department 1 week before flexible cystoscopy. Combination ultrasound identified 25 patients with recurrent tumours and flexible cystoscopy identified 26. Thirty-four patients (68%) preferred ultrasound, 10 (20%) preferred flexible cystoscopy, 3 (6%) preferred general anaesthesia and rigid cystoscopy and 3 (6%) had no preference. The main objection to ultrasound was the use of the transrectal probe. 
Ambulatory stab evulsion phlebectomy for truncal varicose veins. The management of primary varicose veins is evolving. Recovery time, cost, recurrence rate, and cosmesis are critical determinants. Classic "high ligation" and ankle-to-groin stripping is expensive, results in a long convalescence, and may produce unacceptable scarring and possible permanent nerve injury. This report describes the technique of stab evulsion phlebectomy performed in an outpatient setting. Under loco-regional anesthesia, and after high ligation, existing tributary and trunk varicosities are evulsed with specially designed hooks. The multiple stab incisions, 1.5- to 3-mm long, are closed with adhesive strips. Fifty-six patients, with 69 involved limbs, have been operated on during the past 9 months. Postoperative pain and complications were minimal. Convalescence was eliminated and all patients immediately resumed normal daily activities. Cosmesis was excellent. This technique is based on hemodynamically accurate principles. It effectively removes all varicosities, eliminates the proximal source of reflux, and disconnects potentially outflowing perforators, yet leaves in situ undamaged trunk veins, which may be used as potential vein grafts. 
Primary central nervous system lymphoma versus toxoplasmosis in AIDS. The imaging studies of 16 patients with acquired immunodeficiency syndrome (AIDS) and proved primary central nervous system (CNS) lymphoma were reviewed. All studies included computed tomography (CT); six also included magnetic resonance (MR) imaging. A periventricular lesion was seen in 50% of patients. At least one such lesion exhibited subependymal spread or ventricular encasement in 38%. One-third of lesions in three of five patients who underwent nonenhanced CT were hyperattenuating. Five lesions were at least in part hypointense on T2-weighted MR images. The specificity of these findings was evaluated with a similar review of the imaging studies in 28 patients with AIDS and proved toxoplasmosis. Only 3% of lesions were periventricular. None exhibited subependymal spread or encasement. None were hyperattenuating on nonenhanced CT scans. Similar findings in other CNS lesions in AIDS patients could not be found in the literature. A focal enhancing mass with subependymal spread on CT or MR images and hyperattenuation at nonenhanced CT were the most reliable features in distinguishing between primary CNS lymphoma and toxoplasmosis in AIDS patients. 
Predictive accuracy of electrophysiologic localization of accessory pathways. Operative ablation of accessory pathways depends critically on preoperative localization when technical limitations preclude complete intraoperative mapping. To assess the accuracy of localization, 345 patients undergoing operative ablation were studied; 316 (91.6%) had a single accessory pathway and 29 (8.4%) had multiple accessory pathways. The electrophysiologic study was diagnostically complete and accurate in 294 patients (93%) with a single accessory pathway and 19 (61%) with multiple accessory pathways. A left lateral accessory pathway was most accurately localized with excellent sensitivity (99%) and positive predictive value (98.5%). Diagnostic errors occurred in 33 patients because of 1) incorrect localization (n = 16), 2) failure to detect a second pathway (n = 9), and 3) diagnosis of a second pathway not verified intraoperatively (n = 8). Multiple pathways were more prevalent in the group with errors (33.3% vs. 5.8%, p = 0.0001), as were unidirectional pathways (48.5% vs. 24.3%, p = 0.003). It is concluded that preoperative localization of accessory pathways is sufficiently accurate to allow intraoperative mapping to be brief and focused. 
Index for optimum ventricular catheter length. Technical note. The optimum length of a ventricular catheter to be placed in a particular patient may be difficult to determine when either intraoperative ultrasound is not available or considerable time has elapsed between the diagnostic computerized tomography scan and the operation. An index for estimating ventricular length based on the head circumference of the individual is described. This method was tested clinically and proved to be successful. 
The influence of gender on the susceptibility to multiple sclerosis in sibships. A population-based study of pairs of relatives (siblings, second- and third-degree) concordant for multiple sclerosis did not show an excess of like-sexed pairs. In addition, data on human lymphocyte antigen typing for sibling pairs concordant for multiple sclerosis did not find an increase in haplotype sharing for like-sexed pairs. These data do not support the notion that sex-related factors influence multiple-sclerosis susceptibility in families. 
Intermittent short-term negative pressure ventilation and increased oxygenation in COPD patients with severe hypercapnic respiratory failure. With the aim of testing a method that allows increasing concentrations of oxygen to be administered to patients with severe hypoxemia and hypercapnia while avoiding the risk of increasing respiratory acidosis, we studied 17 male patients with advanced chronic obstructive pulmonary disease (COPD) and severe hypercapnic respiratory failure. During 6 h and on one day only, all patients were given intermittent negative pressure ventilation (INPV) together with oxygenation starting at a concentration of 24 percent and increasing to 30 percent. Using this procedure, it was possible to raise arterial PaO2 to safe levels (from 47.2 +/- 3 mm Hg to 61.5 +/- 6 mm Hg, p less than 0.001) without increasing hypercapnia, and a significant drop in PaCO2 levels (from 74.4 +/- 9 mm Hg to 65.6 +/- 12 mm Hg, p less than 0.005) was even observed. One hour after INPV ended, the mean values of PaO2, PaCO2, oxygen saturation, and pH were also significantly better than prestudy values. We conclude that INPV and oxygen therapy with increasing oxygen flow could constitute an alternative option to intubation and mechanical ventilation in cases of severe hypercapnic respiratory failure due to advanced COPD. 
Sustained ventricular tachycardia associated with sarcoidosis: assessment of the underlying cardiac anatomy and the prospective utility of programmed ventricular stimulation, drug therapy and an implantable antitachycardia device. The presentation, cardiac anatomy and utility of programmed ventricular stimulation in seven patients with sustained ventricular tachycardia associated with sarcoidosis are described. The mean patient age was 38 +/- 8 years. Pulmonary involvement was apparent in three patients and no systemic manifestations of sarcoidosis were present in one patient. All patients had electrocardiographic abnormalities at rest and six had a left ventricular ejection fraction less than 45%. All seven patients had left ventricular wall motion abnormalities and five had mitral valve dysfunction. Sustained ventricular tachycardia was easily induced in all patients. Spontaneous sustained ventricular tachycardia was not prevented with corticosteroid administration. Despite antiarrhythmic drug therapy, two patients had sudden cardiac death and an additional four had recurrence of ventricular tachycardia. Four patients had an automatic cardioverter-defibrillator implanted and received drug therapy; all four received appropriate shocks. This report represents the largest descriptive series of consecutive patients with sustained ventricular tachycardia associated with sarcoidosis. Antiarrhythmic drug therapy of ventricular tachycardia in patients with sarcoidosis, even when guided with programmed ventricular stimulation, is associated with a high rate of arrhythmia recurrence or sudden death, or both. Thus, implantation of an automatic antitachycardia device (cardioverter-defibrillator) should be considered as primary therapy in such patients. Furthermore, sarcoidosis should be excluded, with Kveim skin testing if necessary, in any patient with sustained ventricular tachycardia of unknown origin. 
Detection of DNA sequence polymorphisms by enzymatic amplification and direct genomic sequencing. The discovery of RFLPs and their utilization as genetic markers has revolutionized research in human molecular genetics. However, only a fraction of the DNA sequence polymorphisms in the human genome affect the length of a restriction fragment and hence result in an RFLP. Polymorphisms that are not detected as RFLPs are typically passed over in the screening process though they represent a potentially important source of informative genetic markers. We have used a rapid method for the detection of naturally occurring DNA sequence variations that is based on enzymatic amplification and direct sequencing of genomic DNA. This approach can detect essentially all useful sequence variations within the region screened. We demonstrate the feasibility of the technique by applying it to the human retinoblastoma susceptibility locus. We screened 3,712 bp of genomic DNA from each of nine individuals and found four DNA sequence polymorphisms. At least one of these DNA sequence polymorphisms was informative in each of three families with hereditary retinoblastoma that were not informative with any of the known RFLPs at this locus. We believe that direct sequencing is a reasonable alternative to other methods of screening for DNA sequence polymorphisms and that it represents a step forward for obtaining informative markers at well-characterized loci that have been minimally informative in the past. 
Incidence and prevalence of amyotrophic lateral sclerosis in Harris County, Texas, 1985-1988. The incidence of amyotrophic lateral sclerosis was determined in Harris County, Texas, for the period 1985 through 1988. Amyotrophic lateral sclerosis cases were ascertained from four sources: area neurologists, hospitals, death certificates, and the Muscular Dystrophy Association. The age-adjusted incidences of 1.27 per 100,000 person-years in males and 1.03 per 100,000 person-years in females were lower than recent rates in the northern US, Canadian, and northern European studies but higher than rates in southern European studies. Comparisons with other recent incidence studies show less uniformity in occurrence of amyotrophic lateral sclerosis, in both the overall rates and in the age- and sex-specific patterns, than was suggested by mortality studies. The incidence of amyotrophic lateral sclerosis among blacks and whites was similar. Hispanic males had incidences similar to white males, although a deficit of female Hispanic cases was found in Harris County. The prevalence of amyotrophic lateral sclerosis peaked in the 65- to 74-year age group at 33 per 100,000 population among males and 19 per 100,000 population for females. 
Extensive hepatic granulomas associated with peripheral T-cell lymphoma. A case of T-cell lymphoma presenting with marked hepatosplenomegaly and extensive hepatic granulomas is described. A 55-yr-old female experienced long-term liver damage showing histological triaditis with atypical lymphoid cell infiltration and erythrophagocytosis. The patient developed marked hepatosplenomegaly and eventually died of respiratory failure. Neither systemic lymphadenopathy nor hematological disorder was noted until her death. Autopsy revealed small atypical lymphoid cells positive for T-cell marker, as well as extensive infiltration of generalized organs, including the liver, spleen, and lungs. As a result of diffuse proliferation of atypical lymphoid cell admixed with variable reactive cells, mainly at the T-zone, the lymph nodes underwent effacement of normal architecture; however, the peripheral sinuses and the fibrous capsule remained relatively well preserved. These histological features were consistent with a diagnosis of peripheral T-cell lymphoma (PTL). It is interesting to note that there were numerous epithelioid granulomas admixed with a small number of atypical lymphoid cells within the hepatic parenchyma. The atypical lymphoid cells may be responsible for the granulomatous reaction in the liver. To our knowledge, there have been no other reported cases of PTL that presented with numerous epithelioid granulomas confined to the liver. 
Perivalvular extension of infection in patients with infectious endocarditis. Perivalvular extension of infection is a not-infrequent and potentially fatal complication of bacterial endocarditis. Because the efficacy of various modalities in the diagnosis of such complications is not well established, a selective review of the published literature on this issue is worthwhile. The electrocardiogram is the easiest study to obtain. It is quite specific in identifying perivalvular extension of infection when conduction system disease is demonstrated but has a low degree of sensitivity overall. Transthoracic two-dimensional echocardiography, transesophageal echocardiography, and color-flow Doppler echocardiography are the most practical and useful techniques for diagnosis of perivalvular extension of infection. Magnetic resonance imaging also appears to be an effective tool in this setting; however, because of a paucity of clinical data, its precise utility has not yet been determined. Nuclear medicine studies and computed tomography play a minimal role. Cardiac catheterization is as useful as the echocardiographic techniques but is invasive, not as readily available, and significantly riskier in terms of complications. An approach to the diagnosis of perivalvular extension of infection is proposed on the basis of the literature review. 
Microvascular angina. Cardiovascular investigations regarding pathophysiology and management. A significant minority of patients with chest pain who undergo cardiac catheterization are found to have angiographically normal coronary arteries. Over the past 25 years, several studies have shown that a subset have demonstrable abnormalities in coronary flow and cardiac function; however, only a minority of these patients have convincing evidence for myocardial ischemia during stress, and alternative mechanisms have been explored to explain the frequent and debilitating symptoms of pain experienced by the majority of these patients undergoing study. Abnormal visceral nociception appears to be a fundamental abnormality in this population, whether or not demonstrable abnormalities in coronary flow or cardiac function can be demonstrated. 
Bazex syndrome (acrokeratosis paraneoplastica). An analytic review. Bazex syndrome (acrokeratosis paraneoplastica) is characterized by a psoriasiform eruption that favors acral sites and has been associated with an underlying malignancy in all reported cases. Of the 93 patients in this series, 89 were male with a mean age of 60 +/- 8.5 years. Squamous cell carcinomas of the head and neck and squamous cell tumors of unknown primary with cervical lymph node metastases were the most commonly associated neoplasms, suggesting that the factor(s) responsible for the development of the syndrome are relatively specific for tumors of the upper aerodigestive tract. The cutaneous lesions were erythematous to violaceous in color and had associated scale; the most frequently observed sites of involvement were the ears, nose, hands, and feet, including the nails. In 63% of the cases, the cutaneous lesions preceded the initial symptoms or diagnosis of the tumor by an average of 11 months (range, 1-72) and, in general, the eruption was resistant to a variety of topical treatments. Occasionally, a reappearance of the papulosquamous lesions signaled the recurrence of the tumor (6 cases) or the appearance of skin lesions coincided with the development of metastatic disease (3 cases). In 91% (64/70) of the patients, the skin eruption either improved significantly following treatment of the underlying malignancy or did not improve in the setting of persistent tumor. However, even when all of the skin lesions cleared, the nail dystrophy often persisted. Fifteen of the patients developed vesicles, bullae, and crusts in addition to papulosquamous lesions. Possible explanations include the formation of an epidermal-dermal split via a bullous lichen planus-like mechanism, or the coexistence of two diseases; i.e., acrokeratosis paraneoplastica plus either porphyria cutanea tarda, bullous pemphigoid, or epidermolysis bullosa acquisita. One possible explanation for the development of the characteristic cutaneous eruption is an immune reaction, humoral or cellular, directed against a common antigen present on the tumor and the normal skin. Alternatively, tumor production of a keratinocyte growth factor such as TGF-alpha may be involved in the induction of the psoriasiform skin lesions. 
Attenuation of IL-2-induced multisystem organ edema by phalloidin and antamanide. Interleukin 2 (IL-2) is a potent cytokine with diverse effects, including the ability to stimulate lymphocyte differentiation into cells capable of lysing tumor. Its therapeutic efficacy is limited because of side effects such as breakdown of the microvascular barrier and edema. Control of the microvascular barrier is in part regulated by endothelial cell cytoskeletal contractile proteins. This study tests whether the cyclopeptides that maintain actin filament organization and distribution and reduce macromolecular flux across the endothelial cell junction in vitro would similarly maintain barrier tightness and prevent early edema produced by IL-2 in vivo. Anesthetized rats were treated at 30-min periods with intravenous saline (0.5 ml, n = 41), phalloidin (20 micrograms in 0.5 ml, n = 21), or antamanide, (20 micrograms in 0.5 ml, n = 21), starting 30 min before the 1-h infusion of 10(6) U of recombinant human IL-2 or saline. Six hours after the start of IL-2, there was edema in the saline/IL-2 group, as measured by increased wet-to-dry ratios (W/D) in the lungs, heart, and kidney. With saline/IL-2, bronchoalveolar lavage (BAL) fluid contained an elevated protein concentration and higher plasma thromboxane levels compared with controls. The number of neutrophils sequestered in the lungs was more than twice that of saline controls. Phalloidin significantly attenuated edema in lung and reduced BAL protein leak. Antamanide treatment was as effective in limiting lung and heart edema, but, in contrast to phalloidin, antamanide prevented kidney edema and did not lead to an alteration in the liver W/D. Antamanide also prevented BAL fluid protein leak. 
Telangiectatic osteosarcoma. Telangiectatic osteosarcoma is a rare variant of osteosarcoma. In the original report from the authors' institution, a poor prognosis was noted. The authors have updated their experience with this entity. The prognosis for patients with telangiectatic osteosarcoma has improved remarkably. The prognosis in the present series seems to be the same as that for conventional osteosarcoma. Adjuvant chemotherapy seems to help in salvaging patients with metastatic disease. However, in this small series, survival of patients without metastasis is apparently not influenced by whether they received chemotherapy. 
Agonist-sensitive calcium stores in arteries from steroid hypertensive rats. The present study characterizes cellular calcium stores that are sensitive to norepinephrine and caffeine in arteries from deoxycorticosterone acetate hypertensive rats. Mesenteric arteries from normotensive and hypertensive rats were excised and cut into helical strips for isometric force recording. In calcium-free solution, phasic contractile responses to norepinephrine (5.9 x 10(-9) to 5.9 x 10(-6) M), but not caffeine (0.3-30 mM), were greater in hypertensive arteries. D-600, a calcium channel blocker, or removal of the endothelium did not alter phasic contractions to norepinephrine or caffeine. In contrast, contractions to both norepinephrine and caffeine were inhibited by ryanodine, a drug that depletes calcium from intracellular stores. An inhibitor of phospholipase C (2-nitro-4-carboxyphenyl N,N-diphenylcarbamate) attenuated contractions to norepinephrine but not those to caffeine. The augmented response to norepinephrine in hypertensive rats did not occur early after implantation of the mineralocorticoid, suggesting that this vascular change may not play a role in the development of high blood pressure in this experimental model. The augmented response to norepinephrine was reduced in mineralocorticoid-treated rats maintained on a low sodium diet, and these rats had blood pressures in the normotensive range. Because contractile responses to caffeine were not enhanced in arteries from hypertensive rats, we conclude that the cellular store for calcium is not enlarged compared with that in normotensive arteries. In contrast, the mobilization of calcium from cellular stores by norepinephrine is augmented in mineralocorticoid hypertension. This augmented response may be linked to altered phospholipase C activity and thus to an augmented action of inositol trisphosphate that releases calcium from intracellular sites. 
Stage I and II subdiaphragmatic Hodgkin's disease. From January 1971 to December 1986, 521 patients with Hodgkin's disease were evaluated and treated at the Yale University School of Medicine or one of its close affiliates. A total of 258 patients had pathologic stage (PS) I or II disease, with 239 patients having Hodgkin's disease above the diaphragm (ADHD) and 19 patients having Hodgkin's disease below the diaphragm (BDHD). A comparison of patients with BDHD versus patients with ADHD showed that patients with BDHD were older (mean age, 42 versus 28 years of age, P = 0.005), were initially seen less often with nodular sclerosis subtype (32% versus 77%, P = 0.00001), and had a higher male: female ratio (2.8 versus 1.2, P = 0.12). Ten patients with BDHD (53%) had positive findings at staging laparotomy (0 of 4 clinical stage [CS] IA patients and 10 of 15 (67%) CS II patients). Radiation therapy alone was the initial treatment of choice for 74% of patients with BDHD versus 94% of the patients with ADHD. There was no statistical difference in the overall survival or relapse-free survival rates for patients with BDHD versus ADHD (10-year survival rates, BDHD = 73% and ADHD = 81%). However, patients with BDHD who initially had intra-abdominal disease had a statistically significant increase in death rate (60%) due to Hodgkin's disease compared with patients with BDHD who initially had only peripheral nodal disease (0%). Treatment recommendations for patients with BDHD should be tailored to the specific clinical presentation of each patient. For most PS IA/IIA patients initially seen with peripheral nodal disease, radiation therapy alone is a successful treatment program. However, combined modality therapy should be the treatment of choice for patients with BDHD initially seen with intra-abdominal disease. 
Echographic diagnosis of anterior hyaloidal fibrovascular proliferation. High-resolution contact B-scan echographic imaging of the ciliary body and peripheral retina was performed on five eyes with anterior hyaloidal fibrovascular proliferation and media opacity by means of a wide (58 degrees) scanning arc. This technique determined the circumferential and anteroposterior extent of peripheral traction retinal detachment associated with anterior hyaloidal fibrovascular proliferation, which correlated highly with findings at subsequent vitrectomy. Final visual acuity of 20/400 or better was achieved in the two eyes (50%) with more limited peripheral traction detachment. In the presence of media opacity, anterior echographic imaging may allow early detection of traction retinal detachment associated with anterior hyaloidal fibrovascular proliferation and may be useful in characterizing the severity of this condition. 
Pulse oximetry compared with Doppler ultrasound for assessment of collateral blood flow to the hand. Ischaemic injury to the hand after arterial cannulation is a rare but well documented complication and routine testing of the adequacy of collateral circulation is widely advocated. The widespread availability of the pulse oximeter in the operating theatre. its applicability in circumstances where the patient is unable to cooperate, and its dependence on pulsatile blood flow suggest that this device could potentially be usefully applied to the assessment of collateral blood flow. The reliability of the pulse oximeter to detect the presence or absence of collateral circulation was prospectively compared to Doppler ultrasound in 109 hands from 64 adult patients. Nine hands demonstrated inadequate ulnar collateral flow, one hand demonstrated inadequate radial collateral flow and a persistent median artery was found in one hand. In all patients the results of pulse oximeter testing (probe placed on the thumb correlated precisely with the results obtained with the Doppler device (probe located over the lateral aspect of the superficial palmar arch). These results demonstrate pulse oximetry to be a reliable method of assessing collateral blood flow to the hand before arterial cannulation. 
Ionized calcium in blood: studies on patients with pulmonary disease. A new automatic ionized calcium analyser ICA 2 (Radiometer, Copenhagen, Denmark) was used for studies of ionized calcium (cCa2+) in the arterial blood of patients with a compensated respiratory acidosis due to chronic lung disease. The data for 16 patients showed an unexpectedly high level of variation in cCa2+ (range, 1.01-1.25 mmol l-1) despite the fact that there was only a small degree of variability in pH (range, 7.38-7.51). cCa2+ was not correlated with pH as has been observed in acute respiratory disturbances. A highly significant negative correlation was found between cCa2+ and base excess (BE) (r = -0.81, P less than 0.0001), and between cCa2+ and carbon dioxide tension (PCO2) (r = 0.71, P less than 0.002). These correlations differed from those reported previously in acute respiratory disturbances. CCa2+ showed a significant positive correlation with oxygen tension (PO2) (r = 0.71, P less than 0.002). It is concluded that cCa2+ in arterial blood from patients with chronic lung disease is correlated with acid-base and gas quantities in an entirely different manner to that observed in acute acid-base disturbances in normal adults. 
Macrophages, microglial cells, and HLA-DR antigens in fetal and infant brain. Immunohistochemical reactions for macrophages, microglia, and HLA-DR antigens were tested on frozen sections of necropsy brain tissue from 20 fetuses and infants ranging in age from 18 weeks' gestation to 8 months post term. No primary central nervous system disease was present but there were four cases of sudden infant death syndrome (SIDS). Macrophages were detected in all the samples studied and were located in the germinal matrix zone, in perivascular spaces throughout the brain, and in the leptomeninges and subependymal layer. Well differentiated microglia were present in all cases examined after 35 weeks' gestation and less well ramified forms were seen at earlier stages of gestation. HLA-DR antigens were detected on a small number of macrophages, chiefly in a perivascular location, in all but three cases. The fewest reactive cells and the weakest reactions occurred in the youngest fetuses. One case of SIDS showed increased foci of microglia in perivascular white matter: this case and one other case of SIDS were the only cases with well ramified microglia that expressed HLA-DR antigens. These findings may be relevant to an understanding of local immune responses in fetal brain infections, including human immunodeficiency virus infection. 
Immediate mandibular replacement using reconstruction plates. Mandibular reconstruction at the time of tumor resection remains a surgical dilemma. Primary reconstruction allows for immediate reconstitution of mandibular form and function. Various methods have been attempted, but none enjoys uniform success. With advances in the field of microvascular surgery have come numerous options in replacing these defects. These procedures, however, require special surgical teams and are associated with an increase in operative time as well as morbidity at the donor site. An alternative method involves the use of mandibular reconstruction plates to bridge the defect between segments. This review focuses on 19 patients whose jaws were reconstructed in this fashion. Although not free of complications, mandibular plate reconstruction offers the advantages of (1) lack of donor site morbidity, (2) expediency, (3) excellent mandibular contour, and (4) the ability to reconstruct the condyle when necessary. The technique, results, and complications associated with this procedure are discussed. 
Modified approach for ethmoid and anterior skull base surgery. The use of combined craniofacial resection is well established for tumors of the ethmoid bone and the anterior aspect of the base of the skull. Mobilization of the medial fronto-orbital ridge improves the transbasal approach and can be performed with a monobloc bone flap. We describe an en bloc bifrontal craniotomy including the supraorbital ridges and the nasal bones. This provides a wider angle of approach to the anterior aspect of the base of the skull than any other method and avoids retraction of the frontal lobes. This type of bone flap procedure can be performed after a wide periosteal dissection in the coronal area of the scalp alone, without facial skin incision. 
Effects of a twenty-four-hour milrinone infusion in patients with severe heart failure and cardiogenic shock as a function of the hemodynamic initial condition. The systemic and pulmonary arterial hemodynamics of 40 patients with severe congestive heart failure were determined during a 24-hour infusion of milrinone (0.5 micrograms/kg/min) after a loading dose of 50 micrograms/kg. A subgroup (n = 18) with severe cardiac pump dysfunction and three patients in cardiogenic shock were analyzed separately; their hemodynamic response was compared with that of the total group (n = 40). After 15 minutes of intravenous therapy with milrinone, the total group (n = 40) showed an increase of 65% in cardiac index; in the subgroup (n = 18) cardiac index increased by 94% after 15 minutes and by 106% after 30 minutes. Likewise, pulmonary capillary wedge pressure decreased after 30 minutes in both the total group (n = 40) and the subgroup (n = 18). The heart rate showed an overall tendency to decrease. The systolic blood pressure tended upward and remained statistically unchanged in the total group, whereas in the subgroup in which pressure was initially low, there was an increase in the systolic pressure after 1 hour and a further increase after 24 hours. Mean arterial pressure also rose in this subgroup. The early improvement in all measured hemodynamic parameters was sustained throughout the 24-hour infusion period. Development of tolerance was not observed, nor were any clinically symptomatic side effects or symptomatic arrhythmias. Thus intravenous milrinone is a safe medication for the rapid and prolonged improvement in hemodynamics, specifically in patients with severely restricted cardiac pumping function. 
Antihypertensive therapy: taking lipids into consideration. Several antihypertensive agents have been found to influence serum lipid profiles. Thiazide diuretics increase total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels and slightly reduce high-density lipoprotein (HDL) cholesterol. Most beta-blockers substantially increase triglycerides and lower HDL cholesterol. Angiotensin-converting enzyme inhibitors, calcium channel antagonists, alpha- and beta-blockers, and beta-blockers with intrinsic sympathomimetic activity are lipid neutral. alpha 1-Antagonists (e.g., terazosin and prazosin) lower total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels and improve total cholesterol/HDL ratios. Observational epidemiologic studies indicate that the lipid effects of antihypertensive agents are large enough to account for substantial differences in the predicted incidence of coronary heart disease. Combination therapy with the alpha 1-antagonist terazosin plus either thiazides or beta-blockers also ameliorates the adverse lipid effects of these agents used alone. A reasonable approach to managing the lipid problems often associated with hypertension is to advise a cholesterol-lowering, low-sodium diet and weight reduction and to select drugs that alone or in combination do not adversely affect lipid profiles. 
Phasic sleep components in infants with cyanosis during feeding. Although brainstem immaturity has been postulated as one of the pathogenesis underlying cyanosis during feeding (CDF), there has been no widely accepted physiologic parameter that reflects brainstem function. We recently proposed that the dissociation index (DI), one of the phasic sleep parameters, is a reliable and quantitative sleep parameter for assessing brainstem maturation during early infancy. In the present study, we evaluated brainstem impairment in infants with CDF using phasic sleep components. Polysomnographies were obtained for 12 infants with CDF who were equally divided into 2 groups: one had or subsequently experienced apparent life-threatening events or sudden infant death syndrome (ALTE-SIDS group) and the other did not (CDF group). Rapid eye movement density and the number of gross movements (body movements, including the trunk, lasting greater than or equal to 2 sec) in the patients were identical to those in the controls. In the CDF group, the decrease of the average DI value from the controls was significantly less than the decrease in the ALTE-SIDS group. CDF may be a mild expression of brainstem immaturity. DI appears to be useful when evaluating infants with cyanosis during feeding. 
The intranasal ethmoidectomy: an experience with 1,077 procedures. A series of 1,077 intranasal ethmoidectomies (825 with sphenoid sinusotomies) was performed in 600 patients over a 15-year period at The Mount Sinai Medical Center. The technique is a modification of the classical operation originally proposed by Yankauer. The rate of significant complications was 1.1%. A subset of 90 patients underwent 166 procedures and were followed an average of 3.5 years. The patients were analyzed according to whether the disease was focal or diffuse, infectious or polypoid, and whether asthma was present. The surgical success rate was 88% in nonasthmatics, but dropped to 50% in asthmatic patients despite total sphenoethmoidectomy. This underscores the importance of this condition as a biological modifier of surgical prognosis. Accordingly, a system of classification of sinus diseases is proposed based upon disease extent and type and whether asthma is present. 
Chronic diuretic therapy with moderate doses of triamterene is not associated with folate deficiency. The diuretic drug triamterene has previously been shown to be a competitive inhibitor of folate absorption in the rat intestine (J Lab Clin Med 1986;108:272-6). We therefore investigated whether human subjects who are taking the drug on a long-term basis are at increased risk of folate deficiency. In each of two free-living populations, a study was performed to compare the folate status of triamterene users with those not taking the drug. The first population consisted of 272 elderly individuals not living in institutions who were participants in a nutrition status survey and who were taking a variety of antihypertensive medications; 32 of these individuals were daily users of triamterene. The hemoglobin concentration, red blood cell (RBC) count, and mean corpuscular volume (MCV) values were not significantly different between the triamterene users and nonusers. The female triamterene users had a slightly higher serum folate level than the female nonusers (p less than 0.04); a similar pattern was observed among the men, although the difference was not statistically significant. The second population consisted of 27 individuals attending a hypertension clinic; 18 subjects were taking 50 to 150 mg of triamterene per day and nine were taking antihypertensive drugs other than triamterene. The hemoglobin concentration, RBC count, MCV, serum folate values, and RBC folate values were found to not differ significantly between the triamterene users and the hypertensive controls (p greater than 0.05). These data suggest that chronic triamterene administration in individuals not living in institutions, at the doses examined in this study, is not associated with indications of folate deficiency. 
Pulmonary haemosiderosis associated with left atrial myxoma. A patient with features suggesting pulmonary haemosiderosis was found to have a myxoma. The pulmonary lesion cleared after excision of the tumour. 
Fluorescence localization of early colonic cancer in the rat by hematoporphyrin derivative. Laser excitation of hematoporphyrin derivatives (HPD) localizing in tumors of the tracheobronchial tree and bladder is useful in the identification and treatment of those tumors. A comparable utility for HPD in the endoscopic localization of colonic tumors may be possible. In this study the ability of HPD to identify 1,2 dimethylhydrazine (DMH) induced colon cancer in rats is evaluated. A total of 111 rats were studied with HPD. Sixty-nine rats received weekly injections of DMH (20 mg/kg) and 42 received injections of the vehicle alone. Twenty-four hours after the intravenous injection of 5 mg/kg of HPD, 18 DMH-induced tumors were identified by visual fluorescence using excitation by either a blue light (390-436 nm) or an argon laser (488 and 514 nm). This represented 100% of the visually or microscopically detected tumors. Seventy-five fluorescent areas were noted that did not contain evidence of cancer. The majority (63) of false positive areas contained lymphoid follicles. All but 2 false positive areas (73/75, 97%, p less than .001) were seen in DMH-treated animals, suggesting that they were an artifact of DMH treatment. HPD fluorescence did not identify microscopic dysplasia. We conclude that HPD fluorescence is an effective method of identifying early colonic cancer and may have a potential clinical role in patients at high risk for colorectal cancer. 
Acute lower limb ischemia: failure of anticoagulant treatment to improve one-month results of arterial thromboembolectomy. A prospective randomized multi-center study. The value of short-term anticoagulant treatment in improving the early outcome in patients operated on for acute lower-limb ischemia has been debated and so far unproven. In this prospective randomized multi-center study, 188 such patients were randomized on admission, either to preoperative and postoperative anticoagulant medication (AC group, n = 94) or no anticoagulant treatment during the first month after surgery (O group, n = 94). Background factors were evenly distributed in the two groups, and 89% of the cases were considered as embolic. Analysis on an intention-to-treat basis showed no differences in outcome after 30 days. Good results, survivors who had amputation, and patients who died in the two groups are given respectively: AC group, 61%, 9%, 30%; O group, 65%, 11%, 24%. The results were similar in the two treatment groups also if only patients with a cardiac source of embolism were analyzed. Local bleeding complications were more common in the AC group (17% vs 2%, p less than 0.01). It is concluded that preoperative and early postoperative anticoagulant medication should not be routinely administered since such treatment is unlikely to improve the short-term results of lower-limb arterial thromboembolectomy while bleeding complications increase. The possible value of late (beyond 1 month) long-term anticoagulant treatment remains to be studied. 
Intraperitoneal contrast material improves the CT detection of peritoneal metastases. The preoperative detection of peritoneal metastases from gynecologic malignancies is difficult; in particular, CT often fails to detect peritoneal implants. This study was designed to determine if the administration of intraperitoneal iodinated contrast media would increase the CT detection of such peritoneal metastases. Prospectively, both standard and intraperitoneal contrast-enhanced CT studies of the abdomen and pelvis were performed in 16 patients with suspected gynecologic tumors. All patients then underwent operative staging, with the location and number of metastases documented. The intraperitoneal enhanced CT studies were more sensitive in the detection of peritoneal metastases than standard CT examinations. Whereas routine CT detected peritoneal metastases in seven (64%) of 11 patients with surgically proved implants, the intraperitoneal enhanced CT studies detected peritoneal metastases in all 11 patients. Depending on the specific intraperitoneal compartments involved, the sensitivity of intraperitoneal enhanced CT in the detection of peritoneal metastases was two- to fourfold greater than that of standard CT examinations. Our results suggest that intraperitoneal enhanced CT is superior to standard CT in the detection of peritoneal metastases. 
Higher recurrence rate after coronary angioplasty in unstable angina pectoris. PURPOSE: Recurrent stenosis after percutaneous transluminal coronary angioplasty (PTCA) is a significant problem, requiring repeat dilation in about one-third of all treated patients. Various clinical and procedure-related predictors have been proposed. Between 1983 and 1987, 257 patients underwent 322 procedures, where 380 stenoses were attempted. Indications were: stable angina pectoris 73%, unstable angina pectoris 22%, other indication 5%. The primary success rate was defined as a less than 50% remaining postprocedure stenosis. FINDINGS: Repeat angiograms were done for 88% of the initially successful cases, either six months after PTCA or if there was a clinical recurrence. Restenosis was defined as a recurrence of a more than 50% diameter stenosis. The restenosis rate was 33% and was significantly higher (p less than 0.05) for unstable (46%) than for stable angina pectoris (29%). There was a nonsignificant tendency to a higher restenosis rate in the left anterior descending artery than in the other coronary vessels. IMPLICATIONS: The increased restenosis rate seen after PTCA for unstable angina pectoris could be caused by a higher activity in systems affecting the proliferative processes in the smooth muscle cells of the arterial wall, which is thought to form the pathophysiologic basis for restenosis after PTCA. 
Nutritional assessment of patients with extended left ventricular assist device support. The nutritional status of nine patients with end-stage heart disease who were supported by a left ventricular assist device (LVAD) for more than 30 days while awaiting cardiac transplantation was evaluated. Nutritional status was indicated by the following scale: 0-2, adequate nourishment; 3-5, moderate malnourishment; greater than 5, severe malnourishment. This scale was based on serial assessments of albumin, transferrin, total lymphocyte count, percentage of ideal body weight, midarm circumference, triceps skinfold, and arm muscle circumference. Each variable was compared with established standards before implantation and before transplantation times and assessed 1 point if less than the normal value and 0 points if within the normal range. At the time of LVAD implantation, 5 patients had a score of 0-2, 3 patients had a score of 3-5, and 1 patient had a score greater than 5. At the time of cardiac transplantation, 7 patients had a score of 0-2, 2 patients had a score of 3-5, and no patients had a score greater than 5. The patients who were able to meet at least 50% of their daily caloric and protein requirements by oral intake alone were noted. At LVAD implantation, only 2 patients (22%) met this requirement; however, 6 patients (67%) met this requirement at the time of cardiac transplantation. All 9 patients underwent cardiac transplantation, and 8 survived. Thus, it appears that extended LVAD support and maintenance of hemodynamic stability allow patients to regain the desire and ability to achieve adequate nutritional status, which may considerably reduce their perioperative transplant risks. 
Congenital arteriovenous communications and the development of two types of leaking retinal macroaneurysms. We treated a patient with a rare combination of congenital arteriovenous communications and the development of leaking macroaneurysms of different types. Initially, leaking macroaneurysms developed in the shunt area of the arteriovenous communication; later, a preexistent fusiform macroaneurysm in the afferent arteriole of the congenital communication started leaking. Because exudates and fluid from the leaking macroaneurysms reached the fovea, laser treatment was performed to obliterate the macroaneurysms. We assume that after obliteration of the macroaneurysms with laser in the shunt area, the increase of hydrostatic pressure on the thin wall of the fusiform aneurysm of the afferent artery led to its leaking. We saw no signs of vascular occlusion after laser treatment. 
Post-traumatic syringomyelia following uncomplicated spinal fracture. Two cases of post-traumatic syringomyelia presenting 10 and 41 years after spinal injuries that had caused lumbar vertebral fractures but no lasting neurological deficits are reported. In both patients the caudal end of the syrinx cavities, as shown by MRI, corresponded to the level of the previous vertebral fractures. Patients presenting with post-traumatic syringomyelia after uncomplicated spinal fracture are very rare, and the significance of the past history of spinal trauma may be overlooked. 
Stimulation of healing of chronic wounds by epidermal growth factor. We evaluated the effect of topical epidermal growth factor treatment on healing of chronic wounds in a prospective, open-label, crossover trial. Five males and four females who ranged in age from 40 to 72 years (average 57 +/- 9 years) were enrolled. Four patients had adult-onset diabetes mellitus, two had rheumatoid arthritis, two had old burn scars, and one had a failed abdominal incision. The average duration of the ulcers prior to treatment with epidermal growth factor was 12 +/- 5 months (range 1 to 48 months). Following failure of the wounds to heal with conventional therapies, including debridement, skin graphs, and vascular reconstruction, wounds were treated twice daily with Silvadene alone for periods ranging from 3 weeks to 6 months. No evidence of healing was observed in any of the patients' wounds during Silvadene treatment, and patients were crossed over to twice a day treatment with Silvadene containing 10 micrograms epidermal growth factor per gram. Wounds of eight patients healed completely with epidermal growth factor-Silvadene treatment in an average of 34 +/- 26 days (mean +/- SD, range 12 to 92 days) and did not reoccur for periods ranging from 1 to 4 years. One patient failed therapy. These results suggest that topical treatment of chronic wounds with epidermal growth factor may stimulate healing. 
Cognitive outcome following tricyclic and electroconvulsive treatment of major depression in the elderly. OBJECTIVE: This study sought to ascertain the affective and cognitive outcome after tricyclic and electroconvulsive treatment of elderly medical-psychiatric patients meeting diagnostic criteria for major depression, some of whom had normal cognitive functioning and some of whom were cognitively impaired before treatment. METHOD: Patients who met criteria for major depression on the basis of a structured diagnostic interview and who scored 17 or more on the Hamilton Rating Scale for Depression were evaluated with the Mattis Dementia Rating Scale. The patients were then treated in a nonrandom manner with either tricyclic antidepressants or ECT (followed by tricyclic maintenance therapy). The majority of the patients treated with ECT had not responded previously to tricyclics. Follow-up psychometric testing was repeated in 6 months. RESULTS: Among the patients with normal pretreatment cognitive functioning, cognition was generally stable. Among the patients with pretreatment cognitive impairment, a substantial number--including those receiving ECT--demonstrated improvement in cognition. While the majority of patients improved with respect to both their affective and cognitive states, certain treatment-refractory subgroups were nevertheless identified. CONCLUSIONS: The data suggest that cognitive dysfunction associated with depression may improve after treatment in a substantial number of elderly patients, including those receiving ECT. Relapse rates, however, may be relatively high, and residual symptoms may persist, which emphasizes the need for optimal initial and long-term antidepressant strategies for this population. 
Effect of propofol on the incidence of postoperative vomiting after strabismus surgery in pediatric outpatients. Vomiting is a common problem after strabismus surgery in pediatric outpatients. We compared the effects of propofol with and without N2O and droperidol to the effects of a conventional regimen consisting of halothane-N2O-droperidol on the recovery characteristics and the incidence of postoperative emesis after strabismus surgery in 120 ASA physical status 1 or 2 children. After induction of anesthesia with halothane-N2O, patients were randomly assigned to one of four groups. Group A (control) received halothane, 66% N2O, and droperidol 75 micrograms.kg-1; group B, propofol 2 mg.kg-1 bolus followed by infusion of 160 microgram.kg-1.min-1; group C, propofol (as in group B) and 66% N2O; and group D, propofol (as in group B), 66% N2O (as in group C), and droperidol 75 micrograms.kg-1. Patients in group B had more episodes of intraoperative oculocardiac reflex responses than patients in group A, but had shorter times to extubation, oral intake, ambulation, and discharge, as well as a lower incidence of postoperative emesis (P less than 0.05). The addition of N2O to the propofol anesthetic regimen (group C) was associated with an increased incidence of emesis (P less than 0.05), whereas the addition of droperidol to the propofol-N2O regimen (group D) did not affect the incidence of emesis compared to the other three groups. We conclude that maintenance of anesthesia with a total intravenous regimen using propofol results in a more rapid recovery and less postoperative emesis than with a halothane-N2O-droperidol regimen. 
Donor scleral graft patching for persistent filtration bleb leak. We report effective and efficient sealing of a persistent leak in a cystic filtration bleb by applying a full-thickness donor scleral patch. 
Zollinger-Ellison syndrome. A new look at regression of gastrinomas. Of 44 patients with the Zollinger-Ellison syndrome treated at our institution, nine appeared to have undergone "regression" of their gastrinomas. Six of the nine patients had sporadic gastrinomas and became permanently eugastrinemic following excision of nodal metastases and total gastrectomy (n = 4), antrectomy (n = 1), or pancreatoduodenectomy (n = 1) (mean survival, 13 years). The other three patients had Zollinger-Ellison syndrome as part of the multiple endocrine adenopathy type 1 syndrome and became temporarily eugastrinemic after total gastrectomy (mean survival, 11 years). Occult submucosal duodenal-wall microgastrinomas (mean size, 3.0 mm) were found to have been serendipitously excised in four patients. Long-term follow-up of these nine patients, as well as of six other patients described in the literature, demonstrates that excision of occult duodenal-wall gastrinomas provides a plausible explanation for the phenomenon of apparent regression of primary gastrinomas and the eugastrinemia that may follow total gastrectomy. 
Hormonal and metabolic response to operative stress in the neonate. It is evident from this review that newborns, even those born prematurely, are capable of mounting an endocrine and metabolic response to operative stress. Unfortunately, many of the areas for which a relatively well-characterized response exists in adults are poorly documented in neonates. As is the case in adults, the response seems to be primarily catabolic in nature because the combined hormonal changes include an increased release of catabolic hormones such as catecholamines, glucagon, and corticosteroids coupled with a suppression of and peripheral resistance to the effects of the primary anabolic hormone, insulin. 
Continuation of normal neurobehavioural development in fetuses with absent umbilical arterial end diastolic velocities. Detailed serial observations of behaviour were made in four singleton fetuses who were very small for dates and who had persistently absent umbilical artery end diastolic velocities for 2 to 9 weeks duration. All were born preterm for deteriorating maternal disease, and in two there were additional fetal indications for delivery. Behavioural comparison with 45 low risk singleton fetuses, at comparable gestations, revealed no significant differences in the development of behavioural cycles, the proportion of time spent in quiet cycles, or the amount of fetal breathing. None of the fetuses developed an abnormal heart rate pattern. We conclude that prenatal neurobehavioural development may continue apparently unimpaired in the presence of absent umbilical artery end-diastolic velocity of several weeks duration. Long term data of infant outcome are necessary before the clinical significance of this can be assessed. 
Nontraumatic abdominal aortic thrombosis presenting with anterior spinal artery syndrome and pulmonary edema. A 51-year-old woman with a history of breast cancer developed pulmonary edema and lower extremity paraplegia with preservation of proprioception as the initial manifestation of abdominal aortic thrombosis. Back pain was present in the lumbar region radiating to buttocks and legs in a bilateral radicular pattern. Femoral pulses were initially palpable. Aortic angiography revealed complete abdominal aortic occlusion at L3 as well as total occlusion of the bilateral superficial femoral arteries and bilateral common iliac arteries. Transient occlusion of the anterior spinal artery due to aortic thrombosis may cause paraplegia and may also progress to renal failure, bowel infarction, and limb loss if left untreated. Abdominal aortic thrombosis needs to be considered in a patient who presents with an anterior spinal artery syndrome, which, if present, must be treated as rapidly as possible to preserve motor and sensory function. 
Neuro-ophthalmologic signs of AIDS: 50 patients. In 50 hospitalized patients with acquired immunodeficiency syndrome, signs of central eye movement limitation (28 cases) were most common. Peripheral eye movement limitations (18), abnormalities of vision (18), and abnormal spontaneous eye movements (15) occurred with about equal frequency. Meningitis (17), usually due to lymphoma (8) or Cryptococcus (8), was the usual cause of peripheral nervous system involvement, while toxoplasmosis (18) was more common than lymphoma (4) or presumed viral causes (8) in producing CNS dysfunction. The midbrain and pretectal (8) were affected about as often as the pontine tegmentum (9), but rostral brainstem lesions appeared to be the result of toxoplasmosis (4) or lymphoma (3), whereas a viral etiology was the presumed cause of most caudal stem involvement. 
Medullary catecholaminergic neurons in the normal human brain and in Parkinson's disease. Parkinson's disease is thought to cause degeneration of melanin-pigmented catecholaminergic neurons throughout the brainstem, but little quantitative information is available on the fate of catecholaminergic neurons associated with the dorsal vagal complex or medullary reticular formation. We therefore examined these neurons in the normal human medulla and in the brains of patients with Parkinson's disease, using both a melanin stain and immunohistochemical methods with an antiserum against tyrosine hydroxylase. The greatest numbers of catecholaminergic neurons in the ventrolateral reticular formation (A1/C1 group) were located in the far rostral medulla, whereas the largest populations of catecholaminergic cells in the dorsal vagal complex (A2/C2 group) were found at the level of the area postrema. No loss of cells was observed in the A1/C1 group in the parkinsonian brains. In contrast, the A2/C2 group showed moderate loss of neurons, most marked at the level of the area postrema. This difference was entirely due to the loss of neurons in the medial component of the A2 group, a population that normally is only lightly pigmented, while the heavily pigmented neurons in the ventral and intermediate components of the A2 complex were unaffected. Parkinson's disease causes degeneration only of selected populations of medullary catecholaminergic neurons, without apparent relationship to the extent of melanin pigmentation. 
Efficacy of ivermectin for control of microfilaremia recurring after treatment with diethylcarbamazine. I. Clinical and parasitologic observations. We compared the efficacy of a single dose of ivermectin with that of a standard course of diethylcarbamazine (DEC) for the control of microfilaremia in 60 patients with bancroftian filariasis who had developed recurrent microfilaremia after each of three or more prior treatments with DEC. The study was done as a randomized, double-blind trial. Complete, but in some cases, transient clearance of microfilaremia was observed in both treatment groups. At one year, recurrent microfilaremia was present in seven patients treated with ivermectin and in five treated with DEC. Pretreatment levels of microfilaremia were significantly higher in patients who relapsed within one year after treatment than in those who remained amicrofilaremic. Side effects with both treatments were common, but mild. Febrile reactions were more frequent in the ivermectin group; localized reactions consistent with a flare-up of acute filarial disease occurred mostly in the DEC group. We conclude that ivermectin is an effective and practical alternative to DEC for treatment of recurrent microfilaremia due to bancroftian filariasis. 
Cholecystectomy is safer without drainage: the results of a prospective, randomized clinical trial. Drainage after cholecystectomy remains routine despite the lack of scientific supportive data. Numerous clinical studies in the past have attempted to address this controversy but have failed to resolve the issue for different reasons. These include retrospective design, inclusion of only selected cases, and randomization before surgery. In this study 479 patients undergoing cholecystectomy were randomly allocated to a drainage group (a high-pressure suction drain in Morison's pouch for 48 hours) or a nondrainage group. Randomization was performed at the time of peritoneal closure. All patients undergoing cholecystectomy, both elective and urgent, were included and the operations were performed by all grades of surgeons. There were two deaths from cardiopulmonary causes, both in the drainage group. No patient required reoperation in either group. The incidence of both wound infections (15 vs 5; p less than 0.05) and chest infections (56 vs 19, p less than 0.02) was significantly higher in the drainage group. Three hundred fifty-six patients underwent abdominal ultrasonography 72 hours after surgery. The number of subhepatic fluid collections thus detected was significantly higher in the patients who received a drain (17 vs 6, p less than 0.05). None of these collections was clinically significant. The postoperative hospital stay was longer in the patients with drains (10.3 vs 9.1 days), but this difference failed to reach statistical significance. We conclude from this study that the use of a drain after cholecystectomy serves no useful purpose and is potentially harmful. This practice should be abandoned. 
Individualization and enamel histology: a case report in forensic anthropology. The cranium of a native Indian child about six years old was found in 1979 near Taseko River, British Columbia, Canada. While the remains matched the report of a child missing for eight years in terms of race, age at death, locale, and elapsed time since death, the cranium and dentition were basically unidentifiable because of the claimed lack of medical or dental history. There was no dental work, and the parents were unknown or dead. We report the presence, in the dental enamel of the primary and secondary dentition, of stress markers, termed striae of Retzius, whose locations correspond well with anecdotal reports and recently discovered medical records which describe the timing of specific episodes of stress. The enhanced probability of personal identification from dental histological stress markers is evaluated. 
Idiopathic orthostatic hypotension, midodrine, and anaesthesia. A patient with idiopathic orthostatic hypotension receiving chronic oral midodrine therapy required anaesthesia for coronary artery bypass grafting. A perioperative infusion of phenylephrine was substituted for midodrine, an alpha-2 agonist, enabling hypotension resulting from low systemic vascular resistance to be controlled easily. Anticipated adrenergic receptor denervation hypersensitivity was noted. The only significant perioperative problem was one episode of syncope from orthostatic hypotension during the reambulation period. 
Hemidystonia due to a contralateral parieto-occipital metastasis: disappearance after removal of the mass lesion. A patient presented with left-sided hemidystonia. CT revealed a contralateral parieto-occipital mass lesion compressing the basal ganglia, which were spared by the mass. After microsurgical resection of the tumor, which was verified histologically as a metastasis of a large-cell anaplastic carcinoma, the movement disorder dissolved completely. 
Postsepsis bradycardia in children with leukemia. OBJECTIVE: We observed sinus bradycardia in a small number of children with hematologic malignancies who were recovering from sepsis. Our objective was to define this symptom complex and attempt to delineate its etiology. DESIGN: Retrospective chart review. SETTING: A pediatric ICU in a children's oncology hospital. PATIENTS: Children admitted to the ICU over a 24-month period who developed persistent bradycardia (heart rate less than 5% for age for greater than 1 hr) after an episode of sepsis. MEASUREMENTS AND MAIN RESULTS: Seven children developed postsepsis bradycardia. Six patients had a primary diagnosis of acute myelogenous leukemia and one patient had acute lymphocytic leukemia. All patients had positive blood cultures (Streptococcus mitis, n = 4; Escherichia coli, n = 2; and Klebsiella pneumoniae, n = 1). All seven children were clinically recovering from sepsis when the bradycardia developed. Neither hypotension nor other symptom was associated with the bradycardia. No therapy was given for the bradycardia. Echocardiograms and ECGs were normal in all patients, except for the presence of bradycardia. Bradycardia persisted for 24 to 72 hrs. After that time, heart rates slowly increased to the normal range for age. CONCLUSIONS: We speculate that this syndrome may result from alterations in beta-adrenergic receptor function or an unidentified humoral factor produced by the invading organism or as part of the host's response to sepsis. Prior drug therapy or the underlying illness may predispose to this condition, since all the patients had acute leukemia. As the bradycardia was clinically insignificant, invasive therapeutic or diagnostic strategies were not indicated. 
Shock wave-induced pancreatic trauma. A case is described of the appearance of a pancreatic or peripancreatic lesion after left renal calculus fragmentation by extracorporeal shock wave lithotripsy (ESWL). Its anatomical location and subsequent disappearance suggest it was related to trauma caused by the shock waves. The brief literature on pancreatic injury after ESWL is reviewed, and the role of the patient's underlying liver disease in the genesis of this complication is discussed. 
The protective efficacy of recombinant hepatitis B vaccine in newborn infants of hepatitis B e antigen-positive-hepatitis B surface antigen carrier mothers. Recombinant hepatitis B vaccine has been shown to be as safe and effective as plasma-derived vaccines. However, its efficacy in the prevention of perinatal infection has not been fully evaluated in an endemic area. We recruited 110 high risk infants born to hepatitis B e antigen-positive-hepatitis B surface antigen (HBsAg) carrier mothers in a study of recombinant vaccine efficacy. They were randomized into 2 groups, A (54 infants) and B (56 infants), to receive 4 doses of vaccine, containing 20 or 10 micrograms of surface antigen, respectively, at 0, 1, 2 and 12 months of age. An additional 60 high risk infants were recruited later (Group C) and received three 20-micrograms doses of vaccine at 0, 1 and 6 months of age. All infants also received a dose (145 IU) of hepatitis B immunoglobulin soon after birth. Sera were collected at 0, 1, 2, 3, 6, 12 and 14 months of age to assay HBsAg and anti-HBs. At 12 months of age the HBsAg carrier rates were 7.4 and 1.8%, in Groups A and B, respectively. In Group C the HBsAg-positive rate was 3.3%. HBsAg was invariably first observed between 0 and 2 months of age. Virtually all noncarrier infants developed substantial titers of anti-HBs at 12 months of age. No serious adverse effect was observed after vaccination. 
Multiple basal cell carcinomas and HLA frequencies in southern Australia. An association between HLA-DR1 and the development of multiple basal cell carcinomas was detected in southern Australia. A reduction in HLA-DR4 was found in patients with basal cell carcinoma compared with a local control group. The relative risk for HLA-DR1 was 2.1, which was lower than that for persons in farther countries from the equator. 
Successful operation on a coronary arteriovenous fistula in a 74 year old woman. Coronary arteriovenous fistulas are rare and are usually diagnosed in children or young adults. Most are believed to be congenital. A right coronary arteriovenous fistula was first diagnosed in a patient of 74. Despite her age the fistula was successfully operated on and her symptoms were relieved. 
Antitumor activities of interferon alpha, beta, and gamma and their combinations on human melanoma cells in vitro: changes of proliferation, melanin synthesis, and immunophenotype. The antitumor activities of human interferon (IFN) alpha, beta, and gamma alone or in combination were studied on four human melanoma cell lines (StML-11, StML-12, StML-14, and SKMel-28) in various concentrations (1-50,000 IU/ml IFN alpha, 0.1-1000 IU/ml IFN beta, 1-10,000 IU/ml IFN gamma) in vitro. In all experiments IFN beta exhibited the most potent antiproliferative effect of all IFN tested. After 3 d of incubation a 50% growth inhibition was achieved with 20-40 IU/ml for natural IFN beta and with 600-1200 U/ml for recombinant IFN gamma. Substantially higher doses (7,000 to more than 50,000 IU/ml) of recombinant IFN alpha 2a were required to achieve a 50% growth inhibition. A strong synergistic antiproliferative activity resulted from the combination of IFN alpha with IFN gamma and IFN beta with IFN gamma. None of the IFN tested induced terminal differentiation of melanoma cells in vitro. The formation of dendrites was inhibited, and the portion of differentiated cells in vitro was reduced after treatment with IFN in comparison to the untreated controls (untreated controls: 100%; portion of differentiated cells after treatment with IFN alpha: 58%-74%, IFN beta: 48%-96%, IFN gamma: 10%-33%). The melanin synthesis was slightly elevated after treatment with IFN alpha (untreated controls: 100%; after treatment with IFN alpha: 103%-157%, ns.) and decreased significantly after treatment with IFN beta (49%-71%, p less than 0.05) as well as with IFN gamma (80%-88%, ns.). Cell surface markers were modulated varyingly by the IFN: HLA-I antigens were enhanced by all IFN, with IFN beta emerging as the most potent inducer. Only IFN gamma, however, induced a de novo expression of HLA-DR and -DQ antigens and increased the expression of the ICAM-1 molecule and of the melanoma progression marker A.1.43. Possibly, these findings indicate a biologically more aggressive phenotype of melanoma cells. 
Cor triatriatum with isolated pulmonary venous stenosis in an adult: diagnosis with transesophageal two-dimensional echocardiography. The diagnosis of cor triatriatum in an adult was made from routine two-dimensional transthoracic echocardiography. The findings of aliasing and turbulence in the roof of the left atrium suggested pulmonary venous stenosis. A transesophageal echocardiogram defined both the hemodynamic features of nonobstructing cor triatriatum and the presence of isolated pulmonary venous stenosis. The clinical use of transesophageal echocardiography with color flow Doppler in the elucidation of complex anatomic substrate is demonstrated. 
Mastoid surgery in childhood. The presenting features and operative findings in 105 patients aged 16 years or less undergoing mastoid surgery are reviewed. In 94% surgery was for chronic otomastoiditis, usually acquired, and associated with cholesteatoma in 64%. Post-operative otorrhoea persisted beyond 6 months in 44% and contralateral disease required some form of surgical procedure in 20%. Post-operative hearing thresholds were improved or unchanged in the majority of patients, most of whom underwent cortical or modified radical mastoidectomy. An improvement in the therapeutic results of mastoid surgery in childhood is clearly necessary, but requires a greater understanding of the aetiology of chronic middle ear disease. 
Doppler echocardiography for rejection surveillance in the cardiac allograft recipient. Echocardiography is noninvasive, allows real-time visualization of the heart, and can be performed serially without harmful biologic effects. It is also relatively inexpensive compared with other diagnostic modalities used for cardiac transplant rejection surveillance, such as cardiac biopsy, computed tomography, and magnetic resonance imaging. It is free of the potential complications associated with cardiac biopsy, such as accidental disruption of cardiac valves or chordae tendineae, ventricular septal perforation, introduction of bacteria, and the difficulty of obtaining adequate sampling for effective diagnosis as a result of formation of scar tissue. Unlike biopsy, echocardiography does not cause the patient anxiety and discomfort or use many physician and instrument or laboratory resources. Because the results of echocardiography are available within minutes compared with the hours usually needed for biopsy results, it allows prompt decisions regarding patient clinical care and treatment. In our work to date, echocardiography has not replaced the cardiac biopsy in surveillance of rejection in the cardiac transplant patient, but rather has become a useful adjunct to it. When echocardiographic findings indicate changes characteristic of rejection, biopsies are performed earlier, leading to earlier diagnosis and treatment. Furthermore, when echocardiographic findings are stable and negative for rejection, the number of routine cardiac biopsies performed can be reduced. This article discusses the use of echocardiography in surveillance of the cardiac transplant patient and the ability of echocardiography to augment the biopsy and clinical regimens in assessing cardiac allograft rejection. 
Abnormal automatic rhythms in ischemic Purkinje fibers are modulated by a specific alpha 1-adrenergic receptor subtype. BACKGROUND. Recent advances in adrenergic pharmacology have made possible the identification of alpha 1-adrenergic receptor subtypes using the specific blockers chloroethylclonidine and WB 4101. METHODS AND RESULTS. In the present study, we used these two blockers to determine the mechanisms responsible for automatic rhythms occurring during simulated ischemia and reperfusion of isolated canine Purkinje fibers. Experiments were done in the presence of propranolol to minimize beta-adrenergic contributions to the rhythms studied. In the control situation, all fibers showed membrane potentials greater than -90 mV and normal automatic rhythms. During simulated ischemia, membrane potential depolarized to the -60 mV range. Abnormal automaticity was seen in 20% of fibers not treated with phenylephrine and in 50% of those superfused with 1 x 10(-7) M phenylephrine. The incidence of abnormal automaticity was reduced to 0% by WB 4101 (which blocks phosphoinositide metabolic effects of alpha 1-adrenergic stimulation in the heart) and was increased to 90% by chloroethylclonidine (which blocks Na-K pump-stimulating effects of alpha-agonists). Moreover, the ischemic fibers were significantly more hyperpolarized during superfusion with WB 4101 than with chloroethylclonidine. Triggered activity induced by delayed or early after depolarizations was not seen in any experiment. CONCLUSIONS. Automatic arrhythmias induced by alpha 1-adrenergic stimulation during simulated ischemia may be attributed to a specific alpha 1-adrenergic receptor subtype that is blocked by WB 4101. These results have important implications with respect to the induction of arrhythmias in the setting of ischemia and the means for their prevention or treatment. 
Secondary myelodysplastic syndrome complicating therapy for osteogenic sarcoma. A 12-year-old girl with nonmetastatic osteogenic sarcoma received treatment with doxorubicin, methotrexate, cisplatin, cyclophosphamide, bleomycin, and dactinomycin. She developed unexplained persistent pancytopenia after completion of chemotherapy. Twenty-three months after the initial diagnosis of osteosarcoma an evaluation revealed a bone marrow pattern consistent with the diagnosis of refractory anemia with excess blasts, and karyotype analysis showed characteristic findings of therapy-related myelodysplasia (loss of chromosomes 5 and 7, as well as 12p and 17p deletions). Bone marrow transplantation from an human leukocyte antigen (HLA)-compatible sibling donor was performed 26 months after the diagnosis of the primary malignancy. Although it is unproven that the alkylating agents administered to this patient were responsible for the myelodysplastic syndrome, careful follow-up of osteosarcoma patients who receive alkylating agents is warranted. 
Gastrointestinal complications in 4473 patients who underwent cardiopulmonary bypass surgery. Thirty-nine gastrointestinal complications occurred in 35 of 4473 patients (0.78 per cent) who underwent surgery involving cardiopulmonary bypass during an 8-year period. The mortality rate when one of these complications occurred was 22 (63 per cent) representing 11.5 per cent of the 191 deaths from all causes in the series. The relative risk of developing a gastrointestinal complication was 1:249 when the heart was not opened, 1:66 when it was and 1:5 after cardiac transplantation. Gastrointestinal bleeding (n = 20) was the most common complication of whom nine (45 per cent) died, followed by intestinal infarction (n = 12) with eight (67 per cent) deaths and acute pancreatitis (n = 6) all of whom died. There was one death after surgery for gastrointestinal bleeding (n = 7). No patient survived bowel infarction without operation but resection was possible in five of the eight who underwent surgery, four of whom survived. The results demonstrate that surgical intervention is not associated with undue mortality but inappropriate conservative therapy is poorly tolerated in this high-risk group. 
Much ado about gastrin [editorial; comment] The regulation of gastrin secretion from antral G-cells is of major importance in the physiologic control of acid secretion. Gastrin secretion is highly dependent upon gastric intraluminal pH and is inhibited significantly by a pH of less than 3.0. Acute gastric alkalinization greater than pH 6.0 with antisecretory agents such as H2-receptor antagonists or H+/K+ ATPase inhibitors has little impact on fasting serum gastrin levels but promotes an enhanced sustained rise in meal-stimulated gastrin release. Courses of standard therapy with both H2-antagonists and H+/K+ inhibitors cause a significant rise in 24 h integrated plasma gastrin levels that is inversely correlated to the 24-h integrated gastric acidity. The rise in fasting or integrated plasma gastrin levels observed in patients treated with H2-antagonists is small and of unclear clinical significance. Therapy with antisecretory agents leads to earlier ulcer relapse than with other agents. A variety of factors have been proposed to explain the earlier ulcer relapse rate, including secondary hypergastrinemia with rebound acid hypersecretion after discontinuation of the drug. Secondary hypergastrinemia may also lead to tolerance to prolonged courses of H2-antagonists therapy with a decrease in acid inhibition. This may contribute to break-through ulcer recurrence during maintenance H2-antagonist therapy. However, the relative importance of hypergastrinemia and tolerance to H2-antagonists compared with other factors such as baseline gastric acid secretion, smoking status, nonsteroidal anti-inflammatory drug use, and Helicobacter pylori status is difficult to assess. 
Indium-111-leukocyte imaging in acute cholecystitis. Eleven patients with suspected acute cholecystitis underwent sequential 99mTc-iminodiacetic derivative (IDA) and 111In-white blood cell (WBC) imaging to determine if 111In-WBCs accumulate within an acutely inflamed hemorrhagic gallbladder wall and, thus, could be employed as a reasonable alternative to 99mTc-IDA scintigraphy in detecting acute cholecystitis. Seven patients had surgically confirmed acute cholecystitis. Of these cases, five had a true-positive 99mTc-IDA and 111In-WBC, one an indeterminate 111In-WBC and true-positive 99mTc-IDA, and one a true-positive 111In-WBC and false-negative 99mTc-IDA scan. The remaining four patients did not have acute cholecystitis. All visualized their gallbladder within 1 hr after 99mTc-IDA administration and none had 111In-WBC gallbladder wall uptake. Both 111In-WBC and 99mTc-IDA scintigraphy accurately detected acute cholecystitis: hepatobiliary scintigraphy demonstrated a cystic duct obstruction and 111In-WBC imaging detected the inflammatory infiltrate within the gallbladder wall. The sensitivity and specificity of each was 86% and 100%, respectively. 
Recurrent and/or metastatic head and neck squamous cell carcinoma: a clinical, univariate and multivariate analysis of response and survival with cisplatin-based chemotherapy. One hundred two patients with recurrent and/or metastatic head and neck squamous cell cancer were entered into four consecutive phase II trials, all cisplatinum (C-DDP, 100 mg/m2/cycle)-based. The two combinations tried were C-DDP, bleomycin, and fluorouracil (CFB) on 54 patients, and cisplatinum and vindesin in 36 patients (CV). The CFB combination was given with C-DDP by continuous infusion over 96 hours (23 patients) or on day 1 (31 patients). The CV regimen was also given in two different schedules, with VDS at 3 mg/m2/g weekly (12 patients) or by a 96-hour continuous infusion (0.6 to 1.0 mg/m2/d) in 24 patients. The following variables: sex, age, performance status, previous therapy, local recurrence, length of disease-free interval (DFI), distant metastases, weight loss, primary site, histological differentiation, type of chemotherapy, previous chemotherapy, evaluable/measurable disease, erythrosedimentation rate, and their relation with response to chemotherapy (WHO) and survival were submitted to both univariate and multivariate analysis (Cox). Overall response rate (RR:CR + PR) was 25 (28%) of 90. In the CFB protocols, RR was 12 (22%) of 54 vs. 13 (38%) of 36 (P = 0.15, NS) in the CV combination group. For the four different combinations the RR was CFB C-DDPci 7 (30%) of 23, CFB C-DDP 1 hour 5 (16%) of 31, CV VDS weekly 2 (17%) of 12, CV VDSci 11 (45%) of 24. The patient populations were very different, with the latest combination consisting of metastatic patients exclusively. Univariate analysis of multiple variables showed age less than 60 years, PS:0 or 1, no previous therapy, absence of local relapse, metastatic disease, long DFI, and that measurable disease was significant for the probability of response. Median survival was 7 months for the 90 evaluated patients, 5 months for nonresponders, and 9 months for responders (P = 0.01). In the univariate analysis, significant factors for survival were PS:0 or 1, a weight loss below 10%, long DFI, response to chemotherapy, erythrosedimentation rate (ESR) of less than 30 mm/1st hr, presence of bone metastasis, and the number of metastases. Multivariate analysis shows PS, the absence of local relapse, and disease-free interval as significant prognostic factors for response. Multivariate analysis factors of significance for survival were PS, weight loss, and response to chemotherapy. The analysis of the clinical pattern showed an evolution in RR from 3 (8%) of 36 on previously irradiated local recurrent disease to 8 (73%) of 11 in previously untreated patients with metastatic disease at presentation.(ABSTRACT TRUNCATED AT 400 WORDS). 
Visual evoked potentials and background EEG activity in migraine. To investigate whether quantification of the background EEG during a visual evoked potential (VEP) study is of value for the diagnosis of migraine we studied 8 unmedicated migraineurs between attacks, and 10 age-matched controls. Three paradigms were used: the first two concerned pattern-reversal VEPs with different analysis times (500 and 1500 ms), and in the third paradigm the pattern did not reverse. Power spectra were calculated for individual responses, and the delta, theta, alpha and beta areas of the averaged spectra were noted as indicators of background reactivity. Alpha and beta powers were consistently but not significantly higher in the migraine group. The difference was too small to be of value as a diagnostic test. Alpha power was (not significantly) lower in the presence of photic stimulation than in its absence. As this was the case in both groups photic stimulation does not explain the higher alpha powers in the migraine group. We conclude that EEG background activity during the VEP does not distinguish reliably between migraineurs and controls. 
Interferon-gamma reverses bone marrow inhibition following hemorrhagic shock. Hemorrhagic shock has been demonstrated to alter the myelopoietic response to bacterial lipopolysaccharide. Interferon-gamma has been shown to improve the immune response following experimental shock and injury; however, its effect on myelopoiesis is controversial. This study was performed to determine whether treatment with interferon-gamma will improve the bone marrow response to lipopolysaccharide after hemorrhagic shock. Rats subjected to either shock or a sham procedure were allocated into three groups: (1) control rats received no further treatment; (2) lipopolysaccharide-treated rats received saline for 3 days and then were challenged with lipopolysaccharide to stimulate myelopoiesis; and (3) interferon-treated rats received interferon-gamma (7500 U subcutaneously 1 hour after shock and then every day for 3 days) and lipopolysaccharide as in group 2. Serum colony-stimulating factor levels were measured 6 hours and bone marrow white blood cell count and granulocyte-macrophage colony-forming units (CFU-GM) were measured 24 hours following lipopolysaccharide administration. In sham-treated rats, lipopolysaccharide increased CFU-GM 77% compared with controls. In contrast, treatment with lipopolysaccharide decreased CFU-GM 43% following shock. Treatment with interferon-gamma increased CFU-GM in all animals and reversed the decline in CFU-GM seen in shocked lipopolysaccharide-treated animals. Serum colony-stimulating factor levels were unaffected by either shock or interferon-gamma administration. These data demonstrate that interferon-gamma exerts a stimulatory effect on bone marrow following shock and restores the myelopoietic response to lipopolysaccharide. 
Proliferative activity of neuroendocrine tumours of the gastroenteropancreatic endocrine system: DNA flow cytometric and immunohistological investigations. The proliferative activity of 16 tumour specimens from 13 patients with neuroendocrine tumours of the gastroenteropancreatic endocrine system was studied by DNA flow cytometry and immunohistology for the nuclear Ki67 proliferation antigen. Equivalent results were obtained with both methods, which showed the proliferative activity of gastroenteropancreatic neuroendocrine tumours to be heterogeneous. In four malignant small intestinal carcinoids and one extravisceral carcinoid localised in the retroperitoneum the percentage (index) of proliferating tumour cells as measured by DNA flow cytometry ranged from 2.9 to 36.2% corresponding to low, moderate, or high proliferative activity. In four malignant pancreatic endocrine tumours and their metastases indices ranged from 8.7 to 18.3%, corresponding to low, moderate, or high proliferative activity. In four benign pancreatic endocrine tumours indices ranged from 4.3 to 7.7%, all corresponding to low proliferative activity. This heterogeneity of proliferative activity may in part explain the heterogeneous results reported of chemotherapy treatment. As chemotherapy of tumours is largely affected by favourable cell cycling kinetics, individual diagnostic investigations of the proliferative activity of these neuroendocrine tumours may be of value for identifying patients suitable for this treatment. 
Experience with 225 hepatic resections for hepatocellular carcinoma over a 4-year period. During the past 4 1/2 years, we have performed hepatic resection on 225 patients with hepatocellular carcinoma (HCC). These patients included 171 men and 54 women, whose ages ranged from 29 to 84 years with an average of 60 years. Underlying cirrhosis of the liver was found in 67% of the patients and chronic hepatitis in 27%. Patients undergoing hepatic resection were classified into five groups according to curability as follows: Group A, resection of the tumor-bearing segment and one additional segment; Group B, complete resection of the tumor with more than 1.0 cm free surgical margin; Group C, complete resection of the tumor with less than 1.0 cm free surgical margin; Group D, incomplete resection of the tumor; Group E, surgical approach for advanced HCC with tumor thrombi in the main trunk or the first branch of the portal vein and/or the inferior vena cava, with multiple daughter nodules in both lobes and with tumor recurrence. The number of patients in Groups A, B, C, D, and E was 12 (5%), 83 (37%), 58 (26%), 14 (6%) and 58, (26%), respectively. There were 4 deaths (2.4%) among the 167 patients in Groups A to D within 30 days after operation and 12 deaths (20.7%) in Group E. The 3-year survival rate of Groups A, B, C, D, and E was 100%, 74%, 21%, 0%, and 35%, respectively. 
Contralateral primary tumors in breast cancer patients in a randomized trial of adjuvant tamoxifen therapy Prophylactic treatment with the anti-estrogen tamoxifen may reduce the risk of breast cancer because estrogens are thought to act as promoters in the pathogenesis of the disease. This article presents results on the incidence of contralateral new primary tumors among 1846 postmenopausal breast cancer patients included in a randomized trial of adjuvant tamoxifen therapy for 2 or 5 years after surgery versus no adjuvant endocrine therapy. The median follow-up was 7 years (range, 3-13 years). There was a significant reduction of contralateral breast cancer in the 931 patients in the tamoxifen group versus that in the 915 control patients (29 versus 47 cases, respectively; P = .03). The cumulative incidence at 10 years in the tamoxifen group and the control group was 5% and 8%, respectively. Analysis of the relative hazard of contralateral tumor over time showed that the benefit with tamoxifen therapy was greatest during the first 1-2 years, but there was a continued risk reduction during the entire follow-up period, i.e., more than 10 years after cessation of treatment. There was no significant difference in the number of contralateral cancers in the patients randomly assigned to 2 or 5 years of treatment, but the 95% confidence interval of the relative hazard was wide. The proportion of estrogen receptor-negative contralateral breast cancers was higher in the tamoxifen group than in the control group. There was no difference, however, between the two groups in recurrence-free survival time from the diagnosis of the contralateral cancer. 
Immunoblastic lymphoma with abundant clear cytoplasm. A comparative study of B- and T-cell types. The morphologic, phenotypic, molecular genetic, and clinical features of 34 cases of clear-cell immunoblastic lymphoma (IBLC) are described. Sixteen cases were of B-cell type (IBLC-B) and 18 cases were of T-cell type (IBLC-T). There were no significant differences in the morphologic characteristics of the neoplastic cells in the two types, although IBLC-B was less likely to be polymorphic than IBLC-T. Interfollicular proliferation, a higher mitotic rate, infiltration by eosinophils, and an increase in capillary-sized blood vessels were also features of IBLC-T, whereas necrosis and fibrosis were more extensive in IBLC-B. Patients with IBLC-B were predominantly female, whereas those with IBLC-T were predominantly male. The mean age was 62 years for those with IBLC-B and 46 years for those with IBLC-T. Patients with IBLC-B usually had lower-stage disease, but there was no significant difference in survival rate between those with IBLC-B and those with IBLC-T. Although most cases of IBLC have been considered to be of peripheral T-cell origin, the authors conclude that IBLC-B is more common than previously considered and that clear-cell morphologic characteristics are not a reliable indicator of T-cell type. 
Improved survival in patients with poor-prognosis malignant melanoma treated with adjuvant levamisole: a phase III study by the National Cancer Institute of Canada Clinical Trials Group Five hundred forty-three patients with completely resected malignant melanoma who were considered to have a significant risk of developing recurrent disease were randomized to one of four study groups. One group received levamisole 2.5 mg/kg on 2 consecutive days weekly for 3 years, a second group received bacillus Calmette-Guerin (BCG) for 3 years. A third group alternated 8-week courses of BCG and levamisole for 3 years and a fourth group underwent clinical assessment at the same frequency as the three treatment groups. The median duration of follow-up is 8.5 years. The percentage of reduction in the death rate and the recurrence rate in the treatment groups compared with the control group was calculated using the Cox proportional hazards model and adjusted for age, sex, and stage as covariants. The patients treated with levamisole were estimated to have a 29% reduction in both the death rate (P = .08) and the recurrence rate (P = .09) compared with patients receiving no further treatment. Fifty-five patients discontinued levamisole early because of gastrointestinal intolerance or arthralgia, myalgia, fever, and immune leukopenia. The patients treated with BCG alternating with levamisole experienced a 10% reduction in the death rate and a 6% reduction in the recurrence rate, and the patients treated with BCG alone experienced a 4% reduction in the death rate and a 3% increase in the recurrence rate compared with the control group. The degree of improvement experienced by the patients that were treated by levamisole is of sufficient magnitude to warrant further investigation of this dose of levamisole as adjuvant treatment in patients with melanoma. 
Glomerular hypertension in renovascular hypertensive patients. Split intrarenal hemodynamics in stenotic and contralateral kidneys of unilateral renovascular hypertension (RVH) were estimated by Gomez's formulae. Forty patients with essential hypertension and 40 patients with RVH were studied. Split para-amino hippurate and inulin clearances were measured by ureteral catheterization as indexes for effective renal plasma flow and glomerular filtration rates, allowing the estimation of intrarenal hemodynamics such as afferent arteriolar resistance (RA), efferent arteriolar resistance (RE) and glomerular hydrostatic pressure (PG) in each kidney. Normal values of intrarenal hemodynamic parameters were obtained in 24 normotensive subjects without ureteral catheterization, assuming each kidney had the half function of both kidneys. Systemic mean arterial pressure did not differ between essential and renovascular hypertension (141 +/- 3 vs. 148 +/- 3 mm Hg). Effective renal plasma flow and glomerular filtration rates were decreased in the stenotic kidney of RVH (98 +/- 8, 24 +/- 2 ml/min/m2), while increased in the contralateral kidney (195 +/- 11, 48 +/- 2), compared with the right kidney of essential hypertension (162 +/- 8, 33 +/- 1). Although effective renal plasma flow rate was not different from normal (191 +/- 8), glomerular filtration rate was significantly higher in the contralateral kidney of RVH than in normal (38 +/- 1). RA was elevated due to the stenotic lesion in the stenotic kidney (28,500 +/- 1,900 dyns.sec.cm-5), while the elevation in the contralateral kidney (10,800 +/- 600) was less than in the right kidney of essential hypertension (14,900 +/- 1,200). RE (5,800 +/- 300) in both kidneys of RVH was higher than in the right kidney of essential hypertension (4,500 +/- 200). 
Small intestinal lesion resembling graft-vs-host disease. A case report in immunodeficiency and review of the literature. We report graft-vs-host disease-like histology in a small intestinal biopsy specimen that was obtained from a patient with common variable immunodeficiency and related T-cell defect. We include findings from immunohistochemical studies and follow-up information. Review of the literature yielded only a small number of histologically documented cases of this lesion without previous bone marrow transplantation. Awareness of this clinicopathologic entity is important in the interpretation of gastrointestinal biopsy specimens. 
Phase I study of weekly intravenous infusions of CPT-11, a new derivative of camptothecin, in the treatment of advanced non-small-cell lung cancer. 7-Ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy-camptothecin (CPT-11) is a novel camptothecin derivative that has been selected for clinical evaluation because of its broad spectrum of antitumor activity in animal models and its unique inhibitory effects on mammalian DNA topoisomerase I. Seventeen patients with advanced non-small-cell lung cancer were treated with CPT-11 at weekly dose levels ranging from 50 to 150 mg/m2. At least three weekly doses were given to all patients except four, and a total of 74 weekly doses were given to the 17 patients. The dose-limiting toxic effects were myelosuppression (predominantly leukopenia) and unpredictable diarrhea. Gastrointestinal toxic effects were severe and not well controlled by standard therapy in some patients. Interpatient variability of toxic effects was substantial (including two deaths) and did not correlate with the pharmacokinetic parameters of CPT-11 and 7-ethyl-10-hydroxycamptothecin, its major metabolite. Two previously untreated patients, who received doses of 100 and 125 mg/m2, had partial responses lasting 3.2 and 4.0 months, respectively. The maximum tolerated dose on this schedule was 100 mg/m2, which we also recommend as a starting dose for phase II studies. This schedule appears to allow a CPT-11 dose intensity which is double the dose intensity possible on a once-a-month schedule. However, careful supervision to assess gastrointestinal toxic effects and myelosuppression is indispensable because of wide individual differences in drug tolerance. 
Increased survival, limb preservation, and prognostic factors for osteosarcoma. Preoperative intraarterial (IA) cisplatin (CDP) was administered to 92 patients with nonmetastatic osteosarcoma. The ages of the patients ranged from 4 to 28 years. Sixty-four patients (70%) received 2 or 3 preoperative courses and 28 (30%) received 4 or more. Sixty-two specimens were available for pathologic examination to assess the degree of tumor necrosis. More than 90% tumor destruction was observed in 16 of 42 patients (38%) who received 1 to 3 preoperative courses as opposed to 17 of 20 (85%) who received 4 or more courses. Patients who received 4 or more courses had a 2-fold probability of achieving more than 90% tumor necrosis, and 68% underwent conservative surgery. Of those who received 3 or less courses, 23% underwent conservative surgery. Postoperatively, patients were treated with intravenous (IV) CDP alternating with doxorubicin (ADR) (Adriamycin, Adria Laboratories, Columbus, OH). Pulmonary metastases developed in 36 patients, bone metastases in 2, and local recurrence in 6. Two patients died of cardiac failure without evidence of disease. Thus, 46 patients (50%) were continuously free of disease 18 to 78 months after diagnosis. Univariate and multivariate analyses showed that male sex, low grade preoperative chemotherapy-induced necrosis, and nonosteoblastic histologic condition were prognostic factors predictive of recurrence, while male sex and large tumor size were prognostic factors predictive of death. These results are comparable with those reported by other centers and are superior to our previous experiences that yielded survival rates of 5% to 10%. A substantial number of patients also had the opportunity to achieve tumor removal with conservative surgery. 
Mesenchymoma of the chest wall in children. Benign chest wall mesenchymoma in children is an extremely rare disease. Only 20 patients have been reported in the world literature. We report a chest wall mesenchymoma in a 2-year-old boy who was admitted to the hospital after a routine chest roentgenogram showed a mass in the right upper chest wall. The patient was asymptomatic. Clinical examination was negative, but chest roentgenograms and computed tomography showed a mass in the right upper chest wall involving the third rib. A 2 x 2 x 1.5-cm tumor was excised totally with partial resection of the third rib. The histology of the lesion corresponded to a mesenchymoma (hamartoma) of the chest wall. Our patient has been followed up for 8 years without recurrence. 
Management of chiasmal and hypothalamic gliomas of infancy and childhood with chemotherapy. Between March, 1983, and February, 1989, 19 infants or children with chiasmal/hypothalamic gliomas were treated with chemotherapy after either surgical or radiological diagnosis. The patients ranged in age from 15 weeks to 15.6 years (median 3.2 years) at the start of therapy. Twelve patients were treated immediately after diagnosis because of progressive symptoms, and seven received chemotherapy after either radiographic progression or clinical deterioration, including progressive visual loss or intracranial hypertension. Based on biopsy results, seven of these tumors were classified as juvenile pilocytic astrocytomas, two as astrocytomas, two as highly anaplastic astrocytomas, and one as a subependymal giant-cell astrocytoma. There was associated neurofibromatosis in four patients. The two initial patients were treated with either actinomycin D and vincristine or 5-fluorouracil, hydroxyurea, and 6-thioguanine. The remaining patients received nitrosourea-based therapy; 15 evaluable patients were treated with a five-drug regimen that included 6-thioguanine, procarbazine, dibromodulcitol, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), and vincristine and one received 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and 5-fluorouracil. Fifteen of the 18 evaluable patients initially managed with chemotherapy either responded to therapy or their condition stabilized. Median time to tumor progression has not been reached at a median follow-up period of 79 weeks (range 6.6 to 303 weeks), and no tumor-related death has occurred with a median follow-up period of 79 weeks (range 18 to 322 weeks) from the initiation of therapy. The four patients who failed therapy or whose disease progressed after chemotherapy were treated satisfactorily with radiation therapy. Initial improvement or stabilization of visual function was obtained in 16 patients. Endocrine function remained stable in all patients during treatment, although three patients required pharmacological treatment for endocrinopathy that was present at diagnosis. These preliminary results suggest that nitrosourea-based cytotoxic regimens are useful for the initial treatment of children with chiasmal/hypothalamic gliomas, and allow potentially harmful radiation therapy to be deferred until progression of disease. 
Transient prolonged postischemic ventricular dilatation documented by 99mTc MIBI scan. We describe two cases of prolonged postischemic ventricular dilatation during myocardial scintigraphy with 99mTc MIBI, the new perfusion tracer that has only negligible redistribution. Ventricular dilatation, caused by true chamber dilatation and/or subendocardial ischemia, was still present over two hours after the induced ischemic episode, suggesting a prolonged duration of such a commonly believed fleeting scintigraphic finding. 
A randomized clinical study of a calcium-entry blocker (lidoflazine) in the treatment of comatose survivors of cardiac arrest. Brain Resuscitation Clinical Trial II Study Group BACKGROUND. Abnormalities of cellular calcium homeostasis have been implicated in the pathophysiology of postischemic encephalopathy. Calcium-entry-blocking drugs inhibit the influx of calcium into cells and have been shown to mitigate postischemic encephalopathy in animal models. METHODS. Five hundred twenty patients with cardiac arrest who remained comatose after the restoration of spontaneous circulation were randomly assigned to receive three doses of lidoflazine, an experimental calcium-entry blocker, or a placebo and were followed for six months. Four patients were lost to follow-up. Treated patients received an intravenous loading dose (1 mg per kilogram of body weight) of lidoflazine and two subsequent doses (0.25 mg per kilogram) 8 and 16 hours after resuscitation. The investigators were blinded to treatment assignment. RESULTS. There was no statistically significant difference between the lidoflazine group (n = 259) and the placebo group (n = 257) in the proportion of patients who died during the six-month follow-up (82 vs. 83 percent), who survived with good cerebral recovery (15 vs. 13 percent), or who survived with severe neurologic deficit (1.2 vs. 1.9 percent). Analysis of the best level of recovery achieved at any time during follow-up also did not show a difference between the treatment groups: 24 percent of those given lidoflazine and 23 percent of those given placebo recovered good cerebral function (normal or only moderately disabled cerebral performance) at some time. CONCLUSIONS. The administration of lidoflazine after cardiac arrest was not found to be beneficial. Our data do not support the routine use of this calcium-entry-blocking drug in comatose survivors of cardiac arrest. 
The ileal neobladder. The ileal neobladder in many respects approximates the theoretically ideal continent urinary diversion. The technique, while more technically demanding than the performance of the standard ileal loop diversion, is not difficult, particularly for surgeons used to performing radical retropubic prostatectomies. The ileal neobladder appears to approximate most closely the optimal bladder substitution. Although currently feasible only in males, future considerations could conceivably involve urologists working with their colleagues in gynecology and colorectal surgery to extend the benefits of bladder substitution using the ileal neobladder to selected patients having cystectomy for associated gynecologic or colorectal malignancies. 
The intranasal ethmoidectomy: an experience with 1,077 procedures. A series of 1,077 intranasal ethmoidectomies (825 with sphenoid sinusotomies) was performed in 600 patients over a 15-year period at The Mount Sinai Medical Center. The technique is a modification of the classical operation originally proposed by Yankauer. The rate of significant complications was 1.1%. A subset of 90 patients underwent 166 procedures and were followed an average of 3.5 years. The patients were analyzed according to whether the disease was focal or diffuse, infectious or polypoid, and whether asthma was present. The surgical success rate was 88% in nonasthmatics, but dropped to 50% in asthmatic patients despite total sphenoethmoidectomy. This underscores the importance of this condition as a biological modifier of surgical prognosis. Accordingly, a system of classification of sinus diseases is proposed based upon disease extent and type and whether asthma is present. 
Conservative treatment of vesicovaginal fistulas by bladder drainage alone. We describe 4 cases of conservative management of vesicovaginal fistulas occurring as a complication of abdominal and vaginal hysterectomy. In all cases treatment involved simple bladder drainage for periods ranging from 19 to 54 days. At follow-up all patients remained dry. Such spontaneous closure of vesicovaginal fistulas following adequate bladder drainage has not been previously reported. 
Effects of early captopril administration on infarct expansion, left ventricular remodeling and exercise capacity after acute myocardial infarction. In a double-blind study, 99 patients (82 men, age range 40 to 75 years) with acute myocardial infarction (AMI) were randomly assigned to receive captopril or placebo. Treatment began within 24 hours of admission. Serial echocardiographic measurements of endocardial segment lengths and left ventricular (LV) volumes, and ejection fractions were obtained. The 2 groups were matched at baseline except for an excess of previous AMI in the placebo group (13 of 50 vs 2 of 49 patients, p = 0.002). The increase in anterior segment length, from baseline to 2 months, was significantly less in the captopril than in the placebo group (2.8 +/- 1.6 vs 10.4 +/- 2.4mm, 95% confidence interval [CI] -13.5 to -1.7, p = 0.01). The increase in posterior segment length was also less in the captopril group, but the difference was not significant (3.2 +/- 1.2 vs 7.0 +/- 1.8mm, 95% CI -8.0 to 0.5, p = 0.08). Fewer patients in the captopril group demonstrated increases in segment length greater than 2 standard deviations of the measurement error (14 of 70 [20%] vs 29 of 72 [40%] patients, p = 0.009). In patients with anterior AMI, the infarct-containing anterior segment length increased by 4.5 +/- 2.3 mm in the captopril versus 12.4 +/- 3.1 mm in the placebo group (95% CI -15.7 to -0.2, p = 0.046), and fewer patients in the captopril group demonstrated infarct expansion (6 of 20 [30%] vs 13 of 21 [62%] patients, p = 0.04). 
How AIDS forces reappraisal of hepatitis B virus control in sub-Saharan Africa For developing countries the cost-benefit of vaccination in the control of hepatitis B virus (HBV) infection is great since the acute infection is generally subclinical and the benefit is the prevention of small numbers of cases of cirrhosis and hepatocellular carcinoma. Since the pattern of HBV infection in Africa is such that, compared with south-east Asia, infection occurs later in childhood and spread is horizontal rather than vertical, investigation of the method of spread of HBV may result in a means of control other than by vaccination. In the meantime, because of the overlap in the means by which HBV and human immunodeficiency virus (HIV) are spread, it could be worthwhile taking advantage of existing AIDS prevention programmes to educate people about how to avoid both HBV and HIV infections. 
Pulmonary angiitis and granulomatosis. The presentation of a patient with multiple pulmonary nodules with or without cavitation and often with signs of a multisystemic vasculitis should suggest one of the pulmonary angiitis and granulomatosis syndromes. The five conditions traditionally considered together in the category of pulmonary angiitis and granulomatosis differ widely in their cause and pathogenesis and are more appropriately considered as variants or relatives of other processes. The radiologic features of this group of diseases, however, are similar, and it is useful to still consider them together. Table 1 summarizes the radiologic features of these conditions. 
Splanchnic sympathetic nerve activity and circulating catecholamines in the hyperthermic rat. The mechanisms responsible for the initial rise in splanchnic vascular resistance with environmental heating are controversial, and those responsible for the subsequent fall in splanchnic resistance in the severely hyperthermic animal are unknown. Thus we examined the effect of environmental heating on plasma catecholamine concentration, splanchnic sympathetic nerve activity (SNA), and select blood chemistries. In one study, 25 male Sprague-Dawley rats (270-300 g) were assigned to one of five groups on the basis of their core temperature (Tc, 37, 39, 41, 43, or 44 degrees C) at death. Heart rate (HR), mean arterial pressure (MAP), and Tc were monitored during heat stress under alpha-chloralose anesthesia (12.5 mg.ml-1.h-1). At each predetermined Tc, an aortic blood sample was drawn and analyzed for mean plasma concentration of norepinephrine (NE), epinephrine (E), Na+, K+, and lactate. From 41 to 43 degrees C, NE and E rose significantly, and the animals became hyperkalemic and lactacidemic. In a separate study, we quantitated SNA from the greater splanchnic nerve during heat exposure of artificially respired animals anesthetized with pentobarbital sodium (50 mg/kg). MAP, splanchnic SNA, and Tc were recorded. Tc was elevated from 37.0 +/- 0.12 to 41.3 +/- 0.18 degrees C in 70 min by increase of ambient temperature to 38 degrees C in an environmental chamber. Splanchnic SNA was 54 +/- 8 spikes/s at a Tc of 37 degrees C and increased significantly as Tc exceeded 39 degrees C (P less than 0.05). 
Hemodynamic and neurohormonal effects of clonidine in patients with preganglionic and postganglionic sympathetic lesions. Evidence for a central sympatholytic action. BACKGROUND. Clonidine, a partial presynaptic and postsynaptic alpha-adrenoceptor agonist, has been shown to lower blood pressure in normal subjects but not in tetraplegics; however, the mechanisms of this action have not been elucidated. METHODS AND RESULTS. The hemodynamic and hormonal basis of the hypotensive action of clonidine was investigated in tetraplegics with complete cervical spinal cord transection and preganglionic sympathetic denervation, in patients with unilateral brachial plexus injury and postganglionic sympathetic denervation, and in normal subjects. In normal subjects, the fall in blood pressure after clonidine infusion was accompanied by a reduction in cardiac output that was predominantly due to a fall in stroke volume and in heart rate. The lack of fall in blood pressure, cardiac output, and stroke volume in tetraplegics indicates that these effects are exerted at a supraspinal level and require intact descending sympathetic pathways. After clonidine infusion, digital skin vasodilatation occurred in normal subjects, in the innervated but not the denervated limb of patients with unilateral brachial plexus injury, and in tetraplegics, indicating that this response is due to the central sympatholytic effect of clonidine. Plasma norepinephrine was much lower in tetraplegics compared with normal subjects, and after clonidine infusion, it fell substantially in normal subjects alone. Plasma renin activity did not change. Bladder stimulation in tetraplegics resulted in a rise in blood pressure and vasoconstriction in digital skin vessels. The inability of clonidine to significantly reduce or abolish the pressor and digital vasoconstrictor responses after bladder stimulation in tetraplegics indicates that clonidine does not exert a major effect on spinal preganglionic neurons or peripheral presynaptic alpha 2-adrenoceptors. CONCLUSIONS. Therefore, clonidine is a suitable drug for use in analyzing the central supraspinal levels of control in varying circulatory disorders, such as hypertension and postural hypotension. 
Morbidity of modified pelvic lymphadenectomy and radiotherapy for prostatic cancer. The records of 63 patients treated by pelvic lymphadenectomy and radiotherapy at the University of Tennessee, Memphis, Baptist Memorial Hospital of Memphis, and the Memphis Veterans Affairs Hospital were reviewed. Of those patients, 45 received external beam radiation therapy to the prostate while 16 were treated by Iodine-125 implantation. Two patients had only staging lymphadenectomy. The incidence of postoperative and late complications were analyzed. 
Application of smooth Teflon clip to inferior vena cava during radical cystectomy to prevent postoperative pulmonary embolism. Between 1976-1986, a smooth Teflon clip was applied to the inferior vena cava of 56 patients who underwent radical cystectomy for bladder cancer. The purpose of the clip is to narrow the lumen of the inferior vena cava so that large emboli will be trapped and thus prevented from reaching the lungs. These 56 patients were compared with a group of 26 historical controls who underwent radical cystectomy without application of such a clip between 1967-1976. One patient (1.8%) whose vena cava was clipped had a pulmonary embolus which was fatal. Four (15.4%) of the 26 control patients had postoperative pulmonary emboli, the embolic event being fatal in 3 (11.5%). Application of the smooth Teflon clip to the inferior vena cava significantly lessens the incidence of pulmonary embolism following radical cystectomy. 
Paul Broca and the first craniotomy based on cerebral localization. Paul Broca (1824-1880) was a well-known French surgeon-anthropologist-neurologist. Best known for his work on cerebral cortical localization and speech mechanisms, Broca also carefully worked out skull and scalp localization for underlying cortical regions. In 1871, Broca treated a man who had sustained a scalp laceration from a blow to the head without loss of consciousness or skull fracture. The patient exhibited a nonfluent aphasia about 1 month after injury and became progressively obtunded and eventually comatose. Suspecting an intracranial abscess, Broca trephined at the region of the left third frontal convolution and drained an epidural abscess. The patient improved transiently but died a few days later. Autopsy showed a left-sided, predominantly frontal purulent meningoencephalitis. Broca's other neurosurgical contributions included various surgical cases, methods for scalp localization of the cerebral convolutions, extensive studies of skull and brain abnormalities, thermoencephalography, and the stimulation of younger surgical colleagues and neurologists to make practical use of cerebral localization. 
Coronary restenosis: what have we learned from angiography? Coronary restenosis remains a major problem for interventional cardiology not only by virtue of its frequency, but also because of the current inability to prevent it. Symptomatic status and non-invasive evaluation have been used to study restenosis, but both lack specificity and sensitivity, particularly in patients with multivessel disease. Angiography remains the reference standard. Several arbitrary definitions have been used, some related to visual estimates of coronary stenosis and others to quantitative angiographic techniques. In another approach, linear modeling is used to assess minimal luminal diameter of lesions on restudy. Although angiographic studies have been essential in the study of restenosis, questions concerning the underlying mechanism and pathophysiology remain. The development of animal models that closely resemble human restenosis should allow evaluation of pathophysiologic mechanisms and development of new strategies to prevent the problem. 
Mortality due to shigellosis: community and hospital data. Almost all fatal cases of shigellosis occur in developing countries, and data on mortality are generally compiled from three sources: investigations of epidemics caused by Shigella dysenteriae type 1, surveillance of endemic diarrheal disease, and reports from hospitals. Attack rates during epidemics of dysentery due to infection with S. dysenteriae type 1 have ranged from 1% to 33%, and case-fatality rates have ranged from 1% to 7%. In Matlab, a rural district in Bangladesh, most diarrhea-related deaths and approximately 25% of all deaths among children 1 through 4 years of age are attributable to dysentery. In 1984, an epidemic of dysentery was associated with a 42% increase in the death rate in that age group. At the Dhaka Treatment Centre of the International Centre for Diarrhoeal Disease Research, Bangladesh, the fatality rate for 970 inpatients with shigellosis was 11% in 1988, with most deaths occurring among malnourished children who were infected with Shigella flexneri. Control of mortality from shigellosis will require prevention of epidemic S. dysenteriae type 1 disease and endemic S. flexneri infections in children who live in countries with a high prevalence of malnutrition. 
Diclofenac delays healing of gastroduodenal mucosal lesions. Double-blind, placebo-controlled endoscopic study in healthy volunteers. The effects of the water-soluble and delayed-release formulations of a nonsteroidal antiinflammatory drug, diclofenac, on the healing of gastroduodenal mucosal lesions were compared in a double-blind, double cross-over, placebo-controlled endoscopic study conducted in 14 healthy volunteers. Severe endoscopic lesions (petechiae, erosions, ulcers, and esophageal candidiasis) were found only in the group taking the soluble formulation of diclofenac (P less than 0.05 vs placebo). The endoscopic healing of biopsies at one week was delayed by both preparations in comparison to placebo (P less than 0.05 vs placebo). Neither formulation produced significantly more histological inflammation or minor endoscopic lesions (erythema, red striae) than placebo. Both formulations were equally well tolerated and produced no more symptoms than placebo. This study suggests that soluble diclofenac acts topically to delay gastroduodenal healing and produce gastroduodenal injury; it thus provides a model for future studies of the production, perpetuation, and healing of peptic lesions. 
Auriculotemporal syndrome following the preauricular approach to temporomandibular joint surgery. Forty-seven joints in 28 patients were examined 4 months to 10 years after temporomandibular joint (TMJ) surgery via a modified preauricular approach. Many patients had undergone multiple procedures. None of the patients had any subjective or objective evidence of auriculotemporal syndrome (ATS), although patients in previous studies with more extensive incisions have demonstrated ATS. It was concluded that ATS is an unlikely complication following TMJ surgery. A small incision without an oblique superior extension may further reduce the risk. 
Left ventricular hypertrophy: impact of calcium channel blocker therapy. Left ventricular hypertrophy (LVH) of the concentric type is the classic cardiac adaptation to sustained arterial hypertension. Data from the Framingham cohort have shown that patients with LVH have a severalfold higher risk of sudden death, acute myocardial infarction, and other cardiovascular morbidity than those with normal hearts. Common sequelae of LVH are ventricular ectopy, impaired ventricular contractility, myocardial ischemia, and decreased left ventricular filling. The benefits of antihypertensive therapy should not be limited to lowering arterial pressure, but should extend to preventing or reducing target organ damage. A variety of antihypertensive agents, such as calcium channel blockers, angiotensin-converting enzyme inhibitors, antiadrenergic drugs, and, to a lesser extent, beta blockers, have been shown to reduce LVH and to improve left ventricular filling. We have shown that calcium channel blockers diminish ventricular ectopy in parallel with the reduction of LVH, whereas antihypertensive therapy with diuretics neither reduced LVH nor suppressed ventricular ectopy, although it lowered arterial pressure to a similar extent. Whether or not these cardiac changes with antihypertensive therapies will improve cardiovascular morbidity and mortality in patients with LVH remains to be documented. 
Intrarenal pancreatic cyst. A case report of intrarenal true cyst of the pancreas is presented. The patient presented with flank pain. Her diabetes and hypertension were well-controlled. The cause of the pain was presumed to be a cystic renal mass, which proved to be of pancreatic origin only after the pathologic confirmation from the nephrectomy specimen. 
Preeclampsia as the great impostor. In contrast with a generation ago when preeclampsia was misdiagnosed as medical or surgical disease unrelated to pregnancy, today's diagnostic errors are those that consider surgical and medical problems as either pregnancy-induced hypertension or as the hemolysis, elevated liver enzymes, and low platelet count syndrome. Eleven case histories are presented of significant medical or surgical problems that were initially diagnosed as hemolysis, elevated liver enzymes, and low platelet count syndrome or pregnancy-induced hypertension. The incorrect diagnosis of medical-surgical cases during pregnancy often meant that appropriate therapy was delayed and that the rate of iatrogenic prematurity was increased. 
Artificially induced ventricular fibrillation in the management of through-and-through penetrating wounds of the aortic arch: a case report. Case report of a 28-year-old woman in whom a through-and-through knife injury of the aortic arch is presented. The hemorrhage could not be brought under control by conventional means and was handled by artificially induced temporary electric fibrillation of the heart, direct suture, and immediate defibrillation. The patient made an uneventful recovery. 
Profound hypothermia (less than 10 degrees C) compared with deep hypothermia (15 degrees C) improves neurologic outcome in dogs after two hours' circulatory arrest induced to enable resuscitative surgery. Deaths from uncontrollable hemorrhage might be prevented by arresting the circulation under protective hypothermia to allow resuscitative surgery to repair these injuries in a bloodless field. We have shown previously that in hemorrhagic shock, circulatory arrest of 60 minutes under deep hypothermia (tympanic membrane temperature, Ttm = 15 degrees C) was the maximum duration of arrest that allowed normal brain recovery. We hypothesize that profound cerebral hypothermia (Ttm less than 10 degrees C) could extend the duration of safe circulatory arrest. In pilot experiments, we found that the cardiopulmonary system did not tolerate arrest at a core (esophageal) temperature (Tes) of less than 10 degrees C. Twenty-two dogs underwent 30-minute hemorrhagic shock (mean arterial pressure 40 mm Hg), rapid cooling by cardiopulmonary bypass (CPB), blood washout to a hematocrit of less than 10%, and circulatory arrest of 2 hours. In deep hypothermia group 1 (n = 10), Ttm was maintained at 15 degrees C during arrest. In profound hypothermia group 2 (n = 12), during cooling with CPB, the head was immersed in ice water, which decreased Ttm to 4 degrees-7 degrees C. The Tes was 10 degrees C in all dogs during arrest. Reperfusion and rewarming were by CPB for 2 hours. Controlled ventilation was to 24 hours, intensive care to 72 hours. In the 20 dogs that followed protocol, best neurologic deficit scores (0% = normal, 100% = brain death) at 24-72 hours were 23% +/- 19% in group 1 and 12% +/- 8% in group 2 (p = 0.15). Overall performance categories and histologic damage scores were significantly better in group 2 (p = 0.04 and p less than 0.001, respectively). We conclude that profound cerebral hypothermia with CPB plus ice water immersion of the head can extend the brain's tolerance of therapeutic circulatory arrest beyond that achieved with deep hypothermia. 
Dependency of the pulsed Doppler-derived transmitral filling profile on the sampling site. In previous reports that evaluated pulsed Doppler transmitral filling, the sampling site has varied; we examined the effect of the sample volume location on Doppler measurements. Studied were 97 patients: 58 with normal echocardiograms, 20 with mitral regurgitation, and 19 with miscellaneous cardiac diseases. Transmitral filling was recorded at the mitral anulus and at the left atrial and left ventricular (LV) sides of the mitral tips. As the sample volume was moved from the mitral anulus to the LV side, the peak velocity and time-velocity integral of early diastole increased (40.6 +/- 13.8 versus 59.0 +/- 19.0 cm/sec, 5.26 +/- 1.65 versus 8.35 +/- 2.37 cm; p less than 0.001) as did those of late diastole (48.7 +/- 11.5 versus 57.5 +/- 17.0 cm/sec, 3.48 +/- 0.97 versus 4.59 +/- 1.39 cm; p less than 0.001). The late-to-early diastolic peak velocity and time-velocity integral ratios and the late-to-total diastolic time-velocity integral ratio decreased (1.33 +/- 0.51 versus 1.06 +/- 0.41, 0.71 +/- 0.24 versus 0.58 +/- 0.19, 0.40 +/- 0.09 versus 0.36 +/- 0.08; p less than 0.001). The dependency of these indices on the sampling site was in the same degree in all three groups. However, the peak filling rate normalized to mitral stroke volume (4.71 +/- 1.43 versus 4.63 +/- 1.32 l/sec; p = NS) was not influenced by the sample volume location; thus this parameter may be more reliable for assessing LV filling. 
Hemorrhagic cardioembolic stroke: is anticoagulation absolutely contraindicated? Hemorrhagic cerebral embolism should not be considered an absolute contraindication to immediate low-dose systemic anticoagulation. Low levels of anticoagulation may give some protection from recurrent embolism while minimizing the risks of intracranial bleeding. Until further studies are available, these decisions must be made on a case-by-case basis, supported by limited scientific information. 
Laparoscopic cholecystectomy: 111 consecutive cases. Laparoscopic cholecystectomy removes the gallbladder through three or four puncture wounds in the abdominal wall. The technique reduces the recuperative time to full activity, from as long as 4 wk to as little as 3 days, compared with conventional cholecystectomy. We herein present our initial experience with this procedure. In this series of 111 laparoscopic cholecystectomies, there were no mortalities and only one morbidity. Thirty-nine patients (35%) had a history of prior abdominal surgery. Fourteen underwent laparoscopic lysis of adhesions. Intraoperative cholangiograms were performed in 24 patients (21%), demonstrating choledocholithiasis in three. Two of the three patients underwent postoperative endoscopic retrograde cholangiopancreatography (ERCP); in the other, laparoscopic common bile duct exploration was performed. In each case, the common bile duct (CBD) was completely cleared of stones. Incidental laparoscopic appendectomy was also performed in three patients. The average time for completion of laparoscopic cholecystectomy in cases of chronic cholecystitis was 40 min. If the gallbladder was acutely inflamed, the procedure took a mean of 126 min. This series had a higher percentage of patients (19%) with acute cholecystitis then previously reported; therefore, the 2% conversion rate in this series emphasizes the broad applicability of the technique. The average length of stay in the hospital was 1.4 days, and patients returned to work in about 7 days. 
Liver glutathione and cytochrome P450 activity in experimental infection: study of the relative effects of infectious stress and malnutrition. OBJECTIVE: To study the effects of infection and malnutrition on liver glutathione and cytochrome P450 (P450) in rats. DESIGN: Controlled experimental groups (12 groups). ANIMALS: Adult male Sprague-Dawley rats. INTERVENTIONS: Experimental endocarditis, pyelonephritis, or peritonitis were caused. Controls included free-fed rats and sham-operated rats, pair-fed to infected animals. Infection was verified by tissue culture. Rats were killed 3 days (acute infection) or 10 days (chronic infection, except endocarditis) after the induction of infection. RESULTS: Sham rats had lower liver weights, liver/body weight, and liver glutathione values than controls. Infected rats had larger liver weights and liver/body weight ratios and liver glutathione content than shams, and larger liver/body weight ratios than controls (acute infection). Infected rats had lower P450 values than both shams and controls. CONCLUSION: The malnutrition associated with infection caused decreased liver weight and glutathione content. Infection increased the liver weight, and liver glutathione content, but caused severe reduction in liver P450. If the same finding is true in infected patients, it could have consequences for the management of such patients. 
Metsovo lung outside Metsovo. Endemic pleural calcifications in the ophiolite belts of Greece. Endemic PCs and high incidence of malignant mesothelioma from household use of asbestos have been reported in Metsovo in northwestern Greece ("Metsovo lung"). In the present study, we present similar findings in six more areas of Greece. Like Metsovo, all these areas are located within ophiolite belts. Like Metsovo, material similar to "Metsovo whitewash" has been used for various domestic uses. Asbestos fibers (chrysotile, antigorite and tremolite) were found in three of the six areas. Also, in two, MPM has been diagnosed. These findings suggest that "Metsovo lung" occurs in several areas of Greece and has similar etiology and epidemiology. 
Validation of continuous radionuclide left ventricular functioning monitoring in detecting silent myocardial ischemia during balloon angioplasty of the left anterior descending coronary artery. Silent myocardial ischemia has been inferred from transient ST-segment depression during continuous electrocardiographic monitoring. Recently, continuous ambulatory monitoring of left ventricular (LV) function using a radionuclide technique (VEST) has demonstrated episodes of significant silent LV dysfunction in the absence of electrocardiographic changes. To validate the demonstration of silent LV dysfunction with this technique, 12 men were studied during percutaneous transluminal coronary angioplasty. A total of 18 left anterior descending coronary artery balloon inflations were performed. Balloon inflations at 8 +/- 2 atm (4 to 10 atm) lasted 70 +/- 16 seconds. Seventeen of 18 inflations were associated with a decrease in LV ejection fraction greater than 0.10. Mean LV ejection fraction decreased from 0.53 +/- 0.08 to 0.28 +/- 0.11 (p less than 0.0001). In contrast, there was pain in only 10 inflations and ST-segment changes in 7. LV dysfunction was associated with a minimal increase in end-diastolic volume (4 +/- 3%, p less than 0.003), and a major increase in relative end-systolic volume (69 +/- 43%, p less than 0.001). These data suggest that continuous monitoring of LV function with the VEST can sensitively detect silent ischemic decreases in LV function occurring during angioplasty, and provide further validation of the use of this technique for detecting silent myocardial ischemia. 
The metabolic bone disease of primary sclerosing cholangitis. The incidence and severity of osteopenic bone disease in primary sclerosing cholangitis is poorly defined. Clinical, biochemical and radiographic assessment and bone mineral density measurements of the lumbar spine were carried out in two groups of patients. Group 1 consisted of 30 patients with advanced primary sclerosing cholangitis; group 2 consisted of 18 patients with newly diagnosed primary sclerosing cholangitis. Only one patient had bone pain. All patients were normocalcemic; two had elevated serum parathormone levels. Fourteen patients (47%) from group 1 but no patients from group 2 had low serum 25-hydroxyvitamin D levels. Mean bone mineral density was significantly reduced in group 1 patients (0.97 +/- 0.04 gm/cm2) compared with age-matched and sex-matched controls (1.25 +/- 0.01 gm/cm2, p less than 0.0001), and in 15 patients (50%) bone mineral density was below the fracture threshold (0.98 gm/cm2). The bone mineral density in group 2 was not significantly different from controls, and no patient was below the fracture threshold. In neither group did bone mineral density correlate with serum bilirubin, 25-hydroxyvitamin D, fecal fat excretion, previous drug therapy or the presence of chronic ulcerative colitis. Histomorphometrical examination of bone from four group 1 patients showed increased bone resorption, reduced bone formation, moderate-to-severe osteopenia and no osteomalacia. In conclusion, severe osteopenic bone disease is common in advanced primary sclerosing cholangitis and, like that seen in other cholestatis diseases, is consistent with osteoporosis. 
Left ventricular performance during propofol or methohexital anesthesia: isotopic and invasive cardiac monitoring. Using gated radionuclide ventriculography and invasive cardiac monitoring, the effects of propofol and methohexital on left ventricular volumes and function were investigated in 22 unpremedicated patients (ASA physical status III, 50-78 yr) with chronic coronary artery disease (NYHA class II-III). Anesthesia was induced with either propofol or methohexital (2 mg/kg), followed by a maintenance infusion of 100 micrograms.kg-1.min-1. Vecuronium (0.05 mg/kg) was administered and ventilation (FIO2, 1.0) was manually controlled (FECO2, 0.04-0.05). Data acquisitions were serially obtained over 15 min. Propofol and methohexital anesthesia caused an average 15% decrease in mean arterial pressure, associated with a 20% decrease in cardiac index without a decrease in systemic vascular resistance index. It is interesting that the determinants of these hemodynamic effects were different. Heart rate did not change during propofol infusion despite the decrease in mean arterial pressure, whereas heart rate increased during methohexital infusion. In the propofol group, the decrease in cardiac index was associated with decreases in indicators of preload (end-diastolic volume and pulmonary capillary wedge pressure), whereas end-systolic volume and global ejection fraction did not change statistically. In the methohexital group, the decrease in cardiac index was associated with a decrease in global ejection fraction and an increase in end-systolic volume, whereas indicators of preload remained unchanged. It is concluded that methohexital reduces left ventricular performance. In contrast, propofol preserves left ventricular performance despite a likely negative inotropic effect. 
Chemical shift artifact: dependence on shape and orientation of the lipid-water interface. On magnetic resonance images, chemical shift artifact (CSA) can be seen at a planar lipid-water interface oriented within the plane of the phase-encoding and section-select directions (ie, perpendicular to the frequency-encoding direction). Phantoms and a clinical case were used to demonstrate that when a lipid-water interface is curvilinear (eg, spherical) or planar but not oriented along the section-select direction, CSA may be absent or diminished. This effect can be seen at interfaces of normal structures (kidneys, bladder) as well as at interfaces with pathologic lesions such as lipid-containing dermoids. Not only is this effect dependent on section thickness, field of view, matrix size, and receiver bandwidth, but it is also strongly dependent on the orientation of the interface with respect to the section-select direction. Knowledge of the factors that can alter CSA is important since it is used to distinguish lipid-containing from nonlipid-containing structures of similar signal intensities. 
Exercise echocardiography as a screening test for coronary artery disease and correlation with coronary arteriography. We evaluated exercise echocardiography as a screening test for coronary artery disease in 228 patients, all of whom underwent subsequent coronary angiography. After an echocardiogram at rest was obtained, each patient performed maximal, symptom-limited, upright treadmill exercise, immediately after which repeat imaging was performed. The exercise echocardiogram was abnormal if any segment failed to become hypercontractile with exercise, and these regional wall motion abnormalities were used to predict the extent and distribution of coronary disease. At subsequent angiography, coronary stenosis was defined as significant if luminal diameter was reduced greater than or equal to 50%. Compared with electrocardiography, exercise echocardiography was more sensitive (97 vs 51%) and specific (64 vs 62%), and had higher positive (90 vs 82%) and negative (87 vs 28%) predictive accuracies. Exercise echocardiography was also highly predictive of the extent (no, 1-, 2- or 3-vessel disease) and distribution (which vessel) of coronary stenoses. It is concluded that exercise echocardiography is an excellent screening test for the presence, extent and distribution of coronary artery disease. 
Potential of parenteral and enteral nutrition in inflammation and immune dysfunction: a new challenge for dietitians [published erratum appears in J Am Diet Assoc 1991 Aug;91(8):913] Advances in the understanding of the interrelationship between immunology and nutrition indicate that immune dysfunction in critically ill patients is linked with nutrient deficiency and abnormal acute-phase response to illness. Immune dysfunction requires special nutrition therapy and metabolic support; immunoregulation by nutrition manipulation may lead to specific immunotherapies for defined groups of patients. The success of dietary strategies must be measured not only by metabolic indexes but also by effects on immune function. The health profession must combat immune dysfunction and inflammation for the sick and frail patients under its care. 
Cerebrovascular events after myocardial infarction: analysis of the GISSI trial. Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico (GISSI). OBJECTIVES--To describe the epidemiology of cerebrovascular events in patients given or not given fibrinolytic treatment and to assess the prognostic implications and risk factors. DESIGN--Case series derived from the GISSI randomised trial. SETTING--176 coronary care units in Italy giving various levels of care. PATIENTS--5860 patients with acute myocardial infarction treated with 1.5 million units of intravenous streptokinase and 5852 patients not given fibrinolytic treatment. MAIN OUTCOME MEASURES--Cerebrovascular event, sex, age, blood pressure, history of previous infarct, site of infarction, and Killip class. RESULTS--99 of 11,712 patients (0.84%) had a cerebrovascular event. Older age, worse Killip class, and anterior location of infarction seemed to be risk factors for cerebrovascular events (40/3201 aged 65-75 v 42/7295 aged less than 65, odds ratio 2.18; 9/437 class 3 v 55/8277 class 1, 1.81; and 57/4878 anterior v 24/4013 posterior, 1.96). No significant difference was found in the rate of cerebrovascular events between patients treated with streptokinase and controls (45/5852 (0.92%) streptokinase v 54/5860 (0.77) control). More patients in the streptokinase group than in the control group had cerebrovascular events (especially haemorrhagic strokes) on day 0-1 after randomisation (27 streptokinase v 7, control), although this was balanced by late events in control patients (54 streptokinase v 45 control at one year). The mortality of patients who had a cerebrovascular event was higher than that of those who did not (47% (47/99) v 11.6% (1350/11,613]. CONCLUSIONS--Although the incidence of cerebrovascular events complicating myocardial infarction was low, they increased morbidity and mortality. Treatment with streptokinase did not significantly alter the incidence, but age and poor haemodynamic state were associated with an increased risk. 
Treatment of 813 zygoma-lateral orbital complex fractures. New aspects. A 10-year experience with surgical treatment of 813 zygomalateral orbital complex fractures is reviewed. Regardless of the type or severity of the fracture pattern, concomitant fractures of the orbital floor and rim were approached exclusively through the transconjunctival approach without a lateral canthotomy. The advantages of this approach compared with the subciliary access are the avoidance of a visible scar and markedly reduced incidence of postoperative lower eyelid complications such as ectropion and edema. Implants of lyophilized dura or cartilage and autogenous bone were used to reconstruct orbital floor defects. Malar asymmetry is a frequent complication of zygoma fractures resulting from inadequate three-dimensional reduction. Methods for accurate reduction and stabilization, indications for closed and open reduction, and management of the fractured infraorbital rim are emphasized. The indications for miniplates vs wire ligatures for the infraorbital rim are discussed. Long-term follow up and evaluation of the results with regard to the fracture pattern, complications, maxillary sinus dysfunction, and facial and orbital symmetry are presented. 
Altered cell-mediated immunity to group A haemolytic streptococcal antigens in chronic plaque psoriasis. The proliferative lymphocyte response to sonicated group A, beta-haemolytic streptococci (Strep-A) was measured by thymidine incorporation in 78 patients with psoriasis (guttate, chronic plaque or both). Lymphocytes from 72 of these patients were also cultured with streptokinase/streptodornase (SK/SD), and 20 of the patients with chronic plaque psoriasis were further tested with PPD, Candida albicans and sonicated Streptococcus mutans, a bacterial type not associated clinically with psoriasis. The median stimulation index (SI) of the psoriasis group to the Strep-A preparation was significantly higher than that of a group of 27 non-psoriatic individuals (P less than 0.05). Within this group, only the patients with chronic plaque psoriasis (n = 42) showed a significantly increased proliferative response compared to the non-psoriatic controls (median SI = 123.8 and 31.9, respectively, P less than 0.01). Although the lymphocyte response of the chronic plaque group to SK/SD was also markedly higher than that of the control group, this difference did not reach statistical significance. In addition, these patients did not show significantly increased responses to any of the other antigens tested, including S. mutans. No correlation was observed between the degree of proliferation to Strep-A and disease extent or activity. Similarly, ASO titres, which were raised in 11 out of 23 guttate and three out of nine chronic plaque psoriasis patients tested, did not correlate with the proliferative responses observed. 
Asymptomatic celiac and superior mesenteric artery stenoses are more prevalent among patients with unsuspected renal artery stenoses. The prevalence of unsuspected renal artery stenosis among patients with peripheral vascular disease has been reported to be as high as 40%, but the prevalence of asymptomatic celiac and superior mesenteric artery stenoses in these patients is not known. The biplane aortograms of 205 male patients who were military veterans and had aneurysms or occlusive disease were independently reviewed, and medical records were studied to determine associated coronary disease, risk factors, and patient outcome. Fifty-six patients (27%) had a 50% or greater stenosis in the celiac or superior mesenteric artery, and seven patients (3.4%) had significant stenoses in both mesenteric arteries. Patients with celiac or superior mesenteric artery stenoses were older (p = 0.002) and had a higher prevalence of hypertension (p = 0.029) than those without significant mesenteric stenoses. Fifty of the 205 patients had significant renal artery stenoses, and 20 had advanced (greater than 75% diameter loss) renal stenoses. Ten of the 20 patients (50%) with advanced renal stenoses had a concomitant celiac artery stenosis, compared to 40 of the 185 patients (22%) who did not have advanced renal stenoses (p = 0.011). In the present study asymptomatic celiac or superior mesenteric artery stenoses were common among male veterans evaluated for peripheral vascular disease, but the prevalence of significant stenoses in both the celiac and superior mesenteric arteries was low. The prevalence of significant celiac stenosis was higher in patients with advanced (greater than 75%) renal artery stenoses who might be considered for prophylactic renal revascularization. Lateral aortography with evaluation of the celiac artery is always appropriate in these patients. 
Lichen sclerosus and squamous hyperplasia of the vulva. A clinical study of medical treatment. One hundred thirty-eight cases of nonneoplastic epithelial disorders of the vulva treated with medical therapy from 1984 to 1988 were evaluated at the University of Florence, Florence, Italy. The 67 cases of lichen sclerosus were treated with testosterone propionate or progesterone ointment for 32 weeks. The 31 cases of squamous hyperplasia were treated with corticosteroid ointment for 16 weeks. The 40 patients with lichen sclerosus associated with squamous hyperplasia were treated with corticosteroid ointment for 12 weeks and then with testosterone propionate ointment for another 20. To evaluate the efficacy of the treatments, the patients were examined before and after therapy. The evaluation took into account the symptoms and gross appearance of the lesions, which were given a score of 1-3. Considering all the cases evaluated, a total regression of symptoms occurred in 82 patients (59.4%), while a partial regression occurred in 37 (26.8%). Furthermore, there was a total regression of gross changes in 68 cases (49.3%) and a partial one in 43 (31.1%). The best results were obtained with squamous hyperplasia, which lichen sclerosus, alone or associated with squamous hyperplasia, yielded less successful results. 
Results of the Duhamel operation in the treatment of idiopathic megarectum and megacolon. The results of the Duhamel operation in patients with idiopathic megarectum and megacolon have been reviewed. Twenty patients (14 males, six females) underwent the Duhamel operation over a 17-year period for this condition. The mean age at operation was 25 years; the mean age of onset of constipation was 3 years; and the mean follow-up period was 4.5 years. All the resected colons were of enlarged diameter. There was agreement between the preoperative radiographs and the operative specimens with regard to which parts of the rectum and colon were dilated. Subjective feelings of well-being were generally improved by surgery, as was bowel frequency in ten patients. Soiling, straining, abdominal pain and distension were, however, common after operation. Early complications were also common and five patients required further surgery for constipation. The Duhamel operation for megarectum and megacolon is characterized by an improved sense of well-being and improved bowel frequency, but it is associated with the persistence of many symptoms and further surgery is often required. 
Acute transient thrombocytopenia associated with cocaine abuse in pregnancy. A case is described of cocaine-induced severe transient thrombocytopenia associated with a hypertensive crisis at 21 weeks' gestation. Liver function tests and coagulation studies were all within normal ranges. Blood pressure was controlled with hydralazine. This clinical presentation, similar to severe preeclampsia, should be considered in the differential diagnosis of acute hypertension and low platelet count, especially in early gestations when preeclampsia is relatively rare. Unlike severe preeclampsia, for which active intervention and delivery are usually selected, cocaine-related hypertension-thrombocytopenia, especially in very premature gestations, may warrant conservative management. 
Successful treatment of adult Henoch-Schonlein purpura with factor XIII concentrate. We report the cases of three adult patients with severe abdominal complications of Henoch-Schonlein purpura who had low activity of factor XIII during the acute phase of the disease. In all three cases, abdominal symptoms and purpura immediately responded to heat-treated, placenta-derived factor XIII concentrate. No adverse effects were experienced. Factor XIII concentrate replacement should be considered as the initial treatment for severe abdominal symptoms in adult Henoch-Schonlein purpura associated with a decreased level of factor XIII activity. 
An evaluation of multiple clinical variables for hypoxia during colonoscopy. One hundred consecutive patients undergoing routine colonoscopy were evaluated for changes in arterial oxygen saturation levels. All of the patients were monitored with the Nellcor N-200 pulse oximeter (Nellcor Incorporated) by finger probe and received supplemental oxygen when SaO2 levels decreased below 90 per cent. Forty patients demonstrated a decrease in SaO2 to less than 90 per cent after intravenous sedation but prior to colonoscopy, 14 patients demonstrated a decrease in SaO2 to less than 90 per cent during colonoscopy, and 46 patients maintained SaO2 levels greater than 90 per cent at all times. No statistical differences were found when these three groups were compared for age, body surface area, drug dosage, smoking history and a history of pre-existing hypertension, diabetes, arrhythmias, angina or myocardial infarction and pulmonary disease. These data indicate that all patients undergoing colonoscopy should be placed on supplemental oxygen. We further recommend continuous cardiac and pulse oximetry monitoring when available. 
Recurrent pneumoperitoneum following vaginal insufflation. The authors report a case of a 24-year-old nulligravida woman who presented to the hospital with complaints of severe abdominal pain and radiographic evidence of pneumoperitoneum. She had two prior nondiagnostic laparotomies for similar complaints and radiographic findings. After a careful sexual history was taken the patient revealed that she had sexual intercourse preceding every similar episode including this one, during which her partner forcefully blew air into her vagina. Pneumoperitoneum associated with vaginal insufflation has been previously reported in two multigravida patients with and without anatomic abnormalities. When pneumoperitoneum is present in the absence of gastrointestinal symptoms or trauma, a meticulous sexual history should be made to avoid unnecessary laparotomies. 
Coronary stenting with a new, radiopaque, balloon-expandable endoprosthesis in pigs. BACKGROUND. Intracoronary stents may be effective when used as "bail-out" devices for acute complications after percutaneous transluminal coronary angioplasty. Furthermore, preliminary reports have demonstrated some promising results with stents with regard to the reduction of restenosis. Several stent devices are available for preclinical and clinical evaluation. The use of these stainless-steel stents has been limited by poor visibility during fluoroscopy and thrombogenicity during the first days to weeks after implantation. We therefore investigated the immediate and short-term effects on arterial patency of a new, radiopaque, balloon-expandable coil stent in normal coronary arteries of pigs. METHODS AND RESULTS. In 10 animals, a stent was placed in two of the three epicardial coronary arteries. During the implantation procedure, the animals received heparin; after the procedure, no antithrombotic drugs were administered. After 1 week (five animals and 10 stents) or 4 weeks (five animals and 10 stents), repeat angiography was performed, followed by pressure-fixation of the coronary arteries for light and electron microscopic examination. Angiographic analysis revealed that all stented coronary segments were patent and without signs of intraluminal defects. Scanning electron microscopy showed complete endothelial covering of all stents within 7 days. Light microscopy showed a reduced tunica media locally under the stent wires, which resulted from exerted pressure. The neointima on top of the stent wires measured 56 microns (range, 42-88 microns) after 1 week and 139 microns (range, 84-250 microns) after 4 weeks. CONCLUSIONS. Results from this study show that this radiopaque endoprosthesis can be safely placed in normal coronary arteries of pigs. After 4 weeks, all stents were patent and there was no need for additional antithrombotic treatment, whereas neointimal proliferation was limited. 
Promoter region of the human platelet-derived growth factor A-chain gene. The platelet-derived growth factor (PDGF) A- and B-chain genes are widely expressed in mammalian tissues and their homodimeric gene products appear to regulate the autocrine growth of both normal and transformed cells. In this study, we analyzed the 5' flanking sequences of the human PDGF A-chain gene to seek elements important to regulating its transcription. The promoter region was exceptionally G + C-rich and contained a "TATA box" but no "CAAT box." The transcription start site was identified 845 base pairs 5' to the translation initiation site by S1 nuclease mapping and by primer extension. Both in vitro transcription and transient expression of the chloramphenicol acetyltransferase gene linked to the PDGF A-chain 5' flanking sequences established that the putative promoter region was active, and RNase H mapping established that the three characteristic mRNAs (1.9, 2.3, and 2.8 kilobases) used the same transcription start site, which was used in normal endothelial cells and in two human tumor cell lines that express high levels of A-chain transcripts. The results established an exceptionally G + C-rich promoter region and a single transcription start site active for each of the three mRNAs of the PDGF A-chain gene. DNA sites of potential importance in mediating the activation of the PDGF A-chain gene in normal cells and in transformed cell lines expressing high levels of PDGF A chain were identified. 
Operative laparoscopy with the Nd:YAG laser in the treatment of endometriosis and pelvic adhesions. A multicenter, prospective trial was initiated to test the effectiveness and safety of the Nd:YAG laser equipped with artificial sapphire contact tips for the laparoscopic treatment of pelvic pain. Ninety-three women were enrolled in the study, 37 with endometriosis alone, 47 with endometriosis complicated by pelvic adhesions, and 9 women with adhesions alone. In over 90% of adhesions and 96% of endometriotic implants the Nd:YAG laser could be delivered to the site and be used to restore normal anatomy. The exception was deep bowel involvement with endometriosis, which was not treated. The majority of women had marked reduction or resolution of their symptoms for up to 12 months postoperatively. We conclude that the use of the Nd:YAG laser is an appropriate method to laparoscopically treat pelvic pain resulting from endometriosis or pelvic adhesions. 
'Designer drugs'. Treating the damage caused by basement chemists. Use of "designer drugs" has created a new dilemma for physicians. Generally, it is possible to recognize symptoms and signs of intoxication that fit a specific class of substances, such as amphetamine-like effects for the phenylethylamines and opioid effects for the fentanyl analogues. Designer compounds have crossed these boundaries, and toxicology laboratories cannot readily identify them. For now, physicians must rely on clinical presentation and treat accordingly. 
High-energy orbital dislocations: the possibility of traumatic hypertelorbitism. In a 4-year period from 1983 to 1987, 7160 patients with blunt injuries were admitted to the Maryland Institute of Emergency Medical Services Systems Shock Trauma Center. Facial injuries occurred in 10 percent of this population. High-energy fractures (characterized by computed tomography) were seen in approximately 10 percent of these patients. In this high-energy group, five cases of high-energy orbital dislocations, some representing examples of traumatic hypertelorbitism, were observed. They represent 1.5 percent of the 342 midface fractures observed and 4.8 percent of the naso-orbital ethmoid fractures observed (105 patients). One additional patient is described who was seen at the UCLA Medical Center for late repair of the condition. High-energy impacts of the upper midface created fractures of both orbits, zygomas, and nasoethmoidal regions permitting lateral transposition, enlargement, and divergence of the orbits. Interorbital, intercanthal, and interpupillary distances were increased, criteria that confirm the diagnosis of hypertelorbitism. Fifty percent of the patients were bilaterally blind, and one patient sustained unilateral blindness. 
Hemorrhage and intracranial hypertension in combination increase cerebral production of thromboxane A2. BACKGROUND AND METHODS: To determine the effects of reduced cerebral perfusion pressures produced by hemorrhage alone or in combination with intracranial hypertension on thromboxane A2 (TxA2) production, we undertook a randomized study in 38 anesthetized, mongrel dogs. Animals were subjected to 30 mins of hemorrhagic shock with normal (group 1) or increased (group 2) intracranial pressure (ICP). Group 1 animals (n = 22) were hemorrhaged to reduce cerebral perfusion pressure to 40 mm Hg for 30 mins. In group 2 (n = 16), cerebral perfusion pressure was reduced by the combination of less severe hypotension and intracranial hypertension (20 mm Hg). Cerebral and systemic hemodynamic measurements were recorded, including cerebral blood flow (sagittal sinus outflow method); ICP; cerebral perfusion pressure; and arterial and cerebral venous concentrations of TxB2 (double-antibody radioimmunoassay technique), the major metabolite of TxA2. Data were obtained at baseline and at the beginning and end of the 30-min shock period. RESULTS: Hemorrhagic shock significantly (p less than .05) decreased cerebral blood flow in both groups. At the beginning of the shock period, cerebral blood flow was higher in group 1 than in group 2 (p less than .05) and venous-arterial differences in TxB2 increased significantly (p less than .05) in group 2, but not in group 1. At the end of the 30-min shock period, venous-arterial levels of TxB2 remained significantly (p less than .05) higher in group 2. CONCLUSIONS: Increased cerebral production of TxA2 during hypotension accompanied by intracranial hypertension may contribute to the severity of neural damage produced by the combination of head trauma and shock. 
Role of oxygen-derived free radicals in myocardial edema and ischemia in coronary microvascular embolization BACKGROUND. Oxygen-derived free radicals are thought to injure the ischemic heart during coronary microvascular embolization. METHODS AND RESULTS. To test this idea, microspheres (15 microns in diameter) were repetitively administered into the left anterior descending coronary artery to cause microvascular embolization in dogs. Myocardial contractile and metabolic dysfunctions were significantly attenuated after treatments with recombinant human superoxide dismutase, an acyl derivative of ascorbic acid (CV3611, 2-O-octadecylascorbic acid), and xanthine oxidase inhibitor (allopurinol). The free radical scavengers and inhibitor enhanced the coronary hyperemic flow response during embolization, and the total number of microspheres causing maximal embolization was increased by these drugs. When 8-phenyltheophylline was additionally administered with superoxide dismutase, these beneficial effects were abolished, indicating that coronary effects of these drugs may be due to increased release of adenosine during coronary microvascular embolization. CONCLUSIONS. We conclude that oxygen radicals worsen the ischemic injury in coronary microembolization. 
Genesis of arrhythmias in the failing heart and therapeutic implications. Between 50 and 70% of patients with heart failure die suddenly and unexpectedly before they have deteriorated to New York Heart Association class IV symptoms. It has long been known that ventricular ectopy predicts sudden cardiac death in coronary heart disease, and this has also been shown in dilated cardiomyopathy. It is less certain whether antiarrhythmic drugs reduce this risk and improve prognosis. Supraventricular arrhythmias frequently develop in heart failure of all causes. They nearly always cause symptoms, and the establishment of atrial fibrillation may mark a permanent deterioration. Except for sustained ventricular tachycardia, ventricular arrhythmias are often occult. Hypokalemia and digitalis toxicity may have been precipitated by diuretics or interaction with antiarrhythmic drugs. In coronary heart failure, arrhythmias may be related to scar tissue or ischemia, which may also be responsible in dilated cardiomyopathy. Use of inotropes and inodilators may precipitate arrhythmias, whereas drugs that conserve energy or potassium, such as beta blockers and angiotensin-converting enzyme inhibitors, may prevent them. Since suppression of ventricular arrhythmias has not been shown to prevent sudden death or prolong life in patients with heart failure, it may be that such arrhythmias do not directly presage ventricular fibrillation except in so far as they are markers of a poor prognosis with a risk of sudden death. If so, such arrhythmias are most likely to be suppressed by agents that result in improvement of left ventricular function and, through that, prolongation of life. 
Regimen compliance two years after myocardial infarction. Two-years postinfarction, the effect of a nursing intervention at 30 days postinfarction, and intentions, attitudes, and perceived beliefs of others on regimen compliance of myocardial infarction patients was investigated. The sample was comprised of 51 patients (E = 29, C = 22) who participated in a five-phase study over 2 years. No differences were found between experimental and control groups for regimen compliance to activity, stress, and medication prescriptions. The experimental group was significantly more compliant to the diet prescription than the control group. The control group was significantly more compliant than the experimental group with cessation from smoking. Perceived beliefs of others were predictive of compliance for all regimen prescriptions at 2 years. Attitude was also predictive of compliance with the diet, smoking, and stress regimens. 
High-dose cisplatin with dacarbazine and tamoxifen in the treatment of metastatic melanoma. In an attempt to increase the antitumor effect of cisplatin (50 mg/m2) and dacarbazine (350 mg/m2), each repeated on days 1 to 3 every 4 weeks in patients with metastatic melanoma, tamoxifen was added to the regimen. Before the first course of chemotherapy, the patients received a loading dose of tamoxifen (100 mg orally twice a day for 7 days), followed by a maintenance dose of 10 mg orally twice a day and continued throughout the treatment. Aspirin (325 mg orally every other day) was administered at the same time as the tamoxifen in an attempt to reduce the risk of thromboembolic events. The activity of high-dose cisplatin with dacarbazine and tamoxifen was disappointing. Of 23 evaluable patients, only three responded--an overall response rate of 13% (95% confidence limits, 0% to 27%). These responses consisted of one pathologic complete remission in a patient with nodal metastases, one clinical complete remission in a patient with a very large pelvic mass, and one partial response in another patient with nodal metastases. The duration of responses was 12+, 4, and 4 months, respectively. These data do not support a significant interaction between tamoxifen and cisplatin or dacarbazine. Assuming that tamoxifen is important in the cisplatin, dacarbazine, and carmustine combination, as suggested by others, the most relevant interaction may be between tamoxifen and carmustine. 
Cytologic diagnosis of leukemia and lymphoma. Values and limitations. The value and limitations of the cytologic diagnosis of lymphoma and leukemia using a multiparameter approach, including cytomorphology, immunocytochemistry, and flow cytometry, are discussed. Using these diagnostic modalities, most subtypes of lymphoma and leukemia can be classified accurately. The differential diagnoses of the different disease entities also are presented. 
Left ventricular mass in childhood dilated cardiomyopathy: a possible predictor for selection of patients for cardiac transplantation. To determine the relationship of left ventricular hypertrophy (as assessed by mass) to symptoms and cardiac function in chronic childhood dilated cardiomyopathy, 17 long-term survivors (12 asymptomatic, 5 symptomatic) were studied at a median follow-up of 6.25 years (1.25 to 16.8 years). Left ventricular mass, dimension, wall stress, and contractility (relationship between velocity of circumferential fiber shortening and end-systolic wall stress) were assessed by echocardiography. These data were compared to measurements at the onset of disease. At follow-up, mass decreased significantly from the onset in the asymptomatic patients but remained elevated in the symptomatic patients (101 +/- 35 gm/m2 to 54 +/- 12 gm/m2, p = 0.001; 122 +/- 55 gm/m2 to 198 +/- 115 gm/m2, p = 0.23, respectively). Shortening fraction and contractility were both significantly lower in the symptomatic group compared with the asymptomatic group at follow-up (shortening fraction = 21 +/- 7% vs 29 +/- 5%, p = 0.02; contractility = -0.24 +/- 0.14 circ/sec vs -0.05 +/- 0.11 circ/sec, p = 0.01). Follow-up wall stress was slightly higher in symptomatic patients compared with asymptomatic patients. Three symptomatic patients had progressive hypertrophy and either died or required transplantation. Higher left ventricular mass is associated with the presence of symptoms, depressed contractility, and slightly higher wall stress. Persistence or progression of hypertrophy may be a poor prognostic sign in survivors of childhood dilated cardiomyopathy. Measurement of mass may be useful to indicate the necessity for closer follow-up to select patients for cardiac transplantation before hemodynamic decompensation. 
Granulomatous hypersensitivity to Schistosoma mansoni egg antigens in human schistosomiasis. III. In vitro granuloma modulation induced by immune complexes. Granulomatous hypersensitivity to parasite eggs of Schistosoma mansoni is an important factor in the development of morbidity in chronic schistosomiasis. It has been demonstrated previously that the chronic, well-tolerated, intestinal form of schistosomiasis is associated with the establishment and maintenance of a variety of immunoregulatory mechanisms. We have used an in vitro model of granuloma formation for the purpose of studying the regulation of granulomatous hypersensitivity to S. mansoni egg antigens, mediated by immune complexes (IC). Our results show that the peripheral blood mononuclear cells (PBMCs) from patients with active schistosome infections, when treated with sera from chronic schistosomiasis patients, were able to induce an inhibitory activity on in vitro granuloma formation. Significant modulation of the in vitro granuloma reaction remained after treatment of PBMCs with isolated IC or manufactured IC with soluble egg antigen (SEA) and purified IgG from pooled chronic schistosomiasis sera. In contrast to granuloma modulation stimulated with whole molecule IgG-SEA IC, the incubation of PBMCs with F(ab')2 IgG-SEA IC did not induce any suppression of the granulomatous hypersensitivity to SEA. It appears in this model system that IC may inhibit the activity of granuloma formation by stimulating macrophages to release suppressive mediators. We have demonstrated this possibility by inhibition of prostaglandin activity using indomethacin. The addition of indomethacin to the granuloma culture significantly reduced in vitro granulomatous hypersensitivity to S. mansoni eggs in patients with chronic intestinal schistosomiasis and do so by inducing macrophages to secrete prostaglandins. 
Cushing's disease and cutaneous alternariosis. Alternaria species are common plant pathogens, but a rare cause of human infection. We present a patient with cutaneous alternariosis that revealed a relapse of an old case of Cushing's disease. Immunosuppression following the excessive glucocorticoid production seemed to contribute to the development of dermatosis. We also present a review of the literature on the association of Cushing's disease and cutaneous alternariosis. Our case is unique because the ketoconazole therapy that we used was successful in the treatment of both diseases. 
Esophagocutaneous fistula after anterior cervical spine surgery and successful treatment using a sternocleidomastoid muscle flap. A case report. An esophagocutaneous fistula following anterior cervical fusion is rare. A 61-year-old man had cervical myelopathy because of ossification of the posterior longitudinal ligament of the cervical spine. Anterior decompression of the cervical spine and anterior fusion with strut bone grafting were performed. A second anterior fusion was done because the graft was dislodged after the patient fell out of bed one month after surgery. An esophagocutaneous fistula occurred three months after the second anterior surgery. One of the causes of this esophagocutaneous fistula was considered to be a pressure necrosis of the esophagus because of to projection of the bone graft. Conservative treatment, which consisted of wound drainage and intravenous administration of antibiotics, was tried but was unsuccessful. A good result was achieved by cancellous bone grafting, closure of the esophageal fistula, and transposition of a sternocleidomastoid muscle flap to the interspace between the esophagus and the cervical spine. 
Diazepam binding inhibitor and its processing products stimulate mitochondrial steroid biosynthesis via an interaction with mitochondrial benzodiazepine receptors. A recognition site for benzodiazepines structurally different from that linked to various gamma-aminobutyric acid A (GABAA) receptor subtypes is located on the outer mitochondrial membranes of steroidogenic cells. This protein has been signified to be important in the regulation of steroid biosynthesis. Because of its location it is designated herein as the mitochondrial benzodiazepine receptor (MBR). A putative endogenous ligand for MBR is the peptide diazepam binding inhibitor (DBI), previously shown to displace drugs from MBR and to be expressed and stored in steroidogenic cells rich in MBR. The two model systems used to study steroidogenic regulation by DBI were the Y-1 adrenocortical and MA-10 Leydig cell lines previously shown to be applicable in studies of mitochondrial steroidogenesis. Both cell lines contain DBI as well as DBI processing products, including the DBI fragments that on reverse phase HPLC coelute with the naturally occurring triakontatetraneuropeptide [TTN; DBI-(17-50)] and octadecaneuropeptide [DBI-(33-50)]. When DBI purified from rat brain was added to mitochondria prepared from Y-1 and MA-10 cell lines, it increased the rates of pregnenolone formation in a dose-related manner. In both cell lines, maximal stimulation (3-fold) of mitochondrial steroidogenesis was obtained with 0.33 microM DBI, with an EC50 of approximately 0.1 microM. However, DBI concentrations higher than 1 microM caused a smaller increase in pregnenolone formation. Flunitrazepam, a benzodiazepine that binds with high nanomolar affinity to MBR, was recently shown to act as an antagonist of ACTH and LH/hCG-induced steroidogenesis and was found in the present studies to inhibit DBI-stimulated mitochondrial steroidogenesis. During the incubation with mitochondria, DBI was partially processed to different peptide fragments, including octadecaneuropeptide and TTN. To determine whether DBI processing products influence mitochondrial steroid biosynthesis, several DBI fragments and other peptides structurally unrelated to DBI were tested. Among these, only TTN stimulated mitochondrial steroid synthesis in a dose-dependent manner similar to DBI. 
Use of centrally acting sympatholytic agents in the management of hypertension. Considerable evidence suggests that hyperactivity of the sympathetic nervous system is implicated not only in the pathogenesis of essential hypertension but also in several blood pressure-independent complications of essential hypertension. Even with the advent of newer antihypertensive agents, including angiotensin-converting enzyme inhibitors and calcium antagonists, the centrally acting sympatholytics (alpha 2-adrenoceptor agonists) remain a valuable group of medications for the management of hypertension of all grades of severity. Their advantages include efficacy; rarity of contraindication; absence of most metabolic and serious side effects; favorable effects on systemic hemodynamics; lack of true tolerance and infrequency of volume expansion-related pseudotolerance; suitability in the elderly, in isolated systolic hypertension, and in patients with various concomitant conditions, such as diabetes mellitus; ability to reverse left ventricular hypertrophy; and relative low cost. The long duration of action of guanfacine hydrochloride, the most recently marketed agent, and of the transdermal formulation of clonidine is an especially commendable feature. The principal disadvantages of this class of medications are an overlap between the therapeutic dosage and that producing sedation and dry mouth and the potential to cause the discontinuation syndrome and sexual dysfunction. 
Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. MRC Vitamin Study Research Group. A randomised double-blind prevention trial with a factorial design was conducted at 33 centres in seven countries to determine whether supplementation with folic acid (one of the vitamins in the B group) or a mixture of seven other vitamins (A,D,B1,B2,B6,C and nicotinamide) around the time of conception can prevent neural tube defects (anencephaly, spina bifida, encephalocele). A total of 1817 women at high risk of having a pregnancy with a neural tube defect, because of a previous affected pregnancy, were allocated at random to one of four groups--namely, folic acid, other vitamins, both, or neither. 1195 had a completed pregnancy in which the fetus or infant was known to have or not have a neural tube defect; 27 of these had a known neural tube defect, 6 in the folic acid groups and 21 in the two other groups, a 72% protective effect (relative risk 0.28, 95% confidence interval 0.12-0.71). The other vitamins showed no significant protective effect (relative risk 0.80, 95% Cl 0.32-1.72). There was no demonstrable harm from the folic acid supplementation, though the ability of the study to detect rare or slight adverse effects was limited. Folic acid supplementation starting before pregnancy can now be firmly recommended for all women who have had an affected pregnancy, and public health measures should be taken to ensure that the diet of all women who may bear children contains an adequate amount of folic acid. 
Epitope map of neurofilament protein domains in cortical and peripheral nervous system Lewy bodies. A subset of demented elderly patients exhibit large numbers of cortical intraneuronal inclusions similar to the neurofilament (NF)-rich Lewy bodies (LB) found in pigmented subcortical neurons of patients with Parkinson's disease (PD). Because these cortical inclusions may contribute to the emergence of cognitive impairments in afflicted individuals, the authors mapped the distribution of NF epitopes in these so-called cortical LBs. This was done using ethanol-fixed tissues and a large library of monoclonal antibodies (MAbs) with well-characterized binding specificities to various regions of each NF triplet protein. Cortical LBs were examined by light, confocal, and electron microscopy, and they were compared with the subcortical LBs of PD and LBs in the peripheral nervous system (PNS). Monoclonal antibodies specific for the rod regions of each of the three NF subunits, or for phosphate-dependent and independent antigenic sites in the tail region of the high- (NF-H) and middle- (NF-M) molecular weight (Mr) NF subunits as well as other MAbs to the extreme COOH terminus of NF-L and NF-M or the head region of NF-M labeled a variable number of cortical LBs. Remarkably one of these anti-NF MAbs, RMO32, which recognized a phosphorylated epitope in the tail region of NF-M, immunolabeled nearly all cortical LBs, whereas each of the other anti-NF MAbs never labeled more than 10% of ubiquitin- or RMO32-positive cortical LBs. Further LBs in the PNS resembled those in the central nervous system (CNS) in their immunologic properties, and LBs in both sites were dominated by filamentous aggregates at the ultrastructural level. These findings suggest that NF proteins are profoundly altered during their incorporation into cortical and PNS LBs. Further the authors here identified immunologic and ultrastructural properties common to cortical LBs, PNS LBs, and classic substantia nigra LBs in PD. The accumulation of filamentous, perikaryal inclusions rich in NF proteins at diverse sites in the CNS and PNS of patients with a variety of neurodegenerative disorders suggests a widespread disruption of NF metabolism or transport. 
Preventing fetal damage from sexually transmitted diseases. The STDs threaten the reproductive health of women in many ways, ranging from premature births through congenital infections and death. An understanding of the natural history of these diseases permits timely interventions which can mitigate the perinatal damage caused by these infections substantially. Ideally, primary prevention or safer sex will be adopted by sexually active women, thereby reducing the morbidity not only for their offspring but for themselves as well. Antiviral therapy is not yet available for minimizing any hazard of fetal exposure to HPV, HSV, HIV, and hepatitis B viral infections. Early antibiotic therapy should reduce the risk of congenital syphilis and any perinatal hazards associated with chlamydial and gonococcal infections. 
Pharmacology of antimigraine drugs. The drugs used in migraine therapy can be divided into two groups: agents that abort an established migraine attack and agents used prophylactically to reduce the number of migraine attacks. Both groups have drugs that are specific for migrainous headaches and that are non-specific, and are used to treat the accompanying headache (analgesics), vomiting (anti-emetics), anxiety (sedatives and anxiolytics), or depression (antidepressants). The main drugs with specific action on migraine include ergot alkaloids (ergotamine, dihydroergotamine), agonists (sumatriptan) or partial agonists (methysergide) at a specific subtype of 5-HT1-like receptors, beta-adrenoceptor antagonists (propranolol, metoprolol), calcium antagonists (flunarizine) and anti-inflammatory agents (indomethacin). The pharmacological basis of therapeutic action of several of these drugs is not well understood. In the case of the ergot alkaloids and 5-HT1-like receptor agonists, however, it is likely that the antimigraine effect is related to the potent and rather selective constriction of the large arteries and arteriovenous anastomoses in the scalp and dural regions. In addition, these drugs inhibit plasma extravasation into the dura in response to trigeminal ganglion stimulation, but it is possible that this effect is related to the selective vasoconstriction in the extracerebral vascular bed. The selectivity of the pharmacological effects of these antimigraine drugs (constriction of the extracerebral arteries and arteriovenous anastomoses, poor penetration into the central nervous system and the absence of an antinociceptive effect even after intrathecal administration) strongly suggests that excessive dilatation in the extracerebral cranial vasculature, probably initiated by a neuronal event, is an integral part of the pathophysiology of migraine. 
Perivalvular extension of infection in patients with infectious endocarditis. Perivalvular extension of infection is a not-infrequent and potentially fatal complication of bacterial endocarditis. Because the efficacy of various modalities in the diagnosis of such complications is not well established, a selective review of the published literature on this issue is worthwhile. The electrocardiogram is the easiest study to obtain. It is quite specific in identifying perivalvular extension of infection when conduction system disease is demonstrated but has a low degree of sensitivity overall. Transthoracic two-dimensional echocardiography, transesophageal echocardiography, and color-flow Doppler echocardiography are the most practical and useful techniques for diagnosis of perivalvular extension of infection. Magnetic resonance imaging also appears to be an effective tool in this setting; however, because of a paucity of clinical data, its precise utility has not yet been determined. Nuclear medicine studies and computed tomography play a minimal role. Cardiac catheterization is as useful as the echocardiographic techniques but is invasive, not as readily available, and significantly riskier in terms of complications. An approach to the diagnosis of perivalvular extension of infection is proposed on the basis of the literature review. 
Assessing drugs for the treatment of heart failure. The aims of treatment in patients with heart failure, as with any other condition, are to relieve symptoms and prolong life. A secondary objective is to do so at the lowest possible economic cost. When treatment of the cause of heart failure is possible--which usually means some form of surgery, but could include treatment of a primary disease, such as thyrotoxicosis--then this is obviously the treatment of choice. In patients for whom there is no such definitive treatment, a wide and increasing variety of drugs are available. When new antifailure drugs are to be developed there are therefore two problems: first, to ensure that they are more effective than placebo treatment, and second, to compare them with existing drugs. Both of these tests can present ethical difficulties, for it is unreasonable to withhold established effective treatment in order to conduct a placebo-controlled trial, and when drugs are being compared, it is unlikely that any new medication will be dramatically superior to an old one. The more effective the treatments already available, the harder it becomes to evaluate a new drug. 
The extent and time course of motoneuron involvement in amyotrophic lateral sclerosis. The numbers and relative sizes of motor units have been estimated in 373 muscles of 123 patients with ALS: 74 of the muscles were examined on more than one occasion. The median duration between the onset of symptoms and the initial examination was 12 months; by this time, approximately 90% of the tested muscles showed losses of motor units. The evoked motor unit potentials continued to enlarge in most, but not all, muscles as the disease progressed. Once a muscle became affected by the disease process, the average time-course was such that the motor unit population halved in each 6-month period of the first year and diminished more slowly thereafter. A small proportion of patients was encountered in whom the disease progressed much more slowly and there were occasional large fluctuations in the motor unit estimates suggestive of reversible motoneuron dysfunction. 
Prostacyclin production and mediation of adenylate cyclase activity in the pulmonary artery. Alterations after prolonged hypoxia in the rat. Prostacyclin is a critical mediator of structure and function in the pulmonary circulation, causing both the inhibition of vascular smooth muscle growth and vasodilation via the stimulation of adenylate cyclase. To examine the potential role of alterations in prostacyclin production or mechanism of action in chronic hypoxic pulmonary hypertension, we determined the effects of prolonged (7 d) in vivo hypoxia on in vitro prostacyclin synthesis and mediation of adenylate cyclase activity in rat main pulmonary arteries. In control arteries prostacyclin production exceeded that of prostaglandin (PG) E2 by 25-fold, with 42% originating from the endothelium. Studies utilizing indomethacin revealed that endogenous prostaglandins mediate at least 69% of basal adenylate cyclase activity. Prostacyclin-stimulated enzyme activity was enhanced by exogenous GTP, indicating that this is a receptor-mediated process involving G protein amplification. Comparable dose-related responses to prostacyclin and PGE2 suggest that these agents may activate a common receptor. After 7 d of in vivo hypoxia there was a 2.7-fold increase in in vitro prostacyclin production, with equivalent increases in synthesis in the endothelium and vascular smooth muscle. However, despite this increase there was no change in basal adenylate cyclase activity, and this was associated with attenuated sensitivity of the enzyme to prostacyclin stimulation. Concomitant diminution of the response to beta-adrenergic stimulation, with previously-demonstrated beta receptor downregulation and unaltered postreceptor-mediated activity, suggests that the blunted response to prostacyclin is due to receptor downregulation. Parallel studies of the thoracic aorta indicated that these changes are specific to the pulmonary artery. It is postulated that attenuation of the response of adenylate cyclase to prostacyclin may contribute to the structural changes and hypertension observed in the pulmonary vasculature of the rat with chronic hypoxia. 
Prognostic value of a treadmill exercise score in outpatients with suspected coronary artery disease BACKGROUND. The treadmill exercise test identifies patients with different degrees of risk of death from cardiovascular events. We devised a prognostic score, based on the results of treadmill exercise testing, that accurately predicts outcome among inpatients referred for cardiac catheterization. This study was designed to determine whether this score could also accurately predict prognosis in unselected outpatients. METHODS. We prospectively studied 613 consecutive outpatients with suspected coronary disease who were referred for exercise testing between 1983 and 1985. Follow-up was 98 percent complete at four years. The treadmill score was calculated as follows: duration of exercise in minutes--(5 x the maximal ST-segment deviation during or after exercise, in millimeters)--(4 x the treadmill angina index). The numerical treadmill angina index was 0 for no angina, 1 for nonlimiting angina, and 2 for exercise-limiting angina. Treadmill scores ranged from -25 (indicating the highest risk) to +15 (indicating the lowest risk). RESULTS. Predicted outcomes for the outpatients, based on their treadmill scores, agreed closely with the observed outcomes. The score accurately separated patients who subsequently died from those who lived for four years (area under the receiver-operating-characteristic curve = 0.849). The treadmill score was a better discriminator than the clinical data and was even more useful for outpatients than it had been for inpatients. Approximately two thirds of the outpatients had treadmill scores indicating low risk (greater than or equal to +5), reflecting longer exercise times and little or no ST-segment deviation, and their four-year survival rate was 99 percent (average annual mortality rate, 0.25 percent). Four percent of the outpatients had scores indicating high risk (less than -10), reflecting shorter exercise times and more severe ST-segment deviation; their four-year survival rate was 79 percent (average annual mortality rate, 5 percent). CONCLUSIONS. The treadmill score is a useful and valid tool that can help clinicians determine prognosis and decide whether to refer outpatients with suspected coronary disease for cardiac catheterization. In this study, it was a better predictor of outcome than the clinical assessment. 
Radioimmunodetection of neuroblastoma with iodine-131-3F8: correlation with biopsy, iodine-131-metaiodobenzylguanidine and standard diagnostic modalities. Iodine-131-3F8, a murine IgG3 monoclonal antibody specific for ganglioside GD2 was evaluated by radioimmunoscintigraphy in 42 patients with neuroblastoma. Comparison was made with 131I-metaiodobenzylguanidine (MIBG), 99mTc-methylene diphosphonate (MDP) bone scans, as well as computed axial tomography (CT) or magnetic resonance imaging (MRI). Iodine-131-3F8 detected more abnormal sites (283) than [131I] MIBG (138) or 99mTc-MDP (69), especially in patients with extensive disease. In 20 patients with soft-tissue tumors demonstrated by CT/MRI, 131I-3F8 detected the disease in 18. Upon surgical resection, two tumors interpreted as negative with 131I-3F8 imaging revealed ganglioneuroma, one showing microscopic foci of neuroblastoma. In contrast, 131I-3F8 imaging identified tumors that were confirmed histologically as neuroblastomas. In 26 patients with evidence of marrow disease by antibody scans, 14/26 had confirmation by iliac crest marrow aspirate/biopsy examinations. We conclude that 131I-3F8 scintigraphy has clinical utility in the management of patients with neuroblastoma by improving the sensitivity of tumor detection. 
Prognostic significance of the number of metastatic lymph nodes in patients with gastric cancer. To confirm the prognostic significance of the number of the metastatic lymph nodes (MLN) in cases of gastric cancer, the results of surgical treatment of 668 patients with primary gastric cancer were analyzed retrospectively. Five-year survival rates were calculated with reference to the number of MLN, namely, none (89.2%), one to three (77.4%), four to six (55.8%), and seven or more (36.2%). Furthermore, even when the cancer had invaded the serosa, 5-year survival was significantly more frequent in patients with one to three MLN (71.7%) than in those with four to six (35.5%) or more than six (31.5%) (P less than 0.01), and the 5-year survival was close to that of patients with no MLN (70.5%). Not only qualitative but also quantitative evaluation of lymph node metastasis is essential for estimating the prognosis of patients with gastric cancer. 
Culture, illness, and the biopsychosocial model. Family medicine has appropriated the biopsychosocial model as a conceptualization of the systemic interrelationships among the biological, the psychological, and the social in health and illness. For all its strengths, it is questionable whether this model adequately depicts the centrality of culture to the human experience of illness. Culture (as meaning system) is not an optional factor that only sometimes influences health and illness; it is prerequisite for all meaningful human experience, including that of being ill. A more adequate model of the relationship between culture and illness would demonstrate the preeminence of culture in the experience of illness among all people, not just members of "exotic" cultures; would view healers as well as patients as dwellers in culture; would incorporate the role of culture as meaning system in linking body, mind, and world; and would promote the significance of the cultural context as a resource for research and therapy. 
von Willebrand factor and factor VIII in renal transplant recipients under immunosuppression with cyclosporine and steroids. Sequential measurements over 4 months in 17 patients. In 17 consecutive cadaver kidney transplant recipients treated with cyclosporine (CsA) and steroids, the median of antigenic and functional levels of von Willebrand factor (vWF) and factor VIII (FVIII) before transplantation were elevated (vWF:Ag: 206%, vWF:RCof: 202%; FVIII:Ag: 248%, FVIII:C: 224%; normal values 50-150%). Sequential measurements after transplantation and during CsA treatment revealed a transient significant increase of median values with highest amounts of vWF:Ag of 362% (2 p less than 0.0001), FVIII:Ag of 398% (2 p less than 0.001) and FVIII:C of 360% (2 p less than 0.0001) (Friedman test). vWF:RCof did not show statistically significant changes. After 4 months, levels of vWF and FVIII comparable to those obtained before transplantation were observed. In univariate statistical analysis no correlation was found between vWF of FVIII on the one hand and plasma creatinine levels, CsA dose or CsA whole blood through levels on the other hand. However, multivariate statistics revealed to some extent a positive influence of CsA blood levels on vWF:Ag levels. Patients with vascular rejection or chronic CsA nephrotoxicity showed significantly lower levels of vWF:Ag as compared with patients without endothelial cell damage in the kidney (2 p less than 0.05). However, the difference in vWF:Ag levels already existed before transplantation. In contrast to recent reports, plasma vWF levels were not indicative of vascular injury in kidney graft recipients nor was the marked elevation of vWF and FVIII associated with thromboembolic complications ascribed to CsA treatment. 
Liver involvement in Alpers disease. Alpers disease consists of diffuse cerebral degeneration manifested as developmental delay, seizures, vomiting, and progressive neuromuscular deterioration, with liver disease and death. We report the clinical course of the liver disease, histologic progression of the hepatic lesions, and etiologic investigations in five patients (four girls, three kinships). All had grown and developed normally until seen at 6 to 36 months of age (mean 20 months), with vomiting (n = 5), progressive hypotonia (n = 3), or seizures (n = 2). All had been given anticonvulsants, including valproic acid in three. Liver disease was noted at a mean age of 35 months (range 9 to 67 months), with hepatomegaly (two patients), abnormal hepatic synthetic function (three) or transaminase values (three), and cirrhosis in one. Patients survived for a mean of 4.6 weeks (range 1 to 8 weeks) after the identification of liver disease; all died of hepatic failure. Results of evaluation for infectious and metabolic causes of liver disease and causes of degenerative neuromuscular disease were negative in all patients. Premortem liver biopsy specimens (n = 3) demonstrated an early lesion consisting of lobular disarray, microvesicular steatosis, periportal acute and chronic inflammation, and individual hepatocyte necrosis. Autopsy findings (n = 5) consisted of macrovesicular steatosis, massive hepatocyte dropout, and proliferation of bile ductular elements, with almost complete replacement of hepatocytes by proliferating bile ductular elements in two patients. Brain showed characteristic neuronal degeneration. We conclude that Alpers disease can be a cause of rapidly progressive liver failure in early childhood. Although the cause of this autosomal recessive disease is not known, it does not appear to be related to peroxisomal dysfunction. 
Vulnerability of nerve fibres to ischaemia. A quantitative light and electron microscope study. In order to learn more about the vulnerability of nerve fibres to ischemia, a quantitative study of nerve fibre abnormalities was performed on biopsy specimens of the superficial branch of the peroneal nerve from 26 patients with vasculitic neuropathy: 20 had necrotizing arteritis, 5 a lymphocytic, and 1 a leucocytoclastic vasculitis on nerve and/or muscle biopsy. The density of myelinated fibres ranged from 25 to 7880 per mm2 (n = 8470 +/- 706 (SD]. There was a marked inequality in the density of nerve fibres between the fascicles of individual nerves with a mean coefficient of variation of 41 +/- 37 (SD) % versus 7.4 +/- 3.0% in controls. Loss of myelinated fibres, which was greater for fibres larger than 7 microns in diameter, was more severe than that for unmyelinated axons. Regeneration, which was assessed by the number of clustered axons, decreased when the density of myelinated fibres decreased, suggesting that severe nerve ischaemia precludes axonal regeneration. Wallerian degeneration affected on average 58% (range 5-100%) and segmental demyelination, mainly of the secondary type, on average 1.94% (range 1-10%) of teased fibres. It was concluded that (1) myelinated fibres are more vulnerable to ischaemia than unmyelinated axons; (2) large myelinated fibres are affected before the smaller ones; (3) segmental demyelination is uncommon in this context; (4) severe nerve ischaemia precludes axonal regeneration. 
The role of endogenous free radical scavengers on tissue recovery in the experimental ulcer model. The role of lipid peroxidation and endogenous oxygen-derived free radical scavengers on ischemia-reperfusion injury and tissue recovery in rat ulcer model corresponding to the gastric histopathology was investigated. Male Wistar rats weighting 200-250 g were heparinized before occlusion of the celiac axis for 1.5 h. Endogenous CuZn-superoxide dismutase (SOD), Mn-SOD, glutathione peroxidase, fumarase, cytochrome c oxidase, and thiobarbituric acid-reactive compounds as lipid peroxidation products were measured in the gastric tissue at 3 h, and 1, 2, 4, and 7 days after release and in the controls (no occlusion). At 3 h after release, erosion of the gastric mucosa was observed, and gastric ulcers beyond the muscularis mucosae were present in the gastric body 2 days later. Seven days after release, gastric ulcers had disappeared. Activity levels for all five enzymes (CuZn-SOD, Mn-SOD, glutathione peroxidase, fumarase, and cytochrome c oxidase) were low for days 1-4 after release and did not return to control levels by the seventh day. It was observed that the ulcer formation, as evidenced by the histopathology, was significantly related to the levels of endogenous CuZn-SOD, Mn-SOD, glutathione peroxidase, fumarase, and cytochrome c oxidase activities. Thiobarbituric acid-reactive compounds were also low through the entire course of ulcer formation. The study concludes that decreases in the levels of these oxygen-derived free radical scavengers may result in the formation of gastric ulcers; however, endogenous free-radical scavengers may not correspond with tissue recovery. Lipid peroxidation may not be related to ulcer formation. 
Comparison of intravenous urokinase plus heparin versus heparin alone in acute myocardial infarction. Urochinasi per via Sistemica nell'Infarto Miocardico (USIM) Collaborative Group. In a randomized trial of the effects on in-hospital mortality of intravenous urokinase plus heparin versus heparin alone, 2,531 patients with acute myocardial infarction in 89 coronary care units were enrolled for greater than 30 months. Patients admitted within 4 hours of the onset of pain were randomized to receive either intravenous urokinase (a bolus dose of 1 million U repeated after 60 minutes) plus heparin (a bolus dose of 10,000 U followed by 1,000 IU/hour for 48 hours) or heparin alone (infused at the same rate). Complete data were obtained in 2,201 patients (1,128 taking urokinase and 1,073 taking heparin). At 16 days, overall hospital mortality was 8% in the urokinase and 8.3% in the heparin group (p = not significant). Among patients with anterior infarction, mortality was 10.3% in the urokinase and 13.9% in the heparin group (p = 0.09; relative risk = 0.73). The incidence of major bleeding (urokinase 0.44%, heparin 0.37%) as well as the overall incidence of stroke (urokinase 0.35%, heparin 0.20%) was similar in the 2 groups. The rates of major in-hospital cardiac complications (reinfarction, postinfarction angina) were also similar. 
Language functions in progressive supranuclear palsy. Language functions were studied in 6 patients with clinically diagnosed progressive supranuclear palsy who conformed to the characteristic pattern of 'subcortical dementia'. Dysarthria, reading difficulties and disturbances of handwriting were present in all patients. Some patients showed additional deficits including visual dyslexia, constructional dysgraphia and an increased rate of self-corrections and misnamings in object confrontation naming. In most instances, the naming errors referred to an object visually similar to the target object, suggesting that visual misperception is the major cause of the naming disorder. It is concluded that a variety of language impairments may develop secondary to other neurological and neuropsychological changes in progressive supranuclear palsy. 
Periodic and chaotic host-parasite interactions in human malaria. It has been recognized since ancient times that malaria fever is highly periodic but the mechanism has been poorly understood. Malaria fever is related to the parasite growth cycle in erythrocytes. After a fixed period of replication, a mature parasite (schizont) causes the infected erythrocyte to rupture, releasing progeny that quickly invade other erythrocytes. Simultaneous rupture of a large number of schizonts stimulates a host fever response. Febrile temperatures are damaging to Plasmodium falciparum, particularly in the second half of its 48-hr replicative cycle. Using a mathematical model, we show that these interactions naturally tend to generate periodic fever. The model predicts chaotic parasite population dynamics at high multiplication rates, consistent with the classical observation that P. falciparum causes less regular fever than other species of parasite. 
Effect of hypotensive epidural anaesthesia on acetabular cement-bone fixation in total hip arthroplasty. We selected 20 matched pairs of patients who had had total hip arthroplasty by the same surgeon using the same cemented technique. Matching was by age, sex, height, weight and diagnosis. One of each pair had received hypotensive epidural anaesthesia, with less than 300 ml blood loss: the other had normotensive general anaesthesia with more than 500 ml of blood loss. Early postoperative radiographs were evaluated independently by three blinded observers, using a scoring criteria which assessed the quality of the cement-bone interface. The results showed that patients who had received epidural anaesthesia had significantly better radiographic scores (p less than 0.02). Our findings suggest that hypotensive anaesthesia facilitates penetration of cement into bone. 
Echocardiographic estimation of critical left ventricular size in infants with isolated aortic valve stenosis. With the current trend to performing surgical valvotomy for infantile aortic stenosis without cardiac catheterization, there is a need to develop echocardiographic criteria for adequacy of left ventricular size. The echocardiograms and catheterization data of all 25 infants less than 3 months of age undergoing aortic valvotomy for isolated aortic valve stenosis from September 1980 through July 1990 were reviewed. Significant differences (p less than 0.05) between the survivors and nonsurvivors were noted for age at operation (30 +/- 28 vs. 3 +/- 1.5 days), mitral valve diameter (10.1 +/- 1.7 vs. 7.7 +/- 1.5 mm), left ventricular end-diastolic dimension (18.4 +/- 6.4 vs. 11.4 +/- 3 mm), left atrial dimensions (15.3 +/- 3.8 vs. 10 +/- 2.4 mm), left ventricular cross-sectional area on the parasternal long-axis echocardiogram (4 +/- 1.9 vs. 2 +/- 1.9 cm2) and angiographically determined left ventricular end-diastolic volume (43 +/- 23 vs. 11 +/- 5 ml/m2). There was no difference with respect to patient weight, body surface area, aortic root dimension or left ventricular ejection fraction. Left ventricular cross-sectional area less than 2 cm2 as measured on the parasternal long-axis echocardiogram was found in 5 of 7 nonsurvivors and 0 of 12 survivors, making this a risk factor for perioperative death (p less than 0.05). Left ventricular end-diastolic dimension less than 13 mm was found in 5 of 6 nonsurvivors and 2 of 17 survivors, making this another risk factor for early mortality (p less than 0.05). 
Compartment syndrome of the thigh with osteogenesis imperfecta. A case report. Compartment syndrome of the thigh has been sporadically reported in the orthopedic literature. A 27-year-old man with osteogenesis imperfecta sustained a femoral fracture with relatively minor trauma and subsequently developed compartment syndrome of the thigh. Fat embolism syndrome and hyperplastic callus developed postoperatively. 
Acute effects of intravenous nicardipine on hemodynamics and cardiac function in patients with a healed myocardial infarction and no evidence of congestive heart failure. Acute effects of intravenous nicardipine (10 micrograms/kg) on systemic hemodynamics and cardiac function were evaluated in 17 patients with a healed myocardial infarction and no evidence of congestive heart failure. Mean New York Heart Association functional class was 1.6 +/- 0.5 (mean +/- standard deviation). Aortic systolic pressure (p less than 0.001) and left ventricular end-diastolic pressure decreased (10 +/- 3 to 8 +/- 3 mm Hg, p less than 0.01), and systemic vascular resistance decreased significantly (p less than 0.001), whereas pulmonary and right atrial pressure and pulmonary arteriolar resistance did not change. Cardiac and stroke indexes showed biphasic changes. Although positive and negative maximal rate of left ventricular pressures decreased significantly (p less than 0.05 and p less than 0.01, respectively), they did not change significantly when aortic systolic pressure was corrected. There was a significant inverse correlation between the negative rate of left ventricular pressure/aortic systolic pressure before nicardipine infusion and its maximal percent increase after infusion (r = -0.56, p less than 0.05), indicating a beneficial effect on diastolic relaxation in patients with impaired diastolic function. Our data show that a low dose (10 micrograms/kg) of intravenous nicardipine exerts a favorable effect on impaired diastolic function, but depresses left ventricular pump function with much less effect on right heart circulation. 
Bioelectric impedance analysis: experience with male patients with cirrhosis. Bioelectric impedance analysis is a new, convenient and portable method used to estimate total body water and to assess body composition in healthy people. We used the tetrapolar bioelectrical impedance analysis method in 58 cirrhotic patients to assess its clinical applicability. Whole-body resistance, reactance and impedance were measured and compared with those of 30 healthy volunteers matched for age and sex. The resistance and impedance values of ascitic cirrhotic patients (resistance = 461 +/- 80 omega; impedance = 462 +/- 80 omega) and nonascitic cirrhotic patients (resistance = 487 +/- 96 omega; impedance = 489 +/- 97 omega) were comparable with the resistance (488 +/- 44 omega) and impedance (491 +/- 44 omega) of controls. However, a significant (p less than 0.05) reduction in whole body reactance was found in patients with ascites and in those without ascites (34 +/- 9 omega vs. 47 +/- 12 omega) as compared with healthy subjects (56 +/- 7 omega). In 10 ascitic patients total body water was determined both before and after paracentesis; the volume of intraperitoneal fluid removed (7.9 +/- 3.8 L) could not be fully accounted for but only detected as an average volume of 1.9 +/- 1.0 L independently of the initial volume of the ascites. Our data clearly demonstrate that tetrapolar bioelectric impedance analysis is not adequate for measuring variations of "compartmentalized" fluid in the abdomen. 
Experimental hepatocellular carcinoma: MR receptor imaging. Relaxation time measurements and magnetic resonance (MR) imaging were performed in three different animal models of hepatocellular carcinoma (HCC). After intravenous administration of asialoglycoprotein-directed arabinogalactan-stabilized ultrasmall superparamagnetic iron oxide (10 mumol Fe/kg receptor agent), T2 of normal liver decreased from 41.6 msec +/- 1.0 to 19.4 msec +/- 1.7 (P less than .05) in rats. T2 of HCC implanted in normal liver or liver with chronic hepatitis was essentially unchanged. These results were similar to those obtained by administration of a reticuloendothelial cell-directed conventional iron oxide; however, the required dose of receptor agent was lower. MR imaging in a woodchuck model of virally induced HCC confirmed the distribution of the hepatocyte-directed agent to regions of functioning and differentiated hepatocytes but not to malignant tumor tissue. The results suggest that MR receptor imaging may play a role in the differentiation between primary liver tumor and functional liver tissue such as that in normal liver hepatitis or regenerating nodules. 
The beneficial effects of early dexamethasone administration in infants and children with bacterial meningitis. BACKGROUND. In experimental models of meningitis and in children with meningitis, dexamethasone has been shown to reduce meningeal inflammation and to improve the outcome of disease. METHODS. We conducted a placebo-controlled, double-blind trial of dexamethasone therapy in 101 infants and children admitted to the National Children's Hospital, San Jose, Costa Rica, who had culture-proved bacterial meningitis or clinical signs of meningitis and findings characteristic of bacterial infection on examination of the cerebrospinal fluid. The patients were randomly assigned to receive either dexamethasone and cefotaxime (n = 52) or cefotaxime plus placebo (n = 49). Dexamethasone (0.15 mg per kilogram of body weight) was given 15 to 20 minutes before the first dose of cefotaxime and was continued every 6 hours thereafter for four days. RESULTS. The demographic, clinical, and laboratory profiles were similar for the patients in the two treatment groups. By 12 hours after the beginning of therapy, the mean opening cerebrospinal pressure and the estimated cerebral perfusion pressure had improved significantly in the dexamethasone-treated children but worsened in the children treated only with cefotaxime (controls). At 12 hours meningeal inflammation and the concentrations of two cytokines (tumor necrosis factor alpha and platelet-activating factor) in the cerebrospinal fluid had decreased in the dexamethasone-treated children, whereas in the controls the inflammatory response in the cerebrospinal fluid had increased. At 24 hours the clinical condition and mean prognostic score were significantly better among those treated with dexamethasone than among the controls. At follow-up examination after a mean of 15 months, 7 of the surviving 51 dexamethasone-treated children (14 percent) and 18 of 48 surviving controls (38 percent) had one or more neurologic or audiologic sequelae (P = 0.007); the relative risk of sequelae for a child receiving placebo as compared with a child receiving dexamethasone was 3.8 (95 percent confidence interval, 1.3 to 11.5). CONCLUSIONS. The results of this study, in which dexamethasone administration began before the initiation of cefotaxime therapy, provide additional evidence of a beneficial effect of dexamethasone therapy in infants and children with bacterial meningitis. 
Evolution of myocardial ischemia and left ventricular function in patients with angina pectoris without myocardial infarction and total occlusion of the left anterior descending coronary artery and collaterals from other coronary arteries. Repeated episodes of myocardial ischemia might lead to progressive impairment of left ventricular (LV) function. This radionuclide study assessed myocardial ischemia and LV function several years after documented coronary occlusion without myocardial infarction. Over 5 years, 24 consecutive patients, who underwent cardiac catheterization for angina pectoris without myocardial infarction, had isolated total occlusion of the left anterior descending coronary artery with well-developed collateral vessels. Five patients were successfully treated by coronary bypass grafting and 3 by coronary angioplasty. Among the 16 medically treated patients, 1 was lost to follow-up and 1 died (extracardiac death). The mean (+/- standard deviation) follow-up (14 patients) was 48 +/- 15 months. At follow-up, 8 patients still had clinical chest pain, 11 received antianginal therapy, 4 patients had no stress ischemia and the other 10 had greater than or equal to 1 sign of stress ischemia. All patients had a normal LV ejection fraction at rest (mean 60 +/- 3%; range 55 to 65%). Collateral circulation preserves LV function at the time of occlusion and, in some cases, prevents the development of myocardial ischemia; in patients with persisting myocardial ischemia after well-collateralized coronary occlusion, LV function is not impaired at long-term follow-up. 
The prognosis of melanoma patients with metastases to two or more lymph node areas. The prognosis of melanoma patients who present with metastatic involvement of two or more noncontiguous lymph node regions before the detection of extranodal metastases has not been previously reported. We identified 21 patients with metastatic melanoma in at least two nodal basins in a review of 175 patients with melanoma undergoing lymphadenectomy at the National Cancer Institute. The median survival time of these patients was 46 months, with 55%, 27%, and 17% of the patients alive 2, 5, and 10 years, respectively, after the second lymphadenectomy. Because the prognosis of melanoma patients with metastases to two or more regional nodal areas appears equivalent to that of patients with metastatic involvement of only one regional node site, lymphadenectomy of the involved groups should be performed with therapeutically curative intent. 
Hereditary sacral agenesis with presacral mass and anorectal stenosis: the Currarino triad. A family with autosomal dominant inheritance of sacral agenesis is described. Ten members were affected; four had associated presacral teratomas and anterior sacral meningoceles, giving rise to serious complications in three, including bacterial meningitis, local recurrence of teratoma and perianal sepsis. Three of those with presacral masses presented initially with anorectal anomalies. Other associated abnormalities included tethering of the cord, hydrocephalus, duplex ureter, hydronephrosis, vesicoureteric reflux, neurogenic bladder, bicornuate uterus, rectovaginal fistula and hereditary spherocytosis. Early diagnosis and surgical excision of a presacral mass is advised to prevent future morbidity and mortality. 
Treatment of leiomyomata uteri with leuprolide acetate depot: a double-blind, placebo-controlled, multicenter study. The Leuprolide Study Group. The purpose of this study was to evaluate efficacy and safety parameters in women with leiomyomata uteri treated with the GnRH agonist leuprolide acetate depot, 3.75 mg intramuscularly every 4 weeks for 24 weeks. One hundred twenty-eight patients were enrolled in a randomized, double-blind, placebo-controlled multicenter study involving 13 investigative centers. Mean uterine volume decreased by 36% at 12 weeks and 45% at 24 weeks of leuprolide therapy. Patients treated with placebo had increased in mean uterine volume of 16% at 12 weeks and 5% at 24 weeks. Seventy-seven percent of leuprolide-treated patients had a more than 25% reduction in uterine volume, compared with 9% of placebo-treated controls. Mean uterine volume returned to pre-treatment size 24 weeks after cessation of leuprolide treatment. The majority of patients had resolution or improvement of their fibroid-related symptoms after 24 weeks of leuprolide treatment. Of 38 leuprolide-treated patients presenting with menorrhagia, 37 (97%) had resolution of this symptom at the time of the final visit. Although 95% of women treated with leuprolide acetate experienced some side effects related to hypoestrogenism, only five patients (8%) terminated treatment prematurely. We conclude that leuprolide acetate depot treatment of leiomyomata uteri is safe and causes significant but temporary reductions in uterine size and fibroid-related symptoms. 
Effect of bile on growth, peritoneal absorption, and blood clearance of Escherichia coli in E coli peritonitis. The effect of intraperitoneal bile on growth, peritoneal absorption, and clearance of Escherichia coli was determined in E coli peritonitis in the rat. In E coli peritonitis, intraperitoneal bacterial counts gradually decreased, whereas they increased (after 2 hours) with subsequent development of bacteremia in E coli plus bile peritonitis. After an intraperitoneal injection of labeled bacteria, blood radioactivity was only initially lower in E coli plus bile peritonitis compared with E coli peritonitis. Clearance from blood was lower in E coli plus bile peritonitis than in E coli peritonitis. Organ localization was similar in E coli peritonitis and E coli plus bile peritonitis with decreased splenic, increased pulmonary, and unchanged hepatic uptakes compared with controls. Impaired peritoneal absorption of bacteria, together with impaired local host defense, is likely to enhance the noxious effect of bile in E coli peritonitis. 
Recombinant interferon-gamma (rIFN-gamma) in dermatology. This paper gives a short review on the function, pharmacokinetics, and therapeutic application of recombinant interferon-gamma (rIFN-gamma) in dermatology. Simultaneously, our own experiences are presented for 57 patients (phase II study) suffering from genital warts (21 patients), psoriatic arthritis (10 patients), psoriasis vulgaris (three patients), malignant melanoma (six patients), bowenoid papulosis (four patients), Behcet's disease (four patients), basal cell carcinoma (six patients), as well as herpes simplex recidivans, epidermodysplasia verruciformis, and mycosis fungoides (one patient each). We conclude that there might be an indication for treatment with rIFN-gamma in genital warts, bowenoid papulosis, Behcet's disease, and microbial infections, such as leprosy and cutaneous leishmaniasis. Even though there are reports of a limited beneficial effect of rIFN-gamma on arthritis and skin lesions in psoriasis, we failed to observe any in 10 patients. The main side effects in our low-dose study (50-100 micrograms/d) were mild fever (78%), fatigue (78%), and myalgia (65%). Laboratory tests revealed an increase in the serum triglyceride level, in particular, in psoriatic patients. 
Hereditary sacral agenesis with presacral mass and anorectal stenosis: the Currarino triad. A family with autosomal dominant inheritance of sacral agenesis is described. Ten members were affected; four had associated presacral teratomas and anterior sacral meningoceles, giving rise to serious complications in three, including bacterial meningitis, local recurrence of teratoma and perianal sepsis. Three of those with presacral masses presented initially with anorectal anomalies. Other associated abnormalities included tethering of the cord, hydrocephalus, duplex ureter, hydronephrosis, vesicoureteric reflux, neurogenic bladder, bicornuate uterus, rectovaginal fistula and hereditary spherocytosis. Early diagnosis and surgical excision of a presacral mass is advised to prevent future morbidity and mortality. 
Extrapleural pneumonectomy, chemotherapy, and radiotherapy in the treatment of diffuse malignant pleural mesothelioma. Malignant pleural mesothelioma has been considered a uniformly fatal disease associated with a median survival of 4 to 18 months. Extrapleural pneumonectomy alone has proved disappointing in the treatment of this disease, as have chemotherapy and radiotherapy. From 1980 to 1990, 31 patients with pleural mesothelioma underwent multimodality therapy that included extrapleural pneumonectomy with resection of the pericardium and diaphragm. The age of the patients was 53.4 +/- 8.6 years; 26 were male. All patients had the pathologic diagnosis reviewed before treatment. At thoracotomy six patients had residual (unresectable) gross disease, and in 23 there was histologic evidence of disease at the resection margin. The perioperative morbidity and mortality rates were 19% and 6%, respectively. The mean length of hospital stay for the 29 patients who survived the operation was 10.9 +/- 3.5 days. Postoperatively 26 patients received cyclophosphamide, doxorubicin, and cis-platinum chemotherapy with or without radiotherapy. The survival rates were 70% at 1 year and 48% at 2 years. Trends toward improved survival in the patients with complete resections approached but did not reach statistical significance. These data suggest that this multimodality protocol can be administered with acceptable morbidity and mortality. Prospective trials are justified to further clarify the role of this approach. 
Adamantinoid basal cell carcinoma. An ultrastructural study. We describe an adamantinoid basal cell carcinoma that has developed in the mucocutaneous border of the upper lip. An ultrastructural study disclosed three types of cells that were morphologically distinct in the tumor nest. Cells of the first type were basically the same as those of ordinary basal cell carcinoma. Cells of the second type showed varying degrees of cytoplasmic content loss in a worm-eaten pattern and seemed to consist of degenerating cells. Cells of the third type possessed a well-developed rough endoplasmic reticulum filled with medium electron-dense fine substance, which was also seen in the extracellular space. In relationship with the histochemical findings, and based on the histogenesis of adamantinoid basal cell carcinoma, we propose that subpopulations of tumor cells undergo spontaneous degeneration and that the spaces of such disappearing cells are refilled with products containing glycosaminoglycans secreted by another subpopulation of the tumor cells. 
Choledochal cyst and biliary atresia in the neonate: imaging findings in five cases. The radiologic findings in five neonates with choledochal cyst associated with extra-hepatic biliary atresia are described. All five patients (age range, 13-72 days) presented with jaundice and acholic stools. In all four patients who underwent sonographic examination, a cystic structure separate from the gallbladder representing the choledochal cyst was shown. The diagnosis of atresia of the distal common bile duct was made preoperatively in all cases by hepatobiliary scintigraphy. Diagnosis was confirmed by surgical findings and was demonstrated by intraoperative cholangiography in four cases. All patients were successfully treated with surgical intervention within 1 month from the time of diagnosis. Early detection of this rare disorder, which may be distinct from choledochal cyst found in children and adults, is important to prevent fatal complications of biliary obstruction. The combined use of sonography and hepatobiliary scintigraphy can correctly identify this subset of patients with persistent neonatal jaundice and provide valuable information for prompt surgical management. 
HBx gene of hepatitis B virus induces liver cancer in transgenic mice. The exact role of hepatitis B virus in the development of liver cancer is not known. The recent identification of a viral regulatory gene HBx suggests a possible direct involvement of the virus whereby the HBx protein, acting as a transcriptional transactivator of viral genes, may alter host gene expression and lead to the development of hepatocellular carcinoma. We have tested this possibility of placing the entire HBx gene under its own regulatory elements directly into the germline of mice. Transgenic animals harbouring this viral gene succumbed to progressive histopathological changes specifically in the liver, beginning with multifocal areas of altered hepatocytes, followed by the appearance of benign adenomas, and proceeding to the development of malignant carcinomas. Male mice developed disease and died much earlier than females. This transgenic animal model appears ideal for defining the molecular events that follow the expression of the viral HBx gene and are responsible for the development of liver cancer. 
Bacterial translocation in trauma patients. Sepsis and multiple system organ failure (MSOF) are major causes of morbidity and mortality in trauma patients. Bacterial translocation induced by hypotension, endotoxemia, or burns is a reproducible phenomenon in the laboratory. The incidence of bacterial translocation to mesenteric lymph nodes (MLNs) in 29 critically ill patients was evaluated to determine its relationship to subsequent sepsis and MSOF. Bacterial translocation was documented in 3 of 4 patients who underwent laparotomy for gastrointestinal (GI) disease. No trauma patient (25 patients), even at second exploration 3-5 days after injury, had a positive MLN culture. Five patients died; 4 trauma patients, one with GI disease. Forty percent of the trauma patients had major complications, predominantly pulmonary infections with gram-negative bacteria. However, infectious complications and outcome were not related to MLN culture results. The classical progression of bacteria from the gut to the bloodstream via the MLNs may require time and gut mucosal injury. The data suggest that bacterial translocation to the MLNs is not a common occurrence in acutely injured trauma patients. 
Optical properties of normal, diseased, and laser photocoagulated myocardium at the Nd: YAG wavelength. Laser photocoagulation of the myocardium effectively destroys arrhythmogenic foci. The purpose of this study was 1) to compare the optical properties of canine myocardium before and after photocoagulation, 2) to compare the canine model with clinical cases by measuring the optical properties of human myocardium, and 3) to assess the optical properties of human myocardial scar and epicardial fat tissue. Measured optical properties were the absorption coefficient, mu a; scattering coefficient, mu s; and scattering anisotropy factor, g. Optical measurements were performed at 1064 nm wavelength on thin plane parallel tissue slices using the integrating sphere method with glass hemispheres on either side of the sample. The study showed 1) an increase of the scattering coefficient by 40% and a two- to threefold increase in reduced scattering coefficient as a result of photocoagulation; 2) that the mu a (0.035 +/- 0.024 mm-1) and mu s (17.9 +/- 3.8 mm-1) of human myocardium were not significantly different from mu a (0.043 +/- 0.021 mm-1) and mu s (17.3 +/- 2.2 mm-1) of canine myocardium, whereas the human g (0.964 +/- 0.005) was slightly different from the canine g (0.974 +/- 0.008); and 3) that the mu a (0.021 +/- 0.016 mm-1) of epicardial fat and mu s (13.8 +/- 1.1 mm-1) of myocardial scar were significantly lower than those of normal myocardium. A dynamic model of laser-tissue interaction incorporating these changes and inhomogeneities is necessary to better describe light distribution during laser photocoagulation. 
Androgen receptor and the testes influence hypertension in a hybrid rat model. The objective of this study was to determine if males with a deficient androgen receptor would develop hypertension when crossed with a hypertensive parent. Female King-Holtzman rats (n = 15), heterozygous for the testicular feminization (Tfm) gene, were crossed with male spontaneously hypertensive rats (SHR), and blood pressure was measured weekly from 5-14 weeks in the F1 hybrid males. Approximately 50% of the F1 hybrid males were Tfm males and androgen receptor-deficient, and 50% were normal. Blood pressure in the parent King-Holtzman males, Tfms, and female rats was also followed for the same time period. The F1 normal male hybrids had a significantly higher (p less than 0.05) systolic blood pressure than the Tfm hybrid males after 12 weeks (195 +/- 8 versus 170 +/- 8 mm Hg, respectively). Blood pressure in the male and Tfm Holtzman rats was 120 +/- 5 mm Hg and 110 +/- 6 mm Hg, respectively. Castration lowered blood pressure by 38 mm Hg in the hybrid males and 27 mm Hg in the Tfm hybrids. Female F1 hybrids also showed a pressure rise above that of female Holtzman controls (155 +/- 6 mm Hg versus 110 +/- 6 mm Hg, p less than 0.01) but lower than the F1 males and Tfm hybrids. Ovariectomized females with testosterone implants did not show an elevation in blood pressure. Plasma electrolytes, norepinephrine, and cholesterol were not significantly different between normal and Tfm hybrid males. The results suggest that the presence of an androgen receptor and a testis-derived factor mediate the blood pressure rise in the hybrid males. 
Tumor cytokinetic response to total parenteral nutrition in patients with head and neck cancers. Refeeding of patients with malignant tumors may induce tumor-cell DNA synthesis. The present study was aimed at evaluating whether induction of altered cell-cycle kinetics could be induced by intravenous total parenteral nutrition (TPN) in tumor biopsies from head and neck cancers. Nine malnourished patients with squamous cell carcinoma in the head-and-neck area were investigated before and after 5-7 d of continuous TPN. Tumor biopsies were taken in both fasted and fed states for determination of 1) ornithine decarboxylase (ODC) activity, which is rate limiting for polyamine synthesis; 2) flow-cytometric-DNA-distribution measurements; and 3) the fraction of proliferating cells expressed as immunohistochemical reactivity with the monoclonal antibody Ki-67. The histopathological differentiation, the fraction of aneuploidic cells, ODC activity, and Ki-67 reactivity were not significantly related to each other, although the number of aneuploidic cells in replicative phases correlated with the number of cells expressing the Ki-67 antigen (r = 0.86, P less than 0.01). Tumor cytokinetics showed no evidence of being changed by TPN administration. 
Preoperative evaluation of the cardiac patient for noncardiac surgery. In summary, obtaining a comprehensive patient history is a critical part of the diagnostic and risk stratification process of the patient with cardiac disease undergoing non-cardiac surgery. Many of the factors associated with perioperative cardiac morbidity are treatable and early and aggressive management appears to have beneficial effects on morbidity and mortality rates. 
Superior vena cava syndrome caused by an intrathoracic plasmacytoma. A case of an extramedullary intrathoracic plasmacytoma causing superior vena cava syndrome is described. Review of the literature on intrathoracic plasmacytomas and superior vena cava syndrome revealed that no similar cases have been described to date. The initial presentation, management, and response to treatment are described. 
Acinar cell carcinoma of the pancreas: a rare cause of left-sided portal hypertension. Isolated splenic vein obstruction with left-sided portal hypertension is a rare clinical condition. Owing to the close relationship of the splenic vein and the pancreas, this rare phenomenon is usually secondary to pancreatic inflammation or neoplasm. Acinar cell carcinoma has long been recognized as a distinctive, rare type of pancreatic carcinoma. A case of isolated splenic vein obstruction with left-sided portal hypertension secondary to acinar cell carcinoma of the pancreas, which we are reporting here, is thought to the first documented in the literature. 
Proteinase-resistant prion protein accumulation in Syrian hamster brain correlates with regional pathology and scrapie infectivity. Multiple lines of evidence indicate that PrPSc, found only in scrapie, is a necessary component of the infectious scrapie agent. Equally compelling is the evidence that its accumulation in the brain causes the neuropathology characteristic of scrapie. We measured the regional concentration of PrPSc in nine brain regions throughout the course of scrapie in the Syrian hamster following intrathalamic inoculation of prions. PrPSc was compared to the regional concentration of glial fibrillary acidic protein, a measure of reactive astrocytic gliosis. PrPSc was detected first in the thalamus 14 to 21 days postinoculation and next in the septum at 28 days. Initiation of PrPSc synthesis and accumulation in the thalamus was attributable to the inoculum and in the septum to ventricular spread of de novo synthesized PrPSc. The timing and pattern of PrPSc accumulation in all other brain regions suggested transmission along neuroanatomic pathways. Reactive astrocytic gliosis followed PrPSc accumulation in each region by 1 to 2 weeks. Brain PrPSc, determined by summing the concentrations in each brain region, correlated well with scrapie infectivity titers throughout the course of infection (correlation coefficient = 0.975; slope of linear regression line = 1.136). Our results support the hypothesis that PrPSc participates in both the etiology and pathogenesis of prion diseases. 
Squamous cell carcinoma of the upper aerodigestive tract associated with well-differentiated carcinoma of the thyroid gland. The association of squamous cell carcinoma of the upper aerodigestive tract with well-differentiated thyroid carcinomas has rarely been reported in the literature. We report 10 cases illustrating this occurrence. In eight cases, the thyroid carcinoma was discovered accidentally on histological examination of a single neck node, a neck node dissection specimen, an unexpectedly found thyroid nodule, or a systematically resected thyroid lobe, all during surgical treatment of an upper aerodigestive tract carcinoma. In the other two cases, metastatic thyroid neck nodes appeared during the follow-up of a patient with an upper aerodigestive tract carcinoma. No case of upper aerodigestive tract carcinomas was found during the follow-up of thyroid cancer patients. In most cases, adequate thyroid cancer surgery was performed simultaneously or later. Prognosis was essentially determined by the upper aerodigestive tract cancer. 
Mechanisms of gastric mucosal injury and protection. This article emphasizes and reviews the premise that because the pathogenesis of acute gastric mucosal injury is multifactorial, several protective mechanisms should also be considered in analyzing gastric mucosal defense. The first part of the article reviews the pathogenesis of acute gastric mucosal injury by major etiologic factors such as hypoxia and chemical and biological agents, and emphasizes the common endogenous mediators of damage (e.g, endothelins, leukotrienes, thromboxane, platelet-activating factor, monoamines, free radicals, proteases, ammonia, hydrochloric acid, and bile acids--in decreasing potency). The second part of the review is devoted to the gastroprotective mechanisms that are analyzed by anatomical (histologic) location and biochemical processes. The endogenous mediators of acute gastroprotection include prostaglandins, sulfhydryl (SH) compounds, non-SH antioxidants, polyamines, and epidermal growth factor, whereas the protective and mediatory role of glucocorticoids, somatostatin, pentagastrin, histamine, gangliosides, and calcitonin gene-related peptide need further studies. A list of endogenous and exogenous chemicals that exert biphasic, damaging, and protective effects on the gastric mucosa in also included. The final common pathway of acute gastroprotection at the structural and functional level seems to be the preservation of subepithelial microvascular integrity leading to maintenance of mucosal blood flow that allows the energy-dependent rapid restitution (cell migration) from surviving gastric neck cells to repair the superficial epithelial defect. Very new data on the contribution of a histodilutional barrier and release of proteases to gastroprotective processes are also discussed. 
Comorbidities and perioperative complications among patients with surgically treated benign prostatic hyperplasia. We address the question of whether or not age and comorbidity are related to intra- and postoperative complications after a transurethral resection. The data are derived from a retrospective, population-based study conducted in Hagen, Germany, which included all patients with an initial prostatectomy for benign prostatic hyperplasia (N = 621) during the five-year period 1984-1988. Seventy-seven percent of the patients had at least one of the following preoperative risk factors: heart disease, hypertension, smoking, chronic obstructive lung disease, and diabetes. There was no intraoperative death. The risk of intraoperative circulatory complications was found to be related to age only for patients without a history of heart diseases or hypertension. The incidence of major complications was 3.1 percent and was significantly higher in the oldest age group. Three patients (0.54%) died postoperatively in the hospital. Infections were the most frequent postoperative complications. The relationship of age and overall postoperative complications was not statistically significant either for patients with (p = 0.121) or without any comorbidity (p = 0.651). Based on this study it seems reasonable to conclude that age is not a clinically relevant risk factor for perioperative complications in patients who have a transurethral resection for benign prostatic hyperplasia. 
Tolerance of gastric mucosal flap to postoperative irradiation. When malignant lesions of the oral cavity, base of tongue, and oropharynx are treated with radical resection, adequate reconstruction is required. The free gastric mucosal flap with microvascular transfer is being used with increasing frequency at Washington University Medical Center. Because of the advanced nature of the primary lesions, most patients also require postoperative radiation therapy. In this paper the tolerance of the gastric mucosal flap to postoperative radiation therapy is reviewed. The changes resulting from radiation therapy in the mucosal flap were found to be acceptable, and no major complications were encountered. 
Dominantly inherited mitochondrial myopathy with multiple deletions of mitochondrial DNA: clinical, morphologic, and biochemical studies. We studied a large family with a dominantly inherited mitochondrial myopathy characterized by progressive external ophthalmoplegia, dysphagia, cataract, lactic acidosis, exercise intolerance, and early death. Morphologic studies of muscle biopsies suggested mitochondrial heteroplasmy and revealed ragged-red fibers and decreased histochemical reactions for cytochrome c oxidase and succinate dehydrogenase. Biochemistry showed a partial defect of cytochrome c oxidase and a mild generalized reduction of other mitochondrial enzymes requiring mitochondrial DNA-encoded subunits. Southern blot analysis and PCR amplification showed mitochondrial DNA deletions in muscle of all affected members, but not in lymphocytes or fibroblasts, suggesting a tissue-specific distribution. Deletions were multiple and seemed to increase with time and to correlate with the severity of the disease. 
Periventricular lesions in the white matter on magnetic resonance imaging in the elderly. A morphometric correlation with arteriolosclerosis and dilated perivascular spaces. Magnetic resonance imaging (MRI) was performed postmortem on the brains of 40 patients aged over 60 yrs who had died from causes other than brain disease. Periventricular lesions of increased signal intensity on T2-weighted images, graded as moderate or severe, were found in 10% of the patients in the age group between 60 and 69 yrs, and in 50% between 80 and 89 yrs. Macroscopic and microscopic whole-brain sections were studied in 19 brain specimens (8 with normal white matter, 4 with moderate lesions and 7 with severe lesions of the white matter on MRI). The presence or absence of periventricular lesions on MRI correlated well with the severity of demyelination and astrocytic gliosis. Demyelination was always associated with an increased ratio between wall thickness and external diameter of arterioles (up to 150 microns). A variable degree of axonal loss in Bodian-stained sections was present in the white matter of all brains with demyelination. Dilated perivascular spaces were found and studied morphometrically in 9 brain specimens; their presence correlated strongly with corrected brain weight, but incompletely with demyelination and arteriolosclerosis. Our findings suggest that arteriolosclerosis is the primary factor in the pathogenesis of diffuse white matter lesions in the elderly. This is soon followed by demyelination and loss of axons, and only later by dilatation of perivascular spaces. 
Sphincter-sparing surgery. Since World War II, a variety of technical innovations have been introduced to preserve the anal sphincter in patients with chronic ulcerative colitis or tumors of the rectum. Studies of anorectal physiology have yielded guidelines for preserving continence and minimizing morbidity. For example, preservation of the anal rectal angle is essential; the rectal mucosa can be removed without impairing neural mechanisms; construction of a reservoir increases rectal compliance. Following these guidelines, surgeons have introduced new techniques and applications benefiting a larger and more varied patient population. Some technical problems remain, however, and patient selection criteria for restorative rectal surgery need to be refined. 
Efficient management of adrenal tumors. A retrospective analysis was carried out on 121 patients with primary adrenal tumors operated on at 2 Vancouver hospitals between the years 1970 and 1990. The purpose of the study was to identify discriminating factors between the various diagnoses in order to minimize both the time and the cost of the investigative process. There were 57 cortical adenomas, 35 pheochromocytomas, 15 carcinomas, 8 cases of cortical hyperplasia, and 6 miscellaneous tumors. The mean time from the onset of symptoms to diagnosis of those patients presenting with an identifiable syndrome was 48.3 months. Those with a hypertensive syndrome presented significantly later than those with Cushing's syndrome (57.7 months versus 22.8 months, p less than 0.01). There was a significant delay in diagnosis in those patients with hypertension on the basis of an aldosteronoma as compared with those with hypertension secondary to a pheochromocytoma (75.4 months versus 36.1 months, p = 0.02). Cortical carcinomas were significantly larger than benign cortical tumors (12.7 cm versus 5.5 cm). No malignant neoplasm measured less than 5 cm in diameter. Diagnostic sensitivity for intravenous pyelogram (IVP) was 59%, for ultrasound 71%, for venography 50%, for meta-iodobenzylguanidine (MIGB) (pheochromocytoma only) 80%, and for angiography 70%. However, for those patients with adrenal carcinomas, angiography was positive in 100% of cases. Computed tomography (CT) was the most sensitive localizing investigation with a sensitivity of 98%. While other localizing techniques were less sensitive than CT, they may still play a useful role in selected situations. Factors causing delay in diagnosis and the role of the various imaging modalities are discussed. 
Nutritional supplementation, psychosocial stimulation, and growth of stunted children: the Jamaican study. The benefits of nutritional supplementation, with or without psychosocial stimulation, on the growth of stunted children were evaluated. Children aged 9-24 mo with lengths less than -2 SD of the National Center for Health Statistics references (n = 129) were randomly assigned to four groups: control, nutritional supplementation, stimulation, and both interventions. A fifth group with lengths greater than -1 SD was also enrolled. Length, weight, head and arm circumferences, and triceps and subscapular skinfold thicknesses were measured on enrollment and 6 and 12 mo later. Multiple-regression analysis was used to determine the effects of the interventions in which age, sex, initial status, initial dietary intake, and several socioeconomic variables were controlled for. Stimulation had no effect on growth and there was no interaction between the interventions. After 12 mo supplemented children had significantly increased length, weight, and head circumference (all P less than 0.01). The effects of supplementation were not cumulative but occurred in the first 6 mo. 
Gastric carcinoma presenting as an exacerbation of ulcers during pregnancy. A case report. Gastric cancer is unusual during pregnancy. Also, because of the physiologic changes that occur with pregnancy, it is rare to see a worsening of peptic ulcers during pregnancy. A patient with an exacerbation of peptic ulcers presented with gastric carcinoma during pregnancy. 
Stress fractures in athletes. How to spot this underdiagnosed injury. Stress fractures are an increasingly common injury in competitive athletes, especially runners. Amenorrheic athletes are at particularly high risk. A radionuclide bone scan should be considered when the index of suspicion for stress fracture is high. Plain radiographs are of little use in establishing the diagnosis in the early stages of the injury. Early diagnosis and prompt institution of conservative therapy allow for a favorable outcome in most cases. Avoidance of or reduced participation in the inciting activity is important for pain control. Certain stress fractures, such as those involving the femoral neck, should be monitored closely and treated aggressively with internal fixation when conservative measures fail. Runners who have exercise-induced amenorrhea should be advised to decrease their training intensity to a level where menses resume. Cyclic therapy with conjugated estrogens and progesterone should also be considered, as should daily calcium supplementation. 
Mortality, neoplasia, and Creutzfeldt-Jakob disease in patients treated with human pituitary growth hormone in the United Kingdom OBJECTIVE--To determine the cause of death and incidence of neoplasia in patients treated with human pituitary growth hormone. DESIGN--A long term cohort study established to receive details of death certification and tumour registrations through the Office of Population Censuses and Surveys and NHS central register. PATIENTS--All patients (1246 male, 662 female) treated for short stature with pituitary growth hormone under the Medical Research Council working party and health services human growth hormone committee. MAIN OUTCOME MEASURES--Death or development of neoplasia. RESULTS--110 patients died (68 male, 42 female; aged 0.9-57 years) from 1972 to 1990. Fifty three death were from neoplasia responsible for growth hormone deficiency (27 craniopharyngioma, 24 other intracranial tumour, two leukaemia); two from histiocytosis X; and 13 from pituitary insufficiency. Six patients died of Creutzfeldt-Jakob disease, six of other neurological disorders, and eight of acute infection. Other deaths were apparently unrelated to growth hormone deficiency or its treatment. Seventeen tumours (in 16 patients) were identified during or after growth hormone treatment. Four were in patients with previous intracranial neoplasia and two were after cranial irradiation. Thirteen were intracranial, the others being Hodgkin's lymphoma, osteosarcoma, carcinoma of colon, and basal cell carcinoma. CONCLUSIONS--Recurrence or progression of intracranial tumours and potentially avoidable metabolic consequences of hypopituitarism were the main causes of death. Growth hormone treatment probably did not contribute to new tumour development. Creutzfeldt-Jakob disease after pituitary growth hormone treatment continues to occur in the United Kingdom. This cohort must remain under long term review. 
Neutralizing antibodies to interferon-alpha: relative frequency in patients treated with different interferon preparations. The frequencies of antibody development so far reported in patients treated with different interferons (IFNs) are not readily comparable because of differences in treatment regimens and assay methods. Thus the frequency of neutralizing antibody development was analyzed in a large sample of sera derived from a relatively homogeneous group of patients treated with different IFN-alpha preparations. The frequency of developing neutralizing antibody to IFN varied according to the IFN given. Particularly, the seroconversion frequency was significantly higher in patients treated with recombinant IFN-alpha 2a (20.2%) than in patients treated with either recombinant IFN-alpha 2b (6.9%) or IFN-alpha N1 (1.2%), a lymphoblastoid IFN-alpha. Furthermore, sera obtained from patients treated with either recombinant IFN neutralized both types of recombinant IFNs but failed to neutralize IFN-alpha N1. 
Glial fibrillary acidic protein expression in pleomorphic adenoma, chordoma, and astrocytoma. A comparison of three antibodies. Glial fibrillary acidic protein (GFAP) is a major constituent of glial cytoplasmic intermediate filaments. Glial fibrillary acidic protein expression has been accepted as a marker of astroglial differentiation or origin. However, GFAP expression has been demonstrated in a variety of normal and neoplastic tissues outside the central nervous system, including pleomorphic adenomas, chordomas, bone, and cartilage. It has been postulated that coexpression of GFAP and vimentin in neoplastic myoepithelial cells in pleomorphic adenomas reflects early chondroid differentiation. Glial fibrillary acidic protein expression in chondromyxoid and chordoid tumors was studied in formaldehyde solution-fixed, paraffin-embedded sections of 20 pleomorphic adenomas and 10 chordomas by the immunoperoxidase method with the use of commercially available monoclonal (n = 2) and polyclonal (n = 1) antibodies. All pleomorphic adenomas and chordomas demonstrated expression of GFAP with the use of the polyclonal antibody (Biomeda Corp [Foster City, Calif]). Variable expression of GFAP was present in 90% (18/20) and 70% (14/20) of pleomorphic adenomas, and in 20% (2/10) and 0% of chordomas, with the use of the two monoclonal preparations (Dakopatts [Glostrup, Denmark] and BioGenex Laboratories [San Ramon, Calif]), respectively. Normal brain tissue and eight astrocytomas were used as "controls" to compare staining intensity and quality between the polyclonal and monoclonal anti-GFAP antibodies. Glial fibrillary acidic protein positivity with the polyclonal antibody was more intense than that with either monoclonal antibody despite similar (congruent) distributions of tumor cell types that were stained in control brain and astrocytoma tissues. The GFAP polyclonal antibody was more frequently immunoreactive than the monoclonal antibodies, particularly in cells that exhibited chondroid differentiation. These findings may have practical application in surgical pathology. 
Use of endovascular stents in congenital heart disease. BACKGROUND. Balloon expandable intravascular stents have been used to support vessel walls in coronary and peripheral arteries in adults. The purpose of this study was to examine the efficacy and safety of these stents in the treatment of congenital heart disease. METHODS AND RESULTS. Forty-five stents were placed in 30 patients, who were 0.2-30.2 years old (weight, 3.5-76 kg). Patients with areas of stenosis that were difficult to approach surgically were chosen. Stents were mounted over balloons and placed by standard catheterization techniques. Twenty-three patients had branch pulmonary artery stenosis. Thirty-six stents were placed successfully and had reduced pressure gradients from 50.6 +/- 24 to 15.9 +/- 13.4 mm Hg. Five patients had stents placed after atrial surgery: three in obstructed Fontan repairs, one at the superior vena cava-right atrial junction after sinus venous defect repair, and one at the site of a Glenn shunt. Atrial stents reduced pressure gradients from 9.8 +/- 8.2 to 2.0 +/- 2.6 mm Hg. One patient had a stent placed in the descending aorta after coarctation dilation, and the pressure gradient was reduced from 50 to 25 mm Hg. One patient had pulmonary vein dilation with stent placement. Two stents migrated at the time of placement; one required surgical removal, and one was anchored in place by balloon dilation. One patient died within 24 hours of catheterization because of thrombus obstruction of the Fontan repair. Nine patients have undergone recatheterization. All stented vessels have remained at the same caliber as at original stent placement. CONCLUSIONS. We conclude that balloon expandable stents are useful in selected postoperative stenoses in congenital heart disease. 
Intracerebral hemorrhage related to cerebral amyloid angiopathy and t-PA treatment. Tissue plasminogen activator (t-PA) has been approved as thrombolytic therapy for the treatment of acute myocardial infarction, but this agent can cause serious bleeding complications including intracerebral hemorrhages. Mechanisms underlying the development of these hemorrhages have not been clarified. We report a patient who developed two intracerebral hemorrhages shortly after receiving t-PA for the treatment of an acute myocardial infarction, and who was found to have cerebral amyloid angiopathy at autopsy. Staining of cortical sections with Congo red and an antibody directed against beta amyloid protein (A4 peptide) disclosed specific involvement of most of the subarachnoid and superficial cortical vessels in the region of the two hemorrhages. Based on the findings in this patient and in 6 additional patients reported recently, it is likely that cerebral amyloid angiopathy plays a pathogenic role in some intracerebral hemorrhages associated with the administration of t-PA. The cautious use of t-PA with heparin in patients who are elderly or demented may be advisable. 
Radical prostatectomy for stage A adenocarcinoma of the prostate: staging errors and their implications for treatment recommendations and disease outcome. Of 148 patients with clinical stage A1 (32) or A2 (116) disease who had radical prostatectomy only 63% and 62%, respectively, had pathological stage A disease. Although 25% of those with clinical stage A1 and 9% of those with clinical stage A2 disease had no cancer at radical prostatectomy, 12% and 29%, respectively, had pathological stage C disease or higher. Clinical Mayo grade 1 was never associated with extracapsular disease but 60% of those with grade 3 or higher tumor did have extracapsular disease. Over-all survival was comparable to the expected survival. Clinical stage A2 cancer was associated with a significantly higher progression rate (when prostate specific antigen values were considered, p = 0.0011) and cancer death rate (p less than 0.045) than stage A1 disease, whereas pathological stage was not significantly related to disease outcome, possibly because of the use of adjuvant treatment (hormonal or radiation) for some patients with pathological stage C or higher disease. The vagaries of clinical staging associated with stage A disease, as well as the previously documented progression on long-term followup (8 to 10 years) in younger (60 years old or less) patients with stage A1 prostate cancer make radical prostatectomy with its limited morbidity an acceptable treatment choice. 
Group B streptococcal endocarditis of tricuspid valve. We report three cases of group B streptococcal endocarditis of the tricuspid valve. Two patients were intravenous drug abusers. In the literature review, and including our cases, ten patients had group B streptococcal endocarditis of the tricuspid valve. Half of the patients were intravenous drug abusers. Four of the other patients had underlying conditions. All patients were treated with a penicillin with or without an aminoglycoside. Three patients underwent tricuspid valve surgery. The overall mortality was 20 percent. Both patients who died received medical therapy only. 
Coronary artery narrowing due to extrinsic compression by myocardial abscess. A case of aortic valve endocarditis complicated by perivalvular abscess extending into myocardium is presented. Echocardiography and aortography failed to detect the abscess, but coronary angiography revealed its presence by extrinsic compression of left anterior descending and diagonal arteries. Morphological features of this rare cause for coronary narrowing are described. 
Surgical treatment of concomitant urethral diverticulum and stress incontinence. Urinary incontinence is frequently associated with a urethral diverticulum in female patients. Preoperative evaluation including a thorough history and physical examination, voiding cystourethrogram, urethroscopy, and urodynamic studies can diagnose both the urethral diverticulum and any concomitant bladder-urethral dysfunction. Preoperative recognition of stress urinary incontinence or patients at risk for this problem postoperatively permits effective treatment with concomitant transvaginal bladder neck suspension and urethral diverticulectomy. 
Treatment of chronic infected hip arthroplasty wounds by radical debridement and obliteration with pedicled and free muscle flaps. Nine patients with extensive wounds of the hip joint due to chronic infection following total hip arthroplasty or internal fixation of fractures of the femoral head and neck have been treated by serial radical debridements to remove infected bone, contaminated remnants of bone cement, and the surrounding fibrotic soft tissues. The resultant deep cavity extending down to the acetabulum has then been obliterated with either pedicled muscle flaps or free muscle flaps. Subcutaneous or transpelvic transposition of rectus abdominis muscle flaps is preferred for smaller defects, but only the free latissimus dorsi muscle flap provides sufficient volume of tissue to obliterate the more extensive hip defects. Systemic antibiotics have been continued only for a short-term course of 14 days postoperatively. There has been no recurrence of infection, with follow-up ranging between 6 months and 3 1/4 years. One patient has undergone reimplantation of a second custom hip prosthesis into the vascularized bed of a free latissimus dorsi muscle flap. 
A modified technique for obliteration of large bony defects after cystectomy. Thirteen cysts treated by enucleation followed by collapsing an osteoperiosteal flap to eliminate dead space are presented. Four of the cysts were dentigerous and nine were radicular. The bony defects ranged in size from 3 to 7 cm in greatest dimension. Healing by primary intention occurred in all cases. This method has been found to be successful in the obliteration of large bony defects after cystectomy. 
A comparative trial of the reactogenicity and immunogenicity of Takeda acellular pertussis vaccine combined with tetanus and diphtheria toxoids. Outcome in 3- to 8-month-old infants, 9- to 23-month-old infants and children, and 24- to 30-month-old children. The reactogenicity and immunogenicity of the Takeda acellular pertussis vaccine combined with tetanus and diphtheria toxoids were compared in 139 infants aged 3 to 8 months, 60 infants and children aged 9 to 23 months, and 99 children aged 24 to 30 months. Good antibody responses to pertussis toxin (PT), filamentous hemagglutinin (FHA), and agglutinogens occurred in all age groups after both the third and fourth doses. After the fourth (booster) dose, the mean antibody values in initially seronegative infants vaccinated at 3 to 8 months of age were as follows: anti-PT, 67.8 enzyme-linked immunosorbent assay units (EU) per milliliter; anti-FHA, 149.5 EU/mL; the agglutinin titer was 125.6. The values in initially seronegative children vaccinated at 24 to 30 months of age were as follows: anti-PT, 92.9 EU/mL; anti-FHA, 251.7 EU/mL; the agglutinin titer was 275.8. Reactions following immunization were minimal. Except for drowsiness after the first dose in infants, there were no clinically significant differences in reactions between infants and older children. The findings in this study coupled with the recent demonstration of efficacy of this vaccine in 2-year-old children supports the recent Japanese recommendation to lower the age of immunization with acellular pertussis vaccine combined with tetanus and diphtheria toxoids to 3 months. 
Hemifacial spasm in an infant due to fourth ventricular ganglioglioma. Case report. The case of an infant is reported in which hemifacial spasm due to a ganglioglioma of the fourth ventricle was relieved by surgery. Previously described causes of hemifacial spasm are summarized, and the relevance of this case to theories on the pathogenesis of the condition is discussed. 
The influence of severity of spinal cord ischemia in the etiology of delayed-onset paraplegia. To clarify the cause of delayed-onset paraplegia, the authors evaluated the neurologic outcome after temporary (10 to 30 minutes) spinal cord ischemia in the awake rabbit. Loss of motor function occurred in less than 2 minutes in all animals. Restoration of flow within 16 minutes always resulted in full return of function, whereas with occlusion times of greater than 27 minutes all animals remained paralyzed. After temporary occlusion of 20 to 21 minutes, however, 71% of animals returned to normal neurologic function but developed delayed-onset paraplegia 14 to 48 hours later. This appears to be a reliable method for the creation of a model of delayed-onset paraplegia in the awake animal, and will facilitate more detailed studies of the pathophysiology of ischemia-induced paraplegia. 
Long-term results after lateral cranial base surgery. The surgical management of patients with slow-growing benign temporal bone neoplasms has been criticized because of its significant morbidity and mortality compared with results after radiation therapy, but long-term control by irradiation remains unproved. Long-term surgical results have not been studied previously. One hundred twenty-nine skull base operations were performed in 126 patients at the Otology Group, Nashville, Tenn., from January 1970 through May 1987. Fifty-eight patients responded to questionnaires focusing on recovery from loss of cranial nerves. All patients regained some degree of facial function (class V or better), no alimentary tubes or tracheotomies were in use, and no patients had debilitating aspiration. Long-term compensation from the cranial nerve deficits of lateral skull base surgery can be expected in most patients and should not be used as an argument for irradiation in patients with a long life expectancy at time of diagnosis. 
Gastric mucosal pH as a prognostic index of mortality in critically ill patients. OBJECTIVE: To determine if measurements of gastric intramucosal pH have prognostic implications regarding ICU mortality. DESIGN: Prospective comparison of outcome. SETTING: General adult ICUs in two teaching hospitals. PATIENTS: Eighty consecutive patients age 18 to 84 yrs (mean 63.4), 50 men and 30 women, 55% in the medical and 45% in the surgical services. METHODS: Gastric intramucosal pH was measured on ICU admission and again 12 hrs later. A value of greater than or equal to 7.35 was used to differentiate between normal and low gastric intramucosal pH. MEASUREMENTS AND MAIN RESULTS: Fifty-four patients had a normal gastric intramucosal pH and 26 patients had a low gastric intramucosal pH on ICU admission. The mortality rate was greater in the low gastric intramucosal pH group (65.4% vs. 43.6%; p less than .04). The frequency of sepsis and the presence of multisystem organ failure also were greater in the low gastric intramucosal pH group (p less than .01). Further stratification of patients according to gastric intramucosal pH measured 12 hrs after admission showed a greater mortality rate in patients with persistently low gastric intramucosal pH when compared with patients with normal gastric intramucosal pH during the first 12 hrs (86.7% vs. 26.8%; p less than .001). CONCLUSIONS: Measurements of gastric intramucosal pH on ICU admission, and again 12 hrs later, have a high specificity for predicting patient survival in this ICU patient population (77.8% to 80.6%). Furthermore, given its relative noninvasive nature, tonometrically measured gastric intramucosal pH may be a useful addition to patient monitoring in the ICU. 
Allele loss at the retinoblastoma locus in human ovarian cancer. To gain a broad spectrum on allelic loss of specific loci in ovarian tumors, we initially examined DNA from 23 pairs of ovarian tumors and matched peripheral blood lymphocyte samples from the same patients, using 27 polymorphic DNA markers distributed on 13 chromosomes. Significant high frequency of allelic deletion (22%-44%) at chromosome 13 loci (D13S31, D13S32, D13S33, and D13S34) at bands q12-q34 was observed in tumor tissues. These results led us to investigate the loss of heterozygosity at the retinoblastoma (RB) locus in ovarian tumors, because the RB gene is a tumor-suppressor gene located at 13q14. Analysis of the variable number of tandem repeat sequence polymorphism in intron 20 in the RB gene revealed that 6 (30%) of 20 patients with informative samples showed allelic loss at the RB locus in their tumor tissues. This loss, of relatively high frequency, suggests that the RB gene, or a closely linked gene, seems to be involved in the development of ovarian cancer. 
Exertional sudden death in soldiers. To address the problem of a significant rise in the incidence of exertional sudden death worldwide, the medical records and necropsy reports of all deaths that occurred in the Israel Defence Forces (IDF) during 1974-1986 were scrutinized. Twenty male soldiers, aged 18-29 yr, died suddenly and unexpectedly within 24 h of strenuous exercise. Necropsy results, available for 90% of the subjects, included underlying cardiac disease in 50% and noncardiac causes of death in 33.3%; the cause of death was unidentifiable in 16.7% of the subjects. Prodromal symptoms in 70% of the subjects are presented as a main focus of this investigation. The most frequently reported symptom was exertional or nonexertional syncope in 40% of the subjects. Chest pain, acute gastrointestinal symptoms, or febrile disease were reported in 30% of the cases. The findings of this research suggest that syncope is a major antecedent symptom of exertional sudden death. An attack of syncope in young conditioned individuals should be followed by thorough medical surveillance, and strenuous exercise should be avoided until this procedure is completed. Sports and military officials have the obligation to promote awareness that strenuous exercise should not be performed in the presence of acute gastrointestinal symptoms or febrile illness. 
Prevention of portal hypertension and portosystemic shunts by early chronic administration of clonidine in conscious portal vein-stenosed rats. The hemodynamic effects, including mesenteric-systemic shunts of early chronic administration of clonidine, were studied in conscious, unrestrained, portal vein-stenosed rats. In rats receiving early chronic clonidine (600 micrograms.kg-1.day-1 by gavage), begun 3 days before portal vein stenosis and then administered continuously for 10 consecutive days, portal pressure (10.0 +/- 1.5 mm Hg) and degree of mesenteric-systemic shunts (58% +/- 25%) were significantly lower than in the placebo group (15.2 +/- 1.5 mm Hg and 83% +/- 7%, respectively). The effects were observed either 2 to 3 hr or 18 to 24 hr after the last dose of clonidine. In rats receiving clonidine continuously for 5 days, starting 5 days after portal vein stenosis, portal pressure (11.0 +/- 1.3 mm Hg) was significantly lower than in the placebo group, but mesenteric-systemic shunts (82% +/- 8%) were not significantly different. In rats receiving a single oral dose of clonidine (600 micrograms/kg) 10 days after portal vein stenosis, portal pressure (11.8 +/- 2.1 mm Hg), measured 2 to 3 hr after clonidine administration, was significantly lower than in the placebo group. Mesenteric-systemic shunts (83% +/- 8%), however, were not significantly different from the placebo group. In addition, 18 to 24 hr after a single dose of clonidine, hemodynamic values returned to basal conditions. We also demonstrated that chronic clonidine administration begun before portal vein stenosis can reduce the initial increase in portal pressure after this procedure. We concluded that early chronic clonidine administration reduces the severity of portal hypertension and the development of portosystemic shunts in portal vein-stenosed rats. 
Cerebrospinal fluid atrial natriuretic factor in intracranial disease. We tested the hypothesis that the concentration of atrial natriuretic factor in the cerebrospinal fluid is an indicator of brain injury in patients with intracranial disease. Atrial natriuretic factor concentration was measured in 72 samples of cerebrospinal fluid from 28 patients with intraventricular drains and in nine samples from outpatient controls undergoing diagnostic lumbar puncture. Levels were correlated with diagnosis; systemic fluid administration; concentration of atrial natriuretic factor in the plasma; intracranial pressure; sodium, glucose, and protein concentrations, osmolality, and cell count in the cerebrospinal fluid; sodium concentration in the serum; and hemodynamics. Atrial natriuretic factor concentration was highest in cerebrospinal fluid from patients with intracerebral hematoma, followed by those with obstructive hydrocephalus and subarachnoid hemorrhage (19 +/- 2, 13 +/- 3, and 8 +/- 2 pg/ml, respectively); atrial natriuretic factor concentration was less than 4 pg/ml in the controls. Patients treated with fluid restriction had significantly higher atrial natriuretic factor levels than those receiving maintenance or high-volume fluids (16 +/- 3, 8 +/- 2, 10 +/- 1 pg/ml, respectively). The concentration of atrial natriuretic factor in the plasma was significantly elevated in patients with intracerebral hematoma and subarachnoid hemorrhage (155 +/- 38 and 92 +/- 20 pg/ml, respectively) and did not correlate with fluid administration or the concentration of atrial natriuretic factor in the cerebrospinal fluid. Neither cerebrospinal fluid nor plasma concentrations of atrial natriuretic factor correlated with intracranial pressure; cerebrospinal fluid sodium, glucose, or protein concentrations, osmolality, or cell count; serum sodium concentration; or hemodynamics. We conclude that the concentration of atrial natriuretic factor in the cerebrospinal fluid is a nonspecific indicator of brain injury. 
Influence of exercise-induced myocardial ischemia on the pattern of left ventricular diastolic filling: a Doppler echocardiographic study Previous studies using Doppler echocardiography to evaluate left ventricular diastolic filling have shown that myocardial ischemia induced by coronary balloon angioplasty or atrial pacing results in a decrease in the left ventricular inflow peak early (E) to peak atrial (A) velocity ratio. To investigate the effects of exercise-induced ischemia on Doppler-derived filling variables, 20 patients with coronary artery disease and exercise-induced electrocardiographic changes and regional wall motion abnormalities determined by two-dimensional echocardiography were evaluated and compared with 20 patients without evidence of exercise-induced ischemia. Doppler echocardiography was performed at rest and immediately after exercise before the resolution of exercise-induced wall motion abnormalities. Peak E and A velocities increased from rest to postexercise in both the ischemic and nonischemic groups, although the ischemic group demonstrated a greater increase in peak E velocity (from 68 +/- 15 cm/s at rest to 88 +/- 22 cm/s after exercise) than the nonischemic group (70 +/- 13 to 77 +/- 18 cm/s) (p less than 0.05 for the difference in response between groups). Accompanying these changes was a slight increase in the peak E/A velocity ratio in the ischemic group (1.04 +/- 0.28 at rest to 1.13 +/- 0.42 after exercise) versus a decrease in the nonischemic group (1.07 +/- 0.30 to 0.90 +/- 0.28) (p less than 0.05 intergroup difference). 
Long-term consequences of CNS treatment for childhood cancer, Part I: Pathologic consequences and potential for oncogenesis. The pathologic changes associated with the treatment of cancer of the nervous system are reviewed. Computed tomographic, magnetic resonance imaging, and positron emission tomographic findings of these abnormalities are described, followed by discussion of the known histopathologic features. For the most part, pathologic effects are primary vascular and/or demyelinating. We review each of these effects at all levels of the neural axis. This review concludes with a discussion of the risk of developing second malignancies. Although this complication is infrequent, the likelihood that survivors of childhood cancer will develop a second malignancy is 10 times that of age-matched controls. This phenomenon in part relates to genetic predisposition, environmental factors, and host susceptibility. These qualifications not withstanding, most studies implicate central nervous system radiation with and without chemotherapy as the primary etiology for second malignancies. 
Lymphomatous presentation of childhood acute lymphoblastic leukemia. A subgroup at high risk of early treatment failure. Multivariate analyses of the clinical course of 1537 children with acute lymphoblastic leukemia (ALL) identified a subgroup which experienced short remission duration and a high incidence of extramedullary relapse. The patients differed from other ALL patients by the presence at diagnosis of two or more of a constellation of clinical and laboratory features: organomegaly or mass disease, E-rosette positivity, hemoglobin level greater than 10 g/dl, leukocyte count greater than 50,000/microliters, male predominance, and older age. This type of presentation of ALL is referred to as the "lymphoma syndrome" (LS) since such patients exhibit a pattern of several clinical and laboratory features which were observed repeatedly but in differing combinations, and some of which clinically resemble lymphoma. A subsequent database from 2231 patients was analyzed. Patients with a mediastinal mass, massive splenomegaly, or massive adenopathy, alone or in combination, had a worse outcome when the patient also had either leukocytosis, E-rosette-positive lymphoblasts, or a normal or near normal hemoglobin (Hb) level at diagnosis. Similarly, the above three laboratory features alone or in combination did not predict less than 40% disease-free survival (DFS) unless they were accompanied by at least one of the clinical features of mass disease. When at least one clinical feature and at least one laboratory feature were present, the overall DFS was 36% 6 years after diagnosis versus 64% for all other patients. The association of these features with poor prognosis remained significant after adjusting for the level of leukocyte count at diagnosis, age at diagnosis, and sex of the patients. Patients with this recurrent syndrome of features do not represent a homogeneous biologic entity but they constitute a subgroup of patients with ALL having a high risk of treatment failure using current therapies, including failure to achieve remission, early relapse, and increased frequency of relapse in extramedullary sites. They deserve early recognition at diagnosis and selection of treatment strategies appropriate for very high risk ALL. 
Intraoperative use of a 2-mm choledochoscope for the exploration of small bile ducts and the pancreatic duct. Intraoperative visualization of the biliary and pancreatic ducts can be difficult in a nondilated system. Very small extra- and intrahepatic bile ducts occasionally require visualization but do not admit the traditional 6.5-mm intraoperative flexible choledochoscope. We have prospectively examined the use of a 2-mm choledochoscope for the intraoperative evaluation of the biliary and pancreatic ducts in 36 patients. In 27 patients, the choledochoscope was advanced through the cystic duct stump for examination of the common bile duct following cholangiography. The scope was successfully passed into the cystic duct stump and into the common bile duct in 76 per cent of patients. Inability to pass the scope through the cystic duct was usually due to acute angulation of the cystic duct/common duct junction. In an additional five patients, intraoperative cholangiography revealed a filling defect in a very small duct. A choledochotomy was made and the 2-mm choledochoscope was used to exclude the presence of stones in a small bile duct. In four patients the choledochoscope was used during a Puestow procedure to visualize and help extract stones in the tail and head of the gland. No complications occurred in these patients due to the use of the choledochoscope. We conclude that the 2-mm choledochoscope aids in internal visualization of small intra- and extrahepatic bile ducts and the pancreatic duct. It may be useful as an adjunct to cholangiography in determining the nature of filling defects. 
AAEM case report #21: hemifacial spasm: preoperative diagnosis and intraoperative management. A 75-year-old man developed progressive involuntary hemifacial spasm. Electrophysiologic evidence of abnormal cross-transmission between neurons of the facial nerve was demonstrated. Electrodiagnostic studies were used to confirm the diagnosis preoperatively and determine the adequacy of vascular decompression of the facial nerve intraoperatively. 
Generation and cloning of stable human IgE-secreting cells that have rearranged the C epsilon gene. Although the secretion of Ig isotypes other than IgM is generally accompanied by a DNA rearrangement that deletes C mu (and the other IgCH genes located between VDJ and the expressed CH gene), a system has recently been described that generates a high frequency of IgE-secreting cells that have failed to delete IgCH genes or to rearrange their C epsilon genes. These cells, derived from EBV-transformed human PBMC, secrete IgM and IgD as well as IgE. To determine whether the absence of C epsilon rearrangement and CH gene deletion is a general phenomenon for human IgE-secreting cells, we have characterized IgE-secreting cells that are generated by culturing purified human B cells with EBV plus IL-4 in the presence of irradiated human PBMC. In contrast to the earlier observation, we have not been able to detect any cells that demonstrate cytoplasmic staining for IgE and concurrently stain for a second Ig isotype. Stable IgE-secreting cell lines and clones produced by this method have rearranged one of their C epsilon genes and have deleted both C mu genes. These observations demonstrate that the generation of human IgE-secreting cells can involve the same gene rearrangement and deletional mechanisms that lead to the generation of cells that secrete other isotypes. 
Lower-extremity vascular grafts placed for peripheral vascular disease: prospective evaluation with duplex Doppler sonography. Eighty-five men with 92 vascular grafts placed for peripheral vascular disease of the lower extremity underwent a total of 264 examinations with duplex Doppler over a 2.5-year period. In 64 patients who underwent more than one examination, the total follow-up encompassed 740 months. In 220 native femoral arteries (96.0%) the peak systolic velocity (PSV) was higher than that in the graft. Arteriovenous shunting was associated with a normal PSV and a markedly elevated diastolic component at spectral analysis. Focal fluid collections were common initially near the graft and usually disappeared uneventfully. An average PSV of 32 cm/sec or less was always associated with impending occlusion. The sensitivity of an average PSV of 40 cm/sec or less to indicate impending graft occlusion by the next visit was only 33%; the specificity, 94%. At initial examination, stenoses were associated with high PSV focally in the graft or low PSV with absent diastolic flow. 
The role of family structure, functioning, and pain modeling in headache. In an initial attempt to examine relationships between family functioning and chronic headache disorders, the present study examined: a) family structure characteristics, b) family functioning, and c) family pain modeling. Subjects completed an assessment battery consisting of several measures of family functioning. Analyses showed that migraine sufferers (N = 42) as compared to headache-free controls (N = 59) were more likely to describe their families as emphasizing clear organization, structure, rules, and overall control, but less likely to encourage emotional expression. No differences were found between tension headache subjects (N = 43) and headache-free controls. While only an initial exploration of the importance of family characteristics in chronic headache, these results suggest that there are important differences in headache subjects' (particularly migraine) reports of family environment and functioning. 
Community cancer programs as strategic alliances: challenges and guidelines for action. This paper assesses the utility of strategic alliances as a way of expanding and improving the quality of cancer care provided in communities with limited access to major treatment centres. Alliances provide an organizational model for future community-based cancer programs by accommodating a growing need for interdependence among organizations and providers while permitting substantial independence and autonomy. Five managerial challenges to ensuring effective and efficient delivery of cancer services are identified: to secure mutually reinforcing exchanges between and within all levels of cancer care, to develop protocols and programs relevant to the unique characteristics of patients and providers, to provide treatment and cancer control services, to involve interdisciplinary teams of providers at all levels of care and to achieve quality assurance, improvement and evaluation. In addition, the paper includes a set of guidelines to facilitate the implementation of community cancer programs as strategic alliances: reaffirm the role of community oncologists, primary care physicians and nurses as partners in the program; define the structure and culture necessary for commitment rather than simply compliance; redefine the role of management; establish data-monitoring systems; modify reward systems; and set realistic time frames and expectations. 
Abdominal CT findings after liver transplantation in 66 patients. CT scanning is used frequently to assess the condition of patients after liver transplantation. The CT records of 174 adult patients who underwent liver transplantation were studied retrospectively to determine the number and timing of CT studies as well as the frequency and significance of the findings. One-hundred seventy CT scans were obtained in 66 (38%) of the 174 patients, with a mean of 2.6 scans/patient. The interval between transplantation and scanning was 1 day to 24 months; in 59 (89%) of 66 patients, the first CT scan was obtained within 30 days. The acute indications for CT scanning were fever or leukocytosis in 54 (92%) of 59 patients and abnormal liver function tests in five (8%) of 59 patients. CT scans obtained more than 30 days after transplantation were repeat scans in all but seven patients. Indications in this latter group were the same as for the acute group, plus evaluation of hepatic neoplasia in three patients. CT findings included periportal low attenuation in 41 (62%) of 66 patients; ascites in 25 (38%); splenomegaly in 19 (29%); loculated intraperitoneal noninfected fluid collections in 13 (20%); intrahepatic, splenic, pancreatic, or perihepatic abscesses in seven (11%); hepatic infarction in six (9%); splenic infarction in three (4%); and hepatic calcification in two (3%). Other major abnormalities included inferior vena caval thrombosis (one patient), pseudoaneurysm of the hepatic artery with rupture (one patient), and recurrent hepatocellular carcinoma (one patient). CT scanning after liver transplantation is used predominantly in the acute setting to evaluate for liver infarction or intraabdominal abscess. In this setting, CT showed these abnormalities, in addition to tumor recurrence or vascular abnormalities, in 15 (23%) of 66 patients. 
Comparison of allografts and prosthetic valves when used for emergency aortic valve replacement for active infective endocarditis. Aortic valve replacement (AVR) using allografts is an established method of treating aortic valve disease. It is uncertain, however, whether the increased technical demands of allograft AVR can be justified in emergency operations. This study reports 15 patients treated between 1987 and 1990 for acute bacterial or fungal endocarditis involving the aortic valve. Patients underwent emergency AVR because of severe congestive failure, overwhelming sepsis or cerebral emboli. Eight patients received prosthetic valves (group I: 4 mechanical, 4 porcine) and 7 received human allografts (group II: 5 aortic and 2 pulmonary). The groups were comparable in age (group I, 55 years; group II, 51 years), intravenous drug abuse (group I, 1; group II, 3), and previous AVR (group I, 3; group II, 2). One group I and 4 group II patients had septal abscesses. Additional procedures in group I included mitral valve replacement (2), tricuspid valve replacement (1) and aortic root replacement (1). Additional procedures in group II were mitral valve repair (1), root replacement (1), atrial septal defect closure (1) and aortocoronary bypass (1). Mean bypass times (group I, 189 minutes; group II, 204 minutes) and cross-clamp times (group I; 108 minutes; group II, 121 minutes) were similar. Operative deaths occurred in 4 of 8 group I and 1 of 7 group II patients. All surviving patients have been successfully followed (group I, 28 months; group II, 18 months). No group I patient has required reoperation. One group II patients required reoperation for recurrent infection affecting the allograft, and another group II patient died 10 months postoperatively from noncardiac causes. 
Hearing aid prescribing: is the specialist opinion necessary? A restructuring of the service for provision of hearing aids has been proposed by the Royal National Institute for the Deaf. This is based on the assumption that very few patients referred for hearing aids have significant ear disease and it is not necessary for them to see an ENT specialist. The case notes of 200 consecutive patients referred to the Hearing Aid clinic were reviewed. In only half of these would a hearing aid have been prescribed without a specialist opinion. The remainder either did not need a hearing aid or required further investigation and surgical or medical treatment. In addition there was significant evidence of lack of expertise amongst General Practitioners in recognizing ear disorders. It is imperative that any patient requiring a hearing aid be seen by someone experienced in otology rather than be dealt with by the General Practitioner alone. 
Flow cytometric determination of the multidrug resistant phenotype in transitional cell cancer of the bladder: implications and applications. We detail our experience with a monoclonal antibody to detect the cell surface P-glycoprotein product of the multidrug resistance gene (MDR-1) in the human bladder. A total of 32 patients had 44 different specimens analyzed. The samples consisted of 8 normal bladders, 21 transitional cell carcinomas, 1 mucinous adenocarcinoma, 3 P-0 bladder wall specimens and 10 nonmalignant urothelial samples from cystectomies. P-glycoprotein was not detected in the normal adult or pediatric bladder. Bladder specimens from 3 children with a neurogenic bladder revealed enhanced expression (21%, 14% and 4% positivity). Transitional cell carcinoma usually demonstrates low expression at diagnosis (less than 6%), although 3 patients had enhanced initial expression (11%, 12% and 31%). Three patients treated with chemotherapy demonstrated 56%, 76% and 50% expression of MDR-1. Nonmalignant tissue from cystectomy specimens had low expression of MDR-1. The specificity of this system was confirmed with human bladder cell lines. The ability of flow cytometry to detect and quantify the expression of MDR-1 may allow for the early detection of chemotherapy resistance in patients with transitional cell carcinoma treated with systemic and intravesical therapy. 
Administration of sucralfate prolongs survival of animals with experimental peptic ulceration. Ligation of the pig bile duct (BDL) results in 100% incidence of pars esophageal ulceration within 48 hours of the procedure. Usually such ulceration is uniformly fatal unless a highly selective vagotomy is performed simultaneously with the BDL. The administration of sucralfate to pigs with BDL prolonged their survival for up to 7 days, with evidence of healing of the ulcer on macroscopic and histologic observations. An increase in cell proliferation in the squamous epithelium of the ulcerated area was also seen in this sucralfate group. These features were not seen in controls, pigs with BDL only, or pigs with BDL and with magaldrate (Riopone), colloidal bismuth subcitrate (DeNol), or carbenoxolone. Analysis by Sepharose 2B gel filtration showed that there was no significant difference in the amounts of polymeric mucin in any group, with a wide scatter of the data seen especially for pigs in the untreated BDL-only group. This study suggests that sucralfate may enhance healing in this experimental pig ulcer model via a mechanism independent of the stimulation of mucus secretion. We propose that coating the mucosa with sucralfate provides a temporary substitute barrier that creates a microenvironment conducive to wound repair by mucosal proliferation. 
Impact of variability among surgeons on postoperative morbidity and mortality and ultimate survival. OBJECTIVE--To assess the differences among surgeons in postoperative complications, postoperative mortality, and survival in patients undergoing surgery for colorectal cancer. DESIGN--Prospective study of patients with colorectal cancer managed by one of 13 consultant surgeons, none of whom had a special interest in colorectal surgery. SETTING--Royal Infirmary, Glasgow. PATIENTS--645 sequential patients with colorectal cancer presenting over the six years from 1974 to 1979. MAIN OUTCOME MEASURES--Postoperative complications, postoperative mortality (within 30 days), and survival (up to 10 years); predictive factors for postoperative mortality and survival; and relative hazard rate ratios for individual surgeons. RESULTS--The proportion of patients undergoing apparently curative resection varied among surgeons from 40% to 76%; overall postoperative mortality varied from 8% to 30%. After curative resection postoperative mortality varied from 0% to 20%, local recurrence from 0% to 21%, and the rate of anastomotic leak from 0% to 25%. Survival at 10 years in patients who underwent curative resection varied from 20% to 63%, two year survival in those who underwent palliative resection varied from 7% to 32%, and median survival in those who underwent palliative diversion varied from one to eight months. The hazard rate ratios among individual surgeons, taking into account the identified risk factors, varied from 0.56 to 2.03, from 0.17 to 1.92, and from 0.57 to 1.50 for curative resection, palliative resection, and palliative diversion, respectively. CONCLUSION--There were significant variations in patient outcome among surgeons after surgery for colorectal cancer; such differences compromise survival. A considerable improvement in overall survival might be achieved if such surgery were undertaken by surgeons with a special interest in colorectal surgery or surgical oncology. 
Coronary occlusion following diagnostic angiography: salvage by intracoronary stenting. Catheter-induced coronary artery dissection and occlusion is a rare but serious complication of diagnostic cardiac angiography. This report describes the successful management of this complication with an intracoronary stent after prolonged balloon inflations and intracoronary thrombolytic therapy were unsuccessful. 
Trace elements and plasmapheresis. The relationship between serum aluminum (Al), zinc (Zn), copper (Cu), and iron (Fe) and plasmapheresis (PP) treatment was examined. Three patients with rheumatoid arthritis, six with myasthenia gravis, and 6 with multiple sclerosis were studied. Serum Al, Zn, Cu, and Fe were measured before and after PP. Plasma was separated by first filtration; a second filtration separated the plasma components. Three liters of plasma were treated in each PP session. With each PP treatment, total protein (TP) removed was 20 +/- 5% and serum albumin removed was +/- 6%. Serum Al rose significantly (p less than 0.01 from 1.1 +/- 0.2 micrograms/dl pre-PP to 2.8 +/- 0.4 micrograms/dl post-PP. Serum Zn, Cu, and Fe decreased significantly (p less than 0.01) from 86.2 +/- 7.4 micrograms/dl, 126 +/- 18 micrograms/dl, and 108 +/- 14 micrograms/dl pre-PP to 58.4 +/- 10.2 micrograms/dl, 104 +/- 6 micrograms/dl, and 82 +/- 16 micrograms/dl post-PP, respectively. Two days after the end of the six-month PP treatment, serum Al levels rose significantly (p less than 0.01), from 1.1 +/- 0.2 micrograms/dl to 3.6 +/- 0.8 micrograms/dl. However, serum TP, serum albumin, and serum Zn, Cu, and Fe did not change significantly. It thus appears essential in PP treated patients, to remove Al from the blood to protect against aluminum intoxication. 
Analysis of the transition to percutaneous placement of Greenfield filters. To establish whether a transition from surgical to percutaneous placement of Greenfield filters was justified, a review of the safety, efficacy, and cost-effectiveness of the two approaches was conducted. Between 1984 and 1989, 168 filters were placed in 169 patients, 48 surgically and 120 percutaneously. Placement was successful in 45 (94%) of the 48 surgical patients and 120 (99%) of the 121 percutaneous patients. Filter misplacement occurred in three (6%) surgical patients and no percutaneous patients. Clinically evident femoral vein thrombosis occurred in only four (5%) of the percutaneous patients, while inferior vena cava thrombosis occurred in three (3%) of the percutaneous patients. One pulmonary embolus occurred after percutaneous filter placement and resulted in death. The cost of percutaneous placement was 58% that of surgical placement. A retrospective review of the experience in our patient population indicates that safety, cost, and ease of insertion make the percutaneous approach the procedure of choice for Greenfield filter placement. 
Chronic myeloid leukemia in a woman with Still's disease treated with 198Au synoviorthesis. A 32-year-old woman presented with chronic myeloid leukemia 20 years after 2 198Au synoviortheses to her knees for severe juvenile rheumatoid arthritis. She progressed to blast phase of her disease and died from complications of therapy. The literature on rheumatoid arthritis, its therapy, radioisotopes and leukemia is reviewed. 
K-edge digital subtraction arthrography of the painful hip prosthesis: a feasibility study. K-edge energy subtraction radiography is a method for detecting the presence of iodinated contrast material by subtracting two digital radiographs produced by X-ray beams with energies above and below the iodine K edge. We performed a feasibility study on the application of K-edge energy digital subtraction arthrography (KEDSA) to painful hip prostheses. During arthrography, loosening of the prosthesis is implied if contrast material is seen dissecting around the prosthesis, an often difficult detection task because of adjacent prosthesis metal or cement. In conventional arthrography a preliminary mask image is thus used from which films obtained after injection of iodinated contrast material are subtracted. Movement by the patient during this process may preclude subsequent subtraction. With KEDSA, since multiple image pairs may be obtained after the injection of contrast material, the problem of patient motion is virtually eliminated. A conventional X-ray tube operating between 55 and 65 kVp was alternately filtered by iodine and cerium filters to produce the KEDSA images. The apparatus was capable of producing a subtracted image within 3 sec. The technique was applied to phantoms and to six patients immediately after hip arthrography that had been positive for prosthesis loosening. Although of lower spatial resolution, the KEDSA images were, in all cases, positive for loosening in a pattern consistent with the conventional arthrographic images. KEDSA was shown to be successful in detecting extraarticular contrast material. During a single study, subtraction in various imaging planes as well as postexercise subtraction imaging can be accomplished-techniques not heretofore possible in routine subtraction arthrography. 
Twelve-lead electrocardiographic evaluation of ischemia during percutaneous transluminal coronary angioplasty and its correlation with acute reocclusion. The sensitivity of the surface 12-lead electrocardiogram and that of standard (limb-lead) monitoring for the detection of ischemia during percutaneous transluminal coronary angioplasty were compared in 115 patients. The purpose was to identify the electrocardiographic leads that provide the most sensitive indicators of coronary ischemia during percutaneous transaluminal coronary angioplasty and to evaluate the "ischemic fingerprint" that is obtained with 12-lead electrocardiogram during balloon inflation as a predictor of abrupt reocclusion after successful percutaneous transaluminal coronary angioplasty procedures. During balloon inflations of 30 seconds, ischemia was detected in 61 of 145 vessels (42%) by limb-lead monitoring alone versus 130 of 145 vessels (90%) by 12-lead electrocardiography (p less than or equal to 0.001). In the nine patients (7.8%) who experienced abrupt reocclusion within 24 hours, the electrocardiogram during chest pain after percutaneous transaluminal coronary angioplasty was identical to that obtained during percutaneous transaluminal coronary angioplasty ("ischemic fingerprint"). None of the six patients who had chest pain after percutaneous transaluminal coronary angioplasty without evidence of abrupt reocclusion reproduced their ischemic fingerprint. The suggested optimal leads for monitoring ischemia are as follows: left anterior descending coronary artery, V2, and V3; circumflex artery, V2, and V3; and right coronary artery, III and aVF. 
Adenoma of type 2 pneumocytes with oncocytic features. An adenoma of type 2 pneumocytes in the periphery of the left lung was an incidental finding at the autopsy of a 28-year-old woman. Light microscopy revealed a predominantly papillary growth with oncocytic features. Ultrastructurally, multilaminated bodies and many mitochondria were found in the tumor cells and tubular myelin in the extracellular spaces. Immunohistochemistry revealed surfactant apoprotein in tumor cells and extracellularly. 
Vasovagal asystole during spinal anaesthesia. A patient in whom vasovagal asystole was induced by the performance of a spinal anaesthetic in the upright position is described. This illustrates the importance of routine monitoring of the electrocardiograph during regional anaesthesia. The risk of vasovagal syncope may be increased by the use of the sitting position and by the omission of anxiolytic premedication. 
Motor initiation versus execution in normal and Parkinson's disease subjects. We studied motor initiation and execution using wrist extension movements to changing target locations in eight normal subjects and nine Parkinson's disease (PD) patients before and after medications. Late changes resulted in double trajectories, indicating commitment to the initial target acquisition program followed by a correcting movement. There was compensation for earlier changes, even after onset of agonist muscle activity, resulting in a single trajectory, implying that the original trajectory had not yet been specified. However, movements were slowed in PD patients implying an abnormality in the content of the target acquisition program but not in the timing of its specification. In PD patients, the timing of the second movement onset correlated best with the timing of target location change and did not depend on initial movement completion. Thus, PD patients were able to program the second movement while the first movement was under way. 
Sonoelasticity imaging: results in in vitro tissue specimens. The authors present a method for imaging tissue stiffness (sonoelasticity) that has been developed and tested in a laboratory setting by using in vitro canine and human prostate glands. A low-frequency acoustic source was used to induce vibration in tissue under examination, and a color Doppler ultrasound (US) instrument was modified to detect vibration amplitude. The resulting image is a color "map" of tissue vibration superimposed on conventional gray-scale US images. Stiffer tissues vibrated less in response to audible sound, regardless of echogenicity. Normal human and canine prostate glands demonstrated a uniform vibration pattern. Four of four human prostatic adenocarcinomas and two stiff inclusions injected into canine prostate glands demonstrated a lack of vibration in comparison with normal surrounding tissue. The authors conclude that while further study is necessary, sonoelasticity imaging may enhance the detection of neoplasms by enabling their identification solely on the basis of stiffness. 
Prognostic factors associated with recurrence in clinical stage I adenocarcinoma of the endometrium. Two hundred sixty-four consecutive patients with clinical stage I endometrial adenocarcinoma who underwent primary surgical therapy between July 1979 and August 1988 were followed prospectively and evaluated for disease recurrence for 8-112 months (mean 51.5). Thirty-three patients (12.5%) developed recurrence or died of disease. In univariate statistical analysis, prognostic factors significantly associated with disease recurrence were as follows: age (mean 68.6 years with versus 60.3 years without recurrence; P = .0001); histology (adenocarcinoma 8.8%, adenosquamous 35.7%, papillary 25%, clear-cell 57.1%; P less than .0001); tumor grade (grade 1, 7.7%, grade 2, 10.5%, grade 3, 36.1%; P less than .0001); depth of myometrial invasion (none 9.8%, less than one-half 7.4%, one-half or greater 29.6%; P = .0001); lymph node status (negative 8.3%, positive 47.6%; P less than .0001); non-nodal extrauterine disease spread (absent 11.0%, present 50%; P = .0003); peritoneal cytology (negative 9.4%, positive 26.3%; P = .004), and tumor size (2 cm or less 7%, greater than 2 cm 17.3%; P = .05). Cervical extension and uterine size had no significant effect on recurrence. Using multivariate analysis, grade 3 tumor (P = .002), advancing age (P = .004), lymph node metastasis (P = .006), and presence of extrauterine disease spread other than lymph node metastasis (P = .038) were the only variables significantly associated with disease recurrence or death. This study supports the new International Federation of Gynecology and Obstetrics surgical staging system for endometrial cancer. 
Preoperative and postoperative "aneurysm" associated with coarctation of the aorta. The reported incidence of aortic aneurysm after surgical repair or balloon angioplasty for aortic coarctation varies widely. To determine the incidence of aneurysm formation after surgery, preoperative and postoperative cineangiograms from 65 patients who underwent operation at age 1.5 +/- 3.4 years were examined. Repair included a prosthetic patch in 14 patients, end to end anastomosis in 28 and subclavian flap in 23. Aneurysm was documented by change in contour or irregularities in contour at the repair site or by abnormal dimensions at the repair site, defined by the ratio of the widest measurement at the repair site to the measurement of the aorta at the diaphragm. An aneurysmal bulge above the ductus diverticulum was identified in 14 (23%) of 60 patients preoperatively; the area showed no change 4.72 +/- 4.07 years after surgery. Significant changes at the repair site were seen in only three patients, all of whom had Dacron patch repair. One patient had a change in contour at the repair site, one had an abnormally high repair site to diaphragmatic aorta ratio and one had a progressive increase in this ratio. Thus, during childhood years, 3 (5%) of 65 patients were diagnosed as having aneurysm at the surgical repair site. In conclusion, 1) comparison with preoperative cineangiograms, especially for aneurysmal bulges above the ductus arteriosus, is essential before an aneurysm can be attributed to coarctation repair by any technique, and 2) aneurysm developed only in patients subjected to Dacron patch repair. 
Ki-1-positive lymphoma developing 10 years after the diagnosis of hairy cell leukemia. The case is described of a 62-year-old man with a 10-year history of hairy cell leukemia (HCL) who subsequently had a large-cell anaplastic or so-called Ki-1-positive lymphoma. Immunocytochemical staining of the lymphomatous node revealed positivity for Ki-1 (CD30) and epithelial membrane antigen in the tumor cells, and flow cytometric analysis showed simultaneous expression of Leu M5 (CD11c) and Leu 14 (CD22). Although HCL has been reported to coexist with both Hodgkin's disease and non-Hodgkin's lymphoma, the authors believe this is the first case in which a Ki-1-positive lymphoma developed in a patient with HCL. The clinicopathologic and immunologic features of both entities are discussed, as is the association of HCL with other neoplasms. 
Evaluation of a new weaning index based on ventilatory endurance and the efficiency of gas exchange. We hypothesized that the ventilatory capacity needed to wean from mechanical ventilation (mv) depends on two variables: ventilatory endurance and the efficiency of gas exchange. We also hypothesized that these variables could be assessed from data readily available at the bedside, including tidal volume (VT) on mv and during spontaneous breathing (sb), ventilator peak inspiratory pressure (Ppk), and patient negative inspiratory pressure (NIP). Ventilatory endurance was evaluated using a modified pressure-time index: PTI = TI/Ttot x Pbreath/NIP, where Pbreath = Ppk x VTsb/VTmv. Defining VE40 as the minute ventilation needed to bring PaCO2 to 40 mm Hg, the efficiency of gas exchange was evaluated by calculating VE40/VTsb = (VE x PaCO2)mv/VTsb x 40. Because high levels of inspiratory effort might cause patients to reduce VTsb and thereby compromise CO2 elimination, we devised a weaning index (WI) that combines ventilatory endurance and the efficiency of gas exchange: WI = PTI x (VE40/VTsb). The study population comprised 38 patients with chronic obstructive pulmonary disease, adult respiratory distress syndrome, pneumonia, neuromuscular disease, and miscellaneous other conditions. They had been mechanically ventilated more than 3 days and were considered by clinical criteria to be ready for weaning. Of 46 weaning trials, 19 were successful, 2 were partially successful, and 25 failed. PTI and VE40/VTsb were higher in patients who failed (p less than 0.05), but neither variable alone had sufficient sensitivity or specificity to predict the outcome of weaning trials accurately. 
Symptoms associated with tamoxifen treatment in postmenopausal women. Adjuvant breast cancer therapy with tamoxifen is associated with greater disease-free survival and possibly overall survival. Long-term treatment, possibly of indefinite duration, is being evaluated. Compliance with long-term therapy will depend largely on the nature and severity of tamoxifen's side effects. We evaluated the symptoms associated with tamoxifen therapy in 140 postmenopausal women with axillary node negative breast cancer in remission (mean years since menopause, 9.3) enrolled in a placebo-controlled, randomized toxicity study. Tamoxifen recipients reported moderated or severe vasomotor symptoms up to 17%, and gynecologic symptoms up to 4% more frequently than placebo subjects. Persistent vasomotor, gynecologic, or other major side effects were reported by 48% of tamoxifen recipients, and by 21% of placebo subjects. These carefully collected data suggest significant perceived symptom 'cost' of tamoxifen therapy in postmenopausal women, of a magnitude likely to compromise long-term compliance. 
Nephrotoxic potential of Bence Jones proteins BACKGROUND. The renal manifestations of diseases associated with the production of monoclonal light chains--myeloma (cast) nephropathy, light-chain deposition disease, and amyloidosis AL--result from the deposition of certain Bence Jones proteins as tubular casts, basement-membrane precipitates, or fibrils, respectively. For unknown reasons, the severity of the renal manifestations of these diseases varies greatly from patient to patient. We employed an experimental in vivo model to determine the pathologic importance of various Bence Jones proteins. METHODS. Mice were injected intraperitoneally with 300 mg of Bence Jones protein from 40 patients with multiple myeloma or amyloidosis AL and killed 48 hours later. The mouse kidneys were examined by light and electron microscopy, and light-chain deposits were identified immunohistochemically with highly specific antihuman light-chain antiserum. RESULTS. Of the 40 different human Bence Jones proteins studied, 26 were deposited in the mouse kidneys predominantly as tubular casts, basement-membrane precipitates, or crystals; no light-chain deposits were detected in the kidneys of the mice that received the other 14 Bence Jones proteins. Of the 18 patients for whom renal tissue was available for study, the findings in 14 were comparable to those in the mice. Furthermore, the proteins obtained from 22 of the 27 patients whose serum creatinine concentrations equaled or exceeded 168 mumol per liter (1.9 mg per deciliter) were deposited in the mouse kidneys, whereas protein deposition occurred after the injection of proteins from only 4 of the 13 patients with serum creatinine concentrations below 168 mumol per liter. The repeated injection of Bence Jones proteins from two patients who had amyloidosis AL resulted in deposition of the protein in the mouse kidneys as amyloid. CONCLUSIONS. Particular Bence Jones proteins are primarily responsible for producing the distinctive types of protein deposition in renal tissue and the clinical manifestations that occur in patients with light-chain-associated diseases. This experimental model has potential value for the identification of nephrotoxic or amyloidogenic light chains. 
Level of axillary involvement by lymph node metastases from breast cancer is not an independent predictor of survival. We examined the relationship of axillary level of lymph node metastases from clinical stage I and II breast cancer to overall survival and disease-free survival rates in 135 patients who underwent complete axillary lymph node dissection to determine if anatomic level of axillary involvement (I vs II vs III) is an independent prognostic factor. All patients underwent either modified radical mastectomy or lumpectomy with axillary dissection and whole breast radiotherapy for breast cancer. Median follow-up was 6.9 years. We found no difference in overall survival or disease-free survival between patients whose highest or only level of axillary involvement was level I compared with patients whose highest or only level was II. Although patients whose highest level of nodal involvement was III had significantly worse overall survival and disease-free survival rates than patients whose highest nodal involvement was I or II, when patients were stratified by the total number of positive nodes (one to three vs four or more), there was no difference in overall survival or disease-free survival rates between levels I, II, and III. These findings indicate that the level of axillary involvement for stage II breast cancer is not of independent prognostic significance. 
In situ venous valve construction. A technique of in situ deep venous valve construction based on vein wall intussusception is described. The technique has been used to construct a size-matched, autogenous valve in the femoral vein of the dog. Forty-one valves have been constructed. Immediately after construction, all 41 were patent at ascending phlebography and Harvey's test showed them to be competent. Descending phlebography demonstrated competence in 38 valves. Hydrostatic testing was performed on 27 valves in the vertical position at pressure gradients in the range 0.2-250 cmH2O. Of these, 24 valves were fully competent. Six valves were studied at intervals between 1 and 112 days after construction. All six were competent by Harvey's test and five were competent at descending phlebography. There was no evidence of thrombosis in any valve. This technique may be suitable for replacement of deep venous valves in patients with the calf pump failure syndrome caused by deep venous reflux. 
Prognostic importance of collateral flow and residual coronary stenosis of the myocardial infarct artery after anterior wall Q-wave acute myocardial infarction. Residual high-grade coronary stenosis and collateral flow are frequent findings in the chronic phase after a Q-wave acute myocardial infarction (AMI). The prognostic importance of a residual stenosis of the infarct artery and of collateral flow to the infarct area was analyzed in a group of 102 young patients (mean age 35 years, range 22 to 39) who had survived an anterior wall Q-wave AMI. Patients whose only significant lesion (greater than 50% luminal diameter reduction) was in the proximal portion of the left anterior descending artery were enrolled in the study. A 50 to 74% diameter stenosis was present in 33 of 102 patients (32%), 43 (42%) had a 75 to 99% stenosis and 26% had a total occlusion of the infarct vessel. Collateral vessels, which were evaluated by a scoring system, were present in 52 of 102 patients (51%). Four percent had only faint (score 1), 17 of 102 patients (17%) had moderate and 32 patients (31%) had good collateral flow (score greater than 4). The 8-year cumulative mortality was 15.2%--an eightfold increase compared with the age-matched general population. No patient with less than 75% stenosis died during follow-up, whereas the cumulative 8-year mortality was 23 and 17% in patients with a 75 to 99% stenosis or total occlusion, respectively (p less than 0.01). Patients with at least moderate collateral flow had a mortality rate of 21%, versus 8% for patients without or with faint collateral flow (p less than 0.05). 
The recognition and control of occupational disease. Occupational diseases account each year in the United States for an estimated 50,000 to 70,000 deaths and 350,000 new cases of illness. Often, however, occupational diseases are not correctly diagnosed, because they mimic diseases due to other causes and because most physicians are not well trained in their recognition. Opportunities for prevention and treatment are therefore lost. The occupational history is the most effective means for proper diagnosis of occupational illness. It should routinely be obtained for every patient. A brief but systematic guide for obtaining an occupational history is presented in this report. Also, approaches are summarized for the recognition and diagnosis of such important occupational diseases as occupational cancer, asbestosis and other respiratory disorders, and occupational neuropsychologic disorders. The management and prevention of occupational diseases depend on reduction of hazardous exposures in the workplace and better education of workers, industrial managers, and physicians. This report outlines a program for the control of occupational disease based on (1) preventing exposures in the workplace, (2) premarket toxicity testing of new chemicals and technologies, and (3) astute clinical diagnosis. 
Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators BACKGROUND. Without strong evidence of benefit, the use of carotid endarterectomy for prophylaxis against stroke rose dramatically until the mid-1980s, then declined. Our investigation sought to determine whether carotid endarterectomy reduces the risk of stroke among patients with a recent adverse cerebrovascular event and ipsilateral carotid stenosis. METHODS. We conducted a randomized trial at 50 clinical centers throughout the United States and Canada, in patients in two predetermined strata based on the severity of carotid stenosis--30 to 69 percent and 70 to 99 percent. We report here the results in the 659 patients in the latter stratum, who had had a hemispheric or retinal transient ischemic attack or a nondisabling stroke within the 120 days before entry and had stenosis of 70 to 99 percent in the symptomatic carotid artery. All patients received optimal medical care, including antiplatelet therapy. Those assigned to surgical treatment underwent carotid endarterectomy performed by neurosurgeons or vascular surgeons. All patients were examined by neurologists 1, 3, 6, 9, and 12 months after entry and then every 4 months. End points were assessed by blinded, independent case review. No patient was lost to follow-up. RESULTS. Life-table estimates of the cumulative risk of any ipsilateral stroke at two years were 26 percent in the 331 medical patients and 9 percent in the 328 surgical patients--an absolute risk reduction (+/- SE) 17 +/- 3.5 percent (P less than 0.001). For a major or fatal ipsilateral stroke, the corresponding estimates were 13.1 percent and 2.5 percent--an absolute risk reduction of 10.6 +/- 2.6 percent (P less than 0.001). Carotid endarterectomy was still found to be beneficial when all strokes and deaths were included in the analysis (P less than 0.001). CONCLUSIONS. Carotid endarterectomy is highly beneficial to patients with recent hemispheric and retinal transient ischemic attacks or nondisabling strokes and ipsilateral high-grade stenosis (70 to 99 percent) of the internal carotid artery. 
Epidemiologic and clinical aspects of insulin resistance and hyperinsulinemia. Epidemiologic studies have shown that insulin is a risk factor for coronary heart disease (CHD). Clinical studies have also demonstrated positive correlations between insulin and blood pressure, triglycerides, total cholesterol, fibrinogen, and plasminogen activator inhibitor. Moreover, there is an inverse correlation between insulin and high-density lipoprotein (HDL). These studies have provided evidence in support of the biologic plausibility of epidemiologic observations, but they have not clearly established insulin's role in the pathogenesis of human cardiovascular diseases (CVD) such as hypertension. In fact, there is considerable evidence that insulin resistance (abnormal nonoxidative glucose disposal), not hyperinsulinemia, is the primary insulin-related abnormality in human hypertension, and that hyperinsulinemia occurs as a response to insulin resistance. Skeletal muscle appears to be the primary site of insulin resistance in essential hypertension, although other organs, such as the kidneys and liver--key sites for cell and water homeostasis and lipoprotein regulation, respectively--may respond normally to insulin. Adipocytes also appear to be a site of insulin resistance. Thus, the putative interrelationship between hyperinsulinemia and insulin resistance, on the one hand, and with blood pressure and lipoproteins, on the other, is a complex one and may involve organ-specific insulin resistance. Altered cation transport is one of several mechanisms by which insulin resistance might raise blood pressure. The Na+, K(+)-ATPase and Ca(2+)-ATPase pumps are insulin sensitive. Thus, when insulin resistance is present, the activity of these pumps in the smooth muscle of the arterial wall might be reduced. This would lead to an intracellular accumulation of sodium and calcium, thereby sensitizing the vascular wall to pressor substances. Moreover, secondary hyperinsulinemia will occur, and insulin has been shown to stimulate sympathetic nervous system activity and to increase renal tubular absorption of sodium. Insulin is also a growth factor and therefore might have a trophic effect on the vessel wall, one that could initiate and/or sustain hypertension as well as atherosclerosis. Abnormal lipoprotein metabolism is yet another possible explanation for the accelerated atherosclerosis that has been observed in persons with abnormal carbohydrate tolerance and insulin resistance. Hyperinsulinemia and insulin resistance both play a role in the expression of elevated very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) levels as well as in the depression of HDL levels. Coronary risk reduction has been disappointing when blood pressure has been lowered with treatment regimens based on thiazide diuretics and/or beta blockers. Thiazides and some beta blockers may further impair tissue insulin sensitivity and often cause blood lipoprotein abnormalities.(ABSTRACT TRUNCATED AT 400 WORDS). 
The natural history of superficial femoral artery stenoses. Since the natural history of specific superficial femoral artery stenoses is not known, we examined progression rates of superficial femoral artery stenoses in 45 lower extremities found when arteriograms were obtained of 38 patients for symptomatic atherosclerotic disease in the opposite leg or abdomen. These initial superficial femoral artery arteriograms were compared with later arteriograms in 25 limbs, duplex scans in 27 limbs, and both modalities in 7 limbs. After a mean interval of 37 months, most superficial femoral artery stenoses (72%) did not progress. However, 12 superficial femoral artery stenoses progressed (28%; mean follow-up, 37 months, including 7 that occluded (17%). Superficial femoral artery stenoses progressed among patients who complained of symptom progression at a rate faster than that among asymptomatic patients (15.6%/year vs 3%/year; p = 0.006). Superficial femoral artery lesions also progressed more rapidly among patients whose contralateral superficial femoral artery was occluded (10%/year vs 1.6%/year; p = 0.04). By multivariate regression analysis, symptom progression and smoking history were predictive of superficial femoral artery stenosis progression. In the seven patients whose superficial femoral artery stenoses progressed to occlusion, the average rate of stenosis progression was 12%/year (maximum predicted rate, 30% per year by 95% confidence limit). These results indicate that superficial femoral artery stenoses usually progress with synchronous symptomatic deterioration. Other than symptom progression, only cumulative smoking history and contralateral superficial femoral artery occlusion could be associated with superficial femoral artery stenosis progression in this small series. 
Knowledge and beliefs about cancer in a socioeconomically disadvantaged population. Americans living in poverty experience a higher incidence of and greater mortality from cancer than the nonpoor. At least 50% of the difference in mortality is believed to be due to delay in diagnosis, although risk-promoting lifestyles and behaviors also contribute to decreased survival. A potential exacerbating factor among the poor is inadequate information and knowledge about cancer and its treatment. Interviews were conducted with 128 cancer patients from a socioeconomically disadvantaged population to assess knowledge of cancer and its treatment and to evaluate care-seeking behaviors. Results indicated that although patients relied primarily on their physicians for information about their disease and treatment, a number of misconceptions regarding cancer existed in this population. Notably, nearly 50% of the patients surveyed either denied or did not know that smoking was related to the development of cancer. Additionally, patients frequently reported inappropriate care-seeking behaviors when asked to respond to a series of common disease-related signs or symptoms. These findings suggest that misinformation and misconceptions regarding cancer and its treatment among patients in this sample may contribute to inappropriate care-seeking behaviors. 
Comparative safety, tolerance, and pharmacokinetics of amphotericin B lipid complex and amphotericin B desoxycholate in healthy male volunteers. Amphotericin B lipid complex (ABLC), a lipid complex formulation of amphotericin B, and amphotericin B desoxycholate (AB) were compared for safety, tolerance, and pharmacokinetics in two groups of eight healthy male volunteers. After a 1-mg test dose, study drug was infused at 0.1, 0.25, and 0.5 mg/kg; the 0.5-mg/kg dose was not given to subjects receiving AB. ABLC caused few acute adverse effects except for mild somnolence (drowsiness) in six volunteers. In addition, three of eight ABLC recipient had asymptomatic, transient serum transaminase elevations that resolved spontaneously. The AB recipients experienced more acute side effects, but only one had a mild shaking chill: three of eight also experienced sleepiness. No significant changes in vital signs, electrocardiogram, oximetry, pulmonary function, or clinical status were observed in either group. Due to its increased estimate volume of distribution and estimated clearance. ABLC yielded decreased amphotericin B levels and area under the serum concentration versus time curve relative to AB. 
Effects of sleep-induced increases in upper airway resistance on ventilation. To determine the effects of the sleep-induced increases in upper airway resistance on ventilatory output, we studied five subjects who were habitual snorers but otherwise normal while awake (AW) and during non-rapid-eye-movement (NREM) sleep under the following conditions: 1) stage 2, low-resistance sleep (LRS); 2) stage 3-4, high-resistance sleep (HRS) (snoring); 3) with continuous positive airway pressure (CPAP); 4) CPAP + end-tidal CO2 partial pressure (PETCO2) mode isocapnic to LRS; and 5) CPAP + PETCO2 isocapnic to HRS. We measured ventilatory output via pneumotachograph in the nasal mask, PETCO2, esophageal pressure, inspiratory and expiratory resistance (RL,I and RL,E). Changes in PETCO2 were confirmed with PCO2 measurements in arterialized venous blood in all conditions in one subject. During wakefulness, pulmonary resistance (RL) remained constant throughout inspiration, whereas in stage 2 and especially in stage 3-4 NREM sleep, RL rose markedly throughout inspiration. Expired minute ventilation (VE) decreased by 12% in HRS, and PETCO2 increased in LRS (3.3 Torr) and HRS (4.9 Torr). CPAP decreased RL,I to AW levels and increased end-expiratory lung volume 0.25-0.93 liter. Tidal volume (VT) and mean inspiratory flow rate (VT/TI) increased significantly with CPAP. Inspiratory time (TI) shortened, and PETCO2 decreased 3.6 Torr but remained 1.3 Torr above AW. During CPAP (RL,I equal to AW), with PETCO2 returned to the level of LRS, VT/TI and VE were 83 and 52% higher than during LRS alone. Also on CPAP, with PETCO2 made equal to HRS, VT, VT/TI, and VE were 67, 112, and 67% higher than during HRS alone. 
Total arthroplasty of the hip after childhood sepsis. Total hip arthroplasty was performed in 45 hips of 44 patients who had pyogenic arthritis of the hip during childhood. The average age of the patients was 36.4 years (range 19 to 50). The interval between active infection and arthroplasty ranged from 11 to 40 years, and average follow-up was 65.4 months (range 58 to 80). Specimens of tissue taken before and during operation gave negative cultures in all hips, and no patient had reactivation of infection. The mean functional rating of the hips was 58 points before operation and 90 at the final review. Complications were seen in 11 cases (24%), loosening of components occurred in six (13%) and one hip had to be revised for acetabular component migration. Acetabular allografts were required in 27 hips (60%). All allografts united but there was partial resorption of the graft in the non-weight-bearing area in all. 
Hemorrhagic venous infarction after excision of an arteriovenous malformation: case report. A case of arteriovenous malformation (AVM) in which postoperative hemorrhagic infarction developed, probably because of occlusion of the former draining veins, is reported. The hemorrhage developed in the temporal lobe 3 days after the initial operation and was located in the immediate vicinity of the site of the AVM. The following findings suggest that the postsurgical hemorrhage probably resulted from a venous thrombosis: 1) no evidence of residual AVM; 2) delayed onset of the hemorrhage, inconsistent with the time course of a hemorrhage developing according to the breakthrough theory or with insufficient hemostasis with a high-pressure afterload; 3) good correlation between the location of the hemorrhage and the occlusion of the draining veins; and 4) multifocal hemorrhage affecting both the gray matter and the subcortical white matter. Postoperative hemorrhagic infarction caused by thrombosis in the draining veins is rare, but it should be considered as a distinct postoperative complication after removal of an AVM. 
Cell recovery during segmental intestinal perfusion in healthy subjects and patients with Crohn's disease. The recovery of cells arising from small intestinal mucosa alone was studied during continuous perfusion of a closed segment of jejunum. The perfusion technique minimised the contamination of the perfused segment with, for example, proteolytic enzymes from pancreas, allowing recovery of viable cells. The use of hyaluronidase in the perfusion fluid increased the recovery of cells fivefold, the median recovery being 8 x 10(6) cells. The cells were analysed with monoclonal antibodies and flow cytometry. Nearly all cells (98-99%) recovered during perfusion of healthy control subjects and patients with Crohn's disease were epithelial cells. The jejunal cells expressed HLA-DR in similar proportions--around 30%--in patients and control subjects. The ratio between CD4+ and CD8+ lymphocytes was similar (0.2) in control subjects and patients with inactive Crohn's disease but decreased (0.03) in patients with active Crohn's disease in the ileum. 
Candidal mediastinitis after surgical repair of esophageal perforation. Candidal mediastinitis, like Boerhaave's syndrome, is uncommon, and both, if treated late or incompletely, frequently result in death. Early recognition and aggressive medical and surgical intervention are the best means to convalescence and cure in both conditions. 
Postischemic myocardial "stunning". Identification of major differences between the open-chest and the conscious dog and evaluation of the oxygen radical hypothesis in the conscious dog. Recent studies suggest that oxygen-derived free radicals contribute to the pathogenesis of postischemic myocardial dysfunction (myocardial "stunning"). This concept, however, is predicated exclusively on results obtained in open-chest preparations, which are subject to the confounding influence of many unphysiological conditions. The lack of supporting evidence in more physiological animal models represents a major persisting limitation of the oxy-radical hypothesis of myocardial stunning. The goal of this study was to address two fundamental (and related) questions: 1) Does the open-chest animal model alter the phenomenon of myocardial stunning? 2) If so, how valid are the concepts, derived from such a model, regarding the pathogenetic role of oxy-radicals? In part 1 of the study, myocardial stunning after a 15-minute coronary occlusion was compared in 30 pentobarbital-anesthetized open-chest dogs and in 19 conscious dogs. For any given level of collateral flow during occlusion, the recovery of systolic wall thickening after reperfusion was markedly less in open-chest animals. In an additional group of five open-chest dogs, a close inverse relation was noted between body temperature and postischemic wall thickening, indicating that the recovery of the stunned myocardium in acute experiments may vary markedly depending on how temperature is controlled. Because of these major differences between open-chest and conscious dogs, the oxy-radical hypothesis needs to be tested in the latter model. Thus, in part 2 of the study, conscious unsedated dogs undergoing a 15-minute coronary occlusion were randomized to an intravenous infusion of either saline (19 coronary occlusions) or superoxide dismutase (SOD) plus catalase (CAT) (21 coronary occlusions). Despite the fact that the plasma levels of SOD and CAT declined rapidly after reperfusion, postischemic wall thickening was significantly greater in treated compared with control dogs throughout the first 6 hours of reflow. Thus, a brief (60-minute) infusion of SOD and CAT produced a sustained improvement of recovery of contractility. The magnitude of this beneficial effect was a function of the severity of ischemia: the lower the collateral perfusion, the greater the improvement effected by the enzymes. The accelerated recovery produced by SOD and CAT was not followed by any deterioration of contractility, suggesting that postischemic dysfunction is not a teleologically "protective" phenomenon. In conclusion, the severity of myocardial stunning is greatly exaggerated by the unphysiological conditions present in the barbiturate-anesthetized open-chest dog.(ABSTRACT TRUNCATED AT 400 WORDS). 
Suppressor T-cell deficiency in primary sclerosing cholangitis. Case and family study. Primary sclerosing cholangitis is considered to be an autoimmune disease of the liver in which there is an association with the HLA phenotypes B8 and DR3 and in which circulating autoantibodies occur. Abnormalities of immune regulation may be present but whether or not they are primary or acquired is not known. This report is of a patient with primary sclerosing cholangitis who was homozygous for HLA B8 DR3, had a circulating antinuclear antibody, and a defect in nonspecific suppressor T-cell activity despite glucocorticosteroid treatment. Nevertheless, family studies revealed no evidence of an immunoregulatory defect in first-degree relatives despite the presence of Raynaud's phenomenon and malignancy in two sisters. 
Chondroblastomalike extraskeletal chondroma. An unusual extraskeletal tumor occurring in the right thumb of a 44-year-old man exhibited histologically a chondroblastomalike appearance. The tumor was characterized by dense proliferation of chondroblastic cells admixed with a few multinucleated giant cells of osteoclast type. The patient had no evidence of local recurrence or metastasis three-and-a-half years after a simple excision. 
Novel approach to iatrogenic bile peritonitis. Bile peritonitis after injury to the biliary tree is a serious complication that requires exploratory laparotomy. Our patient had an obstructing ampullary carcinoma, and generalized bile peritonitis developed from attempted percutaneous transhepatic cholangiography. The patient's condition was managed by peritoneal lavage and endoscopic transampullary stenting, with immediate relief of pain and toxicity. Exploratory laparotomy was avoided, and an eventual pylorus-sparing Whipple resection was the definitive treatment. We believe this to be the first report of successful nonoperative treatment of a patient with bile peritonitis with obstructive jaundice. 
Prognostic value of galactose elimination capacity, aminopyrine breath test, and ICG clearance in patients with cirrhosis. Comparison with the Pugh score. Seventy-eight patients with cirrhosis were prospectively followed for up to 20 months, on the average. At entry into the study, galactose elimination capacity, aminopyrine breath test, and ICG clearance were measured. At the end of the study, 27 patients had died. Univariate analysis using the Kaplan-Meier method showed that both quantitative liver function tests (galactose elimination capacity: P less than 0.025; aminopyrine breath test: P less than 0.001; ICG clearance: P less than 0.005) and common clinical and biochemical data (encephalopathy: P less than 0.001; ascites: P less than 0.001; serum bilirubin: P less than 0.005; serum albumin: P less than 0.001; prothrombin index: P less than 0.05) were significant predictors of survival. To investigate whether quantitative liver function tests could contribute to a better definition of the prognosis, once Pugh score had already been taken into account, a multiple regression analysis according to the Cox model was performed. Pugh score and galactose elimination capacity resulted in the only independent prognostic covariates. From them a prognostic index was calculated, and the model was validated in an additional sample of 70 patients investigated according to the same protocol. The contribution GEC gave to the assessment of overall prognosis over that obtained using the Pugh score was slight, as estimated by the statistical parameters of the Cox's model, but was significant as assessed by a ROC curve analysis (P = 0.05). These data show that all quantitative liver function tests were predictors of survival in cirrhosis, and that the galactose elimination capacity added some new prognostic information to those already available using the Child-Turcotte-Pugh classification. 
Regional differences in elastic recoil after percutaneous transluminal coronary angioplasty: a quantitative angiographic study. The immediate result of percutaneous transluminal coronary angioplasty is influenced by both plastic and elastic changes of the vessel wall. To evaluate the amount of elastic recoil after coronary balloon angioplasty, the minimal luminal cross-sectional area of the largest balloon used at highest inflation pressure was compared with the minimal luminal vessel cross-sectional area directly after final balloon deflation in 607 lesions (526 patients). Elastic recoil was defined as the difference between balloon cross-sectional area and minimal luminal cross-sectional area of the dilated coronary segment immediately after balloon withdrawal. A videodensitometric analysis technique was used to avoid geometric assumptions on stenosis morphology directly after angioplasty. Mean balloon cross-sectional area was 5.3 +/- 1.6 mm2 and minimal luminal cross-sectional area after angioplasty was 2.8 +/- 1.4 mm2. Reference areas before and after angioplasty did not differ (6.0 +/- 2.6 and 6.2 +/- 2.6 mm2, respectively). Univariate analysis revealed that asymmetric lesions, lesions located in less angulated parts of the artery and lesions with a low plaque content showed more elastic recoil. Lesions located in distal parts of the coronary tree were also associated with more elastic recoil probably related to relative balloon oversizing in these distal lesions. 
Differentiation in B-precursor acute lymphoblastic leukemia cell populations with CD34-positive subpopulations. B-precursor acute lymphoblastic leukemia bone marrow specimens that contained subpopulations of cells with immunophenotypes corresponding to early (CD34) and late (CD20) and (CD22) stages of normal B-cell differentiation were studied. Subpopulations of cells were isolated according to immunophenotype and then analyzed by both a clonogenic assay and molecular genetic methods. Clonal equivalence of the early and late immunophenotypic subpopulations was confirmed for each case by the demonstration of identical lg gene rearrangements. The in vitro colony-forming assay consistently showed a growth advantage for the CD34+ subpopulations over the CD34- subpopulations. CD34 mRNA was detected readily in these isolated precursor cells. When two specimens in which virtually all of the leukemia cells were CD34+ and CD34+CD20+ and CD34+CD22+ subpopulations were also present the CD34 mRNA was limited to the cells without the late-stage differentiation antigens on their surface. Furthermore, the c-myb mRNA was found only in the subpopulations that also contained CD34 mRNA. Our results show that a limited program of differentiation reminiscent of normal B-cell development may be present in this leukemia. 
Global T wave inversion. Because global T wave inversion has not been specifically characterized, 100 electrocardiograms (ECGs) with this pattern (frontal plane T vector -100 degrees to -170 degrees with precordial T inversion) were prospectively collected from approximately 30,000 consecutively interpreted ECGs and analyzed blindly. There was a striking female predominance (82 women vs. 18 men; p less than 0.0005) despite an essentially equal number of female and male hospital admissions. There was a single statistically significant ECG correlate: a more vertical QRS axis in women (+14.1 degrees +/- 45.3 degrees vs. -5.6 degrees +/- 31.3 degrees; p = 0.034). The T waves were basically symmetric (68%), the influence of this factor usually altering the characteristically asymmetric T wave inversions of right bundle branch block (4 of 5) and left ventricular hypertrophy (21 of 36). Asymmetry was mainly associated with digoxin therapy (21 of 32 patients taking digoxin; p less than or equal to 0.0005) and a corrected QT (QTc) interval (0.433 +/- 0.095) shorter than with symmetric T wave inversions (0.507 +/- 0.074; p less than or equal to 0.0005) though not reaching the degree of shortening expected for digitalization. Twenty-eight patients admitted for acute myocardial infarction and 23 for a central nervous system disorder accounted for the majority of patients with symmetric T wave inversion. Fifteen of 18 patients who had coronary angiography had some degree of coronary artery disease: 3 had angiographically normal coronary arteries. 
Somato-somatic referred pain caused by suprasegmental spinal cord tumor. Tactile stimulation of a coin-sized area in a T-2 dermatome consistently triggered a lancinating pain in the ipsilateral C-8 dermatome in a 38-year-old woman. The SEP and an MRI led to a diagnosis of a tumor at the left cervico-medullary junction, much higher than the clinically suspected level. Surgical exploration revealed an exophytic glioma, and the pain was abolished postoperatively. Ephaptic transmission at the tumor site was suspected as a pathophysiologic mechanism. 
Early constrictive pericarditis and anemia after Dressler's syndrome and inferior wall myocardial infarction. Early constrictive pericarditis and anaemia developed in a 52 year old man after he had an inferior wall myocardial infarction complicated by Dressler's syndrome. Total pericardiectomy at the time of coronary artery bypass surgery resulted in complete resolution of signs and symptoms. 
Effect of sinorphan, an enkephalinase inhibitor, on plasma atrial natriuretic factor and sodium urinary excretion in cirrhotic patients with ascites. We examined the acute effects of sinorphan, an inhibitor of enkephalinase, on plasma atrial natriuretic factor (ANF) and urinary sodium excretion in cirrhotic patients with ascites. A single oral dose of sinorphan (100 or 30 mg in 11 and 5 patients, respectively) was administered against placebo according to a double blind cross-over protocol. Basal plasma ANF levels varied over a large range between 2.6-79 pmol/L. Sinorphan, at a dose of 100 mg, inhibited 70% of plasma enkephalinase activity 60 min after ingestion and elicited simultaneously an increase in plasma ANF and cGMP levels 1.8 and 1.5 times basal values, respectively. There was a transient increase in sodium urinary output without a change in creatinine clearance over the initial 2-h period following drug administration. An increase in urinary cGMP was also observed on a longer period of 6 h. Plasma aldosterone decreased significantly, but the lowest concentration was reached 1 h later than the peak of plasma ANF. Mean blood pressure and PRA were unmodified. The effects of 30 mg sinorphan on plasma ANF, cGMP, and aldosterone were also significant, but less marked than those of the higher dose. Therefore, enkephalinase inhibition transiently increases sodium urinary excretion in cirrhotic patients with ascites via a mechanism that is likely to imply reduction of ANF catabolism. These results suggest that ANF could play a role in the control of sodium homeostasis in liver cirrhosis with ascites. 
Aneurysm of the distal anterior inferior cerebellar artery unrelated to the cerebellopontine angle: case report. This is a case report of an unusual aneurysm of the distal anterior inferior cerebellar artery. A 44-year-old woman had a severe frontal headache and vomiting of sudden onset. On the day after admission, the patient began to demonstrate nuchal rigidity and difficulty with upward gaze bilaterally. There were no complaints at this time suggestive of a syndrome of the cerebellopontine angle. A computed tomographic scan revealed an intraventricular hemorrhage of the 3rd and 4th ventricles; however, multiple attempts at four-vessel angiography were required before an aneurysm could be demonstrated. On the 28th hospital day, a suboccipital craniectomy using the retromastoid approach in the lateral position was performed. A saccular aneurysm with a surrounding hematoma in the distal anterior inferior cerebellar artery was found and clipped. The operative findings revealed that the aneurysm was unrelated to the cerebellopontine angle. After surgery, the patient had an uneventful recovery and complete resolution of symptoms. 
Cancer incidence in Norwegian Seventh-Day Adventists 1961 to 1986. Is the cancer-life-style association overestimated? Standardized incidence ratio for cancer in Norwegian Seventh-Day Adventists compared with the general population was not significantly different from unity (men 91, women 97). Persons converting late in life had a higher incidence than those converting at an earlier age. Respiratory cancers (standardized incidence ratio [SIR] 59, 95% CI = 36 to 91) and cancers with an unspecified site (SIR 53, 95% CI = 25 to 97) were rarer and cancer of the uterine corpus (SIR 164, 95% CI = 109 to 237) was more common in Seventh-Day Adventists before the age of 75 years. Inclusion of all registered Seventh-Day Adventists regardless of religious activity and the relatively low cancer incidence rates in the Norwegian population could contribute to the nonsignificant result with regard to total cancer. Main etiologic factors in cancer development in Norway should be sought in areas where Seventh-Day Adventists do not differ from the general population. 
Epileptogenic effect of hypoxia in the immature rodent brain. The response to cerebral hypoxia/ischemia may be different in the neonate compared to other age groups. An in vivo model was developed in the rat to determine whether there are age-dependent differences in the effects of hypoxia on electroencephalographic (EEG) activity. EEG recordings were obtained from Long Evans hooded rats deprived of oxygen at five ages: postnatal days 5 to 7, 10 to 12, 15 to 17, 25 to 27, and 50 to 60. Oxygen concentration was varied from 0, 2, 3, and 4% between animals. EEGs were recorded in all animals before, during, and at 1 hour after exposure to the hypoxic condition and at 1 to 7 days afterward in a subset of animals. All animals were deprived of oxygen until the onset of apnea and bradycardia to 20 to 40% of baseline heart rate values. Hypoxia resulted in isoelectric EEG significantly more frequently in the animals deprived of oxygen at postnatal days 25 to 27 and 50 to 60 than in the younger age groups. A highly significant effect was that the animals deprived at postnatal days 5 to 17 revealed a high incidence of epileptiform EEG activity during hypoxia. In contrast, the older animals exhibited only rare isolated EEG spikes before reaching an isoelectric EEG. The severity of hypoxia-induced epileptiform EEG changes was highest in the animals subjected to moderately hypoxic conditions (3% and 4% oxygen) at postnatal days 10 to 12. Furthermore, epileptiform changes persisted for hours to days following prolonged episodes of hypoxia in the younger animals. This study demonstrates a unique response of the immature brain to exhibit epileptiform activity during hypoxia. 
Childhood cancer among the Polynesian population. From June 1981 through June 1989, 95 Polynesian children were seen for initial care of malignancy at the Princess Mary Hospital for Children (PMHC). The incidence of malignancy in the Polynesian populations served, the histology of the malignancies, and the outcome of therapy were reviewed and compared with 185 non-Polynesian (non-P) patients seen during the same period. Incidence figures for Polynesians and non-P were similar, but histologic patterns differed, showing an increased occurrence of leukemia, particularly nonlymphoblastic leukemia, an increased occurrence of bone tumors, and a decreased incidence of central nervous system tumors for Polynesians. Survival for Polynesian children with acute lymphoblastic leukemia was worse than for non-P. Survival in all other disease categories was similar. 
Hemorrhagic events during therapy with recombinant tissue-type plasminogen activator, heparin, and aspirin for acute myocardial infarction. Results of the Thrombolysis in Myocardial Infarction (TIMI), Phase II Trial. OBJECTIVES: To assess the effects of invasive procedures, hemostatic and clinical variables, the timing of beta-blocker therapy, and the doses of recombinant plasminogen activator (rt-PA) on hemorrhagic events. DESIGN: A multicenter, randomized, controlled trial. SETTING: Hospitals participating in the Thrombolysis in Myocardial Infarction, Phase II trial (TIMI II). INTERVENTIONS: Patients received rt-PA, heparin, and aspirin. The total dose of rt-PA was 150 mg for the first 520 patients and 100 mg for the remaining 2819 patients. Patients were randomly assigned to an invasive strategy (coronary arteriography with percutaneous angioplasty [if feasible] done routinely 18 to 48 hours after the start of thrombolytic therapy) or to a conservative strategy (coronary arteriography done for recurrent spontaneous or exercise-induced ischemia). Eligible patients were also randomly assigned to either immediate intravenous or deferred beta-blocker therapy. MEASUREMENTS: Patients were monitored for hemorrhagic events during hospitalization. MAIN RESULTS: In patients on the 100-mg rt-PA regimen, major and minor hemorrhagic events were more common among those assigned to the invasive than among those assigned to the conservative strategy (18.5% versus 12.8%, P less than 0.001). Major or minor hemorrhagic events were associated with the extent of fibrinogen breakdown, peak rt-PA levels, thrombocytopenia, prolongation of the activated partial thromboplastin time (APTT) to more than 90 seconds, weight of 70 kg or less, female gender, and physical signs of cardiac decompensation. Immediate intravenous beta-blocker therapy had no important effect on hemorrhagic events when compared with delayed beta-blocker therapy. Intracranial hemorrhages were more frequent among patients treated with the 150-mg rt-PA dose than with the 100-mg rt-PA dose (2.1% versus 0.5%, P less than 0.001). The extent of the plasmin-mediated hemostatic defect was also greater in patients receiving the 150-mg dose. CONCLUSIONS: Increased morbidity due to hemorrhagic complications is associated with an invasive management strategy in patients with acute myocardial infarction. Our findings show the complex interaction of several factors in the occurrence of hemorrhagic events during thrombolytic therapy. 
Treatment of unresectable meningiomas with the antiprogesterone agent mifepristone. The possibility that meningioma growth may be related to female sex hormone levels is suggested by several lines of evidence. Meningiomas are twice as common in women as in men, have been observed to wax and wane with pregnancy, and are positively associated with breast cancer. A physiological explanation for these phenomena is provided by the finding of steroid hormone receptors in meningiomas. However, unlike breast cancer, meningiomas are much more commonly positive for progesterone receptors than for estrogen receptors. The authors initiated a study on long-term oral therapy of unresectable meningiomas with the antiprogesterone mifepristone (RU486). Fourteen patients received mifepristone in daily doses of 200 mg for periods ranging from 2 to 31+ months (greater than or equal to 6 months in 12 patients). Five patients have shown signs of objective response (reduced tumor measurement on computerized tomography scan or magnetic resonance image, or improved visual field examination). Three have also experienced subjective improvement (improved extraocular muscle function or relief from headache). The side effects of long-term mifepristone therapy have been mild. Fatigue was noted in 11 of the 14 patients. Other side effects included hot flashes in five patients, gynecomastia in three, partial alopecia in two, and cessation of menses in two. Long-term therapy with mifepristone is a new therapeutic option that may have efficacy in cases of unresectable benign meningioma. 
Transscleral leiomyoma. A bluish-pink epibulbar lesion, which slowly enlarged over a period of 5 years, developed in a 31-year-old woman. The lesion initially resembled a staphyloma, based on the very thinned overlying sclera, but subsequent evaluation suggested that it was a solid mass. At the time of surgical removal, the mass appeared to have originated in the supraciliary region and to have eroded outward through the sclera. Histopathologically, the mass proved to be a leiomyoma. The authors propose theoretic possibilities to explain the location of this rare type of ocular smooth muscle tumor. 
Detection of intraoperative laser injury to the facial nerve by electromyographic monitoring of facial muscles. Injury to the facial nerve is a significant risk during resection of cerebellopontine angle tumors. To minimize the risk of facial nerve injury, intraoperative electromyographic monitoring of facial musculature is frequently used. However, the reliability of such monitoring systems for detection of thermal nerve injury resulting from the use of carbon dioxide lasers has not been systematically evaluated. We determined the sensitivity of a computerized electromyographic monitor for detection of laser facial nerve injury in an anesthetized rat model. The mandibular and buccal branches of the facial nerve were isolated in 12 rats. A carbon dioxide laser was used to create controlled sites of thermal injury to both nerves over a 3-hour period. When a laser injury was created distal to previous injury sites, electromyographic discharge was noted in 72% to 82% of injuries. Laser injury proximal to previous injury sites was detected with 33% efficiency. These detection rates did not change significantly over a 3-hour period. This preliminary data suggests that electromyographic monitoring of facial musculature allows detection of facial nerve injury caused by carbon dioxide lasers. 
Morphologic comparison of frequency and types of acute lesions in the major epicardial coronary arteries in unstable angina pectoris, sudden coronary death and acute myocardial infarction. The frequency and type of acute lesions in the four major (right, left main, left anterior descending, left circumflex) epicardial coronary arteries were examined at necropsy in 14 patients with unstable angina pectoris, 21 patients with sudden coronary death and 32 patients with a fatal first acute myocardial infarction. None of the 67 patients had a grossly visible left ventricular scar (healed myocardial infarct) and only the group with acute myocardial infarction had left ventricular myocardial necrosis. Although the frequency of intraluminal thrombus was similar in patients with unstable angina (29%) and sudden death (29%) and significantly lower than in those with acute infarction (69%) (p = 0.02), the thrombus in the patients with unstable angina and sudden death consisted almost entirely of platelets and was nonocclusive, whereas the thrombus in the group with acute infarction consisted almost entirely of fibrin and was occlusive. The frequency of plaque rupture was insignificantly different in the groups with unstable angina (36%) and sudden death (19%), and was significantly lower than in the group with acute infarction (75%) (p = 0.02). The frequency of plaque hemorrhage was insignificantly different in the groups with unstable angina (64%) and sudden death (38%) and was significantly lower than in the group with acute infarction (90%) (p = 0.04). 
Adrenal hemangioma: an unusual adrenal mass delineated with magnetic resonance imaging. Adrenal hemangioma should be included in the differential diagnosis of any large calcified adrenal mass. We report to our knowledge the eighth surgically removed lesion and describe its appearance on magnetic resonance imaging. This imaging includes features seen in hemangiomas elsewhere, in particular a heterogeneous mass with enhancing peripheral high intensity foci on T1 images. 
A modified technique of pre-operative aortography to demonstrate the complete arterial tree of the lower limb. One hundred consecutive aortograms were studied to establish the efficacy of conventional arteriography in demonstrating distal vessels and the pedal arch. The standard technique was modified by using a long injection time, a large volume of contrast material (iopamidol 370), prolonged filming and multiple exposures of the feet. On the basis of these examinations each limb was classified as having aorto-iliac disease (18 limbs), superficial femoral disease (103 limbs), combined segment disease (28 limbs) or generalised disease (51 limbs). Calf and ankle arteries were seen in 196 of the 200 limbs (98%). Patency of the pedal arch was established in 184 (92%). Fourteen percent of the group of patients with combined segment disease did not have their pedal arch visualised and this group contained most of the examination failures. This modified method of aortography can demonstrate the entire arterial tree from the aorta to the foot in 92% of limbs with symptomatic chronic atherosclerotic disease. This allows the majority of peripheral vascular reconstructions to be planned and performed without the need for intra-operative arteriography. 
Hyperbaric treatment of cerebral air embolism sustained during an open-heart surgical procedure A case of cerebral air embolism sustained during replacement of the mitral valve resulted in postoperative coma and seizures. Hyperbaric treatment, begun 30 hours after the occurrence of the air embolism, resulted in good immediate and long-term recovery. Mild deficits of the left hemisphere were present at follow-up 53 days after the embolus was sustained, and lesser, minimal residua were present at 14-month follow-up. Hyperbaric treatment is the definitive therapy for cerebral air embolism. Although it is most effective when administered early, the outcome may be excellent even with late treatment. 
Growth of human basal cell carcinomas transplanted to C57/Balb/C bgJ/bgJ nu/nu (beige-nude) mice. The purpose of this study was to measure growth parameters of transplanted basal cell carcinoma (BCC) to beige-nude mice during a 4-month observation time. Forty male beige-nude mice were transplanted with human BCC with our reported subcutaneous implantation technique. Initial volume and wet weight were determined for each tumor. The tumors were measured every 2 weeks by calipers with a final volume determined at 120 days, at which time the tumors were harvested, weighed, and processed for routine histology. Thirty-two tumor sites were positive for persistent tumor at harvest. Tumor volumes declined by an average of 51% and average tumor weight by 33%. There were increased numbers of mast cells surrounding the BCC tumor lobules. These results indicate that BCC can survive for 120 days in the beige-nude mouse. 
Carbon dioxide laser energy disperses human papillomavirus deoxyribonucleic acid onto treatment fields. The possibility of dispersing viral deoxyribonucleic acid during carbon dioxide laser treatment of human papillomavirus-containing genital infections has been investigated with a commercially available dot blot hybridization technique. The viral ribonucleic acid probes were specific for groups of human papillomavirus types 6/11, 16/18, and 31/33/35. Laser energy was delivered by continuous-wave mode and the plume of smoke was evacuated by a vacuum suction system. Samples were taken with Dacron swabs from lesional tissues of 43 patients as well as from the treated areas and from the 5 cm surrounding normal skin before and after laser vaporization. Human papillomavirus deoxyribonucleic acid was identified in swabs from 34 of 43 (79%) lesional tissues and 7 of 43 (16%) treatment fields. Although a trend for higher human papillomavirus deoxyribonucleic acid positivity in laser margins after therapy (7/43, 16%) than before (4/43, 9%) was observed, the rates were not statistically significant. It is concluded that carbon dioxide laser energy disperses human papillomavirus deoxyribonucleic acid onto treatment fields and the adjacent normal epithelium. Viral contamination of treated areas may be reduced by positioning the fume evacuator within 1 cm of the field of laser vaporization and cleaning the treated areas and surrounding tissue after therapy. 
Bouveret's syndrome: an unusual twist on the classic cause. Bouveret's syndrome is a duodenal obstruction caused by a gallstone, manifested mostly as a gastric outlet obstruction. We have reported an instance of Bouveret's syndrome caused by two separate stones, either of which could independently have caused the obstruction. It is imperative to be sure that the obstruction is relieved before terminating the operative procedure. 
Angiographic management of retroperitoneal hemorrhage from renal angiomyolipoma in polycystic kidney disease. Angiographic management of bilateral angiomyolipomas complicated by hemorrhage in autosomal dominant polycystic kidney disease is presented. The patient had mild stigmata of tuberous sclerosis, and a family history of tuberous sclerosis and autosomal dominant polycystic kidney disease. The radiographic features at diagnosis, and those present during and after embolization are described. Radiological criteria for diagnosis and successful control of bleeding with intra-arterial selective embolization are discussed. Radiographic features before, during and after embolization are exhibited. 
Specificity of low dose fadrozole hydrochloride (CGS 16949A) as an aromatase inhibitor. CGS 16949A (fadrozole hydrochloride), a potent cytochrome P450-mediated steroidogenesis inhibitor, blocks aromatase at low doses, but other biosynthetic steps at higher concentrations. Recent studies demonstrated inhibition of C11-hydroxylase, corticosterone methyloxidase-II, and deoxycorticosterone to corticosterone conversion with this agent at some-what higher concentrations than those required for blockade of aromatase. Based upon phase I studies, we postulated that relatively selective inhibition of aromatase might be possible if sufficiently low doses of CGS 16949A were used. A phase II study in 54 postmenopausal women with metastatic breast cancer examined the effects of low dose CGS 16949A on estrogen, mineralocorticoid, and glucocorticoid secretion. Two dose schedules and two dose levels were chosen based upon our prior dose escalation protocol study. Plasma estrone, estradiol, and estrone sulfate as well as urinary estrone and estradiol fell equally with 1.8-4 mg CGS 16949A given either on a twice daily or three times daily dose schedule. Isotopic kinetic studies demonstrated an 84% decrease in the rate of conversion of androstenedione to estrone to 0.40 +/- 0.07% (patients receiving 1.8-4 mg CGS 16949A daily). With these three regimens, basal levels of aldosterone and cortisol did not change significantly over a 12-week period of observation. Clinical examination, plasma electrolytes, and urinary sodium/potassium ratios suggested no biological evidence of mineralo-corticoid deficiency. ACTH-stimulated cortisol concentrations, however, were blunted at each dose level compared to pretreatment values. Nonetheless, peak responses exceeded 550 nmol/L, or a basal to peak difference of 190 nmol/L or greater, in 97% of instances. This probably reflected inhibition of C11-hydroxylase, since basal and ACTH-stimulated levels of 11-deoxycortisol were increased in response to CGS 16949A. Androstenedione and 17 alpha-hydroxyprogesterone also exhibited an upward trend in response to drug treatment. ACTH-stimulated aldosterone levels were blunted to a greater extent than those of cortisol, probably as a reflection of corticosterone methyloxidase type II blockade. Overall, the results suggest that CGS 16949A, at doses of 1.8-2 mg daily, blocks aromatase effectively and does not produce clinically important inhibition of cortisol or aldosterone biosynthesis. Thus, this agent can probably be used safely without glucocorticoid or mineralocorticoid supplementation. 
Isolated neurofibromas of the conjunctiva. We studied four histologically verified cases of isolated neurofibromas of the conjunctiva. The histologic pattern was diffuse in two patients, plexiform in one patient, and solitary in one patient. Simple excision was curative in all cases. We emphasize the importance of distinguishing neuromas (which may be associated with multiple endocrine neoplasia) from neurofibromas. 
Double anal canal: complication of rectal fecalith. Fecaliths and stercoraceous ulcerations are well-known complications of chronic constipation. The authors present the case of a double anal canal in an elderly man. This anorectal fistula (complex anal fistula) developed as a complication of an impacted rectal fecalith with resultant stercoraceous ulceration. Eventually, a persistent epithelialized canal developed and was demonstrated at double-contrast barium enema examination. The patient remained continent at all times. 
Vegetative state after closed-head injury. A Traumatic Coma Data Bank Report. To elucidate the clinical course of the vegetative state after severe closed-head injury, the Traumatic Coma Data Bank was analyzed for outcome at the time of discharge from the hospital and after follow-up intervals ranging up to 3 years after injury. Of 650 patients with closed-head injury available for analysis, 93 (14%) were discharged in a vegetative state. In comparison with conscious survivors, patients in a vegetative state sustained more severe closed-head injury as reflected by the Glasgow Coma Scale scores and pupillary findings and more frequently had diffuse injury complicated by swelling or shift in midline structures. Of 84 patients in a vegetative state who provided follow-up data, 41% became conscious by 6 months, 52% regained consciousness by 1 year, and 58% recovered consciousness within the 3-year follow-up interval. A logistic regression failed to identify predictors of recovery from the vegetative state. 
Similar outcome of treatment of B-cell and T-cell diffuse large-cell lymphomas: the Stanford experience. Although previous studies have suggested a relatively poor prognosis for some patients with peripheral T-cell lymphoma, the clinical significance of immunologic phenotype in diffuse large-cell lymphoma (DLCL) remains controversial. One hundred one patients with a uniform morphologic diagnosis of DLCL treated at Stanford between 1975 and 1986 with cyclophosphamide, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), vincristine, and prednisone (CHOP), methotrexate, bleomycin, Adriamycin, cyclophosphamide, vincristine, and dexamethasone ([M]BACOD), or methotrexate, Adriamycin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B) chemotherapy were studied with regard to immunologic phenotype. Immunologic analysis, performed on frozen or paraffin-embedded tissue, identified 77 cases of B-cell origin, 21 cases of T-cell origin, and three cases that lacked B-cell or T-cell markers. Analysis of complete remission (CR) rates (84% v 95%), 5-year actuarial freedom from disease progression (38% v 53%), and 5-year actuarial overall survival (52% v 79%) showed no statistically significant differences in prognosis between B- and T-cell patients, respectively. The 5-year actuarial survival of patients with stage IV T-cell DLCL (56%) also did not differ in a statistically significant way from stage IV B-cell patients (36%). We conclude that treatment selection for DLCL should not be based on immunologic phenotype alone. 
Long survival after excision of a primary malignant melanoma of the oesophagus. A woman who had a large primary malignant melanoma of the oesophagus, with evidence of submucosal invasion and several local metastases, underwent resection two years after the onset of retrosternal pain and has survived for 12 years with no recurrence. 
Beta-adrenergic-antagonist drugs in the prevention of gastrointestinal bleeding in patients with cirrhosis and esophageal varices. An analysis of data and prognostic factors in 589 patients from four randomized clinical trials. Franco-Italian Multicenter Study Group. BACKGROUND. The value of beta-adrenergic-antagonist drug therapy for the prevention of initial episodes of gastrointestinal bleeding in patients with cirrhosis and esophageal varices is uncertain, both positive and negative study results having been reported. METHODS. In this study, we analyzed data on individual patients from four randomized, controlled trials to assess the efficacy of this treatment. Of the 589 patients studied, 286 received a beta-adrenergic-antagonist drug (propranolol in 203 and nadolol in 83) and 303 received placebo. RESULTS. After two years, the mean (+/- SE) percentage of patients who had had no upper gastrointestinal bleeding was 78 +/- 3 percent in the beta-adrenergic-antagonist treatment group and 65 +/- 3 percent in the control group (P = 0.002). The percentage of patients without fatal bleeding was 90 +/- 2 percent in the treatment group and 82 +/- 3 percent in the control group (P = 0.01). The percentage of patients surviving after two years was 71 +/- 3 percent in the treatment group and 68 +/- 3 percent in the control group (P = 0.34). After age and severity of cirrhosis were taken into account, the survival rate was better in the treatment group (P = 0.09). The percentage of surviving patients who had had no bleeding after two years was 62 +/- 3 percent in the treatment group and 53 +/- 3 percent in the control group (P = 0.04). Both propranolol and nadolol prevented a first episode of bleeding. Severe cirrhosis and especially the presence of ascites were associated with bleeding (P less than 0.001) and death (P less than 0.001) in both groups. The efficacy of beta-adrenergic-antagonist therapy in the prevention of bleeding (P less than 0.001) and of fatal bleeding (P = 0.004) and in the prevention of bleeding or death (P = 0.005) was the same after adjustment for cause and severity of cirrhosis, ascites, and size of varices. CONCLUSIONS. Propranolol and nadolol are effective in preventing first bleeding and reducing the mortality rate associated with gastrointestinal bleeding in patients with cirrhosis, regardless of severity. 
Glomerulopathy in patient with Donohue syndrome (leprechaunism). OBJECTIVE: To evaluate renal structure in a child with Donohue syndrome (leprechaunism), who at 10 yr of age was noted to have hypertension, microalbuminuria, and enlarged kidneys, a renal biopsy was performed. RESEARCH DESIGN AND METHODS: The renal biopsy tissue was evaluated by light and electron microscopy with standard stereological techniques to measure glomerular volume, glomerular basement membrane width, fractional mesangial volume, and peripheral capillary filtering surface density. RESULTS: On renal biopsy, there was a marked increase in glomerular volume, glomerular basement width, and mesangial volume, findings similar to those seen in patients with diabetic nephropathy. CONCLUSIONS: This patient with marked insulin resistance associated with Donohue syndrome demonstrates renal and glomerular enlargement and morphometric glomerular changes similar to those seen in patients with diabetic nephropathy. In unusual syndromes with hyperglycemia and hyperinsulinemia, renal structural and functional changes typical of traditional diabetes mellitus may be seen. 
The measurement and manipulation of intralabyrinthine pressure in experimental endolymphatic hydrops. Three to four months after unilateral surgical ablation of the endolymphatic duct and sac, endolymphatic and perilymphatic pressures were measured in both the normal and hydropic ears of 11 guinea pigs. In normal ears, endolymphatic pressure always approximated perilymphatic pressure. Endolymphatic pressure exceeded perilymphatic pressure in all ears with hydrops, except one in which these pressures were equal. The effect of postural inversion on inner ear pressures were studied in both normal and hydropic inner ears. Normal ears showed endolymphatic and perilymphatic pressure to rise equally during this maneuver. In hydropic ears, the difference between endolymphatic and perilymphatic pressure was notably reduced from measurements obtained in the prone position. This study indicates that an alteration in pressure regulation within the inner ear may be important in the pathogenesis and manifestation of experimental endolymphatic hydrops in the guinea pig. Physiologic mechanisms and clinical implications of these results are described. 
Prosthetic replacement of the distal femur for primary bone tumours. Over a 16-year period, 135 custom-made distal femoral prostheses, based on a fully constrained Stanmore-type knee replacement, were used in the treatment of primary malignant or aggressive benign tumours. Survivorship analysis showed a cumulative success rate of 72% at five years and 64% at seven years. Intact prostheses in 91% of the surviving patients gave good or excellent functional results. Deep infection was the major complication, occurring in 6.8% of cases; clinical aseptic loosening occurred in 6.0%. Revision surgery was carried out for loosening and infection, and the early results are encouraging. We conclude that prosthetic replacement of the distal femur can meet the objectives of limb salvage surgery. 
The neurology of endemic cretinism. A study of two endemias. Endemic cretinism is the most severe manifestation of dietary iodine deficiency. Two forms of the syndrome are traditionally described: neurological and myxoedematous. Although this classification highlights the important neurological sequelae of the disorder it implies that myxoedematous cretins have an alternative mechanism. Further, the nature of the neurological deficit associated with both types of endemic cretinism has received scant attention in recent times considering that it remains a common disorder in many parts of the world. The nature and extent of the neurological deficit found in endemic cretinism was investigated in 104 cretins from a predominantly myxoedematous endemia in western China and in 35 cretins from central Java, Indonesia, a predominantly neurological endemia. We found a similar pattern of neurological involvement in nearly all cretins from both endemias, regardless of type (myxoedematous or neurological), and of current thyroid function. Hallmarks of the neurological features included mental retardation, pyramidal signs in a proximal distribution and extrapyramidal signs. Many patients exhibited a characteristic gait. This probably reflected pyramidal and extrapyramidal dysfunction, although joint laxity and deformity were important contributing factors. Other frequently encountered clinical features were squint, deafness, and primitive reflexes. Cerebral computerized tomography (CT) revealed basal ganglia calcification in 15 of 50 subjects. The presence of basal ganglia calcification was confined to cretins with severe hypothyroidism. Otherwise, cerebral CT scanning demonstrated only minor abnormalities which did not contribute to the localization of the clinical deficits. We conclude that the same neurological disorder is present in both types of endemic cretinism reflecting a diffuse insult to the developing fetal nervous system. These clinical findings support the concept of maternal and fetal hypothyroxinaemia, arising from severe iodine deficiency, as the primary pathophysiological event in endemic cretinism. Differences between the two types of cretinism may be explained by continuing postnatal thyroid hormone deficiency in the myxoedematous type, which results in impaired growth, skeletal retardation and sexual immaturity. 
Pulmonary vein thrombosis following bilobectomy. Acute thrombosis of the pulmonary vein following lobectomy or bilobectomy is a rare complication with no standard guideline for diagnosis or management. In this report, we present a case of right upper lobe vein thrombosis following a middle and lower lobectomy. Diagnosis was confirmed by ventilation-perfusion lung scan, pulmonary angiogram, and bronchoscopy. The patient was treated conservatively with no further complications and had a partial recovery of the circulation to the right upper lobe. A review of the literature is also presented along with the experimental data demonstrating the mechanisms of recovery. 
Atypical squamous cells. A case-series study of the association between papanicolaou smear results and human papillomavirus DNA genotype. Thirty women with "atypical" squamous cells but not cervical intraepithelial neoplasia (CIN) on their Papanicolaou smears were tested for the presence of human papillomavirus (HPV) with the Southern blot hybridization technique. The Papanicolaou smears were reviewed for the presence of atypical squamous cells according to Patten's criteria. Comparison groups consisted of 30 patients with normal, 29 patients with CIN I and 24 patients with CIN II Papanicolaou smears. Ten of the 30 women (33%) with atypical cells on Papanicolaou smears were positive for HPV DNA as compared to 17% with normal and 59% with CIN I or II Papanicolaou smears. HPV 16 was present in 70-80% of the HPV DNA-positive patients in each Papanicolaou smear group. Concurrent CIN was also identified on colposcopically directed biopsies in 27% of the patients with squamous atypia. Patients with atypical squamous cells on Papanicolaou smears had coexisting HPV infection and CIN in about one-third of the cases. Colposcopy and further follow-up are recommended for such patients. 
Injury current and gradients of diastolic stimulation threshold, TQ potential, and extracellular potassium concentration during acute regional ischemia in the isolated perfused pig heart. During acute regional myocardial ischemia, a "current of injury" flows between the ischemic and the normal tissue. Its direction and magnitude change during the cardiac cycle. During diastole, the injury current flows intracellularly from the ischemic cells toward the normal cells and tends to depolarize the latter. The gain insight into the possible role of the injury current in arrhythmogenesis, we simultaneously determined diastolic stimulation threshold, [K+]o and TQ potential at multiple sites closely spaced across the cyanotic border in Langendorff-perfused pig hearts during the first 10 minutes after occlusion of the left anterior descending coronary artery. The position of the electrodes relative to the border was validated by their response to 1) regional ischemia and 2) selective perfusion with a high-K+ perfusate of the left anterior descending coronary artery. A temporary decrease of diastolic stimulation threshold preceded a rapid increase in the central ischemic zone; a lasting reduction (by +/- 20%) without a concomitant increase of [K+]o was observed at seven sites (of 39 sites tested), five of which were less than 2 mm outside the electrophysiological border. Moreover, up to 4 mm inside the electrophysiological border, a similar lasting decrease of diastolic stimulation threshold was accompanied by a moderate increase of [K+]o. We conclude that 1) the injury current causes increased excitability in normal tissue close to the "ischemic" border and 2) increased excitability related to a moderately increased [K+]o may persist up to 10 minutes of ischemia at the ischemic side of the border. Both factors may facilitate the induction of life-threatening arrhythmias in acute myocardial ischemia. 
Intraoperative facial nerve monitoring: prognostic aspects during acoustic tumor removal. Intraoperative facial nerve monitoring with electrical stimulation (IFNMES) has become an integral part of acoustic tumor surgery. We reviewed the records of fifty-six patients who underwent translabyrinthine acoustic tumor removal with IFNMES. There was excellent correlation between intraoperative facial nerve activity and immediate postoperative facial nerve function (24 hours after surgery and at hospital discharge). Our data would suggest that patients who exhibit less than 500 microvolts of ongoing EMG activity during surgery, and who yield at least a 500-microvolt contraction when stimulated with 0.05 milliamps at the brainstem after tumor removal, can expect an excellent immediate facial nerve result (grade I or II). 
Diskitis in children. Thirty-six patients diagnosed with diskitis from 1978 to 1988 and followed for an average of 29.2 months were reviewed. The study included 23 boys and 13 girls with an average age of 5.3 years. The initial symptoms varied, but distinct clinical patterns emerged and were identifiable in different age groups. Both the leukocyte count and sedimentation rate were elevated. Routine roentgenograms were positive for intervertebral disk space narrowing in 82% of cases, technetium bone scans positive in 72%, and magnetic resonance imaging positive in all recent cases. Treatment consisted of bed rest for all patients, plaster casts for 50%, antibiotics for 40%, and traction for 23%. Regardless of the treatment combination, the course of the disease in most children is benign. At the completion of the study, all patients were asymptomatic including three children who had recurrences. In spite of being asymptomatic, 74% had persistent roentgenographic changes. The administration of antibiotics appears to be appropriate when indicated, i.e., failure to respond to immobilization. Disk space aspiration or biopsy should be reserved for those cases that are refractory to immobilization and antibiotics. 
The autotransfusion effect of external leg counterpressure in simulated mild hypovolemia. We examined the cardiovascular response of external leg counterpressure in healthy volunteers at 100 mm Hg compression pressure. To stimulate mild hypovolemia, measurements were made with the subjects in a 60 degrees head-up tilt position. Left ventricular end-diastolic volume (LVEDV) and cardiac output (CO) were calculated from two-dimensional echocardiography. Flow through the inferior vena cava (IVC) below the origin of the hepatic veins was determined by the Doppler ultrasound technique. The application of counterpressure significantly increased LVEDV, CO, and arterial blood pressure over that seen with tilting without the device. These responses were accompanied by a small but significant increase in IVC flow. We therefore concluded that external leg counterpressure transferred blood to the central circulation by compression of the venous capacitance vessels (an autotransfusion effect) in mild hypovolemia, but such an effect may not benefit patients in a hypovolemic shock state because of the small amount of translocated blood. 
Cardiovascular reflexes and autonomic dysfunction in Parkinson's disease. Cardiovascular reflexes were analysed in a group of 20 patients suffering from Parkinson's disease and in 12 age-matched healthy subjects, in order to ascertain the incidence and degree of autonomic dysfunction. The following were measured: heart rate variation during normal breathing, postural change (30/15 ratio) and during the Valsalva manoeuvre: blood pressure variation after standing. These measurements were taken at least 12 h after therapy had been withdrawn and were repeated after therapy had been resumed. Significant changes in the different heart rate variation indices were found in the parkinsonian patients which correlated with the duration and severity of the extrapyramidal symptomatology. After standing the patients showed a significant drop in blood pressure, when compared respectively with their base values and with the response in controls. Anticholinergic drugs had no significant effect on the heart rate variation indices, whereas antiparkinsonian therapy seems to have contributed to the drop in blood pressure after standing. 
Dysfibrinogenemia associated with thrombosis and third-trimester fetal loss. A case report. Dysfibrinogenemias are rare genetic disorders that are clinically silent, cause a mild bleeding tendency or have thromboembolic manifestations. During pregnancy they often cause hemorrhage and first-trimester abortions. A patient with a severe thrombotic tendency during pregnancy had a third-trimester fetal loss. 
Comparative effects of APSAC and rt-PA on infarct size and left ventricular function in acute myocardial infarction. A multicenter randomized study. BACKGROUND. Recombinant tissue-type plasminogen activator (rt-PA or alteplase) and anisoylated plasminogen streptokinase activator complex (APSAC or anistreplase) have been demonstrated to limit infarct size significantly and to preserve left ventricular function when injected soon after acute myocardial infarction. However, as yet, the efficacy and safety of these two thrombolytic agents have not been directly compared in one trial; this was the aim of this study. METHODS AND RESULTS. One hundred eighty-three patients suffering from a first acute myocardial infarction were randomly allocated to either APSAC (30 units over 5 minutes) or single-chain rt-PA (100 mg over a 3-hour period) within 4 hours of the onset of symptoms. Global and regional left ventricular function were assessed from contrast angiography an average of 5.3 +/- 2.3 days after initial therapy. Radionuclide angiography and thallium-201 single-photon emission computerized tomography were performed before hospital discharge. Infarct size was assessed by single-photon emission computerized tomography and expressed in percentage of the total myocardial volume. Ninety patients received APSAC and 93 received rt-PA within a mean period of 172 +/- 52 minutes after the onset of symptoms. The two groups were similar in age, location of the acute myocardial infarction, Killip class, and time of randomization. The patency rate of the infarct-related artery was 72% in the APSAC group and 76% in the rt-PA group (NS). Initial and predischarge left ventricular ejection fraction as well as infarct size were similar in both therapeutic groups (0.50 +/- 0.14 versus 0.52 +/- 0.12 for initial and 0.48 +/- 0.10 versus 0.47 +/- 0.10 for predischarge ejection fraction, 11 +/- 7% versus 9 +/- 7% for infarct size, respectively, for APSAC- and rt-PA-treated patients). Bleeding complications requiring blood transfusion occurred in one APSAC patient and in two rt-PA patients. One patient in the rt-PA group died of a massive intracranial hemorrhage. At the end of the 3-week follow-up period, five APSAC patients (5.5%) and seven rt-PA patients (7.5%) had died. CONCLUSIONS. The early infusion of APSAC or rt-PA in acute myocardial infarction produced a similar patency rate, limitation of infarct size, and preservation of left ventricular systolic function with an equivalent rate of bleeding complications. 
Detection of field change in oral cancer using oral exfoliative cytologic study. Four smears were taken from the normal buccal mucosa of 55 oral cancer patients and 76 cancer-free patients. In each case, two were stained by the Papanicolaou method and two underwent Feulgen hydrolysis. Quantitative assessment of nuclear area (NA) and cytoplasmic area (CA) of the Papanicolaou smears was undertaken using a semiautomatic image analysis system. DNA profiles were assessed from the Feulgen smears using a Vickers M85 microdensitometer (Vickers Instruments, York, England) and were found to be diploid for all patients. Results were then analyzed with respect to those patients who took alcohol, tobacco, combination of alcohol and tobacco, and those who took neither. A significant reduction in CA for the oral cancer group (P equals 0.001) but no change in NA (P equals 0.74) was observed. A detailed analysis of alcohol and tobacco habits could identify no significant role for these two factors, in the reduction in cytoplasmic area. Such field change may prove to be of value in predicting the development of second malignant tumors. 
Fever: knowledge, perception and attitudes. Results from a Norwegian population study. To investigate the layman's knowledge, perception and attitudes regarding normal body temperature, fever, infections and the effect of penicillin on virus infections a representative sample of the Norwegian population (619 women and 592 men over the age of 15) was interviewed in 1988 as part of a monthly national opinion poll. One-third thought body temperatures up to 40.5 degrees C to be life-threatening, but the results do not justify the application of the term 'fever phobia' as described in other studies based on non-representative samples. More respondents were afraid of viral infections (48%) than bacterial infections (9%), which may be due to the media focus upon the HIV/AIDS epidemic. Thirty-five per cent believed penicillin to be effective against virus infections. Educational programmes on fever should also include information about virus infections and their treatment. 
Assessment of response to cancer therapy using fluorine-18-fluorodeoxyglucose and positron emission tomography. In order to evaluate the usefulness of 18F-FDG PET in the assessment of therapeutic effects, FDG-PET studies were performed both before and after therapy in 26 patients with miscellaneous malignant tumors. The change in FDG uptake by therapy was compared with the change in tumor size and prognosis. All 26 lesions had a high FDG uptake before therapy. Five of seven lesions which had a relatively low FDG uptake before therapy showed no change or increase in tumor size by therapy. The decreased FDG uptake after therapy was more prominent in the partial response group than in the no change group. FDG uptake before therapy in the non-relapse group was higher than that in the relapse group. However, a decreased FDG uptake did not necessarily indicate a good prognosis. One patient with no change in tumor size and a decreased FDG uptake had no recurrence. This suggests that FDG-PET has a complementary role in the assessment of therapeutic effects. 
Subarachnoid hemorrhage from multiple neurofibromas of the cauda equina: case report. The authors report a case of spinal subarachnoid hemorrhage caused by neurofibromas of the cauda equina. An examination of the literature revealing 13 similar cases and an analysis of this case showing three neurofibromas of the cauda equina prompted an hypothesis emphasizing the origin of bleeding and the difficulties associated with a correct diagnosis. 
Differential effect of compression-ischaemia block on warm sensation and heat-induced pain. The effect of compression-ischaemia nerve block on psychophysical thresholds for warm sensation and heat-induced pain was studied on 19 normal human volunteers. Although those two sensory submodalities should be predicted to block simultaneously, based on the fact that both are served by unmyelinated primary afferents, it was actually found that warm sensation was much more vulnerable to compression-ischaemia than heat-induced pain. This is interpreted as resulting from different summation requirements for each of the two sensory modalities; sensation of warmth depends on spatial summation to a larger extent than heat-induced pain. Such differential vulnerability is in line with recent clinical studies reporting deterioration of warm sensation associated with preservation of heat pain in peripheral nerve disorders caused by diabetes, ageing and other neuropathic processes. 
Acoustic schwannomas in children. The clinical presentation and treatment of three cases of acoustic schwannoma occurring in children are described. All the tumors were detected late, when they had attained a large size and were extremely vascular. The use of preoperative tumor embolization as an adjunct to surgical excision is discussed. 
Hepatofugal arterial signal in the main portal vein: an indicator of intravascular tumor spread. Five patients with thrombosis of the main portal vein underwent Doppler ultrasound (US). Three of these patients had confirmed hepatocellular carcinoma. Doppler US allowed differentiation between bland thrombus and tumor thrombus in two of the three patients. Tumor thrombus of the main portal vein was characterized at US by an intraportal arterial waveform in a hepatofugal direction. 
Differentiation of hydrocephalic calf and human calvariae. Occasionally, partial calvariae of hydrocephalic calves are found in forensic contexts and mistakenly identified as human. Such specimens can be properly identified through immunological assessment of associated soft tissue, microscopic analysis of associated hair, and morphological comparison with documented museum specimens. Morphological comparison should focus on the form of the occiput, supraorbital grooves, and bulbous vault and presence of coronal processes. 
Risk factors for infusion-related phlebitis with small peripheral venous catheters. A randomized controlled trial. OBJECTIVE: To identify risk factors for infusion-related phlebitis with peripheral intravenous catheters. DESIGN: A randomized trial of two catheter materials, with consideration of 21 potential risk factors. SETTING: A university hospital. PATIENTS: Hospitalized adults without granulocytopenia who received a peripheral intravenous catheter. INTERVENTIONS: House officers or ward nurses inserted the catheters, and each insertion was randomized to a catheter made of tetrafluoroethylene-hexafluoropropylene (FEP-Teflon) or a novel polyetherurethane without leachable additives (PEU-Vialon). MEASUREMENTS: Research nurses scored insertion sites each day for inflammation and cultured catheters at removal. RESULTS: The Kaplan-Meier risk for phlebitis exceeded 50% by day 4 after catheterization. intravenous antibiotics (relative risk, 2.00), female sex (relative risk, 1.88), prolonged (greater than 48 hours) catheterization (relative risk, 1.79), and catheter material (PEU-Vialon: FEP-Teflon) (relative risk, 0.73) strongly predicted phlebitis in a Cox proportional hazards model (each, P less than 0.003). The best-fit model for severe phlebitis identified the same predictors plus catheter-related infection (relative risk, 6.19), phlebitis with a previous catheter (relative risk, 1.54), and anatomic site (hand: forearm, relative risk, 0.71; wrist:forearm, relative risk, 0.60). The low incidence of local catheter-related infection was comparable with the two catheter materials (5.4% [95% CI, 3.8% to 7.6%] and 6.9% [CI, 4.9% to 9.6%]); none of the 1054 catheters prospectively studied caused bacteremia. CONCLUSIONS: Multiple factors, including the infusate and the duration of cannulation, contribute to the development of infusion-related phlebitis. The use of peripheral intravenous catheters made of PEU-Vialon appears to pose the same risk for catheter-related infection as the use of catheters made of FEP-Teflon, and PEU-Vialon can permit longer cannulation with less risk for phlebitis. The risk for catheter-related bacteremia with FEP-Teflon and PEU-Vialon catheters is sufficiently low that it no longer seems justifiable to recommend the use of small steel needles for most peripheral intravenous therapy. 
Surgical depilation for the treatment of pseudofolliculitis or local hirsutism of the face: experience in the first 40 patients. Forty patients underwent surgical depilation for pseudofolliculitis barbae or local hirsutism of the face during a 15-year period. The operative method and its results and pitfalls are discussed. Although it is not the treatment of choice, this operation is very useful when other therapy has not been successful. This seems especially true in male-to-female transsexuals. 
Muscle structure and performance capacity of Himalayan Sherpas. The ultrastructure of the vastus lateralis muscle of Sherpas from Nepal [5 males; age 28 +/- 2.8 (SD) yr, indirect maximal O2 consumption 48.5 +/- 5.4 ml.kg(-1).min(-1)] was assessed and compared with those of sedentary lowlanders and of Caucasian climbers before and after high-altitude exposure. The mean cross-sectional area of the fibers was 3,186 +/- 521 microns2, i.e., similar to those of Caucasian elite high-altitude climbers (3,108 +/- 303 microns2) and a group of climbers after a 6- to 8-wk sojourn at 5,000-8,600 m (3,360 +/- 580 microns2) but significantly (P less than 0.05) smaller than that of unacclimatized climbers (4,170 +/- 710 microns2) and slightly, although not significantly, lower than that of sedentary lowlanders (3,640 +/- 260 microns2). The number of capillaries per square millimeter of muscle cross section was 467 +/- 22, not significantly smaller than those of climbers on return from a Himalayan expedition (538 +/- 89) and elite high-altitude climbers (542 +/- 127) but significantly (P less than 0.05) greater than that of sedentary lowlanders (387 +/- 25). The volume density of mitochondria was 3.96 +/- 0.54%, significantly (P less than 0.05) less than the values found for any other investigated group, including sedentary subjects at sea level (4.74 +/- 0.30%). It is concluded that Sherpas, like acclimatized Caucasian climbers, are characterized by 1) facilitated convective and diffusive muscle O2 flow conditions and 2) a higher maximal O2 consumption-to-mitochondrial volume ratio than lowlanders despite a reduced mitochondrial volume density. 
Test-retest reliability of isokinetic knee extension and flexion torque measurements in persons with spastic hemiparesis. The purpose of this study was to evaluate and compare the test-retest reliability of isokinetic torque measurements in the involved and uninvolved knee musculature of 20 subjects with spastic hemiparesis. An isokinetic dynamometer was used to measure maximal voluntary knee extension and flexion at 60 degrees and 120 degrees/s. Peak torque (PT) and average peak torque (APT) data were collected from five repetitions on two separate occasions. Average peak torque was defined as the mean of the PT values obtained during each of the five repetitions. Spasticity was measured in the involved knee musculature prior to isokinetic testing using the Ashworth Scale. Pearson Product-Moment Correlation Coefficients and intraclass correlation coefficients (ICCs) were high (greater than or equal to .90) for both knees for PT and APT at both angular velocities. No clinically meaningful differences were found between the Pearson correlation coefficients and the ICCs of the involved versus the uninvolved knee for any testing conditions. We concluded that isokinetic evaluation of torque, as measured by PT and APT in subjects with spastic hemiparesis, can yield reliable results in both extremities. 
Thrombogenic microballoon for cerebral aneurysms, arteriovenous malformations, and carotid cavernous fistula occlusion. Preliminary technical note. A thrombogenic microballoon was developed to overcome the problems of cerebral aneurysm rupture during microballoon inflation and incomplete aneurysm obliteration by microballoons with subsequent fatal rupture. These complications occur in about 35% of reported series with current microballoon embolization techniques. The wall of the new thrombogenic microballoon allows 80% aneurysm occlusion by inflation, thus avoiding mechanical rupture, and at the same time it produces a blood clot in the space remaining between the microballoon and the aneurysm wall. This clot undergoes fibrosis with firm adherence of the microballoon to the aneurysm wall. Experimental evidence is presented to support these conclusions. This thrombogenic microballoon system is also applicable to carotid-cavernous fistulas and arteriovenous malformations. 
Resternotomy in patients with valved conduits adherent to the sternum. Twenty-two patients with valved conduits adherent to the sternum underwent resternotomy. Mean age was 10 +/- 6 years, and mean conduit age was 4 +/- 4 years. Diagnoses were D-transposition (7), truncus arteriosus (7), univentricular heart (6), Taussig-Bing anomaly (1), and corrected transposition (1). The majority of patients (68%) had reoperation for outgrown or degenerated conduits. In 17 patients, the sternum was opened with a chisel. Two of these patients sustained conduit neointimal collapse from manipulation, and 3 had conduit tear requiring immediate cardiopulmonary bypass through the femoral vessels. In the last 5 patients, the sternum was opened above and below the conduit, and the inner table was chiseled and left attached to the conduit avoiding injury and undue conduit manipulation. Cardiopulmonary bypass and operation were carried out uneventfully. We believe that the recent technique described provides a safe alternative approach to valved conduits adherent to the sternum. 
Dynamic QRS-complex and ST-segment monitoring in acute myocardial infarction during recombinant tissue-type plasminogen activator therapy. The TEAHAT Study Group. Changes of the QRS complex are the electrocardiographic expression of irreversible injury of the myocardium. In humans, the process of infarction occurs over several hours. A more rapid development of QRS changes has been reported in patients treated with thrombolytic agents. Patients with strongly suspected acute myocardial infarction (AMI) included in a placebo-controlled trial of 100 mg of recombinant tissue-type plasminogen activator (rt-PA) were monitored for 24 hours with continuous, on-line vectorcardiography. The magnitude of the QRS vector changes correlated with infarct size estimated by the maximal value of lactate dehydrogenase-1 (r = 0.69, p less than 0.001) as well as with left ventricular ejection fraction 30 days after randomization (r = 0.49, p less than 0.001). Treatment with intravenous rt-PA limited total QRS vector change but the QRS vector changes observed occurred more rapidly and reached a plateau 131 minutes earlier in patients treated with rt-PA than in those receiving placebo (p less than 0.01). A certain pattern of highly variable ST vector magnitude was identified and was associated with higher maximal lactate dehydrogenase-1 values (23 +/- 13 vs 14 +/- 10 mu kat/liter, p less than 0.001) and a tendency to higher 1-year mortality (24 vs 9%, p = 0.08) than in patients without this pattern. In patients with this pattern, rt-PA did not affect maximal lactate dehydrogenase-1, time to maximal creatine kinase and final magnitude of QRS vector change. 
Peripheral pulse pressure patterns in pregnancy hypertension. Maternal heart rate and pulse pressure patterns were examined in 30 hypertensive pregnant women using noninvasive methodology described previously. "Narrow" and "wide" pulse patterns were identified. Narrow cutaneous pulse pressure patterns, which are thought to be caused by vasoconstriction, were associated with lower birth weight infants (1870 +/- 983 versus 3225 +/- 838 g; P less than .001) and earlier deliveries (34.2 +/- 5.2 versus 37.9 +/- 2.8 weeks; P less than .05). The data suggest that these adjunctive maternal cardiovascular-system evaluation techniques may be useful in identifying patients at risk of adverse perinatal outcome by detecting vasospasm of the peripheral microcirculation. 
Detection of paradoxical cerebral echo contrast embolization by transcranial Doppler ultrasound. Contrast echocardiography has been shown to be a sensitive method for detecting patent foramen ovale in embolic stroke, implying paradoxical embolization. However, not all two-dimensional echocardiographic studies are of diagnostic quality, and direct evidence for paradoxical cerebral embolization remains lacking. We addressed these problems by simultaneously using transcranial Doppler ultrasound and contrast echocardiography to compare relative sensitivity and concordance in the detection of right-to-left vascular shunting. Forty-six patients with stroke, transient neurologic defect, or question of atrial septal defect underwent study at rest and during Valsalva strain. Two-dimensional echocardiography detected shunting in 26% at rest and 15% during Valsalva strain, whereas transcranial Doppler study returned rates of 41% and 41%, respectively. Concordance was 82% and 75%, respectively. Discordant studies almost always had evidence of paradoxical contrast embolization by transcranial Doppler and intermediate findings by two-dimensional echocardiography. Transcranial Doppler is a sensitive, unambiguous technique for the detection of anatomic substrates and target organ involvement in patients suspected to have paradoxical cerebral embolization. 
Effect of intrathecal fibrinolytic therapy on clot lysis and vasospasm in patients with aneurysmal subarachnoid hemorrhage. A prospective series of 30 patients with a single, angiographically verified aneurysmal subarachnoid hemorrhage (SAH) was studied for the effect of intrathecal thrombolytic therapy with recombinant tissue plasminogen activator (rt-PA) on outcome, angiographic vasospasm, and computerized tomography (CT) findings after surgery. The patients included fulfilled the following criteria: operation was performed by Day 3 after the hemorrhage, CT showed only blood in the basal cisterns, and the patient had a single aneurysm or multiple aneurysms that could be treated surgically at the same operation. The patients were divided into groups of 10, with patients receiving 3, 10, or 13 mg of rt-PA in a single intracisternal injection at the end of the operation. There were no differences between the treatment groups in overall outcome. One patient from the 3-mg rt-PA group developed a postoperative intracerebral hemorrhage, and one patient from the 10-mg rt-PA group had a postoperative epidural hematoma. There was one death in the 13-mg rt-PA group that was caused by inclusion of a segment of pericallosal artery in the clip. In all treatment groups a reduction was observed in the amount of blood seen on the postoperative CT scans compared to the preoperative CT scans. The reduction in SAH grade between the 10-mg and 13-mg rt-PA groups was significant (p less than 0.05). The difference in the severity of angiographic vasospasm between the 3-mg and 13-mg rt-PA groups was also significant (p less than 0.05). 
Intraoperative electron beam radiation therapy for retroperitoneal soft tissue sarcoma. From December 1981 to December 1989, 20 patients with primary or recurrent retroperitoneal sarcoma received 4000 to 5000 cGy of external beam radiation therapy (EBRT) in conjunction with surgical resection and intraoperative radiation therapy (IORT). Seventeen of 20 patients underwent complete (14 patients) or partial (3 patients) resection. Three patients had shown evidence of metastases after EBRT by the time of surgery. The 4-year actuarial local control and disease-free survival rates of the 17 patients undergoing resection were 81% and 64%, respectively. Twelve patients received IORT at the time of resection for microscopic disease (10 patients) or gross residual sarcoma (2 patients). Of the ten patients receiving IORT for microscopic tumor, one patient has died of local failure and peritoneal sarcomatosis and two patients have died of distant metastases only. The remaining seven patients are disease-free. One patient treated for gross residual sarcoma has experienced a local failure 1 year after IORT and is without disease 7 years after salvage chemotherapy. The other patient treated for gross residual sarcoma has died of local failure. Five patients did not receive IORT at the time of resection because of the extensive size of the tumor bed. Three of these patients are disease-free with one patient alive with lung metastases and one patient dying of hepatic metastases. Aggressive radiation and surgical procedures appear to provide satisfactory resectability and local control with acceptable tolerance. 
Meningioma: the role of a foreign body and irradiation in tumor formation. A case of meningioma is reported. At the age of 18 years, the patient had undergone insertion of a Torkildsen shunt through a posteroparietal burr hole for obstructive hydrocephalus secondary to a tumor of the pineal region, of which no biopsy had been made. After the hydrocephalus was relieved, he underwent irradiation of the tumor. Thirty years later, he was treated for an intracranial meningioma wrapped around the shunt. The tumor followed the shunt in all of its intracranial course. Microscopy disclosed pieces of the shunt tube within the meningioma. The role of a foreign body and irradiation in the induction of meningiomas is discussed, and a comprehensive review of the literature is presented. 
Quantitation of the critically ischemic zone at risk during acute coronary occlusion using PET. Critical myocardial ischemia has been defined experimentally during acute coronary occlusion as flow reduction of 50% or more since cellular ATP depletion begins to occur beyond this flow reduction threshold, placing tissue at risk of cellular injury. To test the hypothesis that critically ischemic fractional left ventricular mass can be measured noninvasively with PET, nine dogs were imaged in a multi-slice positron camera using the perfusion tracer 13N-ammonia, while radiolabeled microspheres were injected into the left atrium during acute coronary occlusion. Images were processed using a 50% threshold and the size of the resulting perfusion defect was expressed as a fraction of total left ventricular image volume. The critically ischemic left ventricular fraction determined in vitro from the microsphere perfusion data, ranged from 5% to 30% of the total left ventricular weight and correlated closely with that determined noninvasively by PET with r = 0.94 (y = 1.05X - 2.0%). We conclude that the fraction of left ventricular myocardium rendered critically ischemic during acute coronary occlusion can be measured accurately and noninvasively in vivo using perfusion imaging with positron emission tomography. 
Progressive deterioration of auditory evoked potentials after excision of an acoustic neurinoma: case report. The authors report the case of a 17-year-old girl who underwent excision of bilateral neurinomas of the cerebellopontine angle. Although her auditory evoked potentials were well maintained during the operation, they deteriorated gradually and progressively for the following 2 months. This seemed to reflect degeneration of the cochlear nerve fibers initiated by operative manipulation in the cerebellopontine angle in a patient who had no hearing when she awoke from surgery. 
Diffuse pulmonary hemorrhage. Diffuse pulmonary hemorrhage is a syndrome consisting of hemoptysis, anemia, and air-space consolidation. The radiologic appearance is non-specific. Pulmonary hemorrhage may be due to a number of different causes. The differential diagnosis and the diagnostic approach are different in the immunologically intact host as compared with the immunocompromised host. This article reviews the main diagnostic considerations in diffuse pulmonary hemorrhage. 
Gonococcal endocarditis complicating pregnancy: a case report and literature review. The incidence of gonorrhea has decreased substantially in the past decade. Disseminated gonorrhea is more common in women than in men, although gonococcal endocarditis is more common in men. Disseminated gonorrhea is most commonly described in women during menses or pregnancy. Only two cases of gonococcal endocarditis during pregnancy have been reported in the literature since 1942. We report a patient who experienced sudden hemodynamic decompensation at 30 weeks' gestation, resulting in fetal death. Aortic valve replacement was performed, but extensive involvement of the aortic root made complete eradication of infection impossible and eventually resulted in maternal death. 
Biomechanical changes at the ankle joint after stroke. The resistance of the relaxed ankle to slow displacement over the joint movement range was measured on both sides of a group of hemiparetic stroke patients, in whom spasticity had been established for at least one year and who showed no clinical signs of contractures. The ankle joints of the age-matched normal subjects were flexible over most of the movement range, showing dramatically increasing stiffness only when the foot was dorsiflexed beyond 70 degrees, with a neutral range between 90-100 degrees, and a less dramatic increase in stiffness during plantarflexion. Hemiparetic patients showed identical curves to the normal subjects on the "healthy" side, ipsilateral to the causative cerebral lesion, but were significantly stiffer in dorsiflexion on the contralateral side, without change in the minimum stiffness range or during plantarflexion. Therefore significant changes in passive biomechanical properties occur at the affected ankle of hemiparetic subjects, predominantly as the result of a loss of compliance in the Achilles tendon, although an increase in the passive stiffness of the triceps surae may also occur. The contribution of these changes to the locomotor disability of hemiparetic patients is discussed. 
Multichannel cochlear implant and electrically evoked auditory brainstem responses in a child with labyrinthitis ossificans. Ossification of the cochlea following meningitis presents a surgical challenge. Electrode mapping, especially in the young child, is difficult given the uncertainty of electrode contact with viable neural elements. This paper reviews surgical technique and the use of auditory brainstem responses to map the electrodes. A 4-year-old child deafened by meningitis at age 20 months had bilateral cochlear ossification by computed tomography. At surgery, a canal wall-down mastoidectomy and closure of the ear canal were performed. A trough around the modiolus was drilled, and the electrode array was placed in it. Post-operatively, the patient gave aversive or no responses to electrode stimulation. To assess electrode function, auditory brainstem responses to individual electrode activation were obtained under general anesthesia. Functioning electrodes could thus be selected for mapping. The patient now responds well to sound. 
Left ventricular diastolic collapse. An echocardiographic sign of regional cardiac tamponade. BACKGROUND. Cardiac tamponade after cardiac surgical procedures is often associated with hemodynamically significant localized pericardial effusions. The localized collection of pericardial effusion in the postoperative period and the atypical presentation of cardiac tamponade limit the use of conventional clinical and echocardiographic signs usually seen with a circumferential pericardial effusion. Observation of left ventricular diastolic collapse in the echocardiogram of a patient with postoperative regional cardiac tamponade prompted us to explore the frequency of this sign in regional cardiac tamponade. METHODS AND RESULTS. We retrospectively analyzed the echocardiograms of 18 patients with postoperative cardiac tamponade for the following echocardiographic findings: right atrial collapse, right ventricular diastolic collapse, left atrial collapse, and left ventricular diastolic collapse. Three of the 18 patients had circumferential pericardial effusion, and 15 had loculated pericardial effusion; in 10, the effusion was predominantly posterior, and in the other five, it extended laterally or inferiorly. The conventional echocardiographic signs of cardiac tamponade such as right atrial collapse, right ventricular diastolic collapse, and left atrial collapse were present in only 3, 1, and 3 of these 15 patients, respectively, but all exhibited left ventricular diastolic collapse. Increasing pressure within the compartment of a loculated pericardial effusion reaching the limit of pericardial distensibility and consequent transient reversal of transmural left ventricular pressure during diastole are most likely the basis for diastolic collapse of the thick-walled ventricle in a setting of regional cardiac tamponade. CONCLUSIONS. We conclude that left ventricular diastolic collapse is a frequent sign of regional cardiac tamponade and could be a useful marker of tamponade in postoperative patients. 
Percutaneous transluminal balloon angioplasty of stenotic standard Blalock-Taussig shunts: effect on choice of initial palliation in cyanotic congenital heart disease. To date, attempted balloon dilation of stenotic standard Blalock-Taussig shunts has been largely disappointing. It has been suggested that this may be due to the use of balloons of insufficient diameter. Balloon dilation of stenotic Blalock-Taussig shunts was attempted with use of relatively large balloons in five patients (11 to 67 months old) with cyanotic heart disease who were becoming progressively cyanotic and polycythemic (hemoglobin 17.9 +/- 1.1 g/dl) because of discrete shunt stenosis at the site of pulmonary anastomosis. Balloon diameters selected were equal to or within 1 mm of the unobstructed proximal shunt diameter. Before balloon dilation the diameter at the site of the stenosis was 2.8 +/- 0.8 mm (range 1.7 to 4); after balloon dilation it was 5.7 +/- 1.1 mm (range 4.5 to 7.5). The diameter increased in all patients (range 2.0 to 3.5 mm); the mean increase was 2.8 +/- 0.2 mm (p less than 0.005). Expressed as a percent, the increase in diameter at the stenosis ranged from 80% to 182.4% (mean 108.2 +/- 16.8%). Before balloon dilation the systemic oxygen saturation was 72.8 +/- 9.2% (range 55% to 80%) and after balloon dilation it was 83.6 +/- 2.9% (range 80% to 87%). A satisfactory increase (range 6% to 25%) in blood oxygen saturation was seen in all patients; the mean increase was 10.8 +/- 3.2% (p less than 0.01). At follow-up, the oxygen saturation by pulse oximetry was 85.8 +/- 2.9% (mean 5.8 +/- 1.7 months after balloon dilation) and the hemoglobin was 15.6 +/- 1.9 g/dl (mean 6.6 +/- 1.5 months after balloon dilation). 
Access to neurological care for minorities. Minority groups comprise a major segment of the estimated more than 34 million Americans without insurance coverage and also the underinsured. Neurologic disease and neurologic complications of the major causes of morbidity and mortality affect minorities protracted by limited access to health care. Hypertension, a major cause of stroke in the black population, is just one example of the impact of accessibility to intervention in central nervous system disease. Health statistics note the persisting gap between minority groups and the nation's norms for life expectancy. Aging America and particularly black elderly women, combined with the lagging infant mortality among minority groups, demonstrate limited access issues beyond economics, reflecting inner city mores, cultural barriers, and communication delay limiting contact with the practicing neurologist. Awareness of such access limitations to neurological care for minorities demands the attention of the practicing neurologist and the neurological societies. 
Cerebral infarction in young people. A study of 148 patients with early cerebral angiography. The aetiology of strokes was studied in a hospital based series of patients aged up to 40 years with precise clinical and radiological criteria. One hundred and forty five patients (75 males and 73 females) aged five to 40 years with cerebral ischaemia were evaluated. Aetiology was heterogeneous and could be classified into seven groups. Cerebral arteriograms were performed in all cases and indicated the aetiological diagnosis in most patients. Embolism was the most frequent recognised abnormality (38.4%). There were no complications of arteriography. Arterial dissections discovered by arteriography were the cause of the stroke in 10.1% of the patients. Atherosclerosis was diagnosed in 32 cases and was the commonest cause (21.6%). In one fifth of cases no cause was found. Contraceptive drugs were considered as potential cause of ischaemic stroke in 11.5%, cardiac diseases in 12.8% and haematological disorders in 8.1%. Other potential causes included migraine, inflammatory diseases, pregnancy and lacunas. Follow up in 126 cases showed that many patients had good functional recovery. 
Arthrodesis of the knee with an intramedullary nail. The cases of twenty patients who had an arthrodesis in which an intramedullary nail was used for stabilization were reviewed at an average follow-up of six years. The predominant indications were infection after total knee arthroplasty and post-traumatic pain and instability. Other indications included aseptic loosening of the components of a total knee arthroplasty, reconstruction after resection of a giant-cell tumor, non-union of a fracture of the distal part of the femur or the proximal part of the tibia, and failed external-compression arthrodesis. Success was achieved in seventeen patients (85 per cent), and functional stability immediately postoperatively was gained in all twenty. Of the three patients in whom the arthrodesis failed, all had sustained an intraoperative fracture, and infection eventually developed. Of the twelve nails that were secured to the greater trochanter with a loop of stainless-steel wire, none showed evidence of proximal migration. Of the eight nails that were not thus secured, two migrated proximally, necessitating removal of the nail. Two drawbacks to this operation are the long duration and the large amount of blood that is lost. The major advantage is that a high percentage of patients have progression to a stable fusion despite serious problems. Furthermore, all but seven patients (including the six who had a tumor or who had sustained an intraoperative fracture) were able to bear full weight by the second postoperative week. Only a few patients needed an external support for walking. 
Role of thromboxane and serotonin as mediators in the development of spontaneous alterations in coronary blood flow and neointimal proliferation in canine models with chronic coronary artery stenoses and endothelial injury. Platelet-mediated obstruction of stenotic and endothelium-injured coronary arteries may be important in the abrupt progression from chronic stable to unstable coronary heart disease syndromes in patients. Transcardiac accumulation of thromboxane A2 and serotonin has been demonstrated in patients as chronic stable angina is converted to unstable angina. In this study in anesthetized open chest dogs with coronary artery stenosis and endothelial injury, thromboxane A2 and serotonin were shown to be important mediators of intermittent coronary obstruction caused by platelet aggregation and dynamic vasoconstriction. Furthermore, thromboxane A2 synthesis inhibitors and receptor antagonists and serotonin receptor antagonists, singly and together, provided substantial protection against repetitive platelet aggregation and dislodgment in canine models with coronary artery stenosis and endothelial injury even when systemic catecholamine concentrations were markedly elevated. These same observations apply in chronically instrumented, awake, unsedated dogs with coronary artery stenosis and endothelial injury in which recurrent platelet attachment and dislodgment cause cyclic flow alterations that may be prevented by thromboxane A2 synthesis inhibitors and receptor antagonists and serotonin receptor antagonists. Chronically instrumented dogs with coronary stenosis and endothelial injury in which recurrent platelet attachment and dislodgment occurred also developed neointimal proliferation of varying severity within 10 days to 3 weeks; the morphologic appearance of the neointimal proliferation was identical to that found in patients who develop restenosis after coronary angioplasty. 
Substitution of leucine for isoleucine in a sequence highly conserved among retroviral envelope surface glycoproteins attenuates the lytic effect of the Friend murine leukemia virus. Friend murine leukemia virus is a replication-competent retrovirus that contains no oncogene and that exerts lytic and leukemogenic properties. Thus, newborn mice inoculated with Friend murine leukemia virus develop severe early hemolytic anemia before appearance of erythroleukemia. To identify the retroviral determinants regulating these effects, we used chimeric infectious constructions and site-directed point mutations between a virulent Friend murine leukemia virus strain and a naturally occurring variant attenuated in lytic and leukemogenic effects. We found that severe hemolytic anemia was always associated with higher numbers of blood reticulocytes with budding retroviral particles. Furthermore, a remarkably conservative leucine to isoleucine change in the extracellular SU component of the retroviral envelope was sufficient to attenuate this lytic effect. Also, this leucine at position 348 of the envelope precursor protein was located within the only stretch of five amino acids that is conserved in the extracellular SU component of all murine, feline, and primate type C and type D retroviral envelopes. This observation suggested an important structural function for this yet undescribed conserved sequence of the envelope. Lastly, we observed that lytic and leukemogenic effects were attenuated by a deletion of a second repeat in the transcriptional enhancer region of the viral long terminal repeats of the variant strain. 
Mesonephric rest hyperplasia. A potential diagnostic pitfall. A case of mesonephric rest hyperplasia, an incidental finding in the hysterectomy specimen of a 48-year-old woman, was initially misdiagnosed as a well-differentiated cervical adenocarcinoma. We highlight the histologic, histochemical, and immunohistochemical features of this potential diagnostic pitfall and review the relevant literature. 
Coarctation: do we need to resect ductal tissue? A review of the literature as well as a retrospective review of 100 neonates undergoing operation for coarctation at Children's Hospital in Boston between 1972 and 1984 has not established clear superiority for either resection and end-to-end anastomosis or subclavian flap aortoplasty with respect to risk of recurrent coarctation. However, there is histological evidence that the juxtaductal coarctation shelf is composed of smooth muscle of ductal origin, which subsequently fibroses. This abnormal tissue may be at risk for late aneurysm development, particularly if balloon dilatation angioplasty is required. The fact that this abnormal tissue is not removed by the subclavian flap procedure is one of the inherent disadvantages of that procedure. Other disadvantages include the need to sacrifice the left subclavian artery and the fact that, unlike resection and end-to-end anastomosis, the subclavian flap procedure does not lend itself to augmentation of the hypoplastic distal aortic arch. Furthermore, occasionally a secondary coarctation membrane is present within the distal aortic arch, and though it is readily detected during the resection procedure, it can be missed with the subclavian flap procedure. Based on these considerations rather than on a demonstrated superiority of either procedure, my colleagues and I currently prefer resection and end-to-end anastomosis over subclavian flap aortoplasty. 
Circus movement atrial flutter in canine sterile pericarditis model. Activation patterns during entrainment and termination of single-loop reentry in vivo. BACKGROUND. Recently, we used a custom designed "jacket" electrode with 127 bipolar electrodes in a flexible nylon matrix to map the total atrial epicardial surface in the in situ canine heart. Atrial flutter in dogs with sterile pericarditis was shown to be due to a single wave front circulating around a combined functional/anatomic obstacle, with the arc of functional conduction block contiguous with one or more of the atrial vessels. METHODS AND RESULTS. In the present study, this model was used to analyze the activation pattern during pacing-induced entrainment and termination of single reentrant loops in a syncytium without anatomically predetermined pathways. Sustained atrial flutter was induced in five dogs with 3-5-day-old sterile pericarditis. Atrial pacing at a cycle length 5-30 msec shorter than the spontaneous cycle length entrained the arrhythmia and could result in a "classical" activation pattern, characterized by an antidromic stimulated wave that collided with the reentrant orthodromic wave front of the previous beat at a constant site. However, two variations of this classical activation pattern were also observed: 1) Pacing at short cycle lengths could lead to localized conduction block in antidromic direction, forcing a change in the pathway of the antidromic wave front. This could prevent the expected shift of the site of collision in antidromic direction. 2) The stimulated orthodromic wave front could also use a pathway different from that of the original reentrant impulse, so that a different circuit was active during the pacing period. Termination of atrial flutter by rapid atrial stimulation was associated with progressive slowing and finally blocking of the paced orthodromic wave front and a progressive shift of the site of collision in antidromic direction. The occurrence of conduction block was determined by the cycle length of stimulation and the number of stimulated beats. A longer train at the critical cycle length or the critical number of beats at a shorter cycle length could reinduce the same reentrant circuit or a different reentrant circuit, respectively, during stimulated cycles following the beat that terminated reentry. CONCLUSIONS. The epicardial activation sequence during entrainment of reentrant arrhythmias does not necessarily follow a standard activation pattern. Instead, the stimulated orthodromic as well as the antidromic wave front might use a pathway different from that of the original reentrant wave front. The mechanisms of termination, failure of termination, and reinitiation of single-loop reentry are similar to those in the "figure-eight" reentrant circuit. 
The use of nasal calcitonin in the treatment of post-traumatic algodystrophy. Calcitonin is widely used in the treatment of algodystrophy but a major disadvantage is the need for its parenteral administration. For this reason, we evaluated the effect of 400 iu of nasal calcitonin in the treatment of post-traumatic algodystrophy in a prospective randomized double-blind study. We found no demonstrable effect on the clinical or skeletal progression of the disorder using sensitive methods of measuring the response to treatment. There was, however, a small but significant hypocalcaemic response in the treatment group despite no change in the other indices of bone turnover. Possible reasons for this lack of clinical and skeletal effect are discussed. 
Blunt traumatic bladder rupture: the role of retrograde cystogram. STUDY OBJECTIVE: We evaluated the importance of microscopic and gross hematuria and the role of retrograde cystography and computed tomography (CT) in the diagnosis of blunt traumatic bladder rupture. DESIGN: All cases at a Level I trauma center between January 1, 1986, and March 31, 1989, were reviewed retrospectively. SETTING: Level I trauma center, university hospital. TYPE OF PARTICIPANTS: All patients with acute blunt abdominal trauma admitted to this Level I trauma center. INTERVENTIONS: The patients' charts were reviewed with emphasis on mode of diagnosis, treatment, and outcome. MEASUREMENTS AND MAIN RESULTS: Twenty-one patients had bladder rupture. All 21 had hematuria with more than 50 RBCs/high-power field, 17 gross and four microscopic. Twenty patients underwent retrograde cystography, which accurately identified bladder rupture, and one was found at laparotomy for other injuries. Seven patients had CT of the abdomen and pelvis, which failed to demonstrate bladder rupture. There were no associated urethral injuries in any of the patients with bladder rupture. CONCLUSION: Significant (more than 50 RBCs/high-power field) hematuria is the principal indication for evaluation for blunt bladder injury, and retrograde cystography is the diagnostic procedure of choice. CT is neither sensitive nor specific enough as primary diagnostic modality. 
A novel mutation in the invariant AG of the acceptor splice site of intron 4 of the beta-hexosaminidase alpha-subunit gene in two unrelated American black GM2-gangliosidosis (Tay-Sachs disease) patients. Samples of genomic DNA from three unrelated American black infants having both biochemical and clinical features of classical infantile Tay-Sachs disease were sequenced following PCR amplification. A G----T transversion was observed in the AG acceptor splice site preceding exon 5 of the beta-hexosaminidase alpha-subunit gene in the first black family. This transversion changed the acceptor splice site from the consensus sequence, AG, to AT, thereby interfering with splicing at this intron 4/exon 5 junction. The proband was homozygous for this mutation; his mother and a brother are heterozygous. The same mutation was found in a second, apparently unrelated, black GM2-gangliosidosis patient. The second patient was a compound heterozygote, as only one allele carried this mutation. The mother and a brother in this second family are carriers for this mutation, while the father and a noncarrier sister are normal for this region of the gene. The third proband did not have this mutation; nor did the mother of a fourth black proband. Eight other independently ascertained non-black, non-Jewish, GM2-gangliosidosis families did not have this mutation. The observation of the same novel mutation in two unrelated black GM2-gangliosidosis patients indicates that the American black population has segregating within it at least one GM2-gangliosidosis mutation which may be specific to this population and not a result of migration. 
Bopindolol: Czechoslovak experience with a new beta blocker in the treatment of hypertension. Bopindolol is a nonselective beta blocker with mild intrinsic sympathomimetic activity. One of the drug's main benefits is its prolonged effect, lasting for 24 hours, which makes it possible to administer bopindolol in a single daily dose, a fact that may improve patient adherence to therapy. A double-blind study was performed in two centers, comparing bopindolol with metoprolol in 86 hypertensive patients. Baseline diastolic blood pressure (BP) was 100 to 120 mm Hg. The effects of bopindolol or metoprolol on BP and heart rate were similar: return to normal values was achieved in 70% of patients with either drug. A 6-month study at another center found that bopindolol did not affect the levels of total cholesterol, low-density and high-density lipoprotein cholesterol or triglycerides. Another 12-month study documented a decrease in total cholesterol, apolipoprotein (apo) A1 and apo B. The apo A/B ratio rose, thus improving the atherosclerotic index. No deterioration of glucose tolerance or immunoreactive insulin response to glucose was seen after 6 months of bopindolol administration. Bopindolol satisfactorily modifies not only resting but also exercise BP during isometric and isotonic load, thus reducing BP fluctuation during physical activities of the hypertensive patient. The drug exerts no effect on renal and liver function, electrolyte balance and hematologic parameters. Bopindolol is a very useful drug of first choice in mild and moderate hypertension. Bopindolol's main advantages include its prolonged action, good tolerance and a beneficial effect on risk factors of atherosclerosis (lipid and carbohydrate metabolism). 
Short and long term outcome of percutaneous transluminal coronary angioplasty in unstable versus stable angina pectoris: a report of the 1985-1986 NHLBI PTCA Registry. In a cohort of 1,720 consecutive patients from the National Heart, Lung, and Blood Institute, Percutaneous Transluminal Coronary Angioplasty (PTCA) Registry (August 1985-May 1986), we compared 768 patients (45%) with stable angina and 952 patients (55%) with unstable angina pectoris. Unstable angina patients exhibited at least one of the following characteristics: new onset angina, rapidly progressing angina, angina at rest, angina refractory to medication, variant angina, acute coronary insufficiency, or angina recurring shortly after an acute myocardial infarct. The distribution of single- and multi-vessel disease was similar among stable and unstable angina patients; multi-vessel disease predominated. Average severity of stenosis and incidence of tubular and diffuse stenosis morphology were higher among patients with unstable angina (both p less than 0.001). Patient success rates were similar in stable and unstable patients. However, on a per lesion basis, overall angiographic success rate and average reduction of severity of stenosis in successfully dilated lesions were significantly higher among patients with unstable angina (both p less than 0.001). Incidence of major patient complications (p less than 0.01) and of emergency coronary bypass surgery (p less than 0.05) were also higher in patients with unstable angina but consistent with their more precarious clinical condition and stenosis morphology. During a two year follow-up, the cumulative distributions of death, myocardial infarct, repeat PTCA, and coronary bypass surgery were not significantly different in patients with stable angina compared to patients with unstable angina. Comparison of the current PTCA Registry cohort with the cases reported in the 1979-1982 Registry revealed a 19% higher success rate for both stable and unstable angina patients. Major complication rates decreased between time periods for stable but not for unstable angina patients. Incidence of emergency bypass surgery decreased more for stable than for unstable angina patients. Coronary angioplasty is indicated in properly selected patients with unstable angina and both single- and multi-vessel coronary disease. 
Experimental treatment of thrombotic vascular occlusion. The role of laser energy in the treatment of thrombotic vascular occlusion was evaluated in two sets of experiments. First, 10 polytetrafluoroethylene grafts were used to replace segments of the superficial femoral arteries in dogs and were thrombosed by distal ligation. Occlusion was maintained for one hour, or for 7, 14, 21, and 28 days in each of two grafts. Patency was restored in all 10 grafts without perforation or anastomotic disruption using a 2 mm hot tip probe powered by an Argon laser. However, increased organization of thrombus related to the duration of occlusion lead to decreased laser channel diameters, and 75% of the 28 day thrombus remained in the graft after recanalization. The second experiments tested the added benefit of thrombolytic infusion following laser recanalization. Bilateral external iliac artery thrombosis was induced in dogs by operative vessel isolation, de-endothelialization, and thrombin injection. At 7 days the efficacy of laser-assisted thrombolysis (LAT) versus enzymatic thrombolysis (ET) alone was compared. Eight vessels underwent ET by urokinase (4000 I.U./min.); 14 vessels were laser recanalized prior to thrombolytic infusion. LAT was performed from a carotid artery approach in 8 vessels (antegrade) and from a femoral artery in 6 vessels (retrograde). In contrast to studies using the hot tip alone, both ET and LAT accomplished complete thrombus removal. However, LAT lead to significant iliac arterial flow in 9 +/- 8 min. (antegrade) and 25 +/- 8 min. (retrograde) while ET required 109 +/- 47 min (p less than 0.01). 
Fetal akinesia deformation sequence (Pena-Shokeir phenotype) associated with acquired intrauterine brain damage. An infant with Pena-Shokeir phenotype was born to a cocaine-using mother. The pathologic findings included polyhydramnios, facial anomalies, arthrogryposis, camptodactyly, pulmonary hypoplasia, and tetralogy of Fallot. The neuropathologic findings were diffuse brainstem and spinal cord neuronal degeneration and focal cerebral infarction, consistent with acquired intrauterine ischemic damage. 
The infectious and hematologic otolaryngic complications of myelosuppressive cancer chemotherapy. The otolaryngologist-head and neck surgeon is frequently consulted to evaluate patients before the administration of myelosuppressive cancer chemotherapy. Fifty consecutive patients treated at the University of Pennsylvania Oncology Center were studied before and during chemotherapy for adult leukemia or bone marrow transplantation. Otolaryngic history, physical examination, radiographic studies, and hematologic surveys were analyzed for the duration of therapy in an attempt to identify risk factors for infectious and hematologic otolaryngic complications. Two-thirds of the patient studied experienced untoward effects that required the further attention of an otolaryngologist-head and neck surgeon. The various complications and associated correlations with the study parameters before and during chemotherapy are discussed. 
Elevated plasma chromogranin-A concentrations in prostatic carcinoma. Chromogranin-A is considered a sensitive immunohistochemical tissue marker in neuroendocrine prostatic carcinoma. We report that the plasma chromogranin-A level was elevated in 48% of 25 patients with stage D2 prostate cancer, and suggest that this marker can be used to monitor the clinical course of these patients. 
Thoracic myelopathy caused by ossification of the ligamentum flavum. Clinicopathologic study and surgical treatment. The authors reviewed 14 patients with thoracic myelopathy caused by ossification of the ligamentum flavum (OLF). The predominant locality of symptomatic OLF was at the thoracolumbar junction, particularly at T10-11 followed by T11-12. At the level of the thickest OLF in each patient, there were three types of OLF from computed tomography and operative findings: a lateral type in 3 patients, diffuse in 8, and thickened nodular in 3. The diagnosis of OLF-related thoracic spinal canal stenosis was best made by enhanced computed tomography. Histologic study revealed that the developmental mode of OLF was mainly endochondral ossification. Numerous fibrocartilaginous cells were found in the increased and swollen collagen fibers forming the hypertrophic ligamentum flavum (HLF). Ossification extended along the superficial layer of HLF. The size or extension of OLF was relevant to the corresponding diathesis of spinalhyperostosis. Results of laminectomy for OLF were poor because of the high occurrence of complications early on or later deterioration. Therefore, laminoplasty is recommended as a successful procedure for OLF-related thoracic myelopathy, avoiding further local mechanical stress due to tensile force. 
Significance of a negative exercise thallium test in the presence of a critical residual stenosis after thrombolysis for acute myocardial infarction. BACKGROUND. After thrombolytic therapy for acute myocardial infarction, increasing emphasis is placed on early submaximal exercise testing, with further intervention advocated only for demonstrable ischemia. Although significant residual coronary artery lesions after successful thrombolysis are common, many patients paradoxically have no corresponding provokable ischemia. METHODS AND RESULTS. The relation between significant postthrombolytic residual coronary artery disease and a negative early, submaximal exercise thallium-201 tomogram was studied among 101 consecutive patients with uncomplicated myocardial infarction and at least 70% residual stenosis of the infarct artery. A negative test occurred in 49 (48.5%) patients with a mean 88% residual infarct artery stenosis. Further characteristics of the group were as follows: mean time to treatment was 3.1 hours; mean age was 54 +/- 10 years; 80% were male; 47% had anterior infarction; 39% had multivessel disease; mean left ventricular ejection fraction was 53 +/- 14%; and mean peak creatine kinase level was 3,820 +/- 3,123 IU/ml. A similar group of 52 (51.5%) patients, treated within 3.3 hours from symptom onset, with a mean postthrombolysis stenosis of 90%, had a positive exercise test. Characteristics of this group were as follows: age was 58 +/- 10 years; 92% were male; 56% had anterior infarction; 40% had multivessel disease; and mean left ventricular ejection fraction was 54 +/- 15%. The peak creatine kinase level associated with the infarction, however, was lower: 2,605 +/- 1,805 IU/ml (p = 0.04). There was no difference in performance at exercise testing with respect to peak systolic pressure, peak heart rate, or time tolerated on the treadmill between the two groups. By multivariate logistic regression, only peak creatine kinase level predicted a negative stress result in the presence of a significant residual stenosis (odds ratio, 4.2; 95% confidence interval, 1.1-16.3). CONCLUSIONS. The explanation for the relatively frequent finding of a negative early stress 201Tl tomogram after apparently successful reperfusion appears to be more extensive myocardial necrosis and not delay in therapy or inadequate exercise performance. 
Therapeutic effects of genetically engineered toxin (DAB486IL-2) in patient with chronic lymphocytic leukaemia. In DAB486IL-2 the receptor-binding domain of native diphtheria toxin is replaced by human IL-2 sequences. This recombinant fusion protein is selectively cytotoxic for cells bearing high-affinity IL-2 receptors--eg, leukaemic cells. A patient with chronic lymphocytic leukaemia who did not respond to gamma interferon and conventional antileukaemic drugs has responded to DAB486IL-2. 
The prevalence of autoantibodies during third-trimester pregnancy complicated by hypertension or idiopathic fetal growth retardation. Lupus anticoagulant, anticardiolipin, antinuclear, anti-deoxyribonucleic acid, antithyroglobulin, and antithyroid microsomal antibodies were assayed during third-trimester pregnancy (100 normal, 100 with complications). In spite of a normal activated partial thromboplastin time in all instances, lupus anticoagulant was further investigated by three additional procedures: tissue thromboplastin inhibition time, platelet neutralization procedure, and cephalin neutralization test. The prevalence of autoantibodies in pregnancies with hypertension reaches 16% (four with lupus anticoagulant, two with anticardiolipin, and two with antithyroid microsomal antibodies), which is significantly greater than that for idiopathic fetal growth retardation (2%) (one with lupus anticoagulant antibodies) and normal pregnancies (3%) (two with antithyroglobulin and one with autithyroid microsomal antibodies) (p less than 0.01). Autoantibodies were equally distributed between patients with gestational hypertension and those with preeclampsia. When compared with the 42 patients with hypertension and no autoantibodies, the eight patients with autoantibody had a more frequent history of fetal growth retardation (p less than 0.05), but there was no difference in the severity of hypertension, the frequency of obstetric complications, or the outcome of pregnancy. They did not require any specific treatment. 
Atrial fibrillation associated with autonomic dysreflexia in patients with tetraplegia. Atrial fibrillation is an arrhythmia characterized by disorganized atrial depolarizations and an irregular ventricular response. Most patients with atrial fibrillation have underlying cardiac pathology. This paper presents the cases of three patients with high-level spinal cord injury and symptoms of autonomic dysreflexia who developed atrial fibrillation without any cardiac or metabolic disease that would predispose them to this. The paper proposes that autonomic dysreflexia might predispose a patient to atrial fibrillation by altering the pattern of repolarization of the atria, making the heart susceptible to a reentrant type of arrhythmia. High-level spinal cord injured patients may be at increased risk for the development of atrial fibrillation, an arrhythmia which, if left untreated, can increase the incidence of an embolic cerebrovascular accident that could further impair the patient's functional status. 
Selection of the approach to the distal internal carotid artery from the second cervical vertebra to the base of the skull. Although several approaches for exposure of distal internal carotid artery lesions have been reported, the precise anatomic levels for which each of these maneuvers are most appropriate have not been well described. Since these techniques may require preoperative preparation, it is useful to determine in advance how much exposure will be needed and to select the most suitable and effective technique. We used anatomic dissection in 12 human cadaver specimens (24 carotid bifurcations) to define the limits of distal internal carotid artery exposure by several commonly advocated methods. The standard anterior approach along the sternocleidomastoid muscle allowed exposure of the internal carotid artery to the level of the upper one third of the second cervical vertebra. The upper limit of this exposure was extended to the middle of the first cervical vertebra by division of the posterior belly of the digastric muscle. Anterior subluxation of the mandible increased the distal exposure of the internal carotid artery to the superior border of the first cervical vertebra. Styloidectomy in combination with the preceding maneuvers extended the exposure an additional 0.5 cm cephalad. Lateral mandibulotomy did not significantly extend exposure beyond that obtained with mandibular subluxation and styloidectomy. Exposure of the internal carotid artery in the 1 cm immediately below the base of the skull required a posterior approach with mastoidectomy. 
Time course of creatine kinase release after termination of sustained ventricular dysrhythmias. Differentiation between primary and secondary (caused by acute myocardial infarction) ventricular fibrillation has important therapeutic and prognostic implications. The diagnosis of myocardial infarction is based on clinical, ECG, and creatine kinase MB isoenzyme (MBCK) activity. Enzymatic criteria might not be able to confirm the diagnosis of myocardial infarction after recent cardioversion. The routine use of electrophysiologic studies involving the induction and termination of ventricular dysrhythmias provides a setting in which enzyme release as a result of cardioversion alone can be examined. Therefore a systematic investigation of the magnitude and time course of creatine kinase (CK) and MBCK release was performed after termination of ventricular dysrhythmias in 57 patients undergoing electrophysiologic studies. Of patients requiring external cardioversion, only 50% had an elevation in CK and MBCK activity. Elevation when present corrected with the number of shocks and cumulative energy delivered. The magnitude of MBCK release exceeded 10% of the total CK activity in 9% of observations. Pace-termination of ventricular tachycardia did not result in enzyme release. Arrhythmia characteristics, coronary artery disease, and left ventricular function did not affect the magnitude of the time course of enzyme release. These data suggest that cardioversion with multiple shocks may result in a component of MBCK release, and thus a false positive diagnosis of primary acute myocardial infarction may be made by relying exclusively on the enzyme release pattern. 
Percutaneous mitral valvuloplasty following surgical repair of sinus venosus atrial septal defect. Mitral valvuloplasty performed 5 y after repair of a sinus venosus ASD was difficult because of a thickened septum, but resulted in improved mitral valve opening and did not lead to ASD. Thus, prior repair of a sinus venosus ASD may not be an absolute contraindication to mitral valvuloplasty. 
Lumbar regional anaesthesia and prophylactic anticoagulant therapy. Is the combination safe? A survey has been carried out in all Danish anaesthetic departments (n = 80) regarding the attitude towards the use of epidural/spinal lumbar analgesia in patients who were receiving prophylactic anticoagulant therapy for the prevention of thromboembolism. About 60% of the departments used the techniques in patients receiving low-dose heparin and no side effects had been experienced. Spinal and epidural anaesthesia were in general regarded as being contraindicated in patients fully anticoagulated with vitamin K antagonists. In the world literature, the attitude towards the combination is conflicting. No randomised trial has been performed and complications are almost entirely confined to patients fully anticoagulated with vitamin K antagonists. Only one case of an epidural haematoma has been recorded when subcutaneous low-dose heparin was used as thromboprophylaxis. 
Local toxicity with subcutaneous methadone. Experience of two centers. We report on 8 patients treated with subcutaneous methadone for cancer-related pain at 2 institutions. The success of other subcutaneous agents for pain control has been well demonstrated. It was felt that methadone would be useful due to its low cost. Unfortunately, 7 of the 8 patients experienced adverse reactions at the subcutaneous sites requiring cessation of subcutaneous methadone. 
Effect of calcification on in vivo mechanical response of rabbit arteries to balloon dilation. BACKGROUND. Atherosclerosis has been associated with loss of artery wall distensibility in human cadavers and in experimental animal models, giving it the lay term "hardening of the arteries." METHODS AND RESULTS. To assess the effect of calcification on arterial distensibility, balloon pressure and volume were recorded during dilation of calcified aortas in Watanabe heritable hyperlipidemic (WHHL) rabbits in vivo. Calcification was induced by dietary supplements of cholesterol, vitamin D2, and calcium. Balloon pressure, volume, and time signals were acquired at high frequency with controls for temperature and balloon inflation rate. Resistance to balloon dilation was minimal in control rabbit aortas (delta Vmax = 5.0 +/- 3.5 microliters) and in excised nonatherosclerotic human coronary arteries, and it was small in aortas from cholesterol-fed rabbits (12.3 +/- 8 microliters), even when lipid levels were markedly elevated by a high cholesterol diet (611 +/- 347 mg/dl). With dietary cholesterol, vitamin D2, and calcium supplements, WHHL rabbits developed mild hypercalcemia (15 +/- 1.9 mg/dl), hypercholesterolemia (1,100 +/- 633 mg/dl), moderate-to-marked aortic calcification, and high resistance to balloon dilation (38 +/- 27) comparable to that seen in angioplasty patients. CONCLUSIONS. It is concluded that experimentally induced calcification decreases the distensibility of the rabbit aorta in vivo and that it yields to balloon dilation by plastic deformation closely resembling that seen in balloon angioplasty of human coronary arteries. These findings suggest that calcification contributes to arterial "hardening" associated with atherosclerosis. 
Relationship between the timing of aneurysm surgery and the development of delayed cerebral ischemia. A consecutive series of 145 patients with acute aneurysmal subarachnoid hemorrhage (SAH) were operated on within 7 days of SAH and were prospectively evaluated over a 4-year period to determine if the timing of aneurysm surgery influenced the development of delayed cerebral ischemia. All patients were managed with a standardized policy of urgent surgical clipping and treatment with aggressive prophylactic postoperative volume expansion. Patients with delayed ischemic symptoms were additionally treated with induced hypertension. Forty-nine patients underwent surgery on Day 0 or 1 (Group 1) post-SAH, 60 patients on Day 2 or 3 (Group 2), and 36 patients on Days 4 through 7 (Group 3). Postoperative delayed cerebral ischemia developed in 16% of (Group 1) patients, in 22% of Group 2 patients, and in 28% of Group 3 patients. Cerebral infarction resulting from delayed cerebral ischemia developed in only 4% of Group 1 patients, 10% of Group 2 patients, and 11% of Group 3 patients. A bad clinical outcome as a result of delayed cerebral ischemia occurred in one Group 1 patient (2%), two Group 2 patients (3%), and one Group 3 patient (3%). Preoperative grade was not significantly correlated with the incidence or severity of delayed cerebral ischemia at any time interval except that patients in modified Hunt and Hess Grade I or II who underwent surgery on Day 0 or 1 after SAH had no strokes or bad outcomes from delayed cerebral ischemia. This study demonstrates that there is no rationale for delaying aneurysm surgery based on the time interval between SAH and patient evaluation. 
Carnitine deficiency associated with ornithine transcarbamylase deficiency. An infant with X-linked recessive ornithine transcarbamylase deficiency is described who also had severe deficiency of plasma and liver carnitine during normoammonemic periods. Treatment with L-carnitine (100 mg/kg/day) for 12 months decreased the frequency of hospitalizations for hyperammonemia, although it did not alter his neurologic status. This report demonstrates that persistent carnitine deficiency may be present in patients with ornithine transcarbamylase deficiency even when plasma ammonia is normal. Carnitine evaluation and supplementation may be important in the treatment of patients with this metabolic disorder. 
Do primary dysfunctions in neural control of arterial pressure contribute to hypertension? This article is a summary of the physiological and clinical evidence that links the cause of essential hypertension to the brain. We stress the potential importance of a biochemical disturbance in the central role of angiotensin II in the regulation of arterial pressure. While the evidence is compelling, we acknowledge the need for further complete studies on this timely subject. 
Oral contraceptive-associated liver cell adenoma and hepatocellular carcinoma. Cytomorphology and mechanism of malignant transformation. From January 1976 to May 1990, 1673 patients with a liver mass or masses detected by imaging techniques underwent percutaneous fine-needle aspiration biopsy of the liver. Of these, 99 were diagnosed cytologically as "hepatocellular carcinoma" and 9 as "consistent with liver cell adenoma." The cytologic diagnoses were confirmed in the follow-up of all cases. Among the 99 patients with hepatocellular carcinoma, 3 had taken oral contraceptives for a period of 10, 11, and 12 years, respectively. The nine patients with liver cell adenoma were all users of oral contraceptives over a period ranging from 5 to 10 years. Of these, two who had taken oral contraceptives for a period of 8 and 10 years, respectively, had foci or areas of liver cell dysplasia within the adenomas. The cytologic criteria for the diagnosis of liver cell dysplasia included cytoplasmic and nuclear enlargement, nuclear pleomorphism together with prominent nucleoli, hyperchromasia and multinucleation. The cytologic features of liver cell dysplasia strikingly mimic hepatocellular carcinoma. From this study, the foci or areas of liver cell dysplasia arising within the liver cell adenomas appear to be the missing link responsible for the transformation of liver cell adenoma to carcinoma. It is believed that liver cell adenomas are not premalignant and may undergo reversible change after withdrawal of causative agents, whereas liver cell dysplasia is an irreversible, premalignant change and will eventually progress to hepatocellular carcinoma. 
Ovarian ablation failures by radiation: a comparison of two dose schedules. Sixty Chinese breast cancer patients underwent ovarian irradiation with one of two dose schedules: 12 Gy/4 fractions/4-6 days or 14 Gy/4 fractions/4-6 days. The ovarian ablation failure rates were 14% and 0% respectively in patients above 40 years of age. The overall ablation failure rate in younger patients was unacceptably high at 35%. The significance of the findings is discussed. 
Olfactory dysfunction in three neurodegenerative diseases. Olfactory dysfunction is among the first signs of Alzheimer's disease (AD), idiopathic Parkinson's disease (PD), and the parkinsonism-dementia complex (PDC) of Guam. We have recently demonstrated that the odor identification and detection deficits of patients with PD are equivalent to those of patients with mild AD when subtle differences in cognitive function are statistically controlled for by analysis of covariance. In contrast, patients with progressive supranuclear palsy (PSP) and patients with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism evidence olfactory function much more similar to that of normal controls. In the present study, we administered the University of Pennsylvania Smell Identification Test and the Picture Identification Test to 24 patients with early signs of the PDC of Guam and statistically compared their test scores to those of 24 early-stage AD and 24 early-stage PD patients of similar age and gender from the United States mainland. Although the PDC group evidenced slightly more difficulty in identifying pictures than did the other 2 groups, the odor identification deficit associated with this disorder was of the same magnitude as that observed in AD and PD, suggesting that olfactory testing cannot be used to distinguish among these 3 diseases and that the olfactory dysfunction of these disorders may reflect a common neurologic substrate. 
Mammographic guidewire localization of nonpalpable breast lesions. Guidewire-directed biopsy is the predominant method of evaluating nonpalpable breast lesions detected by mammography. It is an accurate and safe procedure for obtaining a histologic evaluation of abnormal tissue, leading to early diagnosis and improved survival rates. This report reviews 526 needle localizations and biopsies of nonpalpable breast lesions performed in two community hospitals over a 39-month period and compares early results with those achieved in the last 13 months of the study. This review indicates that as experience in using this modality increased, the cancer detection rate increased and the percentage of invasive cancers decreased. The percentage of cancers detected in the final 13 months of the study (19%, Group II) was higher than in the first 26 months of the study (13%, Group I). Although microcalcifications were found in 24 per cent of the mammograms leading to a diagnosis of cancer, they did not prove to be a reliable indicator of malignancy in this study. 
Parkinson's disease in Ferrara, Italy, 1967 through 1987. Epidemiological surveys on Parkinson's disease that have been carried out in different parts of the world have suggested that the disease is uniformly distributed in white populations. The position with regard to the Mediterranean peoples is still controversial, because of the large variation of the frequencies observed in the different areas that have been investigated. We therefore studied the frequency of Parkinson's disease in the Local Health Service of Ferrara, northeastern Italy (mean population, 187,000). Based on 394 patients, the mean incidence per year for the period from 1967 through 1987 was 10.01/100,000. The incidence rate of Parkinson's disease among cases with early onset was found to be statistically higher in rural areas as compared with urban ones (6.32/100,000 vs 3.11/100,000). Moreover, the study revealed a significantly higher incidence rate among agricultural workers (20.6/100,000). These results would seem to give further support to the hypothesis of a possible causal role of environmental factors that are mainly linked to agriculture, most likely due to the continual exposure to toxic agents in this area. However, further studies, which are not exclusively epidemiological, are necessary before any conclusions may be drawn, because many confounding variables may account for the results from surveys of this type. 
Common bile duct and intrahepatic stones: results of transhepatic electrohydraulic lithotripsy in 50 patients. Percutaneous, transhepatic, intracorporeal, electrohydraulic shock wave lithotripsy was performed in 50 patients after failure of endoscopic treatment (n = 43) or directly in patients with a strictured hepaticojejunostomy (n = 7). Twenty-seven patients had common bile duct stones; 23, intrahepatic stones. Three steps were used: A transhepatic bilicutaneous fistula was created, a wide communication between the bile duct and the gut was established, and contact shock wave lithotripsy was performed under endoscopic guidance. Afterward, 46 patients were free of stones. In four patients with diffuse intrahepatic lithiasis, only 75% of stones could be cleared. Severe complications, seen in 11 patients (hemobilia necessitating transfusion [n = 6], bile duct perforation resulting in cholangitis [n = 3], acute pulmonary edema [n = 1], and hemothorax [n = 1]), were fatal in four patients; all occurred early in the study. The authors modified their technique by dilating the biliary tract in two sessions 3 days apart, waiting 6 days for the tract to mature, and then introducing the cholangioscope directly through the skin, significantly reducing complications and mortality (P less than .005). 
Changes in mucociliary clearance during acute exacerbations of asthma. Previous studies have suggested that mucociliary clearance (MC) is impaired in asthmatic subjects. If so, impaired clearance may be an important factor in acute exacerbation. We proposed that if MC plays a significant role in acute illness, MC should be impaired during the exacerbation but improve after recovery. To test this hypothesis, five asthmatic patients with attacks requiring hospitalization underwent measurement of MC using radiolabeled aerosol and a gamma camera. They were studied on the second or third day after admission with repeat measurements after discharge. Spirometry was performed before all studies. After an equilibrium xenon scan (133Xe), which defined lung borders and measured regional volume, radiolabeled saline particles containing technetium-labeled (99mTC) sulfur colloid were deposited and used to label airway mucus. Deposition patterns were matched by regulating particle distribution and breathing pattern. MC was then measured as percentage retention of radioactivity at 10-min intervals for 2 h. When hospitalized, 96.0 +/- 2.06% (SEM) of the initial radioactivity was retained in the lung after 2 h, indicating little clearance of mucus from the lung. In fact, no significant changes were detected when activity at 120 min was compared with measurements at 10 min (99.2 +/- 0.22%, NS). After discharge clearance was markedly enhanced. That is, retention of lung activity was significantly lower at all time intervals from 10 min onward, with only 70.9 +/- 3.86% retained at 120 min (p = 0.008). During an asthmatic attack warranting hospital admission, MC is significantly impaired, with marked improvement following recovery. 
The effect of ERCP on circulating pancreatic enzymes and pancreatic protease inhibitors. The pathogenesis of endoscopic retrograde cholangiopancreatography (ERCP)-induced pancreatitis is poorly understood. To elucidate a role for pancreatic enzymes in ERCP-induced pancreatitis, we measured serum amylase, lipase, trypsin, and elastase in 25 patients undergoing ERCP. Serum alpha 1-antitrypsin and alpha 2-macroglobulin, two major pancreatic protease inhibitors, also were measured. All pancreatic enzymes measured rose significantly after ERCP. Pancreatic duct cannulation was associated with a greater elevation in serum amylase and lipase. Circulating alpha 2-macroglobulin was reduced by 7% (p = 0.04) 6 h after ERCP, whereas circulating alpha 1-antitrypsin increased over the same time period. Papillotomy, stent placement, or underlying disease did not influence changes any further. Three patients developed ERCP-induced pancreatitis. All three patients had circulating alpha 2-macroglobulin levels below 243 mg/dl (p = 0.03). The ERCP-induced alterations in circulating pancreatic enzymes and their inhibitors are similar to changes seen in clinical pancreatitis. Low circulating alpha 2-macroglobulin levels may predispose to ERCP-induced pancreatitis. 
Stimulation of glucose transport in skeletal muscle by hypoxia. Hypoxia caused a progressive cytochalasin B-inhibitable increase in the rate of 3-O-methylglucose transport in rat epitrochlearis muscles to a level approximately six-fold above basal. Muscle ATP concentration was well maintained during hypoxia, and increased glucose transport activity was still present after 15 min of reoxygenation despite repletion of phosphocreatine. However, the increase in glucose transport activity completely reversed during a 180-min-long recovery in oxygenated medium. In perfused rat hindlimb muscles, hypoxia caused an increase in glucose transporters in the plasma membrane, suggesting that glucose transporter translocation plays a role in the stimulation of glucose transport by hypoxia. The maximal effects of hypoxia and insulin on glucose transport activity were additive, whereas the effects of exercise and hypoxia were not, providing evidence suggesting that hypoxia and exercise stimulate glucose transport by the same mechanism. Caffeine, at a concentration too low to cause muscle contraction or an increase in glucose transport by itself, markedly potentiated the effect of a submaximal hypoxic stimulus on sugar transport. Dantrolene significantly inhibited the hypoxia-induced increase in 3-O-methylglucose transport. These effects of caffeine and dantrolene suggest that Ca2+ plays a role in the stimulation of glucose transport by hypoxia. 
Tegmental dehiscence and brain herniation into the middle ear cleft. The tegmen tympani may occasionally be breached by herniation of the temporal lobe with or without dural cover. The clinical presentation may be obvious with CSF otorrhoea but less so with apparent middle ear effusion, CSF rhinnorrhoea, conductive hearing loss, recurrent meningitis or intracranial sepsis. Diagnosis requires suspicion of the condition, which may be aided by radiological imaging. Surgical repair is to be recommended: various techniques are available but bone enveloped by fascia placed by subtemporal approach is preferred. The features of this problem are highlighted by four cases. 
A case of chronic GM1 gangliosidosis presenting as dystonia: clinical and biochemical studies. Clinical and biochemical studies are reported on a 32-year-old man with GM1 gangliosidosis who presented with a slowly progressive dystonia that began when he was aged 7 years and eventually became almost totally incapacitating at the age of 35. There was only mild intellectual deterioration, but myoclonus, seizures and macular cherry-red spots were never observed. Proton-density and T2-weighted MRI scans showed symmetrical hyperintense lesions of both putamina. No increase of GM1 ganglioside was found in plasma or cerebrospinal fluid, and the metabolism of GM1 ganglioside in cultured skin fibroblasts from the patient was also almost normal, although the residual activity of GM1 ganglioside beta-galactosidase activity was only 10% of normal. These findings suggest that impaired GM1 ganglioside metabolism is not present systemically as it is in the infantile and juvenile types of the disorder, but is mainly confined to the central nervous system in chronic GM1 gangliosidosis. 
Intrathecal baclofen for intractable axial dystonia. Following spinal instrumentation for scoliosis, a patient developed intractable axial dystonia refractory to conservative medical management. We describe the successful treatment of this dystonia with a continuous infusion of intrathecal baclofen and the subsequent long-term management. 
The treatment of metastatic breast cancer. While metastatic breast cancer is not curable, it is treatable. Its treatment is associated with a relatively high rate of success, and patients are able to maintain a good quality of life for periods ranging from a few months to several years. This knowledge should encourage both the patient and the oncologist to maintain treatment as long as potentially effective therapeutic methods are available. Progress is ongoing both in the development of new forms of treatment and in new ways of using and combining already existing therapeutic modalities. There is still no established "best" or "only" first treatment of metastatic breast cancer. When secondary and later treatment is to be undertaken, the task of selecting the most appropriate treatment becomes even more complex. It is only through controlled clinical trials that useful therapeutic guidelines will develop. Treatment is a joint endeavor involving both the physician and the patient. Communication must remain open. In the final stages of the illness, treatment should be directed toward the relief of distressing symptoms and anxiety. 
Cryptococcal pleural effusion preceding cryptococcal meningitis in AIDS. The authors report a case in which a small cryptococcal pleural effusion preceded the development of severe cryptococcal meningitis in an HIV-positive patient. The appearance of an isolated transient pleural effusion is a very unusual presentation for AIDS-related complications. The authors suggest that cryptococcal infection be considered in this setting. 
Smoking-attributable mortality and years of potential life lost--United States, 1988. Smoking is a leading cause of diseases associated with premature mortality in the United States; in 1985, these diseases accounted for an estimated 390,000 premature deaths. In this report, mortality data and estimates of smoking prevalence for 1988 are used to calculate smoking-attributable mortality (SAM), years of potential life lost (YPLL), and age-adjusted SAM and YPLL rates for the United States. Calculations were performed using Smoking-Attributable Mortality, Morbidity, and Economic Cost (SAMMEC II) software, which includes relative risk estimates for 22 adult (i.e., greater than or equal to 35 years of age) smoking-related diseases and relative risk estimates for four perinatal (i.e., less than 1 year of age) conditions. Age-, sex-, and race-specific mortality data for 1988 were obtained from CDC's National Center for Health Statistics. Data on burn deaths caused by cigarettes were obtained from the Federal Emergency Management Agency. The estimated number of deaths among nonsmokers from lung cancer attributable to passive smoking was obtained from a report of the National Academy of Sciences. Age-, sex-, and race-specific current and former smoking prevalence rates in 1988 for adults aged greater than or equal to 35 years and for women aged 18-44 years were estimated by linear extrapolation using National Health Interview Survey data for 1974-1987. 
Questionable cancer practices in Tijuana and other Mexican border clinics. Tijuana, Mexico, has become a refuge for cancer patients who have been convinced that they may be cured of their terminal illness by unconventional, unproved, and disproved methods offered in the border clinics. About a dozen United States promoters have joined with Mexican colleagues to offer a variety of treatments. Some patients are diagnosed using standard methods prior to arrival at the clinics, but many healthy individuals are misdiagnosed as having cancer or "precancer" and are then treated there. Others are told they have been cured or are improving even though they still have active disease. The modalities and regimens used are often referred to as "metabolic therapy" and, for the most part, are either not based on sound scientific principles or have been shown in controlled clinical trials to be useless or even dangerous. A basic metabolic regimen consists of three phases: detoxification with fasting and bowel cleansing, strengthening the immune system with numerous "supplements," and attacking cancer with "natural and non-toxic" chemicals. Popular treatments include injections of hydrogen peroxide, large quantities of pressed liver and carrot juice, coffee enemas, infusions of Laetrile mixed with massive doses of vitamins and dimethylsulfoxide (DMSO), special diets, and a host of other pseudoscientific regimens. Unfortunately, no evidence exists that any of these modalities is more effective than no treatment at all. Patients traveling to the Mexican border clinics for metabolic therapy are subjecting themselves to costly and hazardous regimens, especially if they forgo responsible medical care in the process. The American Cancer Society, therefore, strongly urges individuals with cancer not to seek treatment with metabolic therapies in the Mexican border clinics. 
Ki-67 staining in histological subtypes of breast carcinoma and fine needle aspiration smears. Thirty four cases of invasive breast carcinoma were analysed for heterogeneity of Ki-67 reactivity in a tumour, and proliferative activity in various histological subtypes was compared. The growth factions determined in areas of central and peripheral tumour were the same. Mucinous and lobular carcinoma showed lower Ki-67 activity than ductal carcinomas. When ductal carcinomas were subdivided according to their dominant growth pattern, the carcinomas with a solid or comedo growth pattern showed the highest proliferative activity. These results largely confirm data from previous cell kinetic studies on the incorporation of radioactively labelled thymidine. A correlation between the growth fraction determined by Ki-67 in fine needle aspiration smears and cryostat sections of corresponding tumours was shown, implying that the immunostaining of cytological smears gives a reliable impression of the growth fraction of a tumour and may therefore be used in prospective studies. 
Transmetatarsal amputation: the role of adjunctive revascularization. Over a 12-year period, 160 transmetatarsal amputations were performed in patients with peripheral vascular occlusive disease. The following groups were defined: group 1 - nonreconstructable disease (n = 40); group 2 - transmetatarsal amputation in conjunction with distal revascularization (n = 99); group 3 - reconstructable disease but transmetatarsal amputation performed without simultaneous revascularization (n = 21). There were nine early deaths in the entire series, for an operative mortality rate of 5.6%. The lowest rate of transmetatarsal amputation healing (24%) occurred in group 1. An 86% healing rate was achieved in group 3, but in seven cases (33%) some type of revascularization was required within 3 months of the amputation. In group 2 the healing rate was 62% but reached 83% where the bypass remained patent for at least 3 months after the amputation. Long-term patency rates also affected healing. Healing was not influenced by the number of local procedures (single vs multiple). The presence of severe infection or extensive necrosis necessitated open transmetatarsal amputation in 89 cases; the remaining 71 amputations involved primary closure. Since many patients were treated at a time when diagnostic modalities as well as the operative indications and techniques differed somewhat from the current practice, much of the information regarding group I patients in particular should be considered as a negative historical control and any conclusion from our data should be adjusted accordingly. Healing after amputation at the transmetatarsal level can be expected in the majority of instances in which revascularization can be performed with predictable patency, even when the standard criteria for performing such amputations are liberalized. 
The relationship between esophageal motility disorders and microvascular angina. Patients with unexplained chest pain have caused investigators in cardiology, gastroenterology, and psychiatry to find abnormalities with overlap among the three specialties. This article reviews the data concerning the potential interrelation of chest pain of cardiac or esophageal origin. 
Deep brain stimulation: a review of basic research and clinical studies. Deep brain stimulation for pain control in humans was first used almost 30 years ago and has continued to receive considerable attention. Despite the large number of clinical reports describing pain relief, numerous studies have indicated that the results of these procedures vary considerably. In addition, many neurosurgeons find the procedures unpredictable, and considerable disagreement still exists regarding important issues related to the technique itself. This review gives an historical overview of the relevant basic and clinical literature and provides a critical examination of the clinical efficacy, choice of stimulation sites, parameters of stimulation, and effects on experimental pain. Finally, we give suggestions for future research that could more definitively determine the usefulness of deep brain stimulation for pain control. 
Establishment of cell-to-cell contact by adoptively transferred adherent lymphokine-activated killer cells with metastatic murine melanoma cells. A murine model of pulmonary B16 melanoma was used to study the infiltration into metastases of lymphokine-activated killer (LAK) cells and adherent lymphokine-activated killer (A-LAK) cells and, specifically, to study whether A-LAK cells are able to leave the tumor microcirculation and establish cell-to-cell contact with malignant cells. Fluorescence microscopy demonstrated that A-LAK cells accumulated in metastases twice as efficiently as LAK cells during interleukin-2 stimulation. Electron microscopy of pulmonary metastases 16 hours after administration of 2.5 x 10(7) A-LAK cells revealed A-LAK cells, identified by the presence of typical two-compartment granules, in direct contact with melanoma cells. This finding was confirmed by using A-LAK cells prelabeled with polycationized ferritin. In conclusion, our observations demonstrate unambiguously the ability of adoptively transferred A-LAK cells to establish contact with extravascular metastatic melanoma cells. 
A comparison of hypertensive and nonhypertensive coronary care patients' cardiovascular responses to visitors. Patients with and without hypertension in a coronary care unit (n = 24) were compared with respect to cardiovascular responses to both a family visit and an interview by an investigator. Variables for each of the four cardiovascular indicators (systolic blood pressure, diastolic blood pressure, heart rate, and premature ventricular contractions) included the value before, the highest value during, the lowest value during, and the value after each social interaction condition. The highest group means for systolic blood pressure and heart rate were significantly higher for patients with hypertension than for patients without hypertension under both the interview and visit conditions. Differences in cardiovascular responses were not significantly greater for family visits than for interviews for patients with hypertension compared with those without hypertension. Thus, although hypertensive patients had greater cardiovascular reactivity to both social interaction conditions than nonhypertensive patients in the coronary care unit, family visits were no more physiologically stressful than a comparative interaction condition. 
Surgical manipulation of primate cerebral arteries in established vasospasm. It is generally believed that surgery in the face of angiographic vasospasm is dangerous due to an increased incidence of postoperative cerebral ischemia. One theory is that arterial narrowing is exacerbated by surgical manipulation of vasospastic vessels during aneurysm dissection and clipping. This theory was tested in a primate model of cerebral vasospasm and the results reported. Six monkeys underwent baseline cerebral angiography, followed by induction of subarachnoid hemorrhage (SAH) on both sides of the circle of Willis. An equal amount of fresh autologous blood clot was placed around each internal carotid, anterior cerebral, and middle cerebral artery. Six days later, angiography was repeated and the right craniectomy was reopened for clot evacuation and surgical manipulation of the right cerebral arteries, including placement of a temporary aneurysm clip on the right middle cerebral artery. The left cerebral arteries were not exposed or manipulated, and served as controls. Twenty-four hours later angiography was repeated, then the animals were killed. Equal and significant vasospasm (greater than 40% reduction in vessel caliber compared to baseline, p less than 0.05) was seen in the middle cerebral arteries on both sides of the circle of Willis in all animals 6 and 7 days after SAH. There was no significant change in the severity of vasospasm on Day 7 compared with Day 6 in the right cerebral arteries. Increased risk of postoperative cerebral ischemia for surgery in the peak vasospasm period may be due to mechanisms other than increased arterial narrowing precipitated by surgical manipulation. 
Autopsy-verified pulmonary embolism in a surgical department: analysis of the period from 1951 to 1988. A retrospective analysis was undertaken of all surgical patients in Malmo, Sweden, during the period from 1951 to 1988 in whom pulmonary emboli were found at autopsy. The analysis included a comparison with the earlier analysed and reported time period from 1951 to 1980. A continued high frequency of pulmonary embolism at autopsy was seen during the 1980s (20.3 per cent of deaths, 31.7 per cent of autopsies). Of the 391 autopsy-verified pulmonary emboli found between 1981 and 1988, 113 (28.9 per cent) were considered fatal, 104 (26.6 per cent) contributed to death and 174 (44.5 per cent) were incidental. Few patients had symptomatic deep vein thrombosis or pulmonary embolism before death. The overall frequency of major pulmonary embolism in surgical patients remained unchanged (0.3 per cent). The frequency of major postoperative pulmonary embolism showed an increase during the 1950s and 1960s (maximum 0.4 per cent) but a decrease in the last 5-year period of the 1970s (0.3 per cent), which has earlier been reported upon. This decrease continued during the 1980s (0.2 per cent) (P less than 0.05). An increase was found in the number of patients operated on who had autopsy-proven pulmonary embolism and who received thromboprophylaxis. Pulmonary embolism continues to be a major cause of death in surgical patients; however, postoperative major pulmonary embolism has shown a reduction in the last 15-year period. 
Improvement by acetylcysteine of hemodynamics and oxygen transport in fulminant hepatic failure. BACKGROUND. When administered early after an overdose of acetaminophen, intravenous acetylcysteine prevents hepatic necrosis by replenishing reduced stores of glutathione. How acetylcysteine improves the survival of patients with established liver damage induced by acetaminophen, however, is unknown. This study was undertaken to determine whether the beneficial effect of acetylcysteine under such circumstances could be due to enhancement of oxygen delivery and consumption. METHODS. We studied the effect of acetylcysteine on systemic hemodynamics and oxygen transport in 12 patients with acetaminophen-induced fulminant hepatic failure and 8 patients with acute liver failure from other causes. The acetylcysteine was given in a dose of 150 mg per kilogram of body weight in 250 ml of 5 percent dextrose over a period of 15 minutes and then in a dose of 50 mg per kilogram in 500 ml of 5 percent dextrose over a period of 4 hours; measurements were made before treatment began and after 30 minutes of the regimen. RESULTS. In the patients with acetaminophen-induced liver failure, the infusion of acetylcysteine resulted in an increase in mean oxygen delivery from 856 to 975 ml per minute per square meter of body-surface area (P = 0.0036), due to an increase in the cardiac index from 5.6 to 6.7 liters per minute per square meter (P = 0.0021). Mean arterial pressure rose from 88 to 95 mm Hg (P = 0.0054) despite a decrease in systemic vascular resistance from 1296 to 1113 dyn.sec.cm-5 per square meter (P = 0.027). There was an increase in oxygen consumption from 127 to 184 ml per minute per square meter (P = 0.0007) associated with an increase in the oxygen-extraction ratio from 16 to 21 percent (P = 0.022). The effects in the patients with acute liver failure from other causes were similar. CONCLUSIONS. The increase in oxygen delivery and consumption in response to acetylcysteine may account for its beneficial effect on survival in patients with fulminant hepatic failure induced by acetaminophen. 
CNS pathology in the neurological mutant rats zitter, tremor and zitter-tremor double mutant (spontaneously epileptic rat, SER). Exaggeration of clinical and neuropathological phenotypes in SER. The pathological alterations in the central nervous system (CNS) were examined in three kinds of mutant rat; the zitter (zi/zi; Zi), the tremor rat (tm/tm; Tm) and the spontaneously epileptic rat (SER) which is a double mutant carrying both zitter and tremor genes. Two major alterations demonstrated in these mutants were hypomyelination and vacuolation or spongy degeneration. Hypomyelination was observed predominantly in SER and to a lesser extent in Zi, and was accompanied by a redundant or aberrant myelin sheath formation in addition to a decreased number of myelinated fibres. This appeared to be related to the occurrence of tremor. There was no abnormality in the structure of the myelin lamellae and oligodendrocytes or any destruction of myelin sheaths by phagocytic cells. The number of radial components in CNS myelin was increased almost equally in Zi, Tm and SER. Vacuolation was prominent in SER and Tm, especially in the brainstem and thalamus. Zi also developed mild vacuolation with advancing age. Vacuolation seemed to be related to the epileptic phenomena in SER and Tm. Vacuoles consisted mainly of swollen astrocytic processes and enlargement of the extracellular space, as well as occasional enlargement of periaxonal spaces. Thus both pathological findings--the hypomyelination derived from the zitter mutation with tremor, and the vacuolation from the tremor mutation with epileptic symptoms--were mutually exaggerated in SER. It is postulated that the two different genetic loci with zi and tm mutations interact and synergistically reinforce each other both clinically and pathologically in SER. 
Etiology of infection and morphologic changes in the lungs of Filipino children who die of pneumonia. Histopathologic studies and isolation of virus and bacteria in culture were carried out for 71 children less than 5 years of age with fatal pneumonia. A potential microbial etiology was identified for 61 children (86%): bacteria for 19 (27%), virus for 16 (23%), and virus plus bacteria for 26 (37%). Staphylococcus was the most prevalent pathogen, alone or in combination with other organisms, followed by Pseudomonas aeruginosa. Viral infection may predispose to bacterial infection in some children. A correlation of clinical course, results of cultures, and morphologic changes revealed cofactors that may have contributed to a fatal outcome. Lung abscess, pericarditis, myocarditis, endocarditis, and meningitis were associated with bacterial infection. Many patients in this study had severe bronchopneumonia, with a high prevalence of complications such as abscess (62%), atelectasis (40%), pericarditis (28%), and empyema (7%). Such complications added to multiple infections, measles, and malnutrition contributed to the fatal outcome in these children. 
Cortical dysplasia in temporal lobe epilepsy: magnetic resonance imaging correlations. Cortical dysplasia has been documented in histological specimens surgically removed for treatment of refractory temporal lobe epilepsy. We studied 10 patients with cortical dysplasia and complex partial seizures who underwent temporal lobectomy. Magnetic resonance imaging revealed abnormalities in 5 of the patients who had microscopically detectable major abnormalities. Magnetic resonance imaging revealed an abnormal cortical-white matter architectonic pattern in 2 patients with moderate cortical dysplasia. In the remaining 3 patients, magnetic resonance imaging findings were unremarkable. These observations suggest that magnetic resonance imaging is sensitive in the detection of certain dysplastic lesions in temporal lobe epilepsy. Preoperative identification of these abnormalities by magnetic resonance imaging may permit early and optimal surgical treatment in patients with refractory epilepsy. 
Femoro-femoral or ilio-femoral bypass for unilateral inflow reconstruction? Femoro-femoral and ilio-femoral bypass are two popular options for unilateral inflow reconstruction. In order to evaluate these alternative approaches, the records of 70 consecutive patients who underwent either femoro-femoral (n = 50) or ilio-femoral (n = 22) grafts were retrospectively reviewed. There were 46 men and 24 women, ranging in age from 27 to 84 years (mean: 66 years). Operative mortality was 10% for all femoro-femoral procedures, including 50% for emergent, 14% for synchronous, and 0% for solitary procedures; mortality was 9% for all ilio-femoral grafts including 20% for synchronous and 6% for solitary procedures. Among the elective solitary procedures, there was no significant difference with respect to operative time, blood loss, fluid requirement, time until resuming an oral diet, or duration of postoperative course for the two procedures. Five-year patency was 93% for all ilio-femoral and 57% for all femoro-femoral grafts. Although femoro-femoral bypass has been the more popular option for unilateral inflow reconstruction in this and other institutions, these findings justify the more widespread use of ilio-femoral bypass. 
Cloning and expression of the human vasoactive intestinal peptide receptor. Vasoactive intestinal peptide (VIP) is a neuroendocrine mediator found in the central and peripheral nervous system. Distinct subsets of neural, respiratory, gastrointestinal, and immune cells bear specific high-affinity receptors for VIP, which are associated with a guanine nucleotide-binding (G) protein capable of activating adenylate cyclase. A cDNA clone (GPRN1) encoding the human VIP receptor was identified in libraries prepared from the Nalm 6 line of leukemic pre-B lymphoblasts and the HT-29 line of colon carcinoma cells. The deduced 362-amino acid polypeptide sequence encoded by GPRN1 shares a seven-transmembrane-segment hydropathicity profile with other G protein-coupled receptors. Northern blot analyses identified a 2.7-kilobase transcript of the VIP receptor in Nalm 6 and HT-29 cells as well as in tissues from rat brain, colon, heart, lung, kidney, spleen, and small intestine. COS-6 cells transfected with GPRN1 bound 125I-labeled VIP specifically with a dissociation constant (Kd) of 2.5 nM. VIP--and less effectively secretin, peptide histidine isoleucine (PHI), and glucagon competitively displaced bound 125I-VIP from transfected COS-6 cells, with potencies in the order VIP greater than secretin = PHI much greater than glucagon. VIP stimulated adenylate cyclase activity in stably transfected Chinese hamster ovary K1 cells, inducing a 3-fold increase in the intracellular level of cAMP. When the antisense orientation of the VIP receptor clone was introduced into HT-29 cells, there was a 50% suppression of the specific binding of 125I-VIP and of the VIP-induced increase in cAMP level, relative to untransfected cells. The VIP receptor cloned exhibits less than or equal to 24% homology with other receptors in the same superfamily and thus represents a subset of G protein-coupled receptors for peptide ligands. 
Acinar cell carcinoma of the pancreas: a rare cause of left-sided portal hypertension. Isolated splenic vein obstruction with left-sided portal hypertension is a rare clinical condition. Owing to the close relationship of the splenic vein and the pancreas, this rare phenomenon is usually secondary to pancreatic inflammation or neoplasm. Acinar cell carcinoma has long been recognized as a distinctive, rare type of pancreatic carcinoma. A case of isolated splenic vein obstruction with left-sided portal hypertension secondary to acinar cell carcinoma of the pancreas, which we are reporting here, is thought to the first documented in the literature. 
Incidence of nonmelanoma skin cancer in New Hampshire and Vermont. A survey of skin cancer occurrence between June 1979 and May 1980 among residents of New Hampshire and Vermont identified 277 cases of squamous cell carcinoma and 1761 cases of basal cell carcinoma. The age-adjusted incidence rates for squamous cell carcinoma (32 per 100,000 in men, 8 per 100,000 in women) and for basal cell carcinoma (159 per 100,000 in men, 87 per 100,000 in women) were similar to those reported in other populations in the northern United States. Skin cancer incidence was particularly high among men more than 70 years of age and a large proportion (greater than 30%) of patients 55 years or older had a history of at least one previous skin cancer. 
Clinical and biologic features of childhood T-cell leukemia with the t(11;14). Cytogenetic analysis of cells from 622 consecutive patients with newly diagnosed acute lymphoblastic leukemia (ALL) and successful G-banding chromosome studies disclosed seven cases with the t(11;14)(p13;q11) and one with the t(11;14)(p15;q11). Leukemia cells in all eight cases had a T-cell immunophenotype. The t(11;14)(p13;q11) occurred in 6.8% and the t(11;14)(p15;q11) in 1% of T-cell ALL cases (n = 103). The t(11;14) was associated with presenting clinical features typical of T-cell ALL: male predominance (n = 6), age greater than 10 years (n = 3), hyperleukocytosis (white blood cells greater than 100 x 10(9)/L, n = 5), relatively high hemoglobin level (median, 10.8 g/dL), high serum lactic dehydrogenase level (median, 3248 U/L), presence of mediastinal mass (n = 6), and central nervous system leukemia (n = 2). While there were no significant differences in presenting features between T-cell ALL cases with or without the t(11;14), leukemic cells from patients with the translocations were more likely to coexpress CD4 and CD8 antigens (6 of 6 v 35 of 86 cases tested, P less than .05). Adverse events have occurred in six patients: three central nervous system relapses [including the one with t(11;14)(p15;q11)], two secondary acute myeloid leukemia, and one hematologic relapse. Our results indicate that the t(11;14)(p13;q11) occurs exclusively in T-cell malignancies of intermediate- or late-stage thymocyte differentiation. Additional studies are needed to determine the prognostic implications of these translocations. 
Impaired binding properties of thyroxine-binding globulin in hepatocellular carcinoma and chronic liver disease. To determine the factors underlying the apparent reduction in binding ability of thyroxine-binding globulin in hepatocellular carcinoma, hormone-binding characteristics were further examined in patients with this disease and in control subjects. No differences in affinity constants with respect to triodothyronine or serum thyroxine-binding globulin from hepatocellular carcinoma, cirrhotic and normal subjects were found. The affinity for thyroxine was significantly reduced in hepatocellular carcinoma (0.41 +/- 0.13 x 10(10) mol-1) and cirrhotic (0.65 +/- 0.1 x 10(10) mol-1) patients compared with normal subjects (0.94 +/- 0.7 x 10(10) mol-1). Investigations carried out on liver tissue obtained from patients with hepatocellular carcinoma and chronic liver disease showed that thyroxine-binding globulin within tumor tissue was elevated and bound less exogenous tracer hormone compared with that obtained from nontumor tissue. Tumor-derived thyroxine-binding globulin with altered binding properties is, at least partly, responsible for the abnormal behavior of the serum protein in patients with hepatocellular carcinoma. 
Parenchymal versus reticuloendothelial iron overload in the liver: distinction with MR imaging Parenchymal iron deposition occurs in hemochromatosis, while iron is deposited in reticuloendothelial (RE) cells after blood transfusions or rhabdomyolysis. Magnetic resonance images of patients with decreased liver signal intensity on T2-weighted images at 1.5 T were blindly compared in an effort to distinguish these conditions. In each of five patients with hemochromatosis, the pancreas had low signal intensity, but splenic signal intensity was decreased in only one. In contrast, only three of the 16 patients with RE iron overload had low pancreatic signal intensity, while all of these patients either had low splenic signal intensity (n = 14) or previously underwent splenectomy (n = 2). Distinction among these causes of iron deposition is clinically important because parenchymal iron overload from hemochromatosis may produce significant tissue damage, while the RE iron of transfusions and rhabdomyolysis is of little clinical consequence. 
Long-term follow-up of elderly patients with locoregional breast cancer treated with tamoxifen only. One hundred and thirteen women aged 70 years or more with locoregional breast cancer were treated with tamoxifen alone as primary treatment. They were followed for a minimum of 5 years. Complete response occurred in 38 women, partial response in 17, no change in 34 and progressive disease in 24. Where progressive disease occurred, or where patients relapsed after an initial response, the most suitable conventional therapy was given. The actuarial 5-year survival rate was 49.4 per cent for all patients and was much higher (92 per cent) in those showing an initial complete response. Seventy patients (61.9 per cent) were not controlled by tamoxifen alone to death or most recent follow-up. Tamoxifen provides an alternative treatment for operable breast cancer in older women in the short term and may be particularly suitable for those with concurrent disease or who are unwilling to undergo surgery. The low morbidity rate from tamoxifen must be balanced against the need to maintain close follow-up. In the medium to long term, sole primary treatment by tamoxifen delays more definitive therapy. 
Stability of ethnic differences in children's pressor responses during three annual examinations. In this study, 395 healthy children had blood pressure and heart rate measured both at rest and during a stressful video game. Identical measurement procedures were used for three annual examinations. Consistently, black children demonstrated significantly greater pressor responses than white children. In view of the greater prevalence of hypertension among black adults than white adults, these data suggest that blacks exhibit hemodynamic irregularities well before the onset or diagnosis of hypertension. 
Adrenoceptors on blood cells from patients with primary Raynaud's phenomenon. 1. alpha 2-Adrenoceptors on platelet membranes and beta 2-adrenoceptors on lymphocytes were studied in 24 patients with primary Raynaud's phenomenon and in 24 age- and sex-matched control subjects. In two subgroups, a standardized mental arithmetic test and a finger-cooling test were performed. 2. Baseline blood pressure, heart rate and forearm blood flow did not differ between the two groups. 3. Baseline skin microcirculation (laser Doppler flux) was decreased in primary Raynaud's phenomenon (19 +/- 15 arbitrary units) compared with control subjects (33 +/- 14 arbitrary units) (P less than 0.01). 4. Baseline plasma noradrenaline concentration (2.00 +/- 1.44 versus 1.16 +/- 0.36 nmol/l) and alpha 2-adrenoceptor density (301 +/- 119 versus 210 +/- 82 fmol/mg) were increased in patients with primary Raynaud's phenomenon in comparison with the control subjects. The alpha 2-adrenoceptor density/beta 2-adrenoceptor density ratio in patients with primary Raynaud's phenomenon was, with a value of 0.37 +/- 0.04, higher than in the control subjects, where a value of 0.25 +/- 0.02 was measured (P less than 0.001). Plasma adrenaline concentration, beta 2-adrenoceptor density and the antagonist affinity to both receptor subtypes did not differ between both groups under baseline conditions. 5. Whereas during the finger-cooling test no differences were seen in the responses of the parameters measured, the mental arithmetic test induced an increase in laser Doppler flux in patients with primary Raynaud's phenomenon and a decrease in the control group. 
Variation in management based on type of choledochal cyst. The management of 23 patients treated for choledochal cysts at the Oregon Health Sciences University between 1969 and 1990 is reviewed. The median age was 27 years, with a range from 1 month to 90 years. Seventy-eight percent of patients presented with abdominal pain, and 35% were jaundiced. Three patients presented with cholangitis, two with cyst rupture, and one with recurrent pancreatitis. Nine patients had had previous biliary surgery. The diagnosis was made in all patients with ultrasound and/or cholangiography. Fifteen patients (65%) had type I cysts, 2 had a type II cyst, 5 (22%) had type III cysts, and 1 had a type IV cyst. Stones were present in four (17%) cysts, and all excised cysts were benign. Seventeen patients with type I and II choledochal cysts had complete cyst excision and choledochoenterostomy. Four of five patients with type III cysts had endoscopic cyst incision and drainage, while the fifth patient had transduodenal cyst excision and sphincteroplasty. The patient with a type IV cyst had extrahepatic cyst excision and choledochojejunostomy. There were no operative deaths. Two postoperative complications occurred: cholangitis and a prolonged ileus. All patients had resolution of their pain and jaundice. Two patients had late cholangitis. Cyst excision and choledochojejunostomy are the treatment of choice for types I and II choledochal cysts. Extrahepatic cyst excision and choledochojejunostomy may be adequate treatment for type IV cysts. Endoscopic incision and drainage is appropriate for selected patients with type III cysts. 
Characterization of infectious crystalline keratitis caused by a human isolate of Streptococcus mitis. Streptococcus mitis isolated from a human with infectious crystalline keratitis was injected intrastromally into corneas of adult New Zealand white rabbits that were treated with tetracycline hydrochloride, methylprednisolone acetate, or a combination of tetracycline and methylprednisolone. Animals were followed up for up to 44 days; untreated corneas and those treated with tetracycline developed no disease or "fluffy" stromal infiltrates with overlying epithelial defects representing an abscess. Corneas treated with the combination of tetracycline and corticosteroid usually developed crystalline stromal opacities that on histopathologic examination were shown to be intrastromal aggregates of cocci. Transmission electron microscopy of crystalline lesions within 10 days of infection revealed typical cocci intermixed with a fibrillar material having periodicity characteristic of fibrinogen or fibrin, and immunoperoxidase staining for fibrinogen was positive. By 1 month, electron microscopy revealed aggregates of degenerated bacteria that were surrounded by cellular processes of activated keratocytes. Our studies demonstrate a model for crystalline keratitis in which organisms are seen to reside within the stroma for up to 44 days without an inflammatory response. Periocular corticosteroids appear to be necessary to create this model. It is possible that the organisms are isolated from the host response by fibrin or by keratocytes. 
Application of intraoperative transesophageal echocardiography in infants and small children. Intraoperative echocardiography is gaining increasing acceptance in the assessment of the surgical repair of congenital heart defects. Because of its ideal imaging location, intraoperative transesophageal echocardiography (TEE) has been especially helpful in evaluating pulmonary venous return and the integrity of the left atrioventricular valve following mitral valvuloplasty, complete atrioventricular valve repair and correction of complex congenital heart disease. It has not been routinely used in infants and small children because of a prohibitively large probe size. We report the successful use of a recently developed "pediatric" TEE probe capable of Doppler and color flow imaging in two patients less than 7 years of age. No complications were encountered. Recommendations regarding optimal probe imaging positions in infants are provided. 
Current treatment of patients surviving out-of-hospital cardiac arrest. Most out-of-hospital cardiac arrests result from the sudden onset of a sustained ventricular arrhythmia in the absence of a new myocardial infarction. Individuals who survive cardiac arrest are at high risk for recurrent arrhythmias and sudden unexpected death. To prevent recurrent cardiac arrest, effective treatment must be provided during hospitalization after the initial episode. Caring for the survivor of cardiac arrest requires a detailed clinical investigation to define the underlying cardiac anatomy and left ventricular function and to elucidate the mechanism and characteristics of the patient's arrhythmia. Appropriate antiarrhythmic therapy, such as drugs or a nonpharmacological intervention (eg, implantable cardioverter-defibrillator), is then selected based on these considerations. In addition, ischemia is treated aggressively with beta-adrenergic blocking agents and, when appropriate, with surgical coronary artery revascularization. 
Tissue polypeptide antigen activity in cerebrospinal fluid: a marker of central nervous system metastases of breast cancer. Tissue polypeptide antigen (TPpA) in the cerebrospinal fluid (CSF) was measured in 59 consecutive breast cancer patients with suspected central nervous system (CNS) metastases. Subsequently, we determined that 13 patients had parenchymal brain metastases, 10 had leptomeningeal carcinomatosis, and 36 had no CNS involvement. The concentration of TPpA, which is a nonspecific marker for cell proliferation, was significantly higher in patients with CNS metastases than in those without it (P less than .0001; Mann-Whitney test). A tentative cutoff value for CNS metastases was set at 95 U/L TPpA; the upper limit of values indicating absence of CNS metastases was 89 U/L. Given these cutoff points, the sensitivity of TPpA as a marker for CNS metastases was 74% and the specificity was 100%; the predictive values of positive and negative tests were 100% and 86%, respectively. In 16 patients with CNS metastases, no correlation was found between TPpA activity in corresponding CSF and blood samples (correlation coefficient, Spearman's rho = .4; P greater than .1). In three patients treated for leptomeningeal carcinomatosis, the measurements of CSF TPpA showed correlation between the presence of tumor cells in the CSF and neurological clinical function. TPpA concentrations decreased in parallel with the clinical response and increased prior to CNS disease progression. As a marker for CNS metastases, the level of TPpA in the CSF in breast cancer patients appears to be superior to the level of protein, lactate dehydrogenase, or glucose, which showed very low sensitivity (41%, 47%, and 8%, respectively). For quantitative evaluation of treatment for leptomeningeal carcinomatosis, the TPpA level appears to be valuable and superior to CSF cytology, because tumor cells are not always present in CSF samples from patients with this condition. 
Roles of thrombin and platelet membrane glycoprotein IIb/IIIa in platelet-subendothelial deposition after angioplasty in an ex vivo whole artery model. BACKGROUND. Platelet deposition at the site of injury caused by balloon angioplasty is associated with acute closure and restenosis. METHODS AND RESULTS. In a new ex vivo whole artery angioplasty model, we examined the roles of thrombin inhibition with D-Phe-Pro-ArgCH2Cl (PPACK) and inhibition of the platelet membrane fibrinogen receptor glycoprotein IIb/IIIa (GPIIb/IIIa) with monoclonal antibody 7E3 on platelet deposition at the site of balloon injury. Fresh rabbit aortas were mounted in a perfusion chamber. One half of the mounted arterial segment was dilated with a standard angioplasty balloon catheter and the uninjured half served as the control segment. The vessels were perfused with human blood at physiological pressure and shear rates of 180-250 second-1 for 30 minutes. Platelet deposition was measured using 111In-labeled platelets and scanning electron microscopy. With heparin (2 units/ml) anticoagulation, 8.2 +/- 2.2 x 10(6) platelets/cm2 were deposited at the site of balloon injury compared with 0.7 +/- 0.2 x 10(6) platelets/cm2 on uninjured segments (p less than 0.02, n = 7). PPACK was tested at a concentration (10 microM) that totally inhibited platelet aggregation in response to thrombin. 7E3 was tested at a concentration (10 micrograms/ml) that totally inhibited platelet aggregation. Platelet deposition at the site of balloon injury was reduced 47% by PPACK and 70% by 7E3 compared with heparin. CONCLUSIONS. At shear rates seen in nonstenotic coronary arteries, PPACK and 7E3 are more effective than heparin in reducing platelet deposition at the site of balloon injury. The significant inhibition of platelet deposition by PPACK demonstrates the importance of heparin-resistant thrombin in platelet thrombus formation. The 7E3 results suggest that approximately 70% of platelet deposition at the site of balloon injury is GPIIb/IIIa dependent and that the remaining 30% results from non-GPIIb/IIIa-mediated platelet-subendothelial adhesion. Finally, the ex vivo whole artery system is a useful model for studying platelet-vessel wall interactions under physiologically defined parameters. 
Mycotic (Aspergillus) arteritis resulting in fatal subarachnoid hemorrhage: a case report. A seventy-one year-old Japanese man suffering from carcinoma of the common bile duct died from subarachnoid hemorrhage secondary in intracranial mycotic arteritis (MA). Repeated cultures of the discharge from the draining tubes, the tip of intravenous hyperalimentation catheters, blood, sputum, and urine failed to grow any fungus. Autopsy disclosed MA due to Aspergillus at the terminal portion of the right internal carotid artery close to the posterior communicating artery. 
Inhibitory effect of interleukin-4 on the in vitro growth of Ph1-positive acute lymphoblastic leukemia cells. We investigated the effect of recombinant human interleukin-4 (rhIL-4) on the in vitro growth of human leukemia cells in liquid culture and 3H-thymidine incorporation and found inhibitory effects on the growth of leukemic cells from patients with Ph1-positive acute lymphoblastic leukemia (Ph1 ALL) and three Ph1 ALL cell lines. However, no inhibitory effects were seen in Ph1-positive leukemic cell lines derived from patients with chronic myelogenous leukemia in blast crisis and various types of Ph1-negative leukemia cells, including B-lineage leukemia cells. In a flow cytometry assay of IL-4 receptor (IL-4R), all three Ph1-positive ALL cell lines showed the presence of IL-4R on their cell surfaces, and the IL-4-dependent inhibition on the growth of Ph1-positive ALL cells was abrogated by the addition of either monoclonal or polyclonal antibodies against rhIL-4. Other cytokines, including IL-2, IL-3, granulocyte-macrophage colony-stimulating factor (CSF), granulocyte-CSF, and IL-6, showed no inhibitory effects on the growth of Ph1-ALL cells, but tumor necrosis factor-alpha (TNF-alpha) and interferon (IFN)-alpha, -beta, and -gamma displayed slight inhibitory effects in a high concentration. The growth inhibition induced by rhIL-4 in the Ph1-positive ALL cells was not abrogated by the addition of antibodies against either IFN-gamma or TNF-alpha. Furthermore, these cells showed no significant production of IFN-alpha, -beta, or -gamma or TNF-alpha after exposure to rhIL-4, thus indicating that the growth inhibition of Ph1-positive ALL cells by rhIL-4 is not associated with IL-4-stimulating production of these factors. rhIL-4 caused significant inhibition of the tyrosine kinase activity in these Ph1-positive ALL cells, similar to Herbimycin A, an inhibitor of tyrosine kinase that inhibited the tyrosine kinase activity in these cells. Our finding suggests that the clinical evaluation of rhIL-4 may offer promising therapeutic possibilities for patients with Ph1-positive ALL. 
Aztreonam vs. cefotaxime in the treatment of gram-negative spontaneous peritonitis in cirrhotic patients. Aztreonam and cefotaxime were compared in 44 cirrhotic patients who had 52 episodes of gram-negative spontaneous peritonitis. Patients were randomized into two therapeutic groups of similar characteristics. Group A (28 episodes) received 0.5 gm of aztreonam every 8 hr, and group B (24 episodes) received 1 gm of cefotaxime every 6 hr, for a planned 14-day period. Peak and trough serum and ascitic fluid levels of both antibiotics were several times higher than the minimum inhibitory concentrations of causative microorganisms. Eleven patients (21%) died within the first 48 hr after beginning therapy, which included seven in the aztreonam group and four in the cefotaxime group. In the remaining patients, signs and symptoms of infection were promptly controlled, and ascitic fluid cultures became negative after 48 hr in all cases, except in one patient from the aztreonam group, who was a clinical failure. Two patients from the aztreonam group and one from the cefotaxime group relapsed after treatment. The overall mortality rate was 50%, which was lower than classically reported: 12 patients (43%) died in the aztreonam group, and 14 (58%) died in the cefotaxime group (p = 0.265, NS). Hepatorenal syndrome and digestive tract hemorrhage were the most frequent causes of death occurring after the first 48 hr of treatment. Streptococcal superinfections developed in three patients (14.2%) in the aztreonam group. We conclude that both antibiotics at the low doses used in this study are similarly well tolerated and effective in controlling this infection. Because the use of aztreonam as the initial empirical treatment requires a concomitant antibiotic against gram-positive infections and the possibility of streptococcal superinfections, cefotaxime seems to be a more advantageous therapeutic alternative for this patient population. 
Effects of posture, Valsalva maneuver and respiration on atrial flutter rate: an effect mediated through cardiac volume. The effects of passive upright tilting from 0 degrees to +60 degrees (n = 27), Valsalva maneuver (n = 16) and respiration (n = 10) on the rate of atrial flutter were studied in 27 patients. After tilting to +60 degrees, the atrial flutter cycle length shortened in all patients from 247.5 +/- 7 to 236.7 +/- 6.9 ms (range of shortening 1 to 21 ms, p less than 0.001). The Valsalva maneuver (strain of 40 mm Hg) shortened the flutter cycle length during the strain (phase 2) from 242.2 +/- 4.6 to 230.5 +/- 5 ms (range of shortening 2 to 19 ms, p less than 0.001). In 10 patients whose respiration was monitored, the flutter cycle length consistently prolonged during inspiration and shortened during expiration. Combined beta-adrenergic and muscarinic receptor blockade in six patients did not significantly alter the flutter cycle length at rest or the effects of the various maneuvers on the changes in flutter cycle length. This study revealed that the atrial flutter cycle length can be shortened by passive upright tilting, the strain phase of the Valsalva maneuver and expiration. Changes in flutter cycle length were independent of autonomic tone, implying that by decreasing cardiac volume, these maneuvers affect characteristics of the atrial flutter circuit, thereby producing dynamic changes in the rate of atrial flutter. 
Two cases of neoplastic angioendotheliomatosis presenting with myelopathy. We describe two patients with autopsy-proven neoplastic angioendotheliomatosis (NAE) presenting only as a transverse myelopathy for 10 to 12 months, followed by disseminated intracranial manifestations. Postmortem examination disclosed a vasculocentric distribution of neoplastic cells in various organs that stained positively with B-lymphocyte-specific monoclonal antibody. These cases were unusual because they manifested as an isolated myelopathy for many months. 
DNA ploidy and cell kinetic measurements as predictors of recurrence and survival in stages B2 and C colorectal adenocarcinoma. DNA content and cell proliferation were measured by flow cytometry on paraffin-embedded Stage B2 or C colorectal adenocarcinomas from 694 patients enrolled in adjuvant trials conducted by the North Central Cancer Treatment Group. Patients with diploid tumors had a higher survival rate than those with nondiploid tumors (P less than 0.001). The proliferation index (the sum of the percent of cells in S-phase plus those in G2M phase) was also a strong prognostic factor (P less than 0.001). The ploidy and proliferation data were combined, and the patients in the favorable group (diploid and low proliferative index) had a 5-year survival of 74% compared with 54% for the unfavorable group (high proliferative index or nondiploid, P less than 0.001). This grouping was prognostic for survival in B2 (P less than 0.001), C (P = 0.013), colon (P less than 0.001), and rectal (P = 0.026) patient subsets. This study indicates that cell kinetic parameters are important and independent prognostic factors for Stages B2 and C colorectal cancer. 
Poststenotic dilatation. Partial narrowing of arteries produces poststenotic dilatation. This appears as a dilation of the vessel wall 1 to 3 centimeters distal to the area of a partial stenosis. When a stenotic band is placed in dogs, poststenotic dilatation develops rapidly, often within eight to ten days. Moderate stenoses that produce a bruit and thrill are effective in eliciting poststenotic dilatation, whereas very tight and very mild stenoses usually are ineffective. Thus, development of poststenotic dilatation requires the presence of flow disturbances sufficient to produce an audible bruit and a palpable thrill. Although the exact flow disturbance is uncertain, statis, increased lateral pressure, cavitation, abnormal shear stresses and turbulence all have been postulated to be the cause of poststenotic dilatation. Of these, experimental studies support abnormal shear stresses and turbulence as the most likely causes. Whatever the flow disturbance, it must make the wall vibrate to produce poststenotic dilatation. Vibrations are thought to produce alterations in wall elastin and possibly in vascular smooth muscle tone. This leads to dilatation of the vessel. If the dilatation is slight, removal of the stenosis may cause reversal of poststenotic dilatation with recovery beginning within hours of correction of the stenosis. If the dilated area is enlarged to twice normal diameter, it may exhibit permanent aneurysmal changes and, therefore, requires resections with reanastomosis. Arteries that are dilated to as little as one-third more than normal size may contain areas of ulceration with overlying thrombus. These vessels also may require resection with reanastomosis. 
The effects of shoes on the torsion and rearfoot motion in running. Excessive pronation is accepted as a good indicator for various running injuries. The least amount of pronation takes place when running barefoot. The latest investigations show that this is connected to a large torsional movement between forefoot and rearfoot which can be influenced by the shoe sole construction. The shoes which are in use among runners in track and field are basically of two types, running shoes (in general torsionally stiff) and spikes (torsionally flexible). The possibly varying effect of these shoes on the shoe/foot motion in running is not known. The purpose of this investigation was therefore to show whether the pronation angle and the torsion angle differ when running barefoot, with spikes, and with running shoes (forefoot touchdown, N = 9 left and right). A film analysis provided the angular movements of the lower leg, rearfoot, and forefoot as well as pronation and torsion in the frontal plane. The results show that at touchdown the torsional movements with both shoe types are quite different from those of running barefoot. With shoes, the torsion angle is reduced back to zero--with running shoes more than with spikes--and the pronation angle is increased beyond the barefoot values (P less than 0.01). In order to reduce the risk of injury, both shoe types should be improved--the running shoes with respect to torsion and the spikes with respect to pronation. 
Immunohistochemical studies of blood group-related antigens in human superficial esophageal carcinomas. A total of 63 surgically resected esophageal carcinomas (including 49 superficial esophageal carcinomas) and histologically normal tissue adjacent to the superficial carcinoma (nontumorous epithelium) were examined immunohistochemically for the blood group antigens (BGA) A, B, H, Lewisa, Lewisb, Lewisx, and Lewisy. Deletion of an expected A, B or H antigen occurred in 12 (24.5%) of the 49 superficial carcinomas and three (21.4%) of the 14 advanced carcinomas. Incompatible expression of an unexpected A or B antigens occurred in only one case (1.6%) in the carcinoma. In the clinicopathologic study, there was a significant correlation between immunoreactivity of Lewisa and depth of cancer invasion (chi-square test, P less than 0.05). In the superficial carcinoma, there were significant correlations between immunoreactivity of Lewisx and lymph node status (chi-square test, P less than 0.05), immunoreactivity of Lewisy and prognosis (Z test, P less than 0.05), and incompatible expression of Lewisb for tumor against nontumorous epithelium and histologic variation (chi-square test, P less than 0.01). The functional significance of alternations in BGA expression that may be associated with oncogenesis is not clear. However, immunohistochemical determination of BGA may be a more advantageous marker to predict the patient's clinical course in superficial esophageal carcinoma. 
Extraadrenal retroperitoneal paraganglioma: clinical, pathologic, and CT findings. Paragangliomas of the retroperitoneum arise from specialized neural crest cells distributed along the aorta in association with the sympathetic chain. In order to ascertain characteristic CT features of extraadrenal retroperitoneal paragangliomas to differentiate them from other retroperitoneal tumors, 31 discrete tumors and two cases of paragangliomatosis in 28 patients were reviewed retrospectively, and the CT features were correlated with clinical and pathologic findings. There were 16 men and 12 women. Average age was 37 years (range, 11-70 years). Twenty-four patients (86%) had hypertension. Of these, catecholamine levels were elevated in all 18 patients who had biochemical studies. Four patients (14%) had malignant paragangliomas. The discrete tumors were classified by location as suprarenal (26%), renal hilar (32%), or infrarenal (42%). Suprarenal paragangliomas could not be distinguished from the ipsilateral adrenal gland on CT. The average size of functional tumors was smaller (7.0 cm) than that of nonfunctional tumors (12.0 cm), but the sizes of the two groups overlapped. Smaller tumors were more likely to be homogeneous and have well-defined margins than were larger tumors. Our findings indicate that extraadrenal retroperitoneal paragangliomas are functionally active more often than previously reported and that they are readily detected by CT as soft-tissue masses closely associated with the entire length of the abdominal aorta. However, no CT feature was found that was unique for paraganglioma. 
Upbeat and downbeat nystagmus occurring successively in a patient with posterior medullary haemorrhage. In a patient with posterior medullary haemorrhage, first upbeat and later downbeat nystagmus occurred in the primary position. The lesion was limited to the posterior and medial part of the medulla. Clinical and electro-oculographic examination first showed upbeat nystagmus in the primary position and upgaze, with downbeat nystagmus in downgaze. Two and a half months later, there was downbeat nystagmus in the primary position and downgaze and upbeat nystagmus in upgaze. 
Magnetic resonance imaging of choroidal melanoma with and without gadolinium contrast enhancement. Choroidal melanoma is the most common intraocular tumor and is uniquely suited for evaluation by magnetic resonance imaging (MRI) because of the paramagnetic effect of the melanin molecule. The authors performed T1-, T2-, and proton-density-weighted MRI on 34 patients with choroidal melanoma. Nineteen patients received gadolinium contrast, T1-weighted images were superior in both detecting and delineating tumors, showing increased contrast-to-noise ratios over other images. Gadolinium contrast further increased this ratio. These images are presented as evidence that gadolinium-enhanced MRI is valuable in the evaluation of choroidal melanoma. 
Comparison of standard external CPR, open-chest CPR, and cardiopulmonary bypass in a canine myocardial infarct model. STUDY OBJECTIVES: After cardiac arrest, open-chest CPR (OCCPR) and cardiopulmonary bypass (CPB) have demonstrated higher resuscitation rates when compared individually with standard external CPR (SECPR). We compared all three techniques in a canine myocardial infarct ventricular fibrillation model. TYPE OF PARTICIPANTS: Twenty-six mongrel dogs were block-randomized to receive SECPR and advanced life support (nine), CPB (nine), or OCCPR (eight). DESIGN AND INTERVENTIONS: All dogs received left anterior descending coronary artery occlusion followed by four minutes of ventricular fibrillation without CPR and eight minutes of Thumper CPR. At 12 minutes, dogs received one of three resuscitation techniques. After resuscitation, all animals received four hours of intensive care. Animals that were resuscitated had histochemical determination of ischemic and necrotic myocardial areas. MEASUREMENTS: Intravascular pressures were measured and coronary perfusion pressure was calculated during baseline, cardiac arrest, resuscitation, and postresuscitation periods. Percent necrotic myocardium, percent ischemic myocardium, and necrotic-to-ischemic ratios were determined for resuscitated animals. Epinephrine dosage and number of countershocks were determined for each group. MAIN RESULTS: Nine of nine CPB and six of nine OCCPR, compared with two of eight SECPR animals, were resuscitated (P less than .01). Three of nine CPB and OCCPR and two of eight SECPR dogs survived to four hours (P = NS). Coronary perfusion pressure two minutes after institution of technique was significantly higher with CPB (75 +/- 37 mm Hg) and OCCPR (56 +/- 31 mm Hg) than in SECPR animals (16 +/- 16 mm Hg, P less than .04). Epinephrine required for resuscitation was significantly less with CPB (0.10 +/- 0.02 mg/kg) than for SECPR (0.28 +/- 0.11 mg/kg, P less than .002). The ratio of necrotic to ischemic myocardium at four hours was significantly lower with CPB (0.15 +/- 0.31) and OCCPR (0.39 +/- 0.25) than for SECPR (1.16 +/- 0.31, P less than .02). CONCLUSION: OCCPR and CPB produce higher coronary perfusion pressures and improved resuscitation rates from ventricular fibrillation when compared with SECPR in this canine myocardial infarct cardiac arrest model. CPB and OCCPR yielded similar resuscitation results, although less epinephrine was required with CPB. 
Indices of reperfusion in patients with acute myocardial infarction using characteristics of the CK-MB time-activity curve. The purpose of this study was to identify indices of coronary artery reperfusion in patients treated with thrombolytic therapy for acute myocardial infarction (AMI) by means of characteristics from the serum creatine kinase (CK) isoenzyme MB time-activity curve. Frequent blood sampling as performed in three groups with a first AMI: 29 patients treated with intravenous thrombolytic therapy who had a patent infarct-related artery with normal flow (TIMI-3) at acute catheterization (reperfusion group); four patients with a persistently closed infarct-related artery (no reperfusion group); and 44 patients who did not receive any therapy aimed at coronary reperfusion (no thrombolytic therapy group). In the latter group we prospectively estimated that 25% would have spontaneous reperfusion. A physiologically based computer-calculated multi-compartment method was used to determine the characteristics of the serum CK-MB time-activity curve. In addition to demonstrating an earlier increase, a shorter time to peak of serum CK-MB and a lower estimated infarct size in the reperfusion group (p = 0.025 to 0.00001), the appearance rate constant (k1) and time from estimated initial increase to peak of CK-MB in the blood stream (tRP) were significantly different from those values in the no thrombolytic therapy group (p less than 00001). A cutoff level indicating reperfusion if k1 was greater than 0.185 or tRP was less than 16.5 hours demonstrated overlapping values between these two groups in only four patients (k1), two patients (tRP), and six patients with a combination. 
Ruptured interstitial pregnancy presenting as an intrauterine pregnancy by ultrasound. Interstitial pregnancy is an uncommon subset of ectopic pregnancy in which the conceptum implants in the intrauterine portion of the fallopian tube. These pregnancies tend to progress further before rupture than do other tubal pregnancies and subsequently have greater propensity for massive intra-abdominal bleeding and maternal demise. Abdominal ultrasound can be deceptive in evaluating interstitial ectopic pregnancies. Transvaginal ultrasonography is more sensitive in the diagnosis of early ectopic pregnancy. Knowledge of the application and limitations of both transabdominal and transvaginal ultrasound will assist the emergency physician in the timely evaluation of this potentially lethal condition. 
Carcinoma of the prostate: value of transrectal sonography in detecting extension into the neurovascular bundle. Detection of involvement of the neurovascular bundles (NVB) by tumor is important in deciding whether sexual function can be preserved in patients undergoing radical prostatectomy for prostatic cancer. The nerve branches innervating the corpora cavernosa have a rather constant association with the capsular arteries and veins of the prostate, forming the periprostatic neurovascular bundle, which can be identified intraoperatively and spared during radical surgery, thus preserving potency. We examined 160 patients with biopsy-proved clinical stage A or B adenocarcinoma with transrectal sonography before radical prostatectomy to determine how useful the procedure is for predicting tumor extension into the NVB. Correlation with pathologic serial sections was obtained in each patient. The sonograms depicted the NVB on both sides in 77 patients (50%), on the right side only in 13 (8%), and on the left side only in 36 patients (23%). In 29 patients (19%) neither neurovascular bundle could be identified on the sonograms. Ninety-one tumors in this series showed evidence of extraglandular spread pathologically, which was posterolateral or into the NVB in 70 tumors involving 82 hemispheres. Using transrectal sonography, we correctly identified invasion of the NVB in 54 cases and missed it in 28 cases. NVB invasion was predicted incorrectly with transrectal sonography in 51 cases; absence of involvement of the NVB was correctly predicted in 177 hemispheres. The sensitivity of sonography for predicting invasion of the NVB was 66%, with a specificity of 78% and an accuracy of 75%. Positive predictive values and negative predictive values were 51% and 86%, respectively. We conclude that transrectal sonography currently suffers from lack of sufficient spatial resolution to detect accurately invasion of the NVB. 
C4b-binding protein exacerbates the host response to Escherichia coli. Activated protein C is a plasma anticoagulant. For activated protein C to function as an anticoagulant, it must form a complex with protein S. Protein S anticoagulant activity is neutralized by formation of a reversible complex with C4b binding protein (C4bBP). C4bBP is an acute-phase plasma protein. When C4bBP levels increase, mass action forces the level of free protein S to decrease, giving rise to an acquired functional protein S deficiency. It has been proposed that these elevated C4bBP levels and the resultant acquired deficiency of protein S that occurs in inflammation could contribute to a hypercoagulable state. An experimental model to test this hypothesis was suggested by our previous studies that demonstrated that inhibition of protein C activation rendered baboons hypercoagulable in response to sublethal Escherichia coli infusion (J Clin Invest 79:918, 1987). We have extended these studies to examine the effect of inhibition of protein S activity with C4bBP in the host (baboon) response to infusion of sublethal concentrations of E coli organisms. Five sets of animals were studied: (1) those challenged with sublethal concentrations of E coli alone (0.4 x 10(10)/kg); (2) those supplemented only with C4bBP (20 mg/kg); (3) those challenged with the same level of E coli but supplemented with C4bBP (20 mg/kg); (4) those challenged with sublethal E coli and supplemented with C4bBP (20 mg/kg) and sufficient protein S (2.3 mg/kg) to fill the protein S binding sites on C4bBP; and (5) those challenged with lethal concentrations of E coli. Sublethal E coli infusion (group 1 animals) caused only an acute-phase response with no consumption of fibrinogen, detectable organ damage, or detectable tumor necrosis factor (TNF) in the plasma. C4bBP infusion (group 2 animals) resulted in no significant physiologic changes, no detectable plasma TNF, and little change in fibrinogen level. The group 3 animals, receiving both sublethal E coli and C4bBP, exhibited rapid consumption of fibrinogen, systemic organ damage, and detectable circulating TNF ultimately leading to death. The overall response of this group was very similar to the response of the group 5 animals receiving an LD100 dose of E coli. The group 4 animals, which were treated exactly as above except that C4bBP was supplemented with a slight excess of protein S, responded essentially like those that received sublethal E coli alone. These studies suggest that the elevation of C4bBP during an inflammatory response can contribute to fibrinogen consumption and vascular damage. This vascular damage may be associated with enhanced elaboration of cytokines like TNF.(ABSTRACT TRUNCATED AT 400 WORDS). 
Functional recovery after traumatic transtentorial herniation. To elucidate the factors associated with functional recovery after traumatic transtentorial herniation, we reviewed the records of 153 consecutive patients admitted with clinical signs of transtentorial herniation (altered level of consciousness, anisocoria or pupillary unresponsiveness, and abnormal motor findings). Overall, 28 patients (18%) had a functional outcome: 14 patients (9%) made a good recovery and 14 were moderately disabled. Sixteen patients (10.5%) were severely disabled or vegetative, and 104 (60%) died. Compared with patients who died or were left severely disabled or vegetative, patients who had a good recovery were younger (21 versus 38 years), were significantly more likely to be children (less than or equal to 17 years old) and have anisocoria and a deteriorating Glasgow Coma Score (GCS), and were significantly less likely to be flaccid or have bilaterally fixed pupils; moderately disabled patients also had a lower median age and a higher frequency of anisocoria. There was no difference in the incidence of significant intracranial hematomas between patients with a functional outcome and those with a nonfunctional outcome. Twenty-seven percent of the 95 patients with anisocoria had a good outcome or moderate disability, whereas only 3.5% of the 58 patients with bilaterally fixed and dilated pupils at admission had a functional recovery (P less than 0.05). Age, level of consciousness, and the degree of residual upper brain stem function at admission appear to be the most important determinants of functional outcome after traumatic transtentorial herniation. 
Idiopathic and L-tryptophan-associated eosinophilic fasciitis before and after L-tryptophan contamination. Recently, a causative association has been made between the ingestion of levotryptophan (L-tryptophan) and the eosinophilia-myalgia syndrome (EMS), a new entity manifested by peripheral blood eosinophilia, myalgias, constitutional symptoms, and cutaneous edema with fibrosis. Contaminated levotryptophan preparations produced at a single manufacturing company between October 1988 and June 1989 have been implicated in all EMS cases. In this study, we analyzed retrospectively 49 patients with cutaneous fibrosis for a history of levotryptophan use. Levotryptophan ingestion prior to the onset of their disease was reported by 11 (65%) of 17 patients with eosinophilic fascilitis (EF), two (20%) of 10 patients with localized scleroderma, and none of 22 patients with systemic sclerosis. The onset of levotryptophan-associated cutaneous disease preceded the availability of contaminated levotryptophan preparations in seven (54%) of 13 patients. One patient with levotryptophan-associated generalized morphea also had lichen sclerosus et atrophicus and acanthosis nigricans, findings not previously reported in patients with EMS. In addition, we compared the clinical and laboratory features of levotryptophan-associated EF and idiopathic EF. Myalgias, muscle weakness, paresthesias, morpheaform plaques, cutaneous ulcers, and livedo reticularis were more common in patients with levotryptophan-associated EF. We conclude that levotryptophan-associated EF and localized scleroderma were present before the presumed date of contaminated levotryptophan availability. The clinical spectrum of cutaneous fibrosis associated with the ingestion of levotryptophan includes generalized morphea and EF, which are similar though not identical to their idiopathic counterparts. 
Prevalence and malignant potential of colorectal polyps in asymptomatic, average-risk men. Screening colonoscopy was performed on 119 asymptomatic elderly men with no other risk factors for colonic neoplasms. Ninety adenomas were detected in 49 (41%) subjects. Mean adenoma size was 6.5 mm, with 83 (92%) less than or equal to 10 mm. Forty-nine (54%) adenomas were located proximal to the splenic flexure, and 17 (19%) were classified as tubulovillous or villous. Moderate- to high-grade dysplasia was found in 29 (32%) adenomas and was associated with larger size (p less than 0.0001) and villous architecture (p = 0.0038). Two subjects harbored adenomas with invasive cancer. Seventy-one hyperplastic polyps were found in 40 (34%) subjects. The mean size of hyperplastic polyps was 3.4 mm, and 64 (90%) were located in the left colon. We conclude that, in this population, adenomas are common lesions that are frequently small. However, substantial proportions of these adenomas may be at risk for malignant degeneration due to the presence of villous architecture and higher grades of dysplasia. Because adenomas and hyperplastic polyps are endoscopically indistinguishable, all polyps found at endoscopy should be removed or ablated. 
Direct myocardial revascularization without extracorporeal circulation. Experience in 700 patients Between May 1978 and March 1990, 700 patients were operated on with direct coronary surgery without extracorporeal circulation (ECC): 529 (76 percent) were male and 171 (24 percent) were female. The average age was 64 years (range, 35 to 86 years), 454 (65 percent) had unstable angina, 163 (23 percent) had stable angina, 51 (7 percent) had postmyocardial infarction angina, and 32 (5 percent) had acute myocardial infarction at the moment of the operation. In this series of patients, all branches of the coronary arteries were bypassed; the mammary artery was used in 40 percent of the cases, the average bypass per patient was 2.2 (range, 1 to 5), and 26 percent had associated disease of high risk to undergo ECC. The morbidity was 4 percent and the mortality for this series of patients was 1 percent; the probability of survival at seven years was 90 percent. This experience shows us that this surgery is an alternative in the treatment of coronary disease, especially for aged patients with associated disease, in some cases of acute transmural infarction, and also for patients who need coronary angioplasty. Also, it can improve the relation cost/benefit in coronary surgery. 
Diazepam and intubation in emergency treatment of seizures in children. STUDY OBJECTIVES: This study was undertaken to determine the incidence of endotracheal intubation after the use of diazepam compared with phenobarbital or phenytoin in emergency treatment of seizures in children. DESIGN: The records of all children (98) were reviewed in a case-control fashion. A logistic regression model was used to determine whether there was an association between diazepam administration and intubation, adjusting for all other covariates (age, weight, convulsion time before first anticonvulsant was given, response latency, diagnosis, and therapy). SETTING: All children were treated in an emergency department and then transported to a tertiary pediatric center by a pediatric transport team. TYPE OF PARTICIPANTS: All patients were children, with a median age of 2.7 years (range 0.17 to 15.3 years). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Only the use of diazepam was found to be significantly associated with intubation after adjusting for all other covariates (adjusted odds ratio, 49.4; P less than .001). In the comparison of diazepam versus phenobarbital or phenytoin used as the first anticonvulsant, median response latency did not differ (27.0 vs 32.5 minutes, P greater than .83). CONCLUSION: A significant association was found between diazepam use and intubation. Response latency was not shorter when diazepam was used as the initial anticonvulsant compared with phenobarbital or phenytoin. 
Arterial hemorrhage after pancreatoduodenectomy. The 'sentinel bleed'. Experienced centers report reduced operative mortality after pancreatoduodenectomy for cancer, but significant complications continue to occur in as many as 25% of patients. Anastomotic disruption leads to sepsis in the pancreatic bed where major vascular structures have been exposed by regional lymphadenectomy, creating a setting for arterial erosion or ligature slough and massive hemorrhage. Dehiscence of the pancreatojejunostomy is a particular risk. We treated five patients with arterial hemorrhage after pancreatoduodenectomy, all of whom had had "sentinel" bleeding from the abdominal drains or gastrointestinal tract. Results of endoscopy were misleading in two patients. Three of five patients were saved by prompt recognition, early operation, and, in one instance, angiographic embolization. Sentinel bleeding after pancreatoduodenectomy indicates local sepsis and probable anastomotic dehiscence. Recognition of its significance and prompt response may prevent exsanguination. 
Observer variation in assessing neurophysical signs among patients with head injuries. As an early phase in the development of a valid and reliable measure of the neurophysical sequelae after head injury, we carried out assessments of interrater agreement on representative items. The purpose of this study was to determine the degree of agreement among expert raters who independently measured neurophysical signs on patients undergoing physical rehabilitation after brain injury. Agreement was described using the index of crude agreement, expected agreement and Kappa. Therapists showed a high degree of agreement on those items forming part of a routine neurological assessment: prehension, coordination, voluntary movements and tendon reflexes. Crude agreement ranged from 77.8-100%. There was considerable discordance in assessing muscle tonus, equilibrium and protective reactions, spinal reflexes, tremor and dysmetria (crude agreement ranged from 49.7-97.9%). Although, the number of subjects was small, the information generated from this study will be useful in refining our instrument for the assessment of neurophysical signs. 
Nontraumatic abdominal aortic thrombosis presenting with anterior spinal artery syndrome and pulmonary edema. A 51-year-old woman with a history of breast cancer developed pulmonary edema and lower extremity paraplegia with preservation of proprioception as the initial manifestation of abdominal aortic thrombosis. Back pain was present in the lumbar region radiating to buttocks and legs in a bilateral radicular pattern. Femoral pulses were initially palpable. Aortic angiography revealed complete abdominal aortic occlusion at L3 as well as total occlusion of the bilateral superficial femoral arteries and bilateral common iliac arteries. Transient occlusion of the anterior spinal artery due to aortic thrombosis may cause paraplegia and may also progress to renal failure, bowel infarction, and limb loss if left untreated. Abdominal aortic thrombosis needs to be considered in a patient who presents with an anterior spinal artery syndrome, which, if present, must be treated as rapidly as possible to preserve motor and sensory function. 
Use of the robust sib-pair method to screen for single-locus, multiple-locus, and pleiotropic effects: application to traits related to hypertension. Robust sib-pair linkage analysis can be used as a screening tool in the search for the potential involvement of single-loci, multiple-loci, and pleiotropic effects of single loci underlying phenotypic variation. Four large families were each ascertained through one adult white male with essential hypertension. The robust sib-pair method was used to screen these families for evidence of linkage between 39 quantitative traits related to hypertension and 25 genetic marker loci. All traits were analyzed on the untransformed, square-root and log-transformed scales. Among other findings, there is a suggestion of linkage between the 6-phosphogluconate dehydrogenase locus on chromosome 1p36 and mean fifth-phase diastolic blood pressure. There may also be linkage between the following markers and traits: the adenylate kinase-1 marker and/or the Lewis blood group marker and the traits height, weight, and biacromial breadth; the glyoxylase I marker and the traits upper-arm circumference and suprailiac skinfold thickness; the ABO blood group and adenylate kinase-1 markers on chromosome 9q34 and the third component of complement marker on chromosome 19p13 and dopamine-beta-hydroxylase; and the P1 blood group and the traits weight and 1-h postload serum glucose level. 
Subcutaneous lidocaine for treatment of neuropathic cancer pain. Three patients with terminal malignancy reporting ineffective analgesia using systemic and subsequently spinal opiates were treated with subcutaneous infusion of 10% lidocaine hydrochloride. During the infusion, reasonably stable blood concentrations were achieved and maintained using a subcutaneous infusion at varying dose rates over days to months with improvement of the pain complaints which continued to be refractory to conventional analgesics. Blood lidocaine levels obtained at regular intervals revealed effective concentrations between 2 and 5 micrograms/ml for each patient. 
Not all nonpalpable breast cancers are alike. Clinical and mammographic data of 1009 consecutive patients were correlated with histopathologic data of 1144 biopsy specimens of nonpalpable breast lesions to better define the presentation and biologic behavior of early breast cancer. Patients with malignant neoplasms (269 [24%] of 1144 specimens) were older (mean age, 62.1 years) than patients with benign lesions (mean age, 54.9 years). Furthermore, patients with invasive disease were older (mean age, 63.3 years) than patients with noninvasive disease (mean age, 58.5 years) with an overall increased risk of invasive cancer per year of 1.035. A 58% incidence of invasive cancer was detected for lesions characterized by calcifications, while the incidence of invasive cancer was 84% for isolated mass lesions (relative risk, 4.31 for masses). Isolated mammographic calcifications associated with cancer appeared in a younger population and were significantly associated with noninvasive ductal cancer. Breast cancer presenting as a mammographic mass appeared in an older group and was highly associated with the presence of invasive disease. 
Effect of various lipid emulsions on total parenteral nutrition-induced hepatosteatosis in rats. The effect of various lipid emulsions on the development of fatty liver during total parenteral nutrition (TPN) was investigated in rats given TPN for 7 days. Medium-chain triglycerides (MCT), long-chain triglycerides (LCT), chemically defined triglycerides (CDT; structured lipid with a high purity of 94.3%), and a mixture of MCT and LCT (MIX) were prepared as the lipid emulsions. TPN provided 350 kcal/kg/day, with a nonprotein calorie/nitrogen ratio of 160. The TPN-1 group received 10% nonprotein calories and the TPN-2 group received 30% nonprotein calories. MCT TPN was found to have some disadvantages, especially with regard to nitrogen balance and plasma albumin levels. Total cholesterol and phospholipids tended to be high in the MCT TPN group. The hepatic lipid content was higher in the lipid-free TPN and the MCT TPN groups, and lower in the CDT and LCT TPN groups. Histologically, the livers of the MIX, CDT, and LCT TPN groups showed less fatty change than those of the FREE and MCT groups. 
Anticonvulsant activity of two orally active competitive N-methyl-D-aspartate antagonists, CGP 37849 and CGP 39551, against sound-induced seizures in DBA/2 mice and photically induced myoclonus in Papio papio. Two novel N-methyl-D-aspartate (NMDA) antagonists, DL-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid CPG 37849 and the corresponding 1-ethyl ester CGP 39551, were tested as anticonvulsants in DBA/2 mice and photosensitive Senegalese baboons, Papio papio. In DBA/2 mice, CGP 37849 is more potent than CGP 39551 when administered intracerebroventricularly (i.c.v.) or intraperitoneally (i.p.) (ED50 for suppression of clonic seizures at 60 min: i.c.v. 0.038 and 0.21 nmol; i.p. 3.40 and 19.1 mumol/kg, respectively). When administered orally in mice, the two compounds are approximately equipotent (ED50 CGP 37849, 35.2 mumol/kg; ED50 CGP 39551, 28.1 mumol/kg). The time course of action of CGP 39551 is exceptionally prolonged: 42 mumol/kg i.p. protects against clonic seizures for 48 h. Protection provided by other NMDA antagonists in mice is of much shorter duration: 2-amino-5-phosphono-pentanoic acid (AP5) 1 h, 2-amino-7-phosphono-heptanoic acid (AP7) 4 h, 2-amino-7-phosphono-heptanoic acid 1-ethyl ester 3 h, 4-(3-phosphonopropyl)-2-piperazine carboxylic acid (CPP) 2 h, cis-4-(phosphonomethyl)-2-piperidine-carboxylic acid (CGS 19755) 4 h, and CGP 37849 4 h. After oral administration of the drugs, the therapeutic index (TI = ratio of the ED50 values for rotorod performance and anticonvulsant protection) remains relatively constant at 5.9-7.2 for 3 h (CGP 37849) and 4.0-6.1 for 24 h (CGP 39551). After i.p. administration, the TI values are CGP 37849 at 1 h 2.4, and at 3 h 20.0, CGP 39551 at 1 h 2.3, at 3 h 7.1, and at 24 h 3.6. In baboons, acute administration of CGP 37849 at doses of 48-191 mumol/kg intravenously (i.v.) suppresses photically induced myoclonus for at least 285 min, with severe side effects at the highest dose tested. CGP 39551 at doses of 169-675 mumol/kg i.v. shows weak anticonvulsant activity only at the highest dose tested (accompanied by severe side effects). CGP 37849 at 48-96 mumol/kg orally (p.o.) fails to protect against photically induced myoclonus up to 4 h after administration, but 191 mumol/kg (40 mg/kg) p.o. produces complete suppression of seizures after 24 h. On the other hand, CGP 39551 at 169 mumol/kg (40 mg/kg) p.o. produces total suppression of seizure activity at 4 h with a longer duration of anticonvulsant action (2-3 days).(ABSTRACT TRUNCATED AT 400 WORDS). 
A geriatric-anesthesiologic program to reduce acute confusional states in elderly patients treated for femoral neck fractures. The aim of this study was to evaluate the effect of a geriatric-anesthesiologic intervention program for the prevention and treatment of acute confusional states (ACS) in elderly patients treated for femoral neck fractures. The intervention program was based on the results of previous prospective studies in similar patient populations. The outcome of the intervention, comprising 103 patients, was compared with that of an earlier study comprising 111 patients. The intervention program consisted of pre- and post-operative geriatric assessments, oxygen therapy, early surgery, prevention and treatment of peri-operative blood pressure falls and treatment of post-operative complications. The incidence of ACS was lower, 47.6%, in the intervention study compared with 61.3% (P less than 0.05) in the control study. Furthermore, the ACS that occurred in the intervention study was less severe and of shorter duration than that in the control study. The incidence of post-operative decubital ulcers, severe falls, and urinary retention was also lower. The mean duration of orthopedic ward stay was 17.4 days in the control study and 11.6 days in the intervention study (P less than 0.001). It can be concluded that the intervention program reduced the incidence, severity, and duration of ACS which resulted in a shortened orthopedic ward stay. 
Testicular scanning: evaluating the acute scrotum in the clinical setting. In a retrospective study of patients with acute scrotal pain presenting to the hospitals of Southern Illinois University School of Medicine from January 1982 until September 1987, determination was made of the appropriate use of testicular scan for definitive diagnosis. Though the testicular scan is a highly sensitive and specific examination in the identification of testicular torsion, we believe its routine use in clinical practice is limited. Appropriate utilization of the examination requires its use in high-risk groups with equivocal physical findings or in patients with unusual presentations of age, anatomy, or neurologic deficit. The scan if used for routine screening of the acute scrotum would result in needless delays and unjustifiable expense when it is mandatory that the treatment be immediate surgical exploration. 
Hereditary hyperparathyroidism and multiple ossifying jaw fibromas: a clinically and genetically distinct syndrome. A large previously reported family with hyperparathyroidism has been reinvestigated recently because of the occurrence of multiple ossifying jaw fibromas in two affected members of the third generation similar to the jaw tumors of four of five affected members of the first generation. These maxillary and mandibular tumors can be differentiated from the "brown tumors" of hyperparathyroidism because they can appear and enlarge even though the hypercalcemia is surgically corrected. These tumors are histologically distinct fibroosseous lesions without the giant cells seen in "brown tumors." The parathyroid enlargement was mostly uniglandular, with multiple tumors found occasionally. Studies in DNA linkage were performed within this large family and a similar family in Houston to determine if the gene for this syndrome, termed HRPT2, is linked to DNA markers on chromosome 11, to which the gene for multiple endocrine neoplasia (MEN) type 1 has been linked. (This linkage is supported by our findings in one family with MEN 1 reported here.) Linkage studies were also performed with markers on chromosome 10, to which the genes for MEN 2A and MEN 2B have been linked. Evidence against close linkage with chromosome 10 and chromosome 11 markers suggests that this clinically distinct syndrome is also genetically distinct. 
Carcinoma erysipeloides. We report an 83-year-old woman with carcinoma erysipeloides due to an occult carcinoma. Immunohistochemical study of skin biopsies showed reactivity to S-100 protein and human milk fat globule antigen indicating that the tumour originated in the breast. 
Intraoperative transesophageal echocardiography of atrioventricular septal defect. To determine the accuracy and utility of single-plane transesophageal echocardiography in analyzing atrioventricular (AV) septal defect, intraoperative transesophageal echocardiography was performed before and after institution of cardiopulmonary bypass in 16 patients (age 24 days to 14 years, weight 3 to 47 kg). Prebypass transesophageal echocardiography (including two-dimensional echocardiography, Doppler color flow mapping and pulsed wave Doppler ultrasound) correctly diagnosed divided AV valve, common AV valve and unbalanced AV valve, as well as atrial or ventricular septal defect, or both, in all cases. It correctly analyzed AV valve regurgitation in all 10 patients with right and all 14 with left AV valve regurgitation and correctly analyzed 30 of 33 additional cardiac anomalies. Transesophageal echocardiography was able to detect the absence of normal pulmonary venous connections but failed to demonstrate all of the complex anomalous pulmonary venous connections in three patients with atrial isomerism. Postbypass transesophageal echocardiography documented the absence of a significant residual shunt in 11 of 11 patients undergoing corrective surgery and verified residual AV valve regurgitation in 7 of 9 patients with tricuspid regurgitation and 11 of 13 with mitral regurgitation. Transesophageal echocardiographic information that altered or refined the surgical treatment was obtained in 5 (31%) of 16 patients. Epicardial and transesophageal echocardiography results were concordant in all 13 patients in whom both were performed. Transesophageal echocardiography provides useful and accurate imaging of the important two-dimensional, pulsed wave Doppler ultrasound and Doppler color flow mapping features in AV septal defect. 
Primary angiosarcoma of the brain. We have described a 32-year-old black woman who had a primary angiosarcoma of the right occipital lobe. All three previously reported cases have been fatal within 1 year. Our patient is doing well more than 3 1/2 years after surgery. 
Abnormal liver enzyme-mediated metabolism in Parkinson's disease: a second look. If toxicant exposure contributes to the cause of Parkinson's disease, poor function of detoxifying enzymes could increase vulnerability for Parkinson's disease. Although no hepatic enzyme system has been shown universally to be dysfunctional in Parkinson's disease patients, several have been suggested to be dysfunctional in subgroups, such as those with young age at disease onset. Specific enzymes implicated include several P450 enzymes, most notably P450 IID6, and cysteine dioxygenase. If hepatic enzyme abnormalities contribute to the development of Parkinson's disease, molecular genetic techniques may allow the development of screening tests to identify at-risk subjects in order to intervene with protective therapies. 
Bilateral ureteral obstruction following aortobifemoral bypass graft. In this report we present a case of bilateral ureteral obstruction, a potentially serious late complication of aortic bifurcation surgery. The incidence, aetiology, clinical presentation and treatment are discussed. 
Does patient age or intestinal pathology influence the bacteria found in cases of necrotizing enterocolitis? To evaluate the relationship between bacterial colonization in neonatal peritonitis and patient age or intestinal pathology, we retrospectively reviewed peritoneal culture results from 96 infants having surgery for necrotizing enterocolitis. Microorganisms recovered mirrored those usually found as fecal flora within the neonatal intensive care unit. These reflect, in turn, the abnormal colonization intrinsic to care in the intensive care nursery. Analysis revealed no significant correlation between the disease and either age of the infant or intestinal site of disease. 
Obstruction of the infrarenal portion of the abdominal aorta: results of treatment with balloon angioplasty. Our experience in the treatment of stenoses of the infrarenal portion of the abdominal aorta with balloon angioplasty in 27 patients is reported. Clinical findings were lower limb claudication (all patients), impotence (eight patients), and blue-toe syndrome (two patients). The underlying disease was atherosclerosis in 24 patients and nonspecific aortoarteritis in three patients. Dilatation was successful in all patients. Embolic occlusions of the left common iliac artery (one patient) and left superficial femoral artery (one patient) were the only major complications. Claudication in the affected limb continued in the first patient; the second died when diagnostic angiography, performed 3 months after angioplasty, caused a severe atheroembolus. Of the other 25 patients, nine of the 10 followed up for 13-48 months and all seven followed up for 3-8 months were free of symptoms. Six of eight patients with sexual dysfunction had normal function after angioplasty. Seven patients still awaited follow-up and one was lost to follow-up. Our experience suggests that balloon angioplasty is an effective treatment of stenoses of the infrarenal portion of the abdominal aorta. 
Magnetic resonance imaging of pulmonary artery aneurysm. Pulmonary artery aneurysm is a rare condition. We have presented what we believe to be the first case in the English literature to be diagnosed by magnetic resonance imaging. 
Analysis of anti-tumor antibodies in mice and rabbits induced by monoclonal anti-idiotope antibodies. Eight different mouse monoclonal anti-idiotope antibodies (mAb2) generated against a mouse monoclonal anti-human melanoma proteoglycan Ag (MPG) antibody (mAb1), MEM136, were tested for their ability to induce anti-MPG responses in mice and rabbits. All Ab2 were idiotypically cross-reactive and combining site-specific as demonstrated by competitive cross-inhibition studies and their ability to inhibit the binding of MEM136 to the melanoma cells, Colo38. However, only two Ab2, IM32 and IM06, were able to induce specific anti-TAA-specific (Ab1') responses in rabbits. When IM32 and IM06 were tested in allogeneic stains of mice for the induction of anti-MPG responses, only IM32 produced an Ab1' response. In mice, the Ab3 response induced by IM32 is idiotypically cross-reactive with its Ab1. Furthermore, the IM32-induced murine Ab3 and MEM136 recognized a similar MPG epitope on the melanoma cells because the Ab3 inhibited the binding of MEM136 to melanoma cells. The Ab3 induced by IM32 and IM06 in rabbits also recognized a similar epitope as the Ab1. In rabbits, the Ab3 response induced by IM32 and IM06 were idiotypically cross-reactive with each other. However, additional studies indicated that the majority of Ab3 induced by IM32 were IM32 Id-specific and lacked IM06 idiotopes. Further experimentation indicated that IM32-induced rabbit Ab3 were biologically active as demonstrated by the ability of the Ab3 to inhibit melanoma cell invasion in a Matrigel assay. 
Large amplitude sensory action potentials in myelopathy: an observation. Subjects with at least one sensory action potential (SAP) amplitude greater than 2 SD above the age-matched mean during standard nerve conduction tests were evaluated for evidence of spinal cord disease. From a total of 153 subjects, 16 had at least one large amplitude SAP and 12 of 16 (75%) had a documented myelopathy. While a mechanism has yet to be determined, this observation suggests that SAP amplitudes greater than 2 SD above normal may be correlated with clinical evidence of injury to the central nervous system. 
Recurrent adnexal torsion and cystadenoma of aberrant ovarian tissue. Torsion of the adnexa is rare, and diagnosis is difficult because of the sparse clinical findings. I describe a patient with recurrent torsion of the right adnexa, involving a cystadenoma of aberrant ovarian tissue. Her only symptom was recurrent right-sided pelvic pain. 
Treatment of pseudotumor cerebri by primary and secondary optic nerve sheath decompression. We performed optic nerve sheath decompression in 53 patients (101 eyes) with pseudotumor cerebri and visual loss. Sixty-nine eyes (85 patients) with acute papilledema uniformly had improved visual function after optic nerve sheath decompression. Of 32 eyes with chronic papilledema (18 patients), only ten had improved visual function after optic nerve sheath decompression. This difference was significant (P = .0001). Thirteen eyes required secondary or tertiary optic nerve sheath decompression after an initial successful result. Eleven of 13 eyes had improved visual function after repeat optic nerve sheath decompression. We believe that patients with acute papilledema and visual loss should be offered optic nerve sheath decompression, and if symptoms recur, repeat optic nerve sheath decompression is a safe and effective treatment option. 
A randomized trial of ticarcillin and clavulanate versus gentamicin and clindamycin in patients with complicated appendicitis. Secondary bacterial peritonitis is usually a polymicrobial infection of facultative gram-negative aerobic and anaerobic organisms. Treatment consists of operation and broad-spectrum antibiotic administration. The antibiotic treatment of choice in these infections has been the combination of gentamicin and clindamycin. However, this combination can have toxic side effects and necessitates frequent monitoring of serum levels. Beta-lactam antibiotics provide broad-spectrum coverage and low toxicity, but can be inactivated by species of bacteria producing beta-lactamase enzymes. Clavulanic acid is a potent inhibitor of beta-lactamases and has been shown to extend the efficacy of ticarcillin to bacteria producing these enzymes. This combination was compared with gentamicin and clindamycin in 99 consecutive patients with complicated appendicitis. Eradication of identified pathogens was greater in the ticarcillin and clavulanate group (98 per cent) than in the gentamicin and clindamycin group (92 per cent), even for the subgroup of organisms producing beta-lactamases (97 versus 90 per cent eradication). Complications and clinical response were not significantly different between the two treatment groups. Ticarcillin and clavulanic acid is a safe and effective alternative to gentamicin and clindamycin in the treatment of secondary bacterial peritonitis and offers advantages in dosing simplicity and freedom from ototoxic and nephrotoxic effects. 
The accuracy of malignant diagnoses established by fine needle aspiration cytologic procedures of mammary masses. Fine needle aspiration cytologic studies are being used with increasing frequency to diagnose carcinoma of the breast. To determine whether or not a diagnosis of carcinoma established by cytologic examination is sufficiently accurate to proceed to treatment without tissue confirmation, we have examined our results in a series of 109 patients who had 111 aspiration cytologic procedures followed by open biopsy between January 1985 and June 1987. From this group, 39 specimens were read as malignant and 19 were read as suspicious. Thirty-eight of 39 specimens with positive readings were from lesions that proved to be malignant on subsequent open biopsy. Seventeen of 19 suspicious specimens were also from malignant lesions. Three of 17 specimens that were inadequate and nine of 36 negative specimens were from lesions that were later shown to be malignant. Our single false-positive result occurred on cells that had been air dried during preparation in the early months of experience with this technique at our institution. Re-evaluated later in our series, the same specimen was called suspicious rather than malignant. We conclude that a positive reading on fine needle aspiration is highly accurate. The positive predictive value should be 100 per cent, once experience is gained in preparing and interpreting the material. Open biopsy is necessary for inadequate, negative or suspicious specimens to exclude a malignant lesion if the clinical or mammographic findings are consistent with carcinoma. 
Neurocutaneous melanosis: definition and review of the literature. Neurocutaneous melanosis is a rare congenital syndrome characterized by the presence of large or multiple congenital melanocytic nevi and benign or malignant pigment cell tumors of the leptomeninges. The syndrome is thought to represent an error in the morphogenesis of the embryonal neuroectoderm. We review 39 reported cases of neurocutaneous melanosis and propose revised criteria for diagnosis. Most patients with neurocutaneous melanosis presented in the first 2 years of life with neurologic manifestations of increased intracranial pressure, mass lesions, or spinal cord compression. Leptomeningeal melanoma was present in 62% of the cases, but even in the absence of melanoma, symptomatic neurocutaneous melanosis had an extremely poor prognosis. Useful diagnostic procedures include cerebrospinal fluid cytology and magnetic resonance imaging with gadolinium contrast. Patients may be aided by palliative measures such as shunt placement to reduce intracranial pressure. Dermatologists in their follow-up of patients with large or multiple congenital melanocytic nevi should be aware of this condition, to aid in prompt diagnosis and because the treatment of cutaneous lesions may be altered in the presence of symptomatic neurocutaneous melanosis. 
Extracorporeal shock wave lithotripsy of pancreatic duct stones. Chronic calcifying pancreatitis presents a major clinical problem, often requiring extensive surgery. Extracorporeal shock wave lithotripsy (ESWL) offers a new therapeutic option. We applied ESWL after endoscopic sphincterotomy of the pancreatic orifice in eight patients with impacted pancreatic duct stones. An electromagnetic lithotriptor (Siemens Lithostar, Erlangen, FRG) was used. Patients were treated in prone position under fluoroscopic control. A mean of 6,813 shock waves (range 1,500-10,000) was delivered in one or two sessions. Disintegration of stones was achieved in 6/8 patients, initial relief of pain in 7/8 patients, and total clearance of the pancreatic duct in 3/8 patients. One patient had an exacerbation of her pancreatitis one day after ESWL, which resolved rapidly with medical treatment. No other complications were observed. Four of five patients with fragmented stones had no abdominal complaints at follow-up (mean 17 months, range 3-27). Three patients in whom ESWL was not completely successful (two without and one with partial fragmentation) underwent an operation according to Puestow. Two of them still have abdominal complaints after surgery. From these data, we conclude that ESWL of pancreatic duct stones is a promising new alternative for surgery, when endoscopic stone extraction fails. 
Iron oxide-enhanced MR imaging of the liver and spleen: review of the first 5 years. Superparamagnetic iron oxide (SPIO) particles are a potent new class of MR contrast agents affording improved detection of hepatic and splenic neoplasms. In this report we review the development of this agent through preclinical studies and early clinical results at Massachusetts General Hospital during a 5-year investigation. SPIO particles are sequestered by normal phagocytic Kupffer cells of the reticuloendothelial system (RES) but are not retained in tumor tissue. Consequently, there is a fivefold increase in T2 relaxation between normal RES tissue and tumor, with a comparable advantage in quantitative signal-to-noise ratio, contrast-to-noise ratio, and lesion detectability in the liver and spleen on MR imaging. Increased lesion conspicuity can be exploited to decrease threshold size for lesion detection to less than 3 mm. Clinically beneficial effects occur with a variety of mildly T2-weighted spin-echo pulse sequences; gradient-echo techniques show even greater benefit after administration of SPIO. Metabolically, pharmaceutical-grade preparations are biodegradable and bioavailable, being rapidly turned over into body iron stores and incorporated into erythrocyte hemoglobin. Early dose-escalation clinical trials have identified a probable clinical dose range of 10-20 mumols Fe/kg body weight. In the United States, SPIO compounds evaluated to date are still approved for use in investigational studies only. Newer commercial formulations currently being evaluated may extend clinical safety margins. 
Extended duration of herpes simplex virus DNA in genital lesions detected by the polymerase chain reaction. To evaluate the utility of the polymerase chain reaction (PCR) for documenting herpes simplex virus (HSV) in persons with reactivated genital lesions viral isolation was compared with a recently developed PCR method. Three women experiencing four episodes of recurrent genital herpes were followed for 10 days per episode with daily examination and duplicate swabs of the lesions, one for HSV culture and one for PCR. HSV type 2 was cultured from three of four episodes and the mean duration of viral isolation from recurrent genital lesions was 2.6 days. PCR detected HSV DNA from lesion swabs during all four episodes, and HSV DNA was positive for an average of 6.8 days. HSV DNA was demonstrated in ulcerative lesions on 15 of 17 days versus 3 of 17 days by viral isolation (P less than .01). HSV PCR became negative when the lesions reepithelialized. These data suggest that PCR is a more sensitive measure of HSV infection than routine viral culture and that PCR detects the presence of HSV at times when culture is negative. 
Triple agent immunosuppression in serpiginous choroiditis. Serpiginous choroidopathy is a progressive choroidal inflammatory disorder that typically has a variable saltatory course. Response to steroids is uncertain. By using azathioprine, cyclosporine, and prednisone in combination, the authors have observed rapid remission of active disease in five patients. Remissions have been maintained for periods up to 18 months. Because of the synergistic effects of this combination, doses could rapidly be reduced to maintenance levels without reactivation. Disease in two patients recurred immediately after discontinuation of low-dose therapy but was arrested when therapy resumed. Triple agent immunosuppressive therapy is well tolerated and appears to be effective. 
Hypertension-induced changes of platelet-derived growth factor receptor expression in rat aorta and heart. Hypertension-associated growth of vascular smooth muscle cells might be mediated in vivo by platelet-derived growth factor (PDGF). Our previous investigations in hypertensive rats failed to demonstrate changes in aortic steady-state mRNA levels of PDGF A or B chains. The current studies were performed to determine whether hypertension might affect the expression of PDGF receptors. We studied PDGF alpha- and beta-receptor gene expression by Northern analysis using human and rat cDNA probes. Studies of tissue distribution revealed that PDGF beta-receptor mRNA was most abundant in total aorta and aortic media, whereas the PDGF alpha-receptor mRNA was most abundant in the lung and was expressed at low levels in aortic tissue. Deoxycorticosterone acetate (DOCA)-salt hypertension induced a threefold increase in aortic steady-state PDGF beta-receptor mRNA levels. Aortic PDGF beta-receptor expression also was higher in spontaneously hypertensive rats (SHRs) when compared with age-matched normotensive Wistar-Kyoto (WKY) controls. Aortic PDGF alpha-receptor steady-state mRNA levels were unchanged in DOCA-salt hypertension and were expressed at similar levels in WKY rats and SHRs. Unlike the findings with aorta, cardiac PDGF beta- and alpha-receptor and PDGF B-chain expressions were unchanged in the DOCA-salt model and were decreased in SHRs. These findings indicate that hypertension can increase aortic steady-state mRNA levels for PDGF beta-receptor. They also indicate that tissue-specific expression of the genes of the PDGF ligand/receptor system are differentially regulated in hypertension. 
Subglottic laryngeal closure for aspiration. Aspiration may be life threatening, particularly in those patients with severe central neurological disease. From such a group of patients, several were identified who had severe laryngeal dysfunction and aspiration. The majority of patients in this subgroup existed in a neurologically vegetative state. In an attempt to reduce the degree of aspiration they experienced, the procedure of subglottic laryngeal closure was performed. Essentially, the operation is designed to isolate the tracheal airway from the incompetent larynx. The aim is to protect the lower airway from pharyngeal contamination. In all 5 patients there was a marked improvement in general and pulmonary health. 
Pain in neonatal circumcision. Because newborn circumcision is a quick and safe surgical procedure, any method to relieve pain must be almost risk-free in order to be acceptable. General anesthesia and narcotic analgesia are not appropriate. Dorsal penile nerve block (DPNB) with lidocaine hydrochloride is probably the most effective and safest form of anesthesia for newborn circumcision currently available, but it can cause significant local and systemic reactions. Only a limited number of cases of DPNB have been reported and we feel that this procedure should be used cautiously until there is more published evidence of its safety. Alternative methods of pain relief including oral acetaminophen and topical anesthesia should also be studied. Of special interest is recent evidence that a sucrose-flavored pacifier is an effective analgesic during newborn circumcision. 
Heterogeneity of T cell lymphoblastic leukaemias. Twenty eight out of 170 consecutive cases of acute lymphoblastic leukaemia (ALL) were examined. They were of T cell origin, with the following distribution: seven (28%) cases had pre-T or prothymic features; nine (36%) cases showed early thymocytic features, six (24%) had cortical features; and three (12%) had a "mature" phenotype. The remaining three cases could not be sub-classified. A striking finding was that pre-T ALL differed from intrathymic ALL not only in the absence of both E rosettes and intrathymic differentiation antigens, but also in the expression of two non-lineage specific antigens HLA-DR and CD10. Both antigens appear in the bone marrow from the very first stages of lymphoid differentiation, implying that the origin for pre-T ALL is bone marrow. A comparison of the clinical features of pre-T and thymic ALL showed that pre-T ALL disease showed a pattern more similar to non-T ALL disease: a lower incidence of mediastinal mass, absence of extrahaematopoietic disease, lower white cell counts and haemoglobin concentrations, and a higher incidence of bone pain. No obvious difference in response to treatment was apparent. The results show that T-ALL is not only a heterogeneous immunological group but also suggest that it may have different origins: bone marrow for pre-T ALL and the thymus for thymic ALL. 
A new provocative test for chronic mesenteric ischemia. A new provocative test for chronic mesenteric ischemia is described, based upon the demonstration of a fall in the intramural pH of the small bowel after introduction of a test meal into the stomach. Intramural pH (pHI) is determined indirectly by tonometry, utilizing a tonometer passed per os. Postoperative assessment of revascularization procedures is also possible by the same technique. Application of the test in an 84-yr-old woman showed good correlation between a preoperative fall in jejunal intramural pH and abdominal pain, and the absence of a fall postoperatively after successful revascularization. 
Expression of human HLA-B27 transgene alters susceptibility to murine Theiler's virus-induced demyelination. Infection of certain strains of mice with Theiler's murine encephalomyelitis virus results in persistence of virus and an immune-mediated primary demyelination in the central nervous system that resembles multiple sclerosis. Because susceptibility/resistance to demyelination in B10 congeneic mice maps strongly to class I MHC genes (D region) we tested whether expression of a human class I MHC gene (HLA-B27) would alter susceptibility to Theiler's murine encephalomyelitis virus-induced demyelination. Transgenic HLA-B27 mice were found to co-express human and endogenous mouse class I MHC genes by flow microfluorimetry analysis of PBL. In the absence of the human transgene, H-2stf, or v mice but not H-2b mice had chronic demyelination and persistence of virus at 45 days after infection. No difference in degree of demyelination, meningeal inflammation, or virus persistence was seen between transgenic HLA-B27 and nontransgenic littermate mice of H-2f or H-2v haplotype. In contrast, H-2s (HLA-B27+) mice showed a dramatic decrease in extent of demyelination and number of virus-Ag+ cells in the spinal cord compared with H-2s (HLA-B27-) littermate mice. In addition, none of the eight H-2s mice homozygous for HLA-B27 gene had spinal cord lesions even though infectious virus was isolated chronically from their central nervous system. Expression of HLA-B27 transgene did not interfere with the resistance to demyelination normally observed in B10 (H-2b) mice. These experiments demonstrate that expression of a human class I MHC gene can modulate a virus-induced demyelinating disease process in the mouse. 
Ventricular arrhythmias in children with an apparently normal heart. Ventricular ectopy occurs frequently in normal children. In the presence of a normal heart, these arrhythmias, including asymptomatic, nonsustained ventricular tachycardia, carry a benign prognosis and are not associated with sudden, unexpected death. However, complex ventricular arrhythmias frequently indicate the presence of underlying cardiac disease; patients with such arrhythmias must undergo an appropriately thorough evaluation before decisions regarding prognosis and the need for therapy can be made. 
Does fetal seizure activity mean a poor outcome? A case report. Fetal seizure activity is very rare: only three cases have been reported. A case of fetal seizure activity was detected with ultrasound. Such activity can be associated with a poor outcome. 
Quantification of Helicobacter pylori infection in gastritis and ulcer disease using a simple and rapid carbon-14-urea breath test. Gastric urease was studied isotopically in 230 patients with biopsy-proven normal mucosa or chronic gastritis, including 59 patients with ulcer disease. Carbon-14-urea was given in 25 ml of water without substrate carrier or nutrient-dense meal, and breath samples were collected over a 60-min period. The amount of 14CO2 excreted at 10 min was independent of the rate of gastric emptying and was not quantitatively influenced by the buccal urease activity. The 10-min 14CO2 values discriminated well between Helicobacter pylori positive and negative patients (94% sensitivity, 89% specificity) and correlated with the number of organisms assessed by histology. The test was a good predictor of chronic gastritis (95% sensitivity and 96% specificity), and a quantitative relationship was observed between 14CO2 values and the severity and activity of the gastritis. In H. pylori positive patients, breath 14CO2 was found to be similar in patients with and without ulcer disease, suggesting that the number of bacteria is not a determining factor for the onset of ulceration. 
A long-term study of hepatitis C virus replication in non-A, non-B hepatitis. BACKGROUND. Although antibodies to the hepatitis C virus (HCV) are known to be associated with non-A, non-B hepatitis, little is known about the pattern of HCV replication, its relation to antibody levels, and the clinical course of non-A, non-B hepatitis. METHODS. We measured HCV RNA in serial serum samples from five patients with post-transfusion non-A, non-B hepatitis who were followed for 10 to 14 years after transfusion. We also studied four chimpanzees that were experimentally infected with serum from four of these patients. Serum HCV RNA was detected by a "nested" polymerase-chain-reaction (PCR) assay that used two sets of primers derived from the third (NS3) and fourth (NS4) non-structural gene regions of the HCV genome. RESULTS. HCV sequences were detected by PCR in only two of the five patients and two of the four chimpanzees with the set of primers corresponding to the NS3 region, but in all five patients (and in all four chimpanzees) with the primers from the NS4 region. Serum HCV RNA was first detected within three weeks of transfusion in all five patients and within one week in three patients. The viremia lasted less than 4 months in the patient (and two chimpanzees) with acute, self-limited hepatitis, whereas it persisted for 10 to 14 years in the four patients (and for 1 and 3 years in two chimpanzees) with chronic non-A, non-B hepatitis. Antibodies to HCV were first detected at week 12 to 14; they disappeared after nine years in the patient with self-limited disease and became borderline after five years in one of the patients with chronic disease. CONCLUSIONS. During the early phase of primary HCV infection, there is a period of several months of sero-negativity during which HCV RNA is the only diagnostic marker of infection. The disappearance of HCV RNA from serum appears to correlate with the resolution of non-A, non-B hepatitis, whereas viremia persists in patients whose disease progresses to chronic hepatitis. In contrast, antibody levels do not necessarily remain elevated in patients with chronic disease. 
Narrow-angle glaucoma presenting as acute, painless visual impairment. A 42-year-old woman presented with the acute onset of bilateral blurred vision that occurred immediately after bending over. She denied pain or any other associated symptoms. Markedly increased intraocular pressure readings were found. Treatment for acute narrow-angle glaucoma was initiated, and normal vision returned. This case represents an atypical presentation of acute narrow-angle glaucoma, a true ophthalmological emergency. The pathophysiology and treatment options of this disease process are summarized. 
Assessment of coronary artery disease using single-photon emission computed tomography with thallium-201 during adenosine-induced coronary hyperemia. Thallium-201 myocardial imaging during dipyridamole-induced coronary hyperemia has been an accepted method for diagnosing coronary artery disease (CAD) and risk stratification. Adenosine is a powerful short-acting coronary vasodilator. Initial results of thallium imaging during adenosine infusion have been encouraging. In 132 patients with CAD and in 16 patients with normal coronary angiograms, adenosine was given intravenously at a dose of 0.14 mg/kg/min for 6 minutes and thallium-201 was injected at 3 minutes. The thallium images using single-photon emission computed tomography were abnormal in 47 of the 54 patients (87%) with 1-vessel, in 34 of 37 patients (92%) with 2-vessel and in 40 of 41 patients (98%) with 3-vessel CAD. The sensitivity was 92% in the 132 patients with CAD (95% confidence intervals, 86 to 96%). In patients with normal coronary angiograms, 14 of 16 patients had normal thallium images (specificity, 88%; 95% confidence intervals, 59 to 100%). The results were very similar when subgroups of patients were analyzed: those without prior myocardial infarction, elderly patients and women. The nature of the perfusion defects (fixed or reversible) was assessed in relation to whether the 4-hour delayed images were obtained with or without the reinjection technique. In patients who underwent conventional delayed imaging, there were more fixed perfusion defects than in patients with reinjection delayed imaging (16 vs 0%, p less than 0.0001). The adverse effects were mild, transient and well tolerated. Thus, adenosine thallium tomographic imaging provides a high degree of accuracy in the diagnosis of CAD. The use of the reinjection technique enhances the ability to detect reversible defects. 
Malignant schwannoma associated with xeroderma pigmentosum in a patient belonging to complementation group D. A 43-year-old man with xeroderma pigmentosum, XP97TO, was allocated to complementation group D. He had had moderate photosensitivity at age 1 year and freckles by age 6 but no neurologic abnormalities. Nevertheless, his fibroblasts in culture had the XP-D phenotype. They showed a sevenfold hypersensitivity to killing by 254 nm ultraviolet radiation and a diminished level (29%) of unscheduled DNA synthesis. Phototesting revealed delayed maximum erythema at 72 hours after UVB exposure and a lowered minimal erythema dose. Lentigo maligna developed on the patient's face, and a rapidly growing malignant schwannoma was found on the left trigeminal nerve. This may be the first case of a peripheral nervous tissue neoplasm in xeroderma pigmentosum. 
Adenosine as a vasodilator in primary pulmonary hypertension BACKGROUND. The acute administration of vasodilator drugs to patients with primary pulmonary hypertension has been advocated to identify those with reversible pulmonary vasoconstriction. Unfortunately, the usefulness of the drugs currently available is limited by accompanying systemic hypotension. A vasodilator with effects confined to the pulmonary circulation would therefore be advantageous in such patients. METHODS AND RESULTS. The purine nucleoside adenosine was infused into the pulmonary artery in seven patients with primary pulmonary hypertension (baseline pulmonary vascular resistance [PVR], 442-1,295 dyne/cm/sec-5) to determine its effect on PVR. In all patients, there was a dose-dependent and significant reduction (mean maximal percent decrease from baseline, 38.9%; p less than 0.001) in PVR mediated through a decrease in pulmonary artery pressure and an increase in cardiac output. Systemic vascular resistance (SVR) also decreased, but the ratio of PVR to SVR decreased (maximal mean percent decrease from baseline) by 10.5% (p less than 0.025), indicating that adenosine has a preferential vasodilator effect on the pulmonary circulation when administered in this manner. CONCLUSIONS. Because of its pharmacokinetic and vasodilator properties, adenosine may have a specific role in the investigation of primary pulmonary hypertension. 
Reproducibility of Doppler echocardiographic quantification of aortic and mitral valve stenoses: comparison between two echocardiography centers. Doppler echocardiography has been widely used as a noninvasive method to quantify valvular heart diseases. This study assessed the variability between 2 echocardiography centers concerning 2-dimensional and Doppler echocardiographic results in the quantification of mitral and aortic valve stenoses. Forty-two patients were studied by 2 different echocardiography centers in a blinded, independent fashion. In patients with aortic and mitral valve stenosis, mean and maximal flow velocities were measured. The aortic valve orifice area was calculated according to the continuity equation. Mitral valve orifice area was determined by direct planimetry and by pressure half-time. In patients with an aortic valve stenosis, a close relation between the 2 centers was found for the maximal and mean flow velocities (coefficient of correlation, r = 0.72 to 0.92; coefficient of variation, 3.7 to 7.7%). A close correlation and a small observer variability was found for the flow velocity ratio determined by flow velocities measured in the left ventricular outflow tract and over the stenotic valve (r = 0.88; coefficient of variation, 0.01 +/- 0.009). In contrast, there was a poor correlation between the diameter of the left ventricular outflow tract and the aortic orifice area (r = 0.36 and 0.59, respectively). In patients with a mitral valve stenosis, mean and maximal velocities were closely correlated (r = 0.85 and 0.77, respectively). Velocities were not found to be significantly different between the 2 centers. Variability between the 2 centers for the mitral valve orifice area was 9.8% (2-dimensional echocardiography) and 5.7% (pressure half-time). 
Hypercarbic ventilatory responses of human heart-lung transplant recipients. To evaluate the effects of chronic pulmonary denervation on ventilatory control, we compared the hypercarbic ventilatory responses (HCVR) of 12 human heart-lung transplant recipients (HL) and 24 normal control subjects (C). The six male HL were subsequently compared with eight male heart transplant recipients (H), as well as the 12 male C. All subjects had normal spirometry, but lung volumes of both transplant groups were somewhat less than those of C. The HCVR of HL and C were indistinguishable (2.68 +/- 0.28 versus 2.71 +/- 0.22 L/min/mm Hg, respectively). The increment of mouth occlusion pressure (delta Pm0.1/delta CO2), however, was markedly greater in HL (P much less than 0.01). The three male groups also had equivalent HCVR, and again, the HL had an increased delta Pm0.1/delta CO2. HL men exhibited larger increments of VT and decreased frequency responses during CO2 rebreathing than did male C and H, although these differences were statistically significant only in the comparison between the transplant groups. We conclude that HL with normal spirometry have appropriate HCVR, despite pulmonary denervation. Pm0.1 responses of these subjects are increased, however, reflecting either a compensatory response to greater respiratory impedances or an occult alteration of ventilatory mechanics. Moreover, compared with subjects with similar pulmonary function, e.g., heart transplant recipients, the breathing pattern of HL during progressive hypercarbia is consistent with the absence of vagal-mediated inflation inhibition. 
Antral choanal polyp presenting as obstructive sleep apnea syndrome. Obstructive sleep apnea syndrome (OSAS) in children is commonly caused by adenotonsillar hypertrophy. The diagnostic criteria of OSAS in children are not so well delineated as in adults. We report the first case of antral choanal polyp presenting as OSAS in a 10-year-old boy that initially presented to the child psychiatry service for behavior disturbance, enuresis, and daytime somnolence. Overnight electroencephalogram sleep study revealed events consistent with OSAS. Multiple inhalant allergies, chronic maxillary sinusitis, and obstructive adenoid hypertrophy were diagnosed by the allergy and otolaryngology services. The child was scheduled for adenoidectomy when his sleep apnea symptoms persisted following antimicrobial therapy. Examination under anesthesia revealed a normal adenoid bed and a large left antral choanal polyp. Polypectomy was performed as dictated by parental consent. Postoperatively treatment with an intranasal steroid was begun. However, polypoid nasal mucosa recurred in 2 months and a Caldwell-Luc procedure was performed. Subjective reports following surgery indicated improvement in daytime irritability, attention, and mood. A follow-up overnight electroencephalogram sleep study confirmed resolution of OSAS. 
Hepatitis C virus infection and chronic liver disease in children with leukemia in long-term remission. Antibody to the recently identified hepatitis C virus (HCV) was investigated in sera of 50 leukemic children who had chronic liver disease (CLD), observed for 1 to 12.6 years after therapy withdrawal. All patients were tested for anti-HCV at regular intervals: Ortho-enzyme-linked immunosorbent assay (ELISA) test was performed in all cases. Reactive sera were also tested by recombinant immunoblotting assay to define the specificity of the results obtained by ELISA. Twelve cases (24%) were persistently positive (group A), 11 (22%) were transiently anti-HCV+ positive (group B), and 27 (54%) were negative. Mean SGPT peak during follow-up was significantly higher in group A (P = .014, A v B and P less than .00001, A v C). SGPT normalized off-therapy in 1 of 12 cases (group A), 10 of 11 (group B), and 19 of 27 (group C) (P = .0004, A v B and P = .012, A v C). Accordingly, liver histology, available in 37 patients, showed signs of chronic hepatitis in all patients in group A while most patients in group B and C had less severe liver lesions. These results indicate that HCV plays a significant role in the etiology of chronic hepatitis in leukemic patients and that persistent anti-HCV activity correlates with a more severe CLD, which could jeopardize the final prognosis of children cured of leukemia. 
Fatty infiltration in the liver in medium chain acyl CoA dehydrogenase deficiency. Fatty infiltration of the liver at postmortem examination has been recommended as a criterion for selection of infants who have died suddenly and unexpectedly for further biochemical investigation for disorders of fatty acid oxidation. We describe a boy with medium chain acyl CoA dehydrogenase deficiency who died four months after diagnosis and in whom only minimal hepatic fatty infiltration was found. 
Nuclear DNA content, tumor cell aggregation, and metastatic events in patients with poorly differentiated adenocarcinoma of the stomach. Data on 100 patients who had undergone resection for poorly differentiated adenocarcinoma of the stomach with serosal invasion were examined to assess the prognostic significance of the DNA distribution pattern in relation to the histologic tumor cell aggregation pattern. DNA distribution patterns were classified into low and high ploidies and tumor cell aggregation patterns were classified into free-cell, small nest, and large nest types. The rates of high ploidy in the free-cell, small nest, and large nest types were 23.1%, 48.0%, and 66.7%, respectively, with a significant increase according to the degree of aggregation. The high ploidy group and large nest type had a higher incidence of lymphogenous and hematogenous metastasis than the low ploidy group and free-cell type, respectively. DNA ploidy had no prognostic value for the free-cell type of tumor, but differences in prognosis and the incidence of metastasis between the DNA ploidies were evident in the nest-forming type. Aneuploid tumors consisting of a poorly differentiated adenocarcinoma were those with nest formation, from the standpoint of histologic structure and metastatic behavior. The DNA analysis of poorly differentiated adenocarcinomas was of prognostic value, especially in the nest-forming type. 
Radio-immunoassay detection of interferon-gamma in urine after intravesical Evans BCG therapy Our previous studies suggested that interferon-gamma (IFN gamma) was produced in the local immune response to intravesical BCG. To confirm this we modified a commercially available radio-immunoassay for detection of this lymphokine in urine. The urinary levels of IFN gamma were compared in serial urine samples taken from six patients undergoing treatment with Evans strain BCG and seven patients receiving intravesical mitomycin C/epirubicin. IFN gamma was detected consistently in response to BCG with levels reaching a peak (mean 67.1 U/ml., range 7.9 to 155.9 U/ml.) four to six hours post-instillation whereas after other intravesical agents no IFN gamma was detectable after seven of 13 instillations. After the remaining six instillations lower levels were detected (mean 7.4 U/ml., range 0.6 to 22.4 U/ml.). The difference in peak levels between the two groups was statistically significant (p less than 0.001 Mann Whitney U test). These results are further evidence of specific cellular immune activity in response to intravesical BCG therapy and suggest anti-tumour mechanisms similar to allograft rejection and autoimmunity. 
Asymptomatic bacterascites: is it spontaneous bacterial peritonitis? Asymptomatic bacterascites is defined as the presence of bacteria in ascitic fluid without clinical features of peritonitis or increased ascitic fluid polymorphonuclear cells. Asymptomatic bacterascites is a controversial entity, and little information is available regarding its spontaneous evolution. Clinical features, bacteriological data and outcome in 22 cirrhotic patients with asymptomatic bacterascites are reported and are compared with those of a group of 36 cirrhotic patients with spontaneous bacterial peritonitis. Eleven patients had gram-negative bacteria and 11 had one gram-positive bacteria. Only in three patients (13.6%) did peritonitis develop. Twelve patients received no antibiotic therapy, and in none did peritonitis develop. At 1 month, 27% of patients with asymptomatic bacterascites had died. Patients with asymptomatic bacterascites had less-severe liver disease; they more frequently had gram-positive bacteria in ascitic fluid and had a lower 1-mo mortality rate than did patients with spontaneous bacterial peritonitis. We conclude that asymptomatic bacterascites is usually the transient residence of bacteria in ascitic fluid. Peritonitis rarely develops in patients with asymptomatic bacterascites and, in most of them, antibiotic therapy is not required. 
A randomized comparison of intravenous heparin with oral aspirin and dipyridamole 24 hours after recombinant tissue-type plasminogen activator for acute myocardial infarction. National Heart Foundation of Australia Coronary Thrombolysis Group. BACKGROUND. This study addressed the need for heparin administration to be continued for more than 24 hours after coronary thrombolysis with recombinant tissue-type plasminogen activator (rt-PA). METHODS AND RESULTS. A total of 241 patients with acute myocardial infarction were treated with 100 mg rt-PA and a bolus of 5,000 units i.v. heparin followed by 1,000 units/hr i.v. heparin for 24 hours. At 24 hours, 202 patients were randomized to continue intravenous heparin therapy (n = 99) in full dosage or to discontinue heparin therapy and begin an oral antiplatelet regimen of aspirin (300 mg/day) and dipyridamole (300 mg/day) (n = 103). On prospective recording, there were no differences in the pattern of chest pain, reinfarction, or bleeding complications. Coronary angiography on cardiac catheterization at 7-10 days showed no differences in patency of the infarct-related artery. The proportion of patients with total occlusion (TIMI grade 0-1) of the infarct-related artery was 18.9% in the heparin group and 19.8% in the aspirin and dipyridamole group. In the patients with an incompletely occluded infarct-related artery, the lumen was reduced by 69 +/- 2% of normal in the heparin group and 67 +/- 2% in the aspirin and dipyridamole group. Left ventricular function assessed on cardiac catheterization and radionuclide study at day 2 and at 1 month showed no differences between the two groups. Left ventricular ejection fraction on radionuclide ventriculography at 1 month was 52.4 +/- 1.2% in the heparin group and 51.9 +/- 1.2% in the aspirin and dipyridamole group. CONCLUSIONS. We conclude that heparin therapy can be discontinued 24 hours after rt-PA therapy and replaced with an oral antiplatelet regimen without any adverse effects on chest pain, reinfarction, coronary patency, or left ventricular function. 
Permanent urethral stents for detrusor sphincter dyssynergia. A series of 22 patients, most of whom had spinal injuries with detrusor sphincter dyssynergia, have had Medinvent Wallstents placed across the distal mechanism. All but 8 patients had undergone outflow surgery and 11 had had repeated unsuccessful sphincterotomies. The proximal end of the stent was placed over the verumontanum unless fertility was contemplated, when it was placed immediately below the verumontanum. Fifteen patients achieved complete voiding after placement of the first stent; 3 developed bladder neck obstruction after stenting, but in 1 of these cases resolution occurred after bladder neck incision. The 3 patients with artificial urinary sphincters failed to improve after stenting. Use of the urethral stent for patients with detrusor sphincter dyssynergia and failed sphincterotomy is a major advance. It should probably be the primary treatment in selected cases. Its effect on fertility is currently under assessment. 
Type I human T cell leukemia virus tax protein transforms rat fibroblasts through the cyclic adenosine monophosphate response element binding protein/activating transcription factor pathway. The Tax oncoprotein of the type I human T cell leukemia virus (HTLV-I) activates transcription of cellular and viral genes through at least two different transcription factor pathways. Tax activates transcription of the c-fos proto-oncogene by a mechanism that appears to involve members of the cAMP response element binding protein (CREB) and activating transcription factor (ATF) family of DNA-binding proteins. Tax also induces the nuclear expression of the NF-kappa B family of rel oncogene-related enhancer-binding proteins. We have investigated the potential role of these CREB/ATF and NF-kappa B/Rel transcription factors in Tax-mediated transformation by analyzing the oncogenic potential of Tax mutants that functionally segregate these two pathways of transactivation. Rat fibroblasts (Rat2) stably expressing either the wild-type Tax protein or a Tax mutant selectively deficient in the ability to induce NF-kappa B/Rel demonstrated marked changes in morphology and growth characteristics including the ability to form tumors in athymic mice. In contrast, Rat2 cells stably expressing a Tax mutant selectively deficient in the ability to activate transcription through CREB/ATF demonstrated no detectable changes in morphology or growth characteristics. These results suggest that transcriptional activation through the CREB/ATF pathway may play an important role in Tax-mediated cellular transformation. 
Drainage of a pancreatic pseudocyst: an unusual complication. A 34-year-old white woman had external drainage of a pancreatic pseudocyst. During sinography, contrast medium filled perigastric varices, causing septic shock. From this experience, we believe that although sinograms are helpful, they should be preceded by prophylactic administration of antibiotics and that contrast material should be sterile. The drainage catheter should be removed as soon as possible. 
Pulmonary dysfunction in advanced liver disease: frequent occurrence of an abnormal diffusing capacity. PURPOSE: Abnormalities in pulmonary function have been reported in association with chronic liver disease of varied etiology. The aim of this study was to better define the frequency and nature of these abnormalities in patients who were being evaluated for liver transplantation. PATIENTS AND METHODS: We performed a battery of pulmonary function tests and chest radiographs in 116 consecutive patients (50 men, 66 women; aged 19 to 70 years, mean 44.6 years) with severe advanced liver disease who were hospitalized specifically for evaluation for possible orthotopic liver transplantation and were able to perform technically satisfactory tests. In 17 patients, quantitative whole-body technetium-99m macroaggregated albumin perfusion scanning was also performed for assessment of possible right-to-left shunting through intrapulmonary vascular dilatations. RESULTS: The most commonly affected test of lung function was the single-breath diffusing capacity for carbon monoxide (DLCO), which was abnormal in 48%, 45%, and 71% of patients who never smoked, former smokers, and current smokers, respectively. Ventilatory restriction was noted in 25% of all patients, airflow obstruction (reduced ratio of forced expiratory volume in 1 second to forced vital expiratory volume in 1 second to forced vital capacity) in only 3%, and a widened alveolar-arterial oxygen gradient in 45%. Diffusion impairment was accompanied by a restrictive defect in only 35% of the patients and by an abnormally widened alveolar-arterial oxygen gradient in 60%. When diffusion impairment was accompanied by an oxygenation defect, it was also associated with a significantly increased right-to-left shunt fraction (mean 24.9%) assessed from quantitative whole-body perfusion imaging. On the other hand, isolated diffusion impairment unaccompanied by significant hypoxemia (noted in approximately a third of the patients with a reduced DLCO) was not associated with evidence of significant intrapulmonary shunting (mean right-to-left shunt fraction 6.7%). CONCLUSIONS: Most patients with advanced liver disease have one or more types of abnormality in lung function, a reduced DLCO being the single most common functional defect. Mechanisms accounting for the abnormality in gas transfer may include intrapulmonary vascular dilatations, diffuse interstitial lung disease, pulmonary vaso-occlusive disease, and/or ventilation-perfusion imbalance. 
Comparison of a single layer continuous hand-sewn method and circular stapling in 580 oesophageal anastomoses. A total of 611 patients with carcinoma of the oesophagus or gastric cardia were operated on between July 1982 and December 1989. Resection was performed in 491 patients (one-stage, 483; two-stage, eight), bypass operation in 97, and 23 had exploration alone. The anastomoses of 580 patients with one-stage resection and bypass operations were evaluated. Hand-sewn anastomosis using a single layer of continuous absorbable monofilament suture was performed in 304 patients (221 resections and 83 bypasses). A stapled anastomosis was performed on 276 patients (262 resections and 14 bypasses). Following resection, there were 11 (5 per cent) anastomotic leaks in the hand-sewn group and ten (3.8 per cent) in the stapled anastomosis group (P = 0.69). Excluding anastomotic leaks, hospital mortality and anastomotic recurrence, stricture occurred in 18 of 172 hand-sewn anastomoses (10.5 per cent) and in 57 of 195 stapled anastomoses (29.2 per cent) (P less than 0.001). In patients who had bypass operations there were 12 anastomotic leaks, ten in the hand-sewn group (12.0 per cent) and two in the stapled anastomosis group (14.3 per cent). Only two of the discharged patients with bypass developed anastomotic strictures, a low incidence probably because of short survival. In addition, there were 245 subsidiary anastomoses made in the abdomen by the hand-sewn method as part of the reconstructive procedure, and there was one leak. The results of this non-randomized study suggest that hand-sewn anastomosis using a single layer continuous technique for the oesophagus is as safe as the use of circular staplers; hand-sewn anastomosis is less likely to become stenotic. 
Depression and chronic fatigue in cancer patients. Fatigue is a very common symptom among cancer patients. It is crucial to diagnose those patients for whom the fatigue is a symptom of depression, and to treat them appropriately. The key to providing complete and satisfying care is to identify and address the psychologic, social, and medical vulnerabilities of each cancer patient. No one is in a better position to accomplish that than the primary physician. 
Azathioprine induced liver disease: nodular regenerative hyperplasia of the liver and perivenous fibrosis in a patient treated for multiple sclerosis. Azathioprine hepatotoxicity has been described mainly in renal transplant recipients. Most reported cases are related to lesions of the venous system of the liver: peliosis hepatis, veno-occlusive disease of the liver, perisinusoidal fibrosis, and nodular regenerative hyperplasia of the liver. The most common clinical manifestation of these hepatic vascular lesions is portal hypertension. We present a case of nodular regenerative hyperplasia and perivenous fibrosis in a patient receiving azathioprine for multiple sclerosis. Histological abnormalities were similar to those described in renal transplant patients, and azathioprine was the only potential hepatotoxic agent present. 
The immunogenicity and safety of intradermal hepatitis B vaccine. BACKGROUND. One of the chief barriers to a greater use of hepatitis B vaccine is the high cost of the vaccine itself. A number of small research trials have shown that an adequate immune response can be induced at a much lower cost by administering one tenth of the vaccine using an intradermal technique. The purpose of this study was to ascertain whether these results could be replicated in a larger clinical trial. METHODS. Vaccine recipients included health care providers, police officers, and firefighters. Recipients were given 0.1 mL of plasma-derived hepatitis B vaccine intradermally on days 1, 30, and 180. Antibody response was measured on day 210, with seroconversion defined as a sample-to-negative (S/N) ratio of greater than or equal to 10. Any local and systemic side effects were documented. RESULTS. Six hundred sixteen individuals completed the vaccination series, and seroconversion occurred in 534 (86.7%). The rate of seroconversion in those younger than 40 years was 91.2% and in those 40 years and older was 75.1%. The mean S/N ratio was 154.9 (range 0 to 620) and decreased with increasing age (r = -.25, P = .0001). Side effects were largely limited to local reactions. CONCLUSIONS. The results support the use of the intradermal technique as a cost-effective alternative to the intramuscular route in individuals younger than 40 years. The intradermal technique may be used in older individuals if titers are obtained to assure seroconversion. Because of the restricted availability of the plasma-derived vaccine used in this study, similar trials with recombinant vaccine should be undertaken. 
Temporal changes in the occurrence of hemorrhoids in the United States and England. Although numerous etiologic risk factors have been proposed, the pathogenesis of hemorrhoids remains unknown. The present investigation assesses the temporal distribution of hemorrhoids as depicted by physician visits, hospital discharges, and surgical procedures to provide further insight into potential etiologic risk factors. The analysis was based on five data sources: from the United States, the National Disease and Therapeutic Index (NDTI), the National Hospital Discharge Survey (NHDS), and the Commission on Professional Hospital Activities (CPHA); from England and Wales, the Morbidity Statistics from General Practice (MSGP) and the Hospital In-patient Enquiry (HIPE). Results demonstrated a consistent decline in all data sources from the United States. The decrease occurred in males and females similarly and was most striking in those aged 45-64 years. Physician visits and hospital discharges for hemorrhoids in England and Wales likewise declined although the decrease was not as dramatic. The consistency of the temporal distributions among the two countries, as well as among the different sources, suggests that the observed decline may, in fact, reflect an overall decrease in the occurrence of hemorrhoidal disease. 
Aortoiliac surgery in renal transplant patients. Fifteen patients who had undergone renal transplantation 3 months to 25 years earlier were operated on for treatment of complicated aortoiliac atherosclerosis; eight had aneurysms and seven had stenotic or obstructive lesions. Except for the first patient, operated on in 1973, in whom the kidney was protected by general hypothermia, no special measure was used to protect the kidneys. A transient increase in creatinemia occurred in 11 patients during the postoperative period, whereas creatinine values remained unchanged in the other four. All patients had regained renal function identical to the + preoperative state in less than 10 days; three of them had significant improvement as a result of correction of a lesion that was impairing renal blood flow. Results obtained in this series show that protection of the transplant during aortic surgery is not necessary, provided an adequate surgical technique is used. This technique avoids the complex methods employed in the majority of previously reported cases and appears to be a safe procedure. 
Experimental arterial thrombosis in nonhuman primates. The baboon offers many advantages as an experimental animal to study vascular disease, thrombus formation and dissolution, effects of mediating variables, and the relative efficacy of therapeutic interventions. Each specific application for testing therapeutic agents may require testing in somewhat different model systems. For example, although the arteriovenous vascular graft model is efficient, cost effective, and well adapted to study of interventions for acute arterial thrombosis, surgical endarterectomy extends the evaluation to include interactions with the injured vascular wall. As the antithrombotic products of genetic engineering and molecular biology emerge, it will be increasingly important to have relevant, reproducible, and quantitative approaches to evaluate their effects in vivo. 
Cloning and in vitro expression of a melanoma-associated antigen immunogenic in patients with melanoma. The purpose of this study was to identify human melanoma-associated Ag (MAA) that are immunogenic in patients, because these molecules may be useful immunogens to implement active specific immunotherapy. To this end, an expression cDNA library constructed from the human melanoma cell line A375 was screened with sera from patients with melanoma. A 1029-bp cDNA (designated D-1) was isolated. Its nucleotide sequence showed no significant homology with viral and mammalian sequences stored in GE-NETYX. cDNA D-1 hybridized to a 2.0-kb mRNA species from human melanoma, neuroblastoma, erythroleukemia, B lymphoid, and T lymphoid cell lines but not from a renal carcinoma cell line, PBL, and cultured skin fibroblasts. The D-1 clone produced a fusion protein that displayed a significantly higher reactivity with sera from patients with melanoma than from healthy controls. Furthermore, D-1 fusion protein induced in mice antibodies that immunoprecipitated a 50-kDa component from cultured human melanoma cells. The structural properties of D-1 MAA are different from those of previously described MAA. These results suggest that the approach we have applied may be useful to identify novel MAA expressed by melanoma cells. Furthermore, the immunogenicity of recombinant D-1 protein suggests that it may be a valuable immunogen to implement active specific immunotherapy in patients with melanoma, if additional experiments show that it has the appropriate tissue distribution. 
A randomized clinical trial to compare two different approaches in women with chronic pelvic pain. One hundred six patients with chronic pelvic pain were randomly allocated to one of two treatment groups. In the standard-approach group, organic causes of pelvic pain were excluded first and diagnostic laparoscopy was routinely performed. If no somatic cause could be found, attention was given to other causes such as psychological disturbances. In the second group an integrated approach was chosen. From the beginning equal attention was devoted to somatic, psychological, dietary, environmental, and physiotherapeutic factors. In this group, laparoscopy was not routinely performed. Both groups were similar with respect to clinical characteristics of the patients and the severity of their pain as assessed by various pain parameters. Postcoital pain was reported by 27% of the patients. Twenty percent of the patients had had negative sexual experiences such as childhood sexual abuse or rape. Evaluation of the pain 1 year after the institution of treatment revealed that the integrated approach improved pelvic pain significantly more often than the standard approach for three out of four pain parameters (P less than .01). Laparoscopy played no important role in the treatment of pelvic pain. It is concluded that equal attention to both organic and other causative factors from the beginning of therapy is more likely to result in a reduction of pelvic pain than is a standard approach. 
Multivessel coronary artery disease: a key predictor of short-term prognosis after reperfusion therapy for acute myocardial infarction. Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) Study Group. Results of recent studies have suggested that routine cardiac catheterization may be unnecessary after reperfusion therapy for acute myocardial infarction. Therefore to better define the short-term prognostic value of early coronary angiography, and specifically the prognostic significance of multivessel coronary artery disease, the angiographic findings of 855 patients consecutively enrolled in five phases of the TAMI study were correlated with their in-hospital outcome. All patients received intravenous thrombolytic therapy (tissue plasminogen activator, urokinase, or both agents) and underwent cardiac catheterization within 90 minutes of the initiation of therapy. Multivessel disease, defined as the presence of greater than or equal to 75% luminal diameter stenosis in two or more major epicardial arteries, was documented in 236 patients. When compared with the group of patients without multivessel disease, this group had a higher prevalence of coronary risk factors and more frequently had a history of antecedent ischemic chest pain. Although the severity of the infarct zone dysfunction was similar in the two groups (-2.77 +/- 1.00 vs -2.50 +/- 1.09 SD/chord, p = NS), global left ventricular ejection fraction was lower in the group with multivessel disease (48.6 +/- 12.4% vs 51.8 +/- 10.6%, p less than 0.01). This was associated with a significant difference in the function of the noninfarct zone. Whereas this region was hyperkinetic in the group with minimal or single-vessel disease, it was hypocontractile or dyskinetic in those with multivessel disease (+0.66 +/- 1.53 vs -0.52 +/- 1.73 SD/chord, p = 0.0001). 
Impact of magnetic resonance imaging on the management of diabetic foot infections. This combined retrospective/prospective study evaluated the value of magnetic resonance imaging (MRI) in 18 diabetic patients with apparent foot infections. The goal was to define the impact of MRI on directing the expedient and accurate surgical intervention so important in achieving optimal preservation of limb tissue and function. We found that MRI provides a rapid and reliable means of "viewing" the diabetic foot. Unsuspected or poorly localized abscess cavities can be pinpointed for thorough drainage with minimal exploration. An abscess can be differentiated from cellulitis or osteomyelitis. Moreover, persistent fever following drainage of a foot abscess can be reliably evaluated via MRI, obviating the need for empiric surgical reexploration. This exciting noninvasive imaging technique leads to the most accurate surgical drainage of foot abscesses and, at the same time, can prevent unnecessary surgical exploration of the tenuous diabetic foot. 
Regulation of gene expression in renal compensatory growth. Compensatory renal hypertrophy is characterized by an increase in cell protein content. There are a number of different cellular mechanisms by which such an increase could be mediated. The relative contributions of transcriptional and posttranscriptional regulation of gene expression to the increase in constitutively expressed cellular proteins were examined in mouse kidneys undergoing compensatory growth following unilateral nephrectomy (UNI-NX). Over the 14-day study period, total protein per kidney increased by up to 37%. Northern blot analysis of the expression of the mRNAs for a number of genes associated with cell growth indicated that there was no significant increase in steady-state levels of these selected genes in nephrectomized compared with sham-operated animals. In vitro assays to measure transcriptional regulation of the same set of genes in compensatory growth showed no increase in the rate of transcription. However, transcription of the 18S ribosomal RNA gene was increased 24 hours after nephrectomy. Immunoblots of two representative proteins showed that the concentration of these proteins in total kidney protein remained constant in the different experimental groups. Since total protein increased, the concentration of these proteins in the hypertrophied kidney must have increased. Taken together, these data suggest that posttranscriptional mechanisms may account for the increase in at least some constitutively expressed proteins in cells undergoing compensatory growth. 
Concurrent hydralazine administration prevents nitroglycerin-induced hemodynamic tolerance in experimental heart failure. BACKGROUND. Organic nitrates such as nitroglycerin and isosorbide dinitrate are useful in the treatment of congestive heart failure (CHF), but tolerance develops rapidly during continuous administration. Because combination therapy of nitrate and hydralazine has been shown to provide both short- and long-term benefit but nitrate alone produces hemodynamic tolerance, we questioned whether hydralazine can preserve the favorable preload effects of nitroglycerin. METHODS AND RESULTS. Using an in vivo model of nitroglycerin tolerance in the CHF rat, we examined the effects of hydralazine bolus dosing during continuous nitroglycerin infusion. Continuous infusion of nitroglycerin alone (10 micrograms/min) produced initial reductions in left ventricular end-diastolic pressure of 40-50%, which returned to baseline by 8 hours (tolerance development). Coadministration of hydralazine (2 x 0.1 mg) maintained the effects of nitroglycerin infusion on left ventricular end-diastolic pressure (45% reduction at 10 hours). This hydralazine dose alone reduced left ventricular peak systolic pressure by approximately 12 +/- 3% but had no effect on left ventricular end-diastolic pressure. Hydralazine dosing did not affect steady-state plasma concentrations of nitroglycerin or metabolites, and hydralazine was unable to prevent nitroglycerin tolerance induced in vitro. CONCLUSIONS. The beneficial interaction of hydralazine on the preload effects of nitroglycerin may explain the long-term clinical efficacy of hydralazine/nitrate combination in CHF. Our results also suggest that the mechanism of in vivo nitrate tolerance in CHF may be systemic rather than vascular in origin. 
Clonidine inhibits vesico-sphincter reflexes in patients with chronic spinal lesions. When administered systemically to spinalized animals, clonidine, the prototypic alpha 2 adrenergic receptor agonist, purportedly acts at spinal sites to suppress motor responses related to painful peripheral and vesical stimulation and spasticity, and to improve vesicourethral coordination. Hence, the action of clonidine (400 micrograms in three divided doses in a 16-hour span) on spinal vesical and somatic reflexes was examined in five patients with suprasacral spinal cord lesions by assessing volume-induced micturition reflexes and limb motor discharges that occurred spontaneously or were elicited by noxious and nonnoxious cutaneous stimulation. Clonidine caused a significant reduction in (1) blood pressure, (2) amplitude of detrusor contraction, and (3) vesical external urethral sphincter dyssynergia. Limb motor electromyography discharges were not markedly attenuated, although spatiotemporal changes (eg, irradiation, after-discharges) were observed in some of the patients. The results are ascribed to binding to spinal cord alpha 2 adrenergic receptors located on segmental and intersegmental (propriospinal) interneurons, released from descending inhibition, with greater motor system specificity on striated sphincter innervation. Clonidine may be clinically effective in the treatment of hyperactive micturition reflexes in patients with chronic spinal lesions. 
The effect of caffeine on postprandial hypotension in the elderly In a double-blind, randomized trial the effects of caffeinated and decaffeinated drinks on postprandial hemodynamic and neurohumoral changes were studied in seven fit, elderly subjects after a standard 2.4MJ meal. There was a significant difference in supine postprandial systolic blood pressure between the placebo and caffeine phases (P less than 0.01); at 60 minutes, supine systolic blood pressure had fallen 14 mmHg [95% confidence interval (CI)-7 to-21 mmHg, p less than 0.01) after placebo, but was unchanged after caffeine (+9 mmHg, CI 0 to 18 mmHg, NS]. Similar differences between placebo and caffeine were seen in erect systolic and diastolic blood pressure (P less than 0.01), although orthostatic tolerance was maintained throughout each study period. Postprandial plasma noradrenaline levels were higher (P less than 0.02) and the increase greater (P less than 0.02) after caffeine than after placebo. Caffeine administered at the end of a standard test meal prevents the postprandial fall in blood pressure in fit, elderly subjects. The clinical relevance of this finding has yet to be determined, but it may offer a simple remedy for patients with symptomatic postprandial hypotension. 
Advances in the understanding and treatment of urinary tract infections in young women. Despite relative ease of management, the high rate of urinary tract infections (UTI) among young women presents substantial problems for the health care community. Although the majority of UTIs in young women are simple and uncomplicated, the rate of recurrence is substantial. Each treatment of UTI recurrence brings greater antibiotic resistance, requiring the use of broader spectrum and more expensive antibiotic therapy. Moreover, infection in patients with underlying urinary tract or systemic diseases can lead to serious medical and financial consequences. A better understanding of antibiotic resistance, particularly in regard to beta-lactamase-producing pathogens, has allowed us to develop more appropriate criteria for selecting antibiotics as well as the duration of therapy. The overall cost for treating UTIs in young women is a substantial health care expenditure, and requires an ongoing examination of new information concerning pathogenesis and available antibiotic therapies. 
Staged repair of interrupted aortic arch and ventricular septal defect in infancy. Staged repair of interrupted aortic arch and ventricular septal defect was carried out in 20 infants from 1979 through 1990. Among the important associated cardiac defects were transposition of the great arteries, truncus arteriosus, and anomalous origin of the right pulmonary artery. The first stage, usually consisting of the placement of an 8- or 10-mm polytetrafluoroethylene graft, pulmonary artery banding, and ligation of the patent ductus arteriosus, resulted in 20 survivors (100%) There were two interim deaths (10%) before the second stage of ventricular septal defect closure and pulmonary artery band removal, which had 15 survivors (83%, 15/18). Because the major morbidity and mortality early in this experience could be traced to leaving the pulmonary artery band on too long, early removal (within 2 to 3 months) was begun. Since 1985, 8 (100%) of 8 infants have survived both stages and are now doing well. Because of the relatively large polytetrafluoroethylene graft, only 1 child (aged 9 years) has experienced substantial late aortic arch obstruction and undergone placement of an 18-mm Dacron graft without difficulty. Of interest is the finding that in only 1 (5%) of the 20 patients has major (greater than or equal to 40-mm Hg gradient) left ventricular outflow tract obstruction developed. In summary, the staged repair of interrupted aortic arch with ventricular septal defect has become very reliable despite the condition of the infant or major associated cardiac anomalies and can be recommended for infants at high risk for primary repair. More long-term information will be needed to determine which approach will be the best choice for the majority of infants. 
Colorectal cancer patients with high risk of hematogenous metastasis: correlation with CEA levels in peripheral and draining venous blood during the period of operation. Correlations between carcinoembryonic antigen (CEA) levels of peripheral (p) and draining (d) venous blood during the period of operation, and pre- and post-operatively detected hematogenous metastases were examined in 78 patients with colorectal cancer. The metastases were found in 28 patients (HM group), but not found in the other 50 patients (non-HM group). The mean values (43 and 198 ng/ml) and positive rates (61 and 96%) greater than 5 ng/ml of p- and d-CEA levels in the HM group were significantly higher than those (6 and 14 ng/ml, and 22 and 48%, respectively) in the non-HM group. The differences (mean 184 ng/ml and positive rate 49%) of d-CEA levels between both groups were more significant than those (39 ng/ml and 30%) of p-CEA levels. The mean value (155 ng/ml) and positive rate (82%) greater than 5 ng/ml of the gradient between d- and p-CEA levels (d-p CEA gradient) in the HM group were significantly higher than those (8 ng/ml and 34%) in the non-HM group. These results suggest that patients with a high risk of hematogenous metastases are more effectively checked by the determination of d-CEA levels and d-p CEA gradient than of p-CEA levels, and that they are patients with positive d-CEA and d-p CEA gradient levels. 
Contemporary management of neurofibromatosis. The neurofibromatoses are two distinct entities with different genetic origins. The phenotypic expressions and required treatments are different. The devastating nature of neurofibromatosis-2 may be more effectively controlled through the application of advanced imaging techniques and contemporary neurotologic procedures. The most common manifestation of neurofibromatosis-2 is that of bilateral acoustic neuromas. The eventual total bilateral sensorineural deafness associated with this condition can be obviated in selected cases if the diagnosis is established early. Follow-up data are reported for three patients in whom hearing was preserved in at least one ear. When removal with hearing preservation is not possible, subtotal tumor removal with decompression of the internal auditory canals may delay progression of hearing loss. A new approach to tumors of the pterygomaxillary fossa that have extended to the middle cranial fossa has been successfully applied and is described. 
The effects of chronic endoscopic variceal sclerotherapy on portal pressure in cirrhotics. The effect of obliterating esophageal varices by endoscopic sclerotherapy on portal pressure was prospectively studied in 11 cirrhotic patients with variceal hemorrhage. Portal venous pressure gradient, determined as the difference between transhepatic portal and hepatic vein pressure, increased by a mean of 31.1% +/- 14.5% in 8 (73%) and decreased by a mean of 30.1% +/- 11.7% in 3 (27%) patients, with no statistically significant change overall (P = 0.1). These changes in portal venous pressure gradient occurred despite an improvement in the laboratory and clinical parameters of hepatic function. Deep abdominal sonography with color flow imaging at variceal obliteration showed patent paraumbilical veins in 6 (55%) patients, 3 of whom had decreases in portal venous pressure gradient (29%, 19%, 42.5%) at variceal obliteration. In 5 (45%) patients without patent paraumbilical veins, a statistically significant increase in portal venous pressure gradient between initial endoscopic variceal sclerotherapy and variceal obliteration was noted (P = 0.008). Rebleeding (single episode in all 4 patients, before obliteration in 3 patients) occurred in those with an increase in portal venous pressure gradient; all patients with portal venous pressure gradient decreases were nonbleeders. No correlation between changes in portal venous pressure gradient and time to variceal obliteration, number of sclerotherapy treatments, or rebleeding episodes was observed. Thus, an increase in portal venous pressure gradient was noted in the majority of patients at variceal obliteration. Although the portal venous pressure gradient decrease may be explained by a patent paraumbilical vein, the mechanism of portal venous pressure gradient increase is not clear. It is speculated that this portal venous pressure gradient increase may be caused by an increase in collateral resistance or flow or a combination of both, resulting from obliteration of esophageal varices by endoscopic sclerotherapy. 
Role of emergency medical services. For thrombolytic therapy to be effective in the treatment of acute myocardial infarction, the patient must enter the health care center delivery system in an efficient manner. Some entry delays are due to patient decisions and interactions with others. In the United States, prehospital care is delivered by a variety of different systems, varying from public service types such as fire-department based to private types of service. These personnel vary in level of training from paramedics with a high level of training to Emergency Medical Technicians-Ambulance with basic training (first aid), even less in some areas. The training should be upgraded so that training as an emergency medical technician with the ability to defibrillate would be the minimum level for emergency ambulance personnel; wherever economically and logistically feasible, ambulance personnel should be paramedics. Although the 911 emergency telephone system exists in some areas, there is no centralized, universal system for access, causing confusion and delays in obtaining care in critical situations such as cardiac arrest. There is a need for a national emergency number--911--with the ability to identify the calling number and address. Since dispatchers have little medical dispatch training, needed instructions are not given to the caller, which can reduce the patient's chance of survival. Trained dispatchers are needed to dispatch resources efficiently and to offer assistance until trained rescuers arrive. Ambulances are inefficiently located in some areas of the United States, slowing response to the patient. 
Effort thrombosis of the axillosubclavian vein: a disabling vascular disorder. In the natural history of this disorder, resumption of normal activity after a period of recuperation (following an episode of thrombosis) frequently leads to symptoms of upper extremity venous hypertension exacerbated by using the arms in the overhead position. This position can be demonstrated venographically to further occlude collateral vessels in thoracic outlet. A number of patients develop more extensive symptoms of neurogenic thoracic outlet syndrome. Anticoagulation may protect the collateral vessels and interrupt the period of active clot propagation resulting in a better functional result than would be expected from the natural history of the thrombotic event. In our experience, local Urokinase was the most effective means for reestablishing venous patency. With clot dissolution the underlying compression of the vein at the thoracic outlet can be demonstrated. Balloon angioplasty should not be undertaken in the acute setting nor prior to relieving the tendinous compression. The acute phlebitic process should resolve under the protection of Coumadin for three months. At that time it can be determined more effectively which patients require additional therapy. Removal of the first rib will decompress the axillosubclavian vein and the thoracic outlet collaterals permitting the vein to regain its normal configuration particularly in younger patients with more acute onset of compression. In those patients with more chronic compression the vein becomes stenotic. Improvement of the luminal configuration has been accomplished with transvenous balloon angioplasty without the necessity for venous reconstructive procedures in this series. Patients with Paget-Schroetter syndrome have a symptom complex which often reflects more extensive neurovascular compression at the thoracic outlet than that which might result from venous hypertension alone. Although thrombolytic therapy can restore patency of the axillosubclavian vein, first rib resection is necessary to relieve the external compression. This procedure was very effective in patients who had restoration of subclavian vein patency, and to a lesser degree in those with residual occlusion. 
Paul Broca and the first craniotomy based on cerebral localization. Paul Broca (1824-1880) was a well-known French surgeon-anthropologist-neurologist. Best known for his work on cerebral cortical localization and speech mechanisms, Broca also carefully worked out skull and scalp localization for underlying cortical regions. In 1871, Broca treated a man who had sustained a scalp laceration from a blow to the head without loss of consciousness or skull fracture. The patient exhibited a nonfluent aphasia about 1 month after injury and became progressively obtunded and eventually comatose. Suspecting an intracranial abscess, Broca trephined at the region of the left third frontal convolution and drained an epidural abscess. The patient improved transiently but died a few days later. Autopsy showed a left-sided, predominantly frontal purulent meningoencephalitis. Broca's other neurosurgical contributions included various surgical cases, methods for scalp localization of the cerebral convolutions, extensive studies of skull and brain abnormalities, thermoencephalography, and the stimulation of younger surgical colleagues and neurologists to make practical use of cerebral localization. 
HLA class I antigen expression as a measure of response to antiviral therapy of chronic hepatitis B. HLA class I antigen expression on peripheral blood mononuclear cells was evaluated by flow cytometry in 21 HBeAg-positive patients with chronic hepatitis B. Measurements were made before, during or after treatment with recombinant interferon-alpha-2b, either given alone or after a 6 wk course of prednisone. Immunohistochemical staining for human leukocyte class I antigen was also evaluated in 28 percutaneous liver biopsy specimens either obtained before or after therapy (N = 27) and during therapy in one instance. The amount of HLA class I antigen on peripheral blood mononuclear cells varied markedly among individual patients, but the overall results indicated that the level of inducible antigen did not correlate with increments of ALT during therapy or with a virological response to therapy. Hepatocyte staining for HLA class I antigen was observed in a minority of biopsy specimens (29%) and also did not appear to predict a response or correlate with the severity of histological disease. These data do not support current theories concerning pathogenetic mechanisms in chronic hepatitis B nor do they suggest that spontaneous display of HLA class I antigen on hepatocytes or interferon-induced expression of these antigens on peripheral blood mononuclear cells is a critical determinant for a response to therapy. 
Dispersion of ventricular repolarization in the long QT syndrome. To identify markers of dispersion of the ventricular repolarization in the idiopathic long QT syndrome, body surface potential maps were analyzed in 40 such patients (mean age +/- standard deviation 21 +/- 11 years) and in 30 healthy control subjects (mean age 24 +/- 7 years). In each subject, 117 chest leads were recorded and maps of the integral values of the QRST interval were calculated. A multipolar distribution of the values, a marker of gross electrical inequalities of repolarization, was found only in 4 patients. To detect minor regional disparities of ventricular recovery, all the ST-T waveforms were analyzed in each subject. The ST-T waves were represented by a discrete series of potential values. The "similarity index" was computed by applying a principal component analysis, which represents (in percent) to what extent 1 fundamental pattern of ST-T reproduces all the recorded waveforms. The mean value of the similarity index was significantly lower in patients with long QT syndrome than in control subjects (49 +/- 10 vs 77 +/- 8%, p less than 0.0001). A value less than 61% (corresponding to 2 standard deviations below the mean value for controls) was found in 35 of 40 patients and in only 1 control subject (sensitivity 87%, specificity 96%). Thus, the similarity index is a more sensitive marker than the multipolar distribution of QRST integral maps in revealing electrical disparities of the ventricular recovery times. 
Spatial misregistration of vascular flow during MR imaging of the CNS: cause and clinical significance. Spatial misregistration of signal recovered from flowing spins within vascular structures is a common phenomenon seen in MR imaging of the CNS. The condition is displayed as a bright line or dot offset from the true anatomic location of the lumen of the imaged vessel. Its origin is the time delay between application of the phase- and frequency-encoding gradients used to locate spins within the plane of section. The principal condition necessary for the production of spatial misregistration is flow oblique to the axis of the phase-encoding gradient. Flow-related enhancement (entry slice phenomenon), even-echo rephasing, and gradient-moment nulling contribute to the production of the bright signal of spatial misregistration. Familiarity with the typical appearance of flow-dependent spatial misregistration permits confirmation of a vessel's patency; identification of the direction of flow; estimation of the velocity of flow; and differentiation of this flow artifact from atheromas, dissection, intraluminal clot, and artifacts such as chemical shift. 
Trends in the operative management of invasive squamous carcinoma of the vulva at Indiana University, 1974 to 1988. From January 1974 to March 1988, 150 patients with primary invasive squamous cell carcinoma of the vulva underwent surgery at Indiana University. There has been a trend toward more conservative surgical management of this disease. To determine the impact of this trend on clinical outcome, cases were divided into three groups according to date of operation: group I, 1974 to 1978; group II, 1979 to 1983; and group III, 1984 to 1988. Overall, 80 patients had en bloc radical vulvectomy and groin dissection, 20 had modified radical vulvectomy and bilateral groin dissection through three separate incisions, and 36 had modified radical vulvectomy and unilateral superficial groin dissection. Fourteen patients had other operations. Forty-two patients (27.3%) had radiotherapy in addition to surgery. Among the three groups, there were no differences when mean age, International Federation of Gynecology and Obstetrics stage distribution (1988 system), mean lesion size, mean depth of invasion, or grade distribution were compared. A significant trend toward more conservative surgical therapy was observed. En bloc radical vulvectomy was performed in 77.4% of group I patients, 71.1% of group II patients, and 35.8% of group III patients (p less than 0.001). Mean days of hospitalization were also reduced significantly. Group I had a mean stay of 30 days, group II had a mean stay of 23 days, and group III had a mean stay of 11 days (p less than 0.001). Mean operative blood loss (group I, 754.8 ml; group II, 620.0 ml; group III, 393.6 ml; p = 0.03), mean units of blood transfused (group I, 1.4 units; group II, 1.3 units; group III, 0.4 units; p less than 0.01), and mean hours of operating time (group I, 3.7 hours; group II, 3.7 hours; group III, 3.2 hours; p = 0.02) were also reduced. 
Detubularisation in cystoplasty: clinical review. Cystoplasty using a detubularised bowel segment is preferable to using a tubularised length of intestine. This has been shown experimentally to result in a reduction in the contractility of the neobladder, although contractions are not completely abolished. Incontinence, especially nocturnal, may still be a problem. Assessment of renal function has shown a marked incidence of upper tract dysfunction despite detubularisation. All patients remain at risk of upper tract obstruction following cystoplasty. Because bowel contraction waves are brought on by distension, it may be possible either to postpone or to prevent the onset of contractions by avoiding an excessive build-up of bladder volume. Clean intermittent self-catheterisation is an efficient means of emptying the bladder, although sphincter rebalancing may also be required. 
Altered gallbladder contractility after extracorporeal shock-wave cholecystolithotripsy. Change in gallbladder contractility after biliary extracorporeal shock-wave lithotripsy (ESWL) may significantly influence the clearance of fragments after successful gallstone fragmentation. We assessed changes in gallbladder contractility in response to an oral fatty meal in 50 patients 1 month after biliary ESWL (all fragments were smaller than 3 mm) and also in a separate group of 10 patients 3 months after complete clearance of fragments. The prevalence of persistent lumen-obliterating contraction of the gallbladder after biliary ESWL also was analyzed in 325 patients. Gallbladder contractility remained unchanged in 30, increased in nine, and decreased in 11 of the 50 patients. The average reduction in the fasting gallbladder volume after lithotripsy was 28% (p less than .001). Gallbladder contractility remained unchanged 3 months after complete clearance of fragments in six of 10 patients studied separately. A decrease (n = 2) or increase (n = 2) in contractility was seen in the remaining patients. No significant difference occurred in the average ejection fraction of the gallbladder before lithotripsy and after complete clearance of the fragments. Thirty-four of the 325 patients who have so far undergone biliary ESWL had a completely contracted gallbladder with no lumen visible on sonography. The gallbladder returned to a relaxed state in half of these patients within 1-9 months. Thus, biliary ESWL did not significantly alter gallbladder contractility in 60% of patients. A significant reduction in the volume of the fasting gallbladder occurred after lithotripsy. Successful clearance of fragments did not improve the contractility of stonebearing gallbladders in the majority of patients. 
The modified transcochlear approach to the cerebellopontine angle. We have modified the transcochlear approach to improve exposure of the anterior petrous apex, clivus, anterior cerebellopontine angle, and the prepontine region. These changes include resection of the external auditory canal, middle ear, glenoid fossa, and posterior zygomatic arch. This approach provides improved exposure of the petrous carotid artery, jugular bulb, and clivus. It offers the largest and most lateral access to the anterior cerebellopontine and prepontine region. The results of this approach in 11 patients are discussed. 
Comparison of catheter ablation using radiofrequency versus direct current energy: biophysical, electrophysiologic and pathologic observations. The effects of catheter ablation with radiofrequency versus direct current energy were compared in 18 dogs assigned to two groups (of 9 dogs each). Each dog underwent a single ablation at two sites in the left ventricle at energy levels of 100, 200 or 300 J delivered in unipolar configuration to six dogs each. A transient decrease in left ventricular systolic pressure (from 121.3 +/- 24.5 to 94.2 +/- 18.7 mm Hg, p less than 0.01) and wall motion abnormality were noted in dogs with direct current shock. The left ventricular ejection fraction decreased (from 50 +/- 2% to 34 +/- 3%, p less than 0.001) shortly after direct current ablation but improved 4 weeks later to 43 +/- 3%. There were no significant changes in left ventricular pressure, wall motion or ejection fraction in dogs in the radiofrequency ablation group. Sustained ventricular tachycardia (greater than or equal to 30 s) was seen immediately after direct current shock in all dogs, and one dog died of intractable ventricular fibrillation. A 24-h ambulatory electrocardiographic (ECG) monitor obtained immediately after the procedure showed multiple runs of ventricular tachycardia in all dogs exposed to direct current ablation but in only three dogs that underwent radiofrequency ablation. No differences were found in peak creatine kinase, complete blood count with smear and B-beta 15-42 fibrinopeptide levels. Pathologically, direct current-induced lesions were larger (mean length x width x depth 10.9 x 7.5 x 5.2 vs. 4.8 x 4.6 x 4.3 mm) and were poorly circumscribed with inhomogeneous margins of necrosis. 
The influence of intraoperative hypotension and perioperative blood transfusion on disease-free survival in patients with complete resection of colorectal liver metastases. An increased interest in surgical treatment of liver metastases from colorectal origin has evolved recently. However not all patients benefit from this approach, with early recurrence and death still being encountered. To evaluate clinical as well as perioperative factors that might significantly affect the outcome of patients with completely resected colorectal liver metastases, we examined 116 patients who underwent resection between September 1987 and August 1989. Median follow-up time was 13.2 months (0.6 to 31.4 months). The overall survival rate was 91% at 1 year and 75% at 2 years. Median survival was not reached. Median disease-free survival time was 11.5 months, with 49.4% and 21.2% of the patients being free of disease at 1 and 2 years, respectively. By univariate analysis, site of primary colorectal cancer, preoperative carcinoembryonic antigen (CEA) level, size of metastases, number of metastases, length of operation time, percentage mean arterial pressure, number of hypotensive episodes, duration of hypotensive episodes, and whole blood transfusion significantly affected recurrence rate following resection. However only site of primary tumor, CEA, number of metastases, and number of hypotensive episodes remained significant in the multivariate analysis. The most significant single factor that affected recurrence rate was the number of hypotensive episodes during the operative procedure. It is concluded that hypotensive episodes, even when well controlled, should be avoided during operation to maximize the chances of cure and prolong disease-free survival of patients with colorectal liver metastases. 
Failure of physicians to recognize acetaminophen hepatotoxicity in chronic alcoholics. We encountered six alcoholic patients with severe acetaminophen hepatotoxicity during a 2-year period. All patients had marked elevations of aminotransferases and sometimes remarkably high prothrombin times at, or shortly after, presentation. In five of six cases the diagnosis was missed by the physicians initially caring for the patient. The apparent reasons for the missed diagnosis were insufficient history regarding the use of acetaminophen, an inappropriate reliance on blood acetaminophen levels, and lack of knowledge regarding typical aminotransferase elevations in alcoholic hepatitis vs acetaminophen toxicity. The initial clinical presentation of acetaminophen hepatotoxicity in chronic alcoholics is easily recognized clinically and is distinct from acetaminophen hepatotoxicity in suicide ingestions and from alcoholic hepatitis. Internists and other physicians should be aware of this entity and rely on the clinical picture and the history of acetaminophen use to confirm the diagnosis. 
An alternative explanation for the genesis of closed-lock symptoms in the internal derangement process. Clinical and surgical data on 194 operated joints (135 patients) were used to substantiate a new concept challenging the presumed natural history of temporomandibular internal derangement (ID). A number of findings were incompatible with the traditional depiction of a progressive process based on gradual changes in disc position and shape. These findings were a lack or correlation between increasing age and the stages of the process; the percentage of patients in the third stage (closed lock) with limited opening (less than 25 mm) too severe to be caused solely by a nonreducible, displaced disc; the unexpectedly high incidence (greater than 50%) of normally shaped discs in the third stage of the process. A specific condition of severe and stubborn limited maximal mouth opening caused by total cessation of gliding, liable to occur at any age and unrelated to disc shape or position, which responds successfully to simple treatment by lavage and lysis, pressured injection, or arthrocentesis, was discerned. Lack of gliding was attributed to adherence of the disc to the fossa by a reversible effect such as a vacuum and/or decreased volume of synovial fluid of high viscosity. This condition was deemed worthy of an independent identity, dissociated from disc displacement, as a causative factor in the second and third stages of ID, and particularly as an aid to accurate diagnosis and treatment. 
Intracanalicular acoustic neurinomas. The cases of 16 patients with acoustic neurinomas confined to the intracanalicular area are presented. These represent 2.7% of the 600 patients with acoustic neurinomas consecutively operated upon at the Neurosurgical Clinic at Nordstadt Hospital during the last 8 years. The comparatively earlier onset of vestibular symptoms and signs was characteristic of this group and precipitated diagnosis. The diagnostic reliability of magnetic resonance imaging was at least equivalent to that of air computed tomographic cisternography. Complete tumor removal was accomplished via the suboccipital approach in all patients, with 100% preservation of facial nerve and facial function; the cochlear nerve was preserved anatomically in 100% of the patients and functionally in 57%. No recurrence has occurred during follow-up periods of up to 8 years in all 16 patients. A broad spectrum of the current literature is considered, and purely intracanalicular acoustic neurinomas are discussed with regard to clinical characteristics, diagnostic steps-including neuroradiological and neurophysiological approaches-and surgical treatment and results. 
Acute gall bladder perforation--a dilemma in early diagnosis. Gall bladder perforation is a rare complication of cholecystitis. A definitive diagnosis is uncommon before surgery and the morbidity and mortality associated with this condition are high. We report six patients with gall bladder perforation to show the difficulty of making an early diagnosis. The history and the clinical findings of these patients are reviewed to highlight diagnostic pitfalls. 
Genital human papillomavirus infection in men. Diagnosis and treatment with a laser and 5-fluorouracil. One hundred twenty-eight consecutive men, sexual partners (for more than six months) of women treated for genital condylomata acuminata, were evaluated with colposcopy to assess the percentage of infected men among the couples. Ninety-three (73%) of the men were found to have a genital human papillomavirus infection on colposcopically directed biopsies. All but one patient were treated with outpatient colposcopically guided laser vaporization under local anesthesia (one patient with extensive condylomata required general anesthesia). Two weeks after laser surgery, 5% 5-fluorouracil cream, used in the genital area, was initiated on a weekly basis for two months and every other week for two more months. Patients were followed in the clinic with colposcopy performed every eight weeks for six months to evaluate the regimen's results. Thirty-seven (40%) of the 93 men had "clinically" apparent genital HPV infection, and 56 (60%) of the 93 had "subclinical" disease (as determined with colposcopy). The majority of the patients (87 of 93, or 94%) responded to one laser treatment followed by 5-fluorouracil cream and had no visible lesions at six months. Colposcopic evaluation of the male partners of infected women and laser surgery followed by topical 5-fluorouracil therapy appear to be safe and effective in controlling genital HPV infection. 
3DFT MR angiography of the carotid bifurcation: potential and limitations as a screening examination. The authors compared the three-dimensional Fourier transform (3DFT) time-of-flight magnetic resonance (MR) angiograms in 38 patients initially studied with selective intraarterial digital subtraction angiography (DSA) for suspected arteriosclerotic disease of the carotid bifurcation. MR angiograms were successfully obtained in 65 of the 75 carotid arteries (87%) visualized with DSA. DSA and MR angiographic studies were assessed for percentage area stenosis by two independent observers on two occasions. Statistical tests indicated consistency in interpretation for each observer as well as between observers. No significant difference was found between the two modalities in ability to depict changes in percentage area stenosis. For the 32 right carotid arteries in the comparison, the median for the difference between MR angiography and intraarterial DSA was 1.83% (range, -22.38% to 55.60%); for the 33 visualized left carotid arteries, it was 0.00% (range, -20.55% to 49.95%). Receiver operating characteristic analysis indicated that technically adequate MR angiography may be a sensitive screening examination for stenoses. 
Pericardial haemorrhage causing right atrial compression after cardiac surgery: role of transoesophageal echocardiography. After cardiac surgery transoesophageal echocardiography showed a large thrombus compressing the right atrium in three hypotensive patients. No satisfactory images were obtained by transthoracic imaging, which is often difficult in ventilated patients after cardiac surgery. Transoesophageal echocardiography, however, provided rapid diagnostic information and permitted prompt surgical intervention. 
Plasmapheresis in a case of eosinophilia-myalgia syndrome with ascending polyneuropathy. Eosinophilia-myalgia syndrome complicated by ascending polyneuropathy in a 40-year-old woman is described. High-dose intravenous steroids had no beneficial effect on the clinical course. Dramatic and rapid clinical improvement occurred with the use of plasmapheresis. The use of this therapeutic modality should be considered in patients with a similar clinical presentation. 
The interpretation of dysprosody in patients with Parkinson's disease. Prosodic features in the speech production of 21 patients with idiopathic Parkinson's disease were tested. The appreciation of vocal and facial expression was also examined in the same patients. Significant intergroup differences were found in the prosody production tasks but, in contrast to previous results, not in the receptive tasks on the recognition and appreciation of prosody and of facial expression. The discrepancy between the production and recognition of prosodic features does not support the suggestion that dysprosody in Parkinson's disease is necessarily a disorder of processing emotional information that could be misinterpreted as a dysarthria. 
Phase I/II trial of recombinant human granulocyte-macrophage colony-stimulating factor following allogeneic bone marrow transplantation. Forty-seven patients with hematologic neoplasia received recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) by daily 2-hour infusion following allogeneic bone marrow transplantation from HLA-identical sibling donors in a phase I-II dose-escalation trial. Dose levels ranged from 30 to 500 micrograms/m2/d. At doses at or below 250 micrograms/m2/d, toxicity felt to be caused by rhGM-CSF was negligible. However, three of five patients treated with 500 micrograms/m2/d had unacceptable side effects caused by rhGM-CSF. Two different graft-versus-host disease (GVHD) prophylactic regimens were administered. Twenty-seven evaluable patients were administered regimens that did not contain methotrexate (MTX) (Group I) and reached an absolute neutrophil count of 1,000/microL by a median of day 14. In contrast, 18 patients who received GVHD prophylactic regimens containing MTX (Group II) reached an absolute neutrophil count of 1,000/microL on a median of day 20. Patients in Group I had fewer febrile days and, of those discharged, had shorter initial hospitalizations than patients in Group II. The overall incidence of severe acute GVHD (grade 2 or greater) in the rhGM-CSF-treated patients was 28% and was similar to that in historical "good risk" patients who did not receive rhGM-CSF. These preliminary data suggest rhGM-CSF is unlikely to exacerbate GVHD in HLA-identical sibling donor transplants and indicate the need for randomized trials of rhGM-CSF in allogeneic marrow transplant patients. 
Rhabdomyolysis in children: a 3-year retrospective study. The case reports of 4 pediatric patients illustrate the complex clinical scenarios in which childhood rhabdomyolysis/myoglobinuria occurs. Children ranged in age from 8-18 years. Presumed etiologies of rhabdomyolysis/myoglobinuria included Neisseria sepsis, exertion-related episodes, dialysis disequilibrium, and diabetic ketoacidosis. No child developed respiratory or renal failure. all children were discharged with normal muscle power, indicating the benign nature of this disease and the importance of aggressive management. 
Renal artery stenosis: preliminary results of treatment with the Strecker stent. Use of the Strecker flexible balloon-expandable tantalum stent for treatment of renal artery stenosis after failed angioplasty or transaortic thromboendarterectomy was evaluated in 10 patients (nine hypertensive, one normotensive). Left (n = 3) and right (n = 5) renal arteries were involved; renal artery stenosis in two patients had developed after kidney transplantation. Indications for stent placement were inadequate immediate postangioplasty response (n = 7), development of considerable restenosis after angioplasty (n = 1), and obstructing intimal flaps following transaortic endarterectomy (n = 2). Stent placement was technically successful (less than 20% residual stenosis) and patency was preserved in eight patients. Of the seven hypertensive patients with successful implantation, two were cured, three had improvement, and two had no change at latest follow-up evaluation (mean, 10.6 months; range, 6-12 months). The Strecker stent may be helpful in treating restenosis after failed revascularization procedures, although the precise indication, true safety, and long-term efficacy of stent placement in renal arteries will not be known until trials with more subjects and longer follow-up periods are completed. 
Rest-injected thallium-201 imaging for assessing viability of severe asynergic regions. To evaluate the utility of rest-injected 201Tl initial and delayed images for assessing the viability of severe asynergic regions, we studied 17 patients with apparently prior infarcted myocardium in combination with 99mTc ventriculography before and after revascularization. In 51 regions with severe asynergy, the percent 201Tl uptake was calculated as the ratio of counts on the segment with asynergy to the maximum counts on the normal segment. Eleven of 14 regions with resting 201Tl redistribution (Group 1) had improved wall motion after revascularization. However, 14 of 37 regions without redistribution also improved (Group 2). Twenty-three regions without redistribution or improved wall motion after revascularization (Group 3) had lower regional 201Tl uptake on their delayed images than those in Groups 1 and 2. Moreover, the initial regional uptake of Group 2 was higher than that of Group 3. These results suggest that redistribution on rest-injected 201Tl scans indicates reversibility of severely asynergic myocardium and that high 201Tl uptake in regions without redistribution may predict improvement in wall motion after revascularization. We conclude that 201Tl uptake may be useful as a marker of viability of severe asynergic regions before revascularization. 
Failure of ursodeoxycholic acid to prevent a cholestatic episode in a patient with benign recurrent intrahepatic cholestasis: a study of bile acid metabolism. Ursodeoxycholic acid was administered to a patient with benign recurrent intrahepatic cholestasis to prevent cholestatic episodes. A detailed study of bile acid metabolism in this patient was carried out in the anicteric and icteric phases before and after ursodeoxycholic acid (750 mg/day) administration. Urinary, biliary and serum bile acids were measured by gas chromatography-mass spectrometry and by high-performance liquid chromatography techniques. During the anicteric phase the daily urinary excretion and serum concentrations of bile acids were within normal ranges, indicating normal hepatic uptake and secretion of bile acids during the cholestasis-free period. Only slight qualitative differences from normal individuals were observed; the relative proportions of deoxycholic acid in the bile and serum were higher, and 12-oxo-lithocholic acid was the predominant urinary bile acid. During the icteric phase a marked increase in the urinary excretion of primary bile acids and C-1, C-2, C-4 and C-6 hydroxylated metabolites was found. Serum bile acid concentrations increased before the rise in bilirubin, suggesting an acute disturbance in bile acid transport at the onset of the cholestatic attack. After ursodeoxycholic acid administration in the anicteric phase, bile became enriched with the exogenous bile acid, but little qualitative change was found in the other metabolites present in the urine, serum or bile during the anicteric or icteric phases. Prolonged administration of ursodeoxycholic acid failed to prevent recurrence of a cholestatic episode, suggesting that in benign recurrent intrahepatic cholestasis, oral ursodeoxycholic acid may be of little benefit in the treatment or prevention of cholestasis despite marked enrichment of the bile acid pool with this hydrophilic bile acid. 
Physical and emotional stress associated with components of the infertility investigation: perspectives of professionals and patients. OBJECTIVE: The present study examined patients', nurses', and physicians' perceptions of the physical and emotional difficulty of infertility treatment. DESIGN: A mail survey method was used. PATIENTS, PARTICIPANTS: Participants included 26 patients, 76 nurses, and 71 physicians from infertility clinics in the United States and Canada. MAIN OUTCOME MEASURES: A rating scale measured the physical and emotional difficulty level of 36 components from the infertility investigation. RESULTS: Nurses rated the emotional and physical distress of patients higher than did patients and physicians, whereas patients rated their distress higher than did physicians. Older nurses and physicians inferred lower levels of physical and emotional distress than did their younger counterparts. A greater breadth of experience with infertility treatments was associated with higher ratings of emotional distress by nurses and lower ratings by physicians. CONCLUSIONS: Patients, nurses, and physicians perceive infertility treatment from unique vantage points creating differences in perceptions that have implications for patient care. Factors including era of professional training, stage of life, and changes resulting from advancing technology are viewed as influencing health care professionals' perceptions of infertility distress. 
Renal hemodynamics and the renin-angiotensin-aldosterone system in normotensive subjects with hypertensive and normotensive parents. BACKGROUND AND METHODS. The kidney is important in blood-pressure regulation, but its role in the development of essential hypertension is still subject to debate. We compared renal hemodynamics, measured in terms of the clearance of para-aminohippuric acid and inulin, and the characteristics of the renin-angiotensin-aldosterone system in three groups of normotensive subjects at different degrees of risk for hypertension: 41 subjects with two normotensive parents, 52 with one normotensive and one hypertensive parent, and 61 with two hypertensive parents. The subjects ranged in age from 7 to 32 years. RESULTS. The mean renal blood flow was lower in the subjects with two hypertensive parents than in those with two normotensive parents (mean difference [+/- SE], 198 +/- 61 ml per minute per 1.73 m2 of body-surface area; P = 0.002). Moreover, both the filtration fraction and renal vascular resistance were higher in the subjects with two hypertensive parents (filtration fraction: mean difference, 3.0 +/- 1.1 percentage points; P = 0.006; renal vascular resistance: mean difference, 2.7 +/- 0.8 mm Hg per deciliter per minute per 1.73 m2; P = 0.006). The subjects with two hypertensive parents had lower plasma concentrations of renin (mean difference, 3.3 +/- 1.6 mU per liter; P = 0.03) and aldosterone (mean difference, 111 +/- 36 pmol per liter; P = 0.003) than those with two normotensive parents. The differences could not be explained by the small differences in blood pressure between the groups. The values in the subjects with one hypertensive and one normotensive parent fell between those for the other two groups. CONCLUSIONS. Renal vasoconstriction is increased and renin and aldosterone secretion is decreased in young persons at risk for hypertension. These findings support the hypothesis that alterations in renal hemodynamics occur at an early stage in the development of familial hypertension. 
Acute pulmonary embolism in pediatric patients awaiting heart transplantation. Acute pulmonary embolism with infarction can delay urgently needed heart transplantation and increase the postoperative pulmonary complications. Few data are available concerning pulmonary embolization in the pediatric patient with end-stage congestive heart failure. Sixty-two consecutive pediatric patients awaiting heart transplantation were monitored for evidence of acute pulmonary embolism. Acute pulmonary infarction was documented by ventilation-perfusion scan, pulmonary angiography or pathologic examination in six patients. The prevalence differed by diagnosis; 5 of 36 patients with dilated cardiomyopathy and 1 of 20 patients with congenital heart disease developed acute pulmonary embolism with infarction. No significant difference in age at the time of transplantation evaluation, duration of congestive heart failure, presence of cardiac arrhythmias or degree of cardiac dysfunction was seen between patients with and without pulmonary embolism. Two-dimensional echocardiography failed to detect the presence of an intracardiac thrombus in four of the six patients. Two patients who developed acute pulmonary infarction are alive after successful heart transplantation. The remaining four patients died within 6 weeks of initiation of anticoagulant therapy before transplantation could safely be performed. In summary, pediatric patients with end-stage congestive heart failure are at risk for acute pulmonary embolism. No specific clinical factor identified those patients who developed acute pulmonary infarction. Anticoagulant therapy is strongly recommended in the pediatric patient with poor ventricular function awaiting heart transplantation. 
The role of chronic viral hepatitis in hepatocellular carcinoma in the United States. Although hepatocellular carcinoma is a relatively uncommon tumor in the United States, it is quite common in sub-Saharan Africa and the Far East, where most cases are associated with infection with the hepatitis B virus. We have studied 99 American patients with hepatocellular carcinoma for evidence of hepatitis B or hepatitis C viral infection and compared these findings to those in a group of matched controls with other cancers. The two groups differed in proportion, with hepatitis B surface antigen in serum being significantly higher in patients with hepatocellular carcinoma (7% vs. 0%, p = 0.009). Antibody to hepatitis C virus was also found more frequently in patients with hepatocellular carcinoma (13% vs. 2%, p = 0.002). The relative risk for hepatocellular carcinoma in hepatitis B surface antigen-positive patients was calculated to be 17.3 and for antibody to hepatitis C virus to be 7.3. The attributable fraction of cases related to the hepatitis B surface antigen carrier state was 6.7% and for patients infected with the hepatitis C virus was 11.4%. Approximately three quarters of cases of hepatocellular carcinoma did not have evidence of either hepatitis C or hepatitis B virus infection. These findings provide strong evidence that hepatitis C virus infection is associated with the development of hepatocellular carcinoma, and in the United States may even play a more important role than the hepatitis B virus. 
Compartment syndrome complicating prolonged use of the lithotomy position. Two patients with three postoperative calf compartment syndromes, which followed prolonged lithotomy positioning, will be presented. Potential physiologic mechanisms are described, and a review of current cases in literature are summated. 
Chest pain: an evaluation of the initial diagnosis made by 25 Flemish general practitioners. Twenty-five general practitioners collected information on 318 contacts of patients with a new episode of chest pain, discomfort or tightness. A list of complaints, signs and symptoms were checked, together with the initial diagnosis, made by the GP immediately after the physical examination. The initial diagnosis was compared to a follow-up diagnosis. The gain in certainty was also compared. The GP made a correct initial diagnosis in 82% of patients. In 8% there was a clinically important difference, and seven of 17 episodes of oesophageal disease were missed. For their initial diagnosis, the GP scored 74% certain, 20% uncertain and no diagnosis in 6%. For the final diagnosis, these figures were 88%, 8% and 4%. 
Effects of nonionic versus ionic contrast media on complications of percutaneous transluminal coronary angioplasty. To evaluate the effect of contrast agents on percutaneous transluminal coronary angioplasty (PTCA) complications, 913 patients undergoing 1,058 separate PTCA procedures were prospectively randomized to receive either nonionic iopamidol (Isovue-370) [n = 507 PTCA procedures] or ionic contrast media, meglumine sodium diatrizoate (Renografin-76) [n = 551 PTCA procedures]. Angioplasty operators, technicians, nurses and patients were blinded to the agent used. All patients were pretreated with 0.6 mg of atropine sulfate intravenously before any contrast injections. Hypotension (mean arterial pressure less than 65 mm Hg associated with contrast injections) occurred during 8.5% of PTCA procedures in which the patients were receiving iopamidol and during 9.5% of the procedures in which the patients were given diatrizoate (difference not significant). Bradycardia (heart rate of less than 40 beats/min associated with contrast injections) developed during 5.7% of procedures when patients were given iopamidol and during 5.1% of procedures when patients were given diatrizoate (difference not significant). The need for additional atropine or temporary pacing during the procedure was similar for patients given iopamidol and diatrizoate. The overall incidence of ventricular tachycardia or fibrillation, or both, during the procedure occurred less frequently when iopamidol was used compared with diatrizoate (1 vs 2.5%, p = 0.045). These serious ventricular arrhythmias were attributable to contrast injections in 0.6% of the PTCA procedures when iopamidol was given and in 2.0% of the cases in which diatrizoate was the contrast agent (p = 0.09). Only 1 patient had an allergic reaction to the contrast agent, and this was in a patient who received iopamidol. 
Monocrotaline-induced angiogenesis. Differences in the bronchial and pulmonary vasculature. Vascular corrosion casting was used to search for angiogenesis in the blood vessels of the lungs of rats given monocrotaline. Animals treated with monocrotaline had new well-differentiated arteries and veins on their pleural surfaces. Animals not treated had no large vessel on their pleural surfaces. Animals receiving monocrotaline had capillaries around major arteries that were more dense, widened, and less tubular than normal. These capillaries occasionally occurred in sheets and had blind endings. The control animals had delicate, uniform, tubular capillaries. Alveolar capillaries in both groups showed no evidence of increase in size or number or change in shape. Light microscopy confirmed the finding of new vessels found with the casts. The finding of angiogenesis on the pleural surface and in the bronchovascular bundle, but not in the alveolar capillaries, suggests a basic difference in how these capillary beds respond to angiogenic stimuli. If alveolar capillaries are unable to undergo angiogenesis, concepts of lung development and tumor growth may be significantly altered. The lung may be a unique organ to study angiogenesis because of the different angiogenic potential of its two circulations. Study of these differences may lead to better understanding of inhibition of angiogenesis. 
Pancreaticobronchial fistula causing lung abscess: case report and brief discussion of the literature. A case report of a patient with an abscess of the lung caused by a pancreaticobronchial fistula is presented. The patient was treated by pulmonary resection and distal pancreatectomy-splenectomy. 
Valproate-induced coma with ketosis and carnitine insufficiency. We observed two patients who developed coma following administration of valproate in dosages of 32 to 40 mg/kg per day. Valproate levels were within the therapeutic range, and results of liver function studies were normal. Both patients had ketosis and adipic aciduria. Plasma free carnitine levels were decreased during coma and after recovery. One patient excreted ethylmalonic acid, butyrylcarnitine, and glutarylcarnitine during and after resolution of coma, suggesting a multiple acyl coenzyme A dehydrogenation defect. Low serum carnitine levels may predispose patients to development of altered consciousness when treated with valproate. 
The kissing balloon technique with two over-the-wire balloon catheters through a single 8-French guiding catheter. Some of the newer over-the-wire coronary angioplasty catheters have shaft sizes of 3.0 French (F) or less. The inner diameter of modern 8-F guiding catheters is large enough to accommodate two of such balloon catheters. We report a kissing balloon procedure with two over-the-wire catheters through a single 8-F guiding catheter. 
Autotransplantation of dispersed pancreatic islet tissue combined with total or near-total pancreatectomy for treatment of chronic pancreatitis. Chronic pancreatitis is difficult to treat in patients with a nondilated duct. Patients experiencing intractable pain unresponsive to or judged untreatable by lesser procedures must decide between total pancreatectomy and resultant diabetes or a continuation of their pancreatitis. From 1977 through 1990, 26 patients underwent extensive pancreatectomy and dispersed pancreatic islet tissue autotransplantation for treatment of chronic pancreatitis pain and prophylaxis of surgical diabetes. Of these 26 patients, total (Whipple) or near-total (greater than 95%) pancreatectomy was performed in 24 patients. Of these 24 patients, pain relief could be assessed in 21 patients at 5 to 155 months (mean, 5.7 years), and 19 patients (90%) reported partial or complete remission. Of the patients who underwent total or near-total pancreatectomy, islets were injected intraportally in 22 patients and into the renal subcapsule in two patients. The latter two patients have required insulin since surgery. Of the other 22, one patient died from a complication of the pancreatectomy. Nine of the 21 evaluable recipients of intraportal islet autografts were insulin independent for at least several months after surgery. Five patients are currently insulin independent at 6 years, 4 years, 1.5 years, 9 months, and 5 months after surgery. Of the other four patients, one patient died insulin independent at 6 years, and three patients required insulin beginning 8 to 18 months after surgery. Insulin independence correlated with the number of islets recovered, which in turn correlated inversely with the degree of pancreatic fibrosis. Of our four most recent patients, three patients had mildly to moderately fibrotic glands, and higher numbers of islets were obtained. After total (Whipple) pancreatectomy, these three patients are insulin independent. A liver biopsy was performed in one patient 8 months after total pancreatectomy and islet autotransplantation; numerous clusters of islet cells staining strongly for insulin and glucagon were detected within portal triads on both wedge and needle biopsy specimens. Morbidity related to the intraportal-dispersed pancreatic islet tissue transplantation was low (no disseminated intravascular coagulation, significant portal hypertension, or hepatic dysfunction). Islet autotransplantation can be an effective and safe adjunct to extensive pancreatic resection for those patients who risk surgical diabetes for relief of their chronic pancreatitis pain. 
Recombinant tissue-type plasminogen activator followed by heparin compared with heparin alone for refractory unstable angina pectoris. Patients with unstable angina pectoris who remain symptomatic despite medical treatment are at high risk of death and myocardial infarction. The incidence of refractory unstable angina was examined in a consecutive series of 103 patients who received conventional medical treatment with nitrates, beta blockers, calcium antagonists and aspirin. During 48 hours of continuous electrocardiographic monitoring, 24 patients had greater than or equal to 1 anginal attack, 5 of whom had both painful and painless ischemic episodes. In these 24 patients with unstable angina refractory to conventional medical treatment, the short-term efficacy of recombinant tissue-type plasminogen activator (rt-PA) followed by heparin was assessed and compared with heparin alone in a randomized double-blind trial. Recurrences of ischemic attacks during a 72-hour follow-up period were documented in 9 of the 12 patients given heparin alone. All patients experienced at least 1 symptomatic ischemic episode and 1 patient had both painful and painless ischemia. No patient given rt-PA plus heparin had either symptomatic or asymptomatic ischemic attacks during follow-up. Kaplan-Meier curves analysis demonstrated a significantly higher probability of being ischemia free in the group of patients treated with rt-PA followed by heparin than in the group treated with heparin alone (p less than 0.01). Quantitative coronary arteriography failed to reveal any significant changes of ischemia-related lesions before and after each treatment. This study demonstrates that the combination of rt-PA and heparin has a greater protective effect than heparin alone in treating recurrent ischemic episodes in patients with refractory unstable angina. 
Preoperative high-dose leucovorin/5-fluorouracil and radiation therapy for unresectable rectal cancer. Twenty patients with primary or recurrent unresectable rectal cancer limited to the pelvis were entered on a Phase I trial of preoperative pelvic radiation therapy (RT) (5040 cGy) and two cycles of combined high-dose leucovorin (LV) and 5-fluorouracil (5-FU), followed by surgery and ten cycles of postoperative LV/5-FU (sequential). Maximum tolerated doses (MTD) were determined for preoperative combined LV/5-FU and RT and for postoperative sequential LV/5-FU. 5-FU was escalated 50 mg/m2 while the LV remained constant at 200 mg/m2. The initial doses of 5-FU were combined LV/5-FU and RT (200 mg/m2) and sequential LV/5-FU (325 mg/m2). The median follow-up time was 14 months. The resectability rate was 89%, and the pathologic complete response rate was 21%. The MTD for combined LV/5-FU and RT was 300 mg/m2; therefore, the recommended dose of 5-FU is 250 mg/m2. The recommended dose of 5-FU for sequential LV/5-FU is 375 mg/m2. The dose-limiting toxicities in this trial were diarrhea, tenesmus, increased bowel movements, dysuria, and myelosuppression. For the six patients who received 5-FU at the recommended dose level, the median low counts were leukocyte count, 3.7/microliters (range, 2.4 to 4.9/microliters); hemoglobin, 9.0 g/dl (range, 8.2 to 11.9 g/dl); and platelet count (X1000), 146/microliters (range, 89 to 182/microliters). The incidence rate of any Grade 3 toxicity was 17% (diarrhea and frequent bowel movements). The recommended doses of 5-FU used in this protocol were well tolerated. Because there was a long delay before optimal doses of 5-FU could be delivered, the authors do not recommend that high-dose LV be used in conjunction with combined 5-FU and RT with the treatment regimen as currently designed. However, because the resectability and complete response rates were higher than those previously reported for preoperative RT alone, the authors are encouraged by the combined technique approach. New trials are currently being undertaken to determine if the use of a low-dose LV regimen is more tolerable. 
Siriraj stroke score and validation study to distinguish supratentorial intracerebral haemorrhage from infarction. OBJECTIVES--To develop a simple, reliable, and safe diagnostic tool for acute stroke syndromes in a setting where computerised brain scanning was not readily available and to validate its accuracy with regard to pathological types of stroke. DESIGN--13 clinical variables that potentially might differentiate supratentorial cerebral haemorrhage from infarction were recorded and tested by multivariate analysis in a prospective study of 174 patients with acute stroke. In developing the Siriraj stroke score stepwise discriminant analysis of the variables was followed by a linear discriminant equation to differentiate between supratentorial haemorrhage and infarction. The score obtained was validated against scores in 206 other patients with stroke, computerised brain scans being used for definitive diagnosis. SETTING--Siriraj Hospital Medical School, Mahidol University, Bangkok. SUBJECTS--Prospective study: 174 consecutive patients with acute supratentorial stroke syndrome (not subarachnoid haemorrhage) admitted to Siriraj Hospital during 1984-5; validation study: 206 patients admitted to Siriraj Hospital or another hospital for supratentorial intracerebral haemorrhage or infarction. RESULTS--The Siriraj stroke score was developed and calculated as (2.5 x level of consciousness) + (2 x vomiting) + (2 x headache) + (0.1 x diastolic blood pressure) - (3 x atheroma markers) - 12. A score above 1 indicates supratentorial intracerebral haemorrhage, while a score below -1 indicates infarction. The score between 1 and -1 represents an equivocal result needing a computerised brain scan or probability curve to verify the diagnosis. In the validation study of the Siriraj stroke score the diagnostic sensitivities of the score for cerebral haemorrhage and cerebral infarction were 89.3% and 93.2% respectively, with an overall predictive accuracy of 90.3%. CONCLUSION--The Siriraj stroke score is widely accepted and applied in hospitals throughout Thailand as a simple and reliable bedside method for diagnosing acute stroke. 
Differential modulation by the stress axis of ethanol withdrawal seizure expression in WSP and WSR mice. Withdrawal from both acute and chronic ethanol (EtOH) exposure is associated with increased neural excitability and increased activity of the hypothalamic-pituitary-adrenal axis. There is some evidence that glucocorticoids are necessary for EtOH withdrawal seizure expression. Lines of mice that were selected for severe (WSP) and minimal (WSR) EtOH withdrawal (as estimated from handling-induced convulsion scores) have been shown to differ in their stress response following an acute dose of EtOH. In this study we provide evidence that these lines of mice also differ in their sensitivity to the excitatory effects of glucocorticoids. EtOH withdrawal seizures of WSP mice were significantly increased by chronic and acute corticosterone treatment, whereas those of the WSR mice were unaffected. Neural excitability was decreased in the WSP mice when aminoglutethimide, a glucocorticoid synthesis blocker, was administered. Thus, it appears that genetic differences in EtOH withdrawal seizure severity may be due, in part, to differences in sensitivity to the excitatory effects of glucocorticoids. 
Treatment of critically ill patients with sepsis of unknown cause: value of percutaneous cholecystostomy. Because of the difficulty in diagnosing acute cholecystitis in critically ill patients with severe intercurrent illness by clinical and imaging methods or percutaneous aspiration of the gallbladder, a trial of percutaneous cholecystostomy was performed in 24 patients in the intensive-care unit with persistent, unexplained sepsis after a complete clinical, laboratory, and radiologic search showed no alternative source of infection. Persistent high fevers, despite antibiotic therapy, were present in all patients, with elevated WBC count in 18 patients, vague abdominal tenderness in 11, and septic shock requiring vasopressors in 15. Sonographically, all patients had distended, spherical gallbladders, six had gallstones, eight had wall thickening, three had pericholecystic fluid, and four had Murphy's sign. All patients were seen by a senior abdominal surgeon, who agreed to a trial of percutaneous cholecystostomy. Fourteen patients (58%) responded to percutaneous cholecystostomy, as evidenced by a decrease in WBC count, defervescence, and the ability to be weaned off vasopressors. Bile cultures were positive in four patients. Ten patients (42%) did not respond to percutaneous cholecystostomy; five eventually died of unrelated causes. A respiratory source of infection was eventually found in three of these 10 patients, with no proved source of infection in the remainder. No complications related to catheter insertion occurred in this group of patients. Bile leaks occurred in two patients when the percutaneous cholecystostomy catheter was removed, but without serious consequence. Our experience suggests that a lower threshold for performing percutaneous cholecystostomy in this difficult clinical subset of patients is worthwhile. 
Impaired formation of the ternary insulin-like growth factor-binding protein complex in patients with hypoglycemia due to nonislet cell tumors. In some subjects with hypoglycemia associated with tumors of mesenchymal origin, high insulin-like growth factor-II (IGF-II) levels have been described in serum and in the tumors. Tumor IGF-II of 10-15 kDa circulates in a 60-kDa complex, in contrast to the ternary 150-kDa complex in which serum IGFs normally circulate together with the IGF-binding subunit (IGFBP-3) and the acid-labile subunit (alpha-subunit). This study examines the molecular distribution and complex-forming activity of the components of the ternary complex in the serum of subjects with mesenchymal tumor hypoglycemia. Total serum IGFBP-3 levels were 60% of normal in tumor patients and appeared at 60 kDa on gel chromatography, shifting after tumor removal to 150 kDa. Total alpha-subunit levels were 40% of normal in patients with tumors, increasing after tumor removal to 70% of normal and changing in elution profile from a peak typical of uncomplexed alpha-subunit to the normal broad peak representing both complexed and uncomplexed alpha-subunit. Although low by RIA, alpha-subunit activity in a ternary complex formation assay was normal, indicating that the ability of free alpha-subunit in the patients' circulation to combine with exogenous IGFBP-3 plus IGF-I was not impaired. In contrast, in an assay that tested the ability of IGF-IGFBP complexes in the patients' circulation to combine with pure alpha-subunit, complex formation activity was 75-85% below normal in preoperative sera, despite low normal IGFBP-3 levels. Therefore, the cause of hypoglycemia in these patients may be the inability of complexes between the abnormal tumor IGF-II and IGFBP-3 to be sequestered in the biologically inactive ternary complex. 
The significance of portal vein thrombosis after distal splenorenal shunt. The aims of this study were to determine the incidence of portal vein thrombosis after the distal splenorenal shunt, to identify any predictive factors, and to assess the clinical significance of this complication. Preoperative and postoperative angiograms and clinical evaluation were reviewed in 124 patients who underwent distal splenorenal shunts. Total and partial portal vein thrombosis were seen on 13 (10.5%) and 22 (17.7%) postoperative angiograms, respectively. The only preoperative variable correlating with development of portal vein thrombosis was portal venous perfusion, which was significantly lower in patients with than in those without portal vein thrombosis. In six of 10 patients with postoperative pancreatitis, portal vein thrombosis developed. The frequency of early postoperative complications was significantly greater in patients with total portal vein thrombosis than in those with partial or no thrombosis. Long-term follow-up has shown no significant effects of portal vein thrombosis on late ascites, encephalopathy, or survival. 
Iatrogenic epidermoid cyst of the parotid region following ear surgery. Iatrogenic implantation of squamous epithelium may result in formation of an epidermoid cyst. These cysts have been described in various sites around the head and neck following otological procedures. A case of iatrogenic epidermal cyst in the parotid region following repeated myringoplasty is reported. The clinical features and differential diagnosis are discussed. 
Fatal and other major complications of endoscopic sinus surgery. Endoscopic sinus surgery has become an acceptable technique for the treatment of chronic sinus disease. This report analyzes five complications which came to my attention. Two cases were orbital:1 bilateral blindness due to damage of the optic nerves, and 1 damage of medial rectus muscle. The other 3 cases were intracranial:two cribriform plate damage with frontal lobe injury and hematoma, and 1 damage of the anterior cerebral artery, resulting in death. This rather novel technique, especially when used by less-experienced surgeons, has major complications similar to what has been reported with the traditional intranasal sphenoethmoidectomy. Knowledge of anatomy, good training, and meticulous surgical technique are very important. Endoscopic sinus surgery in patients with extensive pathology should be used with caution, especially if general anesthesia is selected or if excessive bleeding occurs. It would be beneficial to otolaryngologists to have previous experience in the traditional technique before adopting endoscopic sinus surgery to their armamentarium. Even then, major complications may occur in the hands of very experienced surgeons. Early recognition and proper management of these complications are of utmost importance in order to minimize disability or prevent death. 
Brachial plexus anesthesia for outpatient surgical procedures on an upper extremity We retrospectively reviewed 543 brachial plexus blocks performed on 526 outpatients. Most (98%) of the blocks were performed by means of the axillary approach. Various techniques were used, including paresthesia, transarterial fixation, nerve stimulation, or a combination of techniques; a high success rate was achieved with each of them. Only 7% of the blocks were incomplete and thus necessitated either general anesthesia or block supplementation with thiopental sodium and nitrous oxide. No persistent neurologic deficit was ascribed to the anesthetic technique. This review indicates that brachial plexus block, especially with use of the axillary approach, is a safe and effective option for outpatient surgical procedures on an upper extremity. 
Valproate-induced coma with ketosis and carnitine insufficiency. We observed two patients who developed coma following administration of valproate in dosages of 32 to 40 mg/kg per day. Valproate levels were within the therapeutic range, and results of liver function studies were normal. Both patients had ketosis and adipic aciduria. Plasma free carnitine levels were decreased during coma and after recovery. One patient excreted ethylmalonic acid, butyrylcarnitine, and glutarylcarnitine during and after resolution of coma, suggesting a multiple acyl coenzyme A dehydrogenation defect. Low serum carnitine levels may predispose patients to development of altered consciousness when treated with valproate. 
Flecainide acetate treatment of paroxysmal supraventricular tachycardia and paroxysmal atrial fibrillation: dose-response studies. The Flecainide Supraventricular Tachycardia Study Group. The dose-response relations for efficacy and tolerance of the antiarrhythmic drug flecainide acetate were studied in 28 patients with paroxysmal supraventricular tachycardia (Group 1) and 45 patients with paroxysmal atrial fibrillation or flutter (Group 2). Recurrent symptomatic tachycardia was documented with use of transtelephonic electrocardiographic recording. Patients received flecainide in doses of 25, 50, 100 and 150 mg twice daily and placebo for 1 month treatment periods. Among 14 patients in Group 1 who qualified for efficacy analysis, 4 (29%) had no tachycardia while taking placebo. The number with no tachycardia increased with progressively larger flecainide doses; with the 150 mg twice daily dose, 12 (86%) of 14 patients had no tachycardia (p less than 0.01 for overall differences among all treatments). Among 28 patients in Group 2, 2 (7%) had no tachycardia while taking placebo. The number with no tachycardia also increased with progressively larger flecainide doses; with the 150 mg twice daily dose, 17 (61%) of 28 patients had no tachycardia (p less than 0.01 for overall differences among all treatments). Noncardiac adverse experiences were the leading cause of premature study discontinuation during flecainide treatment periods (five patients in Group 1 and six patients in Group 2). 
Effects of H1-antihistamine drug regimen on histamine release by nonlesional skin mast cells of patients with chronic urticaria. Profiles of compound 48/80-induced histamine release (HR) from mast cells of uninvolved skin from patients with chronic urticaria (CU) and from a normal control (NC) group were compared, and the effects of anti-H1 medications were assessed versus placebo. Then, patients with CU (15) and NC subjects (10) were randomly assigned to take either hydroxyzine (100 mg/day), terfenadine (120 mg/day), or placebo for 28 days. The effects of such treatment on the clinical response and on the profile of compound 48/80-induced HR during a 4-hour period were analyzed. Treatment with hydroxyzine in patients with CU improved the clinical symptoms and modified the profile of HR; more histamine was recovered at 1 hour (p less than 0.05) and 2 hours (p less than 0.05), as compared with baseline. Terfenadine and placebo had no effect on the clinical response or on the profiles of HR. In the NC group, the amounts of histamine recovered at 1 hour after challenge with compound 48/80 were lower than amounts of the pretherapy values (p less than 0.01). It could be concluded that (1) the profile of HR in patients with CU is reproducible during a period of 28 days, (2) only hydroxyzine modifies both the clinical response and the profile of HR, and (3) anti-H1 compounds decrease the HR in the NC group. 
Lysis of intraventricular hematoma with tissue plasminogen activator. Case report. A 42-year-old woman suffered a severe intracerebral and intraventricular hemorrhage from a ruptured anterior cerebral artery aneurysm. Evacuation of the frontal hematoma and clipping of the aneurysm was performed but the intraventricular blood clot persisted, causing ventricular dilatation and high intracranial pressure (ICP) 24 hours after surgery despite external ventricular drainage. Over this period of time the patient's clinical condition improved from Grade V to Grade IVb (World Federation of Neurological Surgeons classification). The intraventricular hematoma was lysed with a total of 8 mg recombinant tissue plasminogen activator injected directly into the ventricles on the 1st and 2nd postoperative days, resulting in rapid normalization of ventricular size and ICP. The patient has since made a substantial recovery and has been able to return home. 
Neurophysiological observations on the effects of botulinum toxin treatment in patients with dystonic blepharospasm. Botulinum toxin treatment improves dystonic blepharospasm by inducing transient paresis of the orbicularis oculi muscle. It is not known if it also reduces the enhanced brainstem neuronal excitability found in this disorder. We have performed conventional electromyography (EMG) and blink reflex excitability studies on fifteen patients with blepharospasm before and after botulinum toxin treatment. Denervation signs were found with needle EMG in all treated muscles. Amplitude of the facial compound muscle action potential (CMAP) and R1 response was reduced after botulinum toxin injections. In blink reflex excitability studies, the recovery of R2 response was enhanced after treatment even when patients were tested at the time of maximal benefit from botulinum toxin injections. The results suggest that there is little influence of botulinum toxin treatment upon the enhanced excitability of brainstem interneurons in patients with blepharospasm. 
Quadrilateral space syndrome: diagnosis and operative decompression technique. We present a series of five patients with quadrilateral space syndrome. All patients had the diagnosis made on the basis of (1) tenderness over the quadrilateral space, (2) paresthesia over the lateral shoulder and upper posterior arm, and (3) deltoid weakness associated with decreased shoulder abduction. A history of trauma was present in each patient. The operative technique described utilizes a cosmetically acceptable incision and is without the need to divide the deltoid from its origin on the scapular spine. The technique minimizes postoperative bleeding and facilities rehabilitation. Arteriography of the posterior circumflex humeral artery was not found necessary to make the diagnosis of axillary nerve entrapment in the quadrilateral space. 
Comparative efficacy and safety of intravenous and oral administration of a TRH analogue (RX77368) in motor neuron disease. Ten consecutive patients with motor neuron disease (MND) who had bulbar symptoms received one or two intravenous doses followed by increasing oral doses of a TRH analogue (RX77368). Similar improvements in speech, swallowing and in tongue and jaw movements were seen after iv and oral administration in nine, five and eight patients respectively. The initial time course of improvement correlated with increasing plasma levels of the drug, but most clinical effects persisted when the levels decreased and became undetectable after 24 hours. The oral solution was tasteless and had no, or minimal, side effects. 
Chagas' cardioneuropathy: effect of ganglioside treatment in chronic dysautonomic patients--a randomized, double-blind, parallel, placebo-controlled study. To date, there is no effective pharmacologic treatment for Chagas' cardioneuropathy, one of the most common causes of congestive heart failure and sudden death in the world. Fifty-eight adults with positive serology for Chagas' disease and abnormal autonomic nervous system tests participated in this placebo-controlled clinical trial with Cronassial (mixed gangliosides), 40 mg daily intramuscular injection for 4 or 8 weeks. We measured postural response (heart rate, systolic and diastolic arterial blood pressure changes in response to standing); heart rate changes induced by cough and hyperventilation reflex tests; dizziness on standing; number of stress-induced arrhythmias; and periodic acid-Schiff (PAS)-positive T-lymphocyte percentage in blood samples. Cronassial is safe and significantly improves systolic blood pressure (p = 0.050) and double product responses to postural stress (p = 0.028), hyperventilation heart rate response (p = 0.007), frequency of dizziness episodes (p less than 0.001), number of arrhythmias (p = 0.033), and percentage of PAS-positive T-lymphocyte counts (p less than 0.001) compared with placebo. 
Midline craniectomy for sagittal suture synostosis: comparative efficacy of two barriers to calvarial reclosure. This report quantitatively compares long-term head remolding achieved by two methods for retarding bone reunion after midline craniectomy for sagittal suture synostosis. In one group of six children the adjacent bone edges were overlayed with 1.0-cm-wide U-channel silicone strips, and in the other group, composed of seven patients, a considerably larger extent of the adjacent cranium was covered with silicone sheets. Mean percent change in the cephalic indices of the former group 18 months postoperatively was 9.1% +/- S.D. = 6.7, and of the latter group 23.7% +/- S.D. = 6.0 (p congruent to 0.01). These results indicate that the use of large silicone sheets lead to a significantly greater normalization of cranial proportions. 
Hiccups (singultus): review and approach to management. Hiccups are a common, and fortunately usually transient, benign malady. Occasionally, however, hiccups fail to resolve spontaneously, resulting in patient fatigue and incapacitation and the need for the affected individual to seek medical care for resolution of the problem. The approach to the management of these patients consists of the identification and treatment of serious underlying causes of the episode as well as therapeutic interventions to achieve hiccup resolution. 
The localization and distribution of corticotropin-releasing hormone in the human placenta and fetal membranes throughout gestation. Using immunohistochemical techniques, we have determined the localization and distribution of CRH immunoreactivity (CRH-IR) in the human placenta, fetal membranes, decidua, and umbilical cord. Tissues were obtained at 6-8 weeks of pregnancy, at term, in association with premature birth, and from patients with pregnancy-induced hypertension or diabetes mellitus. A polyclonal antibody to the epithelial cell marker cytokeratin was used to identify trophoblast cells. CRH-IR was not detected in placenta or decidua at 6-8 weeks gestation. In tissues obtained after idiopathic premature delivery after 21 weeks gestation, positive CRH staining was found in placenta in syncytiotrophoblast and intermediate trophoblast, but not cytotrophoblast. CRH-IR was present in intermediate trophoblast cells that had invaded maternal blood vessels in decidua basalis. In the fetal membranes, CRH-IR was localized in the epithelium and subepithelial cells of amnion, in the trophoblast layer, in some cells of the reticular and cellular layers of chorion, and in some stromal cells and invasive trophoblast cells of decidua. CRH-IR was found in the amniotic epithelium of the umbilical cord and in the musculature of the umbilical vessels. This pattern of distribution of CRH-IR was found in tissues from 21 weeks gestation to term and postterm, and was similar in tissues examined from patients with pregnancy-induced hypertension and diabetes mellitus. These results show clearly that in placenta and membranes, CRH is localized primarily to syncytiotrophoblast and intermediate trophoblast, but not to cytotrophoblast cells. We suggest that the localization of CRH-IR is consistent with CRH affecting paracrine/autocrine interactions within the placenta, fetal membranes, and decidua that may be involved in the maturation of the fetal hypothalamic-pituitary-adrenal axis and in the stimulus and maintainance of labor. 
The relationship among canine brain temperature, metabolism, and function during hypothermia. Cerebral protection by hypothermia is commonly attributed to cerebral metabolic suppression. However, at temperatures below 28 degrees C, the relationship of temperature to cerebral metabolic rate of oxygen consumption (CMRO2) has not been well characterized. Accordingly, the relationship between brain temperature and CMRO2 was determined in eight dogs during cooling from 37 to 14 degrees C while the EEG was continuously monitored. Cardiopulmonary bypass was initiated and control measurements were made at 37 degrees C during anesthesia with nitrous oxide 50-60% inspired and morphine sulfate 2 mg.kg-1 intravenously (iv). Upon cooling to 27 degrees C, the nitrous oxide was discontinued and the morphine was antagonized with naloxone 2 mg iv. Measurements were repeated at 27, 22, 18, and 14 degrees C and in four dogs again at 37 degrees C after nitrous oxide 50-60% had been reestablished at 27 degrees C along with administration of morphine sulfate 2 mg.kg-1. For each temperature interval, the temperature coefficient (Q10) for CMRO2 was calculated (Q10 = CMRO2 at x degrees C divided by CMRO2 at [x - 10] degrees C). Between 37 and 27 degrees C the Q10 was 2.23, but between 27 and 14 degrees C the mean Q10 was doubled to 4.53. With rewarming to 37 degrees C, CBF and CMRO2 returned to control levels, and brain biopsies revealed a normal brain energy state. During cooling, the EEG developed burst suppression at or below 22 degrees C. With further cooling, the periods of suppression increased; however, burst activity continued in seven of eight dogs even at 14 degrees C. 
Prognostic factors for local recurrence in the conservatively treated breast cancer patient: a cautious interpretation of the data. Between 1962 and 1984, a total of 433 patients were treated at Yale-New Haven Hospital with conservative surgery and radiation therapy (CS + RT) to the intact breast. As of January 1990, with a minimum assessable follow-up of 5 years and a median follow-up of 8.21 years, there have been a total of 50 breast recurrences resulting in a 5-year actuarial breast recurrence rate of 8%. Of all clinical factors tested, young age was the most significant prognostic factor for local recurrence (P less than .03). In addition, patients with pathologically involved lymph nodes were noted to have a lower local recurrence rate than patients with pathologically negative axillae (P less than .05). These findings were especially notable given the fact that the node-positive group had a higher percentage of T2 tumors and a higher percentage of patients in the young age group. These paradoxical findings, however, may be explained by the fact that 88% of the node-positive patients underwent adjuvant systemic therapy in the form of either systemic chemotherapy or hormonal therapy, while only 8% of node-negative patients underwent any adjuvant systemic therapy. When analyzed as a function of adjuvant therapy, those patients receiving adjuvant therapy had a lower local recurrence rate than those patients not receiving adjuvant therapy (P less than .08). We conclude that adjuvant systemic therapy impacts on the ipsilateral breast recurrence rate in patients treated with CS + RT. The implications of this study in light of the widespread use of adjuvant systemic therapy are discussed. 
Pathophysiology of sciatica. The exact pathophysiologic mechanisms behind sciatica are incompletely known; however, compression of spinal nerve roots is known to be correlated to both pain and neural dysfunction in a segmental distribution of that specific nerve root. Compression per se may impair the transport of nutrients to the nerve tissue in such a way that affects the nerve root function. There also might be a local affect on nerve roots or root sleeves by substances leaking from the degenerated intervertebral discs. 
Surgical management of extracranial vertebral artery occlusive disease. Thirty-seven consecutive patients underwent vertebral artery (VA) reconstruction over a 6 years period (1983-1989). Detailed neurologic, medical, and angiographic information was obtained for all patients. Indications for surgery were as follows: (1) stenosis of VA with symptoms of vertebrobasilar insufficiency; (2) very tight stenosis (greater than 75%) of the dominant VA with stenosis or occlusion of the contralateral VA; (3) very tight stenosis of VA with bilateral occlusion of the internal carotid artery (ICA); (4) very tight stenosis of VA with homolateral ICA lesion eligible for simultaneous repair; (5) very tight stenosis of VA and very tight stenosis of the homo or contralateral carotid siphon. There were 15 isolated vertebral lesions (group I), and 22 were VA lesions associated with lesions of the supraaortic trunks which were simultaneously treated (group II). The reconstructions of the first portion of the VA were 30 (12 of group I and 18 of group II) and reimplantation of the VA into the common carotid artery was the procedure of choice. There were 7 revascularizations of the third portion of the VA at C1-C2 level (3 of group I and 4 of group II): carotid-vertebral bypass, using an autogenous vein graft, was the procedure of choice. Three patients in group II died in the immediate postoperative period from myocardial infarction but no patient presented immediate postoperative neurologic deficits. All symptomatic patients but one were relieved of their symptoms in a median follow-up of 31 months. No postoperative complications were observed. Long-term results were satisfactory in all the 28 patients at their last follow-up visit. 
Transesophageal color Doppler echocardiography of the normal St. Jude Medical mitral valve prosthesis. Transesophageal color flow Doppler findings are reported in 36 patients with a St. Jude Medical mechanical mitral valve prosthesis who had no auscultatory evidence for prosthetic valve dysfunction. Multiple jets consistent with mitral regurgitation originating from the central and lateral portion of the prosthesis were found in all patients. Maximum jet length ranged from 11 to 51 mm (mean 21 +/- 9 mm). Maximum jet area ranged from 0.2 to 4.1 cm3 (mean 1.2 +/- 0.9 cm2). The color M-mode Doppler interrogation showed two distinct components of the regurgitant jet: brief early systolic flow consistent with valve closure followed by holosystolic regurgitant flow consistent with transvalvular leakage. Four patients (11%) had a maximum regurgitant jet length exceeding 30 mm and absence of early systolic closure regurgitant flow by M-mode color imaging, suggesting clinically silent paravalvular leakage. Two pin-sized paravalvular suture line defects were confirmed in one patient at cardiac transplantation. We conclude that transesophageal echocardiography is a highly sensitive method for detection of mitral regurgitation in the St. Jude Medical mitral prosthesis. Clinically silent paravalvular leakage should be suspected if the maximum jet length exceeds 30 mm and color M-mode interrogation fails to demonstrate an early systolic closure regurgitant flow component. 
Factors in recent reductions in liver cirrhosis deaths. Since the mid-1970s, there have been substantial declines in liver cirrhosis deaths in many Western countries following a long period of increases. There is variability in the pattern of changes observed: in a sample of 29 countries between 1974 and 1982-83, seven countries showed a significant linear decline, three revealed a curvilinear pattern, increases were observed in six and the rest (13) showed no notable changes. Although reductions in per capita consumption of alcohol may be a contributing factor, these reductions do not seem to account for all of the decreases in cirrhosis deaths that have been observed. Among other factors that might contribute, changes or increases in treatment for alcohol abuse and AA membership have been most strongly linked to these declines; changes in patterns of consumption, dietary habits, prevention efforts and reduced exposure to predisposing factors may also be involved. In view of the importance of these declines for the understanding and prevention of alcohol problems, further research on this issue, perhaps involving international collaborative studies, is needed. 
Ultrastructural study of glandular epithelium in adenomyosis in comparison with those of proliferative endometrium and well-differentiated endometrial cancer. Adenomyotic glandular tissue from five patients underwent electron microscopic investigation to observe its ultrastructural characteristics. The adenomyotic epithelium was compared with that of proliferative normal epithelium (two patients) and well-differentiated endometrial adenocarcinoma (two patients). The results revealed that morphologically the adenomyotic glandular epithelium is somewhat less differentiated than proliferative endometrium and that its cytoplasmic organelles have some similarities with those of endometrial cancer. Whether these similarities predispose the adenomyotic glandular tissue to malignant degeneration remains to be elucidated. 
Initial clinical experience with a 48 by 48 element biplane transesophageal probe. Recent technologic advances in ultrasound have resulted in the capability of transesophageal echocardiographic imaging in both transverse and longitudinal planes. Previous biplane probes suffered from inferior images because of reduced scan elements. We evaluated the utility of a prototype 48 X 48 element biplane transesophageal probe in 23 consecutive patients. Examinations were well tolerated with no side effects. In comparison to the single transverse plane, imaging with the longitudinal plane gave superior information on prosthetic valve pathology, atrial septal abnormalities, and pathoanatomy of the ascending aorta and mitral valve. Complementary information was provided by the longitudinal plane in patients with endocarditis and vegetations and in mitral protheses. Images obtained with this 48 X 48 element biplane probe along with color and spectral Doppler information were not perceptibly inferior to those obtained by single-plane probes. In conclusion, biplane transesophageal echocardiography with a 48 X 48 element probe indicates a great potential for enhanced three-dimensional understanding of cardiac pathology and diagnostic yield in specific pathologies. 
Klippel-Trenaunay syndrome: the risks and benefits of vascular interventions. Our experience with Klippel-Trenaunay syndrome (KTS), a rare congenital malformation, has increased considerably in recent years and now includes 144 patients (65 male and 79 female patients). Hemangioma was present in 137 patients (95.1%), varicosity in 110 (76.4%), and hypertrophy of the soft tissues or bones in 134 (93.1%). In most patients (71.5%) the disease involved one lower extremity. Diagnostic workup included roentgenogram to document limb length discrepancy, noninvasive arterial and venous evaluation, contrast venography, and nuclear magnetic resonance imaging. Most patients did well without treatment or with elastic compression only. Surgical treatment for the vascular malformation in KTS is rarely needed and it continues to be controversial. To evaluate the risks and benefits of vascular interventions, we examined in detail the clinical histories of nine patients who in the last decade underwent operation for a vascular malformation of the lower extremity. In seven patients we removed varicose veins or resected hemangioma of the lower extremity. Although none was cured, all five who underwent resection of varicose veins and one of the two patients who underwent resection of a hemangioma improved. Two additional patients, however, who underwent resection of varicose veins in another institution had worsening of the symptoms. In one patient we performed deep venous reconstruction for atresia of the superficial femoral vein, using the contralateral saphenous vein. Such operation in KTS has not been reported previously. The patient has a patent graft with a competent valve and clinical improvement 6 months after the operation. Although patients with severe chronic venous insufficiency, disturbing cosmetic appearance, or complications of hemangioma may benefit from surgical treatment, detailed preoperative imaging of the extremity and pelvis with magnetic resonance imaging and contrast venography is needed to decrease complications. Rarely, reconstruction for atresia or hypoplasia of the deep veins may be needed. 
Role of platelet function in symptomatic cerebral vasospasm following aneurysmal subarachnoid hemorrhage. To evaluate the role of platelet function in the pathogenesis of cerebral vasospasm, we compared sequential changes of platelet aggregability and beta-thromboglobulin and thromboxane B2 concentrations in blood samples from the internal jugular and peripheral vein of 13 patients with aneurysmal subarachnoid hemorrhage. Platelet function in blood from the internal jugular vein tended to be enhanced during days 0-1 but recovered to the normal range during days 2-4. After day 5, platelet function showed various patterns depending on the presence of symptomatic vasospasm. In patients without symptomatic vasospasm, sequential changes were relatively minor, with normal or slightly high values. Patients with symptomatic vasospasm already showed high platelet aggregability during the early stage of vasospasm. The concentration of beta-thromboglobulin increased several days after the onset of vasospasm, reaching 80 ng/ml or more in patients with a poor prognosis. Two of the five patients with symptomatic vasospasm showed markedly high concentrations of thromboxane B2 after day 8. These results suggest that vasospasm activates platelets and promotes aggregability and that the resulting increased tendency for thrombus formation may affect the patient's prognosis during the advanced stage. 
The use of releasable sutures in Molteno glaucoma implant procedures to reduce postoperative hypotony. We used releasable sutures to minimize immediate postoperative hypotony and flat anterior chamber in 19 cases of refractory glaucoma requiring insertion of a single-plate Molteno implant in a one-stage procedure. A slip knot using 7-0 nylon suture was fashioned around the Molteno tube under a lamellar scleral flap. In 18 of the 19 eyes, anterior chamber depth was normal immediately after surgery. 
Prevention of vasospasm by clot removal and intrathecal bolus injection of tissue-type plasminogen activator: preliminary report. In this study, we evaluated the efficacy of postoperative intrathecal injections of tissue-type plasminogen activator (tPA) in preventing cerebral vasospasm in cases with a diffuse severe subarachnoid hemorrhage. All 10 cases were graded Group 3 according to the classification of Fisher and associates, and the CT number (Hounsfield number) of the subarachnoid clot was over 75. After clipping the aneurysm and removing the clot, three cisternal drainage catheters were inserted into both sylvian cisterns and the prepontine cistern, and continuous ventricular drainage was performed routinely. Postoperatively, tPA (0.5 mg/2.5 ml) was infused as a bolus into both basal cisterns and the lateral ventricle twice daily for about 6 days. Angiography and cerebral blood flow studies using single photon emission computed tomography were performed on Day 4 or 5 and between Days 7 and 10 after onset of the hemorrhage. To date, there have been no cases that have shown angiographic vasospasm or delayed ischemic neurological deficits. This preliminary study indicates that the intrathecal bolus injection of tPA produces a marked effect on vasospasm. 
Assessment of current International Federation of Gynecology and Obstetrics staging of vulvar carcinoma relative to prognostic factors for survival (a Gynecologic Oncology Group study). Analysis of 588 patients with vulvar carcinoma delineated four risk groups by the proportional hazards model. Groin node status (laterality and number positive) and lesion diameter were the only two important independent prognostic factors. The 5-year relative survival rates were 98%, 87%, 75%, and 29% for the risk group categories of minimal (negative groin nodes and lesion diameter less than or equal to 2 cm), low (one positive groin node and lesion diameter less than or equal to 2 cm or negative groin nodes and fewer than two lesions less than or equal to 8 cm diameter), intermediate (negative groin nodes and lesion diameter greater than 8 cm diameter, one positive groin node and lesion diameter greater than 2 cm, or two unilaterally positive groin nodes and lesion diameter less than or equal to 8 cm), and high (three or more positive groin nodes or two bilaterally positive groin nodes), respectively. Applying the International Federation of Gynecology and Obstetrics staging (1988) to these data discriminated risk of death (caused by recurrent vulvar cancer); the 5-year rates were 98%, 85%, 74%, and 31% for stages I, II, III, and IV, respectively. However, within International Federation of Gynecology and Obstetrics stage III there were 47 low-, 95 intermediate-, and 28 high-risk patients with relative survivals of 95%, 74%, and 34%, respectively. Overall, this assessment validates current International Federation of Gynecology and Obstetrics vulvar carcinoma staging, but further refinements are warranted in stage III. 
Ictal 99mTc-HMPAO SPECT in alternating hemiplegia. 99mTc-hexamethylpropylenamine oxime (99mTc-HMPAO) single-photon emission computed tomography (SPECT) was performed in a patient with alternating hemiplegia during 2 episodes of the disease. The regional cerebral blood flow patterns correlated with the clinical manifestations during both episodes. Hyperperfusion of the contralateral hemisphere was suggested by asymmetric 99mTc-HMPAO uptake, whereas symmetric 123I-N-isopropyl-p-iodoamphetamine uptake was detected during the interictal period. The results suggested that alternating hemiplegia in infants represents an atypical manifestation of epilepsy, despite the lack of paroxysmal electroencephalographic abnormalities during the episodes. 99mTc-HMPAO SPECT appears to be a useful method for detecting transient regional cerebral blood flow alterations during paroxysmal events because the tracer is rapidly available for emergencies and retains a fixed distribution for 5-8 hours, sufficient time to allow for SPECT acquisition. 
Native valve Staphylococcus epidermidis endocarditis: report of seven cases and review of the literature. This report describes seven patients from three university hospitals whose native valve infective endocarditis was caused by Staphylococcus epidermidis. The literature on endocarditis caused by S. epidermidis is also reviewed and the clinical features of patients with native valve endocarditis due to this organism are compared with those of patients from a general series of infective endocarditis cases. Compared with infective endocarditis caused by other organisms, S. epidermidis endocarditis tends to occur more frequently in male patients. Patients with S. epidermidis endocarditis exhibit fewer embolic complications and skin manifestations. The frequency of congestive heart failure is lower in this group. The relative indolent course and apparent rarity of native valve S. epidermidis endocarditis necessitate a high index of suspicion for early diagnosis. 
Preservation of skeletal muscle in tissue transfers using rat hindlimbs. Replantation of major extremities after long periods of ischemia can lead to viable replants in many cases, but functional restoration is often poor owing to fibrosis of the muscle. In this study, maximum hypothermic time in tissue transfers containing skeletal muscle using hindlimbs of Lewis rats preserved in 4 degrees C Euro-Collins solution was investigated. After preserving midthigh amputated legs in this solution for 6, 9, and 12 hours, the legs were transplanted to other inbred rats using microsurgical technique, and 1 week later, gastrocnemii were obtained to analyze ATP, ADP, and AMP using high-performance liquid chromatography. The values were compared with those for healthy legs, nonischemic operated control legs, and legs preserved in the same manner for 6, 9, and 12 hours. Histologic and serologic examinations were conducted. ATP values of the 9-hour preservation group resumed those of the nonischemic operated control group, with the values of the 12-hour preservation group remaining at 61 percent. Histologically, focal necrosis, hyaline degeneration, and regeneration processes were the most characteristic manifestations in the muscles transplanted after cold ischemia of 12 hours. It was concluded that skeletal muscle could be preserved for 9 hours in 4 degrees C Euro-Collins solution. 
Surgical evaluation of Henoch-Schonlein purpura. Experience with 110 children. Henoch-Schonlein purpura is a disorder of unknown origin that is probably related to an autoimmune phenomenon. This report concerns 110 children (mean age, 6.2 years; range, 6 months to 14 years) with Henoch-Schonlein purpura. Seventy-two (65%) had abdominal pain associated with nausea and vomiting, bloody stool, and upper gastrointestinal bleeding. Sixty patients with abdominal pain were evaluated and treated conservatively. However, 12 patients underwent laparotomy. Six underwent unnecessary appendectomy for wrongly diagnosed appendicitis. Bowel resection was performed in one patient for an obstructive ileal lesion. Six additional patients had intussusception; surgery was required in three, while barium enema reduction was successfully accomplished in three others. Massive gastric hemorrhage required ligation, vagotomy, and pyloroplasty in two instances. One child with severe scrotal pain, hemorrhage, and swelling underwent unnecessary scrotal exploration. Four additional patients with similar symptoms avoided operation after a testicular scintiscan demonstrated good blood flow. A high index of suspicion and early diagnosis of Henoch-Schonlein purpura based on clinical, roentgenographic, and laboratory findings may avoid unnecessary operations in most cases. However, life-threatening complications (hemorrhage, obstruction, and intussusception) may occur and require operative intervention. All of the patients survived. 
Effects of atrial natriuretic factor in chronic hypoxic spontaneously hypertensive rats. The present study was designed first to investigate the pulmonary hypertensive effects of chronic hypoxia in spontaneously hypertensive rats and second to compare the cardiovascular effects of atrial natriuretic factor on rats exposed to hypoxia and on control rats kept at sea level. Catheters were placed in the femoral and pulmonary arteries for measurement of mean systemic arterial pressure and mean pulmonary arterial pressure. The cardiac output was measured by thermodilution method. It was found that 4 weeks of simulated 18,000-foot hypoxia led to polycythemia, right ventricular hypertrophy, and pulmonary hypertension, which resulted from an increased pulmonary vascular resistance. However, systemic arterial pressure was not significantly different between the two groups of rats. Atrial natriuretic factor administration decreased systemic arterial pressure and pulmonary arterial pressure to a lesser extent in the hypoxic group compared with the sea level control group. It is concluded that these animals showed an impaired response to atrial natriuretic factor after long-term exposure to hypoxia. 
Disappearance of thalamic pain after parietal subcortical stroke. A hypertensive man had a long standing history of contumacious hyperpathia in the right upper extremity, resistant to medical therapy, secondary to a lacunar infarct in the left thalamus. A second cerebrovascular accident caused a small lesion in the left corona radiata, interrupting the thalamoparietal interconnections, and terminated the pain instantly. Interruption of the subcortical parietal white matter may more effectively control pain than cortical lesions. A few surgeons have successfully treated rebellious chronic pain with stereotaxic operations in the corona radiata, resulting in lesions very similar to our patient's. This overlooked and nearly forgotten technique may still have value in treating selected cases. 
Hepatitis C virus antibodies in subjects with and without liver disease in the United Kingdom. The prevalence of antibody to hepatitis C virus, evidence of previous or current infection with this agent of parenterally transmitted non-A, non-B hepatitis, was determined in 340 subjects residing in the United Kingdom. The antibody was detected in 3 per cent of unselected blood donors and in 60 per cent of patients with chronic post-transfusion non-A, non-B hepatitis. Evidence for infection was also found in 30 per cent of intravenous drug abusers, and in 75 per cent of haemophiliacs receiving commercial factor VIII concentrate. The infection is uncommon in renal units and amongst sexually promiscuous groups attending sexually-transmitted disease clinics. Although the seropositivity rate in primary biliary cirrhosis and chronic B and delta hepatitis was very low (0-2 per cent), in patients with autoimmune and alcoholic liver disease it was 14-16 per cent which, although lower than that quoted in studies from Spain and Italy, is considerably higher than would be expected by chance. The reason for the high incidence of non-A, non-B hepatitis in this latter group of patients is unclear. 
Severe hypertension with segmental renal infarction following surgical removal of a retroperitoneal malignant hemangiopericytoma: a case report. Severe hypertension developed in a fifty-five year-old woman after surgical removal of a retroperitoneal tumor, when the renal artery was injured. Renal arteriography after the surgery demonstrated a segmental infarction of the right kidney. A close relationship between activation of the renin-angiotensin system and the development of severe hypertension was observed. Satisfactory control of blood pressure concomitant with reduction of plasma renin activity was achieved by a combination of an angiotensin-converting anzyme inhibitor, beta-blocking agent, and calcium-entry blocker. The mechanism of activation of the renin-angiotensin system in renal infarction is discussed. 
Atrial natriuretic peptide in dialysis patients under various conditions of volume homeostasis. Atrial natriuretic peptide (ANP) and plasma renin activity (PRA) were studied in 19 patients with end-stage renal disease (ESRD) under haemodialysis (HD). On the basis of clinical findings, patients were divided into three groups: group A, 6 patients, of mean age 41 +/- 15 years, without heart failure and in need of ultrafiltration (658 +/- 282 ml h-1); group B, 6 patients, of mean age 54 +/- 15 years, without heart failure under isovolaemic HD; group C, 7 patients, of mean age 60 +/- 3 years, with heart failure (NYHA III-IV) and in need of ultrafiltration (607 +/- 120 ml h-1). The highest predialysis ANP levels were found in group C (1534 +/- 471 pg ml-1) followed by group A (476 +/- 168 pg ml-1) and group B (236 +/- 138 pg ml-1) (normal range 62 +/- 27 pg ml-1). Systolic and diastolic blood pressure and heart rate did not correlate with ANP levels in either of the groups. However, iso-osmotic reduction of the body weight by ultrafiltration was correlated with decreasing ANP levels during HD (for groups A and C, r = 0.88 and 0.98, respectively). Isovolaemic HD did not alter ANP concentrations (group B). All patients received a volume bolus at the end of HD, and they responded with an instant increase in ANP concentration, which was most pronounced in patients with concomitant heart failure. PRA was not significantly correlated with ANP levels during HD. In conclusion, the results of this study indicate that there is a sensitive response of ANP levels to changes in body fluid status in ESRD. 
Effects of aspirin treatment on diabetic retinopathy. ETDRS report number 8. Early Treatment Diabetic Retinopathy Study Research Group. Aspirin treatment did not alter the course of diabetic retinopathy in patients enrolled in the Early Treatment Diabetic Retinopathy Study (ETDRS). In this randomized clinical trial supported by the National Eye Institute, 3711 patients with mild-to-severe nonproliferative or early proliferative diabetic retinopathy were assigned randomly to either aspirin (650 mg per day) or placebo. Aspirin did not prevent the development of high-risk proliferative retinopathy and did not reduce the risk of visual loss, nor did it increase the risk of vitreous hemorrhage. This was true both for eyes assigned randomly to deferral of photocoagulation and for eyes assigned randomly to early argon laser photocoagulation. The ETDRS results indicate that for patients with mild-to-severe non-proliferative or early proliferative diabetic retinopathy, it is likely that aspirin has no clinically important beneficial effects on the progression of retinopathy. The data also show that aspirin 650 mg per day had no clinically important harmful effects for diabetic patients with retinopathy. These findings suggest there are no ocular contraindications to aspirin when required for cardiovascular disease or other medical indications. 
Medical Research Council European trial of chorion villus sampling. MRC working party on the evaluation of chorion villus sampling. First-trimester chorion villus sampling has the advantage over second-trimester amniocentesis of allowing earlier prenatal diagnosis of various genetic and cytogenetic disorders in the fetus (and therefore earlier termination in affected pregnancies) but the relative safety and diagnostic accuracy remain unclear. Between 1985 and 1989, 3248 women seeking prenatal diagnosis, principally because of their age, were recruited to an international, multicentre, randomised comparison of the safety and diagnostic accuracy of the two techniques--5% of women allocated chorion villus sampling and 8% of those allocated amniocentesis were not tested, usually because of spontaneous miscarriage. 6% and 2% were retested, in most because of sampling failure. The endpoint of a liveborn infant who survived was achieved by 86% of women allocated chorion villus sampling and 91% of those allocated amniocentesis; statistical analysis, after appropriate weighting for a centre's contribution, showed that the typical difference between the groups was 4.6% (95% confidence interval 1.6-7.5%; p less than 0.01). This difference reflected more spontaneous fetal deaths before 28 weeks' gestation (2.9% [0.6-5.3%]); more terminations of pregnancy for chromosomal anomalies (1.0% [0.0-2.1%]); and more neonatal deaths (0.3% [-0.1 to 0.7%]). The difference in neonatal deaths was due to a preponderance of very immature liveborn infants in the chorion villus sampling group, and this factor also explained that group's longer mean stay in hospital. More abnormal diagnoses followed chorion villus than amniotic fluid analyses (5.6% vs 3.9%). This difference was largely due to diagnoses of trisomy 18 and of (usually mosaic) abnormalities known to be confined to the placenta. 3 terminated pregnancies were false positives, 1 tested by chorion villus sampling and 2 by amniocentesis, and 2 other mosaic cases diagnosed by chorion villus sampling may have been false positives. There was 1 false-negative result in the chorion villus sampling group. The possibility of earlier exclusion or diagnosis of some fetal disorders afforded by first-trimester chorion villus sampling must be set against its clinical risks. 
Children with chronic illness: family and parent demographic characteristics and psychosocial adjustment. This paper presents the results of an epidemiologic study that compares and contrasts psychosocial characteristics of parents and family units of children with chronic illness or physical disability (chronic health problems) with those of healthy children. Data were derived from the Ontario Child Health Study of 1869 randomly selected families, with 3294 children aged 4 to 16 years. In the absence of significant differences between parents and families of children with chronic illness alone and those with physical disability, these groups were combined for analysis, for which odds ratios (OR) or t tests were used. Significant positive findings included increased rates of parental treatment for "nerves" (mothers' OR = 2.1, fathers' OR = 1.9) and increased maternal negative affect scores (Bradburn Affect Balance Scale) (P less than .001) among parents of children with chronic health problems. Important negative findings (95% confidence interval of the OR included 1) included no increase in single-parent families (OR = 1.2), social isolation (OR = 1.0), or alcohol problems (OR = 1.2) among parents of children with chronic health problems. Categorically defined family dysfunction did not differ between the two groups (OR = 1.1). These data contrast with several clinic-based studies and suggest that, in a widely generalizable population survey, families of children with chronic health problems including physical disability do not suffer a marked excess of dysfunction, although some indicators of individual parent psychosocial problems were modestly elevated. 
In vivo molecular analysis of lymphokines involved in the murine immune response during Schistosoma mansoni infection. I. IL-4 mRNA, not IL-2 mRNA, is abundant in the granulomatous livers, mesenteric lymph nodes, and spleens of infected mice. Using Northern Blot analysis, the endogenous levels of IL-4 and IL-2 mRNA in the spleens, mesenteric lymph nodes, and granulomatous livers of male CBA/J mice in the acute phase of infection with Schistosoma mansoni have been quantified. High levels of IL-4 mRNA were detected in all three tissues from infected mice, whereas none was detected in tissues from normal, uninfected, age-matched mice. Isolation of the granulomas from the livers of infected mice and subsequent extraction of total RNA from these lesions resulted in a 70-fold enrichment of IL-4 message compared with the whole, unseparated granulomatous liver tissue. Hence, the predominant source of the IL-4 mRNA detected in livers from infected mice appears to be the schistosome egg-induced granulomas within these livers. In contrast, IL-2 mRNA was never detected in any of these tissues from either infected or normal mice. Control experiments were performed that ruled out the possibility that this inability to detect IL-2 mRNA was due to a difference in the efficacy of the IL-4 and IL-2 probes or due to a selective lability of IL-2 message. These data imply that IL-4-producing, Th2 lymphocytes are active in and possibly integral to the granulomatous, delayed-type hypersensitivity response characteristic of this infection, and directly challenges the current hypothesis that delayed-type hypersensitivity responses are exclusively mediated by Th1 lymphocytes. 
Cardiac disturbances during the administration of taxol. The clinical development of taxol, a new antimicrotubule agent with a unique mechanism of cytotoxic action, has proceeded slowly due to serious hypersensitivity reactions (HSRs) and shortages in its supply. Nevertheless, large-scale phase II trials have been initiated as taxol has recently demonstrated impressive activity in advanced and cisplatin-refractory ovarian carcinoma. Furthermore, the incidence of HSRs has been reduced substantially with premedications and modifications in the administration schedule. However, various manifestations of potential cardiotoxicity have been observed in several patients who participated in four phase I and II studies of taxol. Asymptomatic bradycardia has occurred in a high proportion of patients, including 29% of ovarian cancer patients who were treated with maximally tolerated doses of taxol in a phase II study. More profound cardiac disturbances, including a range of atrioventricular conduction blocks, left bundle branch block, ventricular tachycardia (VT), and manifestations of cardiac ischemia, have been observed in seven of 140 patients (5%) who received taxol. Descriptions of these events are presented in this report to alert investigators to the potential for these adverse effects. Although these disturbances did not result in serious sequelae in most patients, investigators should continue to maintain a high degree of caution until precise risk factors, frequency, and clinical significance of these adverse cardiac effects are determined. 
Mycotic (Aspergillus) arteritis resulting in fatal subarachnoid hemorrhage: a case report. A seventy-one year-old Japanese man suffering from carcinoma of the common bile duct died from subarachnoid hemorrhage secondary in intracranial mycotic arteritis (MA). Repeated cultures of the discharge from the draining tubes, the tip of intravenous hyperalimentation catheters, blood, sputum, and urine failed to grow any fungus. Autopsy disclosed MA due to Aspergillus at the terminal portion of the right internal carotid artery close to the posterior communicating artery. 
Evaluation of salvage surgery in heavily irradiated cancer of the buccal mucosa. This report describes the authors' experience with salvage surgery in 78 patients with carcinoma of the buccal mucosa who failed after high-dose radical radiation therapy at Regional Cancer Centre, Trivandrum, India. Forty-four patients (56%) required a hemimandibulectomy for adequate tumor clearance. Fifty-four patients (69%) required a primary reconstructive procedure for wound closure. Follow-up periods ranged from 28 months to 63 months (median follow-up, 41 months). Thirteen patients (17%) developed nonfatal postoperative complications. Thirty-one patients recurred after surgery, five of whom were again salvaged by further surgery. Overall, the recurrence rate was 36%. Most of the recurrences (26/31) were at the primary site. The overall 5-year actuarial disease-free survival after salvage surgery was 59.7%. T stage of the recurrent tumor and its skin infiltration emerged as factors which significantly influenced disease-free survival (P less than 0.05). 
Intra-arterial thrombolytic therapy in the management of acute and chronic limb ischaemia. A group of 54 patients with acute or chronic limb ischaemia were initially treated with low dose intra-arterial thrombolytic therapy using streptokinase (10,000 units h-1) or plasminogen activator (0.5 mg h-1). Complete thrombolysis was obtained in 90 per cent of patients with symptoms of less than 1 week duration, and in 50 per cent with symptoms of greater than 1 week (P less than 0.05). Successful lysis in 36 patients was followed by successful bypass surgery in seven, percutaneous angioplasty in 13, no further treatment in 13, repeat thrombolysis in two and amputation in one. Failed therapy was associated with major amputation in 40 per cent. One patient died of haemorrhage and another of stroke as a direct result of thrombolytic treatment. The most common complication was haematoma at the site of cannulation of the vessel. Intra-arterial thrombolytic therapy can be very useful for the management of acute and chronic limb ischaemia, but complications do occur and patients should be carefully selected. 
Single operator cardiopulmonary resuscitation in ambulances. Which ventilation device? Cardiopulmonary resuscitation en route to hospital is performed by a single-handed operator in many British ambulances. In this study, three emergency ventilation devices, and mouth-to-mouth breathing, were compared for effectiveness in unintubated patients. Seventeen paramedics used each method on a Laerdal manikin in a randomised order, under identical conditions. Three experienced cardiopulmonary resuscitation instructors repeated the tests in a moving ambulance. There were significant differences in minute volume (p less than 0.01) and number of effective chest compressions (p less than 0.05); mouth-to-mouth breathing produced the best overall results and the simplest device was a close second. The value of automatic ventilators for single-operator cardiopulmonary resuscitation in unintubated patients is questioned. 
HTLV-1 associated T cell lymphoma in South East Asia: case report and family study. Geographic clustering of human T cell lymphoma/leukaemia virus type 1 (HTLV-1) infection is well recognised, particularly in south western Japan, parts of West and Central Africa, the south eastern United States and the Caribbean islands. Sporadic cases have been reported in many other parts of the world. The first case of HTLV-1 associated leukaemia/lymphoma (ATLL) in South East Asia is reported. Contact tracing showed a high incidence of carriers among the relatives. 
An inherited defect of neutrophil motility and microfilamentous cytoskeleton associated with abnormalities in 47-Kd and 89-Kd proteins. A 2-month-old male Tongan infant presented with fever, severe skin and mucosal infections, hepatosplenomegaly, thrombocytopenia, and normal neutrophil counts. While polymorphonuclear neutrophil (PMN) morphology was normal, several neutrophil motile functions were found to be altered in the patient. Furthermore, two siblings had died in infancy with a similar clinical picture, raising the possibility of an inherited neutrophil defect. Random migration and chemotaxis, assessed by the under agarose method, were profoundly impaired. Actin polymerization, as measured by flow cytometry of N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)phallacidin (NBD-phallacidin)-stained PMNs, showed lower basal F-actin and a 1.75-fold increase in response to 10(-7) mol/L formyl-methionyl-leucyl-phenylalanine (FMLP) compared with a 4.51-fold increase in control. Microscopic examination of NBD-phallacidin-stained PMN spread on glass showed decreased area of spreading and F-actin-rich filamentous projections distinct from control. The early phase of FMLP-induced right angle light scattering was absent, similar to the effect caused by cytochalasin-B (CB), an inhibitor of actin polymerization. Accordingly, FMLP induced secretion of elastase without the addition of CB. Staphylococcus aureus killing was 50% of control whereas superoxide production response to FMLP and surface expression of CD11b were greater than twice normal. Partial defects in actin polymerization and scatter were seen in the parents and release of elastase, in the absence of CB, was also increased in both parents. Sodium dodecyl sulfate-polyacrylamide electrophoresis of whole cell proteins from the patient showed a marked decrease in an 89-Kd protein (8% of control) and a marked increase in a 47-Kd protein (4.2-fold). Both mother and father had decreased 89-Kd (77% and 42% of control) and increased 47-Kd proteins (2- and 3.4-fold), although neither had recurrent infections or chemotactic defects. These studies describe a new inherited actin dysfunction syndrome associated with severe propensity to fungal infection and draw attention to the proteins of apparent molecular weights of 89 Kd and 47 Kd, which may be of great importance in the regulation of actin polymerization in human PMNs. 
Usefulness of early versus late programmed ventricular stimulation in acute myocardial infarction. To determine the influence of timing on the prognostic value of programmed ventricular stimulation after acute myocardial infarction (AMI), 32 patients were studied on day 19 (early study) and again on day 36 (late study) after AMI using up to 3 extrastimuli. At the early study, sustained monomorphic ventricular tachycardia (VT) was induced in 12 patients (38%), sustained polymorphic VT in 8 (25%), nonsustained monomorphic VT in 1 (3%), nonsustained polymorphic VT in 1 (3%) and no inducible arrhythmia in 10 (31%). At the late study, sustained monomorphic VT, nonsustained monomorphic VT and nonsustained polymorphic VT were induced in 8 patients (25%) each, and no inducible arrhythmia in 8 (25%). Of the 12 patients who had inducible sustained monomorphic VT at the early study, 7 had noninducibility of sustained monomorphic VT at the late study. Of the 20 patients who had noninducibility of sustained monomorphic VT at the early study, 3 had inducible sustained monomorphic VT at the late study. During the follow-up period (mean +/- standard deviation 21 +/- 8 months), there were 2 sudden cardiac deaths and 3 occurrences of sustained VT. Univariate analysis revealed both inducibilities of sustained monomorphic VT at the early study (p = 0.045) and at the late study (p less than 0.001) to be predictive of sudden cardiac death or clinical occurrence of sustained VT. However, inducibility of sustained monomorphic VT at the late study had a higher sensitivity (100%), specificity (89%), positive predictive value (63%) and negative predictive value (100%) than at the early study (80, 70, 33 and 95%, respectively). 
Allochiria vs allesthesia. Is there a misperception? Allochiria is the mislocation of sensory stimuli to the corresponding opposite half of the body or space. Obersteiner (1882) introduced the term allochiria (Greek allos = other + chiria = hand), and more than 20 authors employed it in this context over the next 25 years. Stewart (1894) described a related phenomenon in which stimuli are displaced to a different point on the same extremity. He noted that the displacements were different than allochiria and coined the term allachaesthesia (ie, allesthesia) (Greek allache = elsewhere + aisthesis = perception). Despite this historical background, Jones (1907) redefined both terms in an attempt to increase diagnostic specificity and attributed allochiria to hysteria. Jones' reinterpretation does not appear to be justified historically, etymologically, or scientifically and has resulted in contradictory definitions of allochiria and allesthesia in present-day medical dictionaries and neurologic textbooks. We advocate a return to usage consistent with the original descriptions and word derivations. 
Autologous fat injection for vocal cord medialization in the canine larynx. This study examined the use of autologous fat as an alternative to Teflon and collagen as the implantable material in vocal cord medialization. Five animals underwent left recurrent laryngeal nerve sections with subsequent fat harvest and implantation into the left true vocal cords. Three animals were killed after 48 hours and 2 after 3 weeks; their larynges were examined with light microscopy. The results of the 48-hour samples show mode-rate acute inflammation and few areas of focal necrosis. The 3-week samples show no necrotic foci, minimal foreign-body reaction, and maintenance of structure and volume of the injected fat. Autologous fat may prove to be a valuable alternative to nonautologous injectable material in vocal cord augmentation. 
Performance of age-matched controls on a battery of visuo-spatial neglect tests. Examination of 47 independent elderly subjects, matched with a population of patients with acute stroke, found that 55% made at least one omission on a battery of neglect tests. Up to 43% made omissions on any one test. Increasing age and other evidence of cognitive impairment were associated with impaired performance on the battery. Omissions were attributed to an age-related decline in visuo-spatial function. Cut-off points are provided to distinguish between such age-related impairment and visuospatial neglect. The importance of age-matched control studies in developing tests of cognitive impairment in stroke research is highlighted. 
Hepatoid adenocarcinoma of the renal pelvis producing alpha-fetoprotein of hepatic type and bile pigment. A right renal pelvic mass in a 72-year-old man was resected. The histologic appearance of the tumor was a mixture of tubular adenocarcinoma cells and hepatoid neoplastic cells, and there was a resemblance to hepatoid adenocarcinoma. The intraoperative level of serum alpha-fetoprotein (AFP) was calculated to be 2246 ng/ml, and the postoperative level ranges from 183.6 to 285.6 ng/ml. Lectin binding assays showed that the serum AFP was the hepatic carcinoma type. In a hepatoid portion, an iron-negative, brown to green pigment was positive for bile. Alpha-fetoprotein was immunohistochemically evident in the neoplastic cells. In addition to the hepatic differentiation, the tumor had differentiated into intestinal absorptive or pancreatobiliary tract cells, as deduced from the frequent presence of spicular bodies, a unique light microscopic feature equivalent to microvilli with an actin core. The hepatoid adenocarcinoma is a distinct type of AFP-producing carcinoma present in the organs with epithelium of endodermal origin. Hepatoid adenocarcinoma in the renal pelvis may arise from a metaplasia of neoplastic mesonephric cells into endodermal cells. 
Oral magnesium successfully relieves premenstrual mood changes. Reduced magnesium (Mg) levels have been reported in women affected by premenstrual syndrome (PMS). To evaluate the effects of an oral Mg preparation on premenstrual symptoms, we studied, by a double-blind, randomized design, 32 women (24-39 years old) with PMS confirmed by the Moos Menstrual Distress Questionnaire. After 2 months of baseline recording, the subjects were randomly assigned to placebo or Mg for two cycles. In the next two cycles, both groups received Mg. Magnesium pyrrolidone carboxylic acid (360 mg Mg) or placebo was administered three times a day, from the 15th day of the menstrual cycle to the onset of menstrual flow. Blood samples for Mg measurement were drawn premenstrually, during the baseline period, and in the second and fourth months of treatment. The Menstrual Distress Questionnaire score of the cluster "pain" was significantly reduced during the second month in both groups, whereas Mg treatment significantly affected both the total Menstrual Distress Questionnaire score and the cluster "negative affect." In the second month, the women assigned to treatment showed a significant increase in Mg in lymphocytes and polymorphonuclear cells, whereas no changes were observed in plasma and erythrocytes. These data indicate that Mg supplementation could represent an effective treatment of premenstrual symptoms related to mood changes. 
Quality of life in long-term survivors of CNS tumors of childhood and adolescence. Clinical reports of small numbers of pediatric brain tumor patients observed for brief periods suggest that long-term survivors continue to have major handicaps into adulthood. To quantify these late effects we interviewed 342 adults (or their proxies) who had CNS tumors diagnosed before the age of 20 between 1945 and 1974, survived at least 5 years, and reached 21 years of age. Survivors were 32 years old on average at follow-up. When compared with 479 matched siblings as controls. CNS tumor survivors were more likely to have died or to have become mentally incompetent sometime during the follow-up period. They were more likely to be at risk for such adverse outcomes as unemployment (odds ratio [OR], 10.8; 95% confidence interval [CI], 4.6 to 25.7], to have a health condition that affected their ability to work (OR, 5.9; CI, 3.7 to 9.4), to be unable to drive (OR, 28.8; CI, 6.9 to 119.9), or to describe their current health as poor (OR, 7.8; CI, 1.7 to 35.7). Unfavorable outcomes were more frequent in male survivors than in females, in those with supratentorial tumors compared with infratentorial ones, and in those who received radiation therapy. As clinicians consider improving therapies, they should anticipate late effects, such as those we observed, and attempt to target subgroups for interventions that may improve subsequent quality of life. 
Dog bites in urban children. As a result of a perceived increase in pit bull injuries, all children who presented to The Children's Hospital of Philadelphia during 1989 for evaluation of dog bite injuries were prospectively studied. Epidemiologic information was collected from parents, either at the time of visit or by phone on the following day. A total of 168 children were enrolled; the mean age was 8 years. Males outnumbered females 1.5:1. Most (61%) injuries occurred in or around the home and involved dogs known to the patient (77%). Types of injuries included abrasions (33%), punctures (29%), and lacerations (38%). Thirteen bites had associated complications; nine developed infection. Twelve (7%) children required admission to the hospital. More than 12 different purebreeds or cross-breeds were identified as perpetrators, including German shepherds (n = 35), pit bulls (n = 33), rottweilers (n = 9), and Dobermans (n = 7). Most (54%) animals were contained (ie, leashed, fenced, in-house) at the time of injury. Fewer (46%) were provoked prior to biting. Significantly more pit bull injuries (94% vs 43%, P less than .001) were the consequence of unprovoked attacks and involved freely roaming animals (67% vs 41%, P less than .01). Children aged 5 or younger were more likely to provoke animals prior to injury than were older children (69% vs 36%, P less than .001). It is recommended that families with young children be the target of pet safety education and that measures be sought that would lead to early identification of a potentially dangerous dog and restrict ownership. 
Megaduodenum due to hollow visceral myopathy successfully managed by duodenoplasty and feeding jejunostomy. A 29 year old man with a history of childhood polymyositis developed insulin dependent diabetes and was found coincidentally to have chronic intestinal pseudo-obstruction due to visceral myopathy. Multiple full thickness biopsy specimens showed severe disease in the duodenum and the proximal jejunum only, with less involvement distally. Total parenteral nutrition has been avoided for more than a year by enteral feeding through a fine bore jejunostomy catheter positioned with its tip in the distal jejunum. 
Patient-controlled on-demand epidural fentanyl. A comparison of patient-controlled on-demand fentanyl delivered epidurally or intravenously. A prospective, open, clinical trial is described in which 20 patients having upper abdominal surgery were randomly allocated to receive fentanyl for postoperative analgesia by patient-controlled demand analgesic computer by either the epidural or intravenous route. Hourly pain, sedation and nausea scores were very similar in the two groups during the first 24 hours after surgery. What few differences there were favoured the epidural group. There was a highly significant difference in fentanyl consumption between the two groups, with the intravenous group demanding consistently more than twice as much as the epidural group. 
Etiology of acute respiratory infections in children in tropical southern India. Nasopharyngeal secretions and throat-swab specimens from 809 children less than 6 years old with acute respiratory infection were examined by culture and indirect immunofluorescence for the presence of virus or viral antigen. Blood was cultured for the presence of bacteria in selected cases of lower respiratory infection (LRI); pleural fluid also was cultured in cases of empyema. Viruses were detected in 163 (49%) of 331 children with LRI. Respiratory syncytial virus (RSV) was the commonest agent isolated (106 children). Other viruses isolated included parainfluenza viruses (36 children), adenoviruses (12), and influenza viruses (five). Outbreaks of infection due to RSV occurred during August through October. Pneumonia was the commonest LRI encountered (178 children). Among children with pneumonia, viruses were detected in 65 (37%) of 178 children, and bacteria were isolated from 27 (18%) of the 147 children for whom blood cultures were done. Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus were the common bacterial pathogens isolated. In cases of empyema and pyopneumothorax, S. aureus was the commonest organism isolated. There were 116 children with bronchiolitis, 83 (72%) of whom had viral infections; the majority of these children (81%) had RSV infection. Croup was uncommon (eight cases) and was caused mainly by parainfluenza viruses. 
Paracentesis with intravenous infusion of albumin as compared with peritoneovenous shunting in cirrhosis with refractory ascites. BACKGROUND. There is no satisfactory treatment for refractory ascites in patients with cirrhosis. Both peritoneovenous shunts and paracentesis have been used, but there is uncertainty about their relative merits. METHODS. We studied 89 patients with cirrhosis and refractory ascites who were randomly assigned to receive either repeated large-volume paracentesis plus intravenous albumin or a LeVeen peritoneovenous shunt. Patients in the paracentesis group in whom recurrent tense ascites developed during follow-up were treated with paracentesis, and those in the peritoneovenous-shunt group with diuretic agents or by the insertion of a new shunt if there was shunt obstruction. RESULTS. During the first hospitalization, ascites was removed in all 41 patients in the paracentesis group and in 44 of the 48 patients in the peritoneovenous-shunt group. The mean (+/- SD) duration of hospitalization in the two groups was 11 +/- 5 and 19 +/- 9 days, respectively (P less than 0.01). There were no significant differences in the number of patients who had complications or died. During follow-up, 37 patients in each group were hospitalized again. In the paracentesis group, the number of rehospitalizations for any reason (174 vs. 97 in the peritoneovenous-shunt group) or for ascites (125 vs. 38) was significantly higher, and the median time to a first readmission for any reason (1 +/- 1 vs. 2 +/- 2 months) or for ascites (2 +/- 2 vs. 8 +/- 17 months) was significantly shorter than in the peritoneovenous-shunt group. The total times in the hospital during follow-up, however, were similar in the two groups (48 +/- 49 and 44 +/- 39 days, respectively). Three patients had obstructions of their peritoneovenous shunts during their first hospitalizations, and 15 patients had a total of 20 obstructions during follow-up. Survival was similar in both groups. CONCLUSIONS. The LeVeen shunt and paracentesis are equally effective in relieving refractory ascites. The former may provide better long-term control of ascites, but shunt occlusion is common and survival is not improved. 
Dietary fish oil blocks the microcirculatory manifestations of ischemia-reperfusion injury in striated muscle in hamsters. Epidemiologic observations and experimental studies have demonstrated a protective effect of dietary fish oil on the clinical manifestations of ischemia-reperfusion injury. To investigate the underlying mechanisms, we used the dorsal skinfold chamber model for intravital fluorescence microscopy of the microcirculation in striated muscle of awake hamsters. In control hamsters (n = 7), reperfusion after a 4-hr pressure-induced ischemia to the muscle tissue elicited the adhesion of fluorescently stained leukocytes to the endothelium of postcapillary venules, capillary obstruction, and the break-down of endothelial integrity. These microvascular manifestations of ischemia-reperfusion injury were significantly attenuated in animals (n = 7) when fed with a fish oil-enriched diet for 4 weeks prior to the experiments. In leukocyte total lipids, the fish oil diet resulted in a substantial displacement of arachidonic acid, the precursor of the potent adhesion-promoting leukotriene (LT) B4, by fish oil-derived eicosapentaenoic acid, the precursor of biologically less potent LTB5, emphasizing the mediator role of LTB4 in ischemia-reperfusion injury. These results suggest that the preservation of microvascular perfusion by dietary fish oil contributes to its protective effects on the clinical manifestations of ischemia-reperfusion injury. 
External anal sphincter function in spinal patients. Electromyographic and manometric study. Six patients with complete transection of the spinal cord and six healthy volunteers were examined by using anorectal manometry together with electromyographic (EMG) recording of the external anal sphincter composed of striated muscle. Anal pressure and EMG activity of the external anal sphincter were continuously recorded at rest and during gradual rectal distention (10, 20, 30, 40, and 50 ml) by means of an air-filled balloon eliciting a rectoanal inhibitory reflex (RAIR) at the upper part, and an inflation reflex (IR) at the lower part of the anal canal. All patients and controls had a RAIR for each rectal distention volume. A relationship between the duration of the RAIR and the rectal distention volume was present in controls only. In controls the IR was present for each rectal distention volume, whereas it was present in only one patient for a 40-ml volume. During the resting period, all controls showed continuous tonic EMG activity of the external anal sphincter, but after 30 minutes all the patients showed a decrease and ultimately in five cases a disappearance of the tonic EMG activity of the external anal sphincter. In spinal patients, the presence or absence of EMG activity of the external anal sphincter did not modify the anal canal pressure. These results indicate that: 1) the tonic EMG activity of the external anal sphincter seems to be under the control of supraspinal structures, because in spinal patients it disappears in the absence of sensitive inputs toward the spinal cord; 2) the absence of EMG activity at rest indicates that the external anal sphincter is not implicated in the RAIR disturbances observed in spinal patients; 3) the IR is not a spinal reflex but is under voluntary control, because it is not present in spinal humans; 4) in spinal humans the tonic EMG activity of the external anal sphincter does not play a role in the maintenance of the anal pressure at rest. 
ABO(H) antigens and beta-2 microglobulin in transitional cell carcinoma. Predictors of response to intravesical bacillus Calmette-Guerin. The response of patients with superficial transitional cell carcinoma of the bladder (STCB) to intravesical chemotherapy is variable; some patients enjoy a long period without recurrence, whereas others have recurrence of tumor within 2 years of removal of the primary lesion. Previously, others have demonstrated that the loss of normal cell surface antigens, such as ABO(H) blood group antigens or beta-2 microglobulin (B2M) has been correlated with more aggressive behavior by tumor. In this study, using immunohistochemical techniques, the authors evaluated the initial pretreatment biopsy specimen of bladder tumors for the presence of ABO(H) antigens and B2M. Data from this sample patient population, all with biopsy-proven STCB, indicate that expression of these two markers is predictive of a therapeutic response to prophylactic intravesical bacillus Calmette-Guerin (BCG) (Tice strain) after resection, and that expression of the two markers is of greater predictive value than expression of either antigen alone. 
Modulation of catecholamine cardiomyopathy by allopurinol. It has been suggested that cardiac injury by catecholamines may be the result of coronary constriction leading to ischemic damage. Allopurinol (ALLO) has been shown to reduce the extent of myocardial necrosis in various systems. Hence the possibility that ALLO might limit norepinephrine (NE) injury was tested. Rabbit hearts were infused with NE (3 micrograms/min/kg) for 90 minutes, with or without ALLO (50 micrograms/min/kg). Control specimens infused with saline solution plus ALLO were also prepared. Hearts were excised 48 hours later and studied as isovolumic isolated heart preparations. Peak systolic pressure, coronary flow, and myocardial oxygen consumption were significantly reduced in the hearts infused with NE but not in the NE + ALLO hearts. Myocardial adenosine triphosphate and glycogen concentrations were 29% and 26% lower in the NE hearts compared with control hearts. These reductions were absent in the NE + ALLO group. Moreover, rates of creatine phosphokinase and lactic dehydrogenase release were sharply elevated in the NE hearts but not in those also given ALLO. These findings are consistent with the changes observed histologically. The amount of myocardial damage was less in the ALLO + NE group compared with the NE group (p less than 0.02). This appears to be the first report to demonstrate that ALLO reduces myocyte damage by NE. Possible mechanisms include decreased free radical production, scavenging of free radicals, and preservation of the adenine nucleotide pool. Because xanthine oxidase activity is absent in the rabbit, the latter two mechanisms are more likely explanations for the findings. 
A case of autoerotic asphyxia associated with multiplex paraphilia. During the past 20 years, the sensational aspects of autoerotic fatalities have captured the attention of medical examiners, psychiatrists, law enforcement agents, and the public, as well as the individuals themselves who engage in these dangerous practices. Reports of deaths related to sexual asphyxia have been presented numerous times at national and international meetings and have been the topic of discussion on television talk shows and in the press. Autoerotic fatalities and all the sexual curiosities related to these activities have prompted death scene investigators to publish case reports, and even textbooks, on the subject. The case presented herein is one of a multicomponent paraphilia in which self-asphyxiation (autoasphyxiophilia) led to a fatal autoerotic event. 
Paroxysmal tremor and orofacial dyskinesia secondary to a biopterin synthesis defect. We report a child with a systemic biopterin synthesis defect due to an absence of 6-pyruvoyl-tetrahydropterin synthase who had an unusual presentation, with three episodes of coarse "rubral-like" tremor in arms and legs orofacial dyskinesia between the ages of 3 and 6 months. Response to levodopa therapy and CSF neurotransmitter metabolite concentrations before and after therapy suggests that his clinical syndrome resulted from a secondary dopamine deficiency. 
Metabolic and work efficiencies during exercise in Andean natives. Maximum O2 and CO2 fluxes during exercise were less perturbed by hypoxia in Quechua natives from the Andes than in lowlanders. In exploring how this was achieved, we found that, for a given work rate, Quechua highlanders at 4,200 m accumulated substantially less lactate than lowlanders at sea level normoxia (approximately 5-7 vs. 10-14 mM) despite hypobaric hypoxia. This phenomenon, known as the lactate paradox, was entirely refractory to normoxia-hypoxia transitions. In lowlanders, the lactate paradox is an acclimation; however, in Quechuas, the lactate paradox is an expression of metabolic organization that did not deacclimate, at least over the 6-wk period of our study. Thus it was concluded that this metabolic organization is a developmentally or genetically fixed characteristic selected because of the efficiency advantage of aerobic metabolism (high ATP yield per mol of substrate metabolized) compared with anaerobic glycolysis. Measurements of respiratory quotient indicated preferential use of carbohydrate as fuel for muscle work, which is also advantageous in hypoxia because it maximizes the yield of ATP per mol of O2 consumed. Finally, minimizing the cost of muscle work was also reflected in energetic efficiency as classically defined (power output per metabolic power input); this was evident at all work rates but was most pronounced at submaximal work rates (efficiency approximately 1.5 times higher than in lowlander athletes). Because plots of power output vs. metabolic power input did not extrapolate to the origin, it was concluded 1) that exercise in both groups sustained a significant ATP expenditure not convertible to mechanical work but 2) that this expenditure was downregulated in Andean natives by thus far unexplained mechanisms. 
Abnormal vasomotor changes early after coronary angioplasty. A quantitative arteriographic study of their time course. BACKGROUND. To study the impact of percutaneous transluminal coronary angioplasty (PTCA) on coronary vasomotion, we prospectively analyzed spontaneous changes in coronary diameter and the response to the cold pressor test and intracoronary nitroglycerin in 11 patients subjected to successful single-vessel PTCA. METHODS AND RESULTS. All antianginal medications were stopped 48 hours before each study. The minimum diameter of the PTCA segment and the diameter of a distal segment in the angioplastied vessel and of a segment in a control vessel not manipulated by the balloon catheter or guide wire were measured by computerized edge detection immediately before PTCA and 5 minutes after, 4 hours after, and 8 days after PTCA. At 4 hours, PTCA and distal segments were constricted by 38 +/- 9% and 16 +/- 5%, respectively, compared with the values at 5 minutes (p less than 0.01). Before angioplasty, the cold pressor test caused vasoconstriction of PTCA and distal segments by 23 +/- 6% (p less than 0.0001) and 15 +/- 4% (p less than 0.008), respectively, but no constrictor response was elicited at 5 minutes or 4 hours after angioplasty. Eight days after PTCA, the basal coronary diameters were similar to those observed 5 minutes after PTCA and the response to the cold pressor test was similar to that observed before PTCA. All segments dilated significantly with nitroglycerin at all times, and no vasoconstriction changes were found in the control segments. CONCLUSIONS. Four hours after PTCA, transient spontaneous vasoconstriction of the PTCA and distal segments occurs, which is so intense that the cold pressor test does not cause any further constriction. These abnormalities resolve within 8 days of PTCA. 
The histologic reliability of laser cone biopsy of the cervix. Laser conization of the cervix has been advocated as the technique of choice for the treatment of cervical intraepithelial neoplasia (CIN) in preference to ablative techniques, because it provides a specimen for histologic diagnosis while retaining the advantages of an outpatient procedure with minimal short- and long-term morbidity. To determine whether specimens so obtained are adequate for reliable histologic diagnosis, we reviewed 77 laser conizations performed for lesions confirmed to contain CIN in a colposcopically directed biopsy and satisfying the criteria for local ablation and scored the cones for the presence of epithelial denudation and laser coagulation artifact that interfered with the diagnosis of CIN or the assessment of the margins of excision. Thirty specimens (39%) were negative for CIN. Twenty-eight (36%) showed extensive epithelial denudation, ten (13%) contained coagulation artifact that made recognition of CIN extremely difficult or impossible, and in 11 (14%), assessment of margins was extremely difficult or impossible because of laser coagulation artifact. We conclude that these difficulties with the histologic interpretation of laser cone specimens make it an unsuitable excisional technique when reliable histologic diagnosis of cervical lesions is required. 
Alpha 1 antitrypsin phenotypes and alcoholic pancreatitis. Altered frequencies of alpha 1 antitrypsin phenotypes have been reported in patients with chronic pancreatitis, suggesting a possible genetic basis for individual susceptibility to this disease. Alpha 1 antitrypsin phenotypes, with particular regard to alcoholic pancreatitis, were studied. Patients with alcoholic pancreatitis were compared with alcoholic control subjects with no history of pancreatic disease. Serum alpha 1 antitrypsin concentrations were raised in pancreatitis patients sampled within one month of an acute attack of pancreatitis, but otherwise values were similar to those of control subjects. There were no significant differences in alpha 1 antitrypsin phenotypes between alcoholics with pancreatitis and alcoholic control subjects. This study of alpha 1 antitrypsin phenotypes provides no evidence of an inherited susceptibility to alcoholic pancreatitis. 
Avoidance of cancellation of potential hyperstimulation cycles by conversion to in vitro fertilization-embryo transfer. OBJECTIVE: The study was undertaken to minimize the rate of ovarian hyperstimulation and to avoid cancellation of human treatment cycles in women treated with human menopausal gonadotropin (hMG) for induction of ovulation. SETTING: Patients were treated in the fertility clinic and in vitro fertilization unit of our institution, which is a government, university-affiliated hospital. PATIENTS: Ninety anovulatory patients were treated with hMG. Of these, 12 were at high risk for ovarian hyperstimulation. The criteria for potential ovarian hyperstimulation syndrome were rising excessive 17 beta-estradiol levels of greater than 1,500 pg/mL in the presence of multiple follicles with a mean diameter greater than 15 mm. These patients were transferred for continuation of treatment to our in vitro fertilization-embryo transfer (IVF-ET) unit. INTERVENTIONS: The patients underwent ova retrieval by the ultrasonically guided transvaginal approach. RESULTS: Of the 12 patients, 5 conceived (41.6%). Two patients had a mild ovarian hyperstimulation syndrome, and 1 had a moderate syndrome and was hospitalized for observation for 48 hours. CONCLUSION: In view of the results, we suggest that IVF-ET should be considered in cases in which ovarian hyperstimulation syndrome is imminent, rather than withhold human chorionic gonadotropin and cancelling the treatment cycle. 
Plasma and saliva levels of PGI2 and TXA2 in the headache-free period of classical migraine patients. The effects of nicardipine. The levels of Prostacyclin (PGI2) and Thromboxane A2 (TXA2) were assayed simultaneously (RIA) in the plasma and saliva of 9 patients suffering from classical migraine attacks. The assays were done during an attack-free period. In relation to the control group we observed a significant decrease in the plasma levels of PGI2 together with a sharp increase in TXA2 in saliva. When the patients were treated with nicardipine, a calcium antagonist, the TXA2 increase in saliva did not occur. These results suggest both a systemic and local effect in the classical migraine attacks. We explain and discuss our results by referring to the PGI2: TXA2 equilibrium system. Nicardipine action might be related to its ability to reduce the calcium entry into the cell induced by thromboxane. 
Unusual intramandibular neural tumor. Neural tumors within the jaw bones are exceptional. We present the histologic observation of a central mandibular tumor of neural origin. Immunohistochemistry confirmed the neural nature of the tumor, which had features of a schwannoma (neurilemmoma) together with ganglion cells as seen in ganglioneuroma. Moreover, the association with an intracranial tumor, possibly a meningioma, is emphasized. 
Simultaneous esophageal pH monitoring and scintigraphy during the postprandial period in patients with severe reflux esophagitis. To compare reflux events detected by intraesophageal pH monitoring with that of scintigraphy, we simultaneously performed both techniques along with esophageal manometry in nine patients with severe reflux esophagitis. Two hundred eighteen reflux events were detected in the recumbent posture after a meal during a 40-min interval. Both techniques simultaneously detected only 23% of all reflux events. Scintigraphy alone detected 61% of all reflux events as opposed to 16% for pH monitoring. Of those reflux events diagnosed only by scintigraphy, more occurred while the intraesophageal pH was less than 4 (ie, during an acid-clearing interval) than while the intraesophageal pH was greater than 4 (ie, when intragastric contents were neutralized by the meal). Most reflux events occurred during periods of stable, but low LES pressure. While reflux events diagnosed by scintigraphy significantly decreased during the second of two 20-min postprandial intervals, those by pH monitoring tended to increase. That simultaneous scintigraphy and pH monitoring agreed on less than 1/3 of all reflux events not only underscores the fact that both techniques measured different physical components of the esophageal refluxate (ie, volume vs acid concentration, respectively), but also were influenced by different physiologic events such as the ingestion of a meal, gastric emptying, and esophageal acid clearance. 
Pain centers--organization and outcome. Pain treatment centers have evolved at a rapid rate, but they differ in their complexity and services provided. Patients, as well as primary care physicians, have difficulty in identifying the appropriate center for a specific problem. Guidelines for pain centers have recently been proposed by the International Association for the Study of Pain, along with an attempt at their accreditation. Outcome studies from pain centers have proliferated, with a wide range of treatment programs being reported. Comprehensive multidisciplinary pain centers using the rehabilitation medicine approach are effective in decreasing disability and increasing the productivity of patients with chronic, disabling pain. 
Quantitation of axon loss and conduction block in peroneal nerve palsies. We compared conduction in motor fibers supplying the extensor digitorum brevis (EDB) and anterior lateral compartment (AL) muscles. The object was to determine whether there were any differences in the relative proportions of degenerated and blocked nerve fibers between the longer EDB and shorter AL fibers. In almost every case the percentage of motor fibers undergoing axonal degeneration was greatest in EDB fibers. Conversely, the percentage of conduction block was greatest in the AL motor fibers. As clinical recovery is dependent on AL muscles rather than EDB, electrophysiological study of the relative proportions of degenerated and blocked fibers in the former should provide a more reliable measure of outcome than similar studies of EDB. Conduction velocity distal to the fibular head was not slowed despite the large loss of EDB motor fibers. Evidence for selective involvement of the larger myelinated fibers is, therefore, lacking. The location of the major conduction abnormalities was in almost every case between the mid-fibular head and popliteal fossa. 
Depression and chronic fatigue in the patient with chronic pain. Chronic benign pain is commonly associated with chronic fatigue and depression. Depression and chronic fatigue syndrome are also associated with each other and often include pain. Psychologic factors are prominent in these conditions, and they may share neurobiologic factors as well. Management requires separately addressing each component of patients' distress and usually includes physical rehabilitation, education, administration of nonhabituating medications and often counseling. Depression may be a favorable prognostic sign, as it suggests a treatable condition and provides incentive for recovery. 
Demethylation of CpG islands in embryonic cells. DNA in differentiated somatic cells has a fixed pattern of methylation, which is faithfully copied after replication. By contrast, the methylation patterns of many tissue-specific and some housekeeping genes are altered during normal development. This modification of DNA methylation in the embryo has also been observed in transgenic mice and in transfection experiments. Here we report the fate in mice of an in vitro-methylated adenine phosphoribosyltransferase transgene. The entire 5' CpG island region became demethylated, whereas the 3' end of the gene remained modified and was even methylated de novo at additional sites. Transfection experiments in vitro show that the demethylation is rapid, is specific for embryonic cell-types and affects a variety of different CpG island sequences. This suggests that gene sequences can be recognized in the early embryo and imprinted with the correct methylation pattern through a combination of demethylation and de novo methylation. 
Neisseria lactamica meningitis following skull trauma. A woman developed meningitis due to Neisseria lactamica in association with a cribriform plate fracture. Cerebrospinal fluid antigen tests for Neisseria meningitidis were negative. The patient recovered with intravenous penicillin therapy. N. lactamica can be rapidly distinguished from N. meningitidis by the hydrolysis of ONPG (o-nitrophenyl-beta-D-galactopyranoside). In contrast to N. meningitidis and Neisseria gonorrhoeae, N. lactamica lacks virulence properties. As 100% of N. lactamica strains are susceptible to penicillin and all three previously described patients with N. lactamica meningitis have recovered with penicillin treatment, the reason for distinguishing the organisms in this context is primarily to prevent unnecessary anxiety and prophylaxis among contacts. 
Potential impact of exclusion criteria on results of hypertension trials. Recent trials of antihypertensive therapy, including the Veterans Administration trials, the Hypertension Detection and Follow-up Program, the Multiple Risk Factor Intervention Trial, the Australian Mild Hypertension Trial, and the British Medical Research Council Trial, are reviewed with a particular emphasis on the criteria leading to the exclusion of potentially eligible participants. The observation of all-cause and cause-specific mortality rates in the group ultimately selected to participate in the trial is suggested as an index to the general applicability of trial results. Because end-point rates are fundamental for determining sample size, substantial reduction in these end-point rates by patient exclusion should be taken into account by the trial design. Some recent trials may have generated end-point-event rates so low that the power of the trial to detect reasonable treatment effects was substantially reduced. Future trials should attempt to take this important factor into account at the design stage. 
Seminal vesicle cysts: association with adult polycystic kidney disease. Adult polycystic kidney disease (APKD) is associated with cyst formation in the kidney, liver, pancreas, esophagus, ovary, uterus, and brain. Four patients with APKD (aged 45-65 years) with computed tomographic evidence of seminal vesicle cysts are described. All seminal vesicles contained cystic masses with attenuation values of 0-30 HU. Seminal vesicle thickness was 3-4 cm (normal, 1.5 cm). High-attenuation walls separated the cysts, which were 3-35 mm in diameter. All patients had typical renal stigmata of APKD. None had cysts elsewhere, except one patient with hepatic cysts. Postmortem examination in one patient confirmed the seminal vesicle cysts as well as APKD. It is likely that a basement membrane defect allows cyst formation in multiple organs, presumably including the seminal vesicles. Because of the association of seminal vesicle cysts with ipsilateral urogenital anomalies, and because only 60% of patients with APKD have a relevant familial history, the kidneys of patients with cross-sectional imaging evidence of seminal vesicle cysts should also be studied. 
Penetrating atherosclerotic aortic ulcer with dissecting hematoma: control of bleeding with percutaneous embolization. A case is presented in which left subpleural hematoma and hemothorax resulted from a penetrating atherosclerotic aortic ulcer with an aortic pseudoaneurysm and intramedial hematoma. Percutaneous transfemoral embolization of the ulcer with use of coils and thrombin resulted in stabilization of the patient's hemodynamic status. The patient died 6 days later of pneumonia. In certain clinical situations, treatment of bleeding from penetrating aortic ulcers with percutaneous embolization may stabilize the patient's condition, allowing elective surgical intervention. 
Effect of hypoxic exercise on atrial natriuretic factor and aldosterone regulation. To evaluate the possible physiologic role of atrial natriuretic factor (ANF) in the observed dissociation of aldosterone secretion from the renin-angiotensin system during hypoxic exercise, 12 untrained men, ages 18 to 24, were studied on two separate days for 30 min during hypoxic (16% O2) and normoxic (room air) exercise on a bicycle ergometer. Workloads were adjusted to produce individual heart rates that remained within 70 to 75% of their previously measured maximum. Hemoglobin saturation decreased during hypoxia from 98 +/- 0.1% to 90 +/- 0.4% (P less than .01). Plasma aldosterone levels increased significantly (P less than .01) under both breathing conditions, yet were on average 36% lower during hypoxia than during normoxia (P less than .001). Plasma ANF levels increased during exercise under both conditions (P less than .01), yet levels were 45% greater during hypoxia than during normoxia (P less than .001). Plasma renin activity, adrenocorticotropic hormone, cortisol, potassium, and systolic blood pressure increased during exercise on both study days (P less than .01, compared to basal level), and showed no difference between normoxic and hypoxic conditions. Plasma pH was slightly higher during hypoxic exercise (P less than .05, compared to normoxia). We conclude that acute hypoxemia is a potent enhancing stimulus for ANF release during dynamic exercise and that ANF is probably a contributing factor in the dissociation of aldosterone secretion from the renin-angiotensin system under these conditions. 
Use of technetium-HMPAO to demonstrate changes in cerebral blood flow reserve following carotid endarterectomy. Cerebral perfusion through stenosed internal carotid arteries is usually maintained by autoregulation. However, flow reserve may be reduced, suggesting hemodynamically significant stenosis, and such reduction should be improved by carotid endarterectomy. This concept was studied in 20 subjects with unilateral internal carotid artery stenosis (major stenosis greater than or equal to 70%, minor stenosis less than or equal to 50%). Thirteen had experienced recent transient ischemic attacks and seven had no definite focal symptoms. Subjects underwent Tc-HMPAO cerebral SPECT during acetazolamide dysautoregulation before and after internal carotid endarterectomy. Nine (45%) had perfusion defects that improved after surgery, suggesting surgery had improved cerebral flow reserve. Seven had defects that did not improve after surgery. Four had worsened or new defects after surgery, suggesting perioperative infarcts. The relatively large proportion of patients with improved cerebral blood flow reserve after surgery suggests that this technique may have a significant role to play in assessing which patients might benefit from carotid endarterectomy. 
A comparison of treatment outcomes for black patients and white patients with metastatic breast cancer. The Piedmont Oncology Association experience. Prior studies have shown that black patients with breast cancer have poorer survival times compared with white patients even when adjusted for stage. Seventy-four black patients treated on six Piedmont Oncology Association (POA) protocols were compared with 74 randomly selected white patients treated with the same protocols to determine if race had any independent effect on response, time to progression, or survival time. Patients were evenly matched for pretreatment characteristics with the exception that white patients had a significantly higher percentage of bone metastases and significantly less skin involvement. Response rates and median time to progression were similar for black patients and white patients at 31% and 25%, and 9.3 and 9.1 months, respectively. Black patients had poorer survival times even when adjusting for covariables; median survival time was 14.3 months for black patients and 20.3 months for white patients (P less than 0.05). The reason for this survival difference in Stage IV patients is unclear, but is unlikely to be related to treatment. Additional research in this area will be necessary to resolve this issue. 
Exercise-induced muscle soreness after concentric and eccentric isokinetic contractions. The purpose of this two-part study was to determine whether the amount of exercise-induced muscle soreness differs between subjects who perform concentric and eccentric isokinetic contractions of their quadriceps femoris muscles. In experiment 1, subjects were randomly assigned to either an eccentric or a concentric exercise group and both groups exercised at the same power level. In experiment 2, subjects were randomly assigned to either an eccentric or a concentric exercise group and both groups exercised with maximal effort. Muscle soreness ratings, obtained by using a visual analogue scale, were taken immediately before exercise and at 24 and 48 hours postexercise. Changes in muscle soreness ratings between exercise groups from preexercise to postexercise periods were compared in both experiments, using a one-way between-subjects analysis of variance. There was no difference in the change in muscle soreness from preexercise to post-exercise periods between groups exercising at equal power levels. Subjects who exercised using eccentric contractions with maximal effort demonstrated greater increases in muscle soreness than those who performed concentric contractions. The results suggest that exercise intensity, rather than contraction type, may be the dependent factor in producing exercise-induced muscle soreness. 
Differentiation between hemangiomas and metastases of the liver with ultrafast MR imaging: preliminary results with T2 calculations. We studied the efficacy of T2 measurements at high field strength in distinguishing between liver hemangiomas and hepatic metastases when an ultrafast (single-excitation) MR imaging technique is used. Fourteen patients with known liver tumors were imaged in a 2.0-T prototype ultrafast MR scanner with a spin-echo (infinite TR and TE of 30-340 msec) pulse sequence. Each image was obtained with a total data acquisition time of 20 msec. T2 calculations for hepatic metastases (n = 6) showed a mean of 79.3 +/- 13.5 msec, whereas hemangiomas (n = 8) showed a T2 of 139.8 +/- 18.8 msec (p less than .0001). T2 values of lesions had a smaller relative standard deviation than previously reported, and the range of T2 values of hemangiomas (119-181 msec) and metastases (68-103 msec) did not overlap. Our preliminary results suggest that T2 calculations with ultrafast MR imaging may be useful for differentiating hemangiomas from metastases. We hypothesize that T2 values obtained from ultrafast MR images are more reliable than those obtained from conventional MR images, primarily because of the elimination of T1 information and effects of motion on image signal intensity. 
Thrombolysis in unstable angina: results of clinical studies. Ample evidence exists to support the major role of intracoronary thrombosis superimposed on a disrupted plaque in unstable angina. Consequently, thrombolytic treatment, already established to be highly beneficial in patients with acute myocardial infarction, might also be indicated in patients with unstable angina. The clinical response to thrombolytic treatment has been evaluated in several small-sized studies with inconsistent and somewhat deceiving results. Thus, the role of thrombolysis in the treatment of unstable angina is still controversial. Two ongoing large-scale, randomized, controlled trials, the Third Thrombolysis in Myocardial Infarction (TIMI III) in the United States testing recombinant tissue-type plasminogen activator and UNASEM in Europe testing anisoylated plasminogen-streptokinase activator complex will, it is hoped, solve the debate. At present, early thrombolysis might be considered for the treatment of the subset of patients with severe rest angina associated with transient ST-T ischemic changes. 
Does oximetry contribute to the detection of apneic events? Mathematical processing of the SaO2 signal. The purpose of this study was to assess the ability of continuous nocturnal oximetry to detect sleep apnea syndrome (SAS) and to recognize nonapneic oxyhemoglobin desaturations. Oxygen saturation oscillations, related to successive apneas in SAS or to apneic episodes in COPD or restrictive patients, were quantified using a new index: delta = 1/n sigma 1 n magnitude of delta(SaO2)/delta(t)(12-s intervals) Twenty-six patients (15 SAS, 8 COPD, and 3 restrictive patients) were included in a prospective study comparing nocturnal oximetry and polysomnography over 34 nights. In apneic patients, we found a strong correlation (r2 = 0.73, p less than 0.01) between time spent in apnea and the delta index. In COPD, the number of apneas was also correlated to the delta index (r2 = 0.92, p less than 0.01). A lower threshold for delta of 1.5 is accurate enough to detect apneas if initial SaO2 is greater than 93 percent. If initial SaO2 is greater than 93 percent, the delta threshold should be 0.8 (sensitivity 95 percent). Such a method could contribute to the accurate selection of patients for polysomnography. 
Effect of antibiotics on food intake and absorption of nutrients for children with diarrhea due to Shigella. The effect of antibiotic therapy on intake of food and absorption of nutrients for 19 male children aged 1-5 years with suspected shigella infection was studied. The children were admitted to the hospital with acute diarrhea, high fever, abdominal pain, and greater than or equal to 25 red blood cells and white blood cells per high-power field in the stool. Microbiologic diagnosis was made within 48 hours of admission. On the basis of clinical and microbiologic criteria, children were classified as having mild or severe infection. Ten children with mild infection did not receive antibiotics, whereas nine children with severe infection were treated with ampicillin. After the children were rehydrated, a 72-hour balance study was carried out during the acute stage of infection with Shigella and was repeated 2 weeks after recovery. The levels of consumption of food and absorption of nutrients were estimated. During the acute stage of infection, such levels were higher for the children treated with antibiotics than for the untreated group. During the recovery phase, the levels of intake of food and absorption of nutrients were equal for both groups. Thus, children who are treated with appropriate antibiotics not only may recover from infection with Shigella more rapidly, but they also may be able to absorb nutrients more efficiently. 
Flexible bronchoscopy via the laryngeal mask: a new technique. Malignant tracheal tumours often cause airway obstruction and this may be aggravated by vocal cord paralysis due to invasion of the recurrent laryngeal nerve. Conventional endoscopic techniques performed under general anaesthesia do not give a simultaneous view of vocal cord function and the distal airways. The technique of bronchoscopy via the laryngeal mask allowed full assessment of the cause of stridor in a patient with a malignant tracheal tumour that was causing airways obstruction and vocal cord paralysis. 
On the pathogenesis of diabetic retinopathy. A 1990 update. Although most investigators now agree that chronic hyperglycemia is the basis for diabetic retinopathy, this has not been proven definitively. Even if chronic hyperglycemia is the initial common pathway leading to retinopathy and other complications of diabetes, it appears to act by different mechanisms in different tissues. The enzyme, aldose reductase, may play a major role in the development of diabetic retinopathy, but contradictory evidence exists. At the present time, results of the only study of aldose reductase inhibition and diabetic retinopathy reported in humans were negative. Another mechanism worthy of consideration is nonenzymatic glycation (glycosylation) of proteins, but there is no direct evidence of a causal role in diabetic retinopathy. Several growth factors have been identified in the retina that may promote neovascularization, and at least two inhibitors may prevent the process. There is evidence to support a role for basic and, perhaps, acidic fibroblast growth factors in retinal vasoproliferation. Transforming growth-factor beta, a peptide produced by capillary pericytes and smooth muscle cells and activated by the interaction of these cells with vascular endothelial cells, appears to be an important inhibitor of neovascularization, as is the vascular basement membrane. 
Female urethra: MR imaging. The potential of magnetic resonance (MR) imaging in the evaluation of the female urethra was studied in 64 patients. Spin-echo T1- and T2-weighted images were obtained in all 64 patients, and contrast-enhanced T1-weighted images were also obtained in 27 patients. Urethral pathologic conditions, established with urethroscopy or histologic examination, or both, included urethral diverticula, inflammatory granuloma, and primary and metastatic neoplasms. On T2-weighted images, all normal urethras demonstrated a characteristic targetlike appearance with differentiation among the outer ring of low signal intensity, the middle zone of higher signal intensity, and the center of low signal intensity. After injection of gadopentetate dimeglumine, the targetlike appearance of the normal urethra was seen on the T1-weighted images. Urethral diverticula were detected with MR imaging in all nine patients with that diagnosis, and in each, MR imaging demonstrated urethral expansion, distortion of the zonal anatomy, and presence of fluid in the middle zone. Primary or metastatic urethral neoplasms were also detected with MR imaging in every patient with the diagnosis, but differentiation between benign and malignant disease was not possible. Local staging of primary or metastatic malignant disease was correct in eight of the 11 patients. In three patients, the inflammatory changes could not be differentiated from tumor invasion, resulting in overestimation of tumor extent. 
Purpura fulminans and adrenal hemorrhage due to group Y meningococcemia in an elderly woman. A 70-year-old previously healthy woman was admitted with a 1-day history of malaise, sore throat, nausea, vomiting, rigors, and confusion. She was found to be in septic shock with purpura fulminans and disseminated intravascular coagulation. She died within 36 hours of admission. Blood cultures grew Neisseria meningitidis group Y. Necropsy revealed evidence of shock and bilateral adrenal hemorrhage. 
Intracardiac mobile thrombus and D-dimer fragment of fibrin in patients with mitral stenosis. OBJECTIVE--To investigate the relation between intracardiac thrombus and blood coagulability in patients with mitral stenosis. DESIGN--Prospective study. Cross sectional echocardiography and plasma concentrations of the D-dimer fragment of fibrin were used concurrently to detect intracardiac thrombus in patients with mitral stenosis. SETTING--Department of Medicine, National Cardiovascular Centre, Osaka, Japan. PATIENTS--63 patients with mitral stenosis. None of them had been receiving any anticoagulants or antiplatelet agents. MAIN OUTCOME MEASURES--Plasma concentrations of D-dimer in patients with a mobile intracardiac thrombus, those in patients with a non-mobile intracardiac thrombus, and those in patients without an intracardiac thrombus. RESULTS--A mobile intracardiac thrombus was found in 10 patients and a non-mobile thrombus in eight. The remaining 45 patients had no intracardiac thrombi. Plasma concentrations of D-dimer in the 10 patients with a mobile thrombus were all greater than 300 ng/ml (mean 983.3, 95% confidence interval 498.9 to 1467.7 ng/ml) and they were significantly higher than those in the patients with a non-mobile thrombus (226.2, 33.6 to 418.8 ng/ml) and the patients without an intracardiac thrombus (147.2, 110.4 to 184 ng/ml). CONCLUSIONS--A high plasma concentration of D-dimer seemed to reflect a hypercoagulable intracardiac state and may be a helpful indicator of the possible presence of mobile intracardiac thrombus in patients with mitral stenosis. 
Prospective clinical and manometric study comparing pneumatic dilatation and sublingual nifedipine in the treatment of oesophageal achalasia. A study was carried out in 30 patients affected by a mild or moderate degree of oesophageal achalasia to compare the clinical and manometric effects of sublingual nifedipine and pneumatic dilatation. Sixteen patients were dilated twice with Rider-Moeller dilators and 14 were treated with sublingual nifedipine 10-20 mg 30 minutes before meals. A manometric evaluation was performed before and six months after starting treatment. The clinical evaluation (according to Vantrappen's criteria) was performed every three months for a mean follow up of 21 months. In both groups of patients a significant (p less than 0.001) fall in lower oesophageal sphincter pressure was observed after treatment and excellent or good clinical results were observed in 75% of dilated patients and in 77% of patients treated with nifedipine. One patient could not tolerate nifedipine. No complications were observed after dilatation. It is concluded that longterm treatment with sublingual nifedipine and pneumatic dilatation are equally effective in the treatment of oesophageal achalasia of mild or moderate degree. 
Mutations of the p53 gene in lymphoid leukemia. p53 is currently considered to be a tumor suppressor gene product, and its alterations are suggested to be involved in several human malignancies. Here we show evidence of the possible involvement of p53 gene mutations in lymphoid leukemias studied by reverse transcriptase-polymerase chain reaction, single strand conformation polymorphism analysis, and nucleotide sequencing. Fourteen patients with various leukemias were examined and two with acute lymphoblastic leukemia and one with Waldenstrom's macroglobulinemia were identified to have mutations in the coding region of the p53 gene. These mutations included point mutation, triplet deletion, and single nucleotide insertion. Furthermore, expression of the wild-type p53 mRNA was not detected in the samples from these three patients. In one of them, chromosome 17p was deleted, suggesting the absence of the nonmutated p53 gene, whereas in the other two patients, chromosome 17p seemed to be intact by cytogenetic analysis. Our results suggest that alterations of the p53 gene may have a role in the genesis of some leukemias. 
Changes in quantitative SPECT thallium-201 results associated with the use of energy-weighted acquisition. The effect of utilizing energy-weighted acquisition on quantitative analysis of SPECT thallium-201 images was evaluated by simultaneously acquiring energy-weighted and windowed projection images in ten patients. The paired image sets were processed identically and evaluated by probability analysis of defect magnitude as indicated by a commercially available software analysis package. It was predicted that defect magnitude would increase as a result of improved image contrast. This was confirmed experimentally. One should be cautious in relying on strict quantitative criteria in cardiac studies with thallium-201, especially when major changes in the imaging system or technique are introduced. 
Lymphomatous presentation of childhood acute lymphoblastic leukemia. A subgroup at high risk of early treatment failure. Multivariate analyses of the clinical course of 1537 children with acute lymphoblastic leukemia (ALL) identified a subgroup which experienced short remission duration and a high incidence of extramedullary relapse. The patients differed from other ALL patients by the presence at diagnosis of two or more of a constellation of clinical and laboratory features: organomegaly or mass disease, E-rosette positivity, hemoglobin level greater than 10 g/dl, leukocyte count greater than 50,000/microliters, male predominance, and older age. This type of presentation of ALL is referred to as the "lymphoma syndrome" (LS) since such patients exhibit a pattern of several clinical and laboratory features which were observed repeatedly but in differing combinations, and some of which clinically resemble lymphoma. A subsequent database from 2231 patients was analyzed. Patients with a mediastinal mass, massive splenomegaly, or massive adenopathy, alone or in combination, had a worse outcome when the patient also had either leukocytosis, E-rosette-positive lymphoblasts, or a normal or near normal hemoglobin (Hb) level at diagnosis. Similarly, the above three laboratory features alone or in combination did not predict less than 40% disease-free survival (DFS) unless they were accompanied by at least one of the clinical features of mass disease. When at least one clinical feature and at least one laboratory feature were present, the overall DFS was 36% 6 years after diagnosis versus 64% for all other patients. The association of these features with poor prognosis remained significant after adjusting for the level of leukocyte count at diagnosis, age at diagnosis, and sex of the patients. Patients with this recurrent syndrome of features do not represent a homogeneous biologic entity but they constitute a subgroup of patients with ALL having a high risk of treatment failure using current therapies, including failure to achieve remission, early relapse, and increased frequency of relapse in extramedullary sites. They deserve early recognition at diagnosis and selection of treatment strategies appropriate for very high risk ALL. 
Chronic xerostomia increases esophageal acid exposure and is associated with esophageal injury. OBJECTIVE: To assess the effects of chronic xerostomia on parameters of gastroesophageal reflux and esophagitis. DESIGN: Observational study of a cohort of male patients with xerostomia and age-matched control subjects. SETTING: Tertiary-care Veterans Affairs Medical Center. SUBJECTS: Sixteen male patients with chronic xerostomia secondary to radiation for head and neck cancers or medications. Nineteen age-matched male control subjects with comparable alcohol and smoking histories. MEASUREMENTS AND MAIN RESULTS: Esophageal motility was similar in patients with xerostomia and controls. Clearance of acid from the esophagus and 24-hour intraesophageal pH were markedly abnormal in patients with xerostomia. Symptoms and signs of esophagitis were significantly more frequent in subjects with xerostomia. CONCLUSIONS: Chronic xerostomia may predispose to esophageal injury, at least in part, by decreasing the clearance of acid from the esophagus and altering 24-hour intraesophageal pH. Esophageal injury is a previously unreported complication of long-term salivary deficiency. 
Insulin and glucagon therapy of acute hepatic failure. When insulin and glucagon are administered to rats with severe liver injury, survival is enhanced with an attenuation of the liver injury compared to that of untreated controls. In rats with acute liver injury both hormones produce a rapid normalization of hepatic protein content following initiation of DNA synthesis. When rats receive both hormones after partial hepatectomy, the first burst of DNA synthesis reaches a maximum earlier than that seen in controls. Both hormones enhance the increment of hepatic putrescine essential for DNA synthesis through activation of ornithine decaroxylase and/or spermidine-N1-acetyltransferase. The enhancement of putrescine content by each hormone is additive. Putrescine supplementation promotes hepatic DNA synthesis after hepatectomy. Based on these data, we conclude that a combination of insulin and glucagon is effective in the therapy of acute hepatic failure in rats. The restoration of liver function as well as the stimulation of liver cell proliferation via putrescine production may contribute to this effect. 
Obesity, a disorder of nutrient partitioning: the MONA LISA hypothesis. The mechanisms underlying different types of obesity have been gradually clarified. Animal models with hypothalamic, genetic or dietary obesity have been examined with a feedback model. Four common final pathways are involved in this model. One of these final common pathways is the sympathetic nervous system. Most Obesities kNown Are Low In Sympathetic Activity states the MONA LISA Hypothesis. A second common pathway is the endocrine system involving adrenal glucocorticosteroids. The third common pathway is hyperphagia. Although not essential for most obesities, hyperphagia may be essential in animals with injury to the hypothalamic paraventricular nucleus. The final pathway is reduced physical activity. The tonic activity of these systems and their response to changes in the diet affect nutrient partitioning between fat and protein. This framework has been used to review genetic obesity, hypothalamic obesity and dietary obesity. 
A double-blind, placebo-controlled trial of topical PUVA in persistent palmoplantar pustulosis. The effect of topical PUVA was investigated in the treatment of patients with persistent palmoplantar pustulosis (PPP). In this double-blind, placebo-controlled trial of 27 patients with PPP there was an overall improvement of the hands and feet in both the active and placebo-treated areas and little difference between them. 
Initial two-year results of the Oregon Liver Transplantation Program. During the first 24 months of the Oregon Liver Transplantation Program, which began in October 1988, 94 patients were formally evaluated and 47 adults underwent 54 liver transplantations. Thirty-four percent of patients were veterans. The recipient operation lasted a mean of 7.4 hours (range: 4 to 16 hours). Veno-venous bypass was used routinely at first but selectively later (7 of the last 26 cases), resulting in reduced operating time. Hepatic artery reconstruction was end-to-end anastomosis in 52 cases and iliac conduit in 2. No arterial thrombosis occurred. Biliary reconstruction was choledochocholedochostomy in 83% and choledochojejunostomy in 17%. Biliary complications occurred in 28%. Operative mortality was 2%, and 1-year actual survival was 80%. Patients with hepatitis B fared worse, with four of six dying at a mean of 7.6 months. Overall, the median hospital stay was 30 days. Patients surviving more than 3 months had a mean Karnofsky score of 82%. No significant difference in outcome was noted in patients receiving prophylactic OKT3 monoclonal antibody (used in 45%) versus conventional immunosuppressive therapy. Overall, allograft rejection occurred in 55% of patients. Retransplantation was required in seven patients, three for primary graft nonfunction, two for uncontrolled rejection during induction therapy with OKT3, and two for graft failure secondary to recurrent hepatitis B. 
Evidence for a pathogenic linkage between glomerular hypertrophy and sclerosis. Primary renal disease of immunologic or nonimmunologic mechanisms induces loss of substantial nephron population. It is presumed that the initial loss of functioning nephrons causes alterations of function and metabolism in remnant nephrons, which per se are self-inflictive, leading to further loss of nephrons. The ultimate outcome of this vicious cycle is the end-stage kidney. The potential role of various pathophysiologic mechanisms has been explored. These studies have shown a tight link between glomerular hypertrophy and sclerosis. Analysis of individual glomeruli show a biphasic pattern of these two parameters. Early development of glomerular sclerosis takes place along with the hypertrophy of the glomerulus, and further advancement of sclerosis occurs with shrinkage in glomerular size. Thus, we propose that, after initial nephron loss, the remnant glomeruli are exposed to increased growth-promoting factors, which are self-inflictive in nature due to their capacity to produce excessive amounts of extracellular matrix in the mesangial area. When the excessive matrix obliterates the glomerular capillary lumen, a typical sclerotic lesion appears. This is a vicious and accelerating process, since sclerosis induces further reduction in the nephron population, thereby imposing greater influence of growth-promoting factors even on glomeruli that are initially resistant. 
Endorectal sonography in the evaluation of rectal and perirectal disease. Endorectal sonography initially was developed for evaluation of the prostate and now has been adapted for evaluation of rectal and perirectal disease. We used endorectal sonography to evaluate a spectrum of diseases, including primary and recurrent rectal carcinoma, metastases, villous adenoma, leiomyosarcoma, endometriosis, sacrococcygeal teratoma, chordoma, retroperitoneal cystic hamartoma, pelvic lipomatosis, diverticulitis, and perirectal abscess. The technique has been useful in localization of perirectal abscesses and in sonographically guided biopsy of perirectal masses. Knowledge of normal sonographic anatomy of the rectum is essential in the evaluation of rectal and perirectal disease. In this essay, we describe the technique of endorectal sonography and illustrate the sonographic findings in a variety of diseases. 
Electrophysiologic analysis of early Parkinson's disease. We have been interested in the application of quantitative measures of motor performance as a possible means of early detection of Parkinson's disease. To assess motor function, we have measured movement time (the physiologic correlate of bradykinesia) and reaction time (simple and directional choice) with an upper limb motor task, and tremor with accelerometry and electromyographic recordings. In this report we describe preliminary data from a Parkinson's disease patient group with symptoms of fewer than 2 years' average duration (compared with an age- and gender-matched normal control group) which indicate that precise, quantitative tests of motor function can detect the slight deviations from normal that are present in early Parkinson's disease. It appears that tests of bradykinesia are most sensitive, and detection of rest tremor is most specific. These tests may be applicable in screening individuals who are suspected of having or are "at risk for" Parkinson's disease and other related disorders. 
Total replacement for post-traumatic arthritis of the elbow. Fifty-three of 55 consecutive elbow replacements for post-traumatic arthritis were followed for a minimum of two years (mean 6.3, range 2 to 14.4). The patients presented difficult management problems, having undergone an average of two previous operations per joint; 22 joints had suffered prior complications; 18 had less than 50 degrees of flexion and six were flail. One of three versions of the Coonrad prosthesis was employed in all. During the follow-up period, 10 patients underwent 14 revision procedures for aseptic loosening; 38 elbows are currently without progressive radiolucent lines. In two patients an elbow had to be resected, one for deep infection and the other for bone resorption following a foreign-body reaction to titanium. The current design of the Coonrad prosthesis offers a reliable option for the treatment of post-traumatic arthritis but should be used only in carefully selected patients over the age of 60 years. 
Total excision and extra-anatomic bypass for aortic graft infection. Reports of high mortality and amputation rates following total excision and extra-anatomic bypass for aortic graft infection have prompted the use of alternate approaches including local antibiotics, partial resection, in situ revascularization, and graft excision without revascularization. Experience with aortic graft infection was reviewed to establish current morbidity and mortality rates and evaluate our bias in favor of total excision and extra-anatomic bypass. Aortic graft infection was identified in 32 patients, 8 with aortoenteric fistulas. The mean interval between graft placement and infection was 34 months. History of groin exposure (75%) or multiple prior vascular surgery (50%) was common. Clinical signs included fever and/or leukocytosis (23 patients), false aneurysm (9 patients), graft thrombosis (6 patients), groin infection (11 patients), and gastrointestinal hemorrhage (6 patients). Microbiologic data, available in 26 patients, demonstrated gram-positive organisms in 15 patients and gram-negative in 9. Multiple organisms were seen in 11 patients. Patients were treated by partial removal with (8 patients) or without (4 patients) revascularization or total removal with (18 patients) or without (2 patients) revascularization. Revascularization was by an extra-anatomic route, either simultaneous or staged. Overall morbidity/mortality was less in the revascularized groups (p = 0.01), while late complications were seen only after partial removal (p less than 0.01). The best results were found after total excision with revascularization. No patient in this group experienced late infection or amputation during a mean follow-up of 34 months (range: 1 to 168 months). Complications after total excision and extra-anatomic bypass for aortic graft infection are lower than generally appreciated. This approach should remain the standard to which other approaches are compared. 
Primary squamous cell carcinoma of a gastric remnant. A 77-yr-old male developed primary gastric squamous cell carcinoma 33 yr after gastric resection for peptic ulcer disease. At the time of diagnosis, he was being endoscopically followed for large irregular stomal polyps. Infiltrating squamous cell carcinoma with focal keratinization and stomal polypoid hypertrophic gastritis was found. Previous reports describe adenocarcinoma and adenosquamous carcinoma in gastric remnants. There are various theories as to how such a tumor may arise in this setting. 
Acoustic neuroma: a cost-effective approach. A cost-effective approach to the diagnosis and treatment of acoustic neuromas continues to evolve as diagnostic methods improve. In the past 7 months, since gadolinium-enhanced magnetic resonance imaging (MRI) has become available in our practice, our screening and presurgical workup has changed. The purpose of this article is to outline the current philosophy of the senior authors in relation to acoustic neuroma management on the basis of 72 patients diagnosed from July 1988 to February 1989. With more sensitive diagnostic means, older less sensitive studies may be eliminated from the routine workup, thus maintaining cost-effectiveness while preserving the highest standard of patient care. The body of this article will review our current use of the many available diagnostic options and emphasize a cost-effective approach. 
Aortic valve replacement with omniscience and omnicarbon valves. Clinical results achieved in 100 cases of aortic valve replacement with the Omniscience (O-S) valve during the period from 1980 to 1985 as well as 100 cases of aortic valve replacement with the Omnicarbon (O-C) valve during the period from 1985 to 1989 were studied. Concomitant surgical procedures including mitral valve replacement were performed in 63 patients in the O-S group and 67 patients in the O-C group. Cumulative follow-up in the two groups was carried out for a total of 559 and 273 patient-years, respectively. The overall 4-year actuarial survival rate was 82% +/- 3.8% in the O-S group and 89.5% +/- 3.2% in the O-C group, the corresponding rates for patients undergoing isolated aortic valve replacement being 82.9% +/- 4.2% in the O-S group and 91.9% +/- 3.5% in the O-C group. The overall 4-year actuarial event-free rate with respect to thromboembolic complications was 88.8% +/- 3.3% in the O-S group and 94.4% +/- 2.8% in the O-C group, as compared with the corresponding rates of 89.2% +/- 3.6% in the O-S group and 95.9% +/- 2.8% in the O-C group for patients undergoing isolated aortic valve replacement. The overall rate of valve-related complications, including thromboembolism, anticoagulant-related hemorrhage, perivalvular leak, infection, and structural failure, was 78.8% +/- 4.2% in the O-S group and 89.3% +/- 3.5% in the O-C group (p less than 0.05), and for isolated aortic valve replacement, 79.7% +/- 4.5% in the O-S group and 89.6% +/- 4.1% in the O-C group. 
Results of a multicenter study of the modified hook-titanium Greenfield filter. Initial efforts to modify the stainless steel Greenfield filter for percutaneous insertion led to development of a titanium Greenfield filter, which could be inserted by use of a 12F carrier. This device functioned well as a filter but had an unacceptable 30% rate of migration, tilting, and penetration. Therefore a titanium Greenfield filter with modified hooks was developed and has been tested in 186 patients at 10 institutions. Successful placement occurred in 181 (97%); placement of the remainder was precluded by unfavorable anatomy. A contraindication to anticoagulation was the most frequent indication for insertion (75%). All but two were inserted percutaneously, predominantly via the right femoral vein (70%). Initial incomplete opening was seen in four patients (2%), which was corrected by guide wire manipulation and asymmetry of the legs in 10 (5.4%). Insertion site hematoma occurred in one patient, and apical penetration of the cava during insertion occurred in a second patient. Both events were without sequelae. Follow-up examinations were performed at 30 days at which time 35 deaths had occurred. Recurrent embolism was suspected in six patients (3%) and two of three deaths were confirmed by autopsy. Filter movement greater than 9 mm was seen in 13 patients, (11%) and increase in base diameter greater than or equal to 5 mm was seen in 17 patients (14%). CT scanning showed evidence of caval penetration in only one patient (0.8%). Insertion site venous thrombosis was seen in 4/46 (8.7%) patients screened. The modified hook titanium Greenfield filter is inserted percutaneously or operatively through a sheath, eliminating concern for misplacement from premature discharge. 
Colonic complications after toxic tribal enemas. Tribal enemas obtained from traditional healers are used widely in Southern Africa for a variety of indications. Inclusion of injurious substances such as potassium dichromate may cause serious colonic and renal complications. Nine such patients, in seven of whom chromate use was confirmed, presented after a mean delay of 7.3 days. All patients had bloody diarrhoea and vomiting and three underwent major colonic resection, requiring a total of ten procedures. One patient suffered mechanical perforation of the rectum, with subsequent necrotizing fasciitis, necessitating rectal excision. Eight patients had acute renal failure and seven required dialysis. One patient died. At follow-up one patient has chronic renal failure and only three are completely well. Although local medical practitioners are aware of the problem, the challenge of preventing harmful cultural practices remains. 
Intradermal hepatitis B vaccination. The availability of vaccine since 1982 for immunization against hepatitis B virus (HBV) has had minimal impact on the disease; mass immunization has been suggested. Intradermal vaccination, which has precedent in prophylaxis of other infectious diseases, has been investigated as a low-cost alternative to traditional intramuscular HBV vaccination. Results of open and comparative trials indicate similar seroconversion rates for intradermal and intramuscular HBV vaccination routes in healthy adults. However, antibody titers and, presumably, duration of antibody protection appear to be decreased with intradermal HBV vaccination. Limited data suggest that demographic factors such as age and gender may affect vaccine responsiveness to intradermal HBV vaccine. Adverse skin reactions are common but do not represent a deterrent to continued intradermal HBV vaccination. There is a need for large-scale prospective comparative trials to substantiate the value of intradermal HBV vaccination. Nevertheless, the potential economic and epidemiologic benefit of intradermal vaccination justifies continued investigation for prevention of HBV infection. 
Meckel cave lesions: percutaneous fine-needle-aspiration biopsy cytology. The authors describe the novel combination of two traditional methods to facilitate diagnosis of Meckel cave lesions, which may otherwise require craniotomy to obtain adequate tissue samples. Fine-needle-aspiration biopsy cytology was performed on tissue obtained with a percutaneous approach via the foramen ovale with use of fluoroscopic guidance and intravenous analgesia during an outpatient procedure. This new application of fine-needle-aspiration biopsy cytology results in decreased patient morbidity and significant cost reduction. 
Audit of outpatients: entering the loop. OBJECTIVE--To develop and test a method for routine data collection to observe current practice in outpatient pain clinics. DESIGN--Prospective questionnaire survey completed by consultants on each patient seen during October 1989 to May 1990. SETTING--Outpatient pain clinics of five teaching and five district general hospitals in Scotland and northern England. MAIN OUTCOME MEASURES--Number of new referrals and their source, and characteristics of pain at presentation. RESULTS--4354 forms were completed by 21 consultants over 29 weeks, corresponding to 2241 patients, of whom 981 were new referrals. The proportion of consultations at which new referrals were seen varied among the 10 clinics from 15% to 34%. The difference could not be accounted for by type of hospital. Sources of new referrals varied widely between the clinics (for example, range 22% to 78% for general practitioner referrals), as did new referrals by the type of pain (range 10.8% to 55.2% for low back pain, 10.5% to 32.5% for pain associated with surgery). However, these differences in types of patients seen could not be accounted for by variations in referral patterns among clinics. Problems identified in performing an audit of outpatients included the difficulty of obtaining firm diagnoses, the need for a method to link successive patient contacts, and the complexity of the presenting problem in many patients. CONCLUSIONS--It is possible to collect data for audit routinely in outpatient clinics. Observation of current practice in the clinics suggested possible unmet need or inappropriate management, which may require changes in practice. 
Indications and limitations of aortic valve reconstruction. To elucidate the value of conservative operation for aortic regurgitation, all consecutive patients operated on between July 1988 and July 1990 were reviewed. Of 251 patients with aortic regurgitation, 107 (42.6%) had nonprosthetic operation. The mean age was 23 years, and 90 patients (84.1%) were rheumatic. Two techniques were used: repair (annular and leaflet plasties, 69 cases) and cusp extension with glutaraldehyde-treated pericardium (25 bovine, 13 autologous). There were two hospital deaths (1.8%), both in the repair group, and no late deaths or embolic events. Only 5 patients (4.7%) were anticoagulated. In the repair group there were 12 reoperations, four (5.9%) due to aortic and eight to mitral dysfunction. In the cusp extension group there were two reoperations due to mitral dysfunction. Echocardiographic follow-up showed better results with cusp extension. In conclusion, conservative operation for aortic regurgitation is possible in a high percentage of young rheumatic patients and does not require anticoagulation. Cusp extension is more reliable than repair in terms of early results, although its long-term durability is not yet known. 
Influence of human immunodeficiency virus infection on cell-mediated immunity in chronic D hepatitis. To determine whether the abnormalities of cell-mediated immunity described in chronic D hepatitis are associated with hepatitis D virus (HDV) infection or concomitant human immunodeficiency virus (HIV) infection, serologic and tissue hepatitis B virus (HBV) and HDV markers and T lymphocyte subsets were studied in serum samples from 38 patients with chronic D hepatitis, 26 of whom had HIV infection. Patients with chronic D hepatitis and HIV infection had significantly lower peripheral blood T4:T8 ratios resulting from a significant increase in T8+ (suppressor/cytotoxic) cells, while numbers of T lymphocyte subsets were normal in cases with chronic D hepatitis only. HIV+ patients showed an increase in HBV replication (identified by hepatitis B core antigen in liver and hepatitis B e antigen and HBV DNA in serum) and in HDV replication (tissue D antigen and HDV RNA) without evidence of more active liver disease. Probably the immunologic disturbances detected in chronic D hepatitis are secondary to HIV infection, do not contribute to the pathogenesis of liver injury, and are associated with increased viral B and D replication. 
Differential diagnosis of head and neck lesions based on their space of origin. 2. The infrahyoid portion of the neck. The infrahyoid portion of the neck can be considered as a series of contiguous fascial planes and intervening spaces that lend themselves well to axial imaging. These spaces can serve as a basis on which to formulate differential diagnoses for diseases in this region. This pictorial essay describes the fascia and fascial spaces of the infrahyoid portion of the neck. The contents of each space, the common abnormalities affecting the space, and the characteristic displacements produced by disease in each space are reviewed. 
Congestive heart failure symptoms in patients with preserved left ventricular systolic function: analysis of the CASS registry. The clinical characteristics and long-term survival of 284 patients from the Coronary Artery Surgery Study (CASS) registry data base who had moderate to severe congestive heart failure symptoms and a left ventricular ejection fraction greater than or equal to 0.45 were studied. A control group consisting of registry patients with an ejection fraction greater than or equal to 0.45 who did not have heart failure was used for comparison. Patients who had heart failure were older and more likely to be female and to have a higher incidence of hypertension, diabetes and chronic lung disease than registry patients who did not have heart failure. As a group, patients with heart failure had more severe angina and were more likely to have had a prior myocardial infarction than were registry patients without heart failure. At 6 year follow-up, 82% of patients in the heart failure group survived compared with 91% of patients in the control group (p less than 0.0001). Multivariate analysis using the Cox proportional hazards model identified the following independent predictors of mortality: regional ventricular systolic dysfunction, number of diseased coronary arteries, advanced age, hypertension, lung disease, diabetes, increased left ventricular end-diastolic pressure and heart failure symptoms. Among patients with heart failure, the 6-year survival rate of those who had three-vessel coronary artery disease was 68% compared with 92% for the group without coronary artery disease. However, the 6-year survival rate for patients with heart failure who underwent surgical revascularization of diseased coronary arteries was not significantly improved compared with that of patients treated medically. 
Carcinoid tumour of the gastrointestinal tract: prognostic factors and disease outcome. This study represents retrospective analysis of 87 patients with a carcinoid tumour of the gastrointestinal tract seen and followed in the British Columbia Cancer Agency (BCCA) from 1960 to 1986. In 49 cases, the primary site was the small bowel. The rest of the cases were distributed as follows: 11 appendix, 10 rectum, 5 stomach, and 7 undetermined. We extrapolated the Dukes' and modified Astler-Coller surgicopathological classifications used for colorectal cancer for use in our cases of carcinoid tumour of the gastrointestinal tract. A strong correlation was found, using this staging, with disease-specific survival. Other prognostic factors included histologic differentiation, the presence of macroscopic residual disease after initial surgery, and level of 5-hydroxyindoleacetic acid (5-HIAA) in urine. Among 51 patients with surgically grossly removed disease, there was a tendency for the development of distant and distant/locoregional recurrence more often than locoregional recurrence alone. The liver was the commonest site of distant recurrence. Analysis of the effect of radiotherapy or chemotherapy on carcinoid tumour of the gastrointestinal tract proved unsuccessful because only a small portion of the patients had this treatment, and it was used mainly for palliation. 
Contemporary management of neurofibromatosis. The neurofibromatoses are two distinct entities with different genetic origins. The phenotypic expressions and required treatments are different. The devastating nature of neurofibromatosis-2 may be more effectively controlled through the application of advanced imaging techniques and contemporary neurotologic procedures. The most common manifestation of neurofibromatosis-2 is that of bilateral acoustic neuromas. The eventual total bilateral sensorineural deafness associated with this condition can be obviated in selected cases if the diagnosis is established early. Follow-up data are reported for three patients in whom hearing was preserved in at least one ear. When removal with hearing preservation is not possible, subtotal tumor removal with decompression of the internal auditory canals may delay progression of hearing loss. A new approach to tumors of the pterygomaxillary fossa that have extended to the middle cranial fossa has been successfully applied and is described. 
Growth hormone deficiency following radiation therapy of primary brain tumors in children. The medical records of 123 patients treated for brain tumors at Children's Hospital and Medical Center, Seattle, Washington, between 1985 and 1987 were reviewed. The endocrinological complications of radiation therapy and the effectiveness of growth hormone (GH) replacement therapy were assessed. These were the first 2 years after synthetic GH became available. The disease pathology was confirmed at craniotomy or biopsy in 108 patients. Ninety-five children completed radiation therapy and 65 of these were alive at the time of review; these 65 children represent the study population. The most common tumor types were medulloblastoma, craniopharyngioma, and ependymoma. Endocrine evaluation was initiated with changes in the patients' growth velocity. Patient workup included skeletal x-ray films for determination of bone and analysis of thyroxin, thyroid-stimulating hormone, and somatomedin-C levels. Following 1-dopa and clonidine stimulation, provocative studies of GH levels were performed. Growth hormone failure and short stature were observed in 26 children, most commonly in the 2nd year after tumor treatment. Eight patients with GH failure were also hypothyroid. Hormone replacement therapy was initiated with recombinant GH, 0.05 mg/kg/day, and all children so treated showed an increase in height, with eight patients experiencing catch-up growth. There were no complications of therapy or tumor recurrence. Studies of baseline bone age and somatomedin-C levels on completion of radiation therapy are recommended. Comprehensive endocrine studies should follow changes in the patients' growth velocity. With early GH replacement, catch-up growth is possible and normal adult heights may be achieved. 
Subarachnoid hemorrhage in sickle-cell disease. The neurological complications of sickle-cell disease include cerebral intracerebral hemorrhage; subarachnoid hemorrhage (SAH) has been infrequently reported. Among 325 patients with sickle-cell disease followed at the University of Illinois between 1975 and 1989, 11 cases of SAH were identified. Aneurysms were found in 10 of these patients, three of whom had multiple aneurysms. All of the patients had some degree of anemia and nine underwent craniotomy without hematological or neurological complications. From this review it appears that SAH is not uncommon in sickle-cell disease patients and tends to occur at a younger age and with smaller aneurysm size than in the general population. With proper perioperative management, including exchange transfusions to reduce the proportion of hemoglobin S to less than 30%, these patients can undergo angiography and craniotomy without an increased incidence of complications. The techniques used in managing sickle-cell disease patients with SAH are discussed. 
Selective expression of CD45 isoforms defines CALLA+ monoclonal B-lineage cells in peripheral blood from myeloma patients as late stage B cells. The peripheral blood lymphocytes from 42 patients with multiple myeloma (MM) and 13 patients with monoclonal gammopathy of undetermined significance (MGUS) were studied by three-color immunofluorescence (IF) using antibodies directed to a broad range of B-cell markers (CD19, CD20, CD21, CD24), CALLA (CD10), PCA-1 (a plasma cell marker), and to the high and low molecular weight isoforms of the leukocyte common antigen, CD45RA (p205/220) and CD45RO (p 180). CD45RA is expressed on pre-B and B cells, and a transition from CD45RA to CD45RO defines differentiation towards plasma cells. Peripheral blood mononuclear cells (PBMC) from patients with myeloma included a large subset of B-lineage cells (mean of 39% to 45%) that were CALLA+ and PCA-1+ in all patients studied, including newly diagnosed patients and patients undergoing chemotherapy. Southern blot analysis indicated the presence of monoclonal Ig rearrangements in PBMC and a substantial reduction in the germ-line bands consistent with the presence of a large monoclonal B-cell subset. Avoidance of purification methods involving depletion of adherent cells was essential for detection of the abnormal B cells. Phenotypically, this abnormal B-cell population corresponded to late B or early pre-plasma cells (20% to 80% of PBMC), as defined by the concomitant expression of low densities of CD19 and CD20, moderate densities of CALLA and PCA-1, and strong expression of CD45RO on all B cells, with weakly coexpressed CD45RA on a small proportion. Heterogeneity in the expression of CD45RA and CD45RO within the abnormal B-cell population from any given patient suggested multiple differentiation stages. Abnormal B cells similar to those in MM were also detected in MGUS, although as a lower proportion of PBMC (26%). Abnormal B cells from patients with MGUS expressed predominantly the CD45RO isoform, but had a lower proportion of CALLA+ and PCA-1+ cells than were found on B cells from MM. This work indicates that the large subset of circulating monoclonal B lymphocytes from myeloma patients are at a late stage in B-cell differentiation, continuously progressing towards the plasma cell stage. 
Preventing heel ulcers: a comparison of prophylactic body-support systems. Five commercially available body-support systems used in the prevention of decubitus heel ulcers were objectively compared for their capacity to dissipate or decrease pressure concentration at the most prominent posterior aspect of the heel in bedridden, insensate patients. The Foot Drop Stop, a foam heel suspender, completely eliminated contact between the heel and the bed, and it was the most successful in decreasing pressure concentration. The space boot and foam heel protectors were far more successful than sheepskin rugs or polyester heel protectors, which provided little protection to the prominent heel. 
Unilateral hydrocephalus: prenatal sonographic diagnosis. We studied six cases of unilateral hydrocephalus detected prenatally to analyze the sonographic features of the abnormality and to determine the cause and clinical outcome. In all cases, third-trimester sonograms showed marked unilateral lateral ventriculomegaly (mean atrial width, 4.4 cm) and normal contralateral lateral, third, and fourth ventricles. Five of the six cases had marked thinning of the cortical mantle on the affected side and shift of midline structures to the contralateral side. The causes of unilateral hydrocephalus were agenesis or stenosis of the foramen of Monro in three cases, transient obstruction of the foramen in one fetus with an intraventricular hematoma, underlying brain dysplasia in one fetus with a variant of holoprosencephaly, and undetermined in one case. All six neonates had placement of a ventriculoperitoneal shunt catheter; four of these have had normal cognitive development at follow-up. The remaining two infants have moderate to severe developmental impairment. Unilateral hydrocephalus is a rare anomaly that can be recognized by prenatal sonography. Even though unilateral ventriculomegaly may be marked, early diagnosis and treatment may result in a favorable clinical outcome. 
An overview of ankle arthrodesis. Arthrodesis of the ankle can result in a painless, normal walking gait. However, complications in ankle arthrodesis can be major, and can occur when anatomy, deformity, or bony deficiency is not properly addressed. Nonoperative treatment should always be considered first, and, if possible, an open or arthroscopic ankle debridement can provide significant pain relief. Arthrodesis should be considered after conservative treatment fails. Infections, deformity, sensory deficiencies, and bony defects require special consideration. The use of bone graft and internal or external compression will enhance the likelihood of a successful arthrodesis. 
Glandular odontogenic cyst: clinicopathologic analysis of three cases. The glandular odontogenic cyst is a rare cyst of odontogenic origin, first described in 1988 by Gardner et al. Three previously unreported glandular odontogenic cysts are presented; none recurred after the initial surgical treatment, and one example was associated with a squamous odontogenic tumor-like proliferation in the wall. Ten similar cases were found in the literature, and their clinical and roentgenographic features, and follow-up, have been compared with the present cases. 
Progression of scleral disease. The clinical features of 290 patients with scleral inflammation were reviewed to determine whether a classification based on the anatomical site and clinical appearance of the disease at presentation reflected its natural history. The authors' results confirm that the majority of patients remain in the same clinical category throughout the course of their disease. Of the 104 (35.9%) patients who experienced a recurrence of their disease, only 12 had progressed from diffuse to nodular disease, and 10 patients who originally had nodular disease developed scleral necrosis. Patients with necrotizing scleritis were older than patients in the other groups and more frequently had an associated systemic disease than patients with either diffuse or nodular disease; necrotizing scleritis was the most difficult disease to treat. Diffuse anterior scleritis had a lower incidence of visual loss (9%) than either nodular scleritis (26%) or necrotizing disease (74%), and, therefore, the authors consider nodular scleritis a disease of intermediate severity between diffuse scleritis and necrotizing disease. In this series, 12% of patients presented with posterior scleritis, and visual loss was most frequent in this group (84%). 
Antihypertensive drug treatment. Potential, expected, and observed effects on stroke and on coronary heart disease. The effects of prolonged differences in diastolic blood pressure (DBP) on the risks of stroke and of coronary heart disease (CHD) were estimated from nine major prospective observational studies involving about 420,000 men and women who were followed up for intervals of 6-25 years. The results indicate that a prolonged difference of about 6 mm Hg in DBP was associated with approximately 37% fewer strokes and 23% fewer CHD deaths and nonfatal myocardial infarctions. The effects of equivalent reductions in DBP produced by antihypertensive drug treatment but maintained for only a few years have been estimated in several overviews of randomized trials involving a total of 30,000-40,000 patients. The results of the overviews indicate that treatment reduced the risk of stroke by about 40%, suggesting that most or all the long-term potential benefits for stroke due to lower DBP were achieved within about 3 years of beginning treatment. The risks of nonfatal myocardial infarction and CHD death may have been reduced by about 10% among patients allocated to active treatment; the 95% confidence limits for the difference ranged from about zero to about 20%. Whatever the true effect of treatment on CHD, it would appear somewhat less than the difference in risk estimated from the observational studies for a prolonged difference in DBP of the same size. This apparent shortfall in benefit may reflect a long time-course for changes in DBP to have their full effects on CHD, possible adverse side effects of the principal trial treatments, or both. 
Effect of ventilation with soluble and diffusible gases on the size of air emboli. Pulmonary hypertension resulting from venous air embolism is known to increase after ventilation with highly soluble and diffusible gases. Exacerbation of the hypertension could be due to further blockage of the circulation if the bubbles enlarge as a result of ingress of gas by diffusion. This mechanism has been frequently cited but lacks direct proof. To determine directly whether intravascular air bubbles actually enlarge when highly soluble and diffusible gases are inspired, we used microscopy to measure the size of gas emboli in vivo. When air bubbles were injected into the right atrium, the bubbles that appeared in pulmonary arterioles were larger during ventilation with helium or nitrous oxide than with air. Air bubbles injected into the pulmonary artery enlarged when the inspired gas was changed to helium or nitrous oxide. The direction, magnitude, and timing of changes in bubble size were consistent with a net diffusion of gas into the bubbles. These data support the idea that venous air emboli enlarge during ventilation with soluble and diffusible gases and thereby cause further vascular obstruction. 
Platelet activation in the pathogenesis of unstable angina: importance in determining the response to plasminogen activators. Unstable angina is a clinical syndrome of recurrent myocardial ischemia. In some cases, this reflects episodic platelet activation and coronary thrombosis. Thus, the biosynthesis of thromboxane A2, which is largely derived from activated platelets, is increased, often coincident with chest pain. The major role of platelets in unstable angina may influence the response to plasminogen activators. Platelets increase the resistance of thrombi to lysis, by inducing clot retraction and cross-linking and by releasing inhibitors. Thus, coronary thrombi in unstable angina may be resistant to lysis. Furthermore, both t-PA and streptokinase cause platelet activation and thrombin formation in vivo, possibly via plasmin. Plasmin can activate platelets and factor V directly. These prothrombotic effects of plasminogen activators may limit their activity in unstable angina. At the very least, their therapeutic efficacy may be highly dependent on the coadministration of potent antiplatelet agents and anticoagulants. 
Viral hepatitis. The new ABC's. Hepatitis may be caused by hepatitis A virus, hepatitis B virus, hepatitis C virus (classic non-A non-B viral hepatitis), hepatitis D virus (delta agent), and hepatitis E virus (epidemic non-A non-B viral hepatitis). Cytomegalovirus, Epstein-Barr virus, and herpes simplex virus may also occasionally cause hepatitis. Some forms of hepatitis carry the risks of chronic infection, cirrhosis, or hepatocellular carcinoma. Treatment options for viral hepatitis are limited and, in many cases, still under investigation. Prophylaxis is available for many forms of hepatitis and should be offered to those at risk. 
Reversal of protein-bound vitamin B12 malabsorption with antibiotics in atrophic gastritis. The role of bacteria in the bioavailability of protein-bound vitamin B12 was examined in eight elderly subjects who had atrophic gastritis and in eight normal controls. On separate days and in random order, vitamin B12 absorption tests were performed using either radiolabeled crystalline or protein-bound vitamin B12. At the same time, bacterial samples were collected from the upper gastrointestinal tract. The tests and gastrointestinal aspirates were performed before and during tetracycline therapy. Crystalline vitamin B12 was absorbed to the same extent in the two study groups. Atrophic gastritis subjects absorbed significantly less protein-bound vitamin B12 than normal controls (mean +/- SEM, 0.7% +/- 0.2% vs. 1.9% +/- 0.5%, respectively). However, protein-bound vitamin B12 absorption in these subjects normalized after antibiotic therapy. These results suggest that the small amounts of vitamin B12 released from the protein binders is readily absorbed (as shown in vitro) and/or metabolized by bacteria. 
Telangiectatic osteosarcoma. Telangiectatic osteosarcoma is a rare variant of osteosarcoma. In the original report from the authors' institution, a poor prognosis was noted. The authors have updated their experience with this entity. The prognosis for patients with telangiectatic osteosarcoma has improved remarkably. The prognosis in the present series seems to be the same as that for conventional osteosarcoma. Adjuvant chemotherapy seems to help in salvaging patients with metastatic disease. However, in this small series, survival of patients without metastasis is apparently not influenced by whether they received chemotherapy. 
Large vessel occlusion with vasculitis in systemic lupus erythematosus. Patients with SLE may have acute large vessel occlusion due to vasculitis and/or circulating antiphospholipid antibodies, as illustrated by the case we have reported. Unfortunately, delayed medical attention led to gangrene of the foot and amputation. Early recognition and appropriate treatment may significantly decrease morbidity and mortality. Medical treatment may include corticosteroids, thrombolysis, anticoagulation, or immunosuppression. 
Angiotensin converting enzyme inhibitors. Present and future. The angiotensin converting enzyme (ACE)-inhibiting agents have emerged with the diuretic agents, beta-adrenergic receptor-blocking agents, and calcium antagonists as therapeutic options for major consideration during the initial treatment of hypertensive patients. These compounds antagonize a potent pressor mechanism underlying hypertensive disease. The ACE inhibitors curtail the generation of the potent octapeptide angiotensin II; in addition, degradation of the potent vasodilator bradykinin is inhibited. Hemodynamically, ACE inhibitors reduce arterial pressure through a decreased total peripheral resistance that is unassociated with reflex stimulation of the heart or expansion of intravascular volume. The arteriolar dilation accounting for the decreased vascular resistance seems to occur in each target organ of the disease. Unlike the direct-acting smooth muscle vasodilators or adrenergic inhibitors, ACE inhibitors dilate the efferent as well as the afferent glomerular arterioles and thereby reduce glomerular hydrostatic pressure and renal filtration fraction, even though renal blood flow and glomerular filtration rate are preserved. The ACE-inhibiting compounds not only reduce left ventricular afterload in hypertension but also diminish cardiac mass and wall thicknesses. The mechanism(s) for some of these actions have not yet been defined precisely, but they undoubtedly involve the autocrine/paracrine actions of the renopressor system and their effects in the cellular biologic events of vascular smooth muscle and the cardiac myocyte. It seems plausible and exciting that the "more local" renin-angiotensin systems will be exploited by those ACE inhibitors yet to be synthesized, which will result in new applications for this class of pharmacological agents. 
Use of Valsalva maneuver to unmask left ventricular diastolic function abnormalities by Doppler echocardiography in patients with coronary artery disease or systemic hypertension. It has been suggested that changes in left atrial pressure may mask or mimic left ventricular diastolic function abnormalities detected by Doppler echocardiography. The effect of the Valsalva maneuver on the transmitral flow velocity profile was therefore studied in 28 patients without evidence of coronary artery disease (group 1, mean age +/- standard deviation 50 +/- 8 years) and in 94 patients with evidence of coronary artery disease or systemic hypertension (group 2, mean age 54 +/- 10 years). At baseline, group 2 patients had higher peak late diastolic filling velocity (A), lower peak early (E) to late diastolic filling velocity (E/A) ratio and longer isovolumic relaxation time than group 1, whereas heart rate, E velocity and E deceleration time were similar in both groups. During Valsalva, both groups had similar increases in heart rate and similar decreases in E velocity but E/A ratio decreased significantly only in group 2 because of a lesser decrease in A velocity. The E/A ratio was greater than or equal to 1.0 both before and during Valsalva in all but 1 patient in group 1, whereas in group 2, 32 patients had E/A greater than or equal to 1.0 at rest and during Valsalva, 33 patients had E/A greater than or equal to 1.0 at rest but less than 1.0 both at rest and during Valsalva. Using group 1 as controls, prevalence, specificity and positive predictive value of E/A less than 1.0 in group 2 were 31, 100 and 100% at rest and 66, 96 and 98% during Valsalva. 
Membrane cerebral lipids in Rett syndrome. The lipid membrane composition of cerebral tissue from 5 patients with classic Rett syndrome, ages 12-30 years, and from 14 age-matched controls was studied. The results demonstrated a selective loss of myelin-associated lipids and an enrichment of gangliosides in temporal white matter. The ganglioside pattern revealed an increase of astroglial cell-associated gangliosides and reduced proportions of gangliosides GD1a and GT1b. This latter finding may be crucial in synaptic function. The fatty acid compositions of ethanolamine phosphoglyceride, choline phosphoglyceride, and galactosylceramide were normal. 
Effect of respiratory muscle fatigue on subsequent exercise performance. The purpose of this study was to determine whether induction of inspiratory muscle fatigue might impair subsequent exercise performance. Ten healthy subjects cycled to volitional exhaustion at 90% of their maximal capacity. Oxygen consumption, breathing pattern, and a visual analogue scale for respiratory effort were measured. Exercise was performed on three separate occasions, once immediately after induction of fatigue, whereas the other two episodes served as controls. Fatigue was achieved by having the subjects breathe against an inspiratory threshold load while generating 80% of their predetermined maximal mouth pressure until they could no longer reach the target pressure. After induction of fatigue, exercise time was reduced compared with control, 238 +/- 69 vs. 311 +/- 96 (SD) s (P less than 0.001). During the last minute of exercise, oxygen consumption and heart rate were lower after induction of fatigue than during control, 2,234 +/- 472 vs. 2,533 +/- 548 ml/min (P less than 0.002) and 167 +/- 15 vs. 177 +/- 12 beats/min (P less than 0.002). At exercise isotime, minutes ventilation and the visual analogue scale for respiratory effort were larger after induction of fatigue than during control. In addition, at exercise isotime, relative tachypnea was observed after induction of fatigue. We conclude that induction of inspiratory muscle fatigue can impair subsequent performance of high-intensity exercise and alter the pattern of breathing during such exercise. 
Effect of temporary occlusion of hypogastric arteries on blood loss during radical retropubic prostatectomy. We report on a prospective, partially randomized study of 130 patients, examining the effect of temporary occlusion of the hypogastric arteries on intraoperative blood loss, perioperative blood replacement and change in preoperative to postoperative hematocrit. We observed no significant difference in any of these parameters when comparing patients who did and did not undergo intraoperative occlusion of the hypogastric arteries. These findings suggest that temporary occlusion of the hypogastric arteries during radical prostatectomy does not have a major effect on the blood loss associated with this operation. Extensive collateral circulation to the prostate and a substantial venous component of blood loss may explain these findings. Banking of 3 units of autologous blood preoperatively would have decreased the need for homologous transfusions in the majority of patients. 
Cross-resistance patterns in ACNU-resistant glioma sublines in culture. Three ACNU-resistant clones (R1, R3, and R12) were isolated from 9L rat glioma cells under selection pressure of ACNU in vitro. The authors have investigated the mechanisms of resistance and characteristics of these clones at the cellular level by studying cross-resistance patterns to chemical and physical agents. Although these resistant sublines showed complete cross-resistance to methyl-chloroethylnitrosourea (MCNU), no cross-resistance was observed for other alkylating agents, while each of the resistant sublines showed partial cross-resistance to structurally dissimilar toxic agents (vinblastine, Adriamycin, and VP-16). No difference in ACNU uptake was observed between 9L and R3 cells, and resistance patterns among alkylating agents suggested that the mechanism of ACNU resistance was specific to bifunctional nitrosoureas. Based on a transport study, this multidrug resistance could be explained by reduced intracellular uptake of these drugs, but there seemed little possibility that membrane P-glycoprotein, which usually is observed in typical multidrug-resistant cells, was expressed in these ACNU-resistant cells because enhanced drug efflux was not found in ACNU-resistant sublines. Significant collateral sensitivity to L-asparaginase indicated that ACNU might disturb the asparagine synthetic pathways by its mutagenic action. The increased level of total glutathione in the resistant sublines may be one mechanism of radiation or ACNU resistance. 
Cervicofacial cystic hygroma. Patterns of recurrence and management of the difficult case. Cystic hygromas usually present in infancy or early childhood as compressible masses that may rapidly and intermittently enlarge. While they may arise in any anatomic location, hygromas of the head and neck are especially difficult to manage since enlargement may cause serious sequela such as airway obstruction, feeding difficulties, and speech pathology. Complete extirpation of these lesions is often impossible, and recurrence rates are accordingly high. We reviewed our 10-year experience in treating cervicofacial cystic hygromas. Of 34 patients, 21 had lesions cephalad to the hyoid and 13 had lesions caudal to the hyoid. While none of the 13 children with infrahyoid lesions demonstrated feeding or respiratory difficulties, eight of 21 children with suprahyoid involvement presented with dysphagia or airway compromise. The recurrence rates for infrahyoid and suprahyoid lesions were 15% and 81%, respectively. Those children with suprahyoid hygromas also experienced an increased operative complication rate compared with patients with infrahyoid involvement. Principles of management for suprahyoid and infrahyoid lesions are described, including the specific management of lingual, submandibular, parotid, and parotofacial hygromas. 
Can essential hypertension be subclassified with respect to mechanism? Hypertension may result from a variety of abnormalities. The rise in blood pressure may trigger other secondary events that further influence cardiovascular homeostasis. The ability to measure some markers associated with hypertension or the responsiveness of blood pressure to nutritional interventions or to specific therapeutic agents may also have pathogenetic implications. The ultimate goal of further knowledge in this area should be to understand the fundamental abnormalities responsible for hypertension. Such insight would permit more effective treatment and, perhaps, primary prevention of this ubiquitous and multifaceted disorder. 
Effectiveness of imazodan for treatment of chronic congestive heart failure. The Imazodan Research Group. A 12-week, multicenter, double-blind, randomized, placebo-controlled trial of imazodan, a type III phosphodiesterase inhibitor, was conducted in 147 patients with congestive heart failure to determine clinical efficacy and safety. Patients were randomized to placebo or 2, 5 or 10 mg of imazodan administered twice daily. Patients were maintained on their standard therapy including diuretics, digoxin and an angiotensin-converting enzyme inhibitor. The mean ejection fraction was 23 +/- 10%. Exercise time increased from baseline in all 4 groups. There was no significant difference observed between the placebo group and any of the treated groups with regard to exercise time, ejection fraction, frequency of ventricular premature complexes or ventricular tachycardia. When analyzed by intent to treat, the placebo mortality was 7% (3 of 44) and the imazodan mortality was 8% (8 of 103) (p = not significant). This study failed to demonstrate that imazodan provided any benefit in exercise performance when compared with placebo. 
The anal continence plug: a disposable device for patients with anorectal incontinence. Anorectal incontinence is most commonly found in the elderly, but colorectal surgeons now see an increasing number of younger patients with this condition. Although medical and surgical treatments are available, a proportion of patients remain refractory to therapy. We investigated the efficacy of three designs of anal continence plug. 8 women and 2 men (mean age, 52 years) who were incontinent to both liquid and solid stool tested each plug for three consecutive weeks. 1 patients withdrew from the study. The median weartime for the optimum plug design was 12 h, and there were no episodes of incontinence in 82% of the periods during which the plug was in place. Patients required a median of eleven plugs per week, and in 82% of cases insertion was as easy as with a suppository. Plugs may have a place in the management of patients with anorectal incontinence. 
A review of californium-252 neutron brachytherapy for cervical cancer. Since 1976 a clinical trial has been conducted to test the feasibility, the potential, and to develop methods for using the neutron-emitting radioactive isotope, californium-252 (Cf-252), for the treatment of cervical cancer. A total of 218 patients were treated in the initial study period from 1976 until 1983. The trials initially treated advanced (Stages III and IV) cervical cancer patients using different doses and schedules; they were extended to include unfavorable presentations of Stages I and II because of favorable results in the initial trials. The authors began to treat patients with Stage IB bulky or barrel-shaped tumors and the majority were treated with both radiation and hysterectomy. Actuarial survival was determined for Stage IB disease and was 87% at 5 years and 82% at 10 years. For those tested with preoperative radiation it was 92% at 5 and 87% at 10 years. For Stage II, it was 62% 5 years and 61% at 10. Survival 5 years after combined radiation and surgical therapy for Stage II disease was 68%. For Stage III, it was 33% at 5 years and 25% at 10. However, 5-year survival using the early neutron implant was 46% versus approximately 19% for delayed Cf-252 or cesium 137. Different schedules and sequences of neutrons and photons greatly altered outcome. Neutron treatment before external photon therapy was better for all stages of disease. Only about 5% of all patients developed complications after neutron therapy. No hematologic or mesenchymal second tumors were observed. Neutron brachytherapy was found to be very effective for producing rapid response and greatly improved local control of bulky, barrel, or advanced cervical cancers. The clinical trial identified and evolved schedules, doses, doses per session, and developed methods different from standard photon therapy but highly effective for local control and cure of cervical cancers of all stages. Clinical and radiobiologic understanding for the use of neutron therapy was greatly advanced by this trial. Future trials will focus on patients with advanced disease and will require evaluation of adjuvant chemotherapy studies and neutron-enhancing chemicals. 
Comparison of polyamide and polypropylene membranes for plasma separation. Plasma separation experiments were made with polyamide experimental prototype hollow-fiber plasma filters with surface areas between 0.025 m2 and 0.1090 m2 using bovine blood collected in acid citrate dextrose (ACD). The maximum filtration velocity rose with the wall shear rate gamma w as gamma w 0.72 +/- 0.02 and decreased with the length of fiber L as L-0.41 with a correlation coefficient of 0.97 +/- 0.02. The results were similar to those with polypropylene fibers. We also investigated the occurrence of hemolysis as a function of shear rate and transmembrane pressure. The free hemoglobin concentration of filtered plasma was checked using a U.V. spectrophotometer. It was concluded that polyamide membrane filters can be safely used for plasma separation from blood. 
The relationship of chemotherapeutic and endocrine intervention on natural killer cell activity in human breast cancer. Peripheral blood natural killer (NK) activity against K562 target tumor cells was monitored in patients with breast cancer receiving no treatment, combination chemotherapy, and/or endocrine therapy. NK activity in untreated Stage I patients with no evidence of disease (ned) was significantly higher than in healthy controls. NK activity was shown to decline in individuals with cytotoxic drug therapy (P equals 0.036). There also were reduction in lymphocyte recoveries concomitant with chemotherapeutic intervention (P less than 0.001). Lymphocyte counts were incorporated in a calculation of absolute NK activity that more accurately reflected the significant reduction in NK activity that occurred in patients with localized and systemic disease on chemotherapy. Different chemotherapeutic agents were found to selectively affect NK activity. Stage II patients on phenylalanine mustard (P)/5-fluorouracil (F) (PF) and cyclophosphamide (C)/methotrexate (M)/5-fluorouracil (F) (CMF) protocols showed significant reductions in overall NK activity relative to healthy controls and Stage I patients with ned. Patients on P/doxorubicin (A)/F/tamoxifen (Tx) (PAFT) protocols showed reduced NK activity relative to Stage I patients. Patients on the short-dose C/A (CA) protocol showed normal levels of overall NK activity. High-risk Stage I patients on methotrexate (M)/F (MF)with sequential leucovorin rescue and patients with metastatic disease on endocrine therapy, i.e., Tx or megestrol acetate (Meg) showed overall NK activities in the range of healthy controls. Patients with systemic disease on CMF, CMF/vincristine/prednisone (CMFVP), vinblastine/A/thiotepa/fluoxymesterone (VATH), mitomycin/mitoxantrone (MtMx), and A regimens showed overall levels of absolute NK that were significantly less than either healthy controls or metastatic patients undergoing endocrine therapy. NK cytolytic data, monitored at multiple effector to target ratios, were subjected to exponential regression analysis. The elevation of NK cell responses in Stage I patients with ned and the decline of NK cell responses with cytotoxic chemotherapy were due to alterations in the maximal plateau levels of NK cell cytotoxicity represented by the A (asymptote) values. The k values obtained on regression analysis and indices of the relative killing capacities of individual NK cells remained unaltered in all populations. These results suggest that the cytolytic lymphocyte NK pool, elevated in Stage I patients with cancer, selectively declines as a result of cytotoxic therapy. 
The atrial natriuretic factor hormonal system in the regulation of sodium excretion in dogs with experimental heart failure. In response to a meat meal containing 125 mEq of sodium, conscious dogs (n = 5) with an arteriovenous (AV) fistula and chronic compensated heart failure exhibited temporally related increases in postprandial plasma immunoreactive atrial natriuretic factor (iANF), right atrial pressure, and sodium excretion. In separate experiments, two weeks of dietary sodium restriction produced similar marked stimulation of renin and aldosterone both in normal dogs (n = 5), and in AV fistula dogs (n = 5) with chronic high circulating levels of ANF. Plasma iANF did not change (P greater than .05) in either group. These results suggest that the ANF system is involved in the postprandial regulation of sodium excretion in the AV fistula dogs with compensated heart failure. In the postabsorptive state, however, the activity of the renin-aldosterone axis is closely related to dietary sodium intake and appears to function independently of the ANF system for the prevention of sodium loss. 
Malignant blue nevus. To elucidate the histologic features and biologic behavior of malignant blue nevus (MBN), 12 cases were analyzed in which the tumor showed no junctional activity and arose in a blue nevus background. Seven patients were men and five were women; their mean age was 48.8 years. Eight lesions were on the scalp, and no patient had a family history of melanoma. The histologic appearance of most lesions was a nodule or nodules of malignant cells in a blue nevus. Mitoses were present in all lesions with atypical forms in eight; however the mitotic rate exceeded two per ten high-power fields in only one lesion. Four lesions had necrosis, and four had a heavily pigmented malignant component. Four patients had recurrences; ten patients had metastases, and eight died of their disease. Therefore MBN is an aggressive neoplasm. 
Pheochromocytoma with pyrexia and marked inflammatory signs: a paraneoplastic syndrome with possible relation to interleukin-6 production. Pheochromocytoma can cause several paraneoplastic syndromes. We report a patient with pheochromocytoma who exhibited pyrexia and marked inflammatory signs along with an elevated serum interleukin-6 (IL-6) level. All of these abnormalities disappeared and serum IL-6 became undetectable by removal of the tumor. In addition, immunohistochemical analysis revealed the presence of IL-6 in the tumor cells. It is suggested that pyrexia and the elevation of acute phase proteins can be a paraneoplastic syndrome with pheochromocytoma, and that the elaboration of IL-6 from pheochromocytoma may play an important role in the development of the syndrome. 
Steps towards cost-benefit analysis of regional neurosurgical care OBJECTIVE--To determine the cost of averting death or severe disability by neurosurgical intervention. DESIGN--Retrospective analysis of one year's admissions for neurosurgery; comparison of outcome with expected outcome in the absence of neurosurgical intervention and with the cost of neurosurgery. SETTING--Wessex Neurological Centre. PATIENTS--1026 Patients were admitted to the neurosurgical service in 1984. Of 1185 admissions, 978 case records were available and outcome was known in 919. MAIN OUTCOME MEASURES--Outcome was assessed with the Glasgow outcome scale, modified as necessary, from the case notes, or by letter follow up to the general practitioner. Expected outcomes for each of the 54 diagnoses were derived from both published reports where available and an expert panel of 18 consultant neurosurgeons. The cost of the neurosurgical service for 1983-4 was known from a separate study and the cost per patient was calculated using the length of stay. RESULTS--The cost of neurosurgery in 1983-4 was 1.8 million pounds. In all, 243 deaths or severe disabilities were estimated to have been averted at an average cost of 7325 pounds (range 5000 pounds to 70,000 pounds). The overall cost per quality adjusted life year (QALY) was 350 pounds (range 34 pounds to greater than 400,000 pounds). The cost of long term care for severely disabled survivors is at least 18-fold greater than the cost of neurosurgical intervention to avert such disability. CONCLUSIONS--In Britain neurosurgery is not expensive in comparison with the costs and benefits of other areas of medicine, and the cost per QALY is unexpectedly low except for severe diffuse head injury, malignant brain tumors, and cerebral metastases. The neurosurgical budget should be assessed in the context of managing a patient in hospital and subsequently in the community. 
HLA class I antigen expression as a measure of response to antiviral therapy of chronic hepatitis B. HLA class I antigen expression on peripheral blood mononuclear cells was evaluated by flow cytometry in 21 HBeAg-positive patients with chronic hepatitis B. Measurements were made before, during or after treatment with recombinant interferon-alpha-2b, either given alone or after a 6 wk course of prednisone. Immunohistochemical staining for human leukocyte class I antigen was also evaluated in 28 percutaneous liver biopsy specimens either obtained before or after therapy (N = 27) and during therapy in one instance. The amount of HLA class I antigen on peripheral blood mononuclear cells varied markedly among individual patients, but the overall results indicated that the level of inducible antigen did not correlate with increments of ALT during therapy or with a virological response to therapy. Hepatocyte staining for HLA class I antigen was observed in a minority of biopsy specimens (29%) and also did not appear to predict a response or correlate with the severity of histological disease. These data do not support current theories concerning pathogenetic mechanisms in chronic hepatitis B nor do they suggest that spontaneous display of HLA class I antigen on hepatocytes or interferon-induced expression of these antigens on peripheral blood mononuclear cells is a critical determinant for a response to therapy. 
Malaria in an urban emergency department: epidemiology and diagnostic features of 25 cases. This article presents a retrospective study of 25 patients diagnosed with malaria in an urban emergency department (ED) between June 1986 and June 1989. The mean annual case rate of malaria in this study group was more than three times the national rate. This may be ascribed to the notable ethnic diversity of the population. A history of travel to an area endemic for malaria was eventually elicited from all patients. The most common chief complaint was fever (56%) followed by abdominal pain (12%). Temperatures were elevated in 70% of the patients, with a mean temperature of 102.9 degrees F (39 degrees C). Gender was found to play a role in delaying diagnosis, with women accounting for 83% of a group of patients requiring multiple ED visits before diagnosis. The authors conclude that malaria must be considered when diagnosing patients in ethnically diverse populations. Gender may be associated with a delay in diagnosis. A careful travel history and a peripheral smear are aids in rapid diagnosis. 
Hepatic interferon-alpha gene transcripts and products in liver specimens from acute and chronic hepatitis B virus infection. In this study we have examined the localization of interferon-alpha in liver tissue from acute and chronic hepatitis B virus carriers to establish whether the defect in interferon-alpha production reported in chronic hepatitis B virus infection is at a pretranscriptional or posttranscriptional level using in situ hybridization and immunohistochemical techniques. Interferon-alpha messenger RNA transcripts and the immunoreactive protein were abundant in liver tissue and in particular in hepatocytes from patients with acute hepatitis B virus infection who subsequently recovered. In contrast interferon-alpha polypeptide was present in a significantly lower number of sinusoidal cells, mononuclear cells and hepatocytes in chronic hepatitis B virus carriers. Although a high proportion of patients with chronic hepatitis B virus infection had cells that expressed interferon-alpha messenger RNA transcripts, the number of such cells was significantly less than in acute hepatitis B virus infection, indicating that the defect in the hepatic interferon-alpha synthesis is at the level of gene activation. Furthermore, using double immunohistochemical staining, the number of hepatocytes containing HBcAg correlated inversely with the proportion of neighboring sinusoidal cells expressing interferon-alpha. These data support previous observations that interferon-alpha production is reduced in chronic hepatitis B virus infection and are consistent with the view that this cytokine is important in the clearance of the virus. 
Death by embolization of prosthetic aortic valve. This report describes a case in which a young woman died from embolization of her prosthetic aortic valve. The discussion includes the embolization's association with chronic intravenous narcotism, recurrent bacterial endocarditis, and acute cocaine toxicity. 
Flunarizine in migraine: a minireview. Flunarizine is a non-selective calcium antagonist. It distributes preferentially in the adipose tissue and passes the blood brain barrier. Numerous controlled clinical studies have established that flunarizine is efficacious in migraine prophylaxis, including double-blind studies in which the drug was compared with placebo or other antimigraine drugs. To avoid side effects a special schedule or administration is necessary. Flunarizine has no myogenic effect on smooth muscle cells of the vessles. It is said to be the only calcium antagonist able to protect brain cells against hypoxic damage. In addition, the considerable body of information which shows flunarizine capable of directly influencing the central nervous system, suggests that the drug's anti-migraine action may depend on its ability to influence central phenomena. 
A single-blind comparison of intravenous ondansetron, a selective serotonin antagonist, with intravenous metoclopramide in the prevention of nausea and vomiting associated with high-dose cisplatin chemotherapy Ondansetron (GR 38032F), a selective antagonist of serotonin subtype 3 receptors, is effective in the prevention of emesis associated with cisplatin as well as other chemotherapeutic agents. In this randomized, single-blind, multicenter, parallel group study, we compared the efficacy and safety of intravenous (IV) ondansetron with IV metoclopramide in the prevention of nausea and vomiting associated with high-dose (greater than or equal to 100 mg/m2) cisplatin chemotherapy. Three hundred seven patients receiving their first dose of cisplatin, either alone or in combination with other antineoplastic agents, were randomized to receive ondansetron 0.15 mg/kg IV every 4 hours for three doses or metoclopramide 2 mg/kg IV every 2 hours for three doses, then every 3 hours for three additional doses. The study prohibited the concurrent administration of other antiemetics or dexamethasone. Patients receiving ondansetron had a higher rate of complete protection from emesis (40% v 30%, P = .07), a higher complete plus major response rate (65% v 51%, P = .016), a lower rate of failure (21% v 36%, P = .007), and a lower median number of emetic episodes (one v two, P = .005) than did those receiving metoclopramide. The median time to the first emetic episode was longer on ondansetron (20.5 v 4.3 hours, P less than .001). Adverse events occurred in 48% of patients receiving ondansetron and 69% of those receiving metoclopramide (P less than .001). Akathisia and acute dystonic reactions occurred only on metoclopramide; headache (controlled with acetaminophen) was significantly more frequent with ondansetron. Ondansetron is more effective, produces fewer adverse events, and is easier to administer than metoclopramide for the prevention of emesis associated with high-dose cisplatin chemotherapy. 
Thrombosis and thrombolysis in unstable angina. Pathophysiology of unstable angina involves spasm, plaque rupture, activation of platelets, and coagulation. The incidence and frequency of intracoronary thrombus formation are presently under active assessment in order to establish the potential benefit of thrombolytic therapy. A preliminary study was conducted in patients admitted in our coronary care unit for unstable angina with typical clinical and electrocardiographic criteria and with early coronary angiogram. After exclusion of 4 patients with left main coronary stenosis or contraindications for thrombolysis, 16 patients received thrombolytic infusion and 14 underwent a second coronary angiogram. Seven patients had an intracoronary thrombus (6 nonocclusive, 1 occlusive) and at the second angiogram only 3 nonocclusive thrombi were modified (1 disappeared, 2 were reduced). Moreover, the quantitative Coronary Angiography Analysis System (CAAS) in the 11 cases suitable for analysis did not show any significant changes, especially in the Ambrose type IIB lesions. In-hospital clinical outcome was not influenced by thrombolytic therapy (5 ischemic recurrences, 1 fatal myocardial infarction, 4 emergency and 4 elective revascularization procedures). This short series is in agreement with the literature data. Only one third of patients with active unstable angina remains refractory to conventional therapy. The transient benefit of thrombolysis is limited to patients with demonstrated intracoronary thrombi. Clinical or angiographic improvement are not always in correlation and until now do not seem able to prevent short-term recurrences or the need for revascularization procedures. 
Hypertension in obesity and NIDDM. Role of insulin and sympathetic nervous system. An important link exists between obesity, noninsulin-dependent diabetes mellitus (NIDDM), and hypertension. Most patients with NIDDM are obese; the incidence of hypertension in obesity and NIDDM is substantial, approaching 50% in some studies. Furthermore, hypertension is known to contribute to the increased cardiovascular morbidity and mortality in patients with obesity and NIDDM. Despite the obvious clinical importance, the pathogenesis of hypertension in obesity and NIDDM remains poorly understood. Recent studies have identified hyperinsulinemia and insulin resistance as important threads that tie hypertension, obesity, and NIDDM together. The hypothesis is developed that insulin-mediated sympathetic stimulation contributes to blood pressure elevation in both obesity and NIDDM. Recruited as a mechanism to limit weight gain and restore energy balance, insulin resistance and sympathetic stimulation increase blood pressure by enhancing renal Na+ reabsorption and stimulating the cardiovascular system. In this article, we review the evidence on which this hypothesis is based. 
Intracranial arteriovenous fistula manifesting as progressive neurological deterioration in an infant: case report. This 1-year-old male infant had been diagnosed with cerebral degenerative disease because he developed psychomotor regression, and brain atrophy was demonstrated on computed tomography. He underwent magnetic resonance imaging, which suggested a cerebrovascular malformation. Cerebral angiography disclosed an arteriovenous fistula, fed by an anterior cerebral artery and directly draining into a cortical vein. The occlusion of the feeding artery was followed by a satisfactory recovery. The mechanism of the neurological symptoms in this patient is thought to be caused by a steal phenomenon and compression of the brain stem by venous engorgement in the posterior fossa. 
Low power laser biostimulation of chronic oro-facial pain. A double-blind placebo controlled cross-over study in 40 patients. The efficacy of low power laser stimulation in the treatment of chronic oro-facial pain conditions was investigated in a double-blind placebo controlled modified cross-over study in 40 patients. The laser was an invisible infrared (IR) diode laser with an emission at 904 nanometer (nm). Treatment effect was evaluated by means of VAS-scales and global assessment of pain. Outcome of treatment was correlated to changes in urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA). The clinical impression was that placebo was superior to laser stimulation. No statistically significant difference between the analgesic effect of the laser and placebo irradiation was found on VAS-scales. A significant (P = 0.05) increase in 5-HIAA excretion was found in the placebo group. It is concluded that the possibility of a substantial placebo response should be taken into consideration using 904 nm (IR) lasers for pain treatment in patients with this type of chronic oro-facial pain. 
Colonic epithelial dysplasia or carcinoma in a regional group of patients with ulcerative colitis of more than 15 years duration. Colonoscopic screening for neoplasia was performed in a regional group of ulcerative colitis patients with a disease duration of greater than or equal to 15 years. A total of 121 patients, aged less than 80 years, were invited to participate, of whom 100 (83%) accepted colonoscopy, including biopsies in 15 standard locations of the entire colon, plus additional biopsies from all visible lesions. Unequivocal dysplasia was found in one patient with extensive colitis and a disease duration of 31 years. A polyp with highly differentiated adenocarcinoma was found in the sigmoid colon of a patient with intermittent rectum involvement, 37 years after the ulcerative colitis diagnosis had been made. Biopsy specimens from the remaining 98 patients showed no signs of dysplasia or cancer. Thus the frequency of pre-malignant or malignant changes is very low compared with the results of similar studies, and the rationale for general colonoscopic surveillance programmes for such patients is open to question. 
Important melanocytic lesions in childhood and adolescence. Melanocytic nevi are common in children and adolescents, and the preponderance of these lesions are benign. Congenital melanocytic nevi, dysplastic nevi, and large numbers of common acquired nevi, however, may indicate an increased risk of malignant melanoma. With the exception, possibly, of giant congenital nevi, melanoma associated with these lesions generally occurs in adulthood. Nonetheless, some patients can be identified as being at increased risk for the development of melanoma during childhood. The poor prognosis associated with advanced melanoma and the curability of early lesions underscore the importance of prompt recognition of melanoma when it does occur in children. Furthermore, physicians who care for children are in a key position to decrease risk of melanoma throughout the lifespan by encouraging avoidance of excessive sun exposure during childhood. 
Subcutaneous metoclopramide in the treatment of symptomatic gastroparesis: clinical efficacy and pharmacokinetics. We investigated the safety and efficacy of short-term s.c. administration of metoclopramide in the treatment of symptomatic gastric stasis. Ten patients with gastroparesis, documented by abnormal solid phase radionuclide gastric emptying study, were treated with 10 mg (2 ml) of s.c. metoclopramide every 6 hr for 3 days. Patients gave themselves the injections as outpatients. Questionnaires were then completed concerning symptom relief, local side effects and adverse reactions. A repeat gastric emptying study was obtained immediately after the last dose of metoclopramide. Serum metoclopramide concentrations were obtained at trough, 1, 2, 3, 4 and 5 hr postadministration and serum prolactin levels at trough, 1 and 3 hr. Pharmacokinetic analysis showed mean peak metoclopramide concentration at 30 min of 99.7 +/- 47.1 ng/ml with measured levels of 93.9 +/- 106.83 ng/ml at 60 min and return to trough values by 4 hr; trough prolactins remained elevated above normal values. Gastric stasis improved from a base-line retention of 78.7% of radioisotope at 2 hr to 72.5% after 3 days of therapy (P = .65). Eight patients reported significant improvement in symptomology and two patients reported lessening of symptoms such as nausea, vomiting, bloating, abdominal pain, heartburn and vomiting. The side effects were minimal and did not interfere with completion of the protocol. We demonstrated that s.c. administration of metoclopramide was well accepted by patients and resulted in subjective and objective improvement of gastric stasis. In addition, serum metoclopramide concentrations were comparable with other parenteral routes of administration. Furthermore, serum prolactin levels may provide both a bioassay of efficacy and a marker for monitoring compliance. 
Differential enhancement of interferon-gamma-induced MHC class II expression of HEp-2 cells by 1,25-dihydroxyvitamin D3. Interferon-gamma (IFN-gamma) induces the expression of MHC class II antigens on non-lymphoid cells. In this study we investigated the effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), the most active metabolite of vitamin D3, on the IFN-gamma-induced expression of MHC class II antigens on HEp-2 cells. We found that 1,25(OH)2D3 enhanced the IFN-gamma-induced expression of HLA-DR on these cells. Differential effects on the MHC class II antigens HLA-DR, -DQ and -DP were also observed. 
Reoperations for late complications following abdominal aortic operation. Fifty patients were identified who, following abdominal aortic operation, developed late complications affecting the vascular graft or endarterectomy and who underwent their first reoperation between 1979 and 1989. Thrombosis was the commonest complication affecting 28 (56 per cent) patients, followed by false aneurysm in 11 (22 per cent), enteric fistula in nine (18 per cent) and graft infection in two (4 per cent). The 30-day mortality rate for reoperation was 8 per cent; longer follow-up revealed mortality rates of 22, 50 and 63 per cent at 1, 3 and 5 years respectively. Thirty-four complications required reoperation within 5 years of the original surgery. Reoperation was needed for 35 patients whose original pathology was occlusive disease and for 15 whose original pathology was aneurysm. The nature of the complication was related to initial pathology; thrombosis was far commoner in those with occlusive disease, and enteric fistula and false aneurysm were commoner in those with aneurysmal disease. 
Serial antiarrhythmic drug treatment to maintain sinus rhythm after electrical cardioversion for chronic atrial fibrillation or atrial flutter. The sequential use of different types of antiarrhythmic drugs may improve arrhythmia prognosis in chronic atrial fibrillation or flutter after successful electrical cardioversion. The rationale for serial treatment is that the arrhythmogenic mechanism may vary between patients, leading to different responses to 1 specific drug. To investigate this issue prospectively, 127 patients having chronic fibrillation or flutter exclusively, underwent serial drug treatment with flecainide (stage I) followed by sotalol or, if contraindicated, quinidine (stage II) and eventually amiodarone (stage III). Stages II and III were entered after electrical recardioversion for a recurrence during stages I or II, respectively. Calculated on an actuarial basis, the 2-year cumulative percentage of patients free of the arrhythmia increased from 31% after stage I to 63% at the end of serial treatment. To reach this result, a mean of 1.8 +/- 0.8 cardioversions per patient were needed, with 53 patients progressing to stage II and 34 to stage III. Sixteen patients stopped serial treatment prematurely and 15 patients were considered to have intractable atrial fibrillation at the end of stage III. Incidence of proarrhythmia was low. Multivariate analysis disclosed that an older age, in combination with a large number of previous episodes of arrhythmia, a long previous duration of arrhythmia and presence of mitral valve disease, were predictive for medical refractoriness during serial treatment. It is concluded that serial treatment may improve arrhythmia prognosis in atrial fibrillation or flutter, with an acceptable incidence of proarrhythmic events. 
Correlation between molecular and clinical events in the evolution of chronic myelocytic leukemia to blast crisis. A patient with typical Philadelphia chromosome (Ph1)-positive chronic myelocytic leukemia (CML) was studied during sequential phases of disease: (1) initial chronic phase; (2) myeloid blast crisis; (3) second chronic phase; and (4) accelerated disease. A point mutation in the coding sequence of the p53 gene first appeared concomitantly with the blast crisis and then disappeared with the re-establishment of a second chronic phase. The chromosomal concomitant of the molecular alteration was a deletion of 17p. These observations suggest that abnormalities of the p53 anti-oncogene are temporally related to the clinical progression of some cases of CML and are probably responsible for the development of blast crisis in these cases. 
Correlation of radiologic assessment of lumbar spine fusions with surgical exploration. Although inspection of posterolateral lumbar fusion is the best method of determining its solidity, routine exploration of the fusion is somewhat impractical because of the morbidity and expense involved. Removal of internal fixation devices or implantable batteries or reoperation for failed back surgery enabled the exploration and assessment of lumbar spine fusions in 214 operations on 175 patients. The preoperative radiologic assessment (plain roentgenographs, polytomography, bending films, and computed tomographic scans) were correlated with surgical findings. This study indicated a significant percentage of inaccuracy of all radiologic modalities used. Noncorrelations were present in 36% of plain roentgenographs, 41% of polytomograms, 38% of bending films, and 43% of computed tomographic scans. Radiologic inaccuracy was manifest on both the positive and negative sides. Computed tomographic scanning presented the lowest percentage of inaccuracy (22%) and bending films the highest percentage (27%). Based on these findings, there exists the need for more accurate noninvasive methods to determine the solidity of spine fusions. 
Cervicocranial arterial dissection. Dissection of the cervicocranial arteries is becoming more frequently recognized as a cause of neurological disorders. Typical clinical features seen with dissection include unilateral headache, oculosympathetic palsy, amaurosis fugax, and symptoms of focal brain ischemia. The diagnosis of carotid or intracranial dissection is usually best confirmed by angiography, although magnetic resonance imaging and computed tomography have been shown to visualize intimal dissection. The prognosis in cases of spontaneous dissection is generally benign unless the initial manifestation involves infarction with substantial deficit. The best approach to treatment appears to be the administration of the anticoagulant, heparin, followed by warfarin or antiplatelet therapy. Surgical intervention is reserved for cases of progressive or recurrent ischemic complication that occurs despite the administration of adequate doses of anticoagulants. 
Cholelithiasis after treatment for childhood cancer. The authors evaluated the risk of development of cholelithiasis in 6050 patients treated at a single hospital for various childhood cancers with different therapeutic modalities, including chemotherapy, surgery, radiation therapy, and bone marrow transplantation, from 1963 to 1989. Patients with underlying chronic hemolytic anemia or preexisting gallstones were excluded. Nine female and seven male patients with a median age of 12.4 years (range, 1.2 to 22.8 years) at diagnosis of primary cancer had gallstones develop 3 months to 17.3 years (median, 3.1 years) after therapy was initiated. Cumulative risks of 0.42% at 10 years and 1.03% at 18 years after diagnosis substantially exceed those reported for the general population of this age group. Treatment-related factors significantly associated with an increased risk of cholelithiasis were ileal conduit, parenteral nutrition, abdominal surgery, and abdominal radiation therapy (relative risks and 95% confidence intervals = 61.6 [27.9-135.9], 23.0 [9.8-54.1], 15.1 [7.1-32.2], and 7.4 [3.2-17.0], respectively). There was no correlation with the type of cancer, nor was the frequency of conventional predisposing features (e.g., family history, obesity, use of oral contraceptives, and pregnancy) any higher among the affected patients in this study than in the general population. Patients with cancer who have risk factors identified here should be monitored for the development of gallstones. 
Comparison between anal endosonography and digital examination in the evaluation of anal fistulae. A prospective trial was performed comparing the accuracy of digital examination and anal endosonography in defining the anatomy of anal fistulae. Before operation 38 consecutive patients were assessed by the consultant in charge of the case, by a research fellow and by anal endosonography involving two radiologists. These findings were compared with the operative findings. Consultants correctly identified 26 of 33 internal openings, 29 of 34 primary tracks and 15 of 21 secondary tracks. The research fellow correctly identified 26 internal openings, 24 primary tracks and 10 secondary tracks. There was no significant difference between the accuracy of consultants and the research fellow. Anal endosonography identified 10 internal openings based on initial criteria. This rose to 24 when revised ultrasonographic criteria were applied. There was no statistical difference between consultant assessment and anal ultrasonography in correctly identifying intersphincteric and transphincteric tracks. Ultrasonography is unable to assess primary superficial, suprasphincteric and extrasphincteric tracks or secondary supralevator and infralevator tracks. Consultant assessment of secondary supralevator and infralevator tracks was correct in 78 per cent of cases. 
Towards a less costly but accurate test of gastric emptying and small bowel transit. Our aim is to develop a less costly but accurate test of stomach emptying and small bowel transit by utilizing selected scintigraphic observations 1-6 hr after ingestion of a radiolabeled solid meal. These selected data were compared with more detailed analyses that require multiple scans and labor-intensive technical support. A logistic discriminant analysis was used to estimate the sensitivity and specificity of selected summaries of scintigraphic transit measurements. We studied 14 patients with motility disorders (eight neuropathic and six myopathic, confirmed by standard gastrointestinal manometry) and 37 healthy subjects. The patient group had abnormal gastric emptying (GE) and small bowel transit time (SBTT). The proportion of radiolabel retained in the stomach from 2 to 4 hr (GE 2 hr, GE 3 hr, GE 4 hr), as well as the proportion filling the colon at 4 and 6 hr (CF 4 hr, CF 6 hr) were individually able to differentiate health from disease (P less than 0.05 for each). From the logistic discriminant model, an estimated sensitivity of 93% resulted in similar specificities for detailed and selected transit parameters for gastric emptying (range: 62-70%). Similarly, combining selected observations, such as GE 4 hr with CF 6 hr, had a specificity of 76%, which was similar to the specificity of combinations of more detailed analyses. Based on the present studies and future confirmation in a larger number of patients, including those with less severe motility disorders, the 2-, 4-, and 6-hr scans with quantitation of proportions of counts in stomach and colon should provide a useful, relatively inexpensive strategy to identify and monitor motility disorders in clinical and epidemiologic studies. 
Medulloblastoma: freedom from relapse longer than 8 years--a therapeutic cure? Seventy-seven patients presenting with medulloblastoma between 1958 and 1986 were treated at Stanford University Medical Center and studied retrospectively. Multimodality therapy utilized surgical extirpation followed by megavoltage irradiation. In 15 cases chemotherapy was used as adjunctive treatment. The 10- and 15-year actuarial survival rates were both 41% with an 18-year maximum follow-up period (median 4.75 years). There were no treatment failures after 8 years of tumor-free survival. Gross total removal of tumor was achieved in 22 patients (32%); the surgical mortality rate was 3.9%. No significant difference was noted in the incidence of metastatic disease between shunted and nonshunted patients. The classical form of medulloblastoma was present in 67% of cases while the desmoplastic subtype was found in 16%. Survival rates were best for patients presenting after 1970, for those with desmoplastic tumors, and for patients receiving high-dose irradiation (greater than or equal to 5000 cGy) to the posterior fossa. Although early data on freedom from relapse suggested a possible beneficial effect from chemotherapy, long-term follow-up results showed no advantage from this modality of treatment. The patterns of relapse and survival were examined; 64% of relapses occurred within the central nervous system, and Collins' rule was applicable in 83% of cases beyond the period of risk. Although patients treated for recurrent disease could be palliated, none were long-term survivors. The study data indicate that freedom from relapse beyond 8 years from diagnosis can be considered as a cure in this disease. Long-term follow-up monitoring is essential to determine efficacy of treatment and to assess survival patterns accurately. 
Locally advanced paranasal sinus and nasopharynx tumors treated with hyperfractionated radiation and concomitant infusion cisplatin. Fourteen patients with paranasal sinus complex and nasopharynx tumors were treated at State University of New York Health Science Center at Brooklyn (Brooklyn, NY) with a regimen of split-course hyperfractionated radiation (120 cGy/fraction) and concomitant cisplatin infusion (5 to 7 mg/m2/24 hours). All of the patients had T4 tumors or massively recurrent disease with base of skull or facial bone involvement. Twelve patients were treated with curative intent receiving total doses of 6000 to 6960 cGy (modal 6750 cGy), whereas two patients were treated with less than 5000 cGy as palliation. Eleven of the 12 patients (92%) achieved a complete response, and 7 of 12 (58%) are alive at 35 to 72 months (mean, 47 months). Five patients are alive with no evidence of disease, and two with a local recurrence. Three patients died of distant disease, and two died from a local recurrence. When the response to treatment was analyzed based on tumor volume and radiation dose, only two of nine lesions measuring between 4 to 10 cm failed locally. The two palliative patients had almost complete local clearance of the disease but died at 2 and 8 months, respectively. In nine patients, the eye or optic nerve was included in the treatment field and received between 2000 to 6960 cGy. Only one of these nine patients had ophthalmic complication and this was confined to the cornea. 
Iloprost attenuates the increased permeability in skeletal muscle after ischemia and reperfusion. Increased vascular permeability is an early and sensitive indicator of ischemic muscle injury, occurring before significant histologic or radionuclide changes are evident. We investigated the effect of iloprost, a stable prostacyclin analog, on microvascular permeability in a rat striated muscle model. In six control and six experimental animals the cremaster muscle was dissected, placed in a closed-flow acrylic chamber, and suffused with a bicarbonate buffer solution. Dextran labeled with fluorescein was injected intravenously as a macromolecular tracer, and microvascular permeability was determined on the basis of clearance of the fluorescent tracer. Two hours of ischemia were followed by 2 hours of reperfusion. In the experimental group iloprost (0.5 microgram/kg/min) was given in a continuous intravenous infusion. Microvascular permeability increased significantly during reperfusion in both control and experimental animals (p less than 0.0001). Treatment with iloprost, however, significantly attenuated this response compared to the control group, 4.8 +/- 0.3 versus 7.3 +/- 0.5 microliters/gm/min, respectively (p less than 0.0001). Iloprost decreases the rise in vascular permeability after ischemia and reperfusion. Experimental clinical use of iloprost under controlled conditions in the treatment of patients with acute skeletal muscle ischemia appears justified. 
Exercise training and coronary collateral circulation. This review examines the potential for an exercise-induced increase in coronary collateral circulation, with specific reference to the role and functional significance of collateral vessels, highlighting animal and human studies in particular, and their inherent methodological limitations. Exercise training may enhance myocardial oxygen supply by promoting transient periods of myocardial ischemia, a potent trigger of collateral growth. Some human studies have shown that moderate-to-high intensity training can result in a higher double product at the onset of angina and/or ischemic ST-segment depression, suggesting that myocardial oxygen supply has increased. Attempts to use thallium-201 exercise scintigraphy to assess myocardial perfusion before and after a physical training program have produced conflicting data, whereas angiographic studies in group trials have, without exception, yielded disappointing results. Thus, direct evidence that exercise stimulates collateralization in humans is lacking. 
Detection of human papillomavirus DNA in cancer of the urinary bladder by in situ hybridisation. The association of the human papillomavirus (HPV) with cancer of the urinary bladder was assessed by in situ hybridisation using probes selective for HPV types 6/11 and 16/18 DNA. No hybridisation signal was detected with the type 6/11 probe on 100 formalin-fixed, paraffin-embedded bladder tumours sampled. However, when the same samples were hybridised with the HPV type 16/18 DNA probe, 11 of 66 (16.6%) papillary and 1 of 10 (10%) solid transitional cell carcinomas gave positive signals. These results suggest the involvement of HPV in cancer of the bladder, although the frequency of multiple HPV types in these tumours is uncertain. 
Erythroleukemia in a child associated with monosomy 7. A case of erythroleukemia (EL) associated with monosomy 7 is reported. The EL was diagnosed 20 months after the initial diagnosis of monosomy 7 was made. An immunologic study of the blast cells using a monoclonal antibody was positive for glycophorin A, which suggested that they were of erythroid origin; this was confirmed by electron microscopy. Chemotherapy was started with low dose cytarabine. However, the patient had severe bone marrow suppression and died of pneumonia. Our case shows that monosomy 7 is an abnormality of the pluripotential stem cells, including erythroid cells, that resulted in a true erythroid neoplasm. 
Hypertension associated with increased renin concentrations in nephroblastoma. An infant with severe hypertension who had a nephroblastoma which was secreting active renin is described. Nephroblastoma must be included in the differential diagnosis of hypertension associated with increased renin concentrations, even in the absence of an abdominal mass. 
Differential hemodynamic effects and tolerance properties of nitroglycerin and an S-nitrosothiol in experimental heart failure. S-nitrosothiols are potent in vitro vasodilators, but little is known about their in vivo action. In this study, we compared the effects of S-nitroso N-acetyl penicillamine (SNAP) and nitroglycerin (NTG) on left ventricular (LV) hemodynamics in congestive heart failure rats. By using a twoday crossover design, stepwise i.v. infusions of SNAP or NTG at 3, 5 and 8 micrograms/min were administered for 30 min each, followed by a dose of 10 micrograms/min over the next 10 h. LV end-diastolic and peak-systolic pressures (LVEDP and LVPSP, respectively) were measured at selected intervals. SNAP and NTG produced maximal LVEDP reductions of 46 and 44%, respectively, at the highest infusion rate. However, at the lower doses, greater reductions of LVEDP were seen with SNAP. NTG had a smaller effect on LVPSP (maximum 6% reduction) than SNAP (maximum reduction of 15%). During the 10-h infusion of NTG, LVEDP gradually returned to base-line values, indicating the development of tolerance, despite relatively constant plasma levels of NTG over the infusion period. Tolerance in LVEDP effects was not observed during the 10-h infusion of SNAP. In the presence of NTG tolerance, rats were still responsive to SNAP (mean reduction of LVEDP 24%), suggesting the absence of cross-tolerance between these two nitrovasodilators. These results suggest that SNAP is a more potent in vivo vasodilator than NTG, has more arterial action than NTG and is less prone to produce LV hemodynamic tolerance. 
Pattern of arterial involvement of the head, neck, and eyes in giant cell arteritis: three case reports. The findings of two post-mortem examinations and one CT scan of patients with biopsy proved giant cell arteritis (GCA) are presented. The presence or absence of intracranial involvement in GCA is discussed. 
Coronary artery aneurysms--a case study and literature review. Coronary artery aneurysms are detected with increasing frequency owing to the advent of coronary angiographies. Although most patients with coronary artery aneurysms are asymptomatic, manifestations of myocardial ischemia may occur. The case described herein serves as a basis for a discussion of the pathogenesis, clinical manifestations, detection, and treatment of coronary artery aneurysms. 
Hypercalcemia of advanced malignancy: decision making and the quality of death. Hypercalcemia is a common complication of certain advanced malignancies and although not therapeutically difficult, its presence raises complex ethical issues. Treatment of this condition is most easily justified when the patient is not terminal, the benefits are tangible, and the patient agrees with therapy. Withholding treatment is defensible medically, legally, and morally when a terminal situation is present, when drawbacks exceed the benefits, and when an informed patient declines therapy. Hypercalcemia is one of a number of conditions of dying that can be controlled by the physician. The physician's decision to treat such a condition, in part, depends upon his or her view of a good death. Further study is needed to clarify and avoid those situations of dying which involve suffering. Physicians must begin this difficult analysis and dialogue if they are to fulfill their obligation to minimize suffering in all patients. 
Persistent neurotoxicity of systemically administered interferon-alpha. Fourteen cancer patients had evidence of persistent neurotoxicity of interferon-alpha therapy long after their treatment was discontinued. Although most of the cognitive symptoms were mild to moderate in severity, they were incapacitating to these individuals in their usual work. The neuropsychological test abnormalities were not attributable to subsequent therapy, disease status, or other medical problems. The pattern of deficits was consistent with frontal-subcortical dysfunction. Of the four patients who had follow-up assessment, two had improved and two had deteriorated. These findings suggest that in some cases interferon neurotoxicity is not reversible. 
'Medial maxillectomy' for lateral nasal wall neoplasms. Lateral rhinotomy and "medial maxillectomy," an en bloc resection of the medial maxillary sinus, ethmoid sinus with the lamina papyracea, medial orbital floor, and lacrimal fossa-duct, have been advocated for lateral nasal wall neoplasma. Experience with 35 (of 41) patients followed up at least 30 months (median, 57 months) postoperatively is reported. There was a 9% recurrence for benign tumors and 15% for malignant neoplasms, the latter only in the patients with nonmelanoma malignant neoplasms not receiving postoperative radiotherapy. The most frequent complications were cavity crusting, epicanthal scarring, and epiphora. 
Dementia: case ascertainment in a community survey. The three-stage East Baltimore Mental Health Survey, conducted in 1981 as part of the Epidemiological Catchment Area Program, provided an opportunity to assess the prevalence of dementia and specific dementing disorders in a community-based, cross-sectional sample of the population. From the 3,841 households originally sampled, 810 individuals were selected for clinical psychiatric evaluation. Forty-one individuals were given a provisional diagnosis and referred to Stage 3 for differential diagnosis, with 32 individuals completing this evaluation. Thorough clinical evaluation of these cases resulted in an overall prevalence of dementia of 4.5% in those 65 years of age and older. The prevalence of specific dementing disorders was Alzheimer's disease (AD) (2.0%), Multi-Infarct Dementia (MID) (2.0%) and Mixed Dementia (MD) (0.5%). Prevalence increased with age for all dementias: Non-Whites had higher rates of dementia than Whites; females had higher rates of AD while males had higher rates of MID; and the prevalence of AD increased with increasing education, whereas the prevalence of MID decreased with increased education. Although this study includes only a small number of cases, necessitating some caution in interpreting the results, these figures do represent an estimate of the prevalence of severe dementing disorders and provide a basis for further community study. 
Papular mucinosis in L-tryptophan-induced eosinophilia-myalgia syndrome. Five patients with the L-tryptophan-related eosinophilia-myalgia syndrome had a generalized eruption of flesh-colored papules. In all patients, histologic examination revealed a focal accumulation of mucin in the upper mid dermis, associated with increased dermal cellularity. The mucin was composed predominantly of hyaluronic acid, with small amounts of sulfated acid mucopolysaccharides. The cells within the lesion were fibroblasts. The lesions slowly regressed after L-tryptophan was discontinued. Proposed explanations for the L-tryptophan-related eosinophilia-myalgia syndrome have centered on contaminants, chemically related to L-tryptophan, introduced in the manufacturing process. Tryptophan metabolites have been linked with sclerotic cutaneous diseases but have not been previously implicated in cutaneous mucinoses. 
Fludarabine: a review. The new fluorinated adenine analog, fludarabine, has been tested for efficacy in many tumor types over the past ten years. Two other similar nucleoside analogs are currently available for commercial use. Cytarabine is used principally as an antileukemic agent, and vidarabine as an antiviral. Unlike vidarabine, fludarabine is resistant to deactivation by adenosine deaminase. Data from Phase I and II trials suggest that fludarabine is potentially effective in a number of leukemias, including acute lymphocytic leukemia, acute nonlymphocytic leukemia, and chronic lymphocytic leukemia (CLL). Unfortunately, the doses required to achieve adequate response in the acute leukemias (greater than 75 mg/m2) were above the maximum tolerated dose, resulting in intolerable granulocytopenia, thrombocytopenia, and a life-threatening neurotoxic syndrome. In CLL: however, the dose required to achieve a satisfactory response is well within tolerated limits. Long-term survival statistics are not yet available, but historical perspective strongly correlates response to other agents with increased survival times. Toxicities seen at dose regimens of 15-40 mg/m2/d for five consecutive days include somnolence, metabolic acidosis, confusion, fatigue, nausea, vomiting, increase in serum creatinine and aminotransferase concentrations, and pulmonary and hepatic abnormalities. Mild to severe hematologic toxicity has been observed at all dose levels. 
Endovascular treatment of intracerebral arteriovenous malformations: experience in 49 cases. The authors report the results of treatment in 49 consecutive patients with brain arteriovenous malformations (AVM's) who underwent therapeutic embolization with liquid adhesive agents between 1984 and 1988 at the Toronto Western Hospital. Thirty-three patients had no other treatment and were followed up with angiography at 2 years and clinically from 2 to 6 years. Of the other 16 patients, 10 had adjunctive radiosurgery and six underwent surgical resection following embolization. Seven (14%) of the 49 patients had a morphological cure effected by embolization as evidenced on their 2-year follow-up angiograms: these have remained clinically stable. Twelve patients developed neurological deficits after embolization; eight (16% of the series) were transient and four (8%) were permanent. Two patients (4%) had a delayed hemorrhage after incomplete obliteration of their malformations. Endovascular treatment resulted in clinical improvement in 15 (33%) of the other 46 patients. None of the patients who initially presented with hemorrhage had a rebleed following embolization. It is concluded that endovascular treatment with liquid embolic material can be an integral part of the multidisciplinary treatment protocol for patients with brain AVM's. 
Upper gastrointestinal lesions in elderly patients presenting for endoscopy: relevance of NSAID usage. The occurrence of upper gastrointestinal disease and the relevance of nonsteroidal antiinflammatory drug (NSAID) usage were documented in 511 consecutive patients (321 women, 190 men) over 70 yr old, referred for upper gastrointestinal endoscopy in a district general hospital. The findings were benign esophageal disease (43%), normal (15%), gastric ulcer (11.5%), and duodenal ulcer (11%). Gastric ulcers were more common in women taking NSAIDs (25%) than in NSAID abstainers (7%) p less than 0.001 and male NSAID users (8%) p less than 0.001. Esophagitis and esophageal stricture were not influenced by NSAID usage, but gastric erosions were more common (10% vs. 3%) p less than 0.01. Of 142 patients receiving NSAIDs, 41% presented with hemorrhage, compared with 20.5% of NSAID abstainers (p less than 0.001). Hemorrhage was as common in aspirin takers (15 of 33, 45%) as in standard-dose NANSAID takers (43 of 109, 39%), even though 86% were taking 300 mg of aspirin per day or less. In elderly patients, esophageal disease is common. NSAID use, even low-dose aspirin, is associated with an increased risk of hemorrhage. In females, NSAID usage is associated with gastric ulcer. 
Comparison of restorative proctocolectomy with and without covering ileostomy in ulcerative colitis. The experience of restorative proctocolectomy for ulcerative colitis is reported in 16 consecutive patients with no covering ileostomy (group 2) in comparison with 15 patients with a covering stoma (group 1); in each group a J pouch was constructed. All patients had pre- and postoperative clinical and manometric evaluations of the functional result up to 12 months. There were no deaths or permanent failures. The number of early complications was four in each group. Re-ileostomy was needed in one patient of group 1, and an ileostomy was constructed in three patients of group 2. At 1 year after operation the functional results did not differ between groups 1 and 2 in terms of daily frequency of defaecation (mean 5.6 and 5.4 in 24 h respectively), or in terms of anal basal or maximal squeeze pressures. There was a significant (P less than 0.01) saving in total hospital stay (median 11 days) and in operating theatre time (mean 41 min) in patients with no covering ileostomy. It is concluded that a covering ileostomy may be unnecessary in restorative proctocolectomy, at least in suitable cases with no technical difficulty at the time of operation. 
Characterization of severely and profoundly hearing impaired adults attending an audiology clinic. Despite the fact that around 12 per cent of adult patients attending an audiology department will be severely hearing impaired (pure tone averages of 0.5, 1, 2 and 4 kHz of 70 dB HL or worse in the better hearing ear), their clinical and audiometric characteristics have not been well documented. These characteristics were collected prospectively in 132 adult patients attending a Severe Impairment Clinic, set up to manage their specific problems. The inability to provide sufficient masking makes audiometric assessment of the severity of the impairment uncertain in the poorer hearing ear in 52 per cent of these patients. In addition, the limited bone conduction output makes it almost invariably impossible to assess the masked bone conduction thresholds and hence the air-bone gap in the poorer ear. Hence, accurate characterization is only practical of the better hearing ear in such patients. In 67 per cent of the better hearing ears, there was a mixed hearing impairment, the air-bone gap being 20 dB or greater. The aetiology of the conductive component was almost equally otosclerosis and chronic otitis media. In only 19 per cent was the impairment of a pure sensorineural type, broken down as 6 per cent congenitally acquired, 5 per cent due to meningitis and 9 per cent being adult in onset. In the remaining 14 per cent of patients the type of impairment could not be classified as the bone conductive thresholds were off scale. Having had experience of managing these patients at a special clinic and knowing the workload involved, it is argued that consideration be given to setting up such clinics in most departments. 
Agglutination of blood cardioplegia by cold-reacting autoantibodies. Cold-reacting autoantibodies occasionally occur in patients requiring cardiac operations. This report describes the clinical course of 1 patient with cold-reacting autoantibodies and intracoronary agglutination of the blood cardioplegia solution. Observations made in vivo and in vitro are considered in discussing recommendations for the management of extracorporeal circulation and cardioplegic arrest in patients with clinically silent cold-reacting autoantibodies. 
Toward an integrated understanding of fibromyalgia syndrome. I. Medical and pathophysiological aspects. Fibromyalgia syndrome (FS) is a chronic pain disorder characterized by diffuse musculoskeletal soreness, stiffness, non-restorative sleep and psychological disturbance. At present, much about the etiology, pathological mechanisms and course of FS are unknown. Indeed, standardized diagnostic criteria have only been recently agreed upon. The present paper is the first of a two-part series which reviews the extant empirical literature concerning FS, with a view to arriving at an integrated understanding of the syndrome. The present paper describes the clinical presentation of FS and historical conceptualizations of the disorder. Available research on pathophysiological mechanisms in FS is then presented. In this section we have included literature concerning histology of muscle, sleep architecture, neurotransmitter anomalies and neuropeptide involvement in FS symptomatology. 
Peripheral ameloblastoma: a clinical and histologic study of 11 cases. Peripheral ameloblastoma (PA) is a rare odontogenic tumor. Previously, only 39 cases of PA had been reported in the English literature. In this article 11 additional cases of PA are presented. Concordance with previous cases was evident with regard to race, clinical appearance, and site of predilection. However, differences were observed with regard to age, sex distribution, and predominant histologic pattern. The average age in the current cases is younger, there is no male bias, and the most common histologic pattern is plexiform rather than follicular or acanthomatous. Recurrence following simple excision is rare, but has been reported. Long-term postoperative follow-up is recommended. 
Primary breast lymphoma. Primary breast lymphoma (PBL) is a rare tumor of the breast. Three cases of PBL are being described. All three cases achieved remission following biopsy, chemotherapy, and/or radiotherapy. The literature is extensively reviewed with emphasis on true incidence of PBL and survival rates. 
High-attenuation mediastinal masses on unenhanced CT. On unenhanced CT scans, a variety of mediastinal masses contain areas with attenuation values higher than the attenuation value of the chest wall musculature. The increased attenuation may be diffuse or focal and may be a result of calcium deposition, high iodine content, or areas of acute hemorrhage. This report illustrates the gamut of high-attenuation mediastinal masses seen on unenhanced CT. Masses that are of high attenuation only on IV contrast-enhanced images (e.g., aberrant vessels) are not included. 
Subeschar tissue fluid: a source of cell-mediated immune suppression in victims of severe thermal injury. Thermal injury results in pronounced physiologic alterations in microcirculation at the site of tissue damage. The consequence of these changes is an increase in microvascular permeability, leading to the accumulation of tissue edema, or subeschar tissue fluid (STF). One of the adverse properties of edema is its capacity in vitro to inhibit cell-mediated immune function. Since previous studies evaluated STF collected 5 to 7 days after thermal injury, the present study was designed to determine the time frame during which STF demonstrates its immune suppressive nature. Seven patients with severe thermal injury (30% to 100% total body surface area) were entered into the study. STF was collected in serial fashion, beginning as early as 9 hours after injury and continuing until fascial excision or patient death (maximum of 139 hours after injury). The addition of STF to cultures of lymphocytes obtained from healthy donors resulted in complete inhibition of mitogen-induced lymphocyte proliferation (MILP). Serum collected concomitantly from this group of patients was also capable of inhibiting MILP. From its inception, STF possesses the ability to inhibit MILP; this suppressive nature is stable, persisting for prolonged periods of time. The gradual absorption of STF likely contributes to the serologic evidence of cell-mediated immune suppression documented in victims of severe thermal injury. 
Protooncogenes and growth factors associated with normal and abnormal liver growth. Hepatocyte replication during liver regeneration depends on extrinsic (circulating) and intrinsic (intrahepatic) factors. Two important growth factors produced in the regenerating liver are discussed, TGF alpha, an autocrine, stimulatory growth factor, and TGF beta, a paracrine inhibitory factor. The balance between the activities of these factors is likely to play an important role in regulating hepatocyte proliferation. The expression of some protooncogenes occurs sequentially during the first few hours after partial hepatectomy and is a marker for the entry of hepatocytes into the cell cycle (proliferative competence). As hepatocytes become competent to proliferate, they respond to TGF alpha and other growth factors and enter a proliferative phase. It is possible that TGF beta 1 serves as a stop signal for liver regeneration but the mechanisms by which TGF beta inhibits hepatocyte DNA synthesis are still unknown. 
Relation of psychopathology in general medical inpatients to use and cost of services. The authors investigated the relation between psychopathology in medically ill inpatients and use and cost of medical care services. Of 455 medical inpatients, the Medical Inpatient Screening Test identified 27.9% as very depressed, 27.5% as very anxious, 20.2% as having cognitive dysfunction, and 8.6% as having high pain levels. Overall, the test identified 51% of the patients as having high levels of psychopathology or pain. These subjects had a 40% longer median length of hospital stay and 35% greater mean hospital costs than those with low levels of psychopathology or pain. Patients with greater psychopathology also had higher hospital charges, more procedures during hospitalization, and more discharge diagnoses but did not differ from the other patients in sex, race, age, diagnosis-related group (DRG) major diagnostic category, or DRG weight. 
Enhancement of pulsed-dye laser ablation of arterial tissues with blood medium: effects of laser-induced shock waves. The influence of blood medium on tissue ablation by a pulsed dye laser and its selectivity for atheroma were investigated. The role of shock waves on tissue ablation was also evaluated. Normal and atherosclerotic human aortas were irradiated by a 480 nm pulsed dye laser activated at 5 Hz. The laser was coupled with a single 0.2 mm fiber (Uni-guide) (40 mjoules/pulse) or a multifiber catheter (14 x 150 microns) (100 mjoules/pulse). Shock waves were measured using a fluid-filled catheter connected to a strain gauge manometer. With the Uni-guide, pulse-dye lasing resulted in greater ablation of atheroma in blood (11.6 x 10(-3) mm3/joule, p less than 0.001 versus atheroma measured in saline and normal tissue in blood) followed by normal tissue in blood (2.5 x 10(-3)mm3/joule), atheroma in saline (1.71 x 10(-3)mm3/joule, p less than 0.05 versus normal tissue in saline), and normal tissue in saline (0.54 x 10(-3) mm3/joule). With the multifiber catheter, laser ablation was the greatest in atheroma in blood (0.55 +/- 0.26 mm3/joule p less than 0.001 versus atheroma in saline and normal tissue in blood), followed by normal tissue in blood (0.27 +/- 0.12 mm3/joule), atheroma in saline (0.14 +/- 0.15 mm3/joule, p less than 0.001 versus normal tissue in saline), and normal tissue in saline (0 mm3/joule). The ablation efficiency of the multifiber catheter was greater than that of the Uni-guide (p less than 0.0001). 
Isolated incisional metastases after intraperitoneal radioactive chromic phosphate therapy for ovarian carcinoma. Two women developed apparently isolated recurrences of ovarian carcinoma involving prior incisions after receiving intraperitoneal radioactive chromic phosphate (P-32) adjuvant therapy for early epithelial ovarian carcinoma. Both are alive without evidence of disease at second-look laparotomy after surgical resection of the abdominal wall metastases and cisplatin-based combination chemotherapy. Mechanisms of cutaneous and incisional implantation metastases are discussed. Adjuvant therapy with intraperitoneal P-32 is unable to provide systemic therapy for occult metastatic disease. The favorable outcome in these cases probably reflects limited tumor burden at the time of recurrence and stands in stark contrast to other cases of soft tissue recurrences of ovarian carcinoma reported previously. 
Blockade of the ATP-sensitive potassium channel modulates reactive hyperemia in the canine coronary circulation. The mechanism of reactive hyperemia remains unknown. We hypothesized that reactive hyperemia was related to the opening of ATP-sensitive potassium channels during coronary occlusion. The resulting hyperpolarization of the smooth muscle cell plasma membrane might reduce calcium influx through voltage-dependent calcium channels and result in relaxation of smooth muscle tone and vasodilation. In eight open-chest, anesthetized dogs, 30-second coronary occlusions resulted in an average flow debt repayment of 200 +/- 41%. After low-dose (0.8 mumol/min) and high-dose (3.7 mumol/min) infusion of intracoronary glibenclamide, flow debt repayment fell to 76 +/- 14% and 50 +/- 8%, respectively (p less than 0.05 compared with control for both). The decline in flow debt repayment was due to a significant reduction both in maximum coronary conductance during reactive hyperemia and in its duration. In addition, there was a significant decline in the sensitivity of the coronary circulation to adenosine-induced vasodilation after glibenclamide. While more variable, there was no overall change in the sensitivity of the coronary vasculature to acetylcholine-induced vasodilation after glibenclamide. We conclude that reactive hyperemia is determined in a large part by the ATP-sensitive potassium channel, probably through its effect on membrane potential and voltage-sensitive calcium channels. Because reactive hyperemia was never fully abolished at the highest doses of glibenclamide tested, it is possible that additional mechanisms are involved in the genesis of this complex phenomenon. 
Volume tests for chronic venous insufficiency: an appraisal. Chronic venous disease is increasingly treated surgically with a variety of experimental procedures. Noninvasive volume tests are commonly used before surgery to select patients and after surgery to assess results. Rapid volume changes are considered to indicate regurgitation. Rigorous statistical validation of tests and the confounding nature of unmeasured arterial inflow are seldom considered. Volume changes were measured in 29 control limbs and 35 limbs with venous disease, with mercury-in-silicone rubber strain gauges, for both exercise and elevation. Normalization for arterial flow permitted calculation of the regurgitation rate. Normal (95% confidence) limits for measured and calculated parameters were determined. Specificity was shown by the percent of normal parameter values for control limbs and sensitivity by the percent of abnormal values for extremities with venous disease. Arterial flow significantly altered volume curves. Normalization increased specificity and sensitivity significantly. Calf exercise tests, even normalized, were too insensitive to be reliable. Elevation tests were significantly more sensitive for determining regurgitation. However, exercise tests were useful and supplied important information about the calf muscle pump. We conclude that, as currently used, many limb volume test procedures are unsuitable but could be improved significantly by normalization to reduce the confounding effect of regional arterial flow and use of an elevation test to measure regurgitation. 
Identification of a mutation in porcine ryanodine receptor associated with malignant hyperthermia. Malignant hyperthermia (MH) causes neurological, liver, and kidney damage and death in humans and major economic losses in the swine industry. A single point mutation in the porcine gene for the skeletal muscle ryanodine receptor (ryr1) was found to be correlated with MH in five major breeds of lean, heavily muscled swine. Haplotyping suggests that the mutation in all five breeds has a common origin. Assuming that this is the causal mutation for MH, the development of a noninvasive diagnostic test will provide the basis for elimination of the MH gene or its controlled inclusion in swine breeding programs. 
Severe oral phenytoin overdose does not cause cardiovascular morbidity. STUDY OBJECTIVE: To evaluate the potential for cardiovascular toxicity from severe oral phenytoin overdose. STUDY POPULATION: Fifty-seven patients admitted during a two-year period to an inner-city hospital for severe oral phenytoin overdose, which is defined as a peak level of 40 micrograms/mL or more. METHODS: Case records were reviewed retrospectively for symptoms and signs of phenytoin toxicity, especially circulatory effects. Baseline and toxic 12-lead ECGs, when available, were reviewed in detail. Continuous variables were compared using either paired or unpaired t tests, as appropriate. Significance was taken as P less than or equal to .05. RESULTS: Mean peak phenytoin level was 49.4 +/- 7.7 micrograms/mL. Continuous single-lead ECG monitoring in 36 patients (63%) for a mean of 26.5 +/- 21.6 hours revealed no incidents of dysrhythmia requiring treatment. ECGs recorded during toxicity in 52 cases (91%) revealed no clinically significant abnormalities attributable to phenytoin. ECGs during toxic and baseline states were available for detailed analysis in 15 cases. Ten patients exhibited an increase in PR interval (mean, 19 +/- 10 ms) when toxic, whereas five had a decrease (mean, 18 +/- 11 ms) compared with nontoxic records. No change in heart rate, QRS duration, or corrected QT interval was observed. There were no circulatory complications and no deaths. CONCLUSION: Cardiovascular toxicity is rarely a manifestation of oral phenytoin overdose. Routine management of stable patients with severe phenytoin overdose in a monitored setting is not mandatory. 
Neurotoxicity of intraventricularly administered alpha-interferon for leptomeningeal disease. Nine patients with leptomeningeal disease are reported who were treated with intraventricular alpha-interferon (alpha-IFN). In seven of these patients, a progressive vegetative state developed during treatment. The patients became unresponsive to verbal commands but opened their eyes with auditory or tactile stimulation. It took an average of 3 weeks for these patients to become verbally responsive after treatment was discontinued. Electroencephalographic findings showed evidence of irritative involvement of the deep midline nuclei in 80% of patients. Periventricular white matter changes developed during treatment in three of six patients who underwent computed tomographic scans. All patients with this severe neurotoxicity received whole-brain irradiation before treatment. Possible mechanisms for the development of this neurotoxic syndrome are discussed. The neurotoxicity of alpha-IFN and brain irradiation may be additive, suggesting a cautious approach when using this combination for treatment. 
Effects of positive end-expiratory pressure on splanchnic circulation and function in experimental peritonitis. Splanchnic and central hemodynamic effects of positive end-expiratory pressure (PEEP) were studied in anesthetized pigs using mechanical ventilatory assistance, with or without sepsis (fecal peritonitis). One hour after sepsis, PEEP (10 cm H2O) was applied (n = 6). Another group (n = 6) had sepsis without PEEP. In one group (n = 6) without sepsis, PEEP was applied after 1 hour, while a fourth group (n = 5), without sepsis or PEEP, served as a control. The group with PEEP and sepsis had reduced cardiac index, portal venous blood flow, and liver surface blood flow. The group with PEEP alone had reduced splanchnic circulation by increasing gastrointestinal vascular resistance, while the group with sepsis alone had increased portal vascular resistance. In a separate series with sepsis, intermittent PEEP, and vigorous fluid resuscitation, it was demonstrated that avoiding hypovolemia did not seem to protect from the PEEP effects on the splanchnic circulation. The combination of sepsis and PEEP was not additive on portal blood flow reduction but reduced bile production. 
Factors affecting survival of patients with ruptured abdominal aortic aneurysm in a West Virginia community. The hospital records for patients treated for ruptured abdominal aortic aneurysms in southern West Virginia during a recent five year period were reviewed. The over-all mortality rate was 62 per cent. Patients with intraperitoneal rupture had a higher mortality rate (97 per cent) than patients with retroperitoneal rupture (25 per cent). Patients at increased risk were more than 80 years of age, presented with syncope, experienced a short duration of symptoms before seeking medical attention, had preoperative systolic blood pressure levels of less than 90 millimeters of mercury and had a preoperative hemoglobin level of less than 8. Other factors associated with death were a delay in beginning surgical treatment, a larger total blood loss and amount of blood transfused. The results of multivariate analysis demonstrated that preoperative blood pressure, preoperative hemoglobin, presence of syncope and the amount of blood loss were, in large part, reflections of the type of rupture and had only slight independent relationship to mortality. The most effective method of preventing fatal outcome is elective resection of the aneurysms before rupture occurs. 
Anticonvulsant profiles of the potent and orally active GABA uptake inhibitors SK&F 89976-A and SK&F 100330-A and four prototype antiepileptic drugs in mice and rats. The anticonvulsant profiles of two potent and orally active gamma-aminobutyric acid (GABA) uptake inhibitors, 1-(4,4-diphenyl-3-butenyl)-3-piperidine-carboxylic acid hydrochloride (SK&F 89976-A) and 1-(4,4-diphenyl-3-butenyl)-1,2,5,6-tetrahydro-3-pyridine-carboxylic acid hydrochloride (SK&F 100330-A), were determined with a battery of well-standardized tests in mice and rats and compared with the profiles of phenytoin (PHT), carbamazepine (CBZ), valproate (VPA) and clonazepam (CZP) when subjected to the same tests. ED50 values were calculated and compared with TD50 values for minimal motor impairment to provide protective indexes (PI = TD50/ED50). The anticonvulsant profiles of SK&F 89976-A and SK&F 100330-A were similar and suggest that these compounds raise the threshold for seizure initiation rather than inhibit seizure spread. Like intraperitoneal (i.p.) PHT, CBZ, VPA, and CZP, SK&F 89976-A and SK&F 100330-A inhibited seizures in corneally kindled rats. The profiles of SK&F 89976-A and SK&F 100330-A were most similar to that of CZP and virtually opposite to that of PHT. Intraperitoneal SK&F 100330-A provided complete protection against pentylenetetrazol-induced seizures [subcutaneous (s.c.) PTZ] in mice but was ineffective against seizures induced by maximal electroshock (MES) at doses slightly greater than its TD50. SK&F 100330-A provided complete protection against picrotoxin-induced seizures (s.c. Pic) and against both clonus and forelimb tonic extension induced by NMDA N-methyl-D-aspartate [intracerebral ventricular (i.c.v.)-NMDA] in mice; however, SK&F 100330-A was ineffective against seizures induced by bicuculline (s.c. Bic) and strychnine (s.c. Strych) at doses slightly greater than its TD50. SK&F 89976-A was similar but provided partial protection against NMDA-induced clonus. 
An in vivo model for the neurodegenerative effects of beta amyloid and protection by substance P. Deposition of the beta-amyloid protein in senile plaques is a pathologic hallmark of Alzheimer disease (AD). Focal deposition of beta amyloid in the adult rat cerebral cortex caused profound neurodegenerative changes, including neuronal loss and degenerating neurons and neurites. Chronic induction of the Alz-50 antigen appeared in neurons around focal cortical deposits of beta amyloid. Immunoblot analysis showed that beta amyloid induced Alz-50-immunoreactive proteins in rat cerebral cortex that were very similar to the proteins induced in human cerebral cortex from patients with AD. The neuropeptide substance P prevented beta-amyloid-induced neuronal loss and expression of Alz-50 proteins when coadministered into the cerebral cortex. Systemic administration of substance P also provided protection against the effects of intracerebral beta amyloid. Thus, beta amyloid is a potent neurotoxin in the adult brain in vivo, and its effects can be blocked by substance P. 
Chronic prosthetic vascular graft infection visualized with technetium-99m-hexamethylpropyleneamine oxime-labeled leukocytes Technetium-99m-HMPAO labeled leukocytes demonstrated chronic femoro-femoral prosthetic vascular graft infection several times during an 18-mo period in a 77-yr-old man. The intensity and distribution of the uptake in the graft were fluctuating in different imaging occasions possibly indicating the strength and location of the infection. Gallium-67-citrate imaging showed negative results twice. The reason for negative 67Ga results remained obscure. The infected graft was removed and the patient did well 5 mo postoperatively. 
No effect of zidovudine on hepatitis B virus replication in homosexual men with symptomatic HIV-1 infection. Zidovudine triphosphate inhibits the hepatitis B virus (HBV) DNA polymerase (DNAp) in vitro. Serial measurements of serum HBV DNAp activity and HBV DNA were made in 14 consecutive male homosexual patients starting zidovudine for symptomatic HIV-1 infection. Median duration of treatment was 15 weeks (range 2-72). In the 13 patients with detectable DNAp/DNA pre-treatment, no significant change in either measure of viral replication was observed during the first 16 weeks of treatment compared with the 13 weeks prior to treatment. The lack of response may be due to the opposing effect of immunosuppression, or to a failure of in vivo activity. 
Tumor invasion of the chest wall and mediastinum in lung cancer: evaluation with pneumothorax CT. For preoperative evaluation of chest wall and mediastinal invasion by lung cancer, computed tomography (CT), combined with artificial pneumothorax (pneumothorax CT), was performed in 43 patients with lung cancer in whom conventional CT scans showed that the mass was contiguous to the chest wall (n = 30) and/or mediastinum (n = 25) but without evidence of definite tumor invasion. Invasion was diagnosed on the basis of whether an air space existed between the mass and the adjacent structures. In three patients pneumothorax was not produced. After the procedure, four patients developed symptomatic pneumothorax, and one, subcutaneous emphysema. Comparison of diagnoses based on findings at pneumothorax CT, surgery, and pathologic examination showed that pneumothorax CT is 100% accurate for chest wall invasion and 76% accurate for mediastinal invasion. The authors conclude that this procedure is helpful in accurate evaluation of the T criterion in lung cancer, especially for patients in whom findings at conventional CT suggest tumor invasion of the chest wall and mediastinum. 
Alpha 2 macroglobulin state in acute pancreatitis. Raised values of alpha 2 macroglobulin-protease complexes in severe and mild attacks. Plasma values of C reactive protein, alpha 1 proteinase inhibitor, alpha 2 macroglobulin, and complexed alpha 2 macroglobulin have been determined in serial samples from 27 patients with acute pancreatitis. Complexed alpha 2 macroglobulin was measured by a novel enzyme linked immunosorbent assay with a monoclonal antibody specific for the complexed form. Patients with severe illness had lower concentrations of total alpha 2 macroglobulin and higher concentrations of complexed alpha 2 macroglobulin than those with mild illness, and in the majority of severe attacks the abnormal amounts of complexed alpha 2 macroglobulin were present throughout the eight days of the study. The proportion of total alpha 2 macroglobulin in the uncomplexed form, however, was generally greater than 90%, and in 26% of the mild cases completely normal concentrations of uncomplexed alpha 2 macroglobulin (greater than 99% of total) were found throughout the eight days of the study. This suggests that exhaustion of alpha 2 macroglobulin in plasma is unlikely to be a major factor in the pathogenesis of acute pancreatitis. 
Depression of factor XII-dependent fibrinolytic activity characterizes patients with early myocardial reinfarction after recombinant tissue-type plasminogen activator therapy. Twenty patients with acute myocardial infarction treated with recombinant tissue-type plasminogen activator (rt-PA) had endogenous factor XII-dependent fibrinolytic activity levels measured throughout the hospital period and those levels were prospectively correlated with the incidence of recurrent myocardial infarction until 8 weeks after hospital discharge. Within the follow-up period, recurrent myocardial infarction was observed in 8 patients, whereas the remaining 12 patients showed no clinical evidence of recurrence. The patients in the reinfarction group were characterized by a more pronounced depletion of and sustained lower levels of factor XII-dependent fibrinolytic activity than were the patients with no reinfarction (p less than 0.05). The decrease in fibrinolytic activity during rt-PA therapy was significantly associated with a depletion of functional alpha 2-antiplasmin, the primary plasmin inhibitor. These results indicate that, paradoxically, coronary thrombolysis with rt-PA involves depletion of endogenous factor XII-dependent fibrinolytic activity levels, which constitutes a risk for early myocardial reinfarction. 
Arthroscopic stapling for detached superior glenoid labrum. Superior labral tears of the shoulder involve the biceps tendon and labrum complex which may be detached, displaced inferiorly, and interposed between the glenoid and the humeral head. We have treated ten young athletes with painful shoulders due to this lesion by arthroscopic stapling. Arthroscopy at the time of staple removal, after three to six months, showed that all the lesions had been stabilised. Clinical review at over 24 months showed an excellent or good result in 80%. The two relative failures were due in one to residual subacromial bursitis, and the other to multidirectional shoulder instability. Arthroscopic stapling can restore the shoulder anatomy, and it is recommended for active adolescent athletes with this lesion. 
Percutaneous intra-aortic balloon pump: emphasis on complications. In a review of our 5-year experience with intra-aortic balloon pump (IABP) insertion I examined the complications of percutaneous IABP placement in 93 patients, and compared them with those reported in other studies in the literature. I analyzed several variables that may affect the complication rate. Of 78 patients in our series who had percutaneous IABP cardiac assist, 15 (19%) had complications, which falls into the acceptable range reported by others. Among 15 patients who had surgical placement of an IABP, the complication rate was similar at 20%. The complication rate after IABP insertions done by surgeons primarily in the operating room was compared with that from insertions done by cardiologists in the catheterization laboratory. The overall complication rate was found to be higher in the second group, 28.0% compared with 12.8%. The application of the IABP in cardiogenic shock was associated with a high complication rate (46%). On the other hand, its insertion before cardiac surgery was associated with a relatively low complication rate (9.5%). 
Left ventricular outflow obstruction resulting from insertion of mitral prostheses leaving the native leaflets intact: adverse clinical outcome in seven patients. Left ventricular (LV) outflow obstruction may result from retaining the anterior mitral leaflet when a mitral prosthesis is inserted in the mitral anulus. We retrospectively reviewed the echocardiograms (two-dimensional Doppler and Doppler color flow imaging, or transesophageal with color flow imaging) obtained in seven patients with preoperative mitral regurgitation who had a prosthesis implanted with the native mitral leaflets left intact. Systolic anterior motion of the native anterior mitral leaflet, as seen in dynamic LV outflow tract obstruction, was observed in six of seven patients. LV fractional shortening preoperatively was less than or equal to 0.25 in all (mean 0.20 +/- 0.04) and did not significantly (p = ns) increase postoperatively (mean 0.27 +/- 0.12). Color flow imaging revealed disturbed systolic flow in the LV outflow tract in five patients, and all had systolic anterior motion of the native anterior mitral leaflet. Continuous wave Doppler detected significant systolic LV outflow tract jets in five patients averaging 4.1 +/- 0.9 m/sec. Mitral prosthetic function was normal (pressure half-time of 81 +/- 25 msec and mean gradient of 7 +/- 3 mm Hg +/- SD) in five patients. Clinical follow-up revealed that all had died, six of them within 2 months of their operation. Thus systolic anterior motion of the native anterior mitral leaflet occurs commonly after prosthetic mitral valve insertion with the native leaflets left intact. Continuous wave Doppler often demonstrates increased systolic LV outflow tract velocities consistent with dynamic LV outflow obstruction. 
Periorbital necrobiotic xanthogranuloma and stage I multiple myeloma. Ultrastructure and response to pulsed dexamethasone documented by magnetic resonance imaging. We observed a 40-year-old woman with necrobiotic xanthogranuloma from the inception of indurated eyelid and periorbital infiltrates and concurrent stage I multiple myeloma to resolution of infiltrates in skin and bone marrow after pulsed high-dose oral dexamethasone therapy. Ultrastructural studies revealed lipid vacuoles in epidermal keratinocytes, in dermal histiocytic macrophages, and in vascular and lymphatic endothelial cells. The presence of lipid vacuoles in epidermal keratinocytes has not been reported previously in xanthogranuloma. 
Failed back surgery syndrome: 5-year follow-up after spinal cord stimulator implantation. Spinal cord stimulation, in use for more than 20 years, has evolved into an easily implemented technique, with percutaneous methods for electrode placement. We have reviewed our experience with this technique in treating "failed back surgery syndrome," and have assessed patient and treatment characteristics as predictors of long-term outcome. A series of 50 patients with failed back surgery syndrome (averaging 3.1 previous operations), who underwent spinal cord stimulator implantation, was interviewed by impartial third parties, at mean follow-up intervals of 2.2 years and 5.0 years. Successful outcome (at least 50% sustained relief of pain and patient satisfaction with the result) was recorded in 53% of patients at 2.2 years and in 47% of patients at 5.0 years postoperatively. Ten of 40 patients who were disabled preoperatively returned to work. Improvements in activities of daily living were recorded in most patients for most activities; loss of function was rare. Most patients reduced or eliminated analgesic intake. Statistical analysis (including univariate and multivariate logistic regression) of patient characteristics as prognostic factors showed significant advantages for female patients and for those with programmable multi-contact implanted devices. These results, in patients with postsurgical lumbar arachnoid and epidural fibrosis and without surgically remediable lesions, compare favorably with the results in two separate series of patients with failed back surgery syndrome, in whom 1) surgical lesions were diagnosed and repeated operation performed; and 2) monoradicular pain syndromes were diagnosed and dorsal root ganglionectomies performed at our institution. This suggests the need for further assessment of selection criteria, critical analysis of treatment outcome, and prospective study of spinal cord stimulation and alternative approaches to failed back surgery syndrome. 
Antiplatelet and antithrombotic therapy in unstable angina. In 4 well-controlled clinical trials, aspirin reduced the incidence of coronary events in unstable angina. The benefits were present during the acute, subacute and more chronic phases of the disease and were independent of the doses and of other protocol differences. This benefit of aspirin can be extended to some, but not all, other antiplatelet drugs. In 4 clinical trials, heparin used acutely added substantial benefit to the management of unstable angina, reducing the event rate and also the incidence of refractory angina more than aspirin. The long-term benefit of antithrombin therapy remains to be more thoroughly investigated. Despite these successes, the failure rate of aspirin and of heparin remains high, justifying a continuing search for more potent and safe antiplatelet and antithrombotic drugs. 
Carbon dioxide laser ablation of cutaneous metastases from malignant melanoma. Multiple cutaneous and superficial subcutaneous metastases from malignant melanoma in 30 patients were treated palliatively by carbon dioxide laser ablation when lesions were to numerous, too large or recurring too rapidly for multiple local excisions. The number of lesions per patient ranged from three to 250 (median 30). Patients were treated under local or general anaesthetic and as day cases or inpatients. After a median follow-up interval of 8 months fewer than 1 per cent of lasered metastases have recurred locally. Sixteen patients have developed cutaneous metastases at other sites requiring further treatment. Approximately 2000 lesions have been treated on 64 occasions. Patients reported little or no pain after the operation and required only simple dry dressings. Wounds were completely healed in 2-6 weeks with good cosmetic results. This simple and effective treatment is becoming an alternative to isolated limb perfusion. 
Use of endoscopy in peptic ulcer disease. The diagnosis and treatment of acute bleeding caused by peptic ulcer disease has been greatly facilitated by fiberoptic endoscopy. The basic differentiation between malignant and benign gastric ulcer requires endoscopic confirmation with biopsy. The management of bleeding from peptic ulceration can be enhanced by endoscopic examination as can the prediction of risk for recurrent bleeding or need for surgical intervention. Various therapeutic maneuvers can be performed endoscopically, including monopolar and multipolar cautery, laser and heater probe therapy, and injection of vasoconstrictors to control bleeding. Endoscopic balloon dilation for the management of gastric outlet obstruction is often effective. 
Optic chiasmal neuritis. In four of six patients with clinical optic chiasmal neuritis, MRI demonstrated abnormalities of the chiasm. Optic chiasmal neuritis may be the initial manifestation of multiple sclerosis, a reflection of established CNS demyelination, or an isolated clinical finding. 
MR imaging evaluation of endometrial carcinoma: results of an NCI cooperative study. A prospective study to assess the usefulness of magnetic resonance (MR) imaging in the evaluation of endometrial carcinoma was undertaken by five institutions under the auspices of the National Cancer Institute. Six different MR imagers were used, ranging in magnetic field strength from 0.15 T to 1.5 T. For each unit, appropriate T1- and T2-weighted sequences in the transverse plane and T2-weighted sequences in the sagittal plane were used. Initially, 107 patients were entered in the study, but only 88 fulfilled all the criteria and provide the basis for this study. The abnormality within the endometrial cavity was demonstrated with MR imaging in 81% of the patients. The overall accuracy with MR imaging for staging endometrial carcinoma was 85%. In the evaluation of depth of myometrial invasion for stage I disease, overall accuracy with MR imaging was 74%. The accuracy of MR imaging in assessing tumors confined to endometrium or tumor with superficial myometrial invasion was 89% and decreased to 54% in assessing deep myometrial invasion. The results of this prospective study performed by multiple examiners with vastly different equipment demonstrate the inherent value of MR imaging in the evaluation of this neoplasm. 
Effect of prazosin treatment on HDL kinetics in patients with hypertension. The effect of prazosin treatment on blood pressure, plasma HDL-cholesterol concentration, and apoprotein-AI/HDL (apoAI/HDL) kinetics was studied in 11 patients with mild hypertension. Blood pressure (mean +/- SEM) fell from 143 +/- 1/96 +/- 1 to 134 +/- 1/86 +/- 1 mm Hg after 4 to 5 months of prazosin treatment (P less than .001), associated with an increase in plasma HDL-cholesterol concentration from 38 +/- 2 to 46 +/- 2 mg/dL (P less than .001). Both the fractional catabolic rate (FCR) and total synthetic rate of apoAI/HDL, which were higher than previous reported values for normal individuals, decreased from 0.36 +/- 0.02 to 0.30 +/- 0.02 L/day and 17.4 +/- 1.1 to 13.8 +/- 1.1 mg/kg/min, respectively. These changes were statistically significant, and the post-treatment values for both variables were now within the normal range. When the decay curve was further analyzed by nonlinear curve fitting, it was shown that the return to normal of the FCR of apoAI/HDL in patients treated with prazosin was accounted for by the decrease of the decay constants of the second [p(2)] and third [p(3)] components of the 125I-AI/HDL disappearance curve. In conclusion, abnormalities in HDL concentration and HDL kinetics exist in patients with very mild hypertension. These defects were significantly improved with prazosin treatment, and this may render the compound of particular clinical benefit in the treatment of patients with mild hypertension. 
Paediatric haemangiomas: the role of radiotherapy. Radiotherapy currently maintains an occasional place in the therapy of complicated haemangiomas of childhood. Eight such childhood benign lesions have been so treated at St Bartholomew's Hospital in the last 10 years. The case histories are presented before being discussed in the context of other therapies available (no treatment, steroids, embolism and surgery), radiation technique used and radiation dose prescription advised. 
Fatal human cyclical neutropenia with unresolving tonsillitis and bilateral cervical abscesses. Human Cyclical Neutropenia is a rare haematological disorder, characterized by periodic oscillations in peripheral neutrophil levels from normal to neutropenic, during which patients experience ulcerative stomatitis, fever, malaise and occasional cutaneous and subcutaneous infections. We present our experience with a fatal case of Human Cyclical Neutropenia together with a brief review of the literature and diagnostic criteria. The paper aims to heighten the clinical awareness of the otolaryngologist to the condition. Close co-operation with the haematologist is essential both for diagnosis and management. 
'Medial maxillectomy' for lateral nasal wall neoplasms. Lateral rhinotomy and "medial maxillectomy," an en bloc resection of the medial maxillary sinus, ethmoid sinus with the lamina papyracea, medial orbital floor, and lacrimal fossa-duct, have been advocated for lateral nasal wall neoplasma. Experience with 35 (of 41) patients followed up at least 30 months (median, 57 months) postoperatively is reported. There was a 9% recurrence for benign tumors and 15% for malignant neoplasms, the latter only in the patients with nonmelanoma malignant neoplasms not receiving postoperative radiotherapy. The most frequent complications were cavity crusting, epicanthal scarring, and epiphora. 
Efficacy of slow-release nifedipine on myocardial ischemic episodes in variant angina pectoris. To evaluate the efficacy of slow-release nifedipine (a single dose of 20 mg given at 10 P.M. or 2 doses of 20 mg at 10 P.M. and 6 A.M.) on ischemic episodes in patients with variant angina, a single-blind crossover study with ambulatory electrocardiographic monitoring was performed in 15 patients (13 men and 2 women, mean age 63 years). In all, there were 646 ischemic episodes detected with ambulatory electrocardiographic monitoring during the study period, and 618 episodes of them occurred during placebo periods with a circadian variation. Sixty-nine percent of the episodes in placebo periods were asymptomatic. The number of anginal attacks, nitroglycerin tablets taken, ST-segment elevation and the total ischemic duration significantly decreased during nifedipine therapy compared with results after the placebo therapy period, respectively (p less than 0.01 or 0.05). Twenty-eight ischemic episodes occurred during nifedipine therapy when the plasma level of nifedipine was low. Thus, asymptomatic ischemic episodes more frequently occur than symptomatic episodes and the administration of slow-release nifedipine is highly effective in suppressing not only symptomatic but also asymptomatic myocardial ischemia in patients with variant angina. The timing of the administration of slow-release nifedipine is an important factor in suppressing ischemic episodes. 
Natural history of hepatic haemangiomas: clinical and ultrasound study. Hepatic haemangiomas are the most common benign tumours of the liver and commonly present as incidental findings on sonographic examination of the abdomen. Since little is known of the natural course of these tumours, we performed a clinical and sonographic follow up of 123 haemangioma patients. Our prospective study investigated clinical and sonographic findings in 158 haemangiomas for periods of 12 to 60 months. Ninety nine haemangiomas measured less than 2 cm and had an echogenic pattern; 40 were between 2 cm and 5 cm with a mainly echogenic structure; 19 measured greater than 5 cm and showed a mixed echo pattern. At the first examination only eight patients, all with giant haemangiomas, presented symptoms which could be attributed to the tumour. During follow up only one haemangioma changed in shape and size. One patient who was symptom free at the first examination experienced right upper abdominal quadrant pain during follow up. No deterioration occurred in any of the patients with symptoms at the first examination, and all had a satisfactory quality of life. No complications arose during the follow up period. This study shows that in adults haemangiomas remain stable in size and echo patterns rarely change. Only haemangiomas greater than 5 cm may cause symptoms. Prolonged clinical and sonographic follow up of small and medium sized haemangiomas is not warranted. 
Recent advances in the treatment of breast cancer. Multidisciplinary efforts have defined a number of prognostic factors and newer strategies to improve the outcome of patients with breast cancer. Conservative surgery has led to improved functional and cosmetic results. The development of a number of effective adjuvant regimens has led to improved survival. In patients with stage I disease, several biological characteristics of tumor have been identified that are associated with increased risk of relapse. A multimodality approach to patients with locally advanced disease and inflammatory cancer has resulted in improved survival. A number of hormonal and cytotoxic drug contaminations can palliate metastatic disease, with a small fraction of patients remaining in extended remission. Dose-intensive programs may lead to further improvements in survival of selected patients with this disease. 
Metabolic imaging of patients with cardiomyopathy. The cardiomyopathies comprise a diverse group of illnesses that can be characterized functionally by several techniques. However, the delineation of derangements of regional perfusion and metabolism have been accomplished only relatively recently with positron emission tomography (PET). Regional myocardial accumulation and clearance of 11C-palmitate, the primary myocardial substrate under most conditions, demonstrate marked spatial heterogeneity when studied under fasting conditions or with glucose loading. PET with 11C-palmitate permits the noninvasive differentiation of patients with nonischemic from ischemic dilated cardiomyopathy, since patients with ischemic cardiomyopathy demonstrate large zones of intensely depressed accumulation of 11C-palmitate, probably reflecting prior infarction. Patients with hypertrophic cardiomyopathy and Duchenne's muscular dystrophy demonstrate relatively unique patterns of myocardial abnormalities of perfusion and metabolism. The availability of new tracers and techniques for the evaluation of myocardial metabolism (11C-acetate), perfusion (H2(15)O), and autonomic tone (11-C-hydroxyephedrine) should facilitate further understanding of the pathogenesis of the cardiomyopathies. 
Complications following external beam radiation therapy for prostate cancer: an analysis of patients treated with and without staging pelvic lymphadenectomy. We reviewed the treatment morbidity associated with definitive high energy external beam radiotherapy in 289 consecutive patients with clinically localized prostate cancer (stages A2 to C) treated from 1984 to 1988 inclusively. All patients were treated with 18 mv. photon beams via a 4-field box technique. Radiation doses ranged from 5,858 to 6,900 cGy., with a mean dose of 6,456 cGy. and a median dose of 6,400 cGy. A total of 65 patients underwent extraperitoneal pelvic staging lymphadenectomy before radiotherapy. Complications noted in 42 patients were mild (generally trivial) in 23 and moderate in 19 (6.6%). There were no severe complications. The actuarial incidence of moderate complications was 9% at 5 years. Only 6 patients experienced symptoms for longer than 6 months. The risk of complications was not increased in patients who had undergone prior lymph node dissection, and only 2 of 65 had mild lymphedema, which resolved in both cases. We conclude that high energy external beam radiation for prostate cancer can be delivered with a low risk of serious complications, even in patients who have undergone extraperitoneal staging pelvic lymphadenectomy, provided the patients are treated to limited fields with high energy photons and at doses limited to 6,800 cGy. or less. 
Favorable response to parenteral nutrition and medical therapy in Crohn's colitis. A report of 38 patients comparing severe Crohn's and ulcerative colitis. The courses of 38 patients with severe, uncomplicated acute colitis (16 with Crohn's colitis and 22 with ulcerative colitis) were analyzed retrospectively. The patients were placed on total parenteral nutrition and treated concomitantly with corticosteroids, antibiotics (often metronidazole), sulfasalazine, and/or azathioprine. Fifteen of the 16 Crohn's colitis patients were initially managed without surgery. Four patients subsequently relapsed, two responded to reinstituted medical therapy, and two underwent colon resection 2 and 4 years later. Of 22 ulcerative colitis patients, 16 required surgery during the initial hospitalization, one patient subsequently had surgery, and one died after refusing surgery. Three of the other four continue in remission on medical therapy. Thus, there were significant differences in this series between the clinical courses of severe ulcerative colitis and severe Crohn's colitis. While most of the ulcerative colitis patients with severe disease underwent colectomy, most of the patients with severe but uncomplicated Crohn's colitis responded to aggressive medical therapy, of which total parenteral nutrition and perhaps bowel rest seemed to be an important part. Afterwards, the majority remained in remission on long-term medical therapy. 
Combined intertrochanteric and Chiari pelvic osteotomies for hip dysplasia. Thirty-two dysplastic hips with secondary osteoarthritis, in 28 patients aged 18 to 42 years, were treated by combined intertrochanteric and Chiari osteotomy. They were followed up for 2.5 to 10 years. Pain was the main presenting symptom in all the patients. The indication for surgery was based on the severity of disease with respect to congruency, secondary degenerative change and degree of dysplasia. The average pre-operative Harris hip score was 47.7 and the majority had severe dysplasia with degenerative changes. On final review the average score was 88. The radiographic appearances of degenerative arthritis regressed in 72% of hips and dysplasia was improved in all cases. The results of this conservative form of surgery are better in hips with less severe dysplasia and mild secondary degenerative change. 
Familial aggregation of nasopharyngeal carcinoma and other malignancies. A clinicopathologic description. Nasopharyngeal carcinoma (NPC) occurred in five members in three generations of a white American family of Scandinavian descent. Six other family members had malignancies including malignant melanoma, malignant lymphoma, squamous cell carcinoma of the tongue, adenocarcinoma of the colon, and asynchronous bilateral in situ and invasive ductal carcinomas of the breast. There was also a history of autoimmune disorders and exposure to smoke, fumes, and chemicals in some family members. Regression analysis revealed a significant covariate risk for exposure to smoking, alcohol ingestion, dust, salted or spicy foods, and poorly ventilated conditions. According to segregation analysis, the susceptibility to nasopharyngeal carcinoma and other malignancies in this family was transmitted as an autosomal codominant characteristic. A specific histocompatibility antigen (HLA) haplotype of A1-B37-DR6 was associated with a predisposition for NPC, but no linkage was identified. Laboratory studies in selected family members did not reveal significantly elevated levels of Epstein-Barr virus antibodies or serum carcinoembryonic antigen. No specific karyotypic abnormalities were identified with peripheral blood chromosome analysis. This family was an example of apparent autosomal codominant susceptibility to NPC and other malignancies. The relationship of malignancy to the HLA haplotype of A1-B37-DR6, autoimmune disorders, and cytogenetic abnormalities was intriguing but not defined clearly. 
Glial contribution to seizure: carbonic anhydrase activity in epileptic mammalian brain. The activity of carbonic anhydrase (CA), a glial enzyme, was measured in the epileptic cortex of audiogenic DBA/2 mice and of cats with a freeze lesion. In mice, the activity increased with age from birth to 24 days, but were always higher in audiogenic mice than in normal C57/BL mice, reflecting species differences. The difference between the two strains increased sharply from 25 to 40 days of age, after the period of maximal audiogenic susceptibility. Acetazolamide, a CA-specific inhibitor, greatly decreased the seizure severity score of DBA/2 mice after a single intraperitoneal (i.p.) administration (150 mg/kg). After 24 days of age, when CA activities were high, the effect of acetazolamide was less important, suggesting that the increased cortical CA activity might reflect a protective mechanism. In cats with a freeze lesion, no significant changes in CA activities were observed in the actively discharging primary and secondary foci as compared with the nonepileptogenic perifocal cortex and the control cortex of sham-operated animals. The results indicate that the cortex of genetically susceptible audiogenic mice has an increased CA activity. The hypothesis of an adaptive glial mechanism, relating to the age-dependent decrease of seizure susceptibility in DBA/2 mice, is postulated. 
Hilar and mediastinal lymphadenopathy in the limited form of Wegener's granulomatosis. A patient with the limited form of Wegener's granulomatosis is reported. The case is unusual because of hilar and mediastinal lymphadenopathy, severe ulceration of the respiratory and digestive tracts, and the rapidly fatal outcome. 
Revascularization of infarcted vs. viable myocardium. Effects on symptoms, physical performance and global/regional left ventricular function. Symptoms, physical performance and global vs. regional left ventricular (LV) function were reviewed in 25 patients with postinfarction anterior-apical akinesia and minor dyskinesia who subsequently underwent revascularization of all graftable stenotic vessels. The observed postoperative improvement in functional NYHA capacity and physical performance was not related to significant change in any systolic or diastolic variable of global LV function. 'Nonspecific postoperative septal hypokinesia' developed in most cases. The regional ejection fraction showed slight (nonsignificant) mean increase in the infarcted apex and low anterior wall supplied by the left anterior descending artery, but marked increase in the noninfarcted lateral wall supplied by the left circumflex branch. Hearts with grafted left circumflex artery showed on average lower preoperative and postoperative ejection fraction in the lateral wall than did hearts without such grafting, but the rise in regional ejection fraction was significant only after left circumflex grafting. The clinical response to coronary artery surgery is attributed mainly to functional improvement of non-infarcted myocardium. Revascularization of viable myocardium occurs directly via bypass grafts, but collateral vessels may also contribute. 
A 2-year experience with the Wolf piezoelectric lithotripter: impact of repeat treatment on results and complications. During a 2-year period, 884 extracorporeal piezoelectric lithotripsy treatments have been performed on stones in 388 renal units (kidney and upper ureter) using a Wolf Piezolith device.* Lithotripsy routinely was performed on an outpatient basis without use of anesthesia or premedication. Often, the maximum number of pulses allowable by a Food and Drug Administration protocol (4,000) was delivered and retreatments frequently occurred on successive days. Of the patients 75% were stone-free 3 months after treatment, while another 20% had only residual small fragments. No intrarenal or perinephric hematomas were observed and only 1 patient has had hypertension requiring medication. Renal colic from passage of stone fragments occurred in only 10% of the patients. An aggressive treatment policy using repeat treatments as necessary provides for superior results with this device without an incision or complication. 
Torticollis in children. Torticollis is a common clinical sign that is found in a variety of disorders. Childhood torticollis differs from the adult form in that congenital types are common and many frequently encountered disorders found in adults are unusual. Pediatric torticollis related to otolaryngologic conditions is reviewed, and three illustrative cases are presented. 
Serum-erythropoietin concentration during acute cardiogenic pulmonary edema. Reduced oxygen tension is regarded as the primary physiologic signal for the production of erythropoietin (EPO). There is little information available about early changes of EPO production in man due to severe hypoxia. The purpose of the present study was to examine the time course of EPO in serum of patients with acute cardiogenic pulmonary edema (ACPE). In 29 patients (seventy-five +/- six years, mean age +/- SEM) who were hospitalized within two hours after onset of symptoms of ACPE, serum EPO concentrations were monitored for up to seventy-two hours. At the moment of admission all patients showed significantly increased EPO concentrations of 121 +/- 64 mU/mL (mean +/- SEM) compared with a healthy population (15-35 mU/mL). Twenty-three patients who recovered within thirty minutes (group A) exhibited a quick return of their EPO serum levels to normal. The remaining 6 patients (group B) had a protracted clinical course and their EPO concentration showed a further increase up to the end of the observation period. The comparative monitoring of concentrations of alpha-1-proteinase inhibitor, antithrombin III, C-reactive protein, fibronectin, hapotoglobin, and transerrin in serum and plasma revealed no significant changes. Thus a major contribution of fluid shifts into or from the intravascular compartment to the observed changes in EPO concentration seems to be unlikely. The data suggest that the production and release of EPO in the kidneys due to altered oxygen delivery is a fast-responding mechanism. 
Effect of surgery on the systemic inflammatory response to intermittent claudication The hypothesis that intermittent claudication initiates a systemic inflammatory response was investigated by studying the effect of exercise on markers of neutrophil activation and vascular permeability in 25 claudicants and 10 controls. Urinary albumin excretion, previously demonstrated to reflect vascular permeability, increased significantly after exercise in claudicants and was associated with decreased neutrophil filterability and increased serum lysozyme activity. No similar exercise-induced changes were seen in controls or in claudicants after successful arterial bypass surgery. These results suggest that intermittent claudication is associated with potentially deleterious systemic manifestations that are surgically reversible. 
Temporal arteritis: an atypical presentation. Temporal (giant cell) arteritis is a systemic granulomatous vasculitis primarily involving branches of the carotid arteries in patients aged 50 years and greater. Its classic symptoms and signs are headache and elevated erythrocyte sedimentation rate (ESR), but this is not the only presentation. This case is the first reported in a Korean, whose chief complaint was pain in the tongue and headaches and whose ESR was normal. The diagnosis was confirmed by biopsy. Her symptoms abated when treated with prednisone, but she developed diabetes mellitus, osteoporosis, and compression fracture of lumbar vertebrae while being treated. Primary physicians should become aware of the atypical features of this disease, as well as the potential complications of treatment. 
Pre-travel health, immunization status, and demographics of travel to the developing world for individuals visiting a travel medicine service. It is estimated that five million Americans will travel to the developing world over the next year. This study examines the demographic profile, past medical and immunization history, itinerary, and reason for travel of 2, 445 travelers to the developing world seen at a travel medicine service from 1984 through 1989. The travelers age ranged from three months to 85 years (mean age 43). A chronic medical condition was reported by 654 (27%). Four percent of all travelers were intolerant of sulfonamides, and 9% had contraindications to mefloquine for malaria prophylaxis. Many travelers were due to receive the primary series or updatings of routinely recommended immunizations: 43% for tetanus/diphtheria, 55% of those born after 1956 for measles, and 70% for polio if their travel itinerary included a polio risk. Most travel (71%) was for vacations, 13% was for teaching or study, 11% for business, and 5% for missionary activities. The median duration of travel was 21 days; 5% traveled for more than one year. While over 150 countries were visited, 52% of all travel was to 10 countries in East Africa, the Indian subcontinent, the Far East, and South America. Information about the epidemiology of travel to the developing world can help physicians and travel medicine services develop more effective preventive measures for travelers. 
A review of current drugs for migraine. The current treatments available for migraine are reviewed and may be classified into four basic types. (a) Identification and elimination of migraine trigger factors, which include stress, emotions, fatigue, certain foods and beverages, and certain medications such as oestrogen therapy. (b) Symptomatic treatment of individual attacks. This includes various non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin and paracetamol, and ergotamine, dihydroergotamine and phenothiazines. Morphinomimetics, which are often given for migraine, should really be avoided. (c) Prophylactic treatment which is particularly recommended for patients averaging two or more severe migraine attacks per month. Useful drugs include: beta-adrenergic receptor blockers as first choice, e.g. propranolol, timolol, nadolol and metoprolol; 5-hydroxytryptamine blockers, e.g. pizotifen and methysergide; calcium channel blockers; dihydroergotamine; and NSAIDs. (d) Non-drug treatment which is best combined with identification and elimination of trigger factors, and the use of various relaxation techniques. These four treatment types are covered in some detail, however it is clear that none of them is ideal and side-effects present a problem. Clearly, the continued research and development of novel and specific drugs for migraine is vital. 
Simulation of compartment syndrome by rupture of the deep femoral artery from blunt trauma. Life-threatening hemorrhage of the femoral vasculature from a blunt injury to the thigh without femoral fracture has not been emphasized in the medical literature. Two cases of massive hemorrhage from the deep femoral system resulted from blunt injury to the thigh without femoral fracture. In the first case, a diagnosis of compartment syndrome was based on muscle swelling from the blunt trauma. A fasciotomy uncovered life-threatening bleeding. In the second case, which had a similar history and clinical symptoms, a vascular injury was suspected and an arteriogram was done. Disruption of the deep femoral arterial system was detected, and fluoroscopic embolization controlled the bleeding. A routine fasciotomy was then done. Both patients appeared clinically to have a thigh compartment syndrome, presumably based on injury from the crushed muscle. They both had normal arterial pulsations distal to the injured thigh. The only feature that suggested a vascular injury was a need for transfusion for hemodynamic support in excess of apparent blood loss. Arteriography, with embolization if necessary, is advised for all cases of suspected thigh compartment syndrome in which there is an unexplained need for hemodynamic support by transfusion. 
Porous-coated anatomic total knee arthroplasty. A prospective analysis comparing cemented and cementless fixation. The results of 26 cementless porous-coated anatomic (PCA) total knee arthroplasties (TKAs) were analyzed and compared to 25 cemented PCA TKAs. Identical prospective protocols were followed. The mean preoperative and postoperative knee scores at an average three-year follow-up interval (range, two to five years) were 59.6 and 81.5 for cementless knees compared to 57.6 and 80.4 for cemented knees. The difference was not statistically significant (p greater than 0.10). Blood loss was significantly higher in the cementless knees (p = 0.02). Radiolucent lines, loose beads, and tibial component subsidence were more frequent in cementless knees. No differences between cementless and cemented knees were observed in the femoral components. The PCA femoral components implanted without cement compare favorably to those implanted with cement. The PCA tibial and patellar components are more reliably secured with cement. 
Expression of a mitogen-responsive gene encoding prostaglandin synthase is regulated by mRNA splicing. Rous sarcoma virus was shown to induce in chicken embryo fibroblasts (CEF) a 4.1-kilobase mRNA (designated CEF-147) encoding a 603-amino acid protein. Analysis of the protein sequence showed that it shared 59% amino acid identity with sheep prostaglandin G/H synthase, the enzyme that catalyzes the rate-limiting steps in the production of prostaglandins. Significant differences, at both the protein and mRNA levels, existed between the src oncogene product-inducible prostaglandin synthase and the protein isolated and cloned from sheep seminal vesicle, suggesting that the src-inducible prostaglandin synthase may be a new form of the enzyme. A distinguishing feature of src-inducible prostaglandin synthase mRNA is its low abundance in nonproliferating chicken embryo fibroblasts and its relatively high abundance in src-transformed cells. Additionally, the majority of the src-inducible prostaglandin synthase RNA present in nonproliferating cells was found to be nonfunctional because of the presence of an unspliced intron that separated the signal peptide from the remainder of the protein. Upon mitogenic stimulation, this intron was removed, resulting in the induction of fully-spliced CEF-147 mRNA. 
A pair of monozygotic twins who are concordant for myasthenia gravis but became discordant for systemic lupus erythematosus post-thymectomy. We describe a pair of monozygotic twins who are concordant for myasthenia gravis but discordant for systemic lupus erythematosus (SLE). SLE developed in twin 1 18 years post-thymectomy and has been characterized by recurrent transverse myelitis and optic neuritis. Twin 2 remains well post-thymectomy, except for a skin rash and persistent leukopenia. Both twins have developed autoimmune thyroid disease. We review genetic and environmental factors of importance in the pathogenesis of SLE and discuss the possible role of thymectomy in the etiology of the disease. 
Cause of death in patients attending multiple sclerosis clinics. Between 1972 and 1988, 145 deaths occurred among 3,126 patients attending the Multiple Sclerosis (MS) Clinics in Vancouver, British Columbia (N = 1,583), and London, Ontario (N = 1,543). We could determine the exact cause of death in 82.1% of cases (119 of 145). Of the 119 patients for whom the cause of death was known, 56 deaths (47.1%) were directly attributed to complications of MS. Of the remaining 63 deaths, 18 (28.6%) were suicides, 19 (30.2%) were due to malignancy, 13 (20.6%) to an acute myocardial infarction, seven (11.1%) to stroke, and the remainder (9.5%) to miscellaneous causes, of which two may have been suicides. The proportion of suicides among MS deaths was 7.5 times that for the age-matched general population, and the proportion of MS deaths from malignancy was 0.67 times that for the age-matched general population. The proportion of deaths due to malignancy and stroke was the same for the MS patients and the age-matched general population. 
Tissue plasminogen activator for the treatment of thromboembolism in infants and children. We report our experience with the use of tissue plasminogen activator to treat 12 infants and children with various thromboembolic states after conventional thrombolytic agents had failed. The dosage range was between 0.1 to 0.5 mg/kg per hour. Complete clot dissolution occurred in seven cases after 2 hours to 3 days of therapy. Partial clot dissolution and clinical improvement were noted in another four patients. Bleeding complications were noted in 6 of the 12 patients and included bruising, oozing from various venipuncture sites, and bleeding; these complications were controlled by clinically available means. In all cases with bleeding the dose rate was in the higher range (0.46 to 0.50 mg/kg per hour). In one patient, restlessness, agitation, and screaming were noted during administration of tissue plasminogen activator and when it was reinstituted. We conclude that tissue plasminogen activator is effective in inducing clot lysis in children. Because the effective dose appears to overlap with those causing bleeding, we recommend that a dose of 0.1 mg/kg per hour be started and increased gradually if clot dissolution does not occur, with close monitoring for bleeding. 
Quality of life after bypass surgery for unstable angina. 5-year follow-up results of a Veterans Affairs Cooperative Study To assess the effect of bypass surgery on outcome from unstable angina, 468 patients were randomized to medical treatment (237 patients) or surgery plus medical treatment (231 patients) and have been followed for comparison of survival, cardiac end points, and quality of life; the latter end point is discussed in the present report. Data were available at 3 and 5 years for 80% and 82% of patients in the medical group, respectively, and 77% and 80% of patients in the surgery group, respectively. At 3 months after randomization to therapy, 79.8% of patients in the surgery group reported subjective improvement, compared with 58% of the medical group, 12.6% of the surgery group reported no change compared with 24.5% of the medical group, and 5.5% of the surgery group reported worsening compared with 24.5% of the medical group (p less than 0.01 by chi 2). Similar data were found for chest pain status, and the benefit to the surgery group remained statistically significant through 5 years of follow-up. Crossover rate to surgery was 43% by 5 years. Treadmill duration was increased in the surgery group compared with the medical group (6.5 +/- 0.25 versus 5.3 +/- 0.25 minutes at 6 months, p less than 0.01), and a significant difference was again demonstrated at 3 and 5 years. A trend toward decreased recurrence of unstable angina was present in the surgery group at 1 year (six of 168 [3.6%] versus 13 of 187 [6.9%] in the medical group, p = 0.158), but the two groups were similar at 3 and 5 years. 
Hearing aid evaluation and fitting. Although many patients with hearing loss benefit from medical or surgical intervention, the vast majority have noncorrectable hearing disorders for which rehabilitation through amplification is indicated. There are three goals for the application of hearing aids: (1) to amplify normal conversational speech to levels that are maximally understandable to the patient; (2) to help the patient hear other environmental sounds; and (3) to assist in the educational or habilitative process for those children who sustain hearing loss prior to language and speech development. In addition, there are certain issues that require medical consideration when a wearable device is placed in the ear. This article describes current hearing aid technology; reviews its benefits, limitations, and application for typical patients; discusses the medical aspects of hearing aid fitting; and describes new hearing aid technology on the horizon. 
Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy. X-linked spinal and bulbar muscular atrophy (Kennedy's disease) is an adult-onset form of motorneuron disease which may be associated with signs of androgen insensitivity. We have now investigated whether the androgen receptor gene on the proximal long arm of the X chromosome is a candidate gene for this disease. In patient samples we found androgen receptor gene mutations with increased size of a polymorphic tandem CAG repeat in the coding region. These amplified repeats were absolutely associated with the disease, being present in 35 unrelated patients and none of 75 controls. They segregated with the disease in 15 families, with no recombination in 61 meioses (the maximum log likelihood ratio (lod score) is 13.2 at a recombination rate of 0). The association is unlikely to be due to linkage disequilibrium, because 11 different disease alleles were observed. We conclude that enlargement of the CAG repeat in the androgen receptor gene is probably the cause of this disorder. 
High energy underwater shock wave treatment on implanted urinary bladder cancer in rabbits. The effects of focused high energy shock waves (SW) on the implanted urinary bladder cancer in rabbits were examined. The bladder cancer was exposed to 2000 to 8000 shots of focused SW under ultrasound guidance. Although only focal necrosis of the tumor was seen in the one day SW exposure, wider and deeper tumor necrosis was observed in the tumors following serial SW (2000 to 6000 shots, for two to three days). Eight to 10 day serial SW exposure (6000 to 8000 shots) decreased the tumor growth in comparison with that of the control. Lung metastases examined by periodic chest X-ray after SW treatment revealed that SW did not promote lung metastases. Pathological findings were also in accord with the X-ray examinations. Polyclonal antibody type 4 collagen was used for immunohistochemical staining of vascular wall in bladder cancer. Vascular wall destruction, not found in spontaneous necrotic tumor, were clearly visible in SW induced necrotic area. SW induces vascular damage in the tumor, which may be the primary cause promoting the tumor necrosis. 
Tinnitus. Tinnitus, a common complaint, reportedly affects more than 37 million Americans. Most often, it is associated with a sensorineural hearing loss in the high-frequency range. Tinnitus, however, is a symptom and not a disease. Complacency about this symptom complex may cause physicians to overlook a severe underlying pathologic process. Patients with unilateral tinnitus, pulsatile tinnitus, fluctuating tinnitus, or tinnitus associated with vertigo should undergo thorough assessment, including elicitation of a complete history, physical examination, and audiologic analysis. In many instances, treatment is effective. Masking of tinnitus, medical therapy, and biofeedback and counseling are some measures that have been used in the management of tinnitus. 
Comparison of a single layer continuous hand-sewn method and circular stapling in 580 oesophageal anastomoses. A total of 611 patients with carcinoma of the oesophagus or gastric cardia were operated on between July 1982 and December 1989. Resection was performed in 491 patients (one-stage, 483; two-stage, eight), bypass operation in 97, and 23 had exploration alone. The anastomoses of 580 patients with one-stage resection and bypass operations were evaluated. Hand-sewn anastomosis using a single layer of continuous absorbable monofilament suture was performed in 304 patients (221 resections and 83 bypasses). A stapled anastomosis was performed on 276 patients (262 resections and 14 bypasses). Following resection, there were 11 (5 per cent) anastomotic leaks in the hand-sewn group and ten (3.8 per cent) in the stapled anastomosis group (P = 0.69). Excluding anastomotic leaks, hospital mortality and anastomotic recurrence, stricture occurred in 18 of 172 hand-sewn anastomoses (10.5 per cent) and in 57 of 195 stapled anastomoses (29.2 per cent) (P less than 0.001). In patients who had bypass operations there were 12 anastomotic leaks, ten in the hand-sewn group (12.0 per cent) and two in the stapled anastomosis group (14.3 per cent). Only two of the discharged patients with bypass developed anastomotic strictures, a low incidence probably because of short survival. In addition, there were 245 subsidiary anastomoses made in the abdomen by the hand-sewn method as part of the reconstructive procedure, and there was one leak. The results of this non-randomized study suggest that hand-sewn anastomosis using a single layer continuous technique for the oesophagus is as safe as the use of circular staplers; hand-sewn anastomosis is less likely to become stenotic. 
Allele loss at the retinoblastoma locus in human ovarian cancer. To gain a broad spectrum on allelic loss of specific loci in ovarian tumors, we initially examined DNA from 23 pairs of ovarian tumors and matched peripheral blood lymphocyte samples from the same patients, using 27 polymorphic DNA markers distributed on 13 chromosomes. Significant high frequency of allelic deletion (22%-44%) at chromosome 13 loci (D13S31, D13S32, D13S33, and D13S34) at bands q12-q34 was observed in tumor tissues. These results led us to investigate the loss of heterozygosity at the retinoblastoma (RB) locus in ovarian tumors, because the RB gene is a tumor-suppressor gene located at 13q14. Analysis of the variable number of tandem repeat sequence polymorphism in intron 20 in the RB gene revealed that 6 (30%) of 20 patients with informative samples showed allelic loss at the RB locus in their tumor tissues. This loss, of relatively high frequency, suggests that the RB gene, or a closely linked gene, seems to be involved in the development of ovarian cancer. 
Radioiodinated 1-(5-iodo-5-deoxy-beta-D-arabinofuranosyl)-2-nitroimidazole (iodoazomycin arabinoside: IAZA): a novel marker of tissue hypoxia. 1-(5-Iodo-5-deoxy-beta-D-arabinofuranosyl)-2-nitroimidazole (IAZA) has been synthesised and labeled with 125I. Radioiodinated IAZA was shown to undergo hypoxia-dependent binding in EMT-6 cells in vitro and to have an initial binding rate of 284 pmole/10(6) cells/hr at a substrate concentration of 30 microM. This binding rate is more than three times that of the reference compound, misonidazole (89 pmole/10(6) cells/hr). The elevated binding rate was accompanied by in vitro cytotoxicity 30-40 times greater than that observed for misonidazole. Whole-body elimination and biodistribution studies in BALB/c mice bearing implanted, subcutaneous EMT-6 tumors showed a rapid excretion (greater than 98% in 24 hr) with moderate tissue levels which, in general, declined as a function of blood clearance. Tumor-to-blood ratios of 4.6 (4 hr) and 8.7 (8 hr), with respective tumor uptake values of 2.08% and 1.22% ID/g of tissue, form a rational basis for evaluation of this and related 2-nitroimidazole analogs as radiopharmaceuticals suitable for scintigraphic evaluation of tissue (tumor) hypoxia. 
Gynecologic cytology. Practical considerations and limitations. Diagnostic problems arise as a result of overlap of cytologic criteria of some squamous and glandular lesions of the female genital tract, lack of experience, or an overzealous attempt to interpret some features. This article emphasizes the role and limitations of cytology in the diagnosis of neoplasia and preneoplasia of squamous and glandular elements of the uterus. Sampling techniques greatly influence the pathologist's ability to interpret the material. The classifications and cytologic features of preneoplastic and neoplastic squamous and glandular epithelia, including the new Bethesda System for reporting, are reviewed. Problems in interpretation, particularly of nondysplastic conditions that mimic true neoplasia, and reasons for false-negative and false-positive results are discussed. 
Amnestic effects in mice of four synthetic peptides homologous to amyloid beta protein from patients with Alzheimer disease. Immediate post-training intracerebroventricular administration of a synthetic peptide homologous to beta protein of brain amyloid, [Gln11]beta-(1-28), caused amnesia for footshock active avoidance training in mice in a dose-dependent fashion. This effect was specific to memory processing since the peptide did not cause amnesia when injected 24 hr after training nor did it disturb storage or retrieval of older memories. Shorter fragments of the amyloid beta protein consisting of residues 12-28, 18-28, and 12-20 also were amnestic when given intracerebroventricularly, residues 12-20 being least effective. The hippocampus, a brain structure importantly involved in learning and memory, consistently shows severe pathological changes and deposition of amyloid in patients with Alzheimer disease. Immediate post-training bilateral intrahippocampal injection of [Gln11]beta-(1-28) produced amnesia at much lower doses than did [Gln11]beta-(1-28) injected intracerebroventricularly. Thus these experimental results suggest a possible direct role of amyloid beta protein or fragments thereof in an aspect of the spectrum of cognitive deficit in Alzheimer disease. 
Caffeine self-administration, withdrawal, and adverse effects among coffee drinkers. Twenty-two coffee drinkers (three to seven cups per day) underwent repeated double-blind trials to test for caffeine self-administration, withdrawal, and adverse effects. Each trial consisted first of a randomized crossover period of 1 day of decaffeinated coffee and 1 day of caffeinated coffee (100 mg) to assess withdrawal and adverse effects of caffeine. Next, subjects were given 2 days of concurrent access to the two coffees. The relative use of the two coffees was used to assess caffeine self-administration. Reliable caffeine self-administration occurred in three of 10 subjects in study 1 and seven of 12 subjects in study 2. Withdrawal symptoms were headaches, drowsiness, and fatigue. The major adverse effect from self-administration was tremulousness. The occurrence of headaches on substitution of decaffeinated coffee prospectively predicted subsequent self-administration of caffeine. These results indicate that some coffee drinkers exhibit signs of a caffeine dependence, ie, they self-administer coffee for the effects of caffeine, have withdrawal symptoms on cessation, and experience adverse effects. 
Five-day bismuth-free triple therapy for the eradication of Helicobacter pylori and reduction of duodenal ulcer relapse. Previous studies have demonstrated that the eradication of Helicobacter pylori (H. pylori) is associated with a significant reduction of the rate of duodenal ulcer (DU) relapse. The aim of this study was to assess the long-term effect of a bismuth-free triple therapy on the eradication of H. pylori and reduction of DU relapse. After informed consent, 61 patients with endoscopically proven DU and H. pylori infection detected on 14C-urea breath test (BT) were included in the study. All patients received a combination of furazolidone, amoxicillin, and metronidazole, three times a day, for 5 days, in addition to eventual classical antiulcer agents prescribed by their attending physicians. BT was repeated after an interval of at least 60 days to evaluate H. pylori eradication. Endoscopy and another BT were performed again at 6.5 months after therapy to detect possible recurrences. Forty-eight patients completed the trial: 26 (54%) patients were negative for H. pylori at 6.5 months after the end of treatment, and 22 (46%) persisted H. pylori positive. Ninety-two percent of the patients in whom the bacteria were eradicated showed endoscopically healed ulcers and were asymptomatic, and two that were symptomatic presented only occasional pain not requiring therapy. Among the 22 patients who persisted H. pylori positive, six (27%) showed endoscopically active ulcers (p = 0.012) and eight (36%) patients continued to be symptomatic (p less than 0.01), and were still using antiulcer drugs (p = 0.002) 6.5 months after treatment. It is concluded that combined treatment with furazolidone, amoxicillin, and metronidazole for 5 days represents a well-tolerated, inexpensive, and effective therapeutic regime for the eradication of H. pylori and abolition of DU relapse in more than 50% of the patients during a follow-up period of 6.5 months. 
Plasmapheresis does not increase the risk for infection in immunosuppressed patients with severe lupus nephritis. The Lupus Nephritis Collaborative Study Group. OBJECTIVE: To determine whether plasmapheresis increases the risk for infection in immunosuppressed patients. DESIGN: Randomized, controlled trial. SETTING: Multicenter. PATIENTS: Eighty-six patients enrolled in a trial of plasmapheresis for severe diffuse proliferative lupus nephritis. INTERVENTIONS: Forty-six of the patients received high-dose steroid therapy plus cyclophosphamide therapy for 8 weeks. Thereafter, cyclophosphamide therapy was discontinued, and steroid therapy was tapered (standard treatment group). Forty patients received identical treatment and had 12 plasmapheresis procedures during the first 4 weeks of the treatment. MEASUREMENTS: Patients were examined for the development of infection. MAIN RESULTS: No statistical difference in age, sex, race, serum creatinine level, proteinuria, or complement levels was found between the two groups. Over a follow-up period of 5376 patient-weeks, 74% of patients in the standard treatment group had 62 infections, yielding an aggregate infection rate of 1.15 infections per 100 weeks (median individual infection rate, 1.08; 25th and 75th percentiles, 0.0 and 2.44). This rate was comparable to that seen in the plasmapheresis-treated patients who were followed for 4187 patient-weeks: 68% had 51 infections, for an aggregate infection rate of 1.22 infections per 100 weeks (median individual infection rate, 0.94; 25th and 75th percentiles, 0.0 and 2.32). The infection rate was also comparable in the initial acute phase of the study, despite the fact that patients who received plasmapheresis then had significantly lower immunoglobulin (IgG) levels (P less than 0.001). Neither the site (superficial compared with systemic) nor the nature (conventional compared with unconventional) of infection differed statistically between the two groups. Of 14 patient deaths, 7 were from infection (4 in control group and 3 in the plasmapheresis group). CONCLUSION: Plasmapheresis did not increase the risk for infection in immunosuppressed patients with severe lupus nephritis. 
Anti-tumor activities of immunotoxins made of monoclonal antibody B3 and various forms of Pseudomonas exotoxin [published erratum appears in Proc Natl Acad Sci U S A 1991 Jun 1;88(11):5066] B3 is a monoclonal antibody that reacts with a carbohydrate epitope present on a variety of proteins located on the surface of many cancer cells and a limited number of normal tissues. We evaluated the cytotoxic activity of immunotoxins composed of monoclonal antibody B3 coupled to native Pseudomonas exotoxin (PE) or two recombinant forms of Pseudomonas exotoxin, PEArg57 or LysPE40, a form of PE with a deletion of the cell binding domain. All three conjugates were cytotoxic to human cell lines expressing the B3 antigen on their surface. The survival of each of the three immunotoxins in the circulation of mice was determined after administering the immunotoxin i.v. The half-life in blood of B3-PE and B3-PEArg57 was 20 hr, whereas the half-life of B3-LysPE40 was 4 hr. The short half-life of B3-LysPE40 may be due to the absence of domain I of PE. To determine the therapeutic effects of the three immunotoxins, they were given intraperitoneally to nude mice bearing subcutaneous A431 tumors. All three immunotoxins caused complete regression of 50-mm3 tumors with no toxic effects to the animals at therapeutic doses. Furthermore, substantial regression was also noted with much larger tumors. Our data indicate that the monoclonal antibody B3, when coupled to PE or recombinant forms of PE, may be useful for the treatment of tumors expressing B3 antigen. The therapeutic window was largest with B3-LysPE40, which can be administered in higher doses because it lacks sequences in domain I of PE that enable PE to bind to nontarget cells. 
Prognostic impact of stress testing in coronary artery disease. Observational data prospectively collected permit the examination of a complex set of decisions, including the decision not to perform any stress testing. Patients with or without previous myocardial infarction admitted for coronary evaluation and not submitted to any stress testing because of clinical reasons are at a higher risk for subsequent death. For prognostication, no test has been better validated than exercise electrocardiography: it can identify patients at low and high risk for future cardiac events among those without symptoms, with typical chest pain, and with previous myocardial infarction. In patients with triple-vessel disease, the results of exercise also allow those at low and high risk to be recognized. Both exercise radionuclide angiography and 201Tl scintigraphy (the latter in larger patient populations) have also demonstrated significant prognostic value on patients with or without previous myocardial infarction. Neither one has shown superiority to the other in prognostication. So far, they have been considered the only viable alternatives to exercise electrocardiography stress testing for diagnosis and prognostication. However, their costs limit their extensive application. Preliminary data suggest that intravenous dipyridamole echocardiography can be used for both diagnosis and prognostication of coronary artery disease; moreover, the prognostic information derived from dipyridamole echocardiography testing seems independent of and additive to that provided by exercise electrocardiography. Further prospective studies on larger patient populations are needed to better define the prognostic value of dipyridamole echocardiography testing. 
Intermittent torsion: association with horizontal lie of the testicle. The importance of making an early diagnosis of intermittent testicular torsion cannot be over-emphasized. We report on 3 patients with recurrent episodes of severe testicular pain but who were pain-free at evaluation. All 3 patients were found to have a horizontal lie of the symptomatic testicle and a normal vertical axis in the contralateral asymptomatic testicle. Scrotal exploration revealed a bell-clapper deformity in all 3 patients. A history of recurrent scrotal pain and horizontal testicular lie, even in the absence of pain at the time of physical examination, is a strong indication for exploration and bilateral testicular fixation. 
Characteristics of cirrhosis undiagnosed during life: a comparative analysis of 73 undiagnosed cases and 149 diagnosed cases of cirrhosis, detected in 4929 consecutive autopsies. In 4929 consecutive autopsies performed during a period of 4 years, 222 cases (4.5%) of cirrhosis were found, of which 149 (3%) were detected while the patients were alive (diagnosed cirrhosis) and 73 (1.5%) were not detected while the patients were living (undiagnosed cirrhosis). Fifty-three of the 73 undiagnosed patients appeared to be completely without signs of cirrhosis (silent cirrhosis). In the diagnosed group, 70% of patients died from hepatic causes, in contrast to 16% in the undiagnosed group. At autopsy, the following complications of cirrhosis were found more frequently in the diagnosed group than in the undiagnosed group: ascites (41% vs. 8%), oesophageal varices (44% vs. 10%), splenomegaly (52% vs. 29%). The prevalence of hepatocellular carcinoma did not differ significantly in the two groups (12% vs. 8%). It is concluded that cirrhosis without obvious signs occurs relatively frequently, and that no sensitive non-invasive screening methods are available at present. 
Modeling: optimal marathon performance on the basis of physiological factors. This paper examines current concepts concerning "limiting" factors in human endurance performance by modeling marathon running times on the basis of various combinations of previously reported values of maximal O2 uptake (VO2max), lactate threshold, and running economy in elite distance runners. The current concept is that VO2max sets the upper limit for aerobic metabolism while the blood lactate threshold is related to the fraction of VO2max that can be sustained in competitive events greater than approximately 3,000 m. Running economy then appears to interact with VO2max and blood lactate threshold to determine the actual running speed at lactate threshold, which is generally a speed similar to (or slightly slower than) that sustained by individual runners in the marathon. A variety of combinations of these variables from elite runners results in estimated running times that are significantly faster than the current world record (2:06:50). The fastest time for the marathon predicted by this model is 1:57:58 in a hypothetical subject with a VO2max of 84 ml.kg-1.min-1, a lactate threshold of 85% of VO2max, and exceptional running economy. This analysis suggests that substantial improvements in marathon performance are "physiologically" possible or that current concepts regarding limiting factors in endurance running need additional refinement and empirical testing. 
Prospective study of alcohol consumption and risk of coronary disease in men. Although an inverse association between alcohol consumption and risk of coronary artery disease has been consistently found in several types of studies, some have argued that the association is due at least partly to the inclusion in the non-drinking reference group of men who abstain because of pre-existing disease. The association between self-reported alcohol intake and coronary disease was studied prospectively among 51,529 male health professionals. In 1986 the participants completed questionnaires about food and alcohol intake and medical history, heart disease risk factors, and dietary changes in the previous 10 years. Follow-up questionnaires in 1988 sought information about newly diagnosed coronary disease. 350 confirmed cases of coronary disease occurred. After adjustment for coronary risk factors, including dietary intake of cholesterol, fat, and dietary fibre, increasing alcohol intake was inversely related to coronary disease incidence (p for trend less than 0.001). Exclusion of 10,302 current non-drinkers or 16,342 men with disorders potentially related to coronary disease (eg, hypertension, diabetes, and gout) which might have led men to reduce their alcohol intake, did not substantially affect the relative risks. These findings support the hypothesis that the inverse relation between alcohol consumption and risk of coronary disease is causal. 
EPA in the prevention of restenosis post PTCA. The effect of fish oil on restenosis was evaluated in patients undergoing coronary balloon angioplasty. In addition to routine pharmacotherapy, subjects were given 2.8 g of eicosapentanoic acid (EPA) daily. Treatment was started within twenty-four hours after successful percutaneous transluminal coronary angioplasty (PTCA). After six months of therapy, participants were subjected to coronary arteriography, exercise scintigraphy, exercise electrocardiography, or clinical evaluation. Follow-up evaluation involved 97 coronary lesions in 85 patients. Partial or significant restenosis occurred in 36.5% of patients and 33% of vessels. The presence of severe stenosis before PTCA, dissection, thrombus, multilesion PTCA, and template bleeding time values were not correlated with restenosis. Dilation of the left anterior descending (LAD) and a residual stenosis greater than or equal to 35% were associated with restenosis. Approximately 20% of the patients related difficulty in taking the fish oil. Furthermore, these results show no advantage over expected restenosis rates. 
Comparison of CT, low-field-strength MR imaging, and high-field-strength MR imaging. Work in progress. To assess objectively the sensitivity and specificity of low-field-strength (0.064 T) magnetic resonance (MR) imaging, a prospective blind study of 280 examinations was performed to compare low-field-strength MR imaging with computed tomography (CT) and with high-field-strength (1.5-T) MR imaging of the cranium. The sensitivity (defined as the true-positive rate) with high-field MR imaging was superior to that with low-field MR imaging and CT in helping detect overall abnormalities. Sensitivities were generally similar over a broad range of specific cranial central nervous system diseases. Low-field and high-field MR imaging were equivalent in the blind diagnoses of neoplasms and white matter disease, whereas low-field MR and CT were equivalent in the blind diagnoses of contusion, subdural and epidural hematoma, sinus disease, normality, and abnormality. The specificities with low-field MR imaging and CT were substantially better than those with high-field MR imaging. 
Effect of breast implants on mammography. We developed an experimental, reproducible method of evaluating the radiographic characteristics of breast implants in vitro using a mammographic phantom and a cadaver. Implant shells tested included smooth silicone, textured silicone, and silicone coated with polyurethane foam. Each type of shell was subsequently filled with saline, silicone gel, and peanut oil; the images were recorded radiographically. Textured silicone and smooth silicone shells minimally impair detection of artifacts. Polyurethane-coated shells are less radiolucent but allow visualization of some microcalcifications. Saline and silicone-gel-filled implants are radiopaque regardless of shell type. Textured silicone and smooth silicone shells filled with peanut oil are radiolucent and allow visualization of microcalcifications and most soft-tissue masses. These data demonstrate that radiolucent breast implants are possible, and further efforts are under way to achieve Food and Drug Administration approval for clinical testing. 
Substitution of leucine for isoleucine in a sequence highly conserved among retroviral envelope surface glycoproteins attenuates the lytic effect of the Friend murine leukemia virus. Friend murine leukemia virus is a replication-competent retrovirus that contains no oncogene and that exerts lytic and leukemogenic properties. Thus, newborn mice inoculated with Friend murine leukemia virus develop severe early hemolytic anemia before appearance of erythroleukemia. To identify the retroviral determinants regulating these effects, we used chimeric infectious constructions and site-directed point mutations between a virulent Friend murine leukemia virus strain and a naturally occurring variant attenuated in lytic and leukemogenic effects. We found that severe hemolytic anemia was always associated with higher numbers of blood reticulocytes with budding retroviral particles. Furthermore, a remarkably conservative leucine to isoleucine change in the extracellular SU component of the retroviral envelope was sufficient to attenuate this lytic effect. Also, this leucine at position 348 of the envelope precursor protein was located within the only stretch of five amino acids that is conserved in the extracellular SU component of all murine, feline, and primate type C and type D retroviral envelopes. This observation suggested an important structural function for this yet undescribed conserved sequence of the envelope. Lastly, we observed that lytic and leukemogenic effects were attenuated by a deletion of a second repeat in the transcriptional enhancer region of the viral long terminal repeats of the variant strain. 
The causes and complications of late diagnosis of foreign body aspiration in children. Report of 210 cases. Late diagnoses of foreign body aspiration were defined as occurring beyond 3 days between the aspiration of the foreign body, or onset of symptoms, and correct diagnosis. We reviewed a total of 210 children with late diagnosis of foreign body aspiration. The causes creating late diagnosis of foreign body aspiration in children were as follows: (1) parental negligence (106/210, 50%); (2) misdiagnosis by the fellow professionals and pediatricians (39/210, 19%); (3) the normal chest roentgenographic findings (29/210, 14%); (4) lack of typical symptoms and signs (26/210, 12%); (5) mismanagement (8/210, 4%); and (6) a negative bronchoscopic finding (2/210, 1%). The most common complications encountered were obstructive emphysema (77/186, 41%), mediastinal shift (63/186, 34%), pneumonia (43/186, 24%), and atelectasis (33/186, 18%) in 186 patients who underwent a chest roentgenographic examination. The incidence of major complications was 64% (48/75) in the children who were diagnosed within 4 to 7 days; however, the complication rate was 70% (39/56) in those with a delay in diagnosis of 15 to 30 days, and 95% (20/21) in the cases with a delay in diagnosis of over 30 days after aspirating the foreign bodies. 
Mucin-producing tumor of the pancreas. A new pancreatic tumor, called mucin-producing tumor, has received great attention in Japan. These tumors are found inside the pancreatic duct and produce large quantities of copious mucus. The authors examined 22 cases of these tumors histologically and histochemically. In 12 malignant cases, the tumors inside the ducts consisted of cancerous lesions over small areas along with papillary or atypical hyperplasia. Tumors in ten benign cases mainly consisted of papillary hyperplasia. Except for three patients with carcinoma in situ, cancerous tumors infiltrated the pancreatic parenchyma and, in some cases, were observed invading the bile duct or duodenum. A mucous histochemical study showed evidence of sialomucin in malignant cases; neutral mucin was dominant in benign cases. Characteristics of this disease were also compared with 13 cases of mucinous cystic neoplasm. From the results, it was concluded that these two diseases can be classified into the same conceptual category. 
Hormonal therapy before surgical treatment for uterine leiomyomas. Use of GnRH-A offers a promising medical approach to treating uterine leiomyomas. This therapy can be useful in selected patients, preserving fertility by delaying the need for imminent surgical treatment. In selected perimenopausal women, agonist therapy may, in fact, be an alternative to surgical intervention. Shrinking the size of myomas and reducing uterine volume with these agents have been reported to control symptoms of myoma, making myomectomy or vaginal hysterectomy a safer procedure. Used preoperatively, GnRH-A therapy can also reduce the risk of surgical complications and excessive blood loss. 
The effect of ibuprofen on cardiac performance during abdominal aortic cross-clamping. Decreased cardiac output and increased plasma thromboxane have been observed during aortic cross-clamping under general anesthesia. Amelioration of these changes has been reported by preoperative administration of cyclooxygenase inhibitors, but heterogeneity in patients' intravascular volume status has confounded analysis of the drugs' effects in previous studies. We studied hemodynamic conditions in 24 volume-loaded (pulmonary capillary wedge pressure greater than 10 mm Hg) patients undergoing abdominal aortic aneurysm repair under general plus epidural anesthesia, after preoperative double-blind administration of either ibuprofen 800 mg (n = 12) or placebo (n = 12). The hemodynamic response to aortic cross-clamping was similar in both groups. Pulse and mean arterial pressure remained unchanged; cardiac index decreased after aortic cross-clamping from 2.4 +/- 0.1 (mean +/- standard error of the mean [SEM]) to 2.1 +/- 0.1 1/min/m2 in the ibuprofen group and from 2.5 +/- 0.1 to 2.3 +/- 0.2 1/min/m2 in the placebo group (p less than 0.01 versus preclamp values in both groups, multivariate analysis of variance [MANOVA]), but improved after declamping. Both left and right ventricular stroke work indexes followed a similar pattern. Plasma 6-keto prostaglandin Fl alpha (6-k-PGF1 alpha) increased transiently from a baseline level of 304 +/- 44 to 2083 +/- 698 pg/ml plasma in mixed venous blood 30 minutes after incision in the placebo group (p less than 0.05), but no other significant change in plasma 6-keto prostaglandin Fl alpha or in thromboxane B2 occurred in either group at any other time. 
Rib fractures complicating median sternotomy. The postoperative chest radiographs of 100 consecutive patients undergoing median sternotomy were reviewed for the presence of acute rib fractures. The majority of patients underwent coronary artery bypass grafting. Thirteen patients sustained 15 fractures. Eleven of these fractures were of the left first rib and 7 of the 15 fractures occurred at the costotransverse articulation. The fractures tended to be subtle on the postoperative portable chest radiographs and were initially overlooked in 4 patients. Heavier patients and those with larger body surface areas were more susceptible to the development of fractures. There was no statistical correlation to total operating time, bypass time, or global ischemic time. 
Evaluating genetic association among ovarian, breast, and endometrial cancer: evidence for a breast/ovarian cancer relationship. The possibility of a genetic relationship between ovarian, breast, and endometrial cancer was investigated in data from a large multicenter, population-based, case-control study, the Cancer and Steroid Hormone Study conducted by the Centers for Disease Control (CDC). Age-adjusted relative risks (RRs) for mothers and sisters of 493 ovarian cancer cases, 895 breast cancer cases, and 143 endometrial cancer cases versus 4,754 controls were calculated. Significantly elevated age-adjusted RRs were found for ovarian cancer (RR = 2.8; 95% confidence interval [CI] = 1.6-4.9) and breast cancer (RR = 1.6; 95% CI = 1.1-2.1) among relatives of ovarian cancer probands and for breast cancer (RR = 2.1; 95% CI = 1.7-2.5) and ovarian cancer (RR = 1.7; 95% CI = 1.0-2.0) among relatives of breast cancer probands. Relatives of endometrial cancer probands had an elevated RR for endometrial cancer only (RR = 2.7; 95% CI = 1.6-4.8). The genetic relationship between ovarian, breast, and endometrial cancer was tested using a multivariate polygenic threshold model developed by Smith (1976), which was modified to accommodate three classes of probands. Estimates of heritability for ovarian, breast, and endometrial cancer were 40%, 56%, and 52%, respectively. There was a significant genetic correlation between ovarian and breast cancer (R12 = .484). Evidence for significant genetic overlap between endometrial cancer and either ovarian or breast cancer was not found. These results suggest the existence of a familial breast/ovarian cancer syndrome. Endometrial cancer, while heritable, appears to be genetically unrelated. 
The safety and efficacy of terazosin in the treatment of essential hypertension in blacks. Terazosin, a new selective alpha 1-adrenergic receptor antagonist, has been found to be an effective antihypertensive agent. In a series of studies, the safety and efficacy of terazosin, alone and in combination with other antihypertensive agents, were evaluated in 1180 black patients with mild to moderate essential hypertension. Terazosin was effective in lowering blood pressure when administered alone (in dosages of 1 to 80 mg/day) and when prescribed (in dosages of 1 to 20 mg/day) in combination with other antihypertensive agents. In elderly black patients, terazosin, 1 to 10 mg daily, was as effective in lowering blood pressure as propranolol (40 to 120 mg twice daily). Changes (mean +/- SE) in sitting diastolic blood pressure from baseline were -8.1 +/- 1.4 mm Hg for terazosin and -5.0 +/- 1.5 mm Hg for propranolol. Terazosin (5 mg) combined with methyclothiazide (2.5 to 5 mg) produced a significantly greater (p less than 0.01) antihypertensive effect than that of terazosin alone. Changes (mean +/- SE) in standing diastolic blood pressure from baseline were -7.9 +/- 2.0 mm Hg for terazosin alone, -15.1 +/- 2.1 mm Hg for terazosin plus 2.5 mg of methyclothiazide, and -15.0 +/- 2.0 mm Hg for terazosin plus 5 mg of methyclothiazide. Terazosin had a favorable effect on serum lipid levels and appeared to compensate for the negative lipid effects associated with diuretics and beta-blockers when used in combination with these agents. Terazosin, alone and combined with other antihypertensive agents, was well tolerated with minimal side effects in black hypertensive patients. 
Superficial thrombophlebitis diagnosed by duplex scanning. Since July 1982, this noninvasive vascular laboratory has performed 12,856 lower extermity venous duplex examinations. All cases of acute venous thrombosis have been categorized and entered into a computer data base. One thousand four hundred twelve examinations were positive for acute venous thrombosis. This report analyzes the laboratory's entire experience with superficial thrombophlebitis (SVT). One hundred eighty-six patients were diagnosed by duplex scanning to have SVT. Women outnumbered men 99 to 87. They were slightly older (average age 58.4 +/- 16.2 years) compared with the men (53.8 +/- 14.2 years). Men were more likely to have a complicated course of SVT (40% vs 22%; p less than 0.01). Complications included either radiographically documented pulmonary embolism or deep venous involvement. Fifty-seven (31%) patients had at least one complication of SVT. A series of predisposing factors was analyzed and six factors were associated with an increased risk of complications. They are bilateral SVT (p less than 0.01), age greater than 60 years (p less than 0.01), male sex (p less than 0.01), history of deep venous thrombosis (p less than 0.01), bed rest (p less than 0.02), and presence of infection (p less than 0.02). Location of thrombus within the greater saphenous vein (35%) was most likely to be associated with complications. Isolated varicosities (8%) were least likely to be associated with complications. Duplex scanning identifies a significant number of complications of patients with SVT and should be obtained in cases of saphenous vein involvement or in the presence of associated risk factors. 
Effect of Candida albicans plus histamine on prostaglandin E2 production by peripheral blood mononuclear cells from healthy women and women with recurrent candidal vaginitis. The in vitro production of prostaglandin E2 (PGE2) by peripheral blood mononuclear cells (PBMC) in response to viable Candida albicans, histamine, and C. albicans plus histamine was examined. With PBMC from 10 healthy women, C. albicans but not histamine induced PGE2 at a low level (100 pg/ml). However, C. albicans plus histamine acted synergistically to stimulate PGE2 production (448 pg/ml). PBMC from 8 of 10 women with recurrent candidal vaginitis also produced maximal levels of PGE2 in the presence of C. albicans plus histamine. Production of tumor necrosis factor by PBMC from patients and controls was unaffected by histamine in both the presence and absence of C. albicans. However, unlike the controls, PBMC from six of the patients who were atopic and from two nonatopic patients spontaneously released PGE2 in vitro. Addition of 4 or 10 units/ml interferon-gamma inhibited spontaneous and C. albicans-induced PGE2 production by PBMC. These data reinforce the evidence that immediate hypersensitivity responses may be involved in the etiology of recurrent candidal vaginitis. 
Trunk orientation as the determining factor of the 'contralateral' deficit in the neglect syndrome and as the physical anchor of the internal representation of body orientation in space. The present study examines which egocentric coordinate system determines the border between the disturbed 'contralateral' and the normal 'ipsilateral' side in patients with hemineglect. Based on the observation of significantly longer reaction times for saccades towards stimuli presented in the left visual field (LVF) in right brain-damaged patients with hemineglect, stimuli were presented randomly to the LVF or RVF and the corresponding saccadic reaction times (SRTs) were compared. Beginning with the standard body position generally used for the investigation of neglect patients, where the midlines of head, trunk and visual field are parallel and oriented straight towards the middle of the projection screen, the spatial relation between orientation of head and trunk midlines and location of the target stimuli was systematically varied while holding the retinal projection of the stimuli constant. The deficit in SRTs towards the LVF in 4 right brain-damaged patients with left-sided hemineglect could be compensated for by turning the patients' trunk to the left, such that both LVF and RVF-stimuli were projected to the right, ipsilateral side of trunk space. The results suggest that the spatial orientation of the trunk midline divides our normal perception of space into an egocentric 'left' and an egocentric 'right' sector and seems to be the decisive factor for determining the neglected 'contralateral' part of space in patients with brain-damage. They indicate that the trunk midline constitutes the physical anchor for calculation of the internal egocentric coordinate frame for representing body position with respect to external objects. The hypothesis of Ventre et al. (1984) that deficient reactions to contralaterally located stimuli in neglect patients could be the result of a displacement of these egocentric coordinates towards the non-neglected, ipsilateral side is discussed. 
Perioperative stroke. Part II: Cardiac surgery and cardiogenic embolic stroke. The major mechanism of stroke in cardiac surgery is embolization. The risk is higher in intracardiac than in extracardiac surgery. The incidence of stoke associated with CABG is about 5%. The cerebral protective properties of isoflurane and thiopentone, acid-base management, and monitoring of cerebral perfusion during cardiopulmonary bypass are discussed. Prophylactic carotid endarterectomy for patients with asymptomatic carotid disease before cardiac surgery is not necessary. Symptomatic carotid disease increases the risk of stroke, and the management of patients who have both symptomatic coronary and carotid artery diseases is discussed. Cardiogenic embolism is probably responsible for many perioperative strokes. Patients with atrial fibrillation, valvular disease, and prosthetic heart valves are at high risk of cardiogenic embolism. Strokes associated with cardioversion, pacemaker insertion, coronary arteriography and angioplasty are explored. 
Chemotherapy of metastatic and/or recurrent undifferentiated nasopharyngeal carcinoma with cisplatin, bleomycin, and fluorouracil. Undifferentiated nasopharyngeal carcinoma (UCNT) is known to be radiosensitive and chemosensitive, but the latter has never been studied prospectively with phase II methodology. After an intensive work-up, 49 patients with recurrent (REC) and/or metastatic (MTS) UCNT were treated with three monthly cycles of cisplatin (CDDP) 100 mg/m2 day 1; bleomycin 15 mg intravenously (IV) day 1, and 16 mg/m2/d continuous infusion (CI) days 1 to 5; and fluorouracil (5FU) 650 mg/m2/d CI days 1 to 5 (PBF). Of the 49 patients, 33 were North African. The sex ratio was three males:one female, and the median World Health Organization (WHO) performance status was 1.6. In the 48 patients assessable for response, we observed nine (19%) complete responses (CRs) and 29 (60%) partial responses (PRs) (60%), for a 79% overall response rate (95% confidence interval, 68% to 90%) in the assessable group and a 78% global rate. There were eight CRs (24%) observed in the group without previous chemotherapy (33 patients) compared with one CR in the chemotherapy pretreated group (16 patients). Four patients are still alive without evidence of disease after 52+, 54+, 58+, and 58+ months, respectively. All of them had less than three bone MTS sites, and received radiation therapy in these sites. The results confirm the chemosensitivity of UCNT, and the observation of unmaintained long-term responders makes curability a possible consideration. 
Effect of denervation or unweighting on GLUT-4 protein in rat soleus muscle. The purpose of this study was to test the hypothesis that the decreased capacity for glucose transport in the denervated rat soleus and the increased capacity for glucose transport in the unweighted rat soleus are related to changes in the expression of the regulatable glucose transporter protein in skeletal muscle (GLUT-4). One day after sciatic nerve sectioning, when decreases in the stimulation of soleus 2-deoxyglucose (2-DG) uptake by insulin (-51%, P less than 0.001), contractions (-29%, P less than 0.05), or insulin and contractions in combination (-40%, P less than 0.001) were observed, there was a slight (-18%, NS) decrease in GLUT-4 protein. By day 3 of denervation, stimulation of 2-DG uptake by insulin (-74%, P less than 0.001), contractions (-31%, P less than 0.001), or the two stimuli in combination (-59%, P less than 0.001), as well as GLUT-4 protein (-52%, P less than 0.001), was further reduced. Soleus muscle from hindlimb-suspended rats, which develops an enhanced capacity for insulin-stimulated glucose transport, showed muscle atrophy similar to denervated soleus but, in contrast, displayed substantial increases in GLUT-4 protein after 3 (+35%, P less than 0.05) and 7 days (+107%, P less than 0.001). These results indicate that altered GLUT-4 expression may be a major contributor to the changes in insulin-stimulated glucose transport that are observed with denervation and unweighting. We conclude that muscle activity is an important factor in the regulation of GLUT-4 expression in skeletal muscle. 
Donor limb vascular events following femoro-femoral bypass surgery. A Veterans Affairs Cooperative Study. Three hundred seventeen patients who had femorofemoral bypass surgery were examined for postoperative vascular changes that developed in the donor limb. "Unmasked" claudication developed in 7%, new claudication related to a "steal" developed in 3.5%, progression of preoperative claudication developed in 1%, new rest pain developed in 1.7%, and new necrosis developed in 0.7% of patients. Postoperatively, the donor limb ankle-brachial index decreased 0.30 or greater in 3% of the patients, decreased 0.15 to 0.29 in 6%, and decreased 0.10 to 0.14 in 6% of the patients. Only eight patients (3%) had a clinical and hemodynamic steal. Late vascular procedures for donor iliac stenosis were few, resulting in an iliac percutaneous transluminal angioplasty in 3% and inflow bypasses in 3%. Angiographic patterns of donor and recipient limbs were not predictive of "clinical" or "hemodynamic" steal events. Most new donor limb symptoms of claudication were an unmasking of arterial insufficiency previously present in the donor limb that became apparent when the recipient limb was improved. 
Prosthetic replacement of the distal femur for primary bone tumours. Over a 16-year period, 135 custom-made distal femoral prostheses, based on a fully constrained Stanmore-type knee replacement, were used in the treatment of primary malignant or aggressive benign tumours. Survivorship analysis showed a cumulative success rate of 72% at five years and 64% at seven years. Intact prostheses in 91% of the surviving patients gave good or excellent functional results. Deep infection was the major complication, occurring in 6.8% of cases; clinical aseptic loosening occurred in 6.0%. Revision surgery was carried out for loosening and infection, and the early results are encouraging. We conclude that prosthetic replacement of the distal femur can meet the objectives of limb salvage surgery. 
Electrophysiologic recording and thermodynamic modeling demonstrate that helium-neon laser irradiation does not affect peripheral Adelta- or C-fiber nociceptors. The effect of helium-neon laser irradiation (632.5 nm) on A delta- and C-fiber sensory afferents was investigated in the rabbit cornea, to determine the physiologic basis for reports that low power (0.1-5 mW) helium-neon (He-Ne) lasers produce acute analgesia and alleviate chronic pain. Multiple and single unit extracellular recordings from nociceptive corneal afferent nerves (C-fiber cold, C-fiber chemical, A delta mechanical and A delta bimodal) were used to study the effects of He-Ne laser radiation upon the electrophysiologic responses to mechanical, thermal, chemical and electrical stimulation of the cornea. Action potentials were analyzed for latency, amplitude, rise time, duration and frequency. Exposure of the neural receptive field and/or nerve bundle to a 4-mm diameter He-Ne laser (0-5 mW; 0-1800 sec) did not alter spontaneous or evoked neural activity. In addition, single unit action potential parameters were not altered by laser irradiation. Modeling of thermal changes produced by He-Ne radiation on corneal nerves indicated that effects predicted for receptor and axonal depths in both skin and cornea were minimal (less than 0.15 degrees C) and unlikely to alter sensory transduction or transmission. 
Brain tumor resection aided with markers placed using stereotaxis guided by magnetic resonance imaging and computed tomography. In the operative resection of brain tumors, defining and locating edges of deep-seated tumors or those with indistinct color and consistency can be difficult. This report presents a simple yet precise, alternative method, using the basic Brown-Roberts-Wells or Cosman-Roberts-Wells stereotactic frame, for placement of visual markers to aid in tumor resections. The method can also be extended to the Leksell system. Using routine computed tomographic scanning or magnetic resonance imaging after stereotactic frame application, multiple points along tumor edges were used as target points. In the operating room, standard techniques were used for the skin incision, removal of the bone flap, and opening the dura. At each target point, after opening the dura and using stereotactic coordinates and equipment, a microbiopsy forceps was used to place "micropatties" (each with a string tail) or small catheters with pledgets or catheter tips located at tumor edges. After removing the arc, the tumor resection was accomplished in a conventional nonstereotactic manner by simply following string tails or catheters to the tumor. Gross tumor edges were determined from positions of actual patties or catheter tips. These simple but accurate techniques offer the possibility of tumor resections under stereotactic guidance with equipment readily available to most neurosurgeons. The fidelity of marker placement is also maintained in relation to tumor edges despite shifts in the tumor and/or brain as cystic areas are drained or large amounts of the tumor are resected. 
Strut fracture after Greenfield filter placement. We present the unusual event of strut fracture of a Greenfield filter. This being an extremely rare complication, we postulate a possible cause of fracture and present a review of literature. 
Primary hyperaldosteronism due to a functional black (pigmented) adenoma of the adrenal cortex. The clinical and pathologic findings are reported in a case of primary hyperaldosteronism due to a functional black (pigmented) adenoma of the adrenal cortex. Cortical atrophy of the involved gland was present, the mechanism of which was obscure. 
Prevention of fetal growth retardation with low-dose aspirin: findings of the EPREDA trial. The efficacy of low-dose aspirin in preventing fetal growth retardation was tested in a randomised, placebo-controlled, double-blind trial. A secondary aim was to find out whether dipyridamole improves the efficacy of aspirin. 323 women at 15-18 weeks' amenorrhoea were selected at twenty-five participating centres on the basis of fetal growth retardation and/or fetal death or abruptio placentae in at least one previous pregnancy. They were randomly allocated to groups receiving placebo, 150 mg/day aspirin, or 150 mg/day aspirin plus 225 mg/day dipyridamole, for the remainder of the pregnancy. In the first phase of the trial all actively treated patients (n = 156) were compared with the placebo group (n = 73). Mean birthweight was significantly higher in the treated than in the placebo group (2751 [SD 670] vs 2526 [848] g; difference 225 g [95% CI 129-321 g], p = 0.029) and the frequency of fetal growth retardation in the placebo group was twice that in the treated group (19 [26%] vs 20 [13%]; p less than 0.02). The frequencies of stillbirth (4 [5%] vs 2 [1%]) and abruptio placentae (6 [8%] vs 7 [5%]) were also higher in the placebo than in the treated group. The benefits of aspirin treatment were greater in patients with two or more previous poor outcomes than in those with only one. In the second analysis, of aspirin only (n = 127) vs aspirin plus dipyridamole (n = 119), no significant differences were found. There was no excess of maternal or neonatal side-effects in the aspirin-treated patients. 
Vasoactive intestinal polypeptide inhibits c-myc expression and growth of human gastric carcinoma cells. Vasoactive intestinal polypeptide (VIP) is a gut neuroendocrine polypeptide that increases cyclic adenosine monophosphate (cAMP) production in cells with VIP receptors. Some gastrointestinal cancer cells possess functional receptors for VIP; however, the role of VIP in regulation of growth of gastric cancer cells has not been determined. The purpose of this study was to determine whether VIP and other agents that increase cAMP regulate growth of a human gastric cancer cell line (AGS) and whether these agents regulate expression of c-myc proto-oncogene, which is required for cell proliferation. We measured levels of cAMP by radioimmunoassay, and we used Northern blot analysis to examine c-myc messenger RNA expression. Cell-growth studies were carried out in media supplemented with 3% serum, and cells were counted with a Coulter counter. We found that VIP significantly increased cAMP production of AGS cells in a dose-dependent manner, whereas secretin, glucagon, and peptide histidine methionine (PHM) did not stimulate cAMP production. Exogenous cAMP (8-bromo-cAMP) inhibited AGS cell growth in a dose-dependent manner. VIP acted synergistically with either isobutylmethyl-xanthine or forskolin to inhibit AGS cell proliferation. The increased c-myc expression, which was induced by serum, was inhibited by simultaneous treatment with VIP and isobutylmethyl-xanthine. We have found that AGS cells have specific, functional VIP receptors (activation of which are negatively correlated with cell growth) and that the mechanism by which VIP acts to inhibit cell growth appears to be due, in part, to cAMP-dependent regulation of c-myc proto-oncogene expression. 
Leukotrienes as mediators in ischemia-reperfusion injury in a microcirculation model in the hamster. Leukotriene (LT)B4 promotes leukocyte chemotaxis and adhesion to the endothelium of postcapillary venules. The cysteinyl leukotrienes, LTC4, LTD4, and LTE4, elicit macromolecular leakage from this vessel segment. Both leukocyte adhesion to the endothelium and macromolecular leakage from postcapillary venules hallmark the microcirculatory failure after ischemia-reperfusion, suggesting a role of leukotrienes as mediators of ischemia-reperfusion injury. Using the dorsal skinfold chamber model for intravital fluorescence microscopy of the microcirculation in striated muscle in awake hamsters and sequential RP-HPLC and RIA for leukotrienes, we demonstrate in this study that (a) the leukotrienes (LT)B4 and LTD4 elicit leukocyte/endothelium interaction and macromolecular leakage from postcapillary venules, respectively, that (b) leukotrienes accumulate in the tissue after ischemia and reperfusion, and that (c) selective inhibition of leukotriene biosynthesis (by MK-886) prevents both postischemic leukotriene accumulation and the microcirculatory changes after ischemia-reperfusion, while blocking of LTD4/E4 receptors (by MK-571) inhibits postischemic macromolecular leakage. These results demonstrate a key role of leukotrienes in ischemia-reperfusion injury in striated muscle in vivo. 
Intellectual outcome in children with maple syrup urine disease. We report a controlled study of intellectual outcome in 16 children with maple syrup urine disease (MSUD) that compares the outcome of MSUD diagnosed after symptoms became apparent with that of MSUD diagnosed prospectively and in unaffected siblings and parents. The mean IQ (+/- SD) score in the children with classic MSUD was 78 +/- 24; however, there were two discrete groups: one with normal IQ (greater than 84) whose MSUD had been diagnosed at a mean age of 3.5 days and a second group, with IQ below normal, whose MSUD was diagnosed at a mean of 10 days of age. Affected children treated presymptomatically had higher IQ scores than their affected siblings treated when their disease was symptomatic. Multiple regression analysis indicated that the important influences on IQ were age at the time of diagnosis and long-term metabolic control; control at the time of testing also might have affected performance. The mean score of unaffected siblings was 92 +/- 5 and the mean parental IQ was 83 +/- 9. The mean IQ scores of children with variant MSUD, 97 +/- 4, was similar to that of their parents, 103 +/- 6. This study was not longitudinal and thus could not identify subtle developmental learning problems. We conclude that early and meticulous treatment of MSUD can result in intellectually normal children. 
Ig gene rearrangements on individual alleles of Abelson murine leukemia cell lines from (C57BL/6 x BALB/c) F1 fetal livers. We have previously shown that selection of Ig H chain V region genes used by colonies obtained from splenic B cells and fetal liver pre-B cells was dependent on strain-specific factors. Moreover, by examining the V gene usage in strains congenic at the Igh locus, we also determined that the strain-specific factor was encoded by sequences lying outside of the Igh locus. We decided to examine whether there are differences in Vh gene rearrangement between alleles in an F1 strain. To do this analysis we chose to examine the relative Ig H chain V region gene usage of pre-B cell lines derived from (C57BL/6 x BALB/c)F1 fetal liver cells by Southern blot analysis. We found a high frequency of Vh-gene rearrangements (77% of the alleles had VDJ rearrangements) and these rearrangements occurred to Vh-genes throughout the Vh locus and were not confined to the D-proximal Vh-genes as has been previously observed with lines from other mouse strains. The Vh-gene usage pattern is similar on both alleles indicating that at least one of the determinants of which Vh-gene is used is trans-acting and acts similarly on each allele. Furthermore, one allele, Ighb (donated by the C57BL/6 parent), rearranged Vh-genes more frequently than the other allele, Igha (donated by the BALB/c parent) suggesting that one of the determinants of Vh-gene rearrangement may be acting in an allele-specific manner. 
Peripheral pulmonary adenoid cystic carcinoma with substantial submucosal extension to the proximal bronchus. A rare case of a peripheral pulmonary adenoid cystic carcinoma is presented. Histological examination after lobectomy showed pronounced submucosal invasion of the carcinoma to proximal bronchi. 
Aortic dissection type A surgery: Doppler sonography to evaluate correct carotid artery perfusion during cardiopulmonary bypass. In the surgery of acute aortic type A dissection we have employed preoperative and intraoperative Doppler sonography, to check safe and correct perfusion of the carotid arteries by the cardiopulmonary bypass before instituting cardiac arrest. Ten patients, operated upon for acute aortic type A dissection, were evaluated by means of Doppler sonography and in two patients a very abnormal flow pattern was found in the carotid arteries at the moment of aortic cross-clamping; immediate unclamping allowed temporary antegrade carotid perfusion, while the perfusion technique was readjusted. We report our experience with preoperative and intraoperative Doppler sonography, which appears to be a valuable new method of improving the surgical management of acute aortic type A dissection. 
Randomized comparative trial of indomethacin and ritodrine for the long-term treatment of preterm labor. A randomized prospective trial was performed to compare the efficacy and safety of ritodrine and indomethacin in the long-term treatment of preterm labor. Forty patients with intact membranes in preterm labor at 23 to 34 weeks' gestation were randomized to receive either intravenous ritodrine or oral indomethacin as the first-line tocolytic agent. Successful intravenous ritodrine therapy was followed by oral terbutaline therapy, and indomethacin-treated patients continued to receive oral indomethacin. Treatment failures were defined as progressive preterm labor or patient intolerance, and these patients were treated with intravenous magnesium sulfate. Ritodrine and indomethacin were equally successful in delaying preterm birth as defined by interval to delivery, gestational age at delivery, delivery delayed greater than 7 days, attainment of 35 weeks of gestation, percentage of patients who required magnesium sulfate therapy, percentage of patients who were readmitted with premature rupture of membranes, absence of recurrent preterm labor, and infant birth weight. More than 80% of mothers who received ritodrine voiced complaints of beta-sympathomimetic side effects, and one patient discontinued treatment as the result of intolerance. There were minimal patient complaints with indomethacin use. No statistically significant differences were noted in neonatal outcome as defined by Apgar scores, umbilical cord pH, intensive care days, ventilator days, or neonatal deaths. However, three cases of primary pulmonary hypertension were observed in the indomethacin group. We had not previously observed this problem with short-term (24 to 48 hours) indomethacin therapy. 
Interleukin-2 immunotherapy followed by resection of residual renal cell carcinoma. We administered 10 (E5) units per kg. interleukin-2, 3 times daily, with or without lymphokine-activated killer cells, to 10 patients with metastatic renal cell carcinoma. All patients had metastases to the lung, and 3 of 5 patients who had previously undergone nephrectomy had metastases to the renal fossa. Of the 9 patients who completed at least 1 course of therapy 3 had complete regression of disease outside the abdomen, including 2 who were rendered disease-free after subsequent cytoreductive surgery (nephrectomy in 1 and resection of the renal fossa recurrence in 1). Viable tumor comprised less than 1% of each surgical specimen. Our results support the view that initial treatment with interleukin-2 immunotherapy, followed by abdominal cytoreductive surgery if the peripheral metastases have regressed, may be preferable to the practice of performing abdominal cytoreductive surgery before administering interleukin-2 immunotherapy for patients with widely metastatic renal cell carcinoma. 
Specific adoptive immunotherapy mediated by tumor-draining lymph node cells sequentially activated with anti-CD3 and IL-2. Lymph nodes (LN) draining progressively growing tumors contain tumor-sensitized but not fully functional preeffector lymphocytes. These cells could acquire therapeutic efficacy and be expanded upon sequential culture with anti-CD3 mAb for 2 days followed by incubation in IL-2 for 3 days. Using the weakly immunogenic MCA 106 and MCA 205 murine sarcomas, we have further defined conditions of this anti-CD3/IL-2 activation with which preeffector cells differentiated into immune effector cells. In vitro activation and expansion of effector cells required sequential but independent stimulation with anti-CD3 and IL-2 because the simultaneous presence of both anti-CD3 and IL-2 at either stage did not enhance the efficacy of activation. Generation of effector cells by this two-stage activation was critically dependent on the optimal concentrations of anti-CD3 (1.0 microgram/ml) and IL-2 (2-10 U/ml). However, these conditions were not optimal for inducing the greatest cellular proliferation. In adoptive immunotherapy experiments, although the transfer of anti-CD3/IL-2-activated cells alone could mediate the regression of established metastases, the concomitant administration of IL-2 enhanced the in vivo activity of these cells. More importantly, tumor regression mediated by the anti-CD3/IL-2-activated cells was found to be immunologically specific. The specificity was determined by the tumor that stimulated the preeffector cell response. In spite of their in vivo antitumor effects, the anti-CD3/IL-2-activated tumor-draining LN cells did not exhibit detectable in vitro cytotoxicity against the tumor target in the 4-h 51Cr-release assay. In mice bearing progressive tumor, draining LN contained most preeffector cells. Some preeffector cells were also detected in the spleen whereas mesenteric LN did not demonstrate any reactivity. In kinetics studies, sensitization of preeffector cells in the draining LN occurred between 4 to 6 days after tumor inoculation. As the tumor progressed, the presence of preeffector cells declined gradually suggesting a tumor-induced suppression. These results define the conditions whereby tumor-draining LN cells could be stimulated, in the absence of tumor Ag, to develop into specific therapeutic effector cells. Our findings also raise the possibility of using similar approaches for isolating immune effector cells from cancer patients for adoptive immunotherapy. 
Studying whole-mounted sections of the paranasal sinuses to understand the complications of endoscopic sinus surgery. Endoscopic techniques for paranasal sinus surgery have allowed detailed and complete removal of sinus disease while promising minimum distress to the patient. The telescopic view of the operative field shows detail of the sinus anatomy and its disease, not possible in earlier transnasal techniques. Several articles document the serious complications seen with the endoscopic surgery. To understand the paranasal sinuses and their relationships to the orbit and cribriform plate, blocks of cadaver heads that included the orbit and paranasal sinuses were whole sectioned. It has been possible to see areas of the cribriform and orbital wall that are at risk to produce cerebrospinal fluid rhinorrhea and orbital complications. At the same time, landmarks for avoiding these complications can be defined to guide the surgeon during this dissection as seen through the endoscope. 
Prognostic significance of anticentromere antibodies and anti-topoisomerase I antibodies in Raynaud's disease. A prospective study. Seventy-seven patients with Raynaud's disease were studied for a mean of 4 years (range 1-11 years) to determine the relationship between autoantibodies and long-term clinical outcome. Anticentromere antibodies (ACA) were assayed by indirect immunofluorescence and by immunoblotting of HeLa cell chromosome extracts. Antibodies to topoisomerase I (anti-topo I) were assayed by immunodiffusion and immunoblotting. Antibodies to the major centromeric protein, CENP-B, and anti-topo I were studied by enzyme-linked immunosorbent assay (ELISA). Eight patients developed telangiectasias, 4 developed skin tightening, and 4 developed a connective tissue disease other than scleroderma. The presence of ACA at the start of the study was associated with the development of telangiectasias (P less than 0.003). An initial 100-kd band on immunoblot in conjunction with a positive anti-topo I ELISA result was associated with the development of tight skin (P less than 0.0025), while a 100-kd band with a negative anti-topo I ELISA result was associated with the subsequent development of a connective tissue disease other than scleroderma (P less than 0.0073). Patients who were initially ACA positive, had the 100-kd band on immunoblot, or had positive ELISA results for anti-topo I or for anti-CENP-B were 63-fold more likely to develop signs of connective tissue disease by the end of the study (P less than 0.000009). The presence of any of these autoantibodies was more sensitive (100%), although less specific (75%), than were findings from nailfold capillaroscopy (sensitivity 67% and specificity 95%) in predicting subsequent clinical progression. We conclude that findings of assays for anti-topo I and ACA complement the findings from nailfold capillaroscopy in providing useful prognostic information in Raynaud's disease. 
The role of definitive radiation therapy in squamous cell carcinoma of the oral tongue. Between 1968 and 1985, 114 patients with squamous cell carcinoma of the tongue were evaluated in the Department of Radiation Oncology at the University of Virginia (Charlottesville, VA); of these, 86 received treatment with curative intent. The majority were treated with radiation therapy alone, whereas the remainder were treated with radiation therapy with preoperative or postoperative surgery. There were 17 T1 primary malignancies, 40 T2, 27 T3, and 2 T4. Clinically positive adenopathy was present in 48% of the patients overall and ranged from 35% in the T1 group to 100% in the T4 group. Twenty-six percent of patients either presented with or later had second malignancies. At 36 months, the patient status was evaluated as dead of disease (37%), dead of intercurrent disease (23%), alive with disease (1%), and alive without evidence of disease (38%). Seventy-five patients received external beam therapy and 32 patients received an implant as either all or part of their treatment. Average doses were in the range of 6000 Gy. Adjusted local control rate at 3 years was not statistically different for different treatment techniques used on either T1 or T2 primary malignancies. The rates were 89% versus 88% for T1 lesions treated with definitive radiation therapy versus postoperative radiation therapy. For T2 primary malignancies, the rates were 67%, 71%, and 83% for the definitive, preoperative, and postoperative radiation therapy groups, respectively. For T3 lesions, there was close to statistical significance with the corresponding rates being 47%, 50%, and 100%, respectively. When the effect of implants was examined for T1 and T2 lesions, no difference in local control rate at 3 years was noticed with or without an implant. Survival was improved for the group presenting with positive neck disease when compared with the N0 group. The external beam severe complication rate was less than 5%, and the implant complication rate was 6%. 
Chronic cluster headache associated with a vertebral artery aneurysm. This is a report of a patient with chronic cluster headache-like pain of 12 years duration. Investigation revealed an aneurysm at the junction of the vertebral and posterior inferior cerebellar arteries and after removal the patient experienced resolution of his cluster headache. The headache and aneurysm were both right sided suggesting a possible relationship. 
What is migraine? Controversy and stalemate in migraine pathophysiology. Theories of migraine pathophysiology have evolved from the realms of the supernatural into the scientific arena but their further evolution seems delayed by unproductive controversy about whether or not migraine is primarily a vascular or a neurological dysfunction. This conceptual deadlock needs to be transcended by thinking beyond the neural and vascular systems, and by identifying mechanisms that could affect both to produce the characteristic clinical phenomena of migraine. One theoretical model envisages 5-hydroxytryptamine (serotonin; 5-HT) as a link between the neural and vascular systems, with global alteration of serotonergic neurotransmission affecting not only these systems, but the gastrointestinal tract as well, with incidental reverberations on platelet function. Such altered serotonergic transmission might originate from altered 5-HT receptor dynamics, a molecular change in turn produced by genetic mechanisms. Recognition of the importance of 5-HT receptor function in migraine, most notably that agonists of 5-HT1 receptors abort acute migraine and that antagonists of 5-HT2 receptors prevent migraine, may lead to significant therapeutic advances. The possibility that the "trigeminovascular system" might be the end-stage mechanism that these serotonergic changes detonate to produce the painful reverberations of migraine headache is also important. Seeking ways to muffle these reverberations, or to insulate the system itself from the action of external influences (likely through further study of peptidergic transmission and receptors) might result in more drugs that will abort or prevent migraine. 
Cerebrospinal fluid leaks and meningitis in acoustic neuroma surgery. Cerebrospinal fluid leaks and associated meningitis are the most common life-threatening complications of surgery for acoustic neuromas. This retrospective study reviews 319 patients who had surgery for 321 acoustic tumors at the Sunnybrook Health Sciences Center, University of Toronto, from April 1975 to March 1990. Cerebrospinal fluid leaks occurred after 13.4% of primary tumor operations. Surgical repair was required in 6.2% of all patients; 4.4% needed more than one operation. Meningitis occurred in 5.3% of all patients. These complications were more common in larger tumors and after the combined translabyrinthine middle fossa approach. Transnasopharyngeal eustachian tube obliteration was used to stop recurrent cerebrospinal fluid leaks in two patients. 
Cerebral metastases as first symptom of bronchogenic carcinoma. A prospective study of 37 cases. Among the patients showing evidence of cerebral metastases without previously known cancer history, lung cancer has been found 37 times as the primary tumor in our institution. There were 34 men and three women and all but two were heavy smokers. Only one presented at diagnosis with thoracic symptoms but the chest radiograph was abnormal in 34. The histologic type of the primary tumor was obtained in 32 cases as a result of thoracic investigations and in five cases from metastatic tumor tissue. The primary tumor appeared to be non-small cell lung carcinoma in 26 cases and small cell lung carcinoma in 11 cases. These results show that patients treated with surgery (20 cases) have a better survival (median 10 months versus 4.5) than the others, and among surgically treated patients only those treated with bifocal resection (eight patients) are long-term survivors. Also, in four of six patients, objective regression of the neurologic symptoms was seen after radiation therapy alone. Central nervous system relapse was seen in 12 patients, but in none of the patients treated with postoperative radiation therapy. Conventional chemotherapy (11 patients) induced objective responses only in the small cell type and proved to be too toxic when used simultaneously with radiation therapy in inoperable patients. 
Nasal hyper-responsiveness to histamine, methacholine and phentolamine in patients with perennial non-allergic rhinitis and in patients with infectious rhinitis. Recently it has been shown that patients with atopic rhinitis and with an allergy to house dust mites have a stronger nasal response to insufflation of histamine, methacholine and phentolamine than a control group. This hyper-responsiveness could not be demonstrated in patients with perennial non-allergic rhinitis, unless the patients were selected according to the predominant symptoms in the history. Patients with rhinorrhoea ('runners') proved to be hyper-responsive to methacholine compared with normal controls. The existence of two subpopulations was emphasized by hyper-responsiveness to both histamine and methacholine in the runners group compared with the patients with a stuffy nose ('blockers'). Patients with chronic nasal infections (characterized by recurrent episodes of purulent discharge) showed no hyper-responsiveness at all, indicating that either hyper-reactivity does not play an important part in this patient population or methods to detect hyper-reactivity in this group are inadequate. In contrast to our earlier observations in patients with atopic rhinitis, increased responsiveness to phentolamine could not be detected either in the patients with perennial rhinitis or in the patients with infectious rhinitis, indicating that the possible alpha-adrenergic dysfunction found in patients with atopic rhinitis is restricted to this group. 
Clonality and clonal evolution of hepatocellular carcinoma with multiple nodules. To determine the clonal evolution of hepatocellular carcinoma, the integrated hepatitis B virus DNA patterns of the main tumor, satellites and/or metastatic lesions were analyzed by Southern-blot hybridization in 28 hepatocellular carcinomas, including three HBsAg-seronegative cases. Unicentric or multicentric hepatocellular carcinoma was confirmed by histopathological criteria in 89% of the cases. Among 17 unicentric hepatocellular carcinomas, minor changes of the integration pattern--including partial loss or addition of the integration sites or both--were detected in the metastatic lesions in 29% of the cases. Furthermore, none of five cases with free-form hepatitis B virus DNA in the primary tumor had detectable free hepatitis B virus DNA in the metastatic lesions. These results suggest that the alteration of integrated hepatitis B virus DNA pattern during the course of tumor growth and metastasis may occur more often than previously perceived and that the switch-off of virus replication may be related to tumor metastatic potential. In eight cases with unilateral, multicentric hepatocellular carcinoma, two clones were detected in six cases, three were seen in another and four were seen in one. One case of note was a 9-yr-old boy with two histological types and two different integration patterns, one associated with vascular invasion and lung metastasis. Three patients with bilateral hepatocellular carcinoma were confirmed to have bicentric or tricentric hepatocellular carcinoma rather than intrahepatic dissemination and had survival rates similar to those in unicentric hepatocellular carcinoma. Three invasive HBsAg-seronegative hepatocellular carcinomas were found to have hepatitis B virus DNA integration and were of unicentric origin. 
Endoscopic sphincterotomy: the whole truth. An 8 year experience of 602 patients (median age 76 years) referred for endoscopic management of common bile stones is reported. No patient referred for treatment has been excluded. A diagnostic cholangiogram was achieved in 94 per cent and sphincterotomy was accomplished in 91.5 per cent. The bile ducts were demonstrated to be completely cleared of stones in 491 (81.6 per cent) of 602 patients. A mean number of 1.9 endoscopic retrograde cholangiopancreatography examinations per patient were necessary to achieve this result. Complications of endoscopic sphincterotomy, which were strictly defined, occurred in 10.5 per cent of patients although five patients had two complications (total complication rate 11.3 per cent). The 30-day mortality rate was 2.2 per cent, seven of 13 deaths (1.2 per cent) occurring as a direct result of sphincterotomy. There have been statistically significant improvements in bile duct clearance and complication rates with increasing experience of endoscopists. 
The contributing role of condylar resorption to skeletal relapse following mandibular advancement surgery: report of five cases. The contribution of condylar resorption to relapse following mandibular advancement surgery has not been fully evaluated, yet may contribute substantially to postoperative occlusal and skeletal changes too often considered simply as "relapse." Five cases showing a typical relapse pattern are presented, illustrating the role of condylar resorption. Preoperative factors that may contribute to the development of condylar resorption (age, sex, high preoperative mandibular plane angle, and the presence of preoperative temporomandibular joint disease), as well as intraoperative and postoperative factors, are discussed. A target group is defined in which special considerations should be made with regard to preoperative and postoperative management. 
Type IV procollagen mRNA regulation: evidence for extracellular matrix/cytoskeleton/nuclear matrix interactions in human urothelium. The absence of basement membrane components correlates with tumor stage and progression in human bladder cancers. We have previously shown that invasive tumors possess the ability to degrade basement membrane. However, the presence of basement membrane may be affected not only by its degradation, but by its synthesis and deposition as well. Our results in the present study suggest that while the invasive human transitional carcinoma cell line EJ has an increased amount of type IV procollagen mRNA when compared to the non-invasive RT4 cell line, type IV collagen staining is absent in the invasive EJ cells and intensely present in the non-invasive RT4 cells. Moreover, when EJ cells were grown on an artificial basement membrane (Matrigel), type IV procollagen mRNA expression was down-regulated to the levels seen with the non-invasive RT4 cells. We also discovered that the invasive cells, when grown on Matrigel, appeared morphologically different from the same cells grown on plastic tissue cultures. We conclude that a deficient basement membrane in invasive cancer cells may be due not only to active proteolytic activity but also to an abnormal production and deposition of extracellular matrix components. In addition, we also demonstrated that basement membrane components may have a significant effect on epithelial cell morphology and gene regulation, and that any alterations of the extracellular matrix-cytoskeleton-nuclear matrix interactions can lead to altered gene regulations and cell function. 
Adjuvant chemotherapy enhances long-term survival of patients with advanced gastric cancer following curative resection. We examined the effectiveness of postoperative adjuvant chemotherapy with mitomycin C (MMC), 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur), plus PSK, an immunomodulator, for patients with advanced gastric cancer who underwent histological curative resection. The effect of chemotherapy on prognostic serosal (ps) invasion [ps(-) or ps(+)] and lymph node metastasis [n(-) or N(+)] was examined. One hundred eighteen patients were in the no-chemotherapy group and 137 were on the drugs. The median follow-up time for the 86 survivors at the time of analysis was 13.8 years. With regard to prognostic factors, there were no differences between the two groups. Generalized Wilcoxon test of the two survival patterns revealed a P value of .0351, and the survival rate for 15 years was 45.7% for patients in the no-chemotherapy group and 56.9% for those of the chemotherapy group. In particular, adjuvant chemotherapy was effective for patients with ps(-)n(+) (P less than .05) and ps(+)n(-) (P less than .05), but not for those with ps(-)n(-) and ps(+)n(+). Our findings show that the concomitant prescription of MMC, tegafur, and PSK improves the 15-year survival rate for patients with advanced gastric cancer, following curative resection. As the survival rate is low for the patients with ps(+)n(+), an even more aggressive postoperative chemotherapy is recommended. 
Are depressive symptoms nonspecific in patients with acute stroke? OBJECTIVE: Some investigators have suggested that major depression might be overdiagnosed in stroke patients because of changes in appetite, sleep, or sexual interest caused by their medical illness; others have suggested that depression may be underdiagnosed in stroke patients who deny symptoms of depression because of anosognosia, neglect, or aprosody. The authors' goal was to determine how frequently depressive symptoms occur in acute stroke patients with and without depressed mood to estimate how often diagnostic errors of inclusion or exclusion may be made. METHOD: They examined the rate of autonomic and psychological symptoms of depression in 205 patients who were consecutively hospitalized for acute stroke. Eighty-five (41%) of these patients had depressed mood, and 120 (59%) had no mood disturbance. Forty-six (54%) of the 85 patients with depressed mood (22% of all patients) were assigned the DSM-III diagnosis of major depression. RESULTS: The 120 patients without mood disturbance had a mean of one autonomic symptom, but the 85 patients with depressed mood had a mean of almost four. Tightening the diagnostic criteria to account for one more nonspecific autonomic symptom decreased the number of patients with major depression by only three; adding two more criteria decreased the number by only five. Thus, the rate of DSM-III major depression was 1% higher than the rate with one extra nonspecific autonomic symptom and 2% higher than the rate with two extra criteria. Conversely, loosening diagnostic criteria to account for denial of depressive illness increased the rate of major depression by only 5%. CONCLUSIONS: Both autonomic and psychological depressive symptoms are strongly associated with depressed mood in acute stroke patients. 
Current approaches to chronic pain in older patients. As the population ages, primary care physicians face an increasing number of individuals who suffer from the effects of chronic diseases, including the accompanying chronic pain. This article reviews the common causes of pain in the elderly and suggests a system for assessing its severity. Five different approaches to treating pain in this population are outlined, as are guidelines for managing the potential side effects of treatment. 
Morphometric studies in intraductal breast carcinoma using computerized image analysis. A morphometric study was performed using computerized image analysis on the histologic specimens of 26 patients with intraductal carcinoma of the breast and 26 normal control patients. A significant incidence of necrosis (56%) was observed in the breast ducts containing intraductal carcinoma. This was characterized by one or more areas of necrosis surrounded by a rim of viable tumor cells. The mean diameter of the ducts containing intraductal carcinoma was 349 microns compared with a mean diameter of 90 microns for the normal ducts. The mean diameter of the ducts containing necrosis was 470 microns compared with a mean diameter of 192 microns for the ducts containing a solid pattern of intraductal carcinoma. Central necrosis occurred in 94% of the ducts more than 180 microns in radius, whereas only 34% of the ducts less than 180 microns in size contained necrosis. The width of the viable neoplastic tissue was less than 180 microns in 91% of the ducts. These results are analogous to the findings of Thomlinson and Gray in human lung tumor cords and provide indirect evidence for the existence of a hypoxic compartment in intraductal carcinoma of the breast. This could be an explanation for the higher local failure rate after conservative surgery and irradiation for infiltrating cancers containing an extensive intraductal component. 
A prospective comparison of thromboembolic stockings, external sequential pneumatic compression stockings and heparin sodium/dihydroergotamine mesylate for the prevention of thromboembolic complications in urological surgery. Deep venous thrombosis and pulmonary emboli are reported to occur in up to 66% of the patients undergoing a major urological operation. Thromboembolic stockings, external sequential pneumatic compression stockings and anticoagulant agents, such as heparin sodium plus dihydroergotamine mesylate, have been suggested to decrease the risk of deep venous thrombosis and pulmonary emboli. A total of 74 evaluable patients undergoing a major urological operation was randomized to receive either thromboembolic stockings, external sequential pneumatic compression stockings, or heparin plus dihydroergotamine as prophylaxis against deep venous thrombosis and pulmonary emboli. 111Indium-labeled platelet scans, performed preoperatively and on days 1, 3 and 6 postoperatively, were used to diagnose deep venous thrombosis and pulmonary emboli. Mean patient age was 63 years and all but 1 operation was performed for neoplastic disease. Deep venous thrombosis was detected in 5 of 25 patients (20%) with thromboembolic stockings, 3 of 24 (12.5%) with external sequential pneumatic compression stockings and 2 of 25 (8%) with heparin plus dihydroergotamine. There was no difference in blood loss or complications among the groups. Although statistical significance among the treatment groups was not reached in this study, the trend to a decrease in deep venous thrombosis and pulmonary emboli with external sequential pneumatic compression stockings and heparin plus dihydroergotamine, and an absence of an increase in morbidity in these groups supports the use of these modalities to decrease the morbidity and mortality of deep venous thrombosis and pulmonary emboli. 
Nerve cell loss in the thalamus in Alzheimer's disease and Parkinson's disease. Serial sections through the thalamus from the fixed right cerebral hemispheres of 15 cases (5 Parkinson's disease, 5 Alzheimer's disease (AD) and 5 controls) were used to obtain quantitative estimates of neuronal loss, neurofibrillary tangle formation and Lewy body inclusions within individual thalamic nuclei. Severe neuronal loss and tangle formation were evident in the anterodorsal nucleus from the AD cases. Nerve cell damage was also present in the centromedian nucleus but was not associated with tangle formation and occurred in all but 2 of the brains examined. It is likely that the anterodorsal neurons are damaged locally by the Alzheimer's disease process whereas the changes in the centromedian nucleus may be related to ageing. 
Rupture of the internal elastic lamina and vascular fragility in stroke-prone spontaneously hypertensive rats. We studied a possible relation between stroke and an enhanced susceptibility to rupture of the arterial internal elastic lamina by comparing stroke-prone spontaneously hypertensive rats with spontaneously hypertensive rats, which have a very low incidence of stroke. We quantified interruptions in the internal elastic lamina in certain arteries and studied the effect of beta-aminopropionitrile, an inhibitor of cross-link formation in collagen and elastic fibers, on rupture of the internal elastic lamina and on mortality in these two substrains. To eliminate any influence of higher blood pressure in the stroke-prone rats on the parameters studied, we used antihypertensive treatment to obtain equivalent blood pressures in the two substrains. Results showed that stroke sensitivity was associated with an enhanced early spontaneous rupture of the internal elastic lamina in the caudal artery, an increased susceptibility to beta-aminopropionitrile-induced rupture of the internal elastic lamina, and earlier mortality, mainly from aortic rupture, under beta-aminopropionitrile treatment. These findings suggest that stroke-prone rats have an enhanced minor connective tissue defect that is expressed by rupture of the internal elastic lamina and may be related, at least in part, to their greater vascular fragility and increased susceptibility to stroke. 
Capillary refill--is it a useful predictor of hypovolemic states? STUDY OBJECTIVES: To evaluate whether the capillary refill test can correctly differentiate between hypovolemic and euvolemic emergency department patients. DESIGN: A prospective, nonrandomized, nonblinded time series. SETTING: The orthostatic and hypotensive patients were seen in a university hospital ED with 44,000 visits per year. Blood donors were studied in the hospital's blood donor center. TYPE OF PARTICIPANTS: Thirty-two adult ED patients who presented with a history suggestive of hypovolemia and either abnormal orthostatic vital signs (19) or frank hypotension (13), and 47 volunteer blood donors who ranged in age from 19 to 83 participated. INTERVENTIONS: Capillary refill was measured before rehydration in the ED subjects and, in the donor group, before and after a 450-mL blood donation. MEASUREMENTS: Sensitivity, specificity, accuracy, and positive and negative predictive values were calculated. Analyses were stratified by age, sex, and study group. MAIN RESULTS: For the blood donor group, mean capillary refill time before donation was 1.4 seconds and after donation was 1.1 seconds. Mean capillary refill time for the orthostatic group was 1.9 seconds and for the hypotensive group was 2.8 seconds. When scored with age-sex specific upper limits of normal, the sensitivity of capillary refill in identifying hypovolemic patients was 6% for the 450-mL blood loss group, 26% for the orthostatic group, and 46% for the hypotensive group. The accuracy of capillary refill in a patient with a 50% prior probability of hypovolemia is 64%. Orthostatic vital signs were found to be more sensitive and specific than capillary refill in detecting the 450-mL blood loss. CONCLUSION: Capillary refill does not appear to be a useful test for detecting mild-to-moderate hypovolemia in adults. 
Indications for and the technique of local resection of tumors of the papilla of Vater. Local resection of tumors of the papilla of Vater was performed in six cases (three benign adenomas and three adenocarcinomas). Pathology was suggested in all cases by endoscopic biopsy and confirmed by operative excision. A method of excision of the tumor and reconstruction of the pancreaticobiliary apparatus was used that eliminated all gross and microscopic disease. Only one of the patients with benign disease (familial polyposis) suffered from local recurrence. All three patients with malignant tumors developed local recurrences within 2 years of resection. Local resection seems to be a viable alternative to Whipple's resection in patients with benign tumors. In malignant cases, local resection should be considered only a palliative procedure and confined to elderly patients with severe concomitant disease and patients in whom a more radical procedure would incur an undue surgical risk. 
Influenza A and the virus associated haemophagocytic syndrome: cluster of three cases in children with acute leukaemia. At the height of the United Kingdom influenza A epidemic in December 1989, three children receiving treatment for non-T cell acute leukaemia developed pancytopenia with concomitant influenza A infection. Bone marrow histology showed prominent marrow erythrophagocytosis by morphologically mature histiocytes, consistent with the picture of virus associated haemophagocytic syndrome (VAHS). In two cases there was an initial spontaneous recovery, though recurrence of VAHS developed in one case in association with a different viral infection (cytomegalovirus) following autologous bone marrow transplantation. The third child died from cardiorespiratory failure secondary to infection with influenza A and Klebsiella pneumoniae sepsis. It is suggested that influenza A should be added to the list of infective causative agents. 
Localization of the gene encoding the GABAA receptor beta 3 subunit to the Angelman/Prader-Willi region of human chromosome 15. Deletions of the proximal long arm of chromosome 15 (bands 15q11q13) are found in the majority of patients with two distinct genetic disorders, Angelman syndrome (AS) and Prader-Willi syndrome (PWS). The deleted regions in the two syndromes, defined cytogenetically and by using cloned DNA probes, are similar. However, deletions in AS occur on the maternally inherited chromosome 15, and deletions in PWS occur on the paternally derived chromosome 15. This observation has led to the suggestion that one or more genes in this region show differential expression dependent on parental origin (genetic imprinting). No genes of known function have previously been mapped to this region. We show here that the gene encoding the GABAA (gamma-aminobutyric acid) receptor beta 3 subunit maps to the AS/PWS region. Deletion of this gene (GABRB3) was found in AS and PWS patients with interstitial cytogenetic deletions. Evidence of beta 3 gene deletion was also found in an AS patient with an unbalanced 13;15 translocation but not in a PWS patient with an unbalanced 9;15 translocation. The localization of this receptor gene to the AS/PWS region suggests a possible role of the inhibitory neurotransmitter GABA in the pathogenesis of one or both of these syndromes. 
Effect of hyaluronic acid on postoperative intraperitoneal adhesion formation and reformation in the rat model. The local application of 0.25% or 0.4% HA before the induction of a measured laser injury on the rat uterine horn was associated with a significant reduction (P less than 0.05) in postoperative IP adhesions when compared with the group of animals pretreated with the diluent vehicle PBS or received no pretreatment. However, 0.4% HA, when applied in a similar manner, was ineffective in reducing reformation of adhesions after microsurgical adhesiolysis. 
Cardiac involvement in patients with primary antiphospholipid syndrome. To evaluate cardiac involvement in primary antiphospholipid syndrome, two-dimensional and Doppler echocardiographic studies were performed in 34 consecutive patients with this syndrome. All patients had an increased level of serum anticardiolipin antibodies with no evidence of malignancy or systemic lupus erythematosus. The clinical manifestations of primary antiphospholipid syndrome were arterial thrombosis in 14 patients, venous thrombosis in 6 and recurrent fetal loss in 14. Valvular lesions were observed on two-dimensional echocardiography in 11 patients (32%) (9 women and 2 men), aged 24 to 57 years (mean +/- 1 SD 36 +/- 10). Abnormal echocardiographic findings were observed in 9 (64%) of 14 patients with arterial thrombosis versus 1 (17%) of 6 patients with venous thrombosis and 1 (7%) of 14 patients with recurrent fetal loss. The most common echocardiographic abnormality was mitral leaflet thickening, found in five patients; this was associated with mitral regurgitation in three and with combined mild mitral stenosis and regurgitation in one patient. Localized subvalvular mitral thickening was observed in one patient and calcification of the anulus in another. Aortic valve thickening was observed in two patients, one of whom also had a moderate degree of aortic regurgitation. Vegetation-like lesions on the mitral or aortic valve were found in two patients. It is concluded that valvular lesions are commonly found in primary antiphospholipid syndrome, particularly when the syndrome is manifested by peripheral arterial thrombosis. The location and appearance of valvular lesions in this syndrome are heterogeneous. Most patients have no clinically significant valvular disease. Two-dimensional and Doppler echocardiographic studies are often informative in these patients. 
Cerebral akinetopsia (visual motion blindness). A review. Cerebral akinetopsia is a syndrome in which a patient loses specifically the ability to perceive visual motion following cortical lesions outside the striate cortex. There has been only one good case of akinetopsia in the published literature. Yet that case was immediately accepted by the neurological world. In this, cerebral akinetopsia differs markedly from cerebral achromatopsia, the evidence for which was strongly contested for the better part of a century (Zeki, 1990). This article complements the one on cerebral achromatopsia, traces the history of akinetopsia and enquires into why it was so much more readily acceptable than achromatopsia. 
Normalisation of refractive error after steroid injection for adnexal haemangiomas. A longitudinal study of 27 patients with infantile haemangiomas is reported. It confirmed the efficacy of local steroid injection as a method of treatment; 81.5% of patients showed a marked improvement, with the lesion reducing to 25% or less of its original size. Involution was most marked in the first two weeks but continued for up to four months after injection. Amblyopia was present in 43% of children and was usually the result of induced refractive error rather than obstruction of the visual axis or strabismus. Anisometropia was found in 68% of children, with a high incidence of asymmetric astigmatism on the side of the haemangioma. Following local steroid injection a marked reduction in astigmatism was noted in 53.8% of children, a lesser reduction in 15.4%, and no reduction in 30.8%. Successful treatment of the haemangioma, therefore, may not remove the risk of amblyopia, and regular refraction and visual assessment remain mandatory. 
Association of postoperative apnea, airway obstruction, and hypoxemia in former premature infants. Airway obstruction plays an important role in the pathogenesis of apnea in premature infants who have not previously undergone anesthesia. To determine the role of airway obstruction in postoperative apnea, we studied 74 former premature infants by integrated recordings of nasal airflow, pneumocardiography, and pulse oximetry during the initial 2 h of recovery from inhalational anesthesia. Apnea (greater than 6 s) was classified as central, obstructive, or mixed, wherein mixed apnea consisted of central and obstructive apnea within the same apneic episode. Postoperative apnea was observed in 23 infants, ranging in age from 31-48 weeks postconception: 12 had inguinal herniorrhaphy (hernia group) and 11 had other procedures (other group). Of the 268 apneic episodes in the hernia group, 73% were central, 6% obstructive, and 21% mixed. Infants in the other group had 505 apneic episodes, with a distribution nearly identical to that in the hernia group. Central and mixed apnea occurred in all infants experiencing apnea, except in 1 infant, who had only central apnea, whereas obstructive apnea occurred in only one third of the apneic infants. Arterial hemoglobin desaturation was significantly more frequent at the end of mixed and obstructive apnea than after central apnea (P less than 0.01). In both groups, arterial hemoglobin O2 saturation (SpO2) decreased to less than 80% in approximately 35% of mixed and obstructive apneic episodes, compared to approximately 5% of central apneic episodes. SpO2 remained greater than or equal to 90% in over 80% of central apneic episodes, compared to 40% of mixed and obstructive apneic episodes. 
Combined portal vein and liver resection for carcinoma of the biliary tract. Twenty-nine patients with advanced carcinoma of the bile duct or gallbladder underwent combined portal vein and liver resection. Segmental excision of the portal vein was performed in 16 cases and wedge resection of the vessel wall in 13. The operative mortality rate was 17 per cent. The median survival for the 24 patients who left hospital was 19.8 months. Actuarial survival rates at 1, 3 and 5 years for all 29 patients were 48 per cent, 29 per cent, and 6 per cent respectively, whereas the median survival for 46 patients with unresectable carcinoma was 3 months and the 1 and 3-year actuarial survival rates were 13 per cent and zero respectively. This difference in survival times between patients undergoing hepatectomy with portal vein resection and those with unresectable carcinoma were statistically significant (P less than 0.01). Combined portal vein and liver resection is recommended as a reasonable surgical approach in selected patients with advanced carcinoma of the biliary tract. 
A reappraisal of the coelomic metaplasia theory by reviewing endometriosis occurring in unusual sites and instances. Endometriosis occurring in unusual sites and instances was reviewed for the purpose of exploring the pathogenesis of the disease. Endometriosis is frequently observed in the pelves of menstruating women. It occurs in teenagers even before menarche, in women who have never menstruated, and in postmenopausal women. It affects not only the pelvic organs but also the right-sided thoracic organs and rarely the extremities. It occurs in men who are castrated and treated with estrogen. The affected sites in both common and uncommon endometriosis include cells arising from the coelomic membrane and sites exposed to metaplasia-inducing substances such as estrogen and unknown factors liberated from the degenerating endometrium. This appears to strengthen the coelomic metaplasia theory, although additional basic and experimental data must still be accumulated to confirm this theory. 
Herpes zoster myelitis. We studied the clinical (10 patients) and pathological (9 patients) findings in 13 patients with herpes zoster myelitis, all of whom had systemic illnesses associated with immunosuppression. The median interval between the onset of the herpes zoster rash and myelopathic symptoms was 12 days, and the subsequent median interval to maximal deficit was 10.5 days. Presenting neurological symptoms were characteristically ipsilateral to the rash, with motor dysfunction predominating, followed by a spinothalamic and, less often, posterior column sensory deficit. Pathological involvement was most severe in the dorsal root entry zone and posterior horn of the spinal cord segment corresponding to the involved dermatome. There was variable spread both horizontally and vertically in the spinal cord. Direct varicella-zoster virus (VZV) infection of neuroectodermal cells, particularly oligodendrocytes, was demonstrated by immunostaining viral antigens (8 cases), and by the presence of Cowdry type A intranuclear inclusions (7 cases) and often was associated with focal demyelination (6 cases). In 4 patients a VZV vasculitis was associated with leptomeningitis and haemorrhagic necrosis (spinal cord in 1; brainstem or cerebellum in 3). The protracted evolution in many cases and the pathologically documented direct viral infection of the spinal cord provide a rational basis for the use of antiviral therapy in preventing or attenuating the evolving myelopathy. 
HLA association with dermatitis herpetiformis is accounted for by a cis or transassociated DQ heterodimer. HLA-DR, DQ, and DP restriction fragment genotyping was undertaken in 23 dermatitis herpetiformis patients and 53 healthy control subjects. HLA-DQw2 was present in 100% of patients with dermatitis herpetiformis (23 of 23) versus 40% of control subjects (21 of 53). Significant secondary associations occurred with HLA-DR3 (91% of patients versus 28% of control subjects) and DPw1 (39% of patients versus 11% of control subjects). Dermatitis herpetiformis and coeliac disease thus share an identical HLA class II association. It is likely that HLA class II genes directly influence the immune responses leading to mucosal damage in both diseases. The strongest candidate for disease susceptibility to dermatitis herpetiformis is DQw2. The HLA molecule most likely to be involved in coeliac disease is a specific DQ alpha/DQ beta heterodimer, encoded in cis arrangement in DR3 haplotypes or in trans arrangement in a DR5, 7 genotype. Our data on dermatitis herpetiformis patients fits this model perfectly. All these patients are capable of expressing this molecule, which may be responsible for the gluten sensitive enteropathy seen in a subgroup of patients with dermatitis herpetiformis and coeliac disease. 
Sequences of taxol and cisplatin: a phase I and pharmacologic study. Untreated and minimally pretreated solid tumor patients received alternating sequences of taxol and cisplatin. Sequential dose escalation of each agent using taxol doses of 110 or 135 mg/m2 and cisplatin doses of 50 or 75 mg/m2 resulted in four dosage permutations that induced grades 3 and 4 neutropenia in 72% to 84% and 50% to 53% of courses, respectively. Neutropenia was brief, and hospitalization for neutropenia and fever was required in 13% to 24% of courses. However, further escalation of taxol to 170 or 200 mg/m2 induced grade 4 neutropenia in 79% to 82% of courses. At the highest taxol-cisplatin dose level (200 mg/m2 to 75 mg/m2), the mean neutrophil count nadir was 98/microL, and hospitalization for neutropenia and fever was required in 64% of courses. The sequence of cisplatin before taxol, which has less antitumor activity in vitro, induced more profound neutropenia than the alternate sequence. Pharmacologic studies indicated that this difference was probably due to 25% lower taxol clearance rates when cisplatin preceded taxol. Although neurotoxicity was initially thought to be a potentially serious effect of the combination, mild to modest neurotoxicity occurred in only 27% of patients. Adverse effects also included myalgias, alopecia, vomiting, diarrhea, bradycardia, and asymptomatic ventricular tachycardia. Objective responses were noted in melanoma, as well as non-small-cell lung, ovarian, breast, head and neck, colon, and pancreatic carcinomas. Based on these results, the sequence of taxol before cisplatin at doses of 135 and 75 mg/m2, respectively, is recommended for phase II/III trials, with escalation of taxol to 170 mg/m2 if treatment is well tolerated. 
Nosocomial pneumonia in the critically ill: product of aspiration or translocation? OBJECTIVE: To examine the possibility that nosocomial pneumonias might be caused by the translocation of enteric bacteria and their toxins. DESIGN: Prospectively collected previous database was examined by logistic regression analysis. SETTING: University medical center. PATIENTS: Sixty-two ICU patients. MEASUREMENTS AND MAIN RESULTS: The best stand-alone predictors for nosocomial pneumonia were bleeding from stress ulceration (p less than .001), the severity of illness present (p less than .001), and intramucosal acidosis in the stomach (p = .023), a metabolic indication of mucosal ischemia. Mechanical ventilation (p = .038) and the administration of antacids/cimetidine (p = .054) were also of stand-alone predictive value, but did not significantly improve the best predictive model for nosocomial pneumonia derived from the severity of illness present and the intramucosal pH in the stomach. CONCLUSIONS: The findings are consistent with the hypothesis that ischemic mucosal injury and its associated translocation of enteric bacteria and toxins might be more important in the pathogenesis of nosocomial pneumonia in the critically ill than the aspiration of contaminated nasopharyngeal secretions. 
Intrathecal morphine for postoperative analgesia in children after selective dorsal root rhizotomy. The authors report their experience with low doses (0.007-0.015 mg/kg), moderate doses (0.016-0.025 mg/kg), and high doses (0.026-0.035 mg/kg) of intrathecal morphine for postoperative analgesia after selective dorsal root rhizotomy surgery in 50 children, aged 3 to 12 years. After closure of the dura, a single dose of preservative-free morphine was injected into the subarachnoid space, and patients were assessed for 48 hours for level of comfort and side effects. The three doses of morphine provided equivalent analgesia and similar side effects. The duration of postoperative analgesia ranged from 3 to 48 hours (mean, 12.2 +/- 9.5 h). Common side effects were limited to nausea and vomiting (42%) and mild facial pruritus. No patient experienced late respiratory depression or generalized pruritus. The authors conclude that low doses of intrathecal morphine is as effective as moderate or high doses of morphine for reducing pain in the immediate postoperative period. Intrathecal morphine provides excellent analgesia after selective dorsal rhizotomy. 
Hypopituitarism. The pituitary regulates the body's endocrine system, including the thyroid gland, adrenal cortex, ovaries and testes, through the release of numerous hormones. Pituitary function, in turn, is regulated through complex feedback loops involving the hypothalamus and the target endocrine glands. Hypopituitarism may result from multiple causes, including primary and metastatic cancer, ischemic and granulomatous disease, infection, developmental abnormalities and trauma, which may affect the gland itself (primary hypopituitarism) or the hypothalamus (secondary hypopituitarism). Depending on the anatomic lesion, patients with hypopituitarism may present with signs or symptoms of multiple endocrine abnormalities, such as hypothyroidism, adrenal insufficiency, diabetes insipidus, hypoglycemia, sexual dysfunction and growth retardation. A thorough clinical history, detailed examination, laboratory evaluation of endocrine function and radiographic views of the pituitary and sella turcica can suggest the diagnosis and etiology. Treatment, usually lifelong, may include hormone replacement and medical or surgical correction of the underlying disease. 
Lithotripsy versus cholecystectomy for management of gallstones. A decision analysis by Markov process. Extracorporeal shock-wave lithotripsy is a new treatment method that effectively distintegrates radiolucent gallstones and is associated with a low complication rate. Using the model of a Markov process for decision analysis, survival and costs under four possible strategies to treat gallstones were compared: expectant management with cholecystectomy (EC) or lithotripsy (EL) reserved for symptomatic gallstones; prophylactic cholecystectomy (PC) or lithotripsy (PL) for all gallstones. Life expectancy for the different strategies varies by few days. Only if high annual rates of pain and complication occurred in subjects with silent gallstones would both prophylactic procedures marginally increase life expectancy. Prophylactic cholecystectomy then would be more cost-effective than prophylactic lithotripsy. Expectant strategies remain much cheaper than prophylactic management over a broad range of probability values and procedural costs. Expectant use of lithotripsy costs less than cholecystectomy. A low success rate of lithotripsy would raise the direct costs of lithotripsy above those of cholecystectomy but leave total costs of both strategies in the same order of magnitude. Lithotripsy appears to be a feasible alternative to treat symptomatic but not asymptomatic gallstones. 
Urinary retention after pyeloplasty. A retrospective review of 37 pyeloplasties, performed between 1984 and 1988, revealed that 38% of patients had post-operative retention requiring catheterisation, compared with 8% in an age and sex matched group of patients undergoing cholecystectomy. This suggests that direct surgical trauma to the upper genitourinary system may inhibit bladder function. We therefore suggest that pre-operative catheterisation should be considered in theatre, for patients undergoing pyeloplasty. 
Fatal pulmonary aspergillosis presenting as acute eosinophilic pneumonia in a previously healthy child. A previously healthy boy presented with cough and diffuse pulmonary interstitial infiltrates. Acute eosinophilic pneumonia was diagnosed by bronchoalveolar lavage in the absence of a demonstrable infectious etiologic agent. Corticosteroid therapy resulted in immediate improvement but was followed by respiratory distress and death from invasive aspergillosis and Pseudomonas cepacia sepsis. 
Otolaryngology problems in the immune compromised patient--an evolving natural history. As the human immunodeficiency virus is being detected in increasing numbers of asymptomatic individuals at risk, newer earlier patterns of disease have become apparent--including cranial and cervical herpes zoster, oral hairy leukoplakia, and oral candidiasis--thus linking viral and other disease to the development of acquired immunodeficiency disease (AIDS). Many similarities between patients with AIDS and other immunosuppressed patients have emerged. As immunosuppressed patients survive longer, they begin to manifest cancers such as lymphomas and squamous cell cancers in addition to Kaposi's sarcoma. Otolaryngologists can learn to identify and treat otitis and sinusitis in the immunosuppressed patient, to identify predictive early signs such as oral hairy leukoplakia, herpes simplex virus, and oral candidiasis, and to diagnose and treat Kaposi's sarcomas of the head and neck, lymphomas, squamous cell cancers, and opportunistic infections as the immunodeficiency disease progresses. 
The expression of proliferative-associated nuclear antigen p105 in gastric carcinoma. The expression of proliferation-associated nuclear antigen p105 of gastric carcinomas was studied by multiparameter flow cytometric and immunohistochemical technique. Multiparameter flow cytometric analysis revealed that p105 expression was rarely observed in the resting cells of normal gastric epithelium. On the contrary, the immunofluorescence (IF) intensity of cancer cells in G1 phase was approximately two-fold to three-fold greater than that of G0 phase of cancer cells or normal gastric epithelium. The p105 antigen content of cancer cells increased with cell cycle progression, and increased more rapidly in cells in late S-phase than in cells in G0 and early S-phase. Microphotometric study demonstrated that cells in M-phase exhibited a dramatic increase in the amount of the antigen, and the IF intensity of the mitotic cells were approximately five-fold to ten-fold greater than that of cells in G1 and S-phase. These results indicate that the antigen demonstrated by the p105 monoclonal antibody is present in the G1, S, G2, M-phases, but not in the G0 phase. Immunohistochemical technique demonstrated that patients with lymph node metastases are more likely to have high p105-positive rates than did node-negative patients. The mean p105-positive rates of aneuploid tumors was significantly higher than those of diploid tumors. From these results the authors speculate that the measurement of p105-positive rates may be a powerful prognostic indicator of gastric carcinoma. 
Anterior capsule adherence to iris leading to pseudophakic pupillary block. We present a rare case of anterior capsule adherence to the iris following extracapsular cataract extraction with posterior chamber intraocular lens implantation and leading to pseudophakic pupillary block. There were no synechiae at the pupillary margins associated with the capsule/iris adherence, but aqueous was entrapped behind the iris and intraocular pressure rose. Laser iridotomy was temporarily beneficial, but it had to be repeated several times. 
The renal growth hormone/insulin-like growth factor I axis. Collecting duct is a major site of insulin-like growth factor-I (IGF-I) synthesis within kidney. Production of IGF-I at this site is stimulated by growth hormone (GH). IGF-I produced in collecting duct is likely to act on glomerulus and proximal tubule via IGF-I receptors present at these locations. Renal IGF-I may be causative of the glomerular and proximal tubular hypertrophy that occurs in hypersomatotropic states, of compensatory renal hypertrophy, and of renal regeneration following acute ischemic injury. 
Evaluation of penile dorsal arteries and deep arteries in arteriogenic impotence. The dorsal and deep arteries are the 2 main blood supplies to the penis. High resolution ultrasonography was used to evaluate the role of these 2 sets of arteries in erection. A total of 44 impotent patients entered this study. We used duplex ultrasonography (Diasonic DRF/400) to assess the role of the dorsal and deep arteries in arteriogenic and nonarteriogenic impotent patients. Vascular velocity, as well as the change in diameter, was recorded before and after an intracavernous injection of 60 mg. papaverine. In the arteriogenic impotence group (28 patients, 63.6%), the velocity increments were 37.1 +/- 23.6 (right side) and 35.4 +/- 17.5 (left side) cm. per second in the dorsal arteries, and 8.3 +/- 5.9 (right side) and 12.6 +/- 5.6 (left side) cm. per second in the deep arteries. In the nonarteriogenic group (16 patients, 36.4%) the velocity increments were 46.5 +/- 25.2 and 41.1 +/- 22.4, respectively, in the dorsal arteries, and 37.3 +/- 16.5 and 37.5 +/- 15.8, respectively, in the deep arteries. Comparison of the velocity increments between the arteriogenic and nonarteriogenic groups revealed no difference in the dorsal arteries (p greater than 0.1) but a significant difference was noted in the deep arteries (p less than 0.01). Similar findings were also encountered when the velocities and diameter increments were compared. This study indicates that the deep arteries have an important role in erectile response, while the dorsal arteries are less important. 
Elevation of serum interleukin-6 concentration precedes acute-phase response and reflects severity in acute pancreatitis. Experimental studies have shown that interleukin-6 induces all major acute-phase proteins in the liver, including C-reactive protein. In 50 patients with acute pancreatitis, the serum concentrations of interleukin-6 and C-reactive protein were determined daily during the first week of hospitalization. Patients were divided into three groups according to clinical criteria: mild pancreatitis (less than or equal to 1 complication; n = 25), severe pancreatitis (greater than or equal to 2 complications; n = 15), and lethal outcome (n = 10). Patients with mild disease showed initially slightly elevated levels of interleukin-6 (22.0 +/- 9.8 U/mL) that decreased to low levels within 4 days (5.0 +/- 1.0 U/mL). In patients with severe pancreatitis, serum concentrations of interleukin-6 were initially clearly elevated (35.0 +/- 7.5 U/mL) and remained slightly elevated until day 7 (13.0 +/- 2.0 U/mL). Patients with lethal outcome had markedly elevated initial interleukin-6 concentrations (61.0 +/- 15.0 U/mL) that decreased but were still elevated at day 7 (26.0 +/- 2.5 U/mL). In all three groups, C-reactive protein concentrations followed the course of interleukin-6 concentrations by 1 day. There was a positive correlation between maximal interleukin 6 concentrations and maximal increases in the serum concentrations of C-reactive protein (r = 0.66). At days 1 and 2, increased (greater than 15 U/mL) interleukin-6 concentrations (positive predictive value, 91%; negative predictive value, 82%) predicted a severe or lethal course of the disease more accurately than elevated [greater than 0.10 g/L (greater than 10 mg/dL)] C-reactive protein concentrations (positive predictive value, 67%; negative predictive value, 79%). In conclusion, elevated serum concentrations of interleukin-6 followed by increased levels of C-reactive protein reflect the severity of acute pancreatitis. 
Acquired aphasia, dementia, and behavior disorder with epilepsy and continuous spike and waves during sleep in a child. Severe persistent neuropsychological disorders sometimes develop in the course of a focal epilepsy of unknown origin in previously normal children. Very frequent bilateral focal or generalized discharges are often noted on the sleep EEG records of these patients with no evidence of clinical seizures. The relation between these paroxysms and the observed deterioration remains unclear. We report a child with a partial complex epilepsy and severe disturbances of language, cognition, and behavior acquired in the early years of development who was followed for 15 years. A correlation between the evolution of the striking EEG abnormalities during sleep and the neuropsychological disorders could be established retrospectively. The observed sequence of onset and recovery of the aphasia, the dementia, and the "psychotic" behavior makes a direct causal relation between the deficits quite unlikely. Rather it suggests an association of independent symptoms with a specific language disorder becoming manifest in the course of the evolution. This child shows many of the main characteristics of the syndromes of "acquired aphasia with convulsive disorder" (Landau-Kleffner syndrome) and "epilepsy with continuous spike waves during sleep." Both syndromes describe probably different facets of a similar underlying, still unexplained cerebral dysfunction. 
Optimal dose of lignocaine for preventing pain on injection of propofol. The purpose of this study was to define the optimum dose of lignocaine required to reduce pain on injection of propofol. We conducted a prospective, randomized, double-blind trial on 310 patients undergoing anaesthesia. Patients were allocated to four groups according to the lignocaine dosage: group A (control), no lignocaine; group B, lignocaine 0.1 mg kg-1; group C, lignocaine 0.2 mg kg-1; group D, lignocaine 0.4 mg kg-1. Our results showed that a dose of lignocaine 0.1 mg kg-1 significantly reduced the incidence of pain and that there was no improvement when the dose was increased. 
Morphometric studies in intraductal breast carcinoma using computerized image analysis. A morphometric study was performed using computerized image analysis on the histologic specimens of 26 patients with intraductal carcinoma of the breast and 26 normal control patients. A significant incidence of necrosis (56%) was observed in the breast ducts containing intraductal carcinoma. This was characterized by one or more areas of necrosis surrounded by a rim of viable tumor cells. The mean diameter of the ducts containing intraductal carcinoma was 349 microns compared with a mean diameter of 90 microns for the normal ducts. The mean diameter of the ducts containing necrosis was 470 microns compared with a mean diameter of 192 microns for the ducts containing a solid pattern of intraductal carcinoma. Central necrosis occurred in 94% of the ducts more than 180 microns in radius, whereas only 34% of the ducts less than 180 microns in size contained necrosis. The width of the viable neoplastic tissue was less than 180 microns in 91% of the ducts. These results are analogous to the findings of Thomlinson and Gray in human lung tumor cords and provide indirect evidence for the existence of a hypoxic compartment in intraductal carcinoma of the breast. This could be an explanation for the higher local failure rate after conservative surgery and irradiation for infiltrating cancers containing an extensive intraductal component. 
Sequences of taxol and cisplatin: a phase I and pharmacologic study. Untreated and minimally pretreated solid tumor patients received alternating sequences of taxol and cisplatin. Sequential dose escalation of each agent using taxol doses of 110 or 135 mg/m2 and cisplatin doses of 50 or 75 mg/m2 resulted in four dosage permutations that induced grades 3 and 4 neutropenia in 72% to 84% and 50% to 53% of courses, respectively. Neutropenia was brief, and hospitalization for neutropenia and fever was required in 13% to 24% of courses. However, further escalation of taxol to 170 or 200 mg/m2 induced grade 4 neutropenia in 79% to 82% of courses. At the highest taxol-cisplatin dose level (200 mg/m2 to 75 mg/m2), the mean neutrophil count nadir was 98/microL, and hospitalization for neutropenia and fever was required in 64% of courses. The sequence of cisplatin before taxol, which has less antitumor activity in vitro, induced more profound neutropenia than the alternate sequence. Pharmacologic studies indicated that this difference was probably due to 25% lower taxol clearance rates when cisplatin preceded taxol. Although neurotoxicity was initially thought to be a potentially serious effect of the combination, mild to modest neurotoxicity occurred in only 27% of patients. Adverse effects also included myalgias, alopecia, vomiting, diarrhea, bradycardia, and asymptomatic ventricular tachycardia. Objective responses were noted in melanoma, as well as non-small-cell lung, ovarian, breast, head and neck, colon, and pancreatic carcinomas. Based on these results, the sequence of taxol before cisplatin at doses of 135 and 75 mg/m2, respectively, is recommended for phase II/III trials, with escalation of taxol to 170 mg/m2 if treatment is well tolerated. 
Femoro-femoral or ilio-femoral bypass for unilateral inflow reconstruction? Femoro-femoral and ilio-femoral bypass are two popular options for unilateral inflow reconstruction. In order to evaluate these alternative approaches, the records of 70 consecutive patients who underwent either femoro-femoral (n = 50) or ilio-femoral (n = 22) grafts were retrospectively reviewed. There were 46 men and 24 women, ranging in age from 27 to 84 years (mean: 66 years). Operative mortality was 10% for all femoro-femoral procedures, including 50% for emergent, 14% for synchronous, and 0% for solitary procedures; mortality was 9% for all ilio-femoral grafts including 20% for synchronous and 6% for solitary procedures. Among the elective solitary procedures, there was no significant difference with respect to operative time, blood loss, fluid requirement, time until resuming an oral diet, or duration of postoperative course for the two procedures. Five-year patency was 93% for all ilio-femoral and 57% for all femoro-femoral grafts. Although femoro-femoral bypass has been the more popular option for unilateral inflow reconstruction in this and other institutions, these findings justify the more widespread use of ilio-femoral bypass. 
Valvular heart disease: management and intervention. Clinical overview and discussion. The diagnosis and estimation of severity of valvular disease can usually be made by a well done history and physical examination. We now have a wealth of noninvasive techniques capable of imaging the heart and the great vessels. With Doppler echocardiography and magnetic resonance imaging we are beginning to develop methods that can measure pressures and flow. All of these advances have duplicated to a large extent the information obtainable in the past only from cardiac catheterization and angiography. In some instances, in aortic and mitral stenosis, for example, echo-Doppler evaluation is so good that catheterization is rendered unnecessary. The decision to send patients to surgery without catheterization is especially secure when the valvular obstruction is very severe. When the gradient is only moderately increased, then estimation of severity depends on flow, and in many cases these patients are sent to catheterization before surgery is recommended. With regurgitant lesions there is less confidence with noninvasive techniques that the severity is always correctly estimated, and therefore catheterization and angiography are more often necessary before sending the patient to surgery. At the present time cardiac catheterization and angiography are required 1) whenever there is an inconsistency between the clinical picture and noninvasive information, for example, the symptomatic patient with aortic stenosis who has mild-to-moderate aortic stenosis by echo-Doppler techniques, and 2) whenever additional information not obtainable by noninvasive techniques is necessary, for example, the need to know the status of the coronary arterial circulation. Noninvasive techniques have not in any way replaced a good history and physical examination. 
Malaria in an urban emergency department: epidemiology and diagnostic features of 25 cases. This article presents a retrospective study of 25 patients diagnosed with malaria in an urban emergency department (ED) between June 1986 and June 1989. The mean annual case rate of malaria in this study group was more than three times the national rate. This may be ascribed to the notable ethnic diversity of the population. A history of travel to an area endemic for malaria was eventually elicited from all patients. The most common chief complaint was fever (56%) followed by abdominal pain (12%). Temperatures were elevated in 70% of the patients, with a mean temperature of 102.9 degrees F (39 degrees C). Gender was found to play a role in delaying diagnosis, with women accounting for 83% of a group of patients requiring multiple ED visits before diagnosis. The authors conclude that malaria must be considered when diagnosing patients in ethnically diverse populations. Gender may be associated with a delay in diagnosis. A careful travel history and a peripheral smear are aids in rapid diagnosis. 
Symptomatic xanthogranuloma of choroid plexus with unilateral hydrocephalus. Case report. Xanthogranulomas involving the choroid plexus of the lateral ventricles are generally asymptomatic lesions. The case is reported of a 50-year-old man in whom a xanthogranuloma of the choroid plexus had occluded the left trigone, causing unilateral hydrocephalus of the left temporal horn and neurological symptoms. A review of the literature shows that xanthogranulomas of the glomus of the lateral ventricles differ from the xanthomatous cystic lesions of the third ventricle, which are probably akin to colloid cysts. 
Inherited protein C deficiency and nonhemorrhagic arterial stroke in young adults. Out of a consecutive series of 50 young people less than 45 years old with nonhemorrhagic arterial stroke, three patients had inherited protein C deficiency. CT revealed hypodense areas consistent with the clinical picture, and angiography showed occlusion of some intracranial arterial vessels. Other possible associated causes of stroke were ruled out. One patient had a transient ischemic attack and a peripheral venous thrombosis prior to the actual stroke, whereas the others were completely asymptomatic, as were relatives with the same deficiency. We suggest determining protein C in ischemic stroke of all young adults, especially when major risk factors are excluded. 
Problems in the surgical treatment of interstitial cystitis. Two series of patients with histologically proven interstitial cystitis that was unresponsive to hydrostatic bladder distension and intravesical chemotherapy with dimethyl sulfoxide have been studied. In the first series 24 patients were treated by subtotal cystectomy and substitution cystoplasty without further consideration; 8 of these 24 patients had persistent frequency due to active disease in the remaining trigone and/or urethra and in 2 cases this was severe. Because of this experience the second group of patients had routine biopsy of the trigone and assessment of urethral sensation as part of the initial assessment. In those in whom the trigone was unaffected, treatment was unchanged. If the trigone was affected, total cystourethrectomy was performed with substitution cystourethroplasty unless the patient chose or was advised to avoid surgery altogether or to have a simpler option such as conduit or continent urinary diversion. Trigonal biopsies should be part of the routine assessment of all patients being considered for surgery, since residual active disease is a major cause of dissatisfaction after subtotal cystectomy and substitution cystoplasty. 
Psychological aspects of orthognathic surgery: how people respond to facial change. This study was undertaken to explore the motivations and problems shared by adult orthognathic surgical patients over the age of 25. Objective findings included demographic information and reasons for seeking surgery. The majority of 65 respondents cited functional problems as their primary reason for seeking treatment. Eighty-nine percent were pleased with esthetic changes, and 83% responded that the functional problem had been corrected. For most, the greatest discomfort related to the surgery was the postoperative intensive care unit. Two of the most common side effects of the surgery were the loss of sensation in the lips and chin area and a short period of depression. Women had depression more often than men but were more enthusiastic about the final results of the procedure. Two major areas of interest to surgeons emerged from the research. First, although women have functional problems, the majority seem to have a desire for cosmetic improvement. Having a functional problem seemed to provide the psychological permission necessary to spend the time and money for a cosmetic change. The second point focused on the need for good communication between surgeon and patient. The patients who were more positive toward the procedure and more satisfied with the results were those who were better informed and who thought they had a good system of communication with the orthodontist, surgeon, and their respective staffs. 
Radiotherapy improves the outlook for patients older than 1 year with Pediatric Oncology Group stage C neuroblastoma. Children older than 1 year of age who have neuroblastoma with complete or partial removal of the primary tumor and positive intracavitary lymph nodes (Pediatric Oncology Group [POG] stage C) are a small but higher-risk subset of patients. To further evaluate the importance of identifying patients with POG stage C neuroblastoma and to assess the efficacy and toxicity of adding concurrent radiation therapy (RT) to chemotherapy (CT) in these children, a randomized study was conducted. Eligible patients received cyclophosphamide 150 mg/m2 orally days 1 to 7 and Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH) 35 mg/m2 intravenously (IV) on day 8 (CYC/ADR) every 3 weeks for five courses with or without RT to primary tumor and regional lymph nodes (24 to 30 Gy/16 to 20 fractions). Second-look surgery was advised to evaluate response and to remove residual disease. Continuation therapy alternated CYC/ADR every 3 weeks with cisplatin 90 mg/m2 day 1 followed by teniposide 100 mg/m2 day 3 (CDP/VM) for two courses each. Secondary CT with CDP/VM alone was available for patients not achieving complete response (CR) following induction treatment and second-look surgery. Of 29 eligible patients randomized to CT alone, 13 achieved CR, and nine are disease-free (NED) 1 to 52 months (median, 35 months) off therapy. Twenty-two of 33 eligible cases treated with CT/RT attained CR, and 19 are NED 1 to 77 months (median, 23 months) off therapy. Local and metastatic relapses occurred in both arms. Differences in CR, event-free survival, and survival rates were significant, P = .013, .009, and .008, respectively. Surgical compliance was excellent and complications uncommon. Therapy was tolerable in both groups but hematopoietic toxicity was more common in the CT/RT arm. We conclude that POG stage C neuroblastoma in children older than 1 year of age is a higher-risk group that should be identified, that CT/RT provides superior initial and long-term disease control compared with CT alone in this patient subset, and that the occurrence of metastatic failures in both treatment groups suggests a need for more aggressive chemotherapy. 
Higher recurrence rate after coronary angioplasty in unstable angina pectoris. PURPOSE: Recurrent stenosis after percutaneous transluminal coronary angioplasty (PTCA) is a significant problem, requiring repeat dilation in about one-third of all treated patients. Various clinical and procedure-related predictors have been proposed. Between 1983 and 1987, 257 patients underwent 322 procedures, where 380 stenoses were attempted. Indications were: stable angina pectoris 73%, unstable angina pectoris 22%, other indication 5%. The primary success rate was defined as a less than 50% remaining postprocedure stenosis. FINDINGS: Repeat angiograms were done for 88% of the initially successful cases, either six months after PTCA or if there was a clinical recurrence. Restenosis was defined as a recurrence of a more than 50% diameter stenosis. The restenosis rate was 33% and was significantly higher (p less than 0.05) for unstable (46%) than for stable angina pectoris (29%). There was a nonsignificant tendency to a higher restenosis rate in the left anterior descending artery than in the other coronary vessels. IMPLICATIONS: The increased restenosis rate seen after PTCA for unstable angina pectoris could be caused by a higher activity in systems affecting the proliferative processes in the smooth muscle cells of the arterial wall, which is thought to form the pathophysiologic basis for restenosis after PTCA. 
Pulmonary origin of left anterior descending coronary artery in tetralogy of Fallot. We report the case of a 4-year-old girl with an anomalous origin of the left anterior descending coronary artery from the pulmonary artery in association with tetralogy of Fallot. Creation of an intrapulmonary tunnel from a newly created aortopulmonary window to the coronary ostium in the pulmonary trunk and total repair of tetralogy of Fallot were successfully carried out. The advantage of intrapulmonary tunnel technique (Takeuchi method) for this very rare combination is stressed. 
Operative survival and 40 year follow up of surgical repair of aortic coarctation. OBJECTIVE--To study early and late mortality after surgical correction of coarctation of the aorta. DESIGN--Data on 223 patients operated on at the Westminster Hospital, London, between 1946 and 1981, were collected and updated by questionnaire. PARTICIPANTS--All 223 patients recorded as undergoing operation for aortic coarctation up to the end of 1981. Fifteen of 197 survivors were lost to follow up; most of them were patients from overseas. OUTCOME AND RESULTS--The early mortality (within one month of operation) was 12% overall, 2.6% for elective surgery, and 0% for the 77 patients undergoing surgery since 1968. Survivors were followed up for a total of 3288 patient years; in 27 follow up lasted more than 30 years. In a few it reached 40 years. Twenty two patients died during this period, 18 from causes that could be attributed to coarctation or its repair. Mortality was highest more than 20 years after the operation. CONCLUSION--Repair increased life expectancy in patients with aortic coarctation. Late problems caused by persistent hypertension or recoarctation became apparent in long term survivors. The increased risk of late mortality associated with the duration of preoperative hypertension was not statistically significant. There were no deaths from cerebrovascular accidents. (In an earlier necropsy series cerebrovascular accidents accounted for 11.8% of deaths.) The incidence of deaths from aneurysms resembled that in the earlier necropsy series. 
Pneumoparotid: a case report. Pneumoparotid is an unusual condition resulting from air being forced into the parotid ductal system. When it develops, it is a result of increased intraoral air pressure. Diagnosis is based on the etiologic factor, palpatory evidence of tissue emphysema, the escape of frothy saliva from the involved duct, and the sialographic finding of retained ductal air and ductal infection. 
Vascular trauma as a result of therapeutic procedures for the treatment of malignancy. Twenty-two iatrogenic vascular injuries caused by resection of tumors with local recurrences or adjuvant chemotherapy were treated over a 42-month period in 11 female and 8 male patients with cancer (58% had documented metastases). Sixteen of 22 vascular injuries were caused by intraarterial administration of chemotherapy (8 emboli; 8 direct catheter trauma), and six were caused by resection of tumors with local invasion. The injuries were extremity ischemia (15 extremities in 13 patients), pseudoaneurysm (4), expanding hematoma (3 injuries in 2 patients). Twenty-two surgical repairs included bypass of severely damaged arteries in five, embolectomy in five, interposition grafts in three, pseudoaneurysm resection and primary repair in three, primary repair of three vascular injuries, and one patch angioplasty. Leg amputation was required in two patients. Seventeen of 19 patients had successful vascular repairs with resolution of preoperative indications for vascular repair without intraoperative or postoperative deaths. Long term follow-up (mean, 17 months) showed no recurrence of vascular problems; however, two patients died of metastatic cancer at 6 and 24 weeks after vascular repair. This study supports an aggressive approach to the management of vascular injuries caused by therapeutic interventions for malignancy despite the presence of metastatic disease. 
Abnormal guanine nucleotide regulatory protein in MVP dysautonomia: evidence from reconstitution of Gs. We and others have used the term MVP dysautonomia for a particular subset of hyperadrenergic dysautonomia patients. The role of the stimulatory guanine nucleotide regulatory protein (Gs) in this dysautonomia was studied by cholate extraction of Gs from erythrocytes from 11 normal subjects and 14 symptomatic dysautonomic patients and reconstitution into cyc-S49 lymphoma membranes, which have normal receptor and adenylyl cyclase but lack Gs. Isoproterenol-stimulated adenylyl cyclase activity in the dysautonomia group was increased compared to that in controls [3.66 +/- 0.20 (mean +/- SE; n = 14) vs. 2.87 +/- 0.14 (n = 11) U cyc- reconstituted activity/mg erythrocyte protein; P less than 0.05]. beta-Adrenergic receptor high affinity state formation was greatest in the severely symptomatic group [KL/KH: severe symptoms, 130 +/- 48 (n = 6); mild symptoms, 33 +/- 7 (n = 7); control, 27 +/- 6 (n = 11); severe dysautonomia distinct, P less than 0.017]. Sodium dodecyl sulfate-polyacrylamide gels of cholera toxin-dependent ADP-ribosylated G-proteins yielded no gross distinction between severely symptomatic and control groups. This subset of hyperadrenergic dysautonomia patients, thus, has supercoupled beta 2-adrenergic receptors (increase in both agonist binding and cyclase activation) conferred by an abnormal Gs, whose effects on agonist binding reflect the severity of illness. 
Ischemic complications of abdominal aortic surgery. From 1982 through 1988, 634 consecutive patients underwent abdominal aortic reconstruction for occlusive (37%) or aneurysmal (63%) disease. We studied the ischemic problems affecting the branches of the aorta, excluding the coeliac and superior mesenteric arteries. Ischemic colitis (0.6%), spinal cord ischemia (0.16%), renal insufficiency (17%), and lower limbs ischemia (6.5%) were the major problems encountered. We identified the most significant factors associated with these complications such as hypotension, emergency, hypovolemia, preoperative renal function, suprarenal clamping, the quality of the preoperative investigation, and have suggested some specific preventive measures. 
Asbestos induced pericardial effusion and constrictive pericarditis. The number of disorders attributable to asbestos exposure has increased gradually over the years. The latest to be recorded is pericardial effusion and constrictive pericarditis, and three cases are reported here. A man with bilateral pleural thickening and plaques developed acute pericarditis and an effusion and was treated by pericardiectomy. Two men died from constrictive pericarditis associated with bilateral pleural effusions and diffusion pleural thickening. The pericardium showed nonspecific fibrous thickening. All had been occupationally exposed to asbestos. In the fatal cases the lungs contained amphibole fibres, in keeping with a modest degree of occupational exposure. Asbestos produces progressive fibrosis of the pericardium that is similar to diffuse pleural thickening and may be fatal. Both conditions may develop after relatively short or light exposure. 
The phenotype of the X-linked dystonia-parkinsonism syndrome. An assessment of 42 cases in the Philippines. The clinical phenotype of X-linked recessive torsion dystonia was documented in 42 affected individuals from 21 families. In 7 families, there were 9 sibships (core families) with 2 or more affected individuals available for evaluation. The ages of the patients ranged from 29 to 79 years with a mean of 46.2 +/- 10.1 years; the mean age of onset of dystonia was 35.0 +/- 8.0 years with a range of 12 to 48 years; and the mean duration of illness was 11.1 +/- 7.9 years. First manifestations were noted in the lower extremities in 36%, the axial musculature in 29%, the upper extremities in 23%, and in the head in 12% of the cases. The majority of patients displayed gait abnormalities (90%), leg dystonia (79%), oromandibular dystonia (64%), neck dystonia (57%), blepharospasm (57%), and truncal dystonia (52%). The disease generalized in 90% of the cases within 1 to 11 years of onset (median duration, 5 years). Overall, the condition was disabling, but the Fahn-Marsden disability score did not correlate with age of onset, duration of illness, site of onset, rate of generalization, or presence of parkinsonism. Thirty-six percent of the cases displayed at least 1 of the following "parkinsonian symptoms": bradykinesia, tremor, rigidity, loss of postural reflexes and a shuffling gait. Parkinsonism was diagnosed as definite in 14%, probable in 2%, and possible in 19% of the cases. Given this high association of dystonia and parkinsonism, we propose to call the disorder X-linked dystonia-parkinsonism syndrome (XDP). 
Computer- and robot-assisted resection of thalamic astrocytomas in children. Six children ranging in age from 2 to 10 years who harbored deep benign astrocytomas were operated upon using a computer- and robot-assisted system. A radical excision was achieved in all cases with no significant morbidity nor any mortality. The system consists of an interactive, three-dimensional display of computed tomographic image contours and digitized cerebral angiograms taken using the Brown-Roberts-Wells stereotactic frame. The surgical retractor is held and manipulated using a PUMA 200 robot. The position and orientation of the surgical retractor is displayed on the three-dimensional display. Preoperative planning and simulation are important features of this system. Movement of the brain after removal of the tumor and cerebrospinal fluid is substantial, so the tumor removal is based on visually defined margins. Enhanced computer graphics and robotic devices are important adjuncts to neurosurgical procedures and will find increasing use in the future. 
Randomized trial of doxorubicin, bisantrene, and mitoxantrone in advanced breast cancer: a Southwest Oncology Group study. Four hundred eleven women with metastatic breast cancer were randomly assigned to receive either 60 mg/m2 doxorubicin (130 patients), 320 mg/m2 bisantrene (146 patients), or 14 mg/m2 mitoxantrone (135 patients). The doses were given intravenously every 3 weeks with a cross-over design to determine their relative efficacy and toxicity. To be eligible, patients must have had one previous chemotherapy regimen, and patients who were estrogen receptor positive must have failed endocrine therapy. There were 365 patients assessable for response and 399 assessable for toxic effects. The median age was 57 years; 18% were premenopausal or perimenopausal. Visceral dominant disease was present in 66% of the patients. Ninety-seven percent of the patients had a disease-free interval from diagnosis to first recurrence of less than 1 year. The response rate was 28% with doxorubicin, 13% with bisantrene, and 14% with mitoxantrone (P = .004). Median time to treatment failure was 133 days with doxorubicin, 66 days with bisantrene, and 68 days with mitoxantrone (logrank P = .06). The median survival was 315 days for doxorubicin, 290 days for bisantrene, and 177 days for mitoxantrone (logrank P = .04), although survival at 2 years was similar for all three agents. There were five responses in the 66 patients crossed over to doxorubicin and one response each for patients crossed over to bisantrene (39 patients) or mitoxantrone (63 patients). Toxicity leading to discontinuance of therapy was more common with doxorubicin, and discontinuance of therapy was due primarily to patient's request or cardiotoxicity. The major dose-limiting toxic effect for all three agents was leukopenia. Nausea and vomiting, mucositis, and alopecia were more severe with doxorubicin. Congestive heart failure developed in nine patients treated with doxorubicin, zero patients treated with bisantrene, and two patients treated with mitoxantrone. A decrease in the left ventricular ejection fraction, as defined by moderate to severe Alexander grade changes, was more common in patients treated with doxorubicin (doxorubicin-treated patients = 20%, bisantrene-treated patients = 5%, and mitoxantrone-treated patients = 10%). This study demonstrates that bisantrene and mitoxantrone have only modest activity in metastatic breast carcinoma. The activity of doxorubicin is greater than that of the other two agents, but at a cost of increased toxicity. 
Myocardial infarction with minimal coronary atherosclerosis in the era of thrombolytic reperfusion. The Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) Study Group. The incidence of minimal residual atherosclerotic coronary obstruction after successful intravenous thrombolytic therapy was evaluated in 799 patients with acute myocardial infarction. Minimal residual coronary obstruction (less than or equal to 50%) was observed on selective coronary angiography performed 90 min after initiation of thrombolytic therapy in 43 patients (5.5%). In 42 other patients (5.4%), a greater than 50% but less than 100% residual stenosis noted at 90 min demonstrated further resolution of obstruction to less than 50% at an angiographic follow-up study 7 to 10 days later. Patients with minimal residual coronary obstruction were significantly younger (52 +/- 10.7 versus 56.7 +/- 10 years; p = 0.002) and had less multivessel coronary disease (p less than 0.001), better initial left ventricular ejection fraction (54 +/- 12% versus 50.2 +/- 11.4%; p = 0.006) and a lower in-hospital mortality rate (1% versus 7%; p = 0.04) than did patients who had a significant (greater than 50%) residual coronary obstruction after intravenous thrombolysis. Long-term follow-up study of patients with a minimal coronary lesion (average 1.5 +/- 0.6 years) and those with significant residual stenosis (average 1.6 +/- 0.7 years) demonstrated that the incidence of death (2.4% in patients with minimal stenosis versus 3.5% in those with significant stenosis) and recurrent myocardial infarction (5% each) were similar in both groups. New strategies are needed to prevent coronary rethrombosis in patients with minimal atherosclerosis after thrombolytic therapy for acute myocardial infarction. 
Cor triatriatum with isolated pulmonary venous stenosis in an adult: diagnosis with transesophageal two-dimensional echocardiography. The diagnosis of cor triatriatum in an adult was made from routine two-dimensional transthoracic echocardiography. The findings of aliasing and turbulence in the roof of the left atrium suggested pulmonary venous stenosis. A transesophageal echocardiogram defined both the hemodynamic features of nonobstructing cor triatriatum and the presence of isolated pulmonary venous stenosis. The clinical use of transesophageal echocardiography with color flow Doppler in the elucidation of complex anatomic substrate is demonstrated. 
Regulation of thyrotropin-releasing hormone receptors is cell type specific: comparison of endogenous pituitary receptors and receptors transfected into non-pituitary cells. TRH, which does not elevate cyclic AMP, and elevation of cellular cyclic AMP decrease the density (down-regulate) of TRH receptors (TRH-Rs) on pituitary (GH3) cells. In this study we measured the effects of TRH and elevation of cyclic AMP on TRH-Rs expressed in non-pituitary cells transfected with a recently cloned mouse pituitary TRH-R complementary DNA. In stably transfected rat glioma (C6-2) cells and transiently transfected COS-1 cells TRH caused TRH-R down-regulation while elevation of cyclic AMP caused increases in TRH-R density. Hence, the effects of cyclic AMP on TRH-Rs in transfected C6-2 and COS-1 cells are different from those in GH3 cells while the effects of TRH on TRH-R are similar in all three cell types. These data show that regulation of TRH-Rs is cell type specific. 
Malignant tumours of the middle ear. The authors present 15 patients with middle ear malignant tumours, of which 13 were squamous cell carcinomas, one was a rhabdomyosarcoma and one a malignant lymphoma. In 11 of 13 patients with squamous cell carcinoma, long-standing chronic otitis media preceded the malignant process and only in 2 patients did the tumour develop without previous chronic infection. Most of the patients presented at an advanced stage of the disease: in 6 the tumour had destroyed surrounding bone, commonly involving the endocranium; in 7 the facial nerve was paralysed and in 8 patients there was total hearing loss. The diagnosis of malignant tumour was established before surgery in 5 patients, but 8 patients were operated upon for suspected chronic otitis. Three patients died without treatment and 10 were treated: 3 with radiotherapy because the tumour was inoperable, 3 had surgery only and 4 patients had surgery and received radiotherapy post-operatively. Of 7 operated patients only 2 are alive without signs of tumour. Our findings suggest that otologists should bear in mind this disease in patients with chronic suppurative otitis and accompanying suspected symptoms. In 2 patients with rare types of sarcoma of the middle ear the diagnosis of tumour was established at an advanced stage and they could not be treated. 
Chronic ulcerations following topical therapy with 5-fluorouracil for vaginal human papillomavirus-associated lesions. Applied topically to the vagina, 5-fluorouracil (5-FU) cream is an effective therapy for human papillomavirus (HPV)-associated lesions of the vagina including condylomata acuminata and vaginal intraepithelial neoplasia. Although the acute side effects of 5-FU therapy are well recognized, long-term sequelae of intravaginal 5-FU use have not been described in detail in the literature. To assess the incidence and clinical course of 5-FU-related vaginal mucosal alterations, we studied 220 patients who underwent 5-FU therapy for HPV-associated lesions of the vagina. Eighteen women (8.2%) had epithelial ulcers 6 months after completion of the 5-FU treatment. The incidence of ulcers was higher in women who used 5-FU for longer than 10 weeks compared with those who used it for 10 weeks or less (9.6 versus 5.7%; P = .05). All but one of the mucosal defects were in the vaginal fornices and/or the periphery of the ectocervix. The ulcers were mostly singular and measured 0.5-7 cm in greatest diameter. Fourteen patients (77.8%) had symptoms related to the ulcers including a serosanguineous or watery discharge (55.6%), postcoital spotting or bleeding (44.4%), irregular bleeding unrelated to intercourse (16.7%), and pain (5.6%). Spontaneous healing of the ulcers was protracted. Office methods of therapy including estrogen creams and cauterizing agents failed to accelerate healing as compared with untreated patients. Excision of the ulcer and primary closure of the wound was curative in all four cases in which it was used. We conclude that topical 5-FU therapy may lead to troublesome chronic mucosal ulcers that tend to persist despite conservative treatment attempts. 
Coronary focal ectasia formation following percutaneous transluminal angioplasty. Focal ectasia of the right coronary artery developed following percutaneous transluminal angioplasty. Operative intervention was not deemed necessary. No restenosis was found on repeat coronary angiography. Five-yr follow-up was associated with a benign course. 
Iatrogenic renal disease. We studied iatrogenic problems in nephrology by classifying all patients for nephrology consultation into nine presenting syndromes and seven etiologic groups. One hundred (2.2%) of all admissions were seen in nephrology consultation. Acute renal failure was the most common presenting syndrome, accounting for 59% of the consultations. Forty-one of the 100 consultations (1% of all admissions) had a renewal syndrome of iatrogenic origin. Of these 41 patients, 38 had acute renal failure and three had fluid and electrolyte problems. Twenty of the 41 patients had drug-induced problems. Eighteen of these patients were dehydrated, and in three patients, acute renal failure occurred after surgery. Of the 20 patients with iatrogenic renal problems caused by drugs, seven problems were antibiotic related, five were due to diuretics, four were due to nonsteroidal anti-inflammatory drugs, three were due to angiotensin-converting enzyme inhibitors, and one was from the use of contrast medium. The 41 patients with iatrogenic-related renal disease were older than the other 59 patients (61.8 vs 49.3 years). Iatrogenic renal disease developed in 1% of all patients admitted to a tertiary care hospital, and 12% of these patients died. The most common renal syndrome is acute renal failure, most often caused by nephrotoxic drugs. The incidence can probably be decreased by better monitoring of body weight and fluid balance to prevent dehydration and by the avoidance of nephrotoxic drugs. 
Incidence of neuropathy in 395 patients with ovarian cancer treated with or without cisplatin. In two consecutive trials, a total of 395 patients with ovarian cancer were treated with a combination of hexamethylmelamine, cyclophosphamide, methotrexate, and 5-fluorouracil chemotherapeutic regimens including cisplatin or without this drug. With respect to neurotoxicity, 387 patients were fully eligible. The median follow-up for survival was 45 months. Neurotoxicity in any grade of severity developed in 47% of the patients treated with a cisplatin-containing regimen and in 25% of those treated with the non-cisplatin-containing regimen. The severity of neurotoxicity was much higher, however, in the cisplatin-treated patients. Neurotoxicity-free survival decreased below 50% at cumulative doses of cisplatin between 500 and 600 mg/m2. No additional effect of hexamethylmelamine on the incidence or severity of neurotoxicity could be demonstrated. In patients who survived for more than 5 years, the incidence of cisplatin neuropathy was 61%. Prognostic variables (age, International Federation of Gynecology and Obstetrics [FIGO] stage, performance status, and others) possibly associated with high-risk subgroups could not be identified. The only consistent factor correlated with neurotoxicity was the total dose of cisplatin received. 
Initial clinical experience with a 48 by 48 element biplane transesophageal probe. Recent technologic advances in ultrasound have resulted in the capability of transesophageal echocardiographic imaging in both transverse and longitudinal planes. Previous biplane probes suffered from inferior images because of reduced scan elements. We evaluated the utility of a prototype 48 X 48 element biplane transesophageal probe in 23 consecutive patients. Examinations were well tolerated with no side effects. In comparison to the single transverse plane, imaging with the longitudinal plane gave superior information on prosthetic valve pathology, atrial septal abnormalities, and pathoanatomy of the ascending aorta and mitral valve. Complementary information was provided by the longitudinal plane in patients with endocarditis and vegetations and in mitral protheses. Images obtained with this 48 X 48 element biplane probe along with color and spectral Doppler information were not perceptibly inferior to those obtained by single-plane probes. In conclusion, biplane transesophageal echocardiography with a 48 X 48 element probe indicates a great potential for enhanced three-dimensional understanding of cardiac pathology and diagnostic yield in specific pathologies. 
Risk of adverse events in children completing treatment for acute lymphoblastic leukemia: St. Jude Total Therapy studies VIII, IX, and X. We studied the frequency, causes, and predictors of adverse events in 624 patients who had completed treatment for acute lymphoblastic leukemia (ALL) in three consecutive total therapy studies (VII, IX, and X, 1972 to 1983). Event-free survival in study X was significantly better overall than that in studies VIII and IX (P less than .0001 by the log-rank test). In study X, 75% of the patients were electively taken off therapy, compared with 54% in studies VIII and IX. However, the risks of having an adverse event during the first 5 years after completion of therapy were remarkably similar: 22% (95% confidence interval, 17% to 29%) in study X versus 24% (20% to 29%) in studies VIII and IX. Bone marrow, testicular, and CNS relapses accounted for the majority of failures in both groups (85% in study X and 92% in studies VIII and IX). Late adverse events consisted largely of hematologic relapses and the development of solid tumors. Black race (P = .001) and leukemia without an anterior mediastinal mass (P = .05) were associated with an increased risk of failure after completion of treatment in the two earlier clinical trials, whereas a lower leukemic cell DNA content (DNA index less than 1.16) was the only predictor of late treatment failure in the more recent trial (P = .019). None of the other presenting features that were examined (eg, age, leukocyte count, and sex) had value as predictors of late failure. Thus, improved treatment altered the impact of specific prognostic factors and the distribution of sites of relapse, but it did not significantly affect the risk of delayed failure. 
An open, multicenter trial of recombinant tissue plasminogen activator in acute stroke. A progress report. The rt-PA Acute Stroke Study Group. Sixteen clinical centers in two countries have undertaken a prospective open angiography- and computed tomography scan-based safety and efficacy dose-rate finding study of recombinant (two-chain) tissue plasminogen activator (rt-PA) in acute thrombotic and thromboembolic stroke. Preliminary experience with 71 rt-PA treated patients in seven dose-rate groups has demonstrated both partial and complete recanalization, documented by angiography, although a dose response has not yet been achieved. Hemorrhagic infarction has been documented at all dose rates, and dose-rate independent cerebral hematomas have been observed. The study continues at higher dose rates while still remaining within the safety guidelines. 
Intraoperative identification of cardiac patients at risk to develop postoperative atrial fibrillation. Postoperative atrial fibrillation (AF) is a complication occurring in 11% to 36% of patients after cardiac operations, which results in increased morbidity and hospital costs. A new electrophysiologic screening test was developed to identify those patients at risk for development of postoperative AF. The test was validated in 50 patients (43 men and 7 women) with a mean age of 59.6 +/- 1.3 years who underwent coronary artery bypass grafting with or without other cardiac surgical procedures. After aortic and venous cannulation, but before initiation of bypass, the mid-right atrium was stimulated with a bipolar probe at 25 microA for 3 seconds. Alternating current was increased by 25 microA until AF was induced or up to a maximum of 200 microA. Postoperative AF occurred in 18 patients (36%), 17 of whom had inducible AF (sensitivity = 0.94). Of the remaining 32 AF-free patients, 13 had negative tests (specificity = 0.41). Age and sex were not factors affecting inducibility, although patients who developed AF were older than those who were AF free (63.6 versus 57.3 years, p = 0.02). Length of stay in the intensive care unit was longer for those with postoperative AF than for AF-free patients (3.6 versus 1.9 days, p = 0.02). The negative predictive value of the test was 0.93, and the positive value was 0.47. These data show that this new intraoperative technique may be used to identify patients at risk for postoperative AF. Prophylactic therapy can therefore be directed to only those patients at risk for postoperative AF. 
Two patients with insulin resistance due to decreased levels of insulin-receptor mRNA. Mutations have been identified in the insulin-receptor gene in insulin-resistant patients. We studied two patients with acanthosis nigricans and insulin resistance caused by a decrease in the number of cell surface insulin receptors. Patient 1 was an 11-yr-old boy with a fasting insulin level of 2130 pM; patient 2 was a 14-yr-old girl with hyperandrogenism and a fasting insulin level of 580-740 pM. Based on Southern-blotting studies, the structure of both alleles of the insulin-receptor gene in both patients appeared to be grossly normal. There was no evidence of insertions, deletions, or major rearrangements. Moreover, the nucleotide sequences of all 22 exons of the gene were normal in both patients. Thus, the predicted amino acid sequences of both patients' insulin receptors were normal. In Epstein-Barr virus-transformed lymphoblasts from patient 1, insulin-receptor mRNA levels were so low they could not be detected with an RNase A protection assay, whereas mRNA levels from patient 2 were in the lower half of the normal range. By use of a more sensitive assay based on the polymerase chain reaction, insulin-receptor mRNA could be detected in Epstein-Barr virus-transformed lymphoblasts from both patients. Moreover, because of the existence of silent polymorphisms in the nucleotide sequences, it was possible to differentiate the two alleles of the insulin-receptor gene in both patients. In patient 2, the two alleles were expressed asymmetrically, with 90% of the mRNA molecules having been transcribed from one allele but only 10% transcribed from the second allele. This suggests that there is an unidentified mutation in the underexpressed allele that acts in a cis-dominant fashion to decrease insulin-receptor mRNA levels. However, in patient 1, both alleles were expressed symmetrically in similarly low levels. Although not proven, it seems likely that the mutations that decrease insulin-receptor mRNA levels in patient 1 also map to the insulin-receptor locus. 
Colonic ischemia complicating immunotherapy with interleukin-2 and interferon-alpha. Colonic ischemia (CI) is a rare complication of high-dose interleukin-2 (IL-2) immunotherapy. This complication occurred in three of 141 patients (2.1%) with metastatic cancer treated with high-dose IL-2 therapy; CI only developed in patients receiving interferon-alpha (IFN) with IL-2 (three of 21, 14%) compared with none of 120 in those patients receiving IL-2 alone (P equals 0.0009). Severe diarrhea (greater than or equal to 7 bowel movements/day) also was significantly more common in patients receiving IFN with IL-2 (six of 21, 29%) than in those receiving IL-2 alone (three of 120, 2.5%, P equals 0.001) and preceded the clinical diagnosis of CI in all three patients. Three of nine patients with severe diarrhea had CI. Hematochezia occurred in four patients, all of whom received IFN with IL-2; three had CI, and the other patient had nonspecific colitis. Differences in vasopressor use did not explain the increased risk of CI in patients receiving IFN; those receiving IFN with IL-2 required phenylephrine less often than patients receiving IL-2 alone (P equals 0.01). The administration of lymphokine-activated killer (LAK) cells had no significant effect on the incidence of CI, severe diarrhea, peritonitis, or vasopressor use; two of three patients with CI, however, had their ischemic episode within 24 hours after the last of three LAK cell infusions. In conclusion, CI is an unusual complication of high-dose IL-2 and IFN immunotherapy. In patients receiving such combination therapy, severe diarrhea is a risk factor for the subsequent occurrence of CI. 
Prostate-specific antigen and prostatic acid phosphatase: biomolecular and physiologic characteristics. PSA is a 34-kd 240-amino acid glycoprotein produced by the prostatic epithelial cells. It is a member of the glandular kallikrein gene family and has a high sequence homology with human glandular kallikrein (hGK-1). PSA is a serine protease and has chymotrypsin-, trypsin-, and esterase-like activities. It is secreted into the seminal fluid where it degrades two seminal vesicle proteins that are important components of the semen coagulum, thus playing an important role in semen liquefaction. The production of PSA protein appears to be under the control of circulating androgens acting through the androgen receptor. Therefore, the significance of a low serum PSA value in a patient who has undergone previous antiandrogen therapy may not be the same as that for a patient who has not received endocrine treatment. 
Fatal aortic rupture during balloon dilatation of recoarctation. In an eight year old boy with a patch aortoplasty, the aorta ruptured during balloon angioplasty for recoarctation. At necropsy a 1.5 cm long, full thickness tear and a separate, smaller, intimal tear were found. Histological examination showed thinning of the elastic laminae of the aorta. Angioplasty for recoarctation may be dangerous in patients with a patch aortoplasty. 
The danger of an ultra-early computed tomographic scan in a patient with an evolving acute epidural hematoma. A case of an acute traumatic epidural hematoma that developed after an ultra-early computed tomographic scan of the head is discussed. Serial neurological examinations in patients with head injuries are recommended. 
Principal causes of mechanical bowel obstruction in surgically treated adults in western Turkey. A retrospective study of the principal causes of mechanical bowel obstruction occurring in Western Turkey between 1979 and 1989 was undertaken. The records of 14,777 operations performed in the general surgery departments of two hospitals were reviewed. Mechanical bowel obstruction occurred in 582 patients. Among the causes of mechanical bowel obstruction, adhesions were most common (44.0 per cent), followed by strangulated hernia (23.9 per cent), volvuli (12.7 per cent) and colonic carcinomas (10.1 per cent). A previous appendicectomy appeared to be the most important cause of adhesions causing mechanical bowel obstruction. 
Total body calcium in patients with inflammatory bowel disease: a longitudinal study. 1. Serial measurements of total body calcium have been made by prompt gamma-neutron activation analysis in 13 patients with inflammatory bowel disease over a mean period of 23 months. Changes in spinal trabecular bone mineral density and radial shaft bone mineral content were also assessed by using quantitative computed tomography and single photon absorptiometry, respectively. 2. The mean annual decreases (95% confidence intervals) were: total body calcium, 7.8% (-12.0 to -3.7%; P less than 0.001); spinal trabecular bone mineral density, 2.5% (-5.0 to +0.1%; 0.05 less than P less than 0.1), radial bone mineral content, 2.1% (-3.4 to -0.8%; P less than 0.01). 3. No significant correlations were found between rates of change of the three variables. However, there were significant positive correlations between the baseline values for total body calcium and radial bone mineral content (r = 0.638, P less than 0.05), spinal bone mineral density and radial bone mineral content (r = 0.854, P less than 0.01), and total body calcium and spinal bone mineral density (r = 0.876, P less than 0.001). 4. These results demonstrate rapid decreases in total body calcium in patients with inflammatory bowel disease which, in conjunction with the significant decrease in radial shaft bone mineral content, indicate increased rates of cortical bone loss. Whilst values for bone mass at different skeletal sites showed positive correlations within individuals, no relationship was found between the rates of change in bone mass at these sites. 5. The rapid bone loss observed in some subjects emphasizes the importance of early detection of osteoporosis by bone densitometry and the need for effective prophylactic measures to be established in this group of patients. 
Treatment of meningitis and other infections due to ampicillin-resistant Haemophilus influenzae type b in children. Cefotaxime and other cephalosporins were retrospectively evaluated for the treatment of meningitis and non-central nervous system (CNS) infections due to ampicillin-resistant Haemophilus influenzae type b (Hib). Between January 1985 and February 1989, 45 cases of meningitis and 27 cases of non-CNS infection due to ampicillin-resistant Hib were documented at Texas Children's Hospital in Houston. Of the 45 children with meningitis, 26 (57.8%) were treated with cefotaxime, 11 (24.4%) with chloramphenicol, and three (6.7%) with cefuroxime; five children (11.1%) were initially given chloramphenicol but later received cefotaxime instead. In addition, 14 chloramphenicol-treated patients from a previous study were included in this analysis. There were no significant differences in terms of neurologic sequelae or other complications (except diarrhea) between the cefotaxime and chloramphenicol groups. The efficacy of cefotaxime was equivalent to that of chloramphenicol for the treatment of ampicillin-resistant Hib meningitis. Cefuroxime was as safe and effective as chloramphenicol or cefotaxime for the treatment of non-CNS infections due to ampicillin-resistant Hib. 
Effect of age on use of thrombolytic therapy and mortality in acute myocardial infarction. The MITI Project Group. The findings in 3,256 consecutive patients hospitalized for acute myocardial infarction were tabulated to assess the history, treatments and outcome in the elderly; 1,848 patients (56%) were greater than 65 years of age, including 28% who were aged greater than or equal to 75 years. The incidence of prior angina, hypertension and heart failure (only 3% of patients less than 55 years of age had a history of heart failure compared with 24% greater than or equal to 75 years old) was found to increase with age. Twenty-nine percent of patients less than 75 years of age were treated with a systemic thrombolytic drug compared with only 5% of patients older than 75 years. Mortality rates increased strikingly with advanced age (less than 2% in patients less than or equal to 55, 4.6% in those 55 to 64, 12.3% in those 65 to 74 and 17.8% in those greater than or equal to 75 years). Both the incidence of complicating illness and a nondiagnostic electrocardiogram (ECG) increased with age. In a multivariate analysis of outcome in older patients (greater than or equal to 65 years), adverse events were related to both prior history of heart failure (odds ratio 3.9) and increasing age (odds ratio 1.4 per each decade of age). Outcome was not improved by treatment with thrombolytic drugs, but these agents were prescribed to only 12% of patients greater than 65 years of age, thereby reducing the power for detecting such an effect. 
Pararectus retroperitoneal radical nephrectomy. We describe a new pararectus retroperitoneal approach to the kidney, which allows easy identification and occlusion of the renal vessels before mobilization of the kidney. This approach potentially reduces morbidity, hospital stay and cost. The technique has been used in 4 cases of radical nephrectomy for tumor and in 1 for pyonephrosis. 
The effect of magnesium sulfate on the biophysical profile of normal term fetuses. Forty term pregnant women with singleton breech gestations admitted for external cephalic version underwent biophysical profile testing before any fluid infusion or medication. After magnesium sulfate had been infused for contraction prophylaxis, the maternal serum magnesium level was measured and a second biophysical profile was performed. The mean (+/- SD) serum magnesium was 5.1 +/- 1.0 mg/dL. The biophysical profile score decreased significantly, reflecting a decrease in fetal breathing activity. In patients with therapeutic maternal serum magnesium levels, loss of any component of the biophysical profile other than respiration cannot be attributed to the elevation in magnesium concentration. 
Hemicholinium-3 derivatives A-4 and A-5 alter choline metabolism in NB41A3 neuroblastoma cells. A-4, A-5 and HC-3 are experimental bis tertiary and quaternary amines which have been shown to be potent inhibitors of the sodium-dependent, high affinity choline uptake system. When incubated with neuroblastoma cells, experimental compounds A-4, A-5 and HC-3 inhibit choline metabolism. Over a 24-hr incubation, A-4, A-5 and HC-3 produced a significant decrease in total choline accumulation, choline incorporation into phospholipid and free choline content. However, despite decreases in choline incorporation into phospholipid, no change occurred in content of phosphatidylcholine. Treatment of cells with A-4, A-5 and HC-3 resulted in an increase in the incorporation of S-adenosyl-methionine into phosphatidylcholine. However, the incorporation of ethanolamine or serine into phosphatidylcholine was not increased. Phosphatidylcholine turnover was decreased in cells treated with A-4 and A-5. A-4, A-5 and HC-3 produce significant decreases in choline metabolism; however, the cells are able to maintain membrane integrity by decreasing turnover of phosphatidylcholine and increasing phosphatidylcholine synthesis through the methylation pathway. These studies suggest that the biological effects of A-4 and A-5 are independent of membrane perturbations. 
Cardiac myofibroblasts express alpha smooth muscle actin during right ventricular pressure overload in the rabbit. A number of changes occur in contractile proteins and mechanical performance of the heart within 2 weeks of right ventricular pressure overload in 8- to 12-week-old rabbits. These changes are accompanied by increases in collagen concentration and the ratio of type I to type III collagen. The purpose of the present study was to evaluate the evolution of these connective tissue changes morphologically and to characterize the interstitial cells that might be responsible. The myocardium is infiltrated by mononuclear inflammatory cells 2 days after banding, accompanied by focal myocyte necrosis. By 7 days, the inflammatory infiltrates subside and the damaged myocytes seen at 2 days are replaced by new collagen and a population of spindle-shaped cells, with ultrastructural features of myofibroblasts. A significant proportion of these cells contain alpha smooth muscle actin by immunohistochemical analysis. At 14 days, there is a large increase in stainable collagen with complex remodeling and reduplication of the collagen fiber network of the interstitium. Alpha smooth muscle actin-containing myofibroblasts persist, but their immunoreactivity appears reduced compared with day 7. The authors hypothesize that the interstitial fibroblasts that acquire smooth-muscle-like features in this model play a critical role in the heart's response to severe and sudden mechanical stress and are at least partly responsible for the changes in connective tissue that occur as a result of pressure overload in this model. 
Solitary polyclonal autonomous thyroid nodule: a rare cause of childhood hyperthyroidism. Solitary autonomous thyroid tumors are an unusual cause of hyperthyroidism, particularly in childhood. We describe the youngest individual so far reported with this condition, a 22 month child with a large hyperfunctioning thyroid nodule who became overtly hyperthyroid after iodinated contrast administration. The histology of the nodule was compatible with follicular cell hyperplasia. These tumors are often called toxic adenomas, although there is no solid evidence that they are true neoplasms. We examined the clonal composition of the child's thyroid tumor by X-chromosome inactivation analysis, taking advantage of a polymorphism in the X-chromosome gene phosphoglycerate kinase. The tumor consisted of an even mixture of cells containing activated paternal and maternal PGK alleles, indicating that the tumor was polyclonal. Furthermore, the nodule had no structural rearrangements or activating point mutations of ras oncogenes, which are found in up to 50% of solitary monoclonal follicular adenomas. Solitary hot nodules may at least in some cases be secondary to hyperplasia, and not to clonal expansion of an abnormal, mutated cell. This may also explain the relatively low frequency of malignant transformation observed in hyperfunctioning thyroid tumors. 
Alteration of the pulsatile load in the high-altitude calf model of pulmonary hypertension. We compared main pulmonary arterial elasticity and global pulmonary arterial compliance in control and high-altitude (HA) calves to determine whether 1) changes in pulmonary arterial elasticity are contributing to an increase in the oscillatory load of the right ventricle in this model of pulmonary hypertension and 2) measured changes in stiffness of the HA calves' arterial wall are the result of both an increase in pressure and an alteration of the material properties of the HA calves' arterial wall. Newborn calves were placed at 4,300 m simulated altitude for 14 days, and control calves were kept at 1,500 m. The HA calves were then reacclimatized to 1,500 m for 24 h so that baseline pressures of the two groups were similar. Open-chest main pulmonary arterial and right ventricular micromanometric pressures, ultrasonic main pulmonary arterial diameter, and green dye flow were measured under baseline conditions and then under moderate and severely hypoxic conditions to make measurements at both baseline and increased pulmonary pressures. At elevated pressures, the pressure-diameter relationship was noted to be nonlinear, and a characteristic late systolic peaking of the right ventricular pressure waveform was seen. The Peterson pressure-strain modulus, pulse wave velocity, characteristic impedance, and global compliance (3 element windkessel) were calculated. The calculated variables were all shown to be pressure dependent, and no intrinsic differences in stiffness were seen between the control and HA animals when mean pressure was taken into account. Pulmonary arterial histology demonstrated, however, a characteristic increase in wall thickness in the HA animals. Thus, in this model of pulmonary hypertension, major changes in elasticity and pulsatile load are primarily due to an increase in pulmonary pressure. The structural changes present in the HA calves' arterial wall did not separately produce any measurable changes in arterial distensibility or the oscillatory load. 
Behavioral audiometry. Behavioral audiometry is based on observation of overt responses to controlled auditory stimuli, as contrasted with electrophysiologic procedures, which involve electrophysiologic monitoring or direct recording of the bioelectric correlates of the original signal. When reinforcement is added to the behavioral procedures, the infant or young child provides highly reliable responses, and it is possible to test most infants 6 months of age and older with these procedures. The combination of both behavioral and electrophysiologic procedures can resolve most clinical questions regarding the auditory function of young infants and children. 
Oral acyclovir therapy of recurrent herpes simplex virus type 2 infection of the hand. Acyclovir was evaluated as treatment of recurrent herpes simplex virus type 2 infection of the hand in a double-blind, placebo-controlled crossover study. In nine fully evaluable patients, oral acyclovir (2 g/day in three doses for 10 days) initiated during the earliest phase of a recurrence reduced the mean durations (+/- standard deviation) of clinical symptoms from 10.1 (+/- 3.6) to 3.7 (+/- 3.0) days (P = 0.008), signs from 11.1 (+/- 3.7) to 6.2 (+/- 3.3) days (P = 0.024), and viral positivity from 5.3 (+/- 3.8) to 0.6 (+/- 1.1) days (P = 0.011). 
Patient-controlled analgesia. Does a concurrent opioid infusion improve pain management after surgery? OBJECTIVE.--To assess the influence of a continuous (basal) morphine infusion as part of a patient-controlled analgesia (PCA) system on the postoperative analgesic requirement and on recovery parameters following abdominal hysterectomy. DESIGN.--Single-center, randomized, controlled protocol. SETTING.--University medical center. PARTICIPANTS.--A total of 230 adult women were randomly assigned to receive no morphine infusion (control group) or a continuous 0.5-, 1.0-, or 2.0-mg/h morphine infusion. Each patient was able to self-administer supplemental intravenous bolus doses of morphine (1 to 2 mg) using a PCA infuser. MAIN OUTCOME MEASURES.--Use of the PCA device, opioid-related side effects, recovery times, and the patients' assessment of pain and sedation on linear visual analog scales were recorded during the 72-hour study period. Follow-up questionnaires were completed by the patients and their health care professionals to assess the overall adequacy of PCA therapy. RESULTS.--Patients who received the 2-mg/h morphine infusions received significantly more opioid medication 9 to 72 hours after their operation than those who received no infusion (control group). The presence of a continuous morphine infusion of 0.5 to 2 mg/h did not significantly decrease the number of patient demands or supplemental bolus doses administered compared with the control group. Overall, 168 (84%) of the 199 patients who completed the 72-hour study were able to achieve adequate analgesia without requiring changes in the PCA regimen or experiencing major side effects. Recovery times and outcome variables were similar in all four groups. CONCLUSION.--The routine use of a continuous opioid infusion in combination with a standard PCA regimen does not improve pain management compared with PCA alone after abdominal hysterectomy. 
Leukaemia mortality among relatives of cystic fibrosis patients. A total of 219 families of patients with cystic fibrosis living in Wales were studied for the occurrence of other diseases and for cause of death, and the findings in relation to leukaemia are reported. There were eight deaths due to leukaemia, five of the myeloid type, in first and second degree relatives; this is significantly more than the expected on the basis of national age specific mortality rates. In comparison, mortality among siblings, parents, aunts and uncles, and grandparents from all causes was within the expected. Screening the five patients with myeloid leukaemia for the delta F508 mutation showed that four were carriers of this mutation. It is concluded that carriers of the delta F508 mutation may have an increased risk of developing acute myeloid leukaemia. This could happen through the direct effect of the cystic fibrosis gene itself, or through its influence on another gene, such as the met oncogene, or gene(s) involved in granulocyte function on the long arm of chromosome 7. 
Subclinical cardiac dysfunction in sarcoidosis. Clinically apparent myocardial disease is infrequent in sarcoidosis. However, autopsy data show myocardial involvement in up to 30 percent of patients. Unexplained exertional symptomatology is a common complaint in patients with sarcoidosis. In this study, we investigated whether abnormal cardiac function might limit exercise performance in patients with sarcoidosis without overt cardiac involvement. We studied exercise responses in 35 patients with sarcoidosis and compared them with 28 untrained controls. Seventy-seven percent of the patients were symptomatic. Pulmonary function test results were lower in the group with sarcoidosis than normal controls, but they were within normal range. Only one patient had evidence of ventilatory limitation to exercise. Sixteen (46 percent) patients had abnormally increased heart rates (HRs) at rest prior to exercise testing and/or with exercise. Rapid HRs were confirmed during daily activities by continuous ambulatory electrocardiographic (ECG) monitoring. Left ventricular ejection fraction (LVEF) was measured to determine if systolic dysfunction could account for abnormal HR responses. Of patients with abnormally increased HRs, five had LVEFs less than 50 percent, and eight had normal LVEFs, of whom 75 percent had tachycardia at rest. Retrospective comparison of HR responses and LVEF between patients who did or did not receive corticosteroids revealed no significant differences between groups. We conclude that abnormal HR responses in patients without evident cardiac sarcoidosis are common and exertional symptoms in this population are often associated with chronotropic abnormalities. The exact mechanisms underlying the chronotropic abnormalities are unclear, but they likely include ventricular systolic dysfunction, sinus node dysfunction from granulomatous infiltration, or combinations of the two. 
Effect of massive dose vitamin A on morbidity and mortality in Indian children The effect of vitamin A supplementation on preschool child morbidity and mortality was assessed in a prospective double-blind placebo-controlled study around Hyderabad, India. Every six months 200,000 IU vitamin A was given to 7691 children (treatment group) whereas 8084 children received a placebo (control group). Morbidity and mortality data were collected every three months. Risk of respiratory infection was higher in children with mild xerophthalmia than in children with normal eyes. Vitamin A supplementation had no effect on morbidity status. Mortality rates were similar in the two groups; it was highest in children who did not receive either vitamin A or placebo. The findings suggest that vitamin A supplementation alone may not reduce child mortality. 
Origin of malignant centrofacial granulomas: surface markers and gene rearrangement of malignant cells. Malignant centrofacial granuloma (MCFG) is a clinical entity characterized by a relentless ulceration of the upper airway involving the nose, palate, and face, without any demonstrable etiology. The origin of 11 cases were analyzed with the help of cell-surface immunostaining in all and with T-cell receptor gene (TCR) rearrangement in 3. The results show that most of the cases of MCFG are in fact T-cell lymphomas with cell-surface antigens (CD2, CD7, CD3) consistent with either early or mature T lymphocytes. However, some cases exhibit B-lymphoid (CD19, CD20) or histiomonocytic (CD13, CD14) lineage-specific markers. In conclusion, despite its remarkable clinical unity, MCFG is a heterogeneous group of neoplastic diseases, most but not all of which may be classified as T-cell lymphoma. 
Popliteal aneurysm with spontaneous arteriovenous fistula. This report documents a rare manifestation of aneurysmal disease of the popliteal artery. We describe a popliteal aneurysm presenting with acute venous hypertension due to a spontaneously occurring arteriovenous fistula. The fistula was defunctionalized by treating the aneurysm with a standard technique of exclusion and bypass with resolution of the symptoms of venous hypertension and maintenance of normal distal perfusion. 
Extraocular muscle surgery in myasthenia gravis. Myasthenia gravis is typically a disease of young people in active employment who need a field of binocular single vision. Although it is systemically controllable with a good chance of spontaneous remission, persistent loss of binocularity may cause chronic disability. We report our experience of extraocular muscle surgery in five patients with stable myasthenia gravis and persistent double vision. Extraocular muscle involvement was selective, giving rise to incomitant and concomitant squints, with individual muscle overactions as well as underactions. Treatment was by conventional recession and resection procedures with the additional use of Faden and adjustable sutures where appropriate. In all five cases a larger, stable field of binocular single vision was established. It is concluded that extraocular muscle surgery may be beneficial in selected cases of myasthenia gravis. 
A comparison of sucralfate with placebo in the treatment of esophageal ulcers following therapeutic endoscopic sclerotherapy of esophageal varices--a prospective controlled randomized trial. In 1984 Roark published the first report of a sucralfate treatment of esophageal ulcers after sclerotherapy. Because this was an uncontrolled trial we planned a prospective double-blind placebo-controlled study with 60 patients. After therapeutic paravariceal injection-sclerotherapy of esophageal varices, patients were randomly treated with sucralfate suspension or placebo. Time of treatment was limited to a maximum of 3 weeks and the dosage of sucralfate was 1 g q.i.d. (Ulcogant-Suspension). Healing was assessed by endoscopy at weekly intervals. Fifty-three patients (25 sucralfate, 28 placebo) were evaluable according to the protocol. No patient left the study because of side effects. At the start of the trial, the patients in the sucralfate group showed a larger ulcer area than the placebo group. There was a tendency to faster healing in the sucralfate group, especially in patients with deeper ulcerations. However, there was no significant difference in global healing between both treatment groups after 3 weeks. Sucralfate suspension may be of value in accelerating the healing process in esophageal ulcers after sclerotherapy, especially in patients with deep ulcers. These results should be confirmed in further trials, in which patients should be stratified with respect to their ulcer volume and severity of liver disease. 
Orthostatic vital signs in emergency department patients. STUDY OBJECTIVE: To examine the variability and define the normal ranges of orthostatic vital signs in an emergency department population. DESIGN: Descriptive. TYPE OF PARTICIPANTS: Adult ED patients with no history of recent blood or fluid losses. MEASUREMENTS: Lying and standing heart rate and blood pressure measured by an automated instrument. RESULTS: In 132 presumed euvolemic patients, the statistical normal ranges (mean +/- 2 SD) of orthostatic vital signs were wide: on standing, the heart rate range was from decreases 5.0 to increases 39.4 beats per minute; for systolic blood pressure, the range was decreases 20 to increases 25.7 mm Hg; and for diastolic blood pressure, the range was decreases 6.4 to increases 24.9 mm Hg. In this sample, 43% had "positive" orthostatic vital signs according to currently accepted values. CONCLUSION: The data from this study indicate that there is a wider than expected variation in orthostatic vital signs among presumed euvolemic ED patients. 
Prognosis of symptomatic duodenal adenomas in familial adenomatous polyposis. The frequent association between familial adenomatous polyposis and duodenal tumors is increasingly recognized, yet many patients do not benefit from adequate diagnosis and follow-up of upper gastrointestinal polyps. A retrospective review of 14 patients with duodenal tumors associated with familial adenomatous polyposis was undertaken to assess the impact of early diagnosis by screening asymptomatic patients. Six of eight patients presenting with symptoms suggesting duodenal disease had invasive cancer. Four of these six patients died after surviving a mean of 13 months after diagnosis. In contrast, none of the six patients diagnosed after screening with upper gastrointestinal endoscopy has had invasive carcinoma. Early diagnosis and long-term surveillance of asymptomatic patients with familial adenomatous polyposis affords the opportunity to diagnose and treat duodenal tumors at an early stage, thereby, avoiding the dismal prognosis once invasive cancer has developed. 
Triiodothyronine-enhanced left ventricular function after ischemic injury. Hypothyroidism is associated with profound left ventricular dysfunction. Brain-dead organ donors and patients undergoing cardiopulmonary bypass are chemically hypothyroid with significantly reduced circulating free triiodothyronine (T3). To test the hypothesis that T3 enhances left ventricular function in a hormonally deficient environment, a total of 36 healthy New Zealand White rabbit hearts were studied using a modified Langendorff preparation with Krebs-Henseleit perfusate and intra-ventricular balloon. In 9 normal rabbit hearts a cumulative dose-response curve with logarithmically increasing doses of T3 was obtained. The vehicle solution for T3 dissolution served as control (n = 9). Left ventricular function was assessed from peak developed pressure at baseline and after T3 administration. Triiodothyronine had no effect in normal hearts on peak developed pressure or end-diastolic pressure. In 18 rabbits, the acute effect of T3 administration after ischemia was investigated. Preischemic left ventricular function was measured to serve as baseline, and hearts were subjected to 37 degrees C global ischemia. Triiodothyronine (n = 9) or vehicle (n = 9) was infused during reperfusion, and left ventricular peak developed pressure was measured at 30 and 60 minutes of reperfusion. Recovery of function (expressed as percent return of left ventricular peak developed pressure) was significantly improved within 15 minutes of reperfusion (65.0% +/- 2.1% versus 80.2% +/- 4.1%) and remained significantly improved throughout the reperfusion period (p less than 0.05 by analysis of variance). These data suggest that although T3 possesses no inotropic properties, it significantly improves postischemic left ventricular function. The rapidity of the functional improvement suggests that these effects may be due to plasma membrane-mediated mechanisms. 
Brain protection during circulatory arrest. Previous nuclear magnetic resonance studies in this laboratory have shown a beneficial biochemical effect of antegrade cerebroplegia (CP-A) during hypothermic circulatory arrest. This study compared CP-A with other methods of cerebral protection during hypothermic circulatory arrest to assess the clinical utility of this technique. Twenty-three sheep were divided into four groups: systemic hypothermia alone (SYST) and systemic hypothermia combined with external cranial cooling (EXTNL), retrograde cerebroplegia (CP-R), or CP-A. Cardiopulmonary bypass was started, and the sheep were cooled to 15 degrees C and subjected to 2 hours of circulatory arrest. Cardiopulmonary bypass was restarted, and the animals were rewarmed and weaned from cardiopulmonary bypass. Serial neurological examinations were performed and hourly scores assigned until the animals were extubated. Postanesthetic neurological scores improved in all groups throughout the 6-hour recovery period except the CP-R group. The improvement over time for these scores was similar for the EXTNL and CP-A groups and significantly better than for the SYST or CP-R groups (p = 0.004). The CP-A group had 5 of 7 animals with deficit-free survival despite the similarity in recovery of baseline brainstem function. We conclude that both antegrade infusion of cerebroplegia and external cranial cooling confer distinct cerebroprotective effects after a protracted period of hypothermic circulatory arrest when compared with the other methods studied. 
Diagnosis of cerebral amyloid angiopathy by enzyme-linked immunosorbent assay of cystatin C in cerebrospinal fluid. An abnormally low level of cystatin C in the cerebrospinal fluid is a diagnostic marker for the hereditary form of brain hemorrhage associated with amyloidosis that was first identified in Iceland. We developed an assay for cystatin C to use in the diagnosis of patients with cerebral amyloid angiopathy and brain hemorrhage. This test consists of a sandwich enzyme-linked immunosorbent assay using monoclonal mouse anticystatin C and polyclonal rabbit anticystatin C antibodies. The cystatin C level was assayed in cerebrospinal fluid samples from 29 patients with brain hemorrhage and 45 control patients with other neurological diseases. Fifteen patients with brain hemorrhage showed low cystatin C levels (less than or equal to 70 ng/ml) in a clinical setting in which the positive and negative findings were compatible with a diagnosis of cerebral amyloid angiopathy. Immunohistological examination of brain tissue obtained by biopsy from two of the 15 patients confirmed the diagnosis of cerebral amyloid angiopathy and identified the deposition of cystatin C and beta-protein. This enzyme-linked immunosorbent assay is simple to perform and may be useful for investigating patients suspected of having cerebral amyloid angiopathy with brain hemorrhage and the deposition of cystatin C. 
Pain on intradermal injection with lignocaine. The effect of concentration. Twenty ASA 1 volunteers were each injected intradermally with four solutions containing 0.2 ml of 0.5%, 1%, and 2% lignocaine and 0.9% saline to determine whether the pain experienced on injection was related to the concentration of local anaesthetic. A 10 cm linear analogue pain scoring system was used, and the solutions were ranked from most painful to least painful. There were no differences between the different concentrations of lignocaine and 0.9% saline in the severity of pain experienced. We conclude that any concentration of lignocaine may be used intradermally before inserting intravenous catheters without affecting the degree of pain experienced by that injection. 
Dissociation of second messenger activation by parathyroid hormone fragments in osteosarcoma cells. PTH activates multiple second messengers in its target cells, but the level at which the hormonal signal splits into different pathways is still unknown. To achieve insights on this issue, we have studied the structure-function relationship of PTH by analyzing the effects of bovine PTH-(1-34) [bPTH-(1-34)] and PTH fragments truncated at the N-terminus on the intracellular calcium concentration [( Ca2+]i) and cAMP production in the rat osteogenic sarcoma cell line UMR 106-01. [Ca2+]i was measured in single cells using fura-2. When exposed to 10(-7) M bPTH-(1-34), 20% of the cells responded with a transient increase in [Ca2+]i of variable amplitude. Equimolar doses of bPTH-(2-34), propionyl bPTH-(2-34) [(pbPTH-(2-34)], and bPTH-(3-34) also transiently increased [Ca2+]i, whereas both [tyrosine34]bPTH-(7-34) amide [bPTH-(7-34)] and bPTH-(30-34) were ineffective. The amplitude of the [Ca2+] i transients was dose-dependent, with threshold concentrations of 10(-10) M for bPTH-(1-34) and bPTH-(2-34), and 10(-9) M for bPTH-(3-34). The response rate to the active peptides ranged between 10-30%, without a clear dose-relatedness. A second addition of 10(-7) M bPTH-(1-34) to cells prestimulated with equimolar doses of bPTH-(2-34), pbPTH-(2-34), or bPTH-(3-34) produced another transient, whereas after exposure to 10(-7) M bPTH-(1-34), the cells were completely desensitized to a second homologous stimulation, suggesting that the binding affinity of the truncated peptides for the PTH receptor is lower than that of the intact bPTH-(1-34) fragment. In addition, both bPTH-(1-34) and bPTH-(2-34) dose-dependently stimulated cAMP production, but the former was more potent (ED50 = 10(-9) vs. 10(-7) M, respectively). On the contrary, pbPTH-(2-34), bPTH-(3-34), and bPTH-(7-34) had no effect on cAMP. Pretreating the cells with pertussis toxin to enhance cAMP responses via inhibition of Gi potentiated the effect of bPTH-(1-34) and bPTH-(2-34) and disclosed weak but detectable agonist action of pbPTH-(2-34). These results indicate that specific domains of the PTH molecule are linked to activation of different second messenger pathways; while the first two amino acids are indispensable for activating the cAMP system, generation of the [Ca2+]i signal appears to involve a longer domain, including the amino acid residue in position 3. 
Molecular evaluation of response to all-trans-retinoic acid therapy in patients with acute promyelocytic leukemia. The advent of retinoic acid (RA) in the treatment of acute promyelocytic leukemia (APL) has led to a high frequency of short-lasting complete remissions (CR). We studied the response to RA by molecularly analyzing the RA receptor alpha (RAR alpha) locus, which has recently been shown to be rearranged in all APLs. Southern blot analysis demonstrated that the RAR alpha rearrangements persisted in the APL samples containing maturing myeloid cells 2 to 3 weeks after the start of RA treatment, but disappeared after 5 to 8 weeks, when the patients achieved CR. Our investigations provide clear evidence that CR occurs at molecular level and that there is reconstitution of an apparently normal, nonclonal hematopoiesis. Further, it shows that RA acts by triggering differentiation rather than by exerting a cytotoxic effect on the leukemic clone. 
The role of intraluminal radiotherapy and concurrent 5-fluorouracil infusion in the management of carcinoma esophagus: a pilot study. Fifty patients with carcinoma of the esophagus were entered in a randomized pilot study to test the efficacy of intraluminal radiotherapy (ILRT) and concurrent 5-fluorouracil (5-FU) infusion. The median age was 65 years, with 80% having middle third lesions; in 62%, the lesions were longer than 5 cm. After external beam therapy of 50 Gy in 5 weeks, patients were randomized to receive chemotherapy. Significant improvement in dysphagia was recorded in 76% patients with complete response in 47 cases ranging from 6 to 27 months. The overall survival at 2 years was 15% with ILRT alone versus 22% with ILRT plus 5-FU infusion. 
From tissue angiotensin converting enzyme inhibition to antihypertensive effect. The renin-angiotensin system (RAS) has long been regarded as a classical hormonal system, with angiotensin II (ANG II) being the circulating effector peptide. In recent years, evidence for additional RAS in various organs, including vascular wall, kidney, adrenal gland, heart, and brain, has been obtained. Drugs interfering with the RAS such as the converting enzyme (CE) inhibitors may, therefore, not only inhibit the plasma RAS but also inhibit these tissue RAS. Such a "tissue" RAS inhibition has been repeatedly demonstrated in animal experiments, and in some cases it correlated better with the cardiovascular actions of the CE inhibitors than did inhibition of plasma RAS. In the vascular wall, a local inhibition of ANG II synthesis may contribute not only to the reduction of vascular tone but also to the marked regression of media hypertrophy seen after CE inhibitor treatment. Vascular ANG II generation by CE appears to occur almost exclusively at the luminal surface of the endothelium. Locally formed ANG II may then contribute to the pool of circulating ANG II (endocrine ANG II) or feed back to adjacent cells without being transported by the blood (paracrine ANG II). Thus, CE inhibitors may not have to penetrate into deeper layers of the vascular wall to inhibit the vascular RAS, but may rather prevent the paracrine actions of locally generated ANG II. 
Effect of clean intermittent catheterisation on radiological appearance of the upper urinary tract in children with myelomeningocele. Of the 102 consecutive children with myelomeningocele who were treated by intermittent catheterisation between 1977 and 1985, 89 were investigated with regard to the development of the upper urinary tract. The median follow-up period was 6.7 years. Dilatation and vesicoureteric reflux were assessed by means of repeated urography and voiding cystourethrography. Of the 49 children with normal radiology at the start of catheterisation, all but 2 remained normal. In 27 with isolated dilatation of the upper urinary tract or reflux at the start, 17 subsequently became normal. Dilatation together with reflux was seen in 13 patients at the start; 3 became normal, 4 still had reflux and in 6 patients both dilatation and reflux persisted. Intermittent catheterisation thus had a positive effect on the upper urinary tract in the vast majority of cases. In children with both dilatation and reflux, however, there is a risk of deterioration and they should be followed up closely. 
Helicobacter pylori-negative duodenal ulcer. Most patients with chronic duodenal ulcer (DU) craters have gastritis associated with Helicobacter pylori (HP), now thought to be the major cause of DU. A smaller proportion of DU patients have no detectable HP. In this study, we examined the frequency and causes of HP-negative duodenal ulcers. In 302 consecutive patients with endoscopic diagnosis of duodenal ulcer, 284 (94%) were found to have associated HP gastritis, whereas 18 (6%) were HP-negative on histology, culture, and urease test. The largest subgroup of HP-negative patients (8/18) was made up of those who had been taking nonsteroidal antiinflammatory drugs (NSAIDs), followed closely (4/18) by patients with recent intake of antibiotics. Causes of DU in the remaining subgroups included two patients with duodenal Crohn's disease, two with Gastrospirillum hominis infection, one with penetrating carcinoma of the pancreas and one with no detectable cause. We conclude that, although the most common causal factor of duodenal ulcer is HP, some 6% of DU's will be HP-negative, signaling unusual etiology. It is now important to identify the cause of duodenal ulcer so as to initiate appropriate therapy. 
Epitope map of neurofilament protein domains in cortical and peripheral nervous system Lewy bodies. A subset of demented elderly patients exhibit large numbers of cortical intraneuronal inclusions similar to the neurofilament (NF)-rich Lewy bodies (LB) found in pigmented subcortical neurons of patients with Parkinson's disease (PD). Because these cortical inclusions may contribute to the emergence of cognitive impairments in afflicted individuals, the authors mapped the distribution of NF epitopes in these so-called cortical LBs. This was done using ethanol-fixed tissues and a large library of monoclonal antibodies (MAbs) with well-characterized binding specificities to various regions of each NF triplet protein. Cortical LBs were examined by light, confocal, and electron microscopy, and they were compared with the subcortical LBs of PD and LBs in the peripheral nervous system (PNS). Monoclonal antibodies specific for the rod regions of each of the three NF subunits, or for phosphate-dependent and independent antigenic sites in the tail region of the high- (NF-H) and middle- (NF-M) molecular weight (Mr) NF subunits as well as other MAbs to the extreme COOH terminus of NF-L and NF-M or the head region of NF-M labeled a variable number of cortical LBs. Remarkably one of these anti-NF MAbs, RMO32, which recognized a phosphorylated epitope in the tail region of NF-M, immunolabeled nearly all cortical LBs, whereas each of the other anti-NF MAbs never labeled more than 10% of ubiquitin- or RMO32-positive cortical LBs. Further LBs in the PNS resembled those in the central nervous system (CNS) in their immunologic properties, and LBs in both sites were dominated by filamentous aggregates at the ultrastructural level. These findings suggest that NF proteins are profoundly altered during their incorporation into cortical and PNS LBs. Further the authors here identified immunologic and ultrastructural properties common to cortical LBs, PNS LBs, and classic substantia nigra LBs in PD. The accumulation of filamentous, perikaryal inclusions rich in NF proteins at diverse sites in the CNS and PNS of patients with a variety of neurodegenerative disorders suggests a widespread disruption of NF metabolism or transport. 
Neurosarcoidosis--demonstration of meningeal disease by gadolinium enhanced magnetic resonance imaging. Arriving at a firm diagnosis of neurosarcoidosis continues to pose serious problems, particularly when evidence of granulomatous disease outside the nervous system is lacking. The commonest mode of presentation of neurosarcoidosis is with cranial nerve palsies. Two cases of presumed neurosarcoidosis with cranial nerve palsies showed clear evidence of focal meningeal disease on gadolinium-DTPA enhanced MRI brain scans. Although not specific for sarcoidosis, this technique may be very useful in aiding the diagnosis in suspected cases. 
Interrelationship between histopathologic characteristics of melanoma and estrogen receptor status. To evaluate whether the increase in disease-free survival and survival previously reported for women with melanomas with estrogen receptors (ER) was a reflection of the histopathology of the primary melanoma, the interrelationship of histopathologic characteristics of 143 patients with such tumors was examined. The ER was assayed in the primary tumor from 44 patients and in 99 metastatic deposits from the other patients. Tumor thickness, level of invasion, prognostic index, mitoses/mm2, ulceration, vascular invasion, necrosis, histologic grade, preexisting nevus, and predominant malignant cell type were examined. There was no relationship between ER presence and any histopathologic characteristic examined, irrespective of the tumor source (primary or metastatic). Examination of histopathologic characteristics as a function of sex and receptor status showed a slight but insignificant predominance of more well-differentiated, thinner tumors in women whose lesions were positive for the ER. These results suggest that the increased disease-free survival in patients with ER-positive lesions is not attributable to the pathologic characteristics of the primary tumor examined during this study. 
Benign positional vertigo: incidence and prognosis in a population-based study in Olmsted County, Minnesota. A retrospective review of our population-based medical records linkage system for residents of Olmsted County, Minnesota, revealed 53 patients (34 women and 19 men; mean age, 51 years) with newly diagnosed benign positional vertigo in 1984. The age- and sex-adjusted incidence was 64 per 100,000 population per year (95% confidence interval, 46 to 81 per 100,000). The incidence of benign positional vertigo increased by 38% with each decade of life (95% confidence interval, 23 to 54%). One patient had an initial stroke during follow-up; thus, the relative risk for new stroke associated with benign positional vertigo was 1.62 (95% confidence interval, 0.04 to 8.98) in comparison with the expected occurrence based on incidence rates for an age- and sex-adjusted control population. The observed survival among the 53 Olmsted County residents with benign positional vertigo diagnosed in 1984 was not significantly different from that of an age- and sex-matched general population. Patients with benign positional vertigo seem to have a good prognosis. 
Update: drug therapy for acute myocardial infarction. Acute myocardial infarction is potentially a highly treatable disease. Immediate interventions are directed to decreasing tissue hypoxia with oxygen and improving bloodflow to ischemic myocardium using nitrates and thrombolytic agents. Cardiac workload should be reduced by eliminating endogenous catecholamine release with analgesia and sedation, and beta blockade in patients without CHF to decrease heart rate and myocardial oxygen demand. Treatment of the complications of AMI include dysrhythmia prophylaxis, monitoring and specific therapy. Treatment of pump failure includes using vasodilators, vasopressors and positive inotropic agents. Early recognition and timely initiation of appropriate therapy should be every physician's goal. 
Optic nerve sheath decompression for nonarteritic ischemic optic neuropathy improves multiple visual function measurements. Optic nerve sheath decompression was performed in seven patients with nonarteritic anterior ischemic optic neuropathy. Visual function was evaluated by measurement of visual acuity with standardized Early Treatment Diabetic Retinopathy Study charts, color vision testing, quantitation of relative afferent pupillary defects with neutral-density filters, and Goldmann and Humphrey perimetry. Visual acuity improved markedly in all patients (at least doubling of the visual angle); the peripheral visual field expanded by at least 20 degrees (as measured by Goldmann perimetry) in six patients. Three patients also experienced marked improvement in color vision, relative afferent pupillary defect, and foveal sensitivity. Our experience supports the possible beneficial effect of optic nerve sheath decompression in patients with nonarteritic anterior ischemic optic neuropathy. 
On the mechanisms of ventricular tachycardia acceleration during programmed electrical stimulation. BACKGROUND. The pathophysiological mechanisms leading to acceleration of ventricular tachycardia (VT) are still unclear. METHODS AND RESULTS. High-resolution epicardial mapping was used to study the mechanisms of VT acceleration by programmed electrical stimulation (PES) in a model of sustained reentrant VT in Langendorff-perfused rabbit hearts (n = 40). Three different mechanisms responsible for acceleration of VT were identified: 1) induction of double-wave reentry (n = 6), defined as the occurrence of two successive activation waves circulating in the same direction in the same circuit; 2) change to a functionally determined circuit (n = 4), defined as reentry of the impulse around a functional line of block without involvement of a fixed obstacle; and 3) change of the reentrant circuit to reentry within a different, faster anatomic pathway (n = 3). Analysis of 81 episodes of sustained monomorphic VT induced by PES in 74 patients with clinically documented sustained VT in the setting of chronic coronary artery disease showed that in 22 episodes VT was suddenly accelerated by PES (mean cycle length, from 345 +/- 73 to 277 +/- 71 msec, p less than 0.01). CONCLUSIONS. With the observations made in the experimental model, the following tentative classification of the mechanisms of VT acceleration of the 22 episodes was made: 1) induction of double-wave reentry in two, 2) change to a functionally determined circuit in four, and 3) change to reentry within a faster anatomic circuit in 16. Simple criteria suggest that these mechanisms may apply in the clinical situation. 
Oxygen transport measurements to evaluate tissue perfusion and titrate therapy: dobutamine and dopamine effects. BACKGROUND: Increased cardiac index, oxygen delivery (DO2), and oxygen consumption (VO2) patterns were shown to characterize the physiologic status of surviving high-risk surgical patients, and indicate increased metabolic needs; relatively normal DO2 and VO2 values were found to characterize the sequential pattern of nonsurvivors who developed an early oxygen debt followed by lethal organ failure. The cardiac index, DO2, and VO2 values empirically determined from survivors' patterns were shown to improve outcome in prospective randomized trials. The present study considers these criteria to evaluate the tissue perfusion status as well as the effects of therapy on tissue perfusion and oxygenation. OBJECTIVE: To summarize new information on the temporal patterns of DO2, VO2, and oxygen debt on outcome and the effects of fluids and inotropes on these patterns in a wide range of clinical, temporal, and physiologic conditions. DESIGN: Descriptive analysis based on data gathered prospectively using a specified protocol. PATIENTS: High-risk patients with accidental or elective surgical trauma, and patients with or without sepsis or septic shock and organ failure. SETTING: University-run county hospital with a large trauma service. INTERVENTIONS: Fluids, dobutamine, and dopamine at various times and at various doses throughout critical illness of postoperative, posttraumatic, septic, and hypovolemic patients with and without lethal and nonlethal organ failure. MEASUREMENTS AND MAIN RESULTS: The pattern of DO2 plotted against the corresponding VO2 values in 437 consecutive critically ill surgical patients showed a wide variability and poor correlation probably because complex clinical conditions may obscure the supply-dependent and supply-independent VO2 relationships observed in normal dogs bled or given bacterial infusions. However, the use of specific therapy by well-defined protocols was shown to provide objective evidence of efficacy. Significant increases in DO2 and VO2 were previously shown after whole blood, packed red cells, and colloid administration, but not after crystalloid administration. Dobutamine administration in 715 circumstances in postoperative, traumatic, septic patients and patients with adult respiratory distress syndrome, renal failure, and multiple organ failure significantly improved DO2 and VO2. Dopamine under comparable conditions produced less improvement in DO2 and VO2 than that of dobutamine; most of the VO2 changes were not significant. CONCLUSIONS: The monitored patterns of cardiac index, DO2, and VO2 may be used to evaluate the adequacy of tissue perfusion as well as the relative effectiveness of alternative therapies. Second, these physiologic criteria may be used to titrate therapy in order to achieve optimal outcome. Third, after colloids optimally expand the plasma volume, dobutamine may be used to enhance flow and the distribution of flow in order to improve tissue oxygenation. Vasodilators may be used when hypertensive episodes occur or there is an inadequate response to inotropic agents. Vasopressors are used as a last resort, usually in the terminal or preterminal state. 
New method for dealing with late-presenting spontaneous esophageal ruptures. A new technique is described for dealing with late-presenting spontaneous esophageal ruptures. This method requires only a short period of general anesthesia to drain the periesophageal abscess by a drainage tube inserted into the abscess cavity from the esophagus with the aid of a gastroscope and fluoroscopy. Gastric fluids are diverted from the esophageal rupture with a gastrostomy, and a jejunostomy is used for enteral feeding. The esophagus is retained, and closure of the fistula with resumption of normal swallowing is documented with serial sinograms. 
Nutrition: its relationship to orthopedic infections. The malnutrition of orthopedic surgical patients plays an important role in the development of complications, including infection. A high index of suspicion that malnutrition exists or will soon exist in patients who are subjected to significant stress, trauma, or surgery will lead the clinician to take measures to avoid further protein calorie deficits and replenish the patient's nutritional needs. There are many pathways in which malnutrition causes a propensity for infection, and these have been discussed. Meeting the patient's nutritional needs should avoid some of the complications of infections in orthopedic surgery. 
Tissue oxygenation in hemorrhagic shock measured as transcutaneous oxygen tension, subcutaneous oxygen tension, and gastrointestinal intramucosal pH in pigs BACKGROUND AND METHODS: Tissue oxygenation, measured in peripheral tissue as transcutaneous PO2 (PtCO2) and subcutaneous PO2, was compared with the oxygenation in GI mucosa, which was measured as intramucosal wall pH (pHi), during experimental hemorrhagic shock and resuscitation in pigs. The pigs were hemorrhaged stepwise to a BP of 80 and 45 mm Hg, followed by retransfusion. PtCO2 was measured in the groin and subcutaneous PO2 was measured in the hip region. Intraluminal PCO2 was measured in the stomach, in the small intestine, and the sigmoid colon using silicone catheters. A simultaneous determination of arterial blood HCO3 concentration allowed pHi to be calculated using Henderson-Hasselbalch equation. Cardiac output was determined by thermodilution, and oxygen delivery (DO2) was calculated. RESULTS: Early indications of shock were decreases in PtCO2 and intestinal pHi (p less than .01). All measured variables decreased at the second step of bleeding. PtCO2 and subcutaneous PO2 was correlated to DO2 through the entire experiment (r2 = .25 and .49, respectively). Also, the pHi of the small intestine and the sigmoid colon correlated with DO2 (r2 = .36 and .25, respectively). PtCO2 and subcutaneous PO2 correlated with pHi in the small intestine and sigmoid colon. CONCLUSIONS: PtCO2 and pHi in the small intestine and sigmoid colon were the variables that most rapidly indicated blood volume loss. Subcutaneous PO2 and PtCO2, and small intestine and sigmoid colon pHi were correlated to total body oxygen transport. Peripheral tissue perfusion followed intestinal perfusion to some extent. 
Mechanical cardiac valvular prostheses. Mechanical cardiac valvular prostheses currently enjoy a 60% to 40% market-share advantage over tissue prostheses in the United States and worldwide. Only the Starr-Edwards caged Silastic (Dow Corning) ball, Medtronic-Hall, St. Jude Medical, and Omniscience valves remain available in the United States. Although each valve has certain advantages and disadvantages, no design has achieved functional mechanical perfection. Late follow-up of valve-related complications from the literature favors the St. Jude Medical and Medtronic-Hall valves. 
Sudden death due to disease flare with luteinizing hormone-releasing hormone agonist therapy for carcinoma of the prostate. Luteinizing hormone-releasing hormone agonist therapy for prostate cancer is a new method of management for metastatic disease. During the initial 1 to 2-week period of administration an increase in serum testosterone concentration can lead to an exacerbation of clinical symptoms (flare phenomenon). Two patients are summarized who received luteinizing hormone-releasing hormone agonist therapy without flare blockade and died suddenly during month 1 of therapy. A review of 765 patients in 9 series found 10.9% who suffered disease flare and 15 who died during disease flare. Of these 17 patients 12 were similar to our 2. These data suggest that any patient placed on luteinizing hormone-releasing hormone agonist therapy for prostate cancer merits some form of flare blockade during the initial 1 or 2 months of therapy. 
A nurse-managed special care unit. The authors describe the first year of operation of a nurse-managed intensive care unit (ICU). Concerned with the problems, costs, and inadequacies of caring for long-term patients in traditional ICUs, nurse administrators designed a special care unit that incorporates a physical design facilitating family involvement and rehabilitative care, registered nurse case management, and a shared governance management philosophy. Compared with traditional ICUs, the effectiveness of the special care unit is tested in terms of patient and nurse outcomes. Implications of this innovation for health-care delivery systems and the nursing profession are discussed. 
Resting energy expenditure in chronic cardiac failure. 1. Resting energy expenditure has previously been shown to be elevated in the acute phase of heart failure, but the situation in the compensated state of chronic cardiac failure is unclear. Resting energy expenditure was assessed in 14 patients with stable chronic cardiac failure and 14 matched control subjects by using indirect calorimetry. 2. Resting energy expenditure was significantly elevated in the patients with chronic cardiac failure (112.6 +/- 18.1 versus 87.1 +/- 12.2 kJ day-1 kg-1 total body weight, P less than 0.0002; mean +/- SD) as were resting O2 consumption (3.88 +/- 0.64 versus 3.00 +/- 0.43 ml min-1 kg-1, P less than 0.0002), ventilation (164 +/- 40.3 versus 104 +/- 16.2 ml min-1 kg-1, P less than 0.0001) and heart rate (85.8 +/- 16.9 versus 66.6 +/- 6.9 beats/min, P less than 0.001). Both the resting plasma concentration of noradrenaline (4.48 +/- 1.52 versus 2.28 +/- 0.96 nmol/l, P less than 0.0001) and the serum concentration of free fatty acids (0.78 +/- 0.21 versus 0.57 +/- 0.27 mmol/l, P less than 0.03) were greater in the patients with chronic cardiac failure. Analysis of covariance indicated that most of the difference in resting energy expenditure could be accounted for by the elevated ventilation in the patients with chronic cardiac failure. Arm muscle area, an index of wasting, was lower in the patients with chronic cardiac failure (39.1 +/- 13.1 versus 50.5 +/- 9.4 cm2, P less than 0.02) and resting energy expenditure was found to account for some of this difference. 3. We conclude that an elevated basal metabolism occurs in chronic cardiac failure. 
Complication of a penile prosthesis reservoir: venous compression masquerading as a deep venous thrombosis. We report a case of vascular compromise secondary to the reservoir of an inflatable penile prosthesis. The problem masqueraded as deep venous thrombosis in the lower extremity of a patient 3 years after a spinal cord injury. 
Microangiopathy of the brain, retina, and ear: improvement without immunosuppressive therapy. We describe a pregnant young woman with branch retinal arteriolar occlusions, encephalopathy, and hearing loss in whom we demonstrated a patent foramen ovale. She improved while receiving anticoagulants and no immunosuppressive therapy. The microangiopathic syndrome of retinopathy, encephalopathy, and deafness may be due to a disturbance of coagulation and/or microembolism. 
Choledocholithiasis in acute gallstone pancreatitis. Incidence and clinical significance. A prospective study of choledocholithiasis was performed using 110 patients with presumptive diagnoses of acute gallstone pancreatitis. The incidence of migrating and persistent bile duct stones was determined using stool screening and intraoperative cholangiography, and the clinical significance of continued stone obstruction of the papilla was investigated using ultrasound assessment of migration time and a second evaluation of prognostic signs. Pancreatic inflammation was confirmed at surgery in 51 patients, of whom only 27 had stones in the stools (n = 22) or the bile duct (n = 5), suggesting that choledocholithiasis may not be the sole triggering factor of acute gallstone pancreatitis. Neither delayed migration nor persistent stone obstruction of the papilla promoted pancreatic inflammation. 
A temperature-dependent rabbit model for production of dermal lesions by Haemophilus ducreyi. The fact that optimal in vitro growth of Haemophilus ducreyi occurs at 33 degrees C prompted evaluation of the effect of temperature on the ability of this organism to produce skin lesions in rabbits after intradermal inoculation. Animals housed at a reduced ambient temperature (15-17 degrees C) consistently developed necrotic lesions when injected intradermally with 10(5) cfu of H. ducreyi; this inoculum did not produce necrotic lesions in animals housed at normal room temperature (23-25 degrees C). Lesion production in this new model was dependent on both viability of the H. ducreyi inoculum and replication of these organisms after intradermal injection. Histopathologic examination of the lesions revealed that H. ducreyi infection of the rabbit dermis evolves from an acute inflammatory reaction to abscess formation. Evaluation of three additional strains of H. ducreyi in this model confirmed that lesion formation was not bacterial strain-dependent. This new temperature-dependent rabbit model for productive H. ducreyi infection will facilitate investigation of the molecular pathogenesis of chancroid. 
Cutaneous type of adult T cell leukemia/lymphoma in a French West Indian woman. Clonal rearrangement of T-cell receptor beta and gamma genes and monoclonal integration of HTLV-I proviral DNA in the skin infiltrate. A 45-year-old woman, a native of the French West Indies who had lived in France since 1973, developed multiple cutaneous plaques and nodules in 1987. Histopathologic studies revealed dermal infiltration with mature activated T cells (CD4+, CD25+, DR+) with nuclear convolutions and epidermatotropisim. High titers of specific human T lymphotropic virus (HTLV)-I antibodies were detected in the serum. Molecular analysis of DNA extracted from the skin tumor biopsy specimen showed a clonal integration of an HTLV-I provirus and a T-cell clonal population as demonstrated by T-cell receptor beta and gamma gene rearrangement studies. Neither HTLV-I provirus nor T-cell receptor rearrangements were detected in peripheral blood mononuclear cells DNA despite the presence of rare adult T cell leukemia cells (less than 1%) and a small excess of DR-expressing cells, and detection of HTLV-I Pol and Px sequences by in vitro gene amplification. In this case only gene analysis of the skin lesions made possible an early diagnosis of a cutaneous adult T cell leukemia. This illustrates the need for such molecular studies to differentiate, in HTLV-I seropositive patients from endemic areas, a HTLV-I-induced T cell lymphoma from HTLV-I-nonrelated cutaneous T cell lymphomas. 
Luteinizing hormone (LH) secretory burst duration is independent from LH, prolactin, or gonadal steroid plasma levels in amenorrheic women. The possible presence of LH pulsatile secretion has been studied in patients with hypothalamic amenorrhea [LH plasma levels, less than 3 (n = 35) or greater than 3 IU/L (n = 18)], amenorrhea associated with hyperandrogenemia (n = 31), or hyperprolactinemia (n = 10). Patients were sampled every 10 min for 4 h, and LH plasma concentrations were determined by the use of an immunofluorimetric assay. The program Detect was used for both pulse detection and data deconvolution, i.e. for instantaneous secretory rate computation, on LH time series. The presence of episodic LH secretion was observed in all patients, and LH pulse frequency ranged between 3.5 +/- 0.3 and 3.8 +/- 0.2 peaks/4 h among the four groups. LH pulse amplitude was significantly reduced in patients affected by hypothalamic amenorrhea with LH plasma levels lower than 3 IU/L (0.7 +/- 0.1 IU/L; P less than 0.01) and significantly increased in patients with hyperandrogenic amenorrhea (6.8 +/- 0.3 IU/L; P less than 0.01) compared to levels in the other groups under study. Instantaneous secretory rate computation permitted the optimal resolution of the secretory events and demonstrated that the duration of gonadotrope secretory bursts ranged from 22.8 +/- 1.4 to 26.8 +/- 2.3 min in amenorrheic patients and did not depend on LH, PRL, or sex steroid plasma levels. In conclusion, the present study shows the presence of significant LH pulsatile release in amenorrheic patients, suggesting that in amenorrheic, as in normally cycling, women the secretory bursts from the gonadotropes have the same duration, despite the plasma LH, PRL, or steroid hormone levels. 
Carcinoid tumor of the common bile duct: evidence for its origin in metaplastic endocrine cells. Carcinoid tumors of the extrahepatic bile ducts are extremely rare neoplasms. The authors report the case of a 36-yr-old male patient with a carcinoid tumor that arose in the common hepatic bile duct. The non-neoplastic mucosa showed areas of gastric and intestinal metaplasia that included scattered argyrophil endocrine cells. Since the normal mucosa of the bile ducts lacks the latter type of cells, this case provides evidence for the first time that carcinoid tumors of this anatomic site probably originate from metaplastic endocrine cells. 
Occult pontine glioma in a patient with hemifacial spasm. Hemifacial spasm due to an intracranial mass lesion is rare. We describe a 29-year-old man with hemifacial spasm successfully treated with botulinum A toxin injections for 2 years. The development of acquired diplopia secondary to acquired sixth cranial nerve palsy prompted investigation. Computed tomography done at the time of original diagnosis and on three other occasions (concentrating on the brain stem and cerebellopontine angle) failed to demonstrate an intracranial mass lesion. Magnetic resonance imaging (MRI) showed a large mass lesion in the pons presumed to be a glioma. Patients with hemifacial spasm who have atypical features, especially those with associated neurologic findings, should be screened for tumours. Our case illustrates the superiority of MRI in demonstrating pontine gliomas causing hemifacial spasm. 
Hyperinsulinaemia in thyrotoxic hypokalaemic periodic paralysis. To test the hypothesis that there is an abnormal serum insulin response to a carbohydrate load in thyrotoxic hypokalaemic periodic paralysis (THPP), 18 men with THPP and 15 with uncomplicated thyrotoxicosis were studied during an oral glucose tolerance test. The THPP group had significantly higher fasting insulin concentrations (27.6 [3.6] vs 13.4 [1.8] mU/l; p less than 0.005) and a higher overall insulin response to oral glucose (p less than 0.001 by ANOVA) than the thyrotoxicosis group. There were no significant differences in fasting or stimulated glucose. Hyperinsulinaemia may be an important factor in the precipitation of acute paralysis in THPP. 
Blunt trauma-induced pacemaker failure. A 54-year-old man with an artificial pacemaker sustained blunt trauma to his chest when he was struck with a baseball bat. Within 15 minutes after the injury, the patient experienced cardiovascular collapse. His pacemaker failed, and he required insertion of a temporary transvenous pacemaker. At surgery, the defect was traced to failure of the pulse generator, a rare cause of pacemaker failure. Emergency department evaluation should include prompt and continuous ECG monitoring, an overpenetrated chest radiograph, and telemetry evaluation after discharge. 
MR imaging in fibromatosis: results in 26 patients with pathologic correlation. Fibromatoses are a diverse group of soft-tissue lesions that have been inconsistently categorized and treated. The purpose of our study was to establish the range of appearances of fibromatoses on MR images and perform a pathologic correlation to explain the variable signal-intensity patterns. During a 3-year period, 26 patients with deep fibromatoses were examined with MR. The MR images were evaluated for signal-intensity characteristics, and findings were correlated retrospectively with the pathologic diagnoses. The results showed that the MR appearance of fibromatoses is similar to that of other soft-tissue lesions, and the signal intensities vary greatly from lesion to lesion and within lesions themselves. The fibromatoses were either hyperintense, isointense, hypointense, or of mixed signal intensity relative to adjacent skeletal muscle. The hypointense areas appear to be zones of hypocellularity and dense collagen deposition. Microscopically all of the lesions invaded adjacent structures, but the MR appearances of the margins varied and were judged to be well demarcated (n = 14), intermediate (n = 5), or poorly demarcated (n = 6). Our experience shows that fibromatoses have a variable MR appearance no different from that of other soft-tissue lesions, and this variability reflects the composition and cellularity of the lesions. 
GLI3 zinc-finger gene interrupted by translocations in Greig syndrome families. The Greig cephalopolysyndactyly syndrome (GCPS) is an autosomal dominant disorder affecting limb and craniofacial development in humans. GCPS-affected individuals are characterized by postaxial polysyndactyly of hands, preaxial polysyndactyly of feet, macroephaly, a broad base of the nose with mild hypertelorism and a prominent forehead. The genetic locus has been pinpointed to chromosome 7p13 by three balanced translocations associated with GCPS in different families. This assignment is corroborated by the detection of two sporadic GCPS cases carrying overlapping deletions in 7p13 (ref. 7), as well as by tight linkage of GCPS to the epidermal growth factor receptor gene in 7p12-13 (ref. 8). Of the genes that map to this region, those encoding T cell receptor-gamma, interferon-beta 2, epidermal growth factor receptor, and Hox1.4, a potential candidate gene for GCPS, have been excluded from the region in which the deletions overlap. Here we show that two of the three translocations interup the GLI3 gene, a zinc-finger gene of the GLI-Kruppel family already localized to 7p13 (refs 5, 6). The breakpoints are within the first third of the coding sequence. In the third translocation, chromosome 7 is broken at about 10 kilobases downstream of the 3' end of GLI3. Our results indicate that mutations disturbing normal GLI3 expression may have a causative role in GCPS. 
Supraglottic carcinoma: impact of radiation therapy on outcome of patients with positive margins and extracapsular nodal disease. Seventy-nine patients with supraglottic carcinoma treated between 1966 and 1985 are reviewed. All patients were treated with surgery and postoperative radiation therapy. Thirty-five percent of the patients had positive margins at the site of resection of the primary tumor. Of the 25 patients who had positive nodal disease, 13 patients (52%) had either extracapsular extension or soft-tissue or adjacent organ invasion, referred to in composite as "grave signs." The median follow-up of the patients was 4.9 years and all patients were followed for a minimum of 3 years. The disease-free survival for all patients was 76% at 2 years and 71% at 3 years. The locoregional control rate for all patients was 70%. This study demonstrates that there is no difference in local recurrence or disease-free survival, or time to recurrence relative to the status of the surgical margins, which may be a benefit of the postoperative radiation therapy. This study also demonstrates that there is an increase in the number of patients with grave signs with increasing nodal stage. The rate of neck recurrence in patients with grave signs was substantially higher (54%) than in patients without grave signs (8%), even though these patients also had positive lymph nodes. Interestingly, there was also a higher rate of local recurrence among patients who had grave signs. Patients receiving doses higher than 6000 cGy to the primary site had fewer local failures, although within each group of patients with positive or negative surgical margins the differences in survival were minimal. 
Comparison of the Radiation Therapy Oncology Group and American Joint Committee on Cancer staging systems among patients with non-small cell lung cancer receiving hyperfractionated radiation therapy. A report of the Radiation Therapy Oncology Group protocol 83-11. Since 1973, the Radiation Therapy Oncology Group (RTOG) has staged and stratified patients in non-small cell lung cancer (NSCLC) protocols according to the RTOG staging system. In 1985, the American Joint Committee on Cancer (AJCC) revised its lung cancer staging system, with the principle differences from the RTOG system being the staging of involvement of the chest wall and of contralateral mediastinal and hilar lymph nodes. To determine if the AJCC system discriminated outcome differently than the RTOG system in a nonoperative series, all 850 evaluable patients treated with hyperfractionated radiation therapy (RT) on the RTOG protocol 83-11 were restaged by the AJCC system. There was 67% agreement in patient distribution between the following comparable stages in each system: RTOG Stage II/AJCC Stage II; RTOG Stage III/AJCC Stage IIIA; and RTOG Stage IV/AJCC Stage IIIB. Both systems successfully predicted for survival (P less than 0.001), although the RTOG staging was more discriminating (relative risk ratios, 1.59 versus 1.38). Among the 507 favorable patients (those with less than or equal to 5% weight loss and Karnofsky performance status [KPS] of 70 to 100), the RTOG staging was also more predictive (P = 0.004 versus P = 0.01). When RTOG Stage III (462 patients) was divided into those without contralateral mediastinal or hilar adenopathy (AJCC Stage II/IIIA) and those with (AJCC Stage IIIB), a significant survival (P = 0.0001) was noted with 2-year survival rates of 26% versus 4%, respectively. When AJCC Stage IIIA (348 patients) was divided into the patients without chest wall invasion (RTOG Stage II/III) and those with (RTOG Stage IV), a difference in 2-year survival of 22% versus 10% was observed (P = 0.002). Although both staging systems independently predict for survival, a fusion of both staging systems is the most discriminating of outcome. Future nonoperative studies in locally advanced NSCLC should stratify for contralateral nodal involvement (per AJCC staging) and chest wall invasion (per RTOG staging). 
Survival after resection of carcinoma of the splenic flexure. Nine hundred ten patients undergoing colectomy for colon cancer were studied retrospectively. Seventy-four cancers (8 percent) were located at the splenic flexure. The stage at presentation was no different between splenic flexure cancers and colon carcinomas at other sites. Although splenic flexure cancers had twice the incidence of obstruction as did other colon cancers and obstruction in the overall series adversely affected survival, there was no difference in survival between splenic flexure cancer patients and patients with other colon cancers. 
Cortical magnetic resonance imaging changes in elderly inpatients with major depression. OBJECTIVE: The purpose of the study was to determine if magnetic resonance imaging (MRI) scans of elderly depressed patients differ from MRI scans of age-matched control subjects and age-matched patients with Alzheimer's disease. METHOD: The authors studied 21 patients 60 years or older with major depression, 16 patients with Alzheimer's disease, and 14 age-matched control subjects. RESULTS: Compared to control subjects, depressed patients had greater cerebral sulcal and temporal sulcal atrophy; larger sylvian fissures, lateral ventricles, third ventricles, and temporal horns; and greater severity of subcortical white matter lesions. Depressed patients also had more basal ganglia lesions but similar levels of periventricular hyperintensity. There were no differences between depressed patients with and without delusions on any MRI measure. Depressed patients who received ECT had more temporal horn atrophy and greater subcortical abnormality summary scores than normal subjects. Cortical sulcal atrophy correlated with age at onset of depression. CONCLUSIONS: The findings suggest that elderly hospitalized depressed patients have greater cortical as well as subcortical atrophy and more basal ganglia lesions than age-matched normal control subjects. The correlation of these abnormalities with outcome remains unknown. 
Capsaicin-sensitive nerves mediate esophageal mucosal protection. The esophageal mucosa is exposed to damaging agents both by ingestion and reflux. Using our in vivo rabbit model of esophagitis, we have observed that acute luminal exposure (within 1 to 5 minutes) to potentially harmful agents, such as acid, bile, or ethanol, induces a rapid increase in mucosal blood flow; whereas prolonged exposure (10 to 60 minutes) results in mucosal injury and ablation of blood flow. We have also shown that capsaicin-sensitive mucosal afferent nerves can modulate esophageal blood flow. These findings led us to hypothesize that the reactive increase in blood flow induced by luminal agents represents a mechanism of protection mediated by capsaicin-sensitive nerves. The objective of these experiments was to determine if luminal capsaicin, a specific probe for visceral afferent nerves, could both preserve mucosal blood flow and protect against ethanol injury. Rabbits were subjected to luminal instillation of 50% ethanol with or without 1% capsaicin. Blood flow was measured with microspheres at baseline and after 2 and 10 minutes. Rabbits exposed only to ethanol developed severe mucosal injury coincident with near ablation of mucosal blood flow. In contrast, rabbits exposed to ethanol with capsaicin showed protection of the epithelium with a sixfold increase in mucosal blood flow. We conclude that capsaicin-sensitive nerves in the esophagus are local effectors of mucosal protection by virtue of preserving blood flow. 
Paraprosthetic leak: a complication of cardiac valve replacement. Paraprosthetic leak (PPL) is a rare but potentially serious complication of cardiac valve replacement. Between 1974 and 1988, 1175 prosthetic valves were implanted in 1026 patients by one cardiac surgeon at St. Thomas' Hospital, London. Of these 539 (52.5%) were aortic (AVR), 334 (32.6%) mitral (MVR), 7 (0.7%) tricuspid, and 144 (14%) AV and MV double valve replacements (DVR). There were only 2 triple valve replacements. The prosthetic valves implanted were the Starr-Edwards (7%), Bjork Shiley (11.8%), Lillehei-Kaster (23%), Carpentier-Edwards bioprosthesis (35.2%), Duromedics bileaflet (16.4%) and a variety of other mechanical and bioprosthetic valves (6.6%). Over the 15 year period there were a total of 82 (7%) valve failures of which PPL was diagnosed in 29 (2.5%) valves in 24 patients. Presenting features included cardiac decompensation in 72%, bacterial endocarditis in 12% and haemolytic anaemia in 12%. One patient (4%) had no symptoms. Nineteen patients underwent re-operation. Median time to re-operation was 15 months (range 1-65 months) with a re-operative mortality of 22%. Clinical evidence of prosthetic valve infection was found in 79% of MVR and 67% of AVR. A heavily calcified aortic annulus, found in 47% of patients, may also have contributed to PPL after AVR. 
Sun-related skin diseases. Severe photoaging of the skin, which may be caused by exposure to both natural and artificial ultraviolet light, ultimately results in actinic keratoses and cancer. Cancers are common on the head, neck, arms, and hands. Because of the potential for metastasis, squamous cell carcinomas generally require surgical excision and histologic examination. Although metastasis is rare with basal cell carcinoma, neglected lesions around the eyes, nose, or ears can invade bone, nerves, and cartilage and may cause death. Avoidance of sun, physical protection, and regular use of sunscreens are recommended. 
From Papanicolaou to Bethesda: the rationale for a new cervical cytologic classification. The Bethesda System for reporting cervical/vaginal diagnoses was introduced to replace the numerical Papanicolaou class designations, thereby facilitating precise communication between cytopathologist and clinician. The terminology for squamous epithelial lesions includes the following categories: 1) atypical squamous cells of undetermined significance; 2) squamous intraepithelial lesion (SIL), which encompasses the spectrum of squamous cell carcinoma precursors, divided into low-grade SIL (human papillomavirus [HPV]-associated cellular changes, mild dysplasia, and cervical intraepithelial neoplasia [CIN] I) and high-grade SIL (moderate dysplasia, severe dysplasia, and carcinoma in situ and CIN II and III); and 3) squamous cell carcinoma. The rationale for including HPV-related changes (koilocytosis) with CIN I within low-grade SIL is based on the morphologic, behavioral, and virologic similarity of these two lesions, which precludes their separation in a consistent and reliable fashion. For the same reasons, CIN II and III lesions have been combined within the category of high-grade SIL. The term "atypical squamous cells of undetermined significance" is used for cytologic findings that do not fulfill the criteria for defined benign reactive changes or SIL. Therefore, this term is more restricted in usage as compared with the wide range of interpretations previously ascribed to "atypia" or "inflammatory atypia.". 
Influence of balloon size and stenosis morphology on immediate and delayed elastic recoil after percutaneous transluminal coronary angioplasty. After successful coronary angioplasty, the minimal luminal diameter of the dilated coronary artery segment is generally smaller than the diameter of the largest balloon catheter at the maximal inflation pressure. The determinants of this phenomenon were studied in 28 patients. Biplane angiograms were obtained after intracoronary administration of isosorbide dinitrate (1 mg) before, immediately and 24 h after coronary angioplasty. Balloon and coronary luminal diameters were measured by automated contour detection. Immediately after the procedure, the difference between inflated balloon diameter and minimal luminal diameter averaged 0.93 +/- 0.43 mm for the entire group and was greater both in eccentric stenoses (1.13 +/- 0.39 vs. 0.70 +/- 0.36 mm; p less than 0.01) and after angioplasty with an oversized balloon (1.20 +/- 0.37 vs. 0.71 +/- 0.33 mm; p less than 0.005). At 24 h, the balloon - minimal luminal diameter difference was unchanged at the group level (0.86 +/- 0.38 mm, but the minimal luminal diameter increased significantly in the subgroup of coronary segments dilated with an oversized balloon (1.97 +/- 0.37 vs. 1.81 +/- 0.28 mm; p less than 0.05). Thus, the difference between the minimal diameter of a dilated coronary segment immediately after a successful coronary balloon angioplasty procedure and the maximal diameter of the inflated balloon catheter is dependent both on eccentricity of the stenosis and on the balloon/artery diameter ratio. Moreover, the increase in minimal luminal diameter 24 h after angioplasty performed with an oversized balloon suggest that in addition to elastic recoil partly reversible factors related to vessel barotrauma are involved. 
Immunoreactive transforming growth factor alpha is commonly present in colorectal neoplasia. Surgical specimens from 19 patients with invasive colorectal cancers and 12 specimens of normal mucosa from the same patients were examined immunohistochemically for the production of the immunoreactive (IR-) transforming growth factor (TGF)-alpha and IR-epidermal growth factor (EGF) with an anti-TGF-alpha monoclonal antibody (MAb) OAL-MTG01 and anti-EGF MAb KEM-10. Immunoreactive TGF-alpha was detected in 16 (84.2%) of 19 colorectal cancers. In contrast, there was no IR-TGF-alpha in the gland cells of normal mucosa. Immunoreactive EGF was detected in 7 (36.8%) of 19 colorectal cancers and 1 (8.3%) of 12 cases of normal mucosa. The production of both IR-TGF-alpha and IR-EGF in colorectal cancer did not differ by histologic type and Dukes' stage. Immunoreactive TGF-alpha was detected at significantly higher incidence than IR-EGF in colorectal cancer. These results indicate that IR-TGF-alpha should prove valuable as a possible tumor marker in colorectal cancers, and it may be very useful in understanding the biology of colorectal cancer. 
Comparison of chest pain, electrocardiographic changes and thallium-201 scintigraphy during varying exercise intensities in men with stable angina pectoris. This study was performed to evaluate the presence of angina pectoris, electrocardiographic changes and reversible thallium-201 defects resulting from 2 different levels of exercise in 19 patients with known coronary artery disease and evidence of exercise-induced ischemia. The exercise protocols consisted of a symptom-limited incremental exercise test (Bruce protocol) followed within 3 to 14 days by a submaximal, steady-state exercise test performed at 70% of the maximal heart rate achieved during the Bruce protocol. The presence and time of onset of angina and electrocardiographic changes (greater than or equal to 0.1 mV ST-segment depression) as well as oxygen uptake, exercise duration and pressure-rate product were recorded. Thallium-201 (2.5 to 3.0 mCi) was injected during the last minute of exercise during both protocols, and the images were analyzed using both computer-assisted quantitation and visual interpretations. Incremental exercise resulted in anginal symptoms in 84% of patients, and electrocardiographic changes and reversible thallium-201 defects in all patients. In contrast, submaximal exercise produced anginal symptoms in only 26% (p less than 0.01) and electrocardiographic changes in only 47% (p less than 0.05), but resulted in thallium-201 defects in 89% of patients (p = not significant). The locations of the thallium-201 defects, when present, were not different between the 2 exercise protocols. These findings confirm the sequence of the ischemic cascade using 2 levels of exercise and demonstrate that the cascade theory is applicable during varying ischemic intensities in the same patient. 
Hypoxaemia during anaesthesia--an observer study. We have investigated 296 inpatients in a single-blind observer study to determine the incidence, degree and duration of hypoxaemia during anaesthesia. The clinical recognition of hypoxaemia, period of time until recognition and risk factors were studied. Oxygen saturation (Spo2) was monitored continuously with a pulse oximeter (Ohmeda, model 3700). One or more episodes of mild hypoxaemia (Spo2 86-90%) were recorded in 53% of patients. Severe hypoxaemia with Spo2 values less than 81% were recorded in 20% of patients. The mild hypoxaemic episodes lasted up to 34.6 min (mean 2.3 min) and 70% were not detected by the anaesthetist. In the remaining 30% of episodes, the anaesthetist diagnosed the complication with a mean time delay of 70 s. After intervention a mean time delay of 57 s was recorded until Spo2 exceeded 90%. Utilizing a stepwise multiple logistic regression analysis, we found that risk factors associated with a greater incidence of hypoxaemia were patient age (P less than 0.005) and anaesthetic technique (P less than 0.00001). We conclude that hypoxaemic episodes in our operating rooms are common during anaesthesia and suggest preoxygenation in all patients in addition to administration of supplementary oxygen during arousal from anaesthesia and during transfer to the recovery room. 
Portal venous barium intravasation complicating barium enema examination. Venous intravasation of contrast is a potentially life-threatening complication of the barium enema examination. A patient in whom portal venous contrast intravasation was nearly fatal is presented, and the significant morbidity and mortality from this unusual event is reviewed. Since barium infiltration into the venous system almost always occurs in the setting of altered mucosal integrity, this examination should be used cautiously in patients with inflammatory bowel disease or diverticulitis. Prompt recognition and rapid resuscitation are critical to the survival of patients with contrast intravasation. 
Tricuspid atresia: association with persistent truncus arteriosus. Clinical, echo-Doppler, and pathologic data of a rare case of tricuspid atresia in association with truncus arteriosus are presented. There are only six patients (including the patient reported here) with this anomaly in whom detailed pathologic and/or clinical descriptions are available in the literature. An additional six cases were mentioned in the literature but without any details. A prevalence rate of 1.4% among tricuspid atresia cases is estimated. All infants presented with symptoms of cyanosis and/or congestive heart failure within a few days to 2 months after birth and died shortly thereafter. Cardiomegaly and increased pulmonary vascular markings on the chest x-ray film and left axis deviation with left ventricular hypertrophy on the ECG are usually present. Echocardiographic, catheterization, and angiocardiographic studies are helpful in documenting anatomic and physiologic features of this anomaly. Pathologically, the muscular type of tricuspid atresia, type I or II truncus arteriosus, a large subtruncal VSD, and a hypoplastic right ventricle are present. It is concluded that coexistence of tricuspid atresia and truncus arteriosus is rare; clinical, laboratory, and pathologic features are distinctive; the clinical presentation early in life with rapid demise is common; and prompt palliative surgery immediately after recognition of this anomaly should be undertaken. 
Association of exotoxin-producing group A streptococci and severe disease in children. Clinical features and microbiologic data on all cases of serious (hospitalized) Group A streptococcal infections in children managed at our institution between 1985 and 1988 are presented. All 6 cases were caused by toxin-producing strains. Four of 6 were toxin A-producing strains whereas none of 58 community-acquired (Group A streptococcal) pharyngeal isolates in the same period was a toxin A producer. A review of the literature on the incidence of toxin A-producing strains provides information suggesting a resurgence of such strains in the late 1980s after a relative disappearance of toxin B production in isolates from these patients was also significantly greater than in the isolates acquired from the community in uncomplicated pharyngitis. These findings suggest a role for exotoxin in severe manifestations of Group A streptococcal disease in children. 
Distribution of thymic tissue in the mediastinal adipose tissue. The distribution of thymic tissue in the anterior mediastinal, retrocarinal, and preaortic fat was examined histologically in 27 autopsy subjects. Thymic tissue was found in the anterior mediastinal fat in 12 subjects (44.4%), in the retrocarinal fat in two (7.4%), and in the preaortic fat in none. The finding of ectopic thymic tissue in these areas has not been reported previously, would appear to be surgically inaccessible via a median sternotomy, and may be responsible in part for some of the failures of thymectomy in the treatment of myasthenia gravis. 
Identifying anterior segment crystals. A series of 22 patients with crystals in the anterior segment of the eye was examined by specular microscopy. Of 10 patients with hypermature cataract and hyperrefringent bodies in the anterior chamber cholesterol crystals were identified in four patients and in six of the 10 in whom aspirate was obtained cholesterol crystals were demonstrated in three, two of these having shown crystals on specular microscopy. In 10 patients with intracorneal crystalline deposits, cholesterol crystals were found on specular microscopy, including one case of Schnyder's crystalline corneal dystrophy. Of two patients with multiple myeloma, corneal crystals were demonstrated in one. Crystals of the anterior segment of the eye are most likely to be cholesterol, and identification is important for future treatment. 
Simple examination techniques to aid in the diagnosis of urethral diverticulum. Patients with urethral diverticula classically present with dyspareunia, dribbling of urine, chronic dysuria, and/or a tender suburethral mass. Physical examination, urethroscopy, positive pressure urethrography, and the urethral pressure profile may not confirm the suspected diagnosis. Three simple diagnostic maneuvers are presented to aid in confirming the diagnosis before surgical exploration. 
Symptomatic and silent gall stones in the community. The prevalence of gall stone disease in a stratified random sample of 1896 British adults (72.2% of those approached) was established using real time ultrasound. The prevalence rose with age, except in women of 40-49 years, so that at 60-69 years, 22.4% of women and 11.5% of men had gall stones or had undergone cholecystectomy. The cholecystectomy rate of people with gall stone disease was higher in women than in men (43.5% v 24%, p less than 0.05). Very few subjects with gall stones had convincing biliary symptoms. In women, 10.4% had symptoms according to a questionnaire definition of biliary pain and 6.3% according to conventional history taking, while no men at all admitted to biliary pain. Nevertheless, cholecystectomy in men had nearly always been preceded by convincing biliary symptoms. The age at cholecystectomy was, on average, nine years less than the age at detection of silent gall stones in both sexes. It is concluded that either gall stones are especially prone to cause symptoms in younger people or that there are two kinds of cholelithiasis - symptomatic and silent. The lack of symptomatic gall stones in cross sectional surveys is probably due to their rapid diagnosis and treatment. 
Genetic susceptibility to Parkinson's disease. Genetic factors clearly cause Lewy-body Parkinson's disease (PD) in a subset of autosomal-dominant families. However, most cases of PD are sporadic. The two most likely models of four discussed for sporadic PD are the reduced penetrance model and the multifactorial model. Sporadic PD is likely to be caused by the combined effect of environmental precipitating factors and genetic susceptibility factors. Because the number of major genetic factors is likely to be small, these hypotheses can be tested and genetic factors located using linkage mapping techniques. The affected pair analysis methods are especially suited to PD. Finding the genetic susceptibility factors for PD is important because this may be the fastest way to identify the environmental precipitating factors and because it may lead to prevention of PD. Because of the usefulness of identifying genetic susceptibility factors for PD, we are carrying out linkage studies in a group of 16 large autosomal-dominant families with PD and more than 300 living affected PD pairs. 
The rhombotin family of cysteine-rich LIM-domain oncogenes: distinct members are involved in T-cell translocations to human chromosomes 11p15 and 11p13. A chromosomal translocation in a T-cell leukemia involving the short arm of human chromosome 11 at band 11p15 disrupts the rhombotin gene. This gene encodes a protein with duplicated cysteine-rich regions called LIM domains, which show homology to zinc-binding proteins and to iron-sulfur centers of ferredoxins. Two homologues of the rhombotin gene have now been isolated. One of these, designated Rhom-2, is located on human chromosome 11 at band 11p13, where a cluster of T-cell leukemia-specific translocations occur; all translocation breakpoints at 11p13 are upstream of the Rhom-2 gene. Human and mouse Rhom-2 are highly conserved and, like rhombotin, encode two tandem cysteine-rich LIM domains. Rhom-2 mRNA is expressed in early mouse development in central nervous system, lung, kidney, liver, and spleen but only very low levels occur in thymus. The other gene, designated Rhom-3, is not on chromosome 11 but also retains homology to the LIM domain of rhombotin. Since the Rhom-2 gene is such a common site of chromosomal damage in T-cell tumors, the consistency of translocations near the rhombotin gene was further examined. A second translocation adjacent to rhombotin was found and at the same position as in the previous example. Therefore, chromosome bands 11p15 (rhombotin) and 11p13 (Rhom-2) are consistent sites of chromosome translocation in T-cell leukemia, with the 11p15 target more rarely involved. The results define the rhombotin gene family as a class of T-cell oncogenes with duplicated cysteine-rich LIM domains. 
Different mechanisms of polyuria and natriuresis associated with paroxysmal supraventricular tachycardia. The mechanism of polyuria associated with paroxysmal supraventricular tachycardia (SVT) was investigated in 8 patients. SVT was induced artificially and sustained for 60 minutes. Urine and blood samples were collected every 30 minutes. During the latter half of SVT, urine flow increased twofold in the control subjects before SVT. Urinary sodium excretion increased significantly (p less than 0.01) within 30 minutes after SVT. Urinary excretion of antidiuretic hormone (ADH) decreased (p less than 0.01) during the latter half of SVT and increased (p less than 0.01) after SVT, respectively. Plasma level of ADH did not change during SVT but increased (p less than 0.05) after SVT. The concentration of plasma atrial natriuretic polypeptide (ANP) increased significantly (p less than 0.05) before SVT ended. Urinary excretion of prostaglandin E2 increased significantly (p less than 0.05) after termination of SVT. The percent changes in the urinary excretion of prostaglandin E2 were correlated (r = 0.713, p less than 0.001) with those of ADH. There was also a correlation (r = 0.6, p less than 0.001) between the percent changes in the urinary excretion of prostaglandin E2 and those of sodium. Their findings suggest that the polyuria during SVT is attributed mainly to the inhibition of ADH release and that the natriuresis after SVT is due not only to the increased ANP but also to the increased renal prostaglandin E2 probably stimulated by ADH. 
Comparison of acute and chronic protein-energy malnutrition on host antitumor immune mechanisms. Protein-calorie malnutrition (PCM) is prevalent in cancer patients. However, the effect of PCM on anti-tumor immunity is unclear and critically important in an era of improving results with adoptive immunotherapy. This study examined the effect of short- and long-term PCM on tumor-specific and natural immune effector mechanisms in a murine neuroblastoma (C1300 NRB) model. A/J mice received an isocaloric 2.5% or 24% casein diet for 3 or 8 weeks before inoculation with tumor. Three weeks later lymphocytes from tumor-bearing mice were harvested for determination of cytotoxic T lymphocyte (CTL) generation and natural killer (NK) cell cytotoxicity. Both 3 and 8 weeks of PCM significantly reduced mean total body weight by 25% (p less than 0.001) and 41% (p less than 0.001), respectively, compared with regularly nourished mice. Short-term PCM did not inhibit CTL or NK cytotoxicity, whereas long-term PCM significantly diminished CTL generation (p less than 0.001) but preserved NK cytotoxic function. These results indicate that CTL development against autologous tumor, in contrast to basal NK function, is dependent on host nutritional status. Mean tumor growth, determined by tumor-weight to carcass-weight ratio, was unchanged for both short- and long-term protein-energy deprived groups compared with results in regularly nourished mice. These findings suggest that NK function is the predominant effector mechanism inhibiting C1300 NRB growth and that NK tumoricidal capacity is preserved during PCM. 
Pathophysiology of isolated systolic hypertension in elderly patients: Doppler echocardiographic insights. Systemic hemodynamics were evaluated with aortic pulsed wave Doppler echocardiography in 79 elderly subjects with isolated systolic hypertension participating in the Systolic Hypertension in the Elderly Program (SHEP) and were compared with the values in 39 normal age-matched subjects. Cardiac output was elevated (4.50 +/- 1.13 L/min versus 3.94 +/- 1.12 L/min, p less than 0.05) in patients with isolated systolic hypertension in comparison with values in normal elderly subjects. Systemic vascular resistance did not differ between both groups (2140 +/- 536 dyn.sec/cm-5 versus 2011 +/- 553 dyn.sec/cm-5, p = NS). The mean acceleration of blood during left ventricular ejection was similar in patients with isolated systolic hypertension in comparison with normals (12.6 +/- 5.6 m/sec2 versus 11.5 +/- 3.5 m/sec2, p = NS). Patients with isolated systolic hypertension had significantly decreased arterial compliance, as measured by the stroke volume-to-pulse pressure ratio (0.77 +/- 0.26 cm3/mm Hg versus 1.11 +/- 0.30 cm3/mm Hg, p less than 0.0001). The prevalence of aortic and mitral regurgitation as well as valvular and annular calcification did not differ between analyzed groups. Isolated systolic hypertension in elderly patients appears to be multifactorial, with reduced arterial compliance and increased cardiac output both playing a role. 
Reading problems in adult chronic headache sufferers. In a questionnaire survey we determined the prevalence of problems with reading, at present as well as in the past, in adult chronic headache sufferers as compared with age- and sex-matched controls. The reading problems inquired about were those with reading in general, reading quickly, prolonged reading and reading comprehension. The subjects were also asked about present and past problems with writing, concentrating, performing mathematics and overall learning. Significant differences in the prevalences of the problems studied between the headache sufferers and controls were observed on just two items and only for the female groups. These items were present problems with reading comprehension (39.3% versus 7.5%; p = 0.002) and concentrating (46.4% versus 17.5%; p = 0.015). We concluded that adult female headache sufferers have impaired reading comprehension and concentration abilities which do not seem to originate from the past. 
Paramyotonia congenita and hyperkalemic periodic paralysis map to the same sodium-channel gene locus. Paramyotonia congenita (PC), an autosomal dominant muscle disease, shares some clinical and electrophysiological similarities with another myotonic muscle disorder, hyperkalemic periodic paralysis (HYPP). However, clinical and electrophysiologic differences allow differentiation of the two disorders. The HYPP locus was recently shown to be linked to a skeletal muscle sodium-channel gene probe. We now report that PC maps to the same locus (LOD score 4.4, theta = 0 at assumed penetrance of .95). These linkage results, coupled with physiological data demonstrating abnormal sodium-channel function in patients with PC, implicate a sodium-channel gene as an important candidate for the site of mutation responsible for PC. Furthermore, this is strong evidence for the hypothesis that PC and HYPP are allelic disorders. 
Efficacy of low-molecular-weight heparin in the management of intermittent claudication. Treating chronic arterial occlusive disease with heparin is controversial because of the risks associated with long-term anticoagulant therapy. Low molecular weight (LMW) heparin (mw about 5000 Dalton), which selectively inhibits the Xa factor with minimal risk of hemorrhage, seems to offer new possibilities in the prevention and treatment of both venous and acute arterial thromboembolism. Therefore, 44 patients with intermittent claudication were recruited to a randomized, double-blind, controlled study. Twenty-two were treated for six months with a single daily subcutaneous dose (15,000 UaXa) of LMW heparin and 22 with placebo administered in the same way over the same period of time. After six months, LMW heparin treatment not only improved walking capacity (by lengthening the pain-free walking time by 25%) but also significantly modified the hemorrheologic pattern (by reducing fibrinogen concentrations and whole blood viscosity at low shear rates). LMW heparin also exerted an antithrombotic and profibrinolytic effect by significantly increasing both the anti-Xa factor and plasminogen activity without markedly modifying activated partial thromboplastin time (+20%). No LMW heparin-treated patient hemorrhaged or reported other noteworthy side effects. These results suggest LMW heparin might be a useful drug in the long-term treatment of chronic arterial occlusive disease of the limbs. 
Role of conversion of xanthine dehydrogenase to oxidase in ischemic rat liver cell injury. This study was undertaken to determine whether hepatic ischemia and the subsequent reflow of blood have any effect on the conversion of xanthine dehydrogenase to xanthine oxidase (XO). Ischemia of the liver for 90 or 120 minutes did not permit survival of the animals. XO represented 15% of the total xanthine dehydrogenase plus XO activity in the control liver. XO activity remained unchanged even after 90 minutes of hepatic ischemia, although a marked increase in lipid peroxide in the liver tissue was observed during the reperfusion. When hepatic ischemia was prolonged for 6 hours (animals were dead), XO activity rose to 35% of the total activity. Incubation of the liver at 37 degrees C resulted in a definite change in XO activity dependent on the length of incubation period. Although no significant changes occurred in XO activity during the first 2 hours of incubation, a marked XO conversion was observed between 2 and 4 hours, and a maximal conversion was achieved after 6 hours of incubation. These results suggest that XO newly generated during ischemia has a very limited role in oxygen free radical production after resuming perfusion. 
Increased therapeutic index of antineoplastic drugs in combination with intracellular histamine antagonists. L-Histidinol, a protein synthesis inhibitor and structural analogue of L-histidine, has been demonstrated in chemotherapy-treated mice to be cytoprotective to normal stem cells but to enhance cytotoxicity to tumor cells. N,N-Diethyl-2-[4-(phenylmethyl) phenoxy]ethanamine.HCl (DPPE) is an antagonist of recently described microsomal and nuclear intracellular histamine receptors implicated in the mediation of proliferation and modulation of prostaglandin synthesis. DPPE is cytotoxic to tumor cells in vitro and cytoprotective to the gut in vivo. Noting the similar pharmacologic profiles for histidinol and DPPE and the structural resemblance between histidinol and histamine, we tested 1) whether binding to intracellular histamine receptors may be important to the action of histidinol, 2) whether there exists a differential effect of DPPE and histidinol on proliferating normal and transformed or malignant cells, and 3) whether DPPE, like histidinol, protects host cells from the effects of chemotherapy while augmenting tumor cell kill in vivo. It was observed that histidinol does compete at intracellular histamine receptors in isolated microsomes and nuclei, but with significantly lower affinity than DPPE. Nevertheless, for each agent, potency at intracellular histamine receptors correlates with potency to inhibit DNA and protein synthesis, without cytotoxicity, in normal mitogen-stimulated murine lymphocytes and to kill transformed mouse lymphocytes or MCF-7 human breast cancer cells. As demonstrated previously for histidinol (1-2 g/kg), DPPE (4 mg/kg) protected murine bone marrow progenitors from doxorubicin or fluorouracil, while doses of 4-50 mg/kg significantly enhanced the antitumor activity of doxorubicin and daunorubicin in murine models of early cancer. One postulate to explain the effects of intracellular histamine receptor ligands is that intracellular histamine mediates DNA and protein synthesis, possibly through a downward modulation of growth-inhibitory prostaglandin levels. Antagonism of the intracellular action of histamine at intracellular histamine receptors by DPPE or histidinol may result in differential perturbations of growth/eicosanoid metabolism in normal and malignant cells, thus forming the basis of a new approach to chemotherapy. 
Alfentanil infusion for postoperative pain: a comparison of epidural and intravenous routes. The efficacy of intravenous (iv) and epidural infusions of alfentanil for postoperative pain relief was investigated in 24 patients (ASA physical status 1-2) who were scheduled for abdominal hysterectomy. The patients were allocated randomly to receive either epidural or iv alfentanil. In both groups, a loading dose of 15 micrograms.kg-1 was administered, followed by a constant rate infusion of 18 micrograms.kg-1.h-1 alfentanil for 20 h. Both routes provided similar degrees of analgesia; however, analgesia occurred earlier in the intravenously treated group (P less than 0.03). Mean plasma alfentanil concentrations (Cps) varied between 42 and 82 ng.ml-1 in the iv group and 23 and 68 ng.ml-1 in the epidural group, with higher concentrations in the iv group for the first 60 min only (P less than 0.01). Cps increased with infusion time, suggesting accumulation of alfentanil. After infusion ended, pain recurred at the same time in both groups, whereas the alfentanil Cps still were greater than 45 ng/ml. Postoperative epinephrine concentrations decreased after 60 min of infusion (P less than 0.02), whereas, after 6 h, cortisol levels decreased to preoperative values. Norepinephrine concentrations decreased only slightly. The only clinically meaningful effect on vital signs that occurred was an abrupt reduction of respiratory rate after the iv loading dose. PaCO2 increased to the same extent in both groups during the first 15 min only. The incidence of opioid-related side effects was similar in both groups. These results suggest that the iv and epidural routes were equally effective for providing postoperative pain control and controlling the postoperative response to surgical stress. 
Dendritic hypertrophy in Purkinje neurons of old Fischer 344 rats after long-term ethanol treatment. Metric parameters of Purkinje cell dendritic networks in 24- to 26-month-old Fischer 344 rats were determined after 48 weeks of chronic ethanol intake. Measurements included the total number and length of all segments/network, the total number and length of segments within topologically defined segment categories, and the mean length of segments in each category. A main effect of ethanol was expressed as a significant increase in cumulative length within one category of terminal segments. This increase was the result of a significant increase in mean length/segment in that category. Metric changes in other segment categories were not significant, showing that changes in the networks during ethanol treatment were not distributed randomly. Recovery after ethanol treatment was associated with further nonrandom remodeling of these networks. Significant differences in lengths of terminal segments were no longer present, but internal segments in networks of both pair-fed and ethanol-fed rats were significantly longer. Only one category of internal segments showed this change during recovery. The data showed that long term ethanol treatment in old rats, at a time when effects of aging processes were prominent in Purkinje cell networks, was associated with remodeling of those networks through dendritic extension. This effect was interpreted as compensatory growth in surviving networks following ethanol-related neuronal loss and/or damage to the surrounding neuropil. Recovery from dietary treatment produced further internal remodeling of those networks that was not related specifically to ethanol. It could be shown, however, that the restructuring processes that resulted in longer internal segments after dietary recovery were different in the pair-fed and the ethanolfed rats. 
Combination therapy of OK432 and recombinant human interferon alpha A/D on viral myocarditis in mice starting after infection. We investigated the effects of OK432, recombinant human interferon alpha A/D (rIFN alpha A/D) and a combination of these drugs on murine acute myocarditis due to encephalomyocarditis virus. Mice were administered 1 KE of OK432 and 10(4)U/g of rIFN alpha A/D starting 24 hr after viral inoculation for 14 days. The survival rate of mice having the combination therapy was significantly higher than that of untreated mice on day 21 (15 of 20 vs. 6 of 20, P less than .001), whereas the viral titer in the heart, the heart weight/body weight ratio and the scores for myocardial inflammation and necrosis were significantly lower. On the other hand, therapy with OK432 or rIFN alpha A/D individually improved neither the survival rate nor the extent of myocardial damage. The natural killer cell activity in the combination therapy mice on day 3 after infection was significantly increased in comparison with untreated mice (46.2 +/- 5.5 vs. 37.7 +/- 2.8%, P less than .01), and the cytotoxicity of peritoneal macrophages was increased (45.0 vs. 26.7%). Thus, the combination therapy of OK432 and rIFN alpha A/D was more effective than the therapy with OK432 alone or rIFN alpha A/D alone against acute viral myocarditis when the treatment was started early after infection, and the stimulation of host immunologic response by OK432 may be important for this combination therapy. 
Efficacy and safety of intravenous sotalol for termination of paroxysmal supraventricular tachycardia. The Sotalol Versus Placebo Multicenter Study Group. A double-blind, placebo-controlled, crossover, multicenter study was conducted to study the efficacy and safety of a single intravenous dose of sotalol (1.5 mg/kg over 10 minutes) in achieving normal sinus rhythm in paroxysmal supraventricular tachycardia (SVT) lasting greater than or equal to 15 minutes. Patients were randomized to either sotalol or placebo as initial treatment, and if the SVT was not terminated a crossover was performed after 20 minutes. A total of 43 patients were enrolled, 38 of whom with spontaneous (n = 14) or induced (n = 24) SVT were analyzed for sotalol efficacy. Most patients (n = 27) had atrioventricular (AV) nodal reentrant tachycardia, and an important subgroup (n = 11) had circus movement tachycardia, using an accessory pathway for retrograde conduction. The number of patients converting to sinus rhythm as a result of the initial treatment was significantly higher in the sotalol group than in the placebo group, for spontaneous (p less than 0.005) as well as for induced tachycardia (p less than 0.001). Sinus rhythm was achieved within 30 minutes in 83% of all patients who received sotalol as the first drug, compared with 16% of the patients first receiving placebo (p less than 0.0001). For sotalol safety analysis, 42 patients were included. A total of 37 patients received sotalol, 19 as the first treatment, and 18 as the second treatment, while 25 patients received placebo. A total of 15 possible adverse effects were reported, occurring in 10 patients with sotalol versus 4 with placebo. The only severe side effect (hypotension) necessitating termination of drug administration occurred with placebo. No proarrhythmic effects were observed. 
Oriental cholangiohepatitis: pathologic, clinical, and radiologic features. Oriental cholangiohepatitis, an endemic disease in Southeast Asia, is characterized by recurrent attacks of abdominal pain, fever, and jaundice. Pathologically, the intra- and extrahepatic ducts are dilated and contain soft, pigmented stone and pus. There is proliferation of bile ducts and infiltration of inflammatory cells along the periportal spaces and hepatic parenchyma. Localized intrahepatic segmental ductal stenosis may be present, especially in the lateral segment of the left lobe or posterior segment of the right hepatic lobe. The cause of the disease is not known, but associations with clonorchiasis, ascariasis, and nutritional deficiency have been suggested. Sonographic and CT findings include intra- or extrahepatic duct stones, dilatation of the extrahepatic duct with relatively mild or no dilatation of the intrahepatic ducts, localized dilatation of the lobar or segmental bile ducts, increased periportal echogenicity, segmental hepatic atrophy, and gallstones. Cholangiographic findings include bile duct stones; disproportionately severe dilatation of the extrahepatic ducts with mild or no dilatation of the intrahepatic ducts; and focal strictures, acute peripheral tapering, straightening, rigidity, decreased arborization, and an increased branching angle of the intrahepatic bile ducts. 
Dose-dependent kinetics of orally administered 6-mercaptopurine in children with leukemia. To determine whether the pharmacokinetics of 6-mercaptopurine (6-MP) would show dose dependency, we studied three different single oral doses in eight children (aged 3.6 to 15.1 years) with acute leukemia in remission. Marked interindividual differences in maximum plasma concentration (Cmax) and the area under the plasma concentration-time curve (AUC) were observed when children received the 50 mg/m2 dose. This variability decreased when the doses were increased. Six of the eight children showed a disproportionate increase in the AUC with increasing doses; the other two had a proportionate relationship between the AUC and dose. Overall mean (+/- SD) Cmax and AUC values increased disproportionately (88 +/- 123, to 326 +/- 194, to 653 +/- 344 ng/ml for Cmax, and 147 +/- 180, to 451 +/- 177, to 1291 +/- 415 ng/ml per hour for AUC, respectively) when the dose increased from 50 to 87.5 mg/m2 and then to 175 mg/m2. The results suggest that a saturable first-pass metabolism of oral 6-MP occurs with increasing oral doses in some, but not all, children. Whether and to what extent this pharmacokinetic character of oral 6-MP affects the interindividual difference in systemic exposure to the drug in children with leukemia receiving maintenance therapy require further studies. 
Nerve growth and expression of receptors for nerve growth factor in tumors of melanocyte origin. Nerve growth factor (NGF) stimulates growth and differentiation of sensory and sympathetic neurons. It is not known what role NGF plays in melanoma development, but nevus and malignant melanoma cells express NGF-receptor (NGF-R). We counted nerve fibers within melanocytic nevi, primary cutaneous melanomas, and cutaneous melanoma metastases using a monoclonal antibody (MoAb) as marker against a 200-kD glycoprotein that is expressed on human nerves. The expression of NGF-R was studied in serial cryostat sections using a MoAb against the NGF-R. Compared to normal skin, increased numbers of nerve fibers were found in 72 melanocytic nevi. In congenital nevi their number significantly increased with age. In 47 primary cutaneous melanomas the number of nerve fibers decreased in proportion to tumor thickness. In 33 cutaneous melanoma metastases no accumulation of nerve fibers was found. NGF-R was not expressed in normal skin melanocytes and in the majority of nevus cells in melanocytic nevi. Considerable numbers of NGF-R-positive nervus cells were found only in some congenital nevi and few acquired nevi with dysplastic features. By contrast, in primary and metastatic melanomas higher expression of NGF-R was observed. The increased number of nerve fibers in melanocytic nevi suggests that neurite-promoting factors are produced in situ. Production of such factors appears to be lost in malignant melanoma cells. The finding of an inverse correlation between an abundance of nerve fibers in NGF-R-poor nevi and a high expression of NGF-R in melanomas that show no evidence of nerve growth suggest a role of NGF and its receptor in malignant melanocytic tumors. 
Effects of exercise on transmitral gradient and pulmonary artery pressure in patients with mitral stenosis or a prosthetic mitral valve: a Doppler echocardiographic study. Doppler echocardiography was used to determine changes in transmitral gradient and pulmonary artery pressure after exercise in 12 patients with mitral stenosis and 11 patients with a prosthetic mitral valve. The mean transmitral gradient in the mitral stenosis group was 9 +/- 7 mm Hg at rest and increased to 17 +/- 8 mm Hg after exercise. In patients with a prosthetic mitral valve, exercise resulted in an increase in mean transmitral gradient from 5 +/- 2 to 8 +/- 3 mm Hg. Calculated pulmonary artery systolic pressure increased with exercise from 41 +/- 19 to 70 +/- 32 mm Hg in the mitral stenosis group and from 28 +/- 8 to 39 +/- 15 mm Hg in patients with a prosthetic valve. Exercise Doppler echocardiographic evaluation of changes in transmitral gradient and pulmonary artery systolic pressure was found to be technically simple and an important addition to the noninvasive evaluation of patients with mitral valve disease. 
Multivariate analysis to simplify the differential diagnosis of broad complex tachycardia. Univariate analysis has identified several criteria that aid the differential diagnosis of broad complex tachycardia. In this study of 102 consecutive patients multivariate analysis was performed to identify which of 15 clinical and 11 electrocardiographic variables were independent predictors of ventricular tachycardia. These were shown to be a history of myocardial infarction, the QRS waveforms in leads aVF and V1, and a change in axis from sinus rhythm to tachycardia of more than 40 degrees. If none of the criteria was met, the diagnosis was almost certainly supraventricular tachycardia. If one criterion was met the diagnosis was probably supraventricular tachycardia. If two criteria were met then the diagnosis was probably ventricular tachycardia. If three or four criteria were met, the diagnosis was almost certainly ventricular tachycardia. The predictive accuracy was 93%. This was increased to 95% by including two other criteria--definite independent P wave activity and ventricular extrasystoles with the same QRS configuration as that in tachycardia. These criteria were not included in the multivariate analysis because though they were 100% specific they were seldom seen. These four criteria can be used as simple rules in determining the origin of a broad complex tachycardia. 
Expression of c-erbB-2 oncoprotein in gastric carcinoma. Immunoreactivity for c-erbB-2 protein is an independent indicator of poor short-term prognosis in patients with gastric carcinoma. Correlations of c-erbB-2 protein expression with clinical outcomes of gastric carcinomas were studied in 189 gastric carcinomas. There were 23 (12.2%) carcinomas with evidence of c-erbB-2 protein in which the reaction was localized to the cell membrane. There was no significant association between c-erbB-2 staining and the macroscopic or histologic type of the carcinomas. c-erbB-2-stained tumors were more likely to be associated with serosal invasion, nodal involvement, and peritoneal metastasis, than c-erbB-2-unstained ones. In addition, c-erbB-2 was stained in none of early gastric carcinomas. The 5-year survival rates of the c-erbB-2 protein-positive and the protein-negative group were 11% and 50%, respectively. When the c-erbB-2 tissue status and seven clinicopathologic variables as conventional prognostic factors were entered simultaneously into the Cox regression model, serosal invasion, hepatic metastasis, peritoneal metastasis, nodal status, and c-erbB-2 tissue status emerged as independent prognostic variables. The results suggested that c-erbB-2 protein expression might be enhanced in advanced stages during the progression of gastric carcinoma. In this particular group of patients, immunoreactivity for c-erbB-2 protein is an indicator of poor short-term prognosis. 
Quantitative angiography after directional coronary atherectomy. OBJECTIVE--To assess by quantitative analysis the immediate angiographic results of directional coronary atherectomy. To compare the effects of successful atherectomy with those of successful balloon dilatation in a series of patients with matched lesions. DESIGN--Case series. SETTING--Tertiary referral centre. PATIENTS--62 patients in whom directional coronary atherectomy was attempted between 7 September 1989 and 31 December 1990. INTERVENTIONS--Directional coronary atherectomy. MAIN OUTCOME MEASURES--Increase in minimal luminal diameter of coronary artery segment. RESULTS--Angiographic success on the basis of intention to treat was obtained in 54 patients (87%). In four patients the lesion could not be crossed by the atherectomy device; all four had an uneventful conventional balloon angioplasty. Four of the 58 patients who underwent atherectomy were subsequently referred for coronary bypass surgery because of failure or complications; three of them sustained a transmural infarction. In the successful cases, coronary atherectomy resulted in an increase in the minimal luminal diameter from 1.1 mm to 2.5 mm with a concomitant decrease of the diameter stenosis from 62% to 22%. In the subset of 37 patients in which the changes induced were compared with conventional balloon angioplasty atherectomy increased the minimal luminal diameter more than balloon angioplasty (1.6 v 0.8 mm; p less than 0.0001). Conventional histology showed media or adventitia in 26% of the atherectomy specimens. In hospital complications occurred in six patients who had undergone a successful procedure: two transmural infarctions, two subendocardial infarctions, one transient ischaemia attack, and one death due to delayed rupture of the atherectomised vessel. All patients were clinically evaluated at one and six months. One patient had persisting angina (New York Heart Association class II), one patient sustained a myocardial infarction, one patient underwent a percutaneous transluminal coronary angioplasty for early restenosis, and one patient underwent coronary bypass surgery because of a coronary aneurysm formation. At six months 80% (36/47) of the patients were symptom free. CONCLUSIONS--Coronary atherectomy achieved a better immediate angiographic result than balloon angioplasty; however, in view of the complication rate in this preliminary series, which may be related to a learning curve, a randomised study is needed to show whether this procedure is as safe as a conventional balloon angioplasty. 
Current chemotherapy of head and neck cancer. This article reviews the results of over 50 published trials testing the use of chemotherapy in patients with squamous cell carcinoma of the head and neck. Among the trials using chemotherapy before standard surgery and/or radiotherapy in stage III and IV disease, none has shown an improvement in survival compared with surgery and/or radiotherapy alone. In these studies, the survival at 3 to 5 years has been generally 40% to 50%. Several trials using chemotherapy after standard therapy, however, have reported survival benefits of 10% to 20%, suggested that further evaluation of classic adjuvant chemotherapy in this disease is warranted. Among studies in recurrent head and neck cancer, the most effective chemotherapy regimens appear to be variations of the program consisting of cisplatin followed by a 5-day infusion of 5-fluorouracil. Nevertheless, median survivals in recurrent disease remain short, generally 5 to 10 months. 
Recurrent classic migraine attacks following transdermal scopolamine intoxication. A 20 year old male naval crew-member suffering from sea sickness was treated with transdermal scopolamine (TS). After 5 months of continuous treatment, he developed scopolamine intoxication followed by the appearance of recurrent classic migraine attacks. He had never suffered from headache or migraine prior to TS intoxication. The migraine attacks comprised a prodrome of apathy, bad mood and loss of appetite lasting several hours. An aura of scintillating spots, left arm numbness and paresthesias lasting several minutes was followed by a severe throbbing unilateral headache with photophobia, sonophobia and nausea. After one year of repeated follow-up examination, he continued to suffer from the attacks once every 10 to 14 days, with no identified precipitating factors. We are not aware of similar cases in the medical literature. Although it is not possible to establish TS intoxication as a causal effect of the appearance of classic migraine in our patient, the temporal association and clinical course are very supportive of this assumption. Central nervous system neurotransmitter imbalance of cardiovascular alterations may possibly be implicated. 
Effect of destruction of the vascular endothelium upon pressure/flow relations and endothelium-dependent vasodilatation in resistance beds of spontaneously hypertensive rats. 1. Pressure/flow relationships were determined in the in situ blood-perfused superior mesenteric and hindquarters vascular beds of spontaneously hypertensive rats and Wistar-Kyoto normotensive rats before and after destruction of the endothelium with detergent. The effects of indomethacin on the regression of pressure on flow were also investigated in the spontaneously hypertensive rats, as were the endothelium-dependent relaxations in response to carbachol in the mesenteric bed. 2. In the spontaneously hypertensive rats the regression line of pressure on flow in the two vascular beds was both steeper and more elevated than in the Wistar-Kyoto rats, showing that there was greater resistance to flow in the hypertensive animals. Destruction of the endothelium significantly increased the slope of the regression in both Wistar-Kyoto and spontaneously hypertensive rats: the increases in the Wistar-Kyoto rats were 2.4 +/- 0.3 fold (mesenteric) and 2.0 +/- 0.5 fold (hindquarters) which were comparable with the respective increases of 1.6 +/- 0.3 fold and 1.8 +/- 0.3 fold in the spontaneously hypertensive rats. 3. Indomethacin (5 mg/kg, intravenously) had no effect on the pressure/flow relations in either of the vascular beds of the spontaneously hypertensive rats. 4. The dose-response curves for the endothelium-dependent vasodilatation in response to carbachol were not significantly different in spontaneously hypertensive and Wistar-Kyoto rats. 5. The results suggest that tonic release of endothelium-derived relaxing factor has similar effects in modulating resistance vessel tone in vivo in both hypertensive and normotensive rats. 
Ablepharon macrostomia syndrome. The association of congenital ablepharon with the absence of eyelashes and eyebrows, a wide mouth (macrostomia), and auricular, nasal, genital, and other systemic anomalies has been termed the ablepharon macrostomia syndrome. One such case is reported which illustrates the importance of immediate postnatal ocular management to minimise severe visual loss. 
Drug treatment of hypertension in patients with diabetes mellitus. Patients with diabetes mellitus have an increased prevalence of hypertension and its vascular consequences, including coronary and cerebrovascular disease. Drug treatment of hypertension in diabetic subjects is fraught with potential difficulties, including the altered efficacy of medications, the increased risk of side effects, and the possibility of worsening glycemic control and increasing serum lipid levels. Despite these difficulties, treatment is an important part of reducing morbidity and mortality from vascular events. Antihypertensive therapy may also have the potential to prevent or retard the development of diabetic nephropathy. In this article, we discuss the efficacy and metabolic and nonmetabolic side effects of the various classes of antihypertensive agents in patients with diabetes mellitus and suggest a stepped-care approach to the drug treatment of patients with hypertension and diabetes. 
Effect of radiation on the expression of carcinoembryonic antigen of human gastric adenocarcinoma cells. The changes of antigenic expression of cultured human gastric adenocarcinoma MKN45 cells caused by irradiation were investigated to elucidate the immune responses to localized irradiation. The expression of carcinoembryonic antigen (CEA) showed remarkable increases in the culture supernatant and on the surface of the membrane of irradiated cells. The expression of major histocompatibility complex Class I antigen on the membrane also was enhanced by irradiation. In addition, the irradiated cell groups, when analyzed using a CEA-specific probe, showed remarkable increases in the CEA mRNA. These enhancements increased in the 10-Gy and 15-Gy irradiated populations compared with the 5-Gy irradiated population. These results suggest that the enhancement of expression of CEA by radiation takes place at the CEA gene expression (mRNA) level but not at the protein level. 
Jejunal permeability to water and electrolytes in patients with chronic intrahepatic hypertension: evidence for a role of aldosterone. Acute prehepatic portal hypertension induces intestinal secretion in animal models. In the course of chronic liver disease, however, these changes are not observed, despite higher portal pressures than those found in experimental studies. Eight patients without diarrhoea and with chronic alcoholic liver disease were examined for evidence of increased jejunal secretion; their suprahepatic wedge pressure was raised from 21 to 45 mmHg (mean 34.6 mmHg). Jejunal perfusion with a triple lumen catheter and a proximal occluding balloon was used to study net flows of water and chloride as well as net and unidirectional flows of sodium and potassium. No statistical difference in intestinal flows of water and electrolytes was noted between cirrhotic patients and control subjects after infusion with a 30 mmol/l glucose solution. Infusion with a 30 mmol/l mannitol solution resulted in a lower absorption of water, Na, K, and Cl than with the glucose solution. A higher rate of Na secretion was observed in cirrhotic patients than control subjects after infusion with 30 mmol/l mannitol (p less than 0.01). In addition, the rate of Na secretion was higher in cirrhotic patients than in control subjects (p less than 0.05). There was no correlation between the net flow of Na and the suprahepatic wedge pressure. A second perfusion with a 30 mmol/l glucose solution was given 75 minutes after a bolus injection of spironolactone (400 mg). Net flows of Na and Cl were lower in cirrhotic patients than in control subjects (p less than 0.05) because of a lower absorption of Na. Patients with gradually developing portal hypertension have moderate jejunal secretions of H2O and electrolytes which we assume are partly masked by increased absorption resulting from hyperaldosteronism. In contrast to animal models, this mechanism may be part of the jejunal adaptation to permeability in acute portal hypertension. 
Clinical significance of the large adrenal mass. Current clinical teaching indicates that large (greater than 5 cm in diameter) adrenal masses are often malignant. In a retrospective analysis of patients studied between 1977 and 1988 with computed tomography (CT), adrenal scintigraphy, and when available, magnetic resonance imaging (MRI) 45 were found to have adrenal masses greater than 5 cm (range 5-19 cm) in diameter. Thirty were benign (16 phaeochromocytomas, six adrenocortical adenomas, four adrenal cysts, two myelolipomas, an adrenal hematoma and a ganglioneuroma). Of 15 malignant masses, there were seven adrenocortical carcinomas, five adrenal metastases and three adrenal lymphomas. With the exception of the adrenal myelolipomas, cysts, and the ganglioneuroma neither CT nor MRI demonstrated sufficient diagnostic specificity to distinguish benign from malignant lesions. Functional scintigraphy with 131I-6-beta-iodomethyl-19-norcholesterol for suspected adrenocortical lesions and 131I-metaiodobenzylguanidine for suspected phaeochromocytomas frequently provided useful information. 
Nd:YAG laser hyperthermia treatment of rat mammary adenocarcinoma in conjunction with surface cooling. Electromagnetic radiation ranging from radiofrequency to microwave has classically been used to induce hyperthermia for treatment of cancer. This paper presents a new technique using near infrared radiation from an Nd:YAG laser in conjunction with surface cooling to induce hyperthermia in a rat tumor model. A CW Nd:YAG laser hyperthermia system was used to induce hyperthermic temperatures in chemically (DMBA) induced rat mammary adenocarcinomas. The laser was interfaced to a computer and a thermometry unit that provided feedback to control the tumor temperature between 43.2-43.5 degrees C. A thermocouple was placed at the base of the tumor and its temperature was used to control laser exposure. All tumors were 10 to 20 mm in diameter. Surface cooling methods investigated included forced air flow from a fan, forced oxygen flow plus an IV drip, and forced moist oxygen flow from a nebulizer. Twelve rat mammary adenocarcinomas have been treated with Nd:YAG laser hyperthermia. In 4 treatments, no surface cooling was employed. In one treatment the surface was cooled using oxygen flow plus IV drip. In 7 treatments the skin was cooled using the nebulizer technique. The nebulization provided the most effective and reproducible surface cooling. Nd:YAG laser hyperthermia delivered in conjunction with nebulizer surface cooling produced efficient heating of rat mammary adenocarcinomas. A mean temperature of 42.1 degrees C was obtained at the base of the tumors while the mean surface temperature was 37.0 degrees C. 
Estimates of radiation absorbed dose for intraperitoneally administered iodine-131 radiolabeled B72.3 monoclonal antibody in patients with peritoneal carcinomatoses. Using a newly available model for determining estimates of radiation absorbed dose of radioisotopes administered intraperitoneally, we have calculated absorbed dose to tumor and normal tissues based on a surgically controlled study of radiolabeled antibody distribution. Ten patients with peritoneal carcinomatosis received intraperitoneal injections of the murine monoclonal antibody B72.3 radiolabeled with 131I. Biodistribution studies were performed using nuclear medicine methods until laparotomy at 4-14 days after injection. Surgical biopsies of normal tissues and tumor were obtained. The marrow was predicted to be the critical organ, with maximum tolerated dose [200 rad (2 Gy) to marrow] expected at about 200 mCi (7.4 GBq). In patients with large intraperitoneal tumor deposits, the tumor itself is an important source tissue for radiation exposure to normal tissues. Local "hot-spots" for tumor-absorbed dose were observed, with maximum tumor-absorbed dose calculated at 11,000 rad (11 Gy) per 100 mCi (3.7 GBq) administered intraperitoneal; however, tumor rad dose varied considerably. This may pose serious problems for curative therapy, especially in patients with large tumor burdens. 
The clinical course of perimesencephalic nonaneurysmal subarachnoid hemorrhage We studied the early clinical course of 65 patients with perimesencephalic (nonaneurysmal) subarachnoid hemorrhage. None of the patients rebled; none had delayed cerebral ischemia; and only 3 patients (5%) developed clinical signs of acute hydrocephalus, 2 requiring ventricular shunting. Hyponatremia and electrocardiographic changes were found in the same proportions as in patients with aneurysmal rupture. All patients had a good outcome after 3 months. To control for the influence of the relatively small amount of cisternal blood in perimesencephalic hemorrhage on the absence of delayed cerebral ischemia, we compared these 65 patients with 49 patients who had aneurysmal subarachnoid hemorrhage. This control group with aneurysms was selected according to a similar amount of cisternal blood, a comparable level of consciousness on admission, and absence of other factors known to increase the risk for delayed cerebral ischemia. We found that 4 of the 49 patients with aneurysmal hemorrhage developed delayed cerebral ischemia (Fisher's exact test, p = 0.03); therefore the relatively small amount of blood does not account for the absence of delayed cerebral ischemia in perimesencephalic hemorrhage. Patients with a perimesencephalic pattern of hemorrhage and a normal angiogram should be considered to have a distinct subset of subarachnoid hemorrhage and should be excluded from future treatment trials of patients with subarachnoid hemorrhage. 
The hyperekplexias and their relationship to the normal startle reflex. The startle response to unexpected auditory and somaesthetic stimulation was studied in 8 patients with hereditary or symptomatic hyperekplexia. It was abnormal in its resistance to habituation and in its exaggerated motor response. Both noise and taps to the face and head elicited a normal early blink response, separate from the subsequent true startle reflex. The earliest reflex EMG activity recorded after the blink was in sternocleidomastoid. EMG activity in masseter, and trunk and limb muscles followed later. This pattern of muscle recruitment suggests a brainstem origin for the abnormal startle responses. In addition, the abnormal startle responses exhibited disproportionately long latencies to the intrinsic hand and foot muscles and relatively slow recruitment of caudal muscles. The pattern of muscle recruitment was similar between patients, irrespective of the absolute latency of the response, and regardless of whether stimulation was auditory or somaesthetic. This suggests that auditory and somaesthetic afferents converge on a common brainstem efferent system, and that this system forms the final common pathway for abnormal startle responses of differing latency. The characteristics of this efferent system differ from those previously described in brainstem reticular reflex myoclonus, but are similar to those described in the normal auditory startle reflex in man. This suggests that the abnormal startle response in hyperekplexia, and the normal startle reflex represent pathological and physiological activity in the same brainstem efferent system. 
Granulocyte function in coronary artery disease. Granulocytes defend the body against invading microbes by producing a complex armamentarium of toxic substances, such as proteolytic enzymes, oxygen radicals and arachidonic acid metabolites. Under certain circumstances, however, such compounds may be released in the absence of phagocytosable particles, resulting in injury to normal cell and connective tissue degradation. Recent experimental studies have emphasized the potential role of granulocytes in the pathogenesis of myocardial ischemia. Clinical investigations have also shown alterations in neutrophil function in stable and unstable clinical manifestations of ischemic heart disease. "Priming" of granulocytes in stable forms of coronary disease may predispose to the subsequent development of acute coronary events, whereas activation of neutrophils may lead to alterations in vascular permeability and coronary flow regulation, leading to further myocardial and endothelial injury in acute myocardial infarction, unstable angina and coronary angioplasty. 
Severe lactic acidosis related to acute thiamine deficiency. The authors report a case of severe lactic acidosis in a 3-year-old boy, after 20 days of total parenteral nutrition without vitamin supplementation. This child with acute lymphoblastic leukemia underwent a period of severe refractory lactic acidosis (pH between 6.81 and 7.00 and a serum lactate level up to 38 mmol/liter) leading to cardiac arrest. After the initial resuscitation and the subsequent treatment of shock and vitamin K deficiency, acute peritoneal dialysis was instituted to correct the severe lactic acidosis. Initial low plasma thiamine levels confirmed the diagnosis of thiamine deficiency. An associated transient pancreatic dysfunction was also noted. The patient's overall course with thiamine replacement therapy led to a complete recovery within 5 days and no sequelae were noted after 12 months. 
Assessment of aortic regurgitation by the acceleration flow signal void proximal to the leaking orifice in cinemagnetic resonance imaging. BACKGROUND. The proximal acceleration flow region is a laminar flow field that is located immediately upstream from the leaking orifice. The purpose of this study was to evaluate whether cinemagnetic resonance imaging can provide information regarding the proximal acceleration flow region in patients with aortic regurgitation and to analyze the relation between the area of the proximal acceleration flow delineated by cinemagnetic resonance imaging and the severity of aortic regurgitation delineated by angiography. METHODS AND RESULTS. Thirty-eight consecutive patients who underwent aortography were examined by cinemagnetic resonance imaging. The region of proximal flow acceleration was identified as a semicircular-shaped signal void in the aorta during diastole. Cinemagnetic resonance imaging detected the proximal acceleration flow region in 26 of the 30 patients who were proved to have this lesion (sensitivity, 87%). In eight patients without aortic regurgitation according to aortography, no proximal acceleration flow region was detected (specificity, 100%). The area of the acceleration flow signal void from the long-axis view was well correlated with angiographic degree of aortic regurgitation. CONCLUSIONS. Cinemagnetic resonance imaging is useful in detecting the proximal acceleration flow region and permits noninvasive assessment of the severity of aortic regurgitation. 
Neutrophil activation is confined to the maternal circulation in pregnancy-induced hypertension. The aim of this study was to determine whether neutrophil activation occurs in the fetal circulation in pregnancy-induced hypertension and to correlate this with evidence of neutrophil activation in the maternal circulation. Twenty-one normal pregnancies and 23 complicated by pregnancy-induced hypertension were studied in the third trimester. The mean length of gestation at delivery was significantly shorter (P less than .01) and the mean birth weight percentile was significantly lower (P less than .05) in the hypertensive group; otherwise the groups were comparable. Blood was obtained before cesarean delivery or established labor in the mothers and immediately after delivery from the umbilical vein. Plasma neutrophil elastase, which is released after neutrophil activation, was measured by radioimmunoassay as a marker for neutrophil activation. The mean (+/- standard error) concentration of neutrophil elastase in maternal plasma in the hypertensive group (35.9 +/- 4.7 ng/mL) was significantly higher than in the normal group (20.8 +/- 0.87 ng/mL) (P less than .005). The concentration of neutrophil elastase in umbilical venous plasma was not significantly different between the normal and hypertensive groups. However, significantly higher concentrations of neutrophil elastase were found in the umbilical venous plasma of pregnancies delivered vaginally compared with those delivered by cesarean (P less than .05) regardless of diagnosis. There was no correlation between maternal venous and umbilical venous plasma neutrophil elastase concentrations, birth weight percentile, plasma urate, or platelet count. These data suggest that neutrophil activation is confined to the maternal circulation in pregnancy-induced hypertension where it may contribute to vascular damage and dysfunction in areas such as the placental bed. 
The anterior inferior cerebellar artery in the internal auditory canal. It has been proposed that compression of the auditory and vestibular nerve trunks by vascular loops might be the cause of otherwise unexplained hearing loss, tinnitus, and vertigo, as well as Meniere's disease. We studied the human temporal bone histological collection at the Massachusetts Eye and Ear Infirmary to determine whether audiovestibular symptoms could be correlated with the presence of the anterior inferior cerebellar artery within the internal auditory canal. Anterior inferior cerebellar artery loops were found within the internal auditory canals of 12.3% of 1327 temporal bones, about half the number found when preparations with intact brains are studied. This difference can be attributed to avulsion of the anterior inferior cerebellar artery during removal of the brain at autopsy. There were 5 cases of unexplained unilateral hearing loss with anterior inferior cerebellar artery loops: 3 in the opposite ear and 2 in both ears. There were 2 cases with unilateral unexplained tinnitus with anterior inferior cerebellar artery loops: 1 in the involved ear and 1 in the opposite ear. A case with bilateral tinnitus had an anterior inferior cerebellar artery loop in 1 ear. There were 29 cases of vertigo with no peripheral histopathological correlate or central nervous system disorder; anterior inferior cerebellar artery loops were found in the internal auditory canals of 7 (12.5%) of the 56 ears in this group, which is not significantly different from the 12.3% incidence recorded for the entire collection. In 23 cases of unilateral Meniere's disease, there were anterior inferior cerebellar artery loops in the hydropic ears in 3, the opposite ear in 1, and both ears in 1. We can find no correlation between unexplained hearing loss, tinnitus, vertigo, or Meniere's disease and the presence of the anterior inferior cerebellar artery in the internal auditory canal. 
Identification and characterization of a low-affinity granulocyte-macrophage colony-stimulating factor receptor on primary and cultured human melanoma cells. Hematopoietic growth factor receptors are present on cells of normal nonhematopoietic tissues such as endothelium and placenta. We previously demonstrated functional human granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors on small cell carcinoma of the lung cell lines, and others have reported that certain solid tumor cell lines respond to GM-CSF in clonogenic assays. In the current study, we examine human melanoma cell lines and fresh specimens of melanoma to determine whether they have functional GM-CSF receptors. Scatchard analyses of 125I-GM-CSF equilibrium binding to melanoma cell lines showed a mean of 542 +/- 67 sites per cell with a kd of 0.72 +/- 0.14 nmol/L. Cross-linking studies in the melanoma cell line, M14, showed a major GM-CSF receptor species of 84,000 daltons. Under the conditions tested, the M14 cells did not have a proliferative response to GM-CSF in vitro, nor was any induction of primary response genes detected by Northern analysis in response to GM-CSF. Studies to determine internal translocation of the receptor-ligand complex indicated less than 10% of the 125I-GM-CSF internalized was specifically bound to receptors. Primary melanoma cells from five surgical specimens had GM-CSF receptors; Scatchard analysis was performed on one sample, showing 555 sites/cell with a kd of 0.23 nmol/L. These results indicate that human tumor cells may express a low-affinity GM-CSF receptor protein that localizes to the cell surface and binds ligand, but lacks functional components or accessory factors needed to transduce a signal. 
Primary anterior mediastinal B-cell lymphoma. A clinicopathologic and immunohistochemical study of 16 cases. Sixteen cases of primary anterior mediastinal B-cell lymphoma were characterized by morphologic, immunophenotypic, and clinical profiles. Twelve were men and four were women. The median age was 42 years. Virtually all tumors were of large cell type. Three main morphologic categories were identified, with one rare exception. In some tumors, the cells were compatible with centrocytes and centroblasts (four). Others had cells readily identifiable as centroblasts (six). Both these groups had a variable proportion of cells with multilobed nuclei. A third group was composed mainly of unclassifiable cells with multilobed nuclei (five). All had discernible sclerosis of varying intensity. A wider range of morphologic features and different sex distribution was noticed in comparison with previously reported clear cell features and younger women. The dominant phenotype of these B-cell lymphomas was CD19+, CD22+, CD37+, CD21-, CD30-, CD10-, CD5-, and Ig-negative. The finding of CD21-, Ig-negative phenotype, as observed by the authors and others, overlaps with some high-grade lymphomas of follicular center cell origin but is thought to bear similarity to a noncirculating population of thymic medullary B-cells. The tumors attained large size without peripheral dissemination and responded to chemotherapy as well as radiotherapy. 
Scirrhous carcinoma of the stomach versus hypertrophic gastritis: findings at endoscopic US. To differentiate scirrhous carcinoma from hypertrophic gastritis, 16 patients with scirrhous carcinoma of the stomach and seven patients with hypertrophic gastritis were examined with endoscopic ultrasonography (US) between August 1987 and October 1990. US images of the normal gastric walls of 16 patients with gastric ulcers served as controls. Characteristic features of scirrhous carcinoma included an irregular hypoechoic enlargement of the third (submucosa) and fourth (muscularis propria) layers. The mean thickness of the third and fourth layers was increased sixfold and threefold, respectively, compared with thickness in healthy subjects. In the patients with scirrhous carcinoma, the mucosal layer remained normal in appearance at US, and it was possible to distinguish the five-layer structure of the gastric wall. These findings were prospectively correlated with histopathologic findings in the resected specimens. In contrast, only the mucosal layer was thickened in cases of hypertrophic gastritis. Recognition of these patterns at US can aid in the differential diagnosis of scirrhous carcinoma and such benign diseases as hypertrophic gastritis with a thickened gastric wall. 
Enhanced detection of intracardiac sources of cerebral emboli by transesophageal echocardiography. We performed transesophageal echocardiography in 50 consecutive hospitalized patients with recent transient ischemic attack or stroke of embolic origin to determine whether transesophageal echocardiography is more sensitive than transthoracic echocardiography in detection of possible intracardiac sources of embolism. Twenty-six of 50 patients with a negative transthoracic echocardiogram for potential source of emboli had a transesophageal echocardiography study that demonstrated at least one intracardiac abnormality. Abnormalities noted by transesophageal echocardiography included five of 50 patients with either a left atrial or left atrial appendage clot, four patients with a patent foramen ovale, and nine patients with spontaneous echocardiographic contrast. In 11 of 50 patients with no other source of embolism, we found highly mobile filamentous strands on the mitral valve, which have not been described previously. These mitral valve echo strands may represent a fissured surface or fibrosis that can serve as a nidus for thrombus formation. We detected no unexpected left ventricular thrombus or left atrial myxoma. Factors significantly associated with a greater likelihood of a positive transesophageal echocardiography study included left atrial enlargement, atrial fibrillation, and a calcified or thickened mitral valve. Our study suggests that transesophageal echocardiography is a valuable addition to transthoracic echocardiography in investigating potential intracardiac sources of embolism. 
Ependymoma: internal correlations among pathological signs: the anaplastic variant. In a series of 298 cases of ependymoma, survival analysis identified some prognostic histological factors but failed to demonstrate a worse survival for the anaplastic variant diagnosed with the common criteria used for assessing anaplasia in primitive brain tumors. This finding suggests that either anaplastic ependymoma does not exist, or that the established criteria are not useful in its identification. To solve these problems, the association of histological, immunohistochemical, and ultrastructural signs in 173 intracranial cases was investigated and analyzed by means of contingency tables. Many signs had only focal distribution. Some signs, meaningful for anaplasia, such as very high cell density and number of mitoses, were found to be associated, whereas other signs usually considered indicative of anaplasia, such as endothelial hyperplasia, glomeruli, and necrosers, were not. In addition, pseudorosettes, mesodermic areas, and incomplete formation of perivascular pseudorosettes were signs associated with very high cell density and number of mitoses. Distribution of glial fibrillary acidic protein and vimentin, as well as other immunohistochemical and ultrastructural features, were not helpful, with the exception of microsettes found by electron microscopy. Our conclusion is that the anaplastic variant of ependymoma is recognizable only when some histological prognostic factors, such as cell density and number of mitoses, are maximally expressed. 
Complications of percutaneous intra-aortic balloon pump use in patients with peripheral vascular disease. Percutaneous intra-aortic balloon pump use may carry an increased risk for patients with peripheral vascular disease. To determine the incidence and types of associated complications, the medical records of 144 patients who underwent a total of 153 percutaneous intra-aortic balloon pump insertions were reviewed. Patients were divided into two groups. Group 1 was composed of 20 patients with a history of peripheral vascular disease. Group 2 was composed of 124 patients without such history; they underwent a total of 133 insertions. Nineteen major complications (12%) occurred, 12 in group 1 (60% of 20 insertions) and seven in group 2 (5% of 133 insertions). Major complications were further classified by their nature: embolic, occlusive, and technical. All three types of complications occurred more frequently in group 1. Embolic complications occurred more frequently in patients with aneurysms and proved the most lethal, with two of six deaths in group 1 resulting from this complication. 
Influence of angiotensin converting enzyme inhibition on pump function and cardiac contractility in patients with chronic congestive heart failure. Eleven patients with coronary artery disease and chronic heart failure were studied before and three months after the angiotensin converting enzyme inhibitor enalapril was added to their frusemide medication. The following were measured: left ventricular pressure and volume with transient occlusion of the inferior vena cava, radionuclide angiography, and hormone concentrations in plasma. As in other reported studies, the clinical condition of the patients improved and their exercise tolerance increased moderately. Addition of enalapril reduced end diastolic and systolic pressure, reduced ventricular volume, and concomitantly increased the ejection fraction. The end systolic pressure-volume relation shifted to the left as it did in a similar animal study. In the animal study unloading by a vasodilator did not induce a leftward shift, so it can be inferred that in the present study unloading combined with a decrease in the angiotensin concentration was instrumental in remodelling the heart. Though unloading was expected to have a beneficial effect on the oxygen supply/demand ratio of the heart, the patients still showed the same drop in the ejection fraction during exercise as they did before treatment with enalapril, and early diastolic filling did not improve. Normally, regression of cardiac dilatation is only found if pump function improves; the present study showed that unloading in combination with angiotensin converting enzyme inhibition reshapes the ventricle without improving intrinsic pump function. 
Ambulatory blood pressure monitoring in hypertension. Compared with blood pressure measurements in the office setting, ambulatory blood pressure monitoring offers a more accurate and reliable method of diagnosing and managing hypertension. Indications for ambulatory blood pressure monitoring include borderline hypertension, a discrepancy between home and office blood pressure measurements, persistent blood pressure elevation in the office with no end-organ damage, episodic elevations of blood pressure or suggestive symptoms, hypertension resistant to treatment, episodic angina not related to exercise, end-organ damage but normal office blood pressure readings, and evaluation of the efficacy of antihypertensive agents. Several cases are presented for review. 
Acute leukemia after a primary myelodysplastic syndrome: immunophenotypic, genotypic, and clinical characteristics. We studied the nature of blast cells in 41 patients with acute leukemia following a previous primary myelodysplastic syndrome (MDS) by a combined multiparameter analysis including morphologic, immunophenotypic, and molecular genetic (Igs, T-cell receptor (TCR)-beta, -gamma, and -delta and the major breakpoint cluster region [M-bcr]) investigations. In addition, the clinical and hematologic characteristics according to the immunophenotype of blast cells were analyzed. Our results show that, although the granulocytic and/or monocytic lineages are those most commonly involved in these acute leukemias, other cell components, including the megakaryocytic and lymphoid, may be present (12% and 15% of the cases, respectively). Moreover, both morphologic and phenotypic studies show the frequent coexistence of two or three cell populations. Interestingly, in all cases the lymphoblastic component constantly displayed an early B phenotype (CD19+, CD10-, TdT+). Upon analyzing whether the type of MDS conditioned any differences in the immunophenotype of blast cells, we observed that, although the lymphoid lineage may be involved in all MDS subgroups, some differences emerge within the myeloid leukemic transformations. Thus, the refractory anemias with excess of blasts (RAEB) and RAEB in transformation displayed a significantly higher incidence of myeloblastic and megakaryoblastic transformations, while in the RA, RA with ring sideroblasts and chronic myelomonocytic leukemia, the granulo-monocytic phenotype predominated. In addition, our results show that the clinical and hematologic characteristics of these patients may be partially related to the immunophenotype of the blast cells. Ig heavy chain gene rearrangements were found in two of 19 patients analyzed (11%), one with a hybrid leukemia (lymphoid-myeloid) and the other with a granulo-monocytic phenotype. Two other hybrid transformations analyzed were in germline configuration. Gamma and delta gene rearrangements were found in 21% and 37% of these acute transformation, respectively. The TCR-beta and M-bcr were in germline configuration in all 19 cases studied. In summary, immunophenotype and molecular studies point to a pluripotent stem cell with preferential myeloid commitment as the target cell of leukemias following a primary MDS. 
Early photocoagulation for diabetic retinopathy. ETDRS report number 9. Early Treatment Diabetic Retinopathy Study Research Group. The Early Treatment Diabetic Retinopathy Study (ETDRS) enrolled 3711 patients with mild-to-severe nonproliferative or early proliferative diabetic retinopathy in both eyes. One eye of each patient was assigned randomly to early photocoagulation and the other to deferral of photocoagulation. Follow-up examinations were scheduled at least every 4 months and photocoagulation was initiated in eyes assigned to deferral as soon as high-risk proliferative retinopathy was detected. Eyes selected for early photocoagulation received one of four different combinations of scatter (panretinal) and focal treatment. This early treatment, compared with deferral of photocoagulation, was associated with a small reduction in the incidence of severe visual loss (visual acuity less than 5/200 at two consecutive visits), but 5-year rates were low in both the early treatment and deferral groups (2.6% and 3.7%, respectively). Adverse effects of scatter photocoagulation on visual acuity and visual field also were observed. These adverse effects were most evident in the months immediately following treatment and were less in eyes assigned to less extensive scatter photocoagulation. Provided careful follow-up can be maintained, scatter photocoagulation is not recommended for eyes with mild or moderate nonproliferative diabetic retinopathy. When retinopathy is more severe, scatter photocoagulation should be considered and usually should not be delayed if the eye has reached the high-risk proliferative stage. The ETDRS results demonstrate that, for eyes with macular edema, focal photocoagulation is effective in reducing the risk of moderate visual loss but that scatter photocoagulation is not. Focal treatment also increases the chance of visual improvement, decreases the frequency of persistent macular edema, and causes only minor visual field losses. Focal treatment should be considered for eyes with macular edema that involves or threatens the center of the macula. 
Anaerobic pathogenesis: collagenase production by Peptostreptococcus magnus and its relationship to site of infection. Fifty isolates of Peptostreptococcus magnus from intraabdominal sepsis, nonpuerperal breast abscess, and diabetic foot infections were examined for collagenase activity using bovine type I collagen. Collagenase production was detected in a higher percentage of strains from nonpuerperal breast and diabetic foot specimens (P less than .001). This enzyme may be responsible for P. magnus playing a more central role in the pathogenesis of nonpuerperal breast abscess and diabetic foot disease than in intraabdominal sepsis. 
Comparative effects of pacing-induced and balloon coronary occlusion ischemia on left ventricular diastolic function in man. BACKGROUND. Effects of pacing-induced and coronary occlusion myocardial ischemia on left ventricular (LV) function have been compared only in anesthetized dogs. Diastolic properties of the same LV anterior wall segment were therefore compared in 12 patients with single-vessel proximal left anterior descending coronary artery stenosis at rest, immediately after 7 +/- 1.2 minutes of pacing, and at the end of a 1-minute balloon occlusion of coronary angioplasty (CO). METHODS AND RESULTS. Shifts of the diastolic LV pressure-length relation, derived from simultaneous tip-micromanometer LV pressure recordings and digital subtraction LV angiograms, were used as an index of regional diastolic LV distensibility of the anterior wall segment. Immediately after pacing, LV end-diastolic pressure rose from 13.5 +/- 3.5 to 23.8 +/- 7.0 mm Hg (p less than 0.01 versus at rest) without a significant change of the LV end-diastolic volume index (83.1 +/- 18.9 versus 88.4 +/- 16.5 ml/m2), percentage systolic shortening (%SS) of the ischemic segment fell from 40.1 +/- 10.6% to 25.2 +/- 8.6% (p less than 0.01), and the diastolic LV pressure-radial length (P-RL) plot of the ischemic segment was shifted upward by 7.1 +/- 5.0 mm Hg for portions of the plot that overlapped with the diastolic LV P-RL plot at rest. At the end of CO, LV end-diastolic pressure rose to 20.8 +/- 7.8 mm Hg (p less than 0.01 versus at rest) and the LV end-diastolic volume index rose to 95.6 +/- 16.3 ml/m2 (p less than 0.05 versus at rest, p less than 0.05 versus after pacing). Ejection fraction and %SS of the ischemic segment fell respectively from 76.6 +/- 6.8% to 46.6 +/- 11.4% (p less than 0.01 versus at rest, p less than 0.01 versus after pacing) and from 40.1 +/- 10.6% to 6.4 +/- 8.6% (p less than 0.01 versus at rest, p less than 0.01 versus after pacing). The diastolic LV P-RL plot of the ischemic segment was shifted upward by 3.1 +/- 2.3 mm Hg for portions of the plot that overlapped with the diastolic LV P-RL plot at rest. This upward shift at the end of CO was significantly smaller (p less than 0.05) than that immediately after pacing. At the end of CO, a correlation (p less than 0.03) was observed for the ischemic segment between %SS and upward shift of the diastolic LV P-RL plot. CONCLUSIONS. The upward shift of the diastolic LV P-RL plot, which was used as an index of decreased regional diastolic LV distensibility, was larger immediately after pacing than at the end of CO. Persistent systolic shortening of ischemic myocardium seems to be a prerequisite for a decrease in diastolic distensibility of the ischemic segment because of the higher %SS of the ischemic segment immediately after pacing, and because of the correlation at the end of CO between the upward shift of the diastolic LV P-RL plot and %SS of the ischemic segment. 
A case of cardiac hydatid cyst localized on the interventricular septum and causing pulmonary emboli. Cardiac hydatid cyst is rarely encountered. In this article, a case of hydatid cyst localized in multiple organs including the ventricular septum and causing pulmonary emboli is reported. 
Lung function in former intravenous drug abusers: the effect of ubiquitous cigarette smoking. PURPOSE: To determine whether former intravenous drug abusers (IVDAs) demonstrate reductions in pulmonary function, especially in the diffusing capacity (DLCO), after adjustment for the effects of their ubiquitous smoking habit. Knowledge of baseline DLCO in this high-risk group is important in evaluating the effects of human immunodeficiency virus (HIV) and ensuing opportunistic infections. PATIENTS AND METHODS: Measurements of single-breath DLCO, forced vital capacity (FVC), and forced expiratory volume in 1 second (FEV1) were compared with predictive values that adjust for the effects of smoking. Patients were 98 ambulatory former IVDAs regularly attending a methadone maintenance program (62 men and 36 women; 94 current smokers, two ex-smokers, and two nonsmokers). RESULTS: When adjusted for smoking, FEV1 and DLCO were no different in the study sample than in cross sections of the general population: mean FEV1 105% predicted (men) and 97% predicted (women), mean DLCO 95% predicted (men) and 99% predicted (women). Eleven percent of the IVDAs had abnormal values for DLCO; only one subject had a value less than 50% of predicted. CONCLUSIONS: Most former IVDAs who regularly attend an ambulatory methadone program have normal DLCO values when the effects of smoking are taken into account. A decrease in DLCO in such subjects is presumptive evidence of superimposed disease, most likely related to opportunistic infections or HIV-associated malignancy or alveolitis. 
Noninvasive identification of myocardium at risk in patients with acute myocardial infarction and nondiagnostic electrocardiograms with technetium-99m-Sestamibi. BACKGROUND. Patients who have chest pain without electrocardiographic ST elevation are not candidates for thrombolytic therapy in most clinical trials. This study examined the value of technetium-99m-Sestamibi tomographic imaging to assess myocardial perfusion in patients during chest pain without ST elevation. METHODS AND RESULTS. Tc-99m-Sestamibi was injected in 14 patients who had chest pain without ST elevation, who subsequently developed enzymatic evidence of myocardial infarction within 24 hours. Tomographic imaging was performed 1-6 hours after injection. Thirteen of 14 patients showed significant perfusion defects indicative of acute myocardial infarction consistent with absent perfusion (20 +/- 15% of the left ventricle; range, 2-53%); one patient had normal images. Because of the absence of definitive electrocardiographic changes, only five patients received reperfusion therapy within 6 hours of the onset of chest pain. Regional wall motion abnormalities were present in nine of nine patients undergoing contrast ventriculography and correlated with the location of the Tc-99m-Sestamibi perfusion defect. At the time of subsequent coronary angiography, total arterial occlusion was present in 11 of the 14 patients. The infarct-related artery could be identified in 13 of the 14 patients. In six of these 13 patients, the left circumflex was the infarct-related artery. CONCLUSIONS. Patients who have chest pain without electrocardiographic ST elevation may have arterial occlusion and significant myocardium at risk. Tc-99m-Sestamibi imaging may be of benefit in identifying these patients early so that they can be considered for acute reperfusion therapy. 
Efficacy and safety of a short-term (6-h) intravenous infusion of dopexamine in patients with severe congestive heart failure: a randomized, double-blind, parallel, placebo-controlled multicenter study. Dopexamine hydrochloride is a new synthetic catechol that offers a unique profile of adrenergic and dopaminergic activity. In this multicenter, parallel design, placebo-controlled study, 45 patients with functional class III or IV chronic congestive heart failure were randomized to receive a placebo infusion or one of three different doses of dopexamine. After a 2-h dose titration sequence, patients received a 6-h constant dose infusion. During this 6-h period, dopexamine was infused at rates of 1, 2 and 4 micrograms/kg body weight per min in the low, intermediate and high dose groups, respectively. In patients receiving high dose infusion, dopexamine produced a 78% increase in cardiac index associated with a 43% decrease in systemic vascular resistance and 24% increase in heart rate (p less than 0.05 vs. placebo for all three variables). There was a trend (p = NS) toward a moderate increase in cardiac index at low and intermediate doses. In patients randomized to receive dopexamine, right atrial, systemic arterial, pulmonary artery and pulmonary capillary wedge pressures showed minimal change from baseline and did not differ statistically from the placebo response. Very few patients developed adverse reactions related to dopexamine, although five patients randomized to receive high dose and three patients randomized to receive intermediate dose dopexamine required dose reduction because hemodynamic variables exceeded arbitrary safety limits or the patients developed symptoms related to the study medication. dopexamine in higher doses effectively increases cardiac index in association with a reduction in systemic vascular resistance. Additional clinical studies are indicated to evaluate the merits of dopexamine in comparison with other inotropic and vasodilator medications. 
The treatment of mild hypertension study. A randomized, placebo-controlled trial of a nutritional-hygienic regimen along with various drug monotherapies. The Treatment of Mild Hypertension Research Group. There is no consensus for the optimal treatment program for individuals with mild hypertension, including whether treatment should emphasize life-style changes alone, such as weight loss, reduction of sodium and alcohol intake, and increased physical activity, or whether it should also include a pharmacologic component. The dilemma is accentuated by the availability of many drugs from different classes to lower blood pressure. To study the relative efficacy and safety of a combination of pharmacologic and nutritional-hygienic intervention compared with nutritional-hygienic intervention alone, a double-blind, controlled clinical trial was initiated. Nine hundred two men and women with mild hypertension (average blood pressure, 140/91 mm Hg) were randomized to receive nutritional-hygienic intervention plus one of six treatments: (1) placebo; (2) diuretic (chlorthalidone); (3) beta-blocker (acebutolol); (4) alpha 1-antagonist (doxazosin mesylate); (5) calcium antagonist (amlodipine maleate); or (6) angiotensin-converting enzyme inhibitor (enalapril maleate). After 12 months, weight loss averaged 4.5 kg, urinary sodium excretion was reduced by 23%, and reported leisure-time physical activity was nearly doubled. Systolic and diastolic blood pressure in the group given nutritional-hygienic intervention alone (placebo) were reduced by 10.6 and 8.1 mm Hg, respectively. For participants in the five groups receiving antihypertensive medication in addition to nutritional-hygienic treatment, blood pressure reductions were significantly greater than those achieved with nutritional-hygienic treatment alone (range, 16 to 22 mm Hg for systolic and 12 to 14 mm Hg for diastolic blood pressure). Although differences among treatment groups in certain dimensions of quality of life, self-reported side effects, plasma lipid levels, and biochemical measures were observed, no consistent pattern in the differences was noted. Nutritional-hygienic therapy is an effective first-step treatment for persons with mild hypertension, and significant additional blood pressure lowering with minimal short-term side effects can be achieved by adding one of five different classes of antihypertensive agents. 
Effective aortic regurgitant orifice area: description of a method based on the conservation of mass. The natural history of aortic regurgitation is incompletely understood in part because of the lack of a simple method to estimate the defect size. A method of determining the effective regurgitant orifice area that combines Doppler catheter and Doppler echocardiographic techniques and is based on the principle of conservation of mass (the continuity equation) is described. To validate the application of the Doppler catheter system for measuring regurgitant supravalvular diastolic flow, an in vitro model of retrograde aortic flow was used. These studies indicated that measurements of supravalvular retrograde velocity with the Doppler catheter accurately reflect retrograde diastolic velocity when the aorta is less than 4.8 cm in diameter. Twenty-three patients undergoing cardiac catheterization were studied; 20 of these patients had aortic regurgitation. Retrograde supravalvular diastolic velocity was determined from a Doppler catheter positioned above the aortic valve. The effective regurgitant orifice area was calculated with use of the Doppler catheter-derived regurgitant volume and mean transvalvular diastolic velocity as determined by either catheterization or continuous wave Doppler echocardiography. The catheterization-derived regurgitant orifice area increased with the angiographic grade of as follows: 1+ (0.04 to 0.10 cm2), 2+ (0.15 to 0.49 cm2), 3+ (0.29 to 1.11 cm2) and 4+ (1.24 to 1.33 cm2). By combining Doppler catheter, echocardiographic and cardiac catheterization techniques, the effective aortic regurgitant orifice area may be estimated; this hydrodynamic area correlates with grading by supravalvular aortography. Calculation of this area provides a quantitative alternative to aortography for estimating the severity of aortic regurgitation but should be used with caution in patients with a markedly dilated aorta. 
Long-term inhibition of tumor growth by tumor necrosis factor in the absence of cachexia or T-cell immunity. The relationship between detrimental (cachectic) and beneficial (antitumor) effects of tumor necrosis factor (TNF) was studied in mice bearing murine tumors transfected to secrete human TNF. In vitro, the TNF-producing transfectants were resistant to the secreted TNF and grew at rates similar to those of untransfected cells or transfected cells that did not secrete TNF. However, tumors formed by the TNF-secreting cells in vivo remained much smaller than the nonsecreting (transfected and untransfected) tumors. This inhibition of tumor growth required only relatively low serum levels of TNF, persisted for many weeks, and was independent of T cells since it occurred in nude mice. Growth of the TNF-secreting tumors increased dramatically after treatment with anti-human TNF antibody, indicating that extracellular TNF secreted by the tumor cells was necessary for the tumor inhibition. Severe weight loss characteristic of cachexia only occurred in animals with very high serum TNF levels (250 pg/ml) and could be prevented or reversed by anti-TNF antibody treatment. These data are consistent with the existence of a therapeutic window in which persistent exposure to human TNF can lead to prolonged inhibition of tumor growth in the absence of T-cell immunity or severe weight loss and without development of resistant tumor variants. 
Acute pulmonary hypertensive crisis in a patient with primary pulmonary hypertension treated by both epoprostenol (prostacyclin) and nitroprusside. A 19-year-old girl was diagnosed as having primary pulmonary hypertension that was confirmed by right heart catheterization. Acute right heart failure was associated with syncope. Stabilization, while not achieved with intravenous epoprostenol (Prostacyclin) alone, was achieved with intravenous prostacyclin and nitroprusside. 
Intracranial metastases from malignant pleural mesothelioma. Report of three autopsy cases and review of the literature. We report three cases of brain metastases from malignant pleural mesothelioma that were seen at autopsy. We present a summarized review of 15 similar reports that were previously published. Our study included three aged male patients with a long occupational history of heavy asbestos exposure. In two patients, the metastases were discovered incidentally at autopsy, and there were no neurologic symptoms referred to before death. In the other patient, who had clinically occult mesothelioma, the intracranial tumor was discovered ante mortem: in this patient, the clinical features, as well as a computed tomographic scan, suggested a primary tumor of the brain. Interestingly, the histologic features of the latter case that were seen at autopsy depicted a spindle cell tumor that focally exhibited pseudopalisading, necrosis, vascular buds, which deceptively recalled a glioblastoma. All the three cases shared a basic sarcomatous pattern of malignant pleural mesothelioma in both primary and metastatic tumors. The immunohistochemical profile was consistent with such interpretation. It was concluded that metastases to the brain from malignant pleural mesothelioma, although rare, are not exceptional even if their clinical relevance is not prominent. They are seen concomitantly with high-grade tumors, and by mimicking a primary tumor on a clinical, instrumental, and histologic ground, they may occasionally represent a potential source of diagnostic pitfall. 
Bilateral retinal artery occlusion due to mitral valve prolapse. We report a case of bilateral retinal artery occlusion due to mitral valve prolapse. Most patients with retinal ischaemia in whom it is found have not been previously known to have it. Since it is a common condition it would seem essential that it be included in the differential diagnosis of amaurosis fugax and retinal artery occlusion if future ischaemic events are to be prevented. All patients with retinal ischaemia should have a full cardiovascular examination supplemented by echocardiography. 
Resectable gastric carcinoma. An evaluation of preoperative and postoperative chemotherapy. Patients with locoregional gastric carcinoma often die because of the low rates of curative resection and frequent appearance of distant metastases (mainly peritoneal and hepatic). To evaluate the feasibility of preoperative and postoperative chemotherapy, 25 consecutive previously untreated patients with potentially resectable locoregional gastric carcinoma received two preoperative and three postoperative courses of etoposide, 5-fluorouracil, and cisplatin (EFP). Ninety-eight courses (median, five courses; range, two to five courses) were administered. Six patients had major responses to EFP. Eighteen patients (72%) had curative resections, and three specimens (12%) contained only microscopic carcinoma. At a median follow-up of 25 months, the median survival of 25 patients was 15 months (range, 4 to 32+ months). Peritoneal carcinomatosis was the most common indication of failure. One patient died of postoperative complications, but there were no deaths due to chemotherapy. EFP-induced toxic reactions were moderate. Preoperative and postoperative chemotherapy for locoregional gastric carcinoma is feasible, and additional studies to develop regimens that could result in 5% to 10% complete pathologic responses may be warranted. 
Stunned left ventricular myocardium after exercise treadmill testing in coronary artery disease. Myocardial stunning (postischemic ventricular dysfunction) occurs in dogs after coronary stenosis following treadmill exercise. Less data are available in humans regarding development of stunned myocardium after exercise. Regional wall motion changes were evaluated in 22 patients with known coronary artery disease using 2-dimensional echocardiography and exercise treadmill testing. Wall motion was scored as 1 = normal, 2 = hypokinetic, 3 = akinetic, 4 = dyskinetic. At least 1 left ventricular segment with normal resting function developed an increase in wall motion score at 15 or 30 minutes compared with values at rest. The wall motion score in the midportion of the ventricular septum increased from 1.0 at rest to 1.6 (p less than 0.004) at 30 minutes after exercise; the basal inferior wall score worsened from 1.0 at rest to 1.9 (p less than 0.01) at 30 minutes after exercise. Coronary angiographic data in these patients revealed that left anterior descending narrowing correlated best with left ventricular septal wall motion abnormalities, whereas right coronary artery and circumflex narrowing best correlated with inferior and posterior wall motion abnormalities. Eight normal adult volunteers with no history of myocardial ischemia also underwent 2-dimensional echocardiography and exercise testing. No wall motion abnormalities were observed at any time after exercise. The present study suggests that in patients with coronary artery disease, exercise treadmill testing may induce regional wall motion abnormalities of the left ventricle that persist greater than or equal to 30 minutes after exercise, an observation consistent with the phenomenon of stunned myocardium. 
Hepatobiliary complications of polyarteritis nodosa. Although polyarteritis nodosa (PAN) may result in thrombosis or aneurysm formation in any organ in the body, hepatobiliary complications are unusual. We reviewed seven cases that demonstrated the diagnostic difficulties and therapeutic options available in the management of hepatobiliary PAN. No consistent sign that indicated the severity of hepatobiliary PAN could be identified. In cases of thrombotic PAN, acalculus cholecystitis usually could be diagnosed preoperatively. Early tissue diagnosis and aggressive intervention are required for appropriate patient treatment. If the diagnosis is unclear, a preoperative muscle or skin biopsy specimen is often helpful in establishing a tissue diagnosis of PAN, even if no obvious pathologic condition is evident. Patients who undergo celiotomy for acalculus cholecystitis or peritoneal signs of an unclear origin should have tissue specimens (gallbladder wall, liver, or omentum) submitted for pathologic study. Angiography may be diagnostic preoperatively or when results of biopsies are equivocal. In addition, early angiography can define the extent of visceral involvement and permit control by embolization of hemorrhage secondary to aneurysm rupture. Awareness of the possibilities of thrombotic, ischemic, or bleeding complications from PAN allows more aggressive and rapid management of abdominal complaints, especially in patients who are receiving immunosuppressant therapy. 
Problems and coping strategies of individuals with traumatic brain injury and their spouses. A pilot investigation is reported on the problems and coping strategies of 20 married men and 11 married women with traumatic brain injury (TBI) and their able-bodied spouses. All injured subjects experienced severe head injury at least one and a half years earlier. A structured, small-group discussion process was used to elicit a prioritized list of problems and a similar list of coping strategies. Individuals with TBI and their spouses identified problems in living as most important; loss of employment and restrictions on autonomy were reported as the most problematic. Men with TBI placed priority on controlling their anger, whereas, women with TBI were concerned with their mood disorders, particularly depression. Women with TBI and able-bodied wives of men with TBI placed high priority on the use of support groups as a coping strategy. Men placed higher priority on individualistic approaches to adjustment, such as suppression of feelings. A number of testable hypotheses resulted from the pilot study. 
Production of endothelium-derived contracting factor is enhanced after coronary reperfusion. To determine whether coronary reperfusion enhances the production of endothelium-derived contracting factor, we investigated dogs subjected to global cardiac ischemia (45 minutes) followed by reperfusion (60 minutes). Segments of reperfused and control coronary arteries were suspended in organ chambers to measure isometric force. Perfusate hypoxia caused endothelium-dependent contraction in the control and reperfused arteries. However, reperfused arteries exhibited hypoxic contraction that was significantly greater than control segments. The hypoxic contractions in both the control and reperfused arteries could be inhibited by NG-monomethyl-L-arginine (L-NMMA), the blocker of endothelial cell synthesis of nitric oxide from L-arginine. The action of L-NMMA could be reversed by L-arginine but not D-arginine. Thus, after reperfusion, augmented production of endothelium-derived contracting factor occurs by an L-arginine-dependent pathway. We hypothesize that nitric oxide produced by L-arginine metabolism combines with superoxide anion to produce the peroxynitrite anion (ONOO-), which is metabolized to endothelium-derived contracting factor or induces its synthesis. Augmented production of endothelium-derived contracting factor would favor vasospasm after reperfusion. 
Risk factors for stroke in patients with nonrheumatic atrial fibrillation: a case-control study. PURPOSE: Randomized controlled trials have demonstrated that anticoagulant therapy is very effective at preventing stroke among patients with nonrheumatic atrial fibrillation. However, these trials have reported too few strokes for powerful risk factor analysis. Observational studies may provide additional information. The purpose of this study was to identify risk factors in a larger number of patients with stroke and nonrheumatic atrial fibrillation, using case-control methodology. PATIENTS AND METHODS: We identified all patients discharged from one hospital over an 8-year period who met our case definition of nonrheumatic atrial fibrillation and ischemic stroke (n = 134), and compared them with contemporaneous control subjects who were discharged with nonrheumatic atrial fibrillation without stroke (n = 131). RESULTS: Cases and controls were similar in terms of duration of atrial fibrillation; proportion with paroxysmal atrial fibrillation; percentage with a past medical history of angina, myocardial infarction, congestive heart failure, diabetes, or smoking; and mean left atrial size. In contrast, cases were significantly older than controls (78.5 versus 74.8 years, p = 0.002) and more likely to have a history of hypertension (55% versus 38%, p = 0.0093). The relative odds for stroke was 1.91 for patients with hypertension, 1.73 for patients older than 75 years, and 3.26 for patients with both factors. CONCLUSIONS: Our analysis suggests that age and hypertension should be considered when deciding upon long-term anticoagulant therapy to prevent stroke in patients with nonrheumatic atrial fibrillation. 
Natural history of dilated cardiomyopathy in children. To assess the natural history and potential risk factors in childhood dilated cardiomyopathy, we investigated 25 patients (ages 9.6 +/- 4.4 years) who presented after they were 2 years old. All patients had symptoms of congestive heart failure and reduced contractility with a dilated left ventricle at presentation. Two factors at presentation were significantly different between patients who died less than 1 year after the presentation (n = 14) and those who survived for more than 1 year (n = 9); cardiothoracic ratio (65.1% +/- 6.8% vs 57.1% +/- 6.1%, p less than 0.01) and left ventricular ejection fraction (31.3% +/- 7.0% vs 40.0% +/- 6.2%, p less than 0.05). Irrespective of intensive medical therapy, dilated cardiomyopathy in children had a poor prognosis; the actuarial survival rate was 41% at 1 year and 20% at 3 years. Other forms of therapy should be considered in the early stages of dilated cardiomyopathy in this high-risk group. 
Immunophenotyping of lymphocytes in liver tissue of patients with chronic liver diseases by flow cytometry. Immunological factors are important in the pathogenesis of a spectrum of hepatobiliary diseases. To characterize the nature of specific immunological responses in liver disease, we determined lymphocyte changes in liver tissue and in blood using flow cytometry. A total of 113 liver biopsy specimens was collected from patients with the following diseases: 19 chronic hepatitis B; 39 chronic non-A, non-B hepatitis; 27 alcoholic liver disease; 10 hepatic malignancy; 8 autoimmune hepatitis; 6 fatty liver and 4 primary biliary cirrhosis. The lymphocytes were isolated from the liver biopsy specimens by mechanical and enzymatic methods. The lymphocyte yield was 7,901 +/- 575 cells/mg of liver tissue. The viability of lymphocytes was 97.7% +/- 0.3%. Lymphocytes were stained with four pairs of two-color mixed fluorescein-conjugated monoclonal antibodies, including T4-T8 (CD4/CD8), T11-B1 (CD2-CD20), NKH1-T8 (CD56-CD8), IL-2R1-T11 (CD25-CD2), and the ratios were determined by an Epics Profile flow cytometer. Immunophenotyping of lymphocytes in whole blood samples was simultaneously analyzed. Variability in lymphocyte yield and different patterns of lymphocyte subsets were found in the liver biopsy specimens. The yields of lymphocytes from patients with chronic non-A, non-B and autoimmune hepatitis were highest, and the lowest yield was from patients with fatty liver. Patients with primary biliary cirrhosis, fatty liver and hepatic malignancy had relatively high ratios of CD4/CD8, CD56/CD8 and CD25/CD2; whereas patients with chronic hepatitis B, autoimmune hepatitis and non-A, non-B hepatitis had lower ratios of CD4/CD8, CD56/CD8 and CD25/CD2. No difference in lymphocyte ratios between the patients with cirrhotic and noncirrhotic alcoholic liver disease was found. 
An evaluation of immunohistologic stains for immunoglobulin light chains in bone marrow biopsies in benign and malignant plasma cell proliferations. Bone marrow specimens from 226 patients with a variety of benign and malignant plasma cell proliferations were studied to assess the reliability of immunohistologic studies in their evaluation. The clonality of the bone marrow plasma cells was compared with results of serum and urine electrophoreses. Discordance was observed most frequently in cases in which a paraprotein was demonstrated, but no monoclonality was detected by immunoperoxidase (16 cases). Of these 16 cases, 9 had 5% or less bone marrow plasma cells. In only one case was the light chain class of the bone marrow plasma cells different from that of the paraprotein. If discordant cases with 5% or less plasma cells are eliminated, the overall concordance was 97%. The authors' findings indicate that immunohistologic studies for immunoglobulin light chains in Zenker-fixed decalcified bone marrow biopsy sections are reliable in the evaluation of patients with plasma cell proliferations when the marrow contains more than 5% plasma cells. 
Coronary recanalization rate after intravenous bolus of alteplase in acute myocardial infarction. The demonstration in animals that recombinant tissue-type plasminogen activator produces prolonged thrombolysis after its clearance from the circulation has prompted a few pilot studies of bolus administration in patients. Alteplase (bolus dose of 70 mg) resulted in the highest recanalization rate in our previous pilot study comparing bolus doses of 50, 60 and 70 mg of alteplase in patients with acute myocardial infarction. The aim of the present trial was to assess the efficacy and safety of the same bolus dose in a larger number of patients. A further objective was to study the angiographic reocclusion rate at 12 to 24 hours in patients who had a recanalized infarct-related coronary artery at 90 minutes and were randomized at that time to a bolus dose or an infusion for 3 hours of 30 mg of alteplase. Sixty patients with acute myocardial infarction and angiographically documented total occlusion of the infarct-related coronary artery before thrombolysis were treated within 5 hours of onset of symptoms with an intravenous 70-mg bolus dose of alteplase (or 80 mg if body weight was greater than or equal to 90 kg). Each patient received 5,000 IU of heparin intraarterially and 100 mg of aspirin by mouth before administration of alteplase. Coronary angiography was repeated 60 and 90 minutes after alteplase administration. The recanalization rate of the infarct-related coronary artery was 55% (95% confidence interval, 43 to 66%) at 60 minutes and 48% (95% confidence interval, 37 to 60%) at 90 minutes. Pretreatment levels of lipoprotein (a) were not significantly related to recanalization. 
Symptomatic intrasellar arachnoid cyst: case report. A case of a large symptomatic intrasellar arachnoid cyst with suprasellar extension is reported. A 53-year-old man was admitted because of decreased visual acuity. Magnetic resonance imaging showed a large intrasellar cyst extending into the suprasellar cistern, with compression of optic nerves. The intensity of the cyst was identical to that of the surrounding subarachnoid space on both T1-, T2-, and proton density-weighted images. Transsphenoidal surgery was performed, but subsequent refilling of the cyst required additional transcranial surgery. Analysis of the cerebrospinal fluid-like cystic fluid revealed high levels of protein and pituitary hormones. Histological study revealed that the cyst wall was composed of connective tissue and arachnoid cells, which were ultrastructurally characterized by a number of desmosomes. Diagnostic, surgical, and pathological features of intrasellar arachnoid cysts are discussed. 
Evidence of malignant features in histologically mature teratoma. A total of 33 specimens from 29 patients with residual stable teratoma and mature growing teratoma after chemotherapy was analyzed for clinicopathological and deoxyribonucleic acid (DNA) flow cytometric variables, as well as the presence of proliferative antigen and tumor marker levels in an attempt to explain their clinical behavior. We compared the flow cytometric and histological data of these stable and growing teratomas, and of nonseminomatous germ cell tumors before chemotherapy. The DNA content of residual teratoma did not differ significantly from that of the primary testicular tumors (1.38 versus 1.48). Histological analysis of stable and growing teratomas revealed no significant difference but proliferative cellular nuclear antigen was expressed mainly in the epithelial component of the growing teratoma. alpha-Fetoprotein, beta-human chorionic gonadotropin and carcinoembryonic antigen were elevated in the fluid of 6 excised teratomas, while concomitant serum levels were normal. The aneuploidy and elevated cystic fluid tumor markers confirm the malignant phenotype of post-chemotherapy residual teratomas. Therefore, complete surgical removal is essential despite the benign histological appearance. 
HIV-2 infection among prostitutes working in The Gambia: association with serological evidence of genital ulcer diseases and with generalized lymphadenopathy. Three hundred and fifty-five prostitutes working in The Gambia were enrolled in a study of retroviral infections. Eight-seven (24.6%) were infected with HIV-2 only, two (0.6%) with HIV-1 only, four (1.1%) had sera showing double HIV-1/HIV-2 reactivity, and 37 (10.4%) were seropositive for HTLV-I. After allowing for socioeconomic and serological variables in a multivariate analysis, HIV-2 infection was associated with serological evidence of a previous episode of syphilis [a rapid plasma reagin (RPR) positive/Treponema pallidum haemagglutination assay (TPHA) positive; odds ratio (OR) = 2.18, 95% confidence interval (CI) = 1.19-3.98], with having antibodies against Haemophilus ducreyi (OR = 2.05, 95% CI = 0.89-4.70) or against HTLV-I (OR = 2.17, 95% CI = 0.91-5.19). HIV-2-seropositive prostitutes were three times more likely [17 out of 78 (22%) versus 15 out of 219 (7%), P less than 0.001] to have generalized lymphadenopathy than those who were seronegative. These data suggest that genital ulcer diseases may facilitate the transmission of HIV-2, and that HIV-2 rapidly induces the appearance of generalized lymphadenopathy in a substantial proportion of infected individuals. 
Aortic dissection type A surgery: Doppler sonography to evaluate correct carotid artery perfusion during cardiopulmonary bypass. In the surgery of acute aortic type A dissection we have employed preoperative and intraoperative Doppler sonography, to check safe and correct perfusion of the carotid arteries by the cardiopulmonary bypass before instituting cardiac arrest. Ten patients, operated upon for acute aortic type A dissection, were evaluated by means of Doppler sonography and in two patients a very abnormal flow pattern was found in the carotid arteries at the moment of aortic cross-clamping; immediate unclamping allowed temporary antegrade carotid perfusion, while the perfusion technique was readjusted. We report our experience with preoperative and intraoperative Doppler sonography, which appears to be a valuable new method of improving the surgical management of acute aortic type A dissection. 
Diagnosis and monitoring of subarachnoid hemorrhage by transcranial color-coded real-time sonography. Thirty-six patients with acute spontaneous subarachnoid hemorrhage (26 caused by rupture of an aneurysm) were examined by transcranial color-coded real-time sonography by using a 2.25-MHz ultrasound transducer. In 20 of these 26 patients (76%), the aneurysm could be identified by a characteristic abnormal blood flow pattern within the aneurysm in coronal and axial scanning planes by transcranial color-coded real-time sonography. Blood within the basal cisterns, on top of the tentorium, and within the ventricles and parenchyma was sonographically detected by increased echodensity in 75%. In addition, cerebrospinal fluid circulation disturbances and cerebral vasospasm were detected in two-dimensional B-mode images in 85% and 100%, respectively. In Doppler mode, intravascular blood flow velocity could be quantified. We conclude that transcranial color-coded real-time sonography, a new, noninvasive method for diagnosis and follow-up of patients with subarachnoid hemorrhage, allows detection of the primary vascular lesion and monitoring of complications. 
Hypotensive anesthesia for scoliosis surgery in Jehovah's Witnesses. Hypotensive anesthesia has been advocated in spinal surgery for the purpose of diminishing operative blood loss. This study evaluated its effectiveness in 12 Jehovah's Witnesses undergoing Harrington instrumentation and fusion who refused transfusion. Previous series from this institute did not use deliberate hypotension because of routinely low blood loss. Compared with matched controls operated on under normotensive anesthesia, the Jehovah's Witness patients had lower absolute blood loss but also shorter operative time. Applied linear-regression analysis demonstrated that the diminished blood loss was associated with shorter operative time (P = 0.0002) rather than lower blood pressure. The majority of blood losses in spinal instrumentation with fusion occurs with decortication. This rapid bleeding occurs at venous pressures which are unaffected by arterial blood pressure manipulation. The authors conclude that spinal surgery is possible in Jehovah's Witnesses without transfusion and that operative technique is the single most important determinant of blood loss. 
Binding and internalization of transforming growth factor-beta 1 by human hepatoma cells: evidence for receptor recycling. Cellular processing of 125I-labeled transforming growth factor-beta 1 was investigated in the human hepatoma cell lines Hep G2 and Hep 3B. Binding of 125I-transforming growth factor-beta 1 to cell surface receptors was specific, saturable and calcium-independent. Both cell lines exhibited a single class of high-affinity (Kd = 2.2 x 10(-10) mol/L) binding sites (4.5 x 10(3) for the Hep G2 cell; 1.5 x 10(3) for the Hep 3B cell) for both human and porcine transforming growth factor-beta 1. Binding was temperature dependent, time dependent and pH dependent. Cell-bound 125I-transforming growth factor-beta 1 was removed by brief exposure to acidic medium (pH less than 4) but was converted into an acid-resistant state rapidly after shifting the cells to 37 degrees C. Spontaneous dissociation of bound ligand over a 6 hr period at 4 degrees C was less than 10%. Disuccinimidyl suberate was used to covalently label 125I-transforming growth factor-beta 1 to cell-surface binding sites. Labeling of the ligand/receptor complexes was inhibited by unlabeled transforming growth factor-beta 1 but was unaffected by other growth factors. The radiolabeled complexes showed approximate molecular weights of 280,000, 85,000 and 65,000 when run on reducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Cell-bound 125I-transforming growth factor-beta 1 was internalized and degraded at 37 degrees C, and the products were released into the medium as trichloroacetic acid-nonprecipitable radioactivity. The lysosomotropic base chloroquine and the carboxylic ionphore monensin inhibited degradation and release of 125I-labeled products from the cells. 
A prospective, controlled analysis of endoscopic cytotechniques for diagnosis of malignant biliary strictures. We prospectively collected brushings and bile for cytology in 30 consecutive patients with bile duct strictures (17 malignant, 13 benign) who were assessed by endoscopic retrograde cholangiography. When appropriate, the cellular debris on stents that were removed from individuals who were managed with these devices was evaluated for malignant cells as well. Our aim was to assess the value of these endoscopic cytotechniques for making a diagnosis of obstructing cancer of the biliary tract. A cumulative total of 78 specimens were obtained. Overall, sensitivity was highest for stent (36%) and brush (33%) cytology, compared with results obtained from bile (6%). If the results for all methods are combined, 47% of patients with cancer (eight of 17) could be diagnosed by one or more cytological technique. There were no false-positive results (specificity, 100%). Our results show that brush and stent cytology are nearly equivalent for detecting cancer, but because a diagnosis is delayed until the endoprosthesis is removed (mean 3.4 months), the brush technique is preferred. Results for bile cytology are marginal. Specificity for these cytotechniques is high; therefore, a positive result by any method is sufficient evidence for cancer, and other invasive diagnostic procedures are unnecessary. 
Coordinate regulation of HOX genes in human hematopoietic cells. Hematopoiesis is a continuous process in which precursor cells proliferate and differentiate throughout life. However, the molecular mechanisms that govern this process are not clearly defined. Homeobox-containing genes, encoding DNA-binding homeodomains, are a network of genes highly conserved throughout evolution. They are organized in clusters expressed in the developing embryo with a positional hierarchy. We have analyzed expression of the four human HOX loci in erythroleukemic, promyelocytic, and monocytic cell lines to investigate whether the physical organization of human HOX genes reflects a regulatory hierarchy involved in the differentiation process of hematopoietic cells. Our results demonstrate that cells representing various stages of hematopoietic differentiation display differential patterns of HOX gene expression and that HOX genes are coordinately switched on or off in blocks that may include entire loci. The entire HOX4 locus is silent in all lines analyzed and almost all the HOX2 genes are active in erythroleukemic cells and turned off in myeloid-restricted cells. Our observations provide information about the regulation of HOX genes and suggest that the coordinate regulation of these genes may play an important role in lineage determination during early steps of hematopoiesis. 
Epilepsy surgery in the posterior cortex. Fourteen (74%) of 19 patients obtained a significant reduction in seizures after posterior corticectomy; 6 (32%) were seizure-free over a median follow-up of 3.7 years (range, 1 to 14 years). Surgery included limited resections of the occipital lobe in 16 patients, posterior temporal region in 11, and posterior portion of parietal lobe in 7. Surgical failure related to probable multiple areas of epileptogenesis (4 patients), or limited resections (2 patients) to preserve visual fields (2 patients) and to avoid dyslexia (1 patient). Of 14 patients without a complete hemianopia preoperatively, 6 (43%) developed a new or increased visual field deficit, 2 (14%) of which were hemianopia. Four (36%) of 11 occipital lobe resections resulted in a new or increased visual field deficit: quadrantanopia in 3 and hemianopia in 1. Visual phenomena were the most common initial ictal symptoms, occurring in 13 (68%) of the 19 patients. Twelve patients had complex partial seizures: in 2, always without warning; in 7, always following an aura, usually visual; and in 3 patients, with or without warning. Scalp electroencephalography identified the origin of most recorded seizures in 12 (63%) of the 19 patients. A principal interictal spike focus appeared in 15 patients (79%), and always correlated with the epileptogenic lobe as defined by scalp and/or subdural-recorded seizures (14 patients) or by clinical analysis and computed tomography (1 patient). 
Arterial hemorrhage after pancreatoduodenectomy. The 'sentinel bleed'. Experienced centers report reduced operative mortality after pancreatoduodenectomy for cancer, but significant complications continue to occur in as many as 25% of patients. Anastomotic disruption leads to sepsis in the pancreatic bed where major vascular structures have been exposed by regional lymphadenectomy, creating a setting for arterial erosion or ligature slough and massive hemorrhage. Dehiscence of the pancreatojejunostomy is a particular risk. We treated five patients with arterial hemorrhage after pancreatoduodenectomy, all of whom had had "sentinel" bleeding from the abdominal drains or gastrointestinal tract. Results of endoscopy were misleading in two patients. Three of five patients were saved by prompt recognition, early operation, and, in one instance, angiographic embolization. Sentinel bleeding after pancreatoduodenectomy indicates local sepsis and probable anastomotic dehiscence. Recognition of its significance and prompt response may prevent exsanguination. 
Venous haemangioma of the neck and mediastinum. A case of cervico-mediastinal venous haemangioma with diffuse upper respiratory airway involvement is reported. The lesion was considered to be an ordinary supraglottic haemangioma at first. We recommend that adult cases of laryngeal haemangioma should be carefully examined for extra-laryngeal lesions. 
Evidence for superoxide radical-dependent coronary vasospasm after angioplasty in intact dogs. BACKGROUND. Active oxygen species can influence vascular tone and platelet activation through a variety of mechanisms. This study assessed the role of the superoxide anion, the hydroxyl radical, and hydrogen peroxide in vasoconstriction and mural thrombosis after coronary artery angioplasty in intact dogs. METHODS AND RESULTS. Injury was induced by inflation of a balloon catheter 50 +/- 6% above baseline arterial diameter; dogs were followed for 2 hours before death. Epicardial coronary diameters at arteriography and extent of thrombus deposition at serial histological sections were analyzed in controls (n = 20) and in dogs pretreated with superoxide dismutase (SOD, a superoxide radical scavenger, n = 10); other dogs were pretreated with the hydrogen peroxide scavenger catalase (n = 8), the iron chelator deferoxamine (n = 6), or the hydroxyl radical scavenger 1,3-dimethyl-2-thiourea (n = 9). Angioplasty-induced injury was similar among groups. After angioplasty, control dogs exhibited localized and persistent vessel constriction, which was maximal at the initial 5 minutes (28.9 +/- 6.3% diameter decrease versus baseline). Corresponding arterial diameters of SOD-treated dogs were 24-69% larger (95% confidence interval, p less than 0.001) than controls at 5 minutes and, on average, 32% larger than controls thereafter (p less than 0.01). Vasoconstriction was not prevented by the other treatments. The SOD dose used accounted for inhibition of zymosan-stimulated blood cytochrome c reduction versus baseline (7 +/- 3 versus 30 +/- 6 nmol/min/10(6) cells, respectively, p = 0.003); such inhibition occurred in no other group. Prevalence of mural thrombosis was similar among all groups, but large thrombi (greater than 15% of lumen area) were absent in SOD-treated dogs, contrary to control group (p = 0.028); other groups were similar to control. In the absence of injury, SOD alone induced no change in coronary diameter, coronary blood flow, or platelet aggregation. CONCLUSIONS. These data provide evidence implicating the superoxide radical in the genesis of vasoconstriction after coronary angioplasty in vivo. Such effects seem to be independent of its conversion to hydroxyl radicals and availability of hydrogen peroxide or catalytic iron complexes. 
Valproate in the treatment of persistent chronic daily headache. An open label study. Thirty patients with persistent chronic daily headache, unresponsive to various combinations of pharmacological and nonpharmacological treatment were selected for an open label study using divalproex sodium. All patients had normal liver function tests. After a baseline observation period of 1 month, patients were given divalproex sodium 1000 to 2000 mg per day, for a period of 3 months. Blood valproic acid levels were kept between 75 and 100 mcg/ml. Liver function studies and blood ammonia levels were obtained periodically. Based on weekly headache index, headache-free days, dysfunctional days and patients' general well-being rating and physicians' global assessment, two thirds of the patients improved significantly. The common side effects included weight gain, tremor, hair loss and nausea. Liver functions were unaffected by treatment. The possible mechanism of action of valproate in headache is discussed. Valproate appears to be a worthwhile addition to the prophylactic treatment of chronic recurrent headache. 
Sequential administration of recombinant human interleukin-2 and dacarbazine in metastatic melanoma: a multicenter phase II study. Twenty-five assessable patients with metastatic melanoma have been entered in a multicenter phase II study of two induction cycles of human recombinant interleukin-2(IL2), 18 x 10(6) IU/m2/d continuous intravenous (IV) infusion on days 1 to 5 and days 12 to 17. Dacarbazine (DTIC), 850 mg/m2 IV bolus was given on day 26. The cycle was repeated at 5 weeks. Maintenance therapy was scheduled 3 weeks after the completion of induction treatment, consisting of IL2, 18 x 10(6) IU/m2/d for 5 days alternating with DTIC, 850 mg/m2 IV every 3 weeks, for a total of 18 weeks. Six patients responded (24%); two complete and four partial. Stable disease was seen in five patients. None of the six patients with more than two sites of metastases responded. Maximum response was observed in the first 3 months of treatment. Progression-free periods of 6 months and longer were seen in the two complete responders (8 and 17+ months), in two of the four partial responders (7 and 12+ months), and in three of the five patients with stable disease (9+, 15, and 17+ months). Toxicity included fever, skin rash, fatigue, anorexia, and diarrhea in most patients. Two patients had a weight gain of more than 10%. Eight patients needed intensive care for the observation and treatment of a myocardial injury (one patient), ventricular tachycardia (one), hypotension and oliguria (four), and sepsis (two). Sequential treatment with IL2 and DTIC appears to be effective but not clearly better than could be expected of IL2 alone. 
Total parenteral nutrition-induced steatosis: reversal by parenteral lipid infusion. Prolonged use of total parenteral nutrition (TPN) may be associated with hepatic complications, primarily steatosis and cholestasis. A case is reported of an 18-year-old woman with chronic idiopathic intestinal pseudo-obstruction syndrome who was on prolonged home parenteral nutrition without lipid supplementation and developed steatosis. This finding was reversed by addition of lipid emulsion, at a dose of 0.5 g/kg/day, to the parenteral nutrition solution. The lack of lipid supplementation as a possible cause of steatosis, as well as other mechanisms of liver steatosis associated with TPN, are discussed. 
Case-control study of leukaemia and non-Hodgkin's lymphoma in children in Caithness near the Dounreay nuclear installation [published erratum appears in BMJ 1991 Apr 6;302(6780):818] OBJECTIVE--To examine whether the observed excess of childhood leukaemia and non-Hodgkin's lymphoma in the area around the Dounreay nuclear installation is associated with established risk factors, or with factors related to the plant, or with parental occupation in the nuclear industry. DESIGN--Case-control study. SETTING--Caithness local government district. SUBJECTS--14 cases of leukaemia and non-Hodgkin's lymphoma occurring in children aged under 15 years diagnosed in the area between 1970 and 1986 and 55 controls matched for sex, date of birth, and area of residence within Caithness at time of birth. MAIN OUTCOME MEASURES--Antenatal abdominal x ray examination; drugs taken and viral infections during pregnancy; father's occupation; father's employment at Dounreay and radiation dose; distance of usual residence from the path of microwave beams, preconceptional exposure to non-ionising radiation in the father; and other lifestyle factors. RESULTS--No raised relative risks were found for prenatal exposure to x rays, social class of parents, employment at Dounreay before conception or diagnosis, father's dose of ionising radiation before conception, or child's residence within 50 m of the path of microwave transmission beams. Results also proved negative for all lifestyle factors except an apparent association with use of beaches within 25 km of Dounreay. However, this result was based on small numbers, arose in the context of multiple hypothesis testing, and is certainly vulnerable to possible systematic bias. CONCLUSION--The raised incidence of childhood leukaemia and non-Hodgkin's lymphoma around Dounreay cannot be explained by paternal occupation at Dounreay or by paternal exposure to external ionising radiation before conception. The observation of an apparent association between the use of beaches around Dounreay and the development of childhood leukaemia and non-Hodgkin's lymphoma might be an artefact of multiple testing and influenced by recall bias. 
Use of i.v. radionuclide total body arteriography to evaluate arterial bypass shunts--a new method--a review of several cases. Currently, Doppler ultrasound and contrast angiography are the main imaging procedures being used to evaluate arterial bypass shunts. IV radionuclide total body arteriography (TBA) is another useful imaging procedure for evaluation of bypass shunts. The authors reviewed 33 patients, 19 women and 14 men, ranging in age from forty-three to eighty-five, who had TBA done after arterial bypass surgery. Ten patients had multiple shunts and 5 had multiple follow-up studies. In total there were 80 shunts, including 43 femoropopliteal, 16 axillofemoral, 1 axillopopliteal, 13 crossover femorofemoral, and 7 aortofemoral shunts. Sixty-two of the 80 shunts were patent, 14 were occluded, and 4 had partial occlusion. The results were confirmed by Doppler studies, contrast angiograms, and/or surgical exploration without false positives or false negatives. Since the radiotracer used was 99mTc-labeled red blood cells, a MUGA study can also be performed immediately following TBA in the same injection. Twenty-eight patients had gated cardiac blood pool studies (MUGA) done; 16 had abnormal wall motion and diminished ventricular function. TBA requires only a single IV injection of radiotracer (less than 1 cc) in the upper limb. The imaging times for total body arterial and perfusion images are seventy seconds and five minutes respectively. Both total body arterial and perfusion images clearly demonstrated the entire course of shunts (single or multiple); underlying and coexisting arterial abnormalities, e g, occlusive disease (27 patients), or aneurysm (3 patients); and related perfusion changes in the extremities. TBA has unique features. It permits a complete, excellent visualization of the bypass graft without the hazard of contrast media injection. It is a simple and a virtually noninvasive procedure, particularly useful for preoperative workups and postoperative follow-ups. 
Temporarily implanted urethral coil stent for the treatment of recurrent urethral strictures: a preliminary report. A new urethral stent developed for use in recurrent urethral strictures is presented. This metallic coil is self-expanding when released from its introducing catheter. The stent was used in 18 patients with recurrent strictures necessitating frequent dilation or urethrotomy. The stent is introduced under fluoroscopic guidance after internal urethrotomy or simple dilation. Strictures of 5 to 60 mm. were treated successfully with this device. All strictures were distal to the external sphincter. No serious complications attributed to the device were recorded. When necessary, the stent could be repositioned either under fluoroscopic control or endoscopically. This device can hold the stenotic area of the urethra open for long intervals allowing for complete healing. Even after 6 months the stent is not covered with urethral epithelium and does not become incorporated into the urethral wall. It can be removed easily without an operation by simple manipulation. The large internal caliber permits passage of endoscopes up to 17F in patients who require cystoscopy. The device can be removed before transurethral resections and then a new stent can be inserted at the end of the procedure. Mean followup of our patients with the stent indwelling was 8 months (range 4 to 11 months). Followup after removal of the stent (6 patients) was 3 to 8 months (mean 5 months). The patients voided well during followup and were fully continent. No incrustations were noted in the removed stents even after 6 months and no stent became obstructed due to tissue proliferation or incrustation. In 1 patient the stricture recurred after 3 months and a new stent was inserted. Urine sterilization was obtained in 7 patients with infected urine after relatively short courses of antibiotics. This stent seems to be a promising tool for the nonoperative treatment of recurrent urethral strictures. 
Mother and child. Trauma in pregnancy. The role of the emergency physician in optimizing outcome for the maternal and fetal victims of trauma is pivotal. Knowledge of the anatomic and physiologic changes of pregnancy aid in understanding the nuances of care of the pregnant trauma patient. Both catastrophic and noncatastrophic trauma can be managed with confidence and expertise by recalling the maternal and fetal pathophysiologic responses to trauma. Burns and electrical injuries carry significant fetal risks, which may be minimized by rapid and knowledgeable emergency care. 
Cilioretinal artery occlusion in young adults with central retinal vein occlusion. Ten patients, all younger than 50 years of age, had a temporal cilioretinal artery occlusion associated with a nonischemic central retinal vein occlusion. On fluorescein angiography, the cilioretinal artery eventually filled in all but one eye. The cilioretinal artery showed pulsations on fluorescein angiography in five eyes. The central retinal vein occlusion eventually resolved and the fundus assumed a normal appearance in all nine of the followed cases. Eight of nine eyes that underwent follow-up examination had final visual acuity of 20/30 or better. The occlusion of the central retinal vein produces an elevation of intraluminal capillary pressure because the central retinal artery continues to pump blood into the retina. Because the perfusion pressure of the cilioretinal artery is lower than the central retinal artery, it becomes relatively occluded. The prognosis for these patients is generally good unless the entire parafoveal capillary net is affected by the cilioretinal artery that is occluded. 
Perilymphatic fistula: analysis of free amino acids in middle ear microaspirates. High-performance liquid chromatography was used to determine 19 free amino acid concentrations in perilymph, serum/plasma, and red blood cell intracellular fluid. Significant differences were found between perilymph and these fluids. Free amino acid analysis was then used to quantitatively analyze middle ear microaspirates in order to test the hypothesis that perilymph is a potential source of clear fluid in perilymphatic fistulas (PLF). Fourteen unknown samples from patients with visually identified PLF, including patients with no identifiable otic capsule defect, were studied. Six samples on amino acid pattern analysis were correlated most similarly with perilymph (rrho greater than 0.95). Four of these six samples were scored on the basis of quantitative amino acid values as similar to perilymph. However, three samples of clear fluid were more similar to serum/plasma than to perilymph on both amino acid pattern and quantitative amino acid score analysis. These results objectively suggest perilymph as a potential source of clear fluid in some patients with a diagnosis of PLF. Not all clear fluid observed in the middle ear, however, is potentially perilymph. 
Predictors of clinical response in hirsute women treated with spironolactone. OBJECTIVE: To examine the clinical efficacy of low dose spironolactone in hirsute women. DESIGN: Retrospective. SETTING: Outpatient endocrinology clinic. PATIENTS: One hundred nine consecutive women prescribed 75 to 100 mg/d spironolactone for at least 4 months in whom adequate follow-up data were available. RESULTS: Hirsutism improved in 72% of the women. Women with regular menses, whether or not they used oral contraceptives (OCs), had the highest response rate to spironolactone (78%), whereas women with irregular menses who did not use an OC had the lowest response rate (55%). Favorable responses were associated with increased severity of hirsutism (P = 0.04) and lower serum dehydroepiandrosterone sulfate levels (P = 0.05). Responders and nonresponders did not differ significantly in age (P = 0.10), duration of hirsutism (P = 0.14), pretreatment serum testosterone (T) (P = 0.48), or body mass index (P = 0.11). However, when each parameter was divided into subsets, trends toward decreasing response were observed with increasing age, duration of hirsutism over 15 years, and increasing serum T level. CONCLUSION: Low-dose spironolactone improves hirsutism in a majority of hirsute women, irrespective of age, severity or duration of hirsutism, menstrual status, or serum hormone levels. 
Quantitative analysis of basal dendrites of prefrontal pyramidal cells after chronic alcohol consumption and withdrawal in the adult rat. The effects of chronic alcohol consumption and withdrawal on the organization of the basal dendrites of layer III pyramidal cells of the prelimbic cortex were studied in groups of rats fed on alcohol for 6 or 18 months, and in a group fed for 12 months, then switched to water for a further 6 months (withdrawal group). Three-dimensional analysis of the dendritic arborizations showed an age-dependent increase in several dendritic parameters, but a net stability was found in the metrical parameters between alcohol-fed and respective control rats. Conversely, a dendritic impoverishment occurred in the withdrawal group. The linear density of dendritic spines remained stable in all groups studied. Together with the previously found marked loss of the neurons after alcohol consumption and withdrawal, these findings point to a decrease in the available targets for afferents and therefore to the presence of probable functional alterations as a consequence of those in the connectivity patterns of the prelimbic area occurring under these conditions. 
Endometriosis in episiotomy scar with anal sphincter involvement. Report of a case. A case of endometriosis in an episiotomy scar with involvement of the external anal sphincter is presented. The clinical, operative, and pathologic findings are reported. The question of etiology and treatment is discussed, and the literature is reviewed. Wide excision of the ectopic endometrial tissue with primary reconstruction of the external sphincter was curative, and the functional result was excellent. It is suggested that this treatment policy should be recommended for these cases. 
Aortic dissection resulting from tear of transverse arch: is concomitant arch repair warranted? Forty-seven patients with aortic dissection resulting from a primary tear located in the transverse aortic arch underwent surgical treatment. Twenty-six patients had acute type A, 7 had acute type B, 7 had chronic type A, and 7 had chronic type B aortic dissections. Of the 33 patients with acute dissections, 11 (7 acute type A and 4 acute type B) underwent concomitant arch repair with an operative (less than or equal to 30 days) mortality rate of 55% (35% to 73%, +/- 1 asymmetric 70% confidence limit) (2 of 7 acute type A and 4 of 4 acute type B). Concomitant arch repair was omitted in 22 patients with acute dissections (19 acute type A and 3 acute type B); the operative mortality rate was 41% (29% to 54%) (7 of 19 acute type A and 2 of 3 acute type B) (p = not significant versus arch repair). The overall survival rate for those with arch repair was 45% +/- 15% (+/- 1 standard error of the estimate) at 4 years, compared with 43% +/- 11% for patients without arch repair (p = not significant). Considering the type of dissection, the 4-year survival estimate for patients with acute type A dissections who underwent arch repair (5 hemiarch and 2 total arch) was 71% +/- 17% (versus 44% +/- 12% for acute type A patients without arch repair). There were no survivors among the 4 patients with acute type B dissections who had an arch repair (1 hemiarch and 3 total arch), whereas patients with acute type B dissections who did not undergo concomitant arch repair had a 4-year survival estimate of 33% +/- 27% (p = not significant versus arch repair). Four other patients with acute type B dissections resulting from an arch tear were managed medically and tended to have a slightly better prognosis (2-year survival estimate of 75% +/- 22% versus 14% +/- 13% for all surgically treated acute type B patients), but again this difference was not statistically significant. Multivariate analysis of the 47 surgical patients revealed that advanced age (p = 0.0008), preoperative dissection complications (p = 0.02), and other coexistent medical problems (p = 0.03) were the only significant, independent determinants of overall mortality. Initial arch repair was not a significant predictor. Nine percent (2/22) of patients with acute type A dissections who initially underwent isolated ascending aortic replacement required subsequent arch replacement; 1 died after reoperation.(ABSTRACT TRUNCATED AT 400 WORDS). 
The eosinophilia-myalgia syndrome: the Los Alamos Conference. On June 12 and 13, 1990 the Los Alamos National Laboratory in cooperation with the New Mexico Department of Health and Environment, the Centers for Disease Control (CDC), the Food and Drug Administration (FDA), and the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health (NIH) hosted a conference on the eosinophilia-myalgia syndrome. Fifty presentations covered a variety of important issues which are summarized herein. 
Interleukin-7 differentiates a subgroup of acute lymphoblastic leukemias. The bone marrow stromal cell-derived growth factor interleukin-7 (IL-7) is known to stimulate growth of normal human B-cell precursors. In the present report, we have examined the effect of IL-7 on neoplastic B-cell precursors. Leukemic cells from 20 patients with common acute lymphoblastic leukemia (ALL) were highly purified by removing contaminating T cells and monocytes by rosetting with immunomagnetic beads. IL-7 markedly reduced the DNA synthesis in leukemic cells from three patients. This inhibition of DNA synthesis was accompanied by maturation of the cells, as demonstrated by the induced expression of the differentiation antigens CD19, CD20, CDw75, and surface mu-chain, and a decreased expression of terminal deoxynucleotidyl transferase. By examining G1 parameters, such as MYC, 4F2, and transferrin-receptor levels analyzed by flow cytometry as well as RNA and the cell cycle regulated antigen Ki67, it appeared that the cells were inhibited late in G1. Leukemic cells from the majority of the cases (12 of the 20 patients) responded to IL-7 with enhanced DNA synthesis without detectable maturation, as has been reported for their normal counterparts. Low molecular weight B-cell growth factor greatly potentiated the IL-7-induced growth stimulation of these cells. Thus, we have shown that IL-7 is capable of inhibiting proliferation of leukemic cells isolated from a subgroup of ALLs, and that this growth inhibition is accompanied by maturation of the cells. 
Magnesium inhibits the hypertensive but not the cardiotonic actions of low-dose epinephrine. Intravenous magnesium supplementation is often used to control cardiac arrhythmias and coronary artery vasospasm resulting from disturbances of magnesium homeostasis after coronary artery bypass surgery. Many such patients also require inotropic drug support of depressed myocardial function. However, increased serum magnesium concentrations directly depress cardiac contractility in animals and may interfere with catecholamine actions. To determine whether small intravenous doses of magnesium sulfate (MgSO4) interfere with the cardiotonic actions of epinephrine, we examined the hemodynamic effects of MgSO4 and epinephrine infusion in 17 cardiac surgical patients on their 1st postoperative day in a prospective, controlled study. In 11 patients, infusion of MgSO4 (7-mg.kg-1 bolus followed by 10 mg.kg-1.h-1 as a continuous infusion) increased serum magnesium concentrations by 44% (mean +/- standard error of the mean [SEM] of 0.8 +/- 0.1 to 1.2 +/- 0.1 mM; P less than 0.01) but had no significant effect on heart rate; mean arterial, central venous, or pulmonary arterial occlusion pressures; or cardiac output. Epinephrine infusion (30 ng.kg-1.min-1) significantly increased cardiac index (2.7 +/- 0.1 to 3.1 +/- 0.21.min-1.m-2; P less than 0.05); this effect was not altered by MgSO4 administration (n = 11). However, MgSO4 significantly blunted epinephrine's hypertensive action and prevented a significant increase in mean arterial pressure during concurrent MgSO4-epinephrine administration. Six placebo control patients were given two sequential infusions of epinephrine separated by a placebo infusion to rule out an effect of time on the hemodynamic response to epinephrine. Mean arterial pressure and cardiac index responses to epinephrine were identical before and after placebo infusion. 
Diagnostic importance of the radiographic density of noncalcified breast masses: analysis of 91 lesions. Radiographic density is considered an important feature in the evaluation of noncalcified breast masses, yet no studies assessing its value have been published. The radiographic densities of 91 biopsy-proved, nonfatty, noncalcified breast masses were evaluated by three mammographers. The density determinations made by each observer were compared with the histologic outcome for the 51 benign and 40 malignant lesions. With the kappa statistic, interobserver agreement was relatively poor (0.22 to 0.49), and intraobserver agreement for one expert mammographer was 0.50. When the majority opinion of the mammographers was used, sensitivity was 48%, specificity was 80%, and both positive and negative predictive values were 66%. As a solitary feature in lesion analysis, mammographic density is difficult to assess and is of limited value for the prediction of the benign or malignant nature of noncalcified breast masses. 
Retrograde suction decompression of an ophthalmic artery aneurysm using balloon occlusion. Technical note. A large ophthalmic artery aneurysm was ligated using a modification of the retrograde suction technique described by Batjer and Samson. Temporary proximal occlusion of the internal carotid artery was accomplished with a double-lumen balloon catheter, and distal occlusion was performed with a temporary clip. The aneurysm was collapsed by gentle aspiration through the distal lumen of the balloon catheter. This greatly facilitated dissection and clip ligation of the aneurysm. 
Patterns in visual interpretation of coronary arteriograms as detected by quantitative coronary arteriography. In part 1 of a three-part study, 14 novice readers and 6 experienced cardiologists interpreted phantom images of known stenosis severity. No difference between the interpretations of experienced and novice readers was detectable. Visual estimates of "moderately" severe stenosis were 30% higher than actual percent diameter stenosis. In part 2 of the study, visual interpretation of percent diameter stenosis from 212 stenoses on 241 arteriograms was compared with quantitative coronary arteriographic assessment. The visual analysis overestimated disease severity in arteries with greater than or equal to 50% diameter stenosis (except for right coronary lesions) and underestimated severity in all arteries with less than 50% diameter stenosis. Of the 241 arteriograms, 40 had quantitative and visual analysis of all three coronary arteries for assessment of significant disease. In only 62% of the cases did visual and quantitative methods agree on the presence of severe disease; visual estimates diagnosed significantly (p less than 0.05) more three-vessel disease. In part 3 of the study, comparison of percent diameter stenosis by visual estimate with quantitative coronary arteriographic assessment before and after balloon angioplasty of 38 stenoses showed that visual interpretation significantly (p less than 0.001) overestimated initial lesion severity and underestimated stenosis severity after angioplasty. 
Headache syndromes as detected by configural frequency analysis. Data on headache symptoms obtained in two samples (N = 422 and 304) by means of questionnaires were subjected to configural frequency analysis (CFA). This not widely-known method tests whether certain symptom combinations appear more often or less often than expected by chance. In both samples symptom combinations corresponding to the syndromes of migraine with aura, migraine without aura and tension headache did indeed occur with significant frequency. The same clear-cut symptom patterns appeared when patients with preceding visual disturbances were excluded from analysis. These results seem to lend strong support to a categorical model of headache, rather than to the concept of headache as a spectrum. 
Phenytoin-induced hemocytophagic histiocytosis indistinguishable from malignant histiocytosis. We have reported a case of phenytoin-induced hemocytophagic histiocytosis indistinguishable on clinical and histopathologic grounds from malignant histiocytosis. We emphasize the need to investigate for microbiologic causes and drug ingestion, even if the diagnosis of malignant histiocytosis is plausible. We think that reactive and malignant histiocytosis are not really two distinct entities with different etiologies, but a continuum of host responses to several insults with different degrees of aggressiveness depending on the host immune status. 
Radiologic findings of clonorchiasis. Clonorchiasis is a trematodiasis caused by chronic infestation of liver flukes, Clonorchis sinensis. The adult flukes reside in the medium-sized and small intrahepatic bile ducts and, occasionally, in the extrahepatic bile ducts, gallbladder, and pancreatic duct. The result is mechanical obstruction, inflammatory reaction, adenomatous hyperplasia, and periductal fibrosis. Signs and symptoms are usually mild and nonspecific, but heavy infestation results in obstructive jaundice. The disease has a close relationship with recurrent pyogenic cholangitis and cholangiocarcinoma. In this article, the radiologic findings, including cholangiography, sonography, and CT of clonorchiasis are reviewed in light of the pathophysiology of the disease. The relationship to recurrent pyogenic cholangitis and to cholangiocarcinoma is discussed. 
An immunoinhibitory cell wall glycoprotein (mannan) from Trichophyton rubrum. Trichophyton rubrum causes 90% of chronic dermatophyte infections. Most patients with widespread chronic T. rubrum infection fail to express a delayed hypersensitivity reaction to intradermally injected trichophytin. We propose that cell-mediated immunity to T. rubrum may be suppressed in chronic infections by the mannan cell wall component of the fungus. The proposed suppressive effect of T. rubrum mannan on cell-mediated immunity was tested by measuring the ability of extracted mannan to inhibit lymphoproliferative responses of human mononuclear leukocytes to antigens, mitogens, and an anti-T-cell receptor antibody (anti-CD3) in vitro. Mannan was found to be highly antigenic in two of five donors and weakly antigenic in the other three. Despite its antigenic property, mannan exhibited a dose-related ability to inhibit lymphoproliferation stimulated by other agents including 1) antigens from Candida albicans, T. rubrum, and tetanus toxoid (ID50 = 250 micrograms/ml); 2) anti-CD3 antibody (ID50 = 250 micrograms/ml); and 3) Phaseolus limensis mitogenic lectin (ID50 = 64 micrograms/ml). Mannan added to cultures later than 24 h after initiation had no inhibitory influence, but culture of cells with mannan for a period of 24 h prior to the addition of stimulus enhanced the inhibitory effect of the glycoprotein. Lymphoproliferation in response to recombinant interleukin-2 (IL-2) was not inhibited. The influence of time of addition of mannan and the failure of mannan to inhibit IL-2-stimulated lymphoproliferation demonstrate that the suppressive effect of mannan must be pharmacologic rather than cytotoxic. The observed ability of T. rubrum cell wall mannan to suppress cell-mediated immune function in vitro may provide an important clue to a mechanism enabling the fungus to avoid elimination in chronically infected patients. 
Polycystic kidneys, pancreatic cysts, and cystadenomatous bile ducts in the oral-facial-digital syndrome type I. Oral-facial-digital syndrome type I is a group of X-linked dominant conditions, lethal in utero in male individuals. Internal anomalies are less well documented than are external findings. We report a case of typical phenotype and absent family history of kidney disease in a 15-year-old white girl (46,XX) who died of renal failure and massive cerebral hemorrhage. At necropsy, the kidneys were greatly enlarged but of fairly normal shape. The cortex was replaced by thin-walled spherical cysts, 0.5 to 2.0 cm in diameter; the majority of the smaller cysts were located deep in the cortex, and the medulla contained lesser numbers of larger cysts. No distal urinary tract obstruction was present. Microdissection revealed cysts and diverticula located in all segments of the nephrons and collecting ducts. Uninvolved nephrons showed diffuse hypertrophy. These findings were correlated with immunoperoxidase stains using peanut lectin, Lotus tetragonolobus agglutinin, antibodies to cytokeratins, stage-specific embryonic antigen-1, Tamm-Horsfall protein, and epithelial membrane antigen. Other visceral anomalies included biliary cystadenomatous proliferation in the liver and pancreatic cysts. The renal changes are similar to those of autosomal dominant (adult-type) polycystic disease. 
Effect of the tibial cut on subsidence following total knee arthroplasty. In 33 total knee arthroplasties (TKAs) using instrumentation designed to cut the tibia with 0 degree posterior slope, ten tibial components demonstrated at least 2 mm of tibial component subsidence. These subsided components were implanted onto tibiae with an average of 8 degrees +/- 2 degrees difference between the preoperative, anatomic posterior slope and their postoperative posterior slope. The remaining 23 components, without subsidence, were implanted onto tibiae cut within 2 degrees +/- 2 degrees of their anatomic slope. To help understand these clinical observations, a laboratory study was performed to compare the load carrying capacity and the stiffness of tibial subchondral bone following two types of tibial cuts: one made perpendicular to the long axis of the tibia and the other made parallel to the articular surface of the tibia. Mock tibial baseplates mounted on paired cadaver tibiae were loaded in compression and force displacement curves were recorded. Tibiae cut parallel to the surface exhibited 40% greater load carrying capacity and 70% greater stiffness than the paired tibiae cut perpendicular to the long axis. The biomechanical data of this study indicated that cutting the tibia perpendicular to the long axis results in weaker bone that may be inadequate to support a tibial component. This may explain the higher incidence of clinical subsidence if the tibial cut is not made approximately parallel to the anatomic slope. 
Finapres: a noninvasive device to monitor blood pressure. Often, obstetric patients are not evaluated in preliminary studies during the development of new medical devices. The purpose of this study was to compare the Finapres digital probe with oscillometric and arterial line devices for recording blood pressures in low- and high-risk pregnant women. A total of 38 women were studied, including 24 with pregnancy-induced hypertension, two with chronic hypertension, two with cardiac disease, and ten who had no risk factors but requested epidural catheter placement. The comparison of Finapres or oscillometric recordings with direct arterial values confirmed that systolic recordings were imprecise for both devices (r = 0.80 and r = 0.64, respectively). Diastolic recordings (Korotkoff sound, phase 4) from the Finapres were accurate compared with the arterial values (r = 0.84). The Finapres performed at least as reliably as the oscillometric monitor in assessing blood pressure in our pregnant population and provided continuous measurements. When very accurate systolic recordings are needed, arterial catheter placement may be necessary. 
Some perspectives on peptic ulcer. In this article, the author comments on the following topics: whether peptic ulcer is a disease or just the sign of another process; whether the crater has a multifactorial origin; the ubiquity of Helicobacter pylori and the conclusion that a specific strain will doubtless prove to be the cause of some, but not all, ulcers; the inherent definitional problem of "nonulcer dyspepsia"; and the controversy over how much gastric acid needs to be reduced to speed the healing of peptic ulcer. 
Hepatocyte proliferation in stepwise development of experimental liver cell cancer. Cell proliferation is the most central and key phenotypic property of cancer including hepatocellular carcinoma. Hepatocyte proliferation is central not only at the late steps in carcinogenesis, the cancer, but at the earliest known step, initiation. Compensatory or regenerative hepatocyte proliferation is essential to initiation with chemical carcinogens but primary hyperplasia is ineffective. During promotion, hepatocyte proliferation is the major change seen as clonal proliferation to generate nodules occurs. During progression, autonomous hepatocyte proliferation balanced by cell loss makes its appearance. This continues in a balanced fashion with only a slight excess of proliferation over loss until the earlier steps in malignancy at which time the balance is disrupted. 
Splenosis: an unusual cause of intraabdominal hemorrhage. A 31-year-old female presented to the emergency department with an acute onset of severe abdominal pain. She developed hypovolemic shock from an intra-abdominal bleed. At laparotomy she was found to be bleeding from two areas of splenosis on the uterine ligament. The patient had sustained a ruptured spleen 22 years prior and had no symptomatology from her areas of splenosis. A short review of splenosis is presented. 
Streptokinase and recombinant tissue plasminogen activator (rt-PA) are equally effective in treating acute myocardial infarction. In recent trials, patients with myocardial infarction who received either recombinant tissue-type plasminogen activator (rt-PA) or streptokinase showed essentially no difference in the amount of myocardial salvage, in mortality reduction, or in the incidence of bleeding complications. These findings thus failed to fulfill the expectation that rt-PA would be twice as effective as streptokinase as a thrombolytic agent. The basis for this mistaken prediction was an unfortunate overemphasis on an inadequate surrogate endpoint, namely, the patency or reperfusion rate at 90 minutes after the start of therapy. Using the 90-minute patency or reperfusion rate as an endpoint has several serious limitations. First, it is an observation made at only one point in time during a dynamic process that may change even during the infusion proper. Second, a single view at 90 minutes completely disregards the possibility of subsequent reocclusion which often occurs within 1 hour after treatment. Third, an image at 90 minutes is more a reflection of the speed of thrombolysis than of whether lysis will eventually occur; the pace of clot lysis depends on both the agent used and the age of the thrombus. Fourth, lysis at 90 minutes is of minimal relevance for myocardial salvage unless observed within the time frame when infarction size can be limited significantly, which is generally less than 4 hours between symptom onset and the time that reperfusion is accomplished. Fifth, a stable state of vessel patency is meaningful for mortality reduction even if stabilization occurs after completion of the infarction. Such "late," but lasting, patency is a critical component of the "open vessel" principle and explains, at least in part, the survival benefit that accrues to patients treated even 24 hours after the onset of symptoms. There is currently no evidence that rt-PA has a more beneficial effect on survival or function than does streptokinase or any other plasminogen activator used in treating acute myocardial infarction; nor is there any evidence that patients who receive rt-PA therapy show a decreased incidence of bleeding complications compared with those who receive streptokinase, despite the relative fibrinogen-sparing attribute of rt-PA. Given the poor predictive value of the 90-minute angiogram for ultimate clinical advantage of one agent over another, studies that are limited to this endpoint are of marginal use in evaluating treatment regimens used in mortality studies. The best evidence to date indicates that streptokinase and rt-PA are of equivalent value for survival after acute myocardial infarction, a conclusion that can be justifiably challenged only with a valid mortality study. 
Successful transcatheter embolization of pseudoaneurysm associated with pancreatic pseudocyst. Hemorrhage into a pancreatic pseudocyst is a rare event, but is the most rapidly lethal complication of chronic pancreatitis. Visceral-vessel aneurysms are an unexpectedly common finding in arteriography of patients with chronic pancreatitis. This case report describes bleeding from an anterior superior pancreaticoduodenal artery aneurysm, caused by chronic pancreatitis. The aneurysm was successfully treated by embolization with a steel coil. 
Concealed rhythms by double ventricular parasystole. Electrocardiograms taken from 11 patients in sinus rhythm with ventricular ectopic rhythms from two different foci were analyzed to find the number of sinus beats, S, between the ectopic rhythms (S values). Three out of 11 patients had the S values typical for concealed ectopic rhythms. One of them had concealed bigeminy of 2n-1 form that occasionally shifted to 2n form. Following the shift, S values of 2n-1 form were always achieved by the occurrence of double ventricular ectopic rhythms in succession. Concealed trigeminy of 3n and 3n-2 form was seen in the other two patients. Double ventricular ectopic rhythms had bizarre abnormal QRS complexes of two different morphologies and were inscribed in opposite directions. Ectopic rhythms in each case had parasystolic characteristics. These observations suggest bifocal automaticity as a mechanism for bidirectional ventricular tachycardia. 
Cerebral vasculopathy associated with collateralization resembling moya moya phenomenon and with anti-Ro/SS-A and anti-La/SS-B antibodies. We describe a 48-year-old, previously healthy, anti-Ro/SS-A and anti-La/SS-B antibody positive black woman with negative risk factors for atherosclerosis, who developed mental status and personality changes over a 6-12-month period, and progressive cortical blindness over a 2-week period. Angiographic and computed axial tomographic studies of the brain demonstrated multiple large areas of infarction correlating with stenosis and occlusions of the internal carotid and posterior cerebral arteries. Moya moya-like findings were prominent radiographically. Results of angiographic, computed tomographic, and magnetic resonance imaging studies were interpreted as being compatible with large, medium, and small vessel disease, most likely a vasculitis. 
Myocardial and aerobic requirements for an upper body exerciser: implications for cardiac rehabilitation. To assess the cardiorespiratory, hemodynamic, and electrocardiograph (ECG) responses to an upper body exercise device, we studied ten cardiac men (mean age +/- SD = 58.0 +/- 6.5 years) who performed three five-minute exercise bouts at metronome settings of 20, 50, and 80 clicks per minute. Operation of the device involved shuttling a plastic buoy on two 6-m waxed ropes between two persons. Aerobic requirements were generally appropriate for arm training, corresponding to mean values of 5.3, 7.0, and 10.1 ml.kg-1.min-1 at the three progressive metronome settings. Perceived exertion (Borg, 6 to 20 scale) at these work rates was 8.3, 10.4, and 14.6, whereas average heart rate and systolic blood pressure responses were 77, 85, and 114 beats.min-1 and 145, 158, and 175 mmHg, respectively. Continuous ECG monitoring during upper body exercise revealed no significant ST-segment depression or serious arrhythmias. The device appears to be a safe and effective complement to a cardiac exercise training program. 
Carcinoma and DNA aneuploidy in Crohn's colitis--a histological and flow cytometric study. Twenty four patients with longstanding colonic Crohn's disease were examined prospectively with colonoscopy and multiple biopsy sampling in order to detect histological dysplasia or abnormal aneuploid DNA content, or both. Biopsy specimens were taken from 10 predetermined locations in the colon and rectum. No patient had definite dysplasia but three displayed DNA aneuploidy (12.5%), and one of these subsequently developed a carcinoma (Dukes' C at operation) in the ascending colon. No concomitant dysplasia was detected but the carcinoma as well as other parts of the mucosa were DNA aneuploid. It is concluded that dysplasia is rare in patients with Crohn's colitis, but findings of DNA aneuploidy warrant vigilance in follow up as this may indicate impending carcinoma. Further prospective studies are needed before the predictive value of DNA aneuploidy can be determined and before general recommendations of colonoscopic surveillance, as in longstanding ulcerative colitis, can be made. 
Ocutome lensectomy: results and complications. We describe the results and the complications encountered in 69 lensectomies performed via a limbal approach with the Ocutome vitrectomy instrument, in which it was the intention at surgery to maintain the integrity of the posterior capsule. After operation 87% improved in visual acuity, and 68% achieved 6/12 or better. The main early complications encountered were perioperative rupture of the posterior capsule and iris damage. The main late complications were postoperative thickening of the posterior capsule, retinal detachment, and bullous keratopathy. Of the eyes in which the posterior capsule remained intact after operation 17% developed thickening of the posterior capsule to a degree that required capsulotomy over a mean follow-up period of 50 months. 
Avascular necrosis of bone in children undergoing allogeneic bone marrow transplantation. Avascular necrosis of bone (AVNB) is reported in two children after allogeneic bone marrow transplantation. Preparation therapy for transplantation included cyclophosphamide and total body irradiation. Corticosteroids, cyclosporine A, and methotrexate were used for graft-versus-host-disease prophylaxis. The possible role of combination therapy in development of AVNB is discussed, but a direct relationship with single agents was not found. However, an early diagnosis is important to institute conservative treatment and prevent irreversible damage to affected joints. Magnetic resonance imaging was found to be more sensitive than plain radiography in early detection of AVNB. 
Cerebral dural sinus thrombosis. Cerebral dural sinus thrombosis is an unusual syndrome in which a patient presents with a severe headache that may be associated with diverse neurologic and physical findings. The case of a 31-year-old woman with headache, vomiting, generalized tonic-clonic seizure, and subsequent dense hemiplegia is presented. The patient was diagnosed as having a cerebral dural sinus thrombosis, but only after the diagnosis was missed initially. The syndrome may be difficult to detect because it can mimic several other entities. There are several known or suspected predisposing factors. The syndrome, diagnostic modalities, and therapeutic options are reviewed. 
Isradipine, a calcium antagonist, in the control of hypertension following coronary artery-bypass surgery. Arterial hypertension is common after coronary artery-bypass grafting (CABG) surgery and may lead to postoperative complications. Therefore, the effects of the calcium antagonist isradipine were studied in 10 postoperative CABG patients who had a mean arterial pressure (MAP) above 100 mm Hg. Isradipine, given as a continuous infusion, reduced MAP to the range of 85 +/- 5 mm Hg in all patients within 15 min. Systemic vascular resistance fell and cardiac output increased in all patients. A slight increase in heart rate was seen in some, but not all, patients. There were no adverse effects. In conclusion, isradipine appears to be a useful agent in the treatment of postoperative hypertension following CABG surgery. 
Pulmonary vascular distensibility of arterial, middle, and venous regions in newborn lambs. The pulmonary circulation in the adult is characterized by being relatively distensible, but whether the newborn lung shares this feature is less certain. We perfused isolated lungs treated with indomethacin from lambs of four ages (less than 1, 2-4, 12-14, and 30-32 days) to determine the effects of increasing left atrial pressure on the pulmonary vascular pressures measured by vascular inflow and outflow occlusion. An index of pulmonary vascular distensibility was assessed by comparing the slope of the pulmonary vascular pressure at the upstream end of a region as a function of the pressure at the downstream end of the region. A vascular distensibility index (VDI) of 1 indicates a rigid nondistensible system, whereas a VDI less than 1 indicates some degree of distensibility. During normoxia, lungs from all age groups were relatively indistensible as determined by VDI for the total vasculature (VDItotal) as well as for the different regions based on occlusion pressures (VDIarterial, VDImiddle, and VDIvenous). There were significant effects of age on the VDItotal, with decreases in the normoxic values occurring over the first 12-14 days of age, indicating an increase in pulmonary vascular distensibility. Only the VDIvenous was similarly affected by increasing neonatal age. Hypoxia significantly reduced the VDItotal in these same age groups. In addition, hypoxia, which increased the pressure gradients of the arterial and middle regions, significantly increased the VDIarterial in the youngest and oldest age groups but significantly decreased the VDImiddle at all ages by approximately 50%. In summary, we observed age-related changes in the vascular distensibility of the pulmonary circulation, with the VDItotal decreasing with increasing postnatal age. 
Congenital malignant melanoma of the eye. Twenty-three cases of congenital malignant melanoma have previously been reported. Here the authors report the first case of a congenital malignant melanoma arising in the eye. A newborn girl had a large pigmented ocular tumor, hepatomegaly, and multiple pigmented skin and choroidal lesions. The histopathologic diagnosis was of a malignant melanoma with hepatic metastases. The skin and choroidal lesions were considered to be congenital melanocytic nevi. The most plausible pathogenetic link between these two conditions was that the malignancy had arisen as a second-hit mutation within a choroidal congenital melanocytic nevus. Despite widespread metastases the baby, treated by surgery and chemotherapy, survives in good health, aged 2 years, 10 months. 
Association of nm23-H1 allelic deletions with distant metastases in colorectal carcinoma. A prospective study analysed the prognostic value of nm23-H1 allelic deletions in colorectal cancer. Of 21 patients with no evidence of distant metastases at initial operation, 11 showed nm23-H1 allelic deletions (including 1 homozygous deletion); 10 had no nm23-H1 deletions. After median follow-up of 25 months, distant metastases had developed in 8 of 11 (73%) patients with nm23-H1 deletions but in only 2 of 10 (20%) without nm23-H1 deletions (p less than 0.03). Tests with probe YNZ 22.1, near p53, showed no significant association with distant metastases. nm23-H1 may be, or may be located near, a late-acting suppressor gene in colorectal carcinoma, in which deletions may have prognostic value. 
Suppression by traumatic brain injury of spontaneous hemodynamic recovery from hemorrhagic shock in rats. The effects of brain trauma on cardiovascular and endocrine responses to hemorrhage were investigated. Forty anesthetized rats were randomly assigned to one of four groups of 10 rats each: a control group (Group C): a group with induction of hemorrhage at 16.2 ml/kg/10 min (Group H); a group with fluid-percussion brain injury at a peak pressure of 1.7 atm and an impulse duration of 25 msec (Group T); and a group receiving hemorrhagic shock following brain trauma (Group TH). Group C and T rats showed no significant alterations in cardiovascular function. At the end of hemorrhage there were no significant differences between Groups TH and H in the nadirs of mean arterial blood pressure (MABP) (mean values +/- standard error of the mean: 42 +/- 2 vs. 40 +/- 4 mm Hg) and stroke volume index (SVI) (0.61 +/- 0.11 vs. 0.66 +/- 0.10 ml/bt/kg); however, 1 hour post-hemorrhage recovery was blunted in Group TH compared to Group H (MABP 56 +/- 4 vs. 65 +/- 3 mm Hg; cardiac index 182 +/- 15 vs. 220 +/- 15 ml/min/kg; and SVI 0.71 +/- 0.06 vs. 0.81 +/- 0.06 ml/bt/kg). Since the two groups showed no significant differences in heart rate, preload (central venous pressure), and afterload (systemic vascular resistance), the reduced cardiac index recovery in Group TH is believed due to the attenuation of cardiac contractile performance. The Group TH preparation potentiated hormonal responses to hemorrhage with significantly higher epinephrine and aldosterone levels than in Group H. Brain trauma enhanced the norepinephrine response to hemorrhage, even at an injury level that by itself did not result in an increase in this hormone. Group TH rats also had significantly lower blood pH and HCO3 levels. The data suggest that brain trauma suppresses MABP and cardiac index recovery after hemorrhage mainly by inhibiting cardiac contractile performance, probably due to high catecholamine levels and severe metabolic acidosis. 
Fine-needle aspiration biopsy of thyroid nodules. A cost-effective diagnostic plan. Fine-needle aspiration biopsy is a safe and accurate method for diagnosing thyroid nodules. Personnel who have experience with the aspiration technique and with the cytologic classification of specimens are crucial to accurate results. One important advantage of using fine-needle biopsy to initially screen patients with nodules is that it can save substantially on healthcare resources. 
Return of interdigestive motor complex after abdominal surgery. End of postoperative ileus? Gastrointestinal mechanical activity was studied in 13 patients after different surgical procedures in a fasted and fed state and after pharmacological stimulation. Mechanical activity was recorded by means of a multi-pressure sensor probe placed intraoperatively into the jejunum. Abdominal surgery abolished normal motility only for a short period of time. The time for the reappearance of regular recurring activity fronts varied with the type of the surgical procedure from 3 hr after cholecystectomy to the sixth postoperative day after colon resection. The fed pattern occurred after the first postoperative interdigestive motor complex in all experiments. Stimulation was observed with ceruletide, which induced contractile activity in the small intestine during postoperative ileus. No coordinated caudad propagating activity was observed. The postoperative interdigestive motor complex did not correlate in time with the first passage of flatus and stool in our patients. Thus, the restoration of motility in the small intestine did not coincide with the clinical relief from the so-called "physiological" postoperative ileus. 
The medial temporal lobe memory system. Studies of human amnesia and studies of an animal model of human amnesia in the monkey have identified the anatomical components of the brain system for memory in the medial temporal lobe and have illuminated its function. This neural system consists of the hippocampus and adjacent, anatomically related cortex, including entorhinal, perirhinal, and parahippocampal cortices. These structures, presumably by virtue of their widespread and reciprocal connections with neocortex, are essential for establishing long-term memory for facts and events (declarative memory). The medial temporal lobe memory system is needed to bind together the distributed storage sites in neocortex that represent a whole memory. However, the role of this system is only temporary. As time passes after learning, memory stored in neocortex gradually becomes independent of medial temporal lobe structures. 
Dysfunction of the beta- and alpha-adrenergic systems in a model of congestive heart failure. The pacing-overdrive dog. The functional integrity of the beta- and alpha-adrenergic stimulatory pathways in a rapid ventricular pacing model of congestive heart failure in dogs was investigated; normal dogs served as controls. Total beta-adrenergic receptor density was 35% lower (p less than 0.01) in the pacing-overdrive dogs, and the beta-adrenergic receptor-mediated stimulation of adenylate cyclase (Vmax) was found to be 68% and 72% lower (p less than 0.01) in the left and right ventricles of the paced dogs. In addition, the basal adenylate cyclase activity was found to be 56% and 68% lower (p less than 0.01) in the left and right ventricles of the failing heart. Similarly, the Vmax of 5'-guanylylimidodiphosphate (GppNHp) and forskolin stimulation of adenylate cyclase activity was significantly lower, 70% and 55%, respectively (p less than 0.01), in both ventricles of the paced dogs. However, although the concentration yielding half-maximal velocity for beta-agonist and GppNHp stimulation of adenylate cyclase was similar in both groups, that for forskolin stimulation of the enzyme was significantly increased (p less than 0.01). Pertussis toxin-mediated ADP-ribosylation of membranes from control and failing hearts revealed a significant decrease in the inhibitory guanine nucleotide binding protein content (48 +/- 9%, p less than 0.01) in the hearts of the paced dogs. Moreover, although the pertussis toxin treatment increased the basal and the forskolin-stimulated adenylate cyclase activity in both normal and failing heart membranes, the adenylate cyclase activity remained significantly depressed in the failing heart after pertussis toxin treatment (p less than 0.01). Consistent with the depressed adenylate cyclase activity, mechanical studies on isolated papillary muscles and trabeculae revealed a decrease in baseline total tension (from 7.0 +/- 0.7 to 3.8 +/- 0.4 g/mm2, p less than 0.01) and dT/dt (from 26 +/- 8 to 13 +/- 1 g/mm2/sec, p less than 0.01) in the pacing-overdrive model. Tension generation and dT/dt observed in the paced dogs in response to increasing concentrations of forskolin demonstrated a rightward shift in the dose-response curve and a decrease in maximal forskolin stimulation (p less than 0.01). Similarly, maximal tension and dT/dt in the presence of isoproterenol was significantly lower than in the normal dogs (p less than 0.01). The decrease in beta-adrenergic responsiveness was accompanied by a decrease and rightward shift in alpha 1-adrenergic responsiveness (increase in tension was 1.1 +/- 0.1 g/mm2 in paced dogs versus 2.1 +/- 0.1 g/mm2 in controls, p less than 0.01).(ABSTRACT TRUNCATED AT 400 WORDS). 
No effect of zidovudine on hepatitis B virus replication in homosexual men with symptomatic HIV-1 infection. Zidovudine triphosphate inhibits the hepatitis B virus (HBV) DNA polymerase (DNAp) in vitro. Serial measurements of serum HBV DNAp activity and HBV DNA were made in 14 consecutive male homosexual patients starting zidovudine for symptomatic HIV-1 infection. Median duration of treatment was 15 weeks (range 2-72). In the 13 patients with detectable DNAp/DNA pre-treatment, no significant change in either measure of viral replication was observed during the first 16 weeks of treatment compared with the 13 weeks prior to treatment. The lack of response may be due to the opposing effect of immunosuppression, or to a failure of in vivo activity. 
Growth prognosis and growth after menarche in primary hypothyroidism. The long term growth of 20 girls and nine boys with juvenile primary hypothyroidism was studied until they reached final height. At diagnosis the girls had a mean age of 8.8 years (range 3.0-13.0); mean bone age was 5.4 years. The mean age of the boys at diagnosis was 9.5 years (range 3.7-14.2); mean bone age was 6.3 years. The patients were treated with thyroxine 100 micrograms/m2/day and serum thyroxine concentrations were maintained in the normal range. During treatment the rate of skeletal maturation exceeded the change in chronological age. Initial mean height SD score for bone age before treatment in the girls was +0.59 and after 11 years of treatment fell to -0.55 Mean height SD score for bone age in the boys decreased from +1.6 to -0.87 during treatment. In the girls the onset of puberty was 1.2 years later than the normal population but the duration of puberty was reduced. Mean age (SD) of menarche was 13.8 (1.7) years. The pattern of growth in girls with treated hypothyroidism was abnormal as growth continued after menarche, at a time when normal girls have almost stopped growing. During the second year after menarche our patients still had a mean growth velocity of 4.1 cm/year. Our data suggest that juvenile primary hypothyroidism results in a permanent height deficit. In addition, there is a loss of the normal harmony between growth and sexual maturation in girls, despite adequate treatment, in that growth continues for much longer after menarche than in normal girls. 
Intraperitoneal hemorrhage from hepatocellular carcinoma: emergency chemoembolization or embolization. From 1982 to 1990, 38 patients with intraperitoneal hemorrhage from hepatocellular carcinoma (HCC) underwent treatment with emergency embolization with or without anticancer drug and iodized oil. Before emergency embolization, 24 patients had a serum total bilirubin value of 3.0 mg/dL or less (group A) and 14 patients had hyperbilirubinemia, with a serum bilirubin level greater than 3.0 mg/dL (group B). Successful hemostasis was achieved in all patients. The mean length of survival was 165 days in group A and 13 days in group B. A significant correlation (P less than .00003) between serum bilirubin level and prognosis was obtained. While tumor thrombus in the portal vein made the prognosis poor, there was no significant difference in prognosis between groups with and without tumor thrombus (P = .145). Emergency embolization is an effective treatment in patients with intraperitoneal hemorrhage from HCC. The prognosis for patients with HCC depends on the serum bilirubin level before embolization. 
Racial (black-white) differences in serum lipoprotein (a) distribution and its relation to parental myocardial infarction in children. Bogalusa Heart Study. BACKGROUND. The value of lipoprotein (a) [Lp(a)] in the prediction of coronary artery disease risk very early in life remains to be established in different racial groups. METHODS AND RESULTS. Serum Lp(a) distribution and its relation to parental histories of myocardial infarction were examined in 2,438 children (8-17 years old) from a biracial community. Parental myocardial infarction was used as a surrogate measure of future risk of disease in the offspring. Lp(a) levels averaged 1.7-fold higher in blacks than in whites (p less than 0.0001). A small but significant sex difference (females greater than males, p less than 0.05) was seen in both races. Race was the only independent variable that contributed appreciably (9%) to the variability of Lp(a) in serum. White children with parental myocardial infarction (n = 90) had increased levels of Lp(a) compared with those without parental myocardial infarction (22.4 versus 17.1 mg/dl, p less than 0.01). Furthermore, among white children, the prevalence of parental myocardial infarction was higher in those with Lp(a) levels of more than 25 mg/dl than in those with values of 25 mg/dl or less (9.5% versus 5.4%, p less than 0.01). In contrast, the relation of Lp(a) to parental myocardial infarction was not seen in black children. No associations were observed between parental myocardial infarction and serum levels of any of the lipids or lipoprotein cholesterol classes in children of either race. CONCLUSIONS. Serum Lp(a) levels may prove valuable in the assessment of coronary artery disease risk early in life among white populations. These findings also emphasize the need to evaluate the atherogenic potential of Lp(a) in different racial groups. 
Brucella meningoencephalitis associated with cerebrospinal fluid shunt in a child: case report. Brucella meningoencephalitis is rare in young children. We describe a patient who developed Brucella meningoencephalitis at the age of 20 months while he had a ventriculoperitoneal shunt in situ for treatment of hydrocephalus. This patient was treated with streptomycin and rifampicin. The shunt was left in situ, and all the clinical and laboratory test abnormalities subsided with this management. We propose that in a patient with Brucella meningoencephalitis, the cerebrospinal fluid shunt system can be left in situ and treatment with appropriate combination of antibiotics should prove to be successful. 
Posterior chamber IOL implantation with suboptimal posterior capsular support. A posterior chamber intraocular lens (PC/IOL) was implanted in 24 patients with suboptimal posterior capsular support due to preoperative or intraoperative rupture of the posterior capsule or zonules in which at least six clock hours of peripheral zonular support remained. The PC/IOLs were implanted, with ciliary sulcus haptic placement, with special attention to sulcus fixation of the haptics over the zone of residual zonular support. All of the IOLs have remained centered after a mean follow-up 10.5 months. We conclude that a PC/IOL can be successfully implanted and its position maintained if at least six clock hours of peripheral zonules remain. 
Anti-V region antibodies as "almost clonotypic" reagents for the study of cutaneous T cell lymphomas and leukemias. Despite recent advances in the understanding of normal T lymphocyte immunobiology, there has been little progress in characterizing the non-HTLV cutaneous T-cell lymphomas and leukemias (CTCL) Mycosis Fungoides and Sezary syndrome. The two major impediments to in vitro studies of these malignancies have been the contamination of CTCL cells with normal T cells and the inability to induce a vigorous proliferative response or establish long-term cultures with standard T-cell mitogens. The ideal reagent for identifying CTCL cells in a given patient would be tumor specific. Although a monoclonal antibody to the clonotypic antigen receptor on CTCL cells would approach this ideal, it is not currently feasible to generate such antibodies for each CTCL patient. As a compromise, we chose to test an "almost clonotypic" reagent by examining whether monoclonal antibodies directed at the variable (V) region of the T-cell antigen receptor could be applied to CTCL. We identified three Sezary patients, who by standard T-cell phenotype and Southern blot analysis for clonality had a virtually pure peripheral blood population of leukemic cells (PBL). We then screened the PBL of these patients with a panel of seven commercially available monoclonal anti-V region antibodies and found one patients' cells reacted greater than 99% with alpha V beta 5. The other patients' cells were non-reactive. In addition, we utilized a solid-phase system to cross-link V beta 5 on the one CTCL patients' PBL cells, and found that they proliferated vigorously in the presence of 10 units of IL-2 and IL-4. Parallel cultures have been maintained for one month by restimulation twice a week. These findings suggest that anti-V region antibodies should prove useful for investigating the immunobiology of CTCL. 
Roentgenographic dimensions of the upper airway in snoring patients with and without obstructive sleep apnea. The purpose of this study was to examine whether a simple test, such as routine roentgenographic views of the upper airway, is useful in identifying anatomic narrowing of the airway in patients with sleep apnea. To accomplish this, we prospectively studied a group of 117 patients (95 male and 22 female subjects) referred for evaluation of heavy snoring and possible obstructive sleep apnea. All patients had full nocturnal polysomnography, including measurements of snoring. Lateral view of the airway obtained after swallowing contrast material was used to measure pharyngeal diameters at three sites along the airway. All measurements were performed with the patients standing and supine. We used three different definitions of sleep apnea (apnea/hypopnea index of 10, 20, and 40), and compared airway diameters between the apneic and nonapneic snorers. Only when sleep apnea was defined as greater than 40 apneas plus hypopneas per hour of sleep was there a significant difference in airway diameter at the tip of the palate and 1 cm distal to it between apneic and nonapneic snorers. Both groups of patients demonstrated a significant reduction in the retropalatal distance on assumption of the supine posture. Stepwise, forward, multiple linear regression analysis showed that the retropalatal distance and airway diameter at the tip of the palate and 1 cm distal to it were significant predictors of snoring, but not apnea. We conclude that (1) airway diameters account for some of the variability in snoring, and (2) they do not differentiate between apneic and nonapneic snorers. 
Liver function tests abnormalities in patients with inflammatory bowel disease receiving artificial nutrition: a prospective randomized study of total enteral nutrition vs total parenteral nutrition. Liver and biliary abnormalities are well-known complications of inflammatory bowel disease (IBD). It has been suggested that using total parenteral nutrition (TPN) may further impair liver function in these patients; this seems not to be so with total enteral nutrition (TEN). However, prospective trials comparing the incidence of liver function test (LFT) abnormalities with either TPN or TEN have not been carried out. Twenty-nine IBD inpatients with normal LFT, randomized to receive either TEN with a polymeric diet or isocaloric, isonitrogenous "all-in-one" TPN because of protein-energy malnutrition and/or severe disease, were included in the study. Sixteen patients (five with ulcerative colitis and 11 with Crohn's disease) received TEN, and 13 patients (eight ulcerative colitis and five Crohn's disease) were on TPN. All patients were on systemic steroids, and nine of them were on oral metronidazole. Both groups were homogeneous regarding age, sex, diagnosis, disease activity, nutritional status, daily nutrient supply, and days on artificial nutrition. Serum albumin levels significantly increased with TEN (32 +/- 1 to 38.2 +/- 1.6 g/liter, p less than 0.01), but not with TPN (32.1 +/- 2.2 to 33.9 +/- 1.4 g/liter, NS). Clinical improvement occurred in both groups of patients as shown by the change in the disease activity indexes. In all cases, measurements of serum alkaline phosphatase, serum bilirubin, aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyltransferase were performed weekly. There were no significant differences in the initial LFT between both groups. 
Superoxide dismutase in psoriasis, squamous cell carcinoma and basal cell epithelioma: an immunohistochemical study. Monoclonal antibodies against human Cu,Zn-superoxide dismutase (SOD) and Mn-SOD were used to stain frozen sections of normal and abnormal human skin. In normal human epidermis, the Cu,Zn-SOD antibody almost exclusively stained the basal cells. Mn-SOD antibody weakly stained the whole of the epidermis but more predominantly the basal cell layer. In psoriasis, Cu,Zn-SOD antibody mainly stained the basal cells of the lowest parts of the elongated rete ridges. Basal cells corresponding to the tip of the dermal papillae were weakly stained. Mn-SOD staining was considerably decreased in the psoriatic epidermis. In squamous cell carcinoma, staining with both Cu,Zn-SOD and Mn-SOD antibodies was decreased, and single cells positive for Cu,Zn-SOD were scattered throughout the tumour nests. In basal cell epithelioma, Cu,Zn-SOD staining was intense and diffusely distributed throughout the tumour nests, while Mn-SOD staining was absent. 
Time trends in incidence rates of acute, non-traumatic extremity ischaemia: a population-based study during a 19-year period. Time trends in the occurrence of acute limb ischaemia were studied from 1965 to 1983 in a defined geographical area in Sweden. Data were obtained from a computerized register which covers all instances of inpatient care for a population of 1.3 million. Analysis based on 5394 first admissions for acute arterial occlusion revealed that the annual number increased by 2.7 per cent yearly in women and 3.9 per cent in men whereas the age-adjusted incidence remained stable for women and increased by 2.6 per cent yearly for men. A study of 1189 patients who underwent surgical procedures showed that the annual number of embolectomy procedures increased 7.6 per cent for females and 8.6 per cent for males. The corresponding age-adjusted incidence rose annually by 3.0 per cent for women and by 7.5 per cent for men. The introduction of the Fogarty catheter and an increasing interest in vascular surgery may have contributed to the increasing rates of operations during the period of study. 
Trypanosoma cruzi: a carbohydrate epitope defined by a monoclonal antibody as a possible marker of the acute phase of human Chagas' disease. An IgM monoclonal antibody (MAb) against a carbohydrate epitope present in Trypanosoma cruzi trypomastigote excretory-secretory antigens and expressed by different developmental stages of the parasite (epimastigote, trypomastigote and intracellular amastigote) was linked to a solid phase matrix and used as an antigen-capture antibody. Human serum complexes containing the epitope were then detected by using specific secondary antibodies against human immunoglobulin isotypes. Results of detection of IgM, IgG, and IgA serum complexes (SC) containing a T. cruzi polypeptide epitope showed that SC could be detected in 69% of the 13 Chagasic acute phase sera studied with IgG, in 84% with IgM, and in 75% with IgA. Only 16% (IgG-SC), 8% (IgM-SC), and 10% (IgA-SC) of chronic sera from 50 patients were positive. No patients with toxoplasmosis or rheumatoid factor were positive. Of the 11 leishmaniasis sera studied, four had IgG-SC, two had IgA-SC, and five had IgM-SC. Of the eight Yanomamo Indians infected by Onchocerca volvulus, three were found to have IgG-SC, two had IgM-SC, and two had IgA-SC. Thirteen sera from healthy individuals living in an endemic area were also studied. One subject had IgG IgM and IgA-SC. The results presented in this study show for the first time, the specific detection of IgM, IgG, and IgA immune complexes using a MAb against T. cruzi. The presence of the epitope in association with IgM antibodies in sera from patients with the acute phase of the disease suggests that this antigen(s) carrying the epitope that reacts with the MAb could be a marker(s) of active infection. In addition, the specificity of the serum complex capture assay allowed the detection of Chagas' disease in two different endemic areas (Argentina and Venezuela). 
Primary tracheojejunal shunt operation for voice restoration following pharyngolaryngoesophagectomy. A primary tracheojejunal shunt operation was performed for voice restoration following pharyngolaryngoesophagectomy with free jejunum reconstruction for advanced hypopharyngeal cancer. A fistula was created between the membranous part of the trachea and the lower part of the transplanted jejunum. The membranous part of the trachea was tubed to construct the tracheojejunal shunt. All three patients who had the tracheojejunal shunt operation retained phonatory function. Pitch formation was seen in the voice waveform with use of the tracheojejunal shunt. No leakage was seen at all during deglutition and a swallowing function was obtained in all patients who had the tracheojejunal shunt. 
Late potentials are unaltered by ventricular filling pressure reduction in heart failure. Exacerbation of heart failure may increase susceptibility to arrhythmias. Therefore tests to assess the risk of arrhythmia, performed after hemodynamic improvement, may be of limited value. To determine whether hemodynamic improvement alters ventricular late potentials detected by signal-averaged ECG, we studied 27 consecutive patients with dilated heart failure (left ventricular ejection fraction 0.20 +/- 0.06, 15 with coronary artery disease) before and 3 +/- 2 days after tailored vasodilator and diuretic therapy reduced ventricular filling pressures. QRS duration, terminal QRS amplitude (root mean square [RMS]), and low-amplitude (less than 40 microV) signal (LAS) duration were determined by an automated algorithm from the vector magnitude of the QRS high-pass filtered at 25 Hz and at 40 Hz. Despite marked decreases in pulmonary capillary wedge (27 +/- 7 to 16 +/- 5 mm Hg, p less than 0.001) and right atrial (13 +/- 7 to 7 +/- 4 mm Hg, p less than 0.001) pressures and a 20% increase in cardiac output, there was not a significant change in QRS duration, RMS, or LAS. Before and after therapy late potentials, defined as abnormal QRS duration RMS, or LAS, were present in 14 (52%) patients with filtering at 25 Hz and in 22 (81%) patients with filtering at 40 Hz. The signal-averaged ECG after hemodynamic improvement predicted the results during exacerbation of heart failure in all patients. Thus in patients with advanced heart failure the signal-averaged ECG obtained after hemodynamic improvement reflects the findings during exacerbation of heart failure. 
A novel cyclin encoded by a bcl1-linked candidate oncogene We have previously identified a candidate oncogene (PRAD1 or D11S287E) on chromosome 11q13 which is clonally rearranged with the parathyroid hormone locus in a subset of benign parathyroid tumours. We now report that a cloned human placental PRAD1 complementary DNA encodes a protein of 295 amino acids with sequence similarities to the cyclins. Cyclins can form a complex with and activate p34cdc2 protein kinase, thereby regulating progress through the cell cycle. PRAD 1 messenger RNA levels vary dramatically across the cell cycle in HeLa cells. Addition of the PRAD1 protein to interphase clam embryo lysates containing inactive p34cdc2 kinase and lacking endogenous cyclins allows it to be isolated using beads bearing p13suc1, a yeast protein that binds cdc2 and related kinases with high affinity and coprecipitates kinase-associated proteins. Addition of PRAD1 also induces phosphorylation of histone H1, a preferred substrate of cdc2. These data suggest that PRAD1 encodes a novel cyclin whose overexpression may play an important part in the development of various tumours with abnormalities in 11q13. 
Use of the perforated balloon catheter to infuse marker substances into diseased coronary artery walls after experimental postmortem angioplasty. A perforated balloon catheter was used in human coronary arteries after postmortem angioplasty had been performed. The catheter used has a standard angioplasty balloon with a pattern of laser-produced holes, 25 microns in size, which generate streams of fluid under pressure. Studies of the routes by which marker substances enter diseased arterial tissue when infused by the perforated balloon after experimental angioplasty are described. A colored marker dye entered the new crevices and dissection planes created by the angioplasty, but did not extend greater than 2 cm either proximal or distal to the perfused segment. Horseradish peroxidase entered tissue not only from the lumen and adventitia as occurs with its infusion into normal tissue with the perforated balloon, but also extended from new crevices and dissection planes created by the angioplasty. Platelet aggregation, coagulation and cell proliferation, the likely causes of restenosis after angioplasty, originate in the sites of greatest tissue disruption and blood stasis. These postmortem studies suggest that active drugs are delivered to the arterial wall in a manner likely to be effective in preventing these events. 
Acquired Brown's syndrome associated with hypogammaglobulinemia. We describe a 10-year-old girl with hypogammaglobulinemia who presented initially with painless progressive diplopia on right upward gaze and associated tenderness in the area of the superior oblique tendon (Brown's syndrome). She was given prednisone (40 mg/day) with gradual improvement of her symptoms. Prednisone was tapered and her symptoms remained unchanged for 10 months. She then experienced rapid deterioration. Prednisone was reinstituted with similar improvement and then therapy was switched to naproxen. She remains with only slight diplopia on extreme upward gaze. 
Improving results in the treatment of gastric cancer: an 11-year audit. Of 280 patients presenting to one hospital with gastric cancer between 1975 and 1985, 97 (35 per cent) did not undergo surgery and 29 per cent (54 out of 183) of those who did had no resection performed. The 30-day operative mortality rate in the study period was 15 per cent (28 out of 183) but in the subsequent 4-year period this fell to 7 per cent (5 out of 69). The survival rate correlated significantly with depth of invasion but not with tumour site or degree of differentiation. The incidence of early gastric cancer in this series was 5 per cent but the 5-year survival rate in this group was 52 per cent suggesting that the true incidence might be even lower. The overall 5-year survival rate in our area 20 years ago was only 5.2 per cent but in this series it was 11 per cent overall and 24 per cent after resection, and with actuarial correction 15 per cent overall and 28 per cent after resection. The continuing improvement in operative mortality rates and in 5-year survival rates gives grounds for optimism, but the disease must be diagnosed earlier if this improvement in outlook is to continue. 
gamma-Hydroxybutyrate: a health-food product producing coma and seizurelike activity. Sixteen cases of adverse effects due to a new health-food product, gamma-hydroxybutyrate (GHB), were reported to the San Francisco Bay Area Regional Poison Control Center in the 5-month period from June to October 1990. Cases have also been reported in eight other states. Adverse effects included coma (four patients) and tonic-clonic seizurelike activity (two patients). Doses ranged from 1/4 teaspoon to 4 tablespoons. Acute symptoms resolved within 7 hours. GHB was investigated as an anesthetic agent during the 1960s until seizures and lack of analgesia precluded its use. It was recently introduced in the health-food market as a food supplement for body builders with claims of anabolic effects by stimulating growth hormone release. GHB remains under investigational new drug status with the Food and Drug Administration and is illegal for over the counter sale. The Food and Drug Branch of the California Department of Health Services has prohibited further sale of this product in California as have health departments in Florida and South Carolina; however, new cases continue to be reported. Health professionals should be aware of the potential health hazards of GHB. 
Constitutive expression of multiple growth factor genes by melanoma cells but not normal melanocytes. In a panel of metastatic melanoma cell lines we found steady-state mRNA transcripts for multiple growth factors including basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF)-A, PDGF-B, transforming growth factor (TGF)- beta 1, TGF- alpha, melanoma growth-stimulating activity (MGSA), interleukin (IL)-1 alpha, and IL-1 beta but not insulin-like growth factor (IGF)-1 or IGF-2. Expression of growth factor genes was constitutive because prior to RNA extraction melanoma cells were maintained in a chemically defined culture medium free of exogenous growth factors. Each of four cell lines had an individual pattern of expression of either two, four, five, or seven growth factors; however, all cell lines shared expression of the bFGF gene. Two strains of normal melanocytes expressed TGF- beta 1 but not bFGF, PDGF, TGF- alpha , or MGSA mRNA at detectable levels. We tested growth-modulatory effects of the growth factors most frequently expressed by melanoma cells (bFGF, TGF- alpha, TGF- beta, PDGF). None of these stimulated melanoma cell growth consistently, whereas exogenous, acid-activated TGF- beta inhibited melanoma growth at concentrations greater than 10 ng/ml, suggesting that bioactive TGF- beta may represent a physiologic growth inhibitor. Neither neutralizing antisera to PDGF or TGF- alpha nor a monoclonal antibody to the epidermal growth factor (EGF)-receptor inhibited melanoma cell growth. Our results indicate that multiple growth factors are expressed simultaneously and constitutively by melanoma cells but not normal melanocytes in culture. Expression of bFGF is a common feature underscoring the significance of bFGF as an autocrine factor for melanoma cells as described earlier. Secreted PDGF and TGF- alpha are apparently not involved in or not essential for autocrine growth stimulation of melanoma cells. 
Events in the Cardiac Arrhythmia Suppression Trial (CAST): mortality in the entire population enrolled [published erratum appears in J Am Coll Cardiol 1991 Sep;18(3):888] To test the hypothesis that suppression of ventricular arrhythmias by antiarrhythmic drugs after myocardial infarction improves survival, the Cardiac Arrhythmia Suppression Trial (CAST) was initiated. Suppression was evaluated before randomization during an open label titration period. Patients whose arrhythmias were suppressed were randomized in the main study and those whose arrhythmias were partially suppressed were randomized in a substudy. Overall survival and survival free of arrhythmic death or cardiac arrest were lower [corrected] in patients treated with encainide or flecainide than in patients treated with placebo. However, the death rate in patients randomized to placebo therapy was lower than expected. This report describes the survival experience of all patients enrolled in CAST and compares it with mortality in other studies of patients with ventricular arrhythmias after myocardial infarction. As of April 18, 1989, 2,371 patients had enrolled in CAST and entered prerandomization, open label titration: 1,913 (81%) were randomized to double-blind, placebo-controlled therapy (1,775 patients whose arrhythmias were suppressed and 138 patients whose arrhythmias were partially suppressed during open label titration); and 458 patients (19%) were not randomized because they were still in titration, had died during titration or had withdrawn. Including all patients who enrolled in CAST, the actuarial (Kaplan-Meier) estimate of 1-year mortality was 10.3%. To estimate the "natural" mortality rate of patients enrolled in CAST, an analysis was done that adjusted for deaths that might be attributable to encainide or flecainide treatment either during prerandomization, open label drug titration or after randomization. Because the censoring procedure excluded patients treated with encainide or flecainide after randomization, the mortality estimate will be less than the unadjusted mortality estimate of 10.3%. 
Left-sided pleural effusion secondary to splenic vein thrombosis. A previously unrecognized relationship. The association of left-sided pleural effusion and subcapsular splenic hematoma was reported in 1980. We describe a patient in whom a left-sided pleural effusion resulted from splenic vein thrombosis, a relationship not previously reported. Splenectomy was performed, demonstrating the spleen to be enlarged and hemorrhagic. The pleural effusion did not recur after splenectomy. The three effusions due to splenic hematomas reported previously cleared only after splenectomy, suggesting splenectomy may be necessary to prevent reaccumulation. We propose possible pathophysiologic mechanisms and recommend that splenic vein thrombosis be considered in the differential diagnosis of unexplained left-sided pleural effusions. 
Adrenal carcinoma presenting as a lesion resembling cutaneous angiosarcoma. A case is reported of adrenal carcinoma presenting as an angiosarcoma-like metastasis in the scalp. Adrenal carcinoma is a rare tumor, and it metastasizes to skin rarely. The authors discuss the features of this tumor that led to a diagnosis of angiosarcoma and the means by which such a metastasis may be distinguished from vascular tumors. 
Outcome of patients who were admitted to a new short-stay unit to "rule-out" myocardial infarction. For emergency room patients with a low probability of acute myocardial infarction, we established a new short-stay coronary observation unit, a 2-bed nonintensive care unit with telemetry monitoring adjacent to the emergency room. Of 512 consecutive admissions to the coronary observation unit, 425 (83%) were discharged home without evidence of acute myocardial infarction or serious complications (mean length of stay, 1.2 days; median length of stay, 1 day); 87 (17%) were transferred to other hospital beds. The rate of acute myocardial infarction was 3%. No deaths and only 1 serious complication occurred in the coronary observation unit. At 6 month follow-up, the cardiac survival rate was 99% for patients sent home directly from this unit. It is concluded that the coronary observation unit is safe and adequate for ruling out acute myocardial infarction in a defined subset of patients. Short-stay units, however, encourage early discharges which, when premature, may miss patients who are at risk of having complications shortly thereafter. Strategies such as mandatory but expeditious predischarge stress testing to encourage early but not premature discharge may augment the efficiency of coronary observation units. 
Necrotizing fasciitis and nonsteroidal anti-inflammatory drugs. We have presented a case of fulminant necrotizing fasciitis that occurred after excessive NSAID intake with granulocytopenia. This case parallels those previously reported as outlined in the above discussion. We concur with previous investigators who have concluded that NSAIDs should be used with caution in patients with phlebitis or apparently benign inflammatory cutaneous lesions. 
Preservation of pulsatile luteinizing hormone release during postpartum lactational amenorrhea. To evaluate the pulsatile mode of immunoactive LH release during physiological lactational amenorrhea, we withdrew blood samples at 10-min intervals for 24 h from breastfeeding women (n = 9) at both 3 weeks and 3 months postpartum. Nonlactating women (n = 7) were sampled similarly in the early follicular phase of the normal menstrual cycle. Objective LH pulse analysis revealed that the mean frequencies of pulsatile LH release were similar at both times postpartum and in menstruating young women. By 3 months postpartum, mean serum PRL concentrations had declined 50%, and serum LH peak areas doubled. In contrast, LH interpulse interval, peak duration, and maximal, incremental, and fractional LH pulse amplitude did not change significantly. When deconvolution analysis was used to assess pituitary responses to two pulses of exogenous GnRH at 3 months (vs. 3 weeks) postpartum, we found significant increases in maximal LH secretory rates and the total mass of LH secreted. There was no change in the duration or timing of the evoked LH secretory burst and/or the estimated half-life of endogenous LH. In summary, during lactational amenorrhea, pulsatile LH release occurs at a mean frequency no different from that in the normal early follicular phase. As hyperprolactinemia wanes, there is increased pituitary responsiveness to exogenously administered GnRH and a doubling of spontaneous serum LH concentration peak areas. Such amplitude changes are consistent with the hypothesis of increased endogenous GnRH drive (e.g. augmented GnRH secretion per burst and/or increased pituitary responsiveness to available GnRH) during recovery of the postpartum hypothalamopituitary-ovarian axis. 
Rapid changes of atrial natriuretic peptide concentration during percutaneous transluminal coronary angioplasty. In 34 patients undergoing routine coronary angioplasty, concentrations of atrial natriuretic peptide (ANP), plasma renin (PR), and plasma aldosterone (PA) were estimated before, during, and after vessel occlusion and were correlated with hemodynamic changes. For the group as a whole, averaged right atrial pressure rose significantly (p less than 0.001) from 4.4 +/- 1.8 mm Hg at baseline to 6.7 +/- 3.0 mm Hg during vessel occlusion, and average right atrial ANP concentrations increased significantly (p less than 0.005) from 50.1 +/- 18.8 pg/ml to 59.7 +/- 21.4 pg/ml during balloon inflation. Data analysis of subgroups did not show any differences in right atrial pressure elevations between patients with left anterior descending artery (LAD) or right coronary artery (RCA) disease; ANP elevation was significant only in patients with LAD occlusion (p less than 0.001). In individual patients no statistically significant correlations were found to be present between changes in right atrial pressures and changes in atrial ANP concentrations. During vessel occlusion, PR dropped from 0.86 +/- 1.11 ng/ml/hr to 0.65 +/- 0.85 ng/ml/hr (p less than 0.001) in all patients, and PA decreased from 63.0 +/- 50.9 ng/ml to 52.2 +/- 43.4 ng/ml (p less than 0.01). Our data support the concept that, although an increase in right atrial pressure leads to ANP release in the majority of patients, atrial pressure and stretch are not the only regulatory factors of ANP release in humans. 
Primary ankylosing spondylitis, psoriatic and enteropathic spondyloarthropathy: a controlled analysis. Within our ankylosing spondylitis (AS) population (n = 1331), 85% (n = 1128) had primary AS (1 degree AS), 9% (n = 121) had psoriatic AS (PsAS) and 6% (n = 82) enteropathic AS (IBDAS). In an attempt to explore further the relationship between 1 degree AS and the secondary spondyloarthritides, we evaluated 121 consecutive patients with PsAS and 82 with IBDAS, as well as 202 controls with primary disease. The patients were matched for sex and age at review PsAS:48.1 (SD 11.3) years vs 1 degree AS:48.4 (SD 11.5), and IBDAS:46.0 (SD 12.7) vs 1 degree AS:45.9 (SD 12.7). The sex distribution for IBDAS (M:F, 1:1), was significantly less (p less than 0.001) than that for PsAS (M:F, 3.5:1) or 1 degree AS (M:F, 2.4:1). Overall, compared to 1 degree AS the PsAS and IBDAS tended to have greater disease severity as defined by e.g., (1) those taking non-steroidal antiinflammatory drugs, 86 vs 72% (p less than 0.01) and 71 vs 60% (p less than 0.05), respectively; (2) decreased spinal mobility (scale 0-8) 5.0 (SD 2.0) vs 4.4 (SD 2.3); p = 0.029 and 4.9 (SD 2.0) vs 3.9 (SD 2.4); p = 0.024, respectively; and (3) PsAS resulted in a higher AIMS pain score; 4.9 (SD 2.5) vs 4.0 (SD 2.4): p = 0.042. By contrast, peripheral joint involvement, number of total hip replacements and capacity for employment were similar in all 3 groups. In conclusion (1) among the AS population the prevalence of 1 degree AS, PsAS and IBDAS is 90, 6 and 4%, respectively. 
Chronic wounds and delusions of parasitosis in the drug abuser. Plastic surgeons are routinely consulted about the care of difficult or chronic wounds. Most of these wounds have a physiologic basis and are treated according to basic wound-healing principles. Patients with factitious wounds are difficult to treat and present diagnostic dilemmas. We present a case and review of the literature of drug-induced delusions of parasitosis to inform plastic surgeons of this important entity and for consideration in the differential diagnosis of chronic wounds. 
Usefulness of transesophageal echocardiography in the diagnosis of conditions mimicking aortic dissection. Between September 1987 and April 1989, forty patients suspected to have aortic dissection were evaluated by transesophageal echocardiography. Aortic dissection was identified in 18 patients. This study evaluated the ability of transesophageal echocardiography in the assessment of the 22 patients in whom aortic dissection was not found. A range of pathologic conditions was diagnosed in these patients. Five patients had ischemic heart disease when they were initially seen. Among the remaining 17 only one patient had a normal aorta. Aortic disease was present in the other 16 patients with aortic dilatation in 10. Atheromas were detected in seven patients with concomitant aortic dilatation in five of them. An extrinsic aortic mass was present in two patients. Transesophageal echocardiography correctly identified an anastomotic leak at the site of left coronary artery implantation in a patient with a recent Bentall procedure, and a large mobile clot within the proximal descending aorta in a patient with blunt chest trauma. These findings obviated the need for other tests in 15 patients and led to surgery in four with no ancillary tests performed in three of them. Thus transesophageal echocardiography has an important role in assessing patients with suspected dissection. Aortic disease is common even in patients in whom aortic dissection is excluded, and some of the conditions can be just as life-threatening as dissection. Transesophageal echocardiography not only reliably identifies dissection but can also detect luminal and extraluminal diseases not adequately visualized by other modalities. 
Tegmental dehiscence and brain herniation into the middle ear cleft. The tegmen tympani may occasionally be breached by herniation of the temporal lobe with or without dural cover. The clinical presentation may be obvious with CSF otorrhoea but less so with apparent middle ear effusion, CSF rhinnorrhoea, conductive hearing loss, recurrent meningitis or intracranial sepsis. Diagnosis requires suspicion of the condition, which may be aided by radiological imaging. Surgical repair is to be recommended: various techniques are available but bone enveloped by fascia placed by subtemporal approach is preferred. The features of this problem are highlighted by four cases. 
Prospective evaluation of unilateral adrenal masses in patients with operable non-small-cell lung cancer. Although adrenal metastases are frequently noted with non-small-cell lung cancer (NSCLC) at autopsy, their incidence in patients with operable NSCLC is unclear. We prospectively assessed consecutive patients with otherwise operable NSCLC for the incidence and histology of unilateral adrenal masses. Assessment included blood chemistries, lung function tests, bronchoscopy, chest x-ray, bone scan, and computed tomography (CT) of the head, chest, and upper abdomen. Of 246 patients with otherwise operable NSCLC, 10 (4.1%) had a unilateral adrenal mass. Unilateral adrenal masses were needle-aspirated under CT control. If cytology was nondiagnostic, adrenalectomy was performed. Four (40%) of 10 patients had adrenal metastases proven by needle aspiration. Of the six (60%) patients with benign unilateral adrenal masses, one was demonstrated by needle aspiration. In the other five patients, a nondiagnostic needle aspiration led to adrenalectomy, which yielded two adenomas, two hyperplastic nodules, and one hemorrhagic cyst. There was no significant difference between the patients with benign and metastatic unilateral adrenal masses with respect to patient age or stage and size of adrenal mass. Patients with benign unilateral adrenal masses underwent curative resection of their NSCLC and had significantly prolonged survival compared with patients with metastatic unilateral adrenal masses treated with chemotherapy (P = .037). Median survival of patients with benign and metastatic unilateral adrenal masses was greater than 30 months and 9 months, respectively. In conclusion, the presence of unilateral adrenal masses in patients with otherwise operable NSCLC should not preclude thoracotomy without pathologic proof of metastatic disease. 
Palliation of malignant tracheal strictures using silicone T tubes. The use of silicone T tubes for intubation of malignant tracheobronchial strictures may provide some degree of palliation of this distressing condition. It was used in seven patients with malignant lesions and two with benign strictures (resulting from tracheal trauma and lung transplantation). Four patients (two with cancer) are still alive and well with the tube in position. All patients noted improvement in dyspnoea and stridor. The main problems were tube migration (one patient), tracheo-oesophageal fistula (one patient), and blockage of the tube by tumour (two patients) or encrusted secretions (three patients). Airway patency was restored when the tube was blocked by cleaning or by laser resection of the tumour. With careful supervision and education of the patient intubation can give useful palliation to patients with distressing upper airways obstruction. 
Self-referred mammography patients: analysis of patients' characteristics. Among mammography patients, a small but growing group of highly motivated women refer themselves directly for screening without the suggestion of their physicians. We surveyed 485 patients during a 3-month period to study how self-referred mammography patients differ from physician-referred patients. Self-referred patients were more likely than physician-referred patients to have a family income of more than $30,000 per year, to be college graduates, and to consider their health as good or excellent. A large percentage of self-referred patients performed other health-promoting practices, but were not significantly more likely to do these than were physician-referred patients. Women who referred themselves were more likely to have a friend with breast cancer and to believe that cancer could be cured. They expressed much less worry about radiation exposure and were more likely to consider $50.00 an appropriate charge for a screening mammogram. By far, the greatest motivator for self-referred patients was health promotion and disease prevention. Self-referred mammography patients tend to be wealthier, more education, and less concerned about the cost and radiation dose of mammography when compared with physician-referred mammography patients. 
Genotypic analysis of diffuse, mixed cell lymphomas. Comparison with morphologic and immunophenotypic findings. Malignant lymphoma, diffuse, mixed small and large cell type, as defined in the Working Formulation, is heterogeneous both morphologically and immunophenotypically and, in some cases, clonality may be difficult to determine. Because gene rearrangement analysis has been shown to be a sensitive method for determining clonality, the authors genotyped 20 cases and compared the results with histologic and immunophenotypic findings. Immunophenotypic studies demonstrated that all lesions were composed predominantly of T cells. In addition, in eight cases either a monoclonal B-cell population (five lesions) or an aberrant immunophenotype (two T, one B) was detected, supporting a malignant diagnosis. In seven of these eight lymphomas, genotypic analysis confirmed the presence of a population of clonal cells. One case with an abnormal T-cell phenotype was germline. In 12 cases the immunophenotypic results were uncertain (i.e., no clonal population or abnormal immunophenotype was identified). Genotypic analysis provided evidence of clonality in eight. In four cases with uncertain immunophenotypic results, a clonal population also could not be identified with the use of Southern blot analysis. Thus, the authors conclude that gene rearrangement analysis is a valuable tool in the study of diffuse mixed cell lymphomas and is complementary to immunophenotypic studies. In addition, the authors analyzed the major breakpoint region of the bcl-2 protooncogene on chromosome 18, either by Southern blot analysis and/or with the polymerase chain reaction. The authors identified the t(14;18)(q32;q21) translocation in seven B-cell lymphomas, five of which were not considered to be of follicular center cell type on the basis of morphologic findings. These results suggest that the histologic spectrum of follicular center cell lymphomas is greater than is appreciated in the literature. 
Direct myocardial revascularization without extracorporeal circulation. Experience in 700 patients Between May 1978 and March 1990, 700 patients were operated on with direct coronary surgery without extracorporeal circulation (ECC): 529 (76 percent) were male and 171 (24 percent) were female. The average age was 64 years (range, 35 to 86 years), 454 (65 percent) had unstable angina, 163 (23 percent) had stable angina, 51 (7 percent) had postmyocardial infarction angina, and 32 (5 percent) had acute myocardial infarction at the moment of the operation. In this series of patients, all branches of the coronary arteries were bypassed; the mammary artery was used in 40 percent of the cases, the average bypass per patient was 2.2 (range, 1 to 5), and 26 percent had associated disease of high risk to undergo ECC. The morbidity was 4 percent and the mortality for this series of patients was 1 percent; the probability of survival at seven years was 90 percent. This experience shows us that this surgery is an alternative in the treatment of coronary disease, especially for aged patients with associated disease, in some cases of acute transmural infarction, and also for patients who need coronary angioplasty. Also, it can improve the relation cost/benefit in coronary surgery. 
Clues and pitfalls in stereotactic biopsy of the central nervous system. We present a 6-year experience on 307 stereotactic biopsy specimens of the central nervous system using Leksell's and Talairach's systems independently and either Leksell or Sedan needles. Patients with deep cerebral lesions (basal ganglia, parasellar, pineal, or third ventricle), those located in highly functional areas or those poorly defined on imaging studies, as well as candidates for brachytherapy, were selected. Smear examination during surgery was a routine procedure followed by conventional histologic methods. Ages ranged from 8 months to 81 years (mean, 33.64 years). The series comprised 258 tumors, 28 nonneoplastic cases, and 21 nondiagnostic samples. Of the 258 tumors, 179 were supratentorial, 28 were infratentorial, 36 were of the pineal area, and 15 were from sellar and suprasellar regions. Results of the histologic examination showed the following: astrocytic tumors, 148 (57.36%); oligodendroglial, 25 (9.68%); ependymal, six (2.32%); primitive neuroectodermal tumors, 17, including 14 pineoblastomas (5.45%) and three medulloblastomas (1.16%), seven lymphomas (2.71%), seven meningiomas (2.71%), four schwannomas (1.55%), eight craniopharyngiomas (3.10%), 12 germinomas (4.65%), and 20 metastases (7.78%). Nontumoral cases included six arteriovenous malformations, six pyogenic lesions, seven infarcts, two hematomas, one multiple sclerosis plaque, one Fahr, one progressive multifocal leukoencephalopathy, one tuberculosis, one cysticercosis, and one Chagas' encephalitis. Awareness of the cerebellar granular layer in infratentorial targets as well as glial reaction around craniopharyngiomas is essential to avoid misdiagnosis. Difficulties were basically differential diagnosis between well-differentiated astrocytomas vs glial reaction, as well as poorly differentiated neoplasms vs metastases. 
Functional results after total or near total glossectomy with laryngeal preservation. Locally advanced tongue cancer is a devastating disease for which there are limited therapeutic options that will result in a high rate of cure while preserving function. To determine the oncologic effectiveness of total or near total glossectomy with laryngeal preservation and the possibility of speech and swallowing rehabilitation following treatment, we reviewed our experience with 27 patients treated between 1982 and 1989. Twenty-four patients were eligible for 2-year follow-up and their disease-specific survival was 51%. Swallowing was achieved initially in 18 patients (67%), while 12 had successful long-term deglutition (44%). Oral communication was accomplished in 25 patients (92%). Significant aspiration occurred in three patients and was severe enough to require interval laryngectomy in two patients. The role of laryngeal suspension, palatal augmentation prosthesis, and videofluoroscopy as rehabilitation adjuncts for the total glossectomy patient are described. 
Effect of primary-stage feline immunodeficiency virus infection on subsequent feline calicivirus vaccination and challenge in cats. The effect of experimental primary-stage feline immunodeficiency virus (FIV) infection on feline calicivirus (FCV) vaccination and challenge in cats was studied. Clinical signs of acute FCV disease were more widespread in the cats which were infected with FIV than in those which were not. FIV infection also prolonged shedding of FCV, with more of the FIV-infected cats becoming chronic carriers. Although vaccination induced protection against acute FCV disease, this was to a lesser degree in FIV-infected cats. Vaccination by itself also appeared to enhance long-term virus shedding. There was evidence of an impaired anamnestic FCV-neutralizing antibody response in FIV-infected cats following FCV challenge. 
Congenital atresia of left main coronary artery: proposed mechanism for severe disabling angina in a patient with non-atherosclerotic single right coronary artery--a case report. A patient with progressive disabling angina was found to have a single right coronary artery with atresia of the left main coronary artery, and absence of any obstructive coronary disease. The patient required aortocoronary by-pass surgical reconstruction of a left main coronary artery to control her angina. Possible mechanisms for the development of her anginal pain are briefly discussed. 
Clinical effects of allopurinol on intractable epilepsy. We studied the clinical efficacy of allopurinol as add-on therapy in 31 patients with intractable epilepsy. When administered for a short time, allopurinol was effective in 17 patients (55%); 8 were seizure-free, 8 had 75% decrease in seizure frequency, and 1 had greater than 50% decrease. Allopurinol was most effective in patients with localization-related epilepsy, especially in secondarily generalized tonic-clonic seizures. Allopurinol was not as effective in patients with Lennox syndrome or West syndrome, or in severe myoclonic epilepsy in infants. When allopurinol was administered greater than 1 year, its initial effectiveness continued in 8 of 14 patients who exhibited initial improvement. In 2 of the remaining 6 patients, the initial improvement disappeared during the course of treatment but control was regained by increasing the dosage of allopurinol. Mild side effects were observed in 4 patients (13%): drowsiness in 3 and abdominal pain in 1. Allopurinol may be a useful antiepileptic drug (AED), and a double-blind placebo-controlled trial should be performed. 
Coronary angiography after thrombolytic therapy for acute myocardial infarction. PURPOSE: To review the status of emergency, urgent, routine, and selective angiography after intravenous thrombolytic therapy. DATA SOURCES: Relevant English-language articles published from January 1985 to July 1990 were identified through MEDLINE. STUDY SELECTION: For emergency angiography, four major randomized studies were reviewed and data from nine studies that incorporated rescue coronary angioplasty were pooled for meta-analysis. For urgent angiography, two controlled trials were reviewed. Comparisons of routine and selective angiography were done using data from two dedicated, large-scale, controlled trials and the ancillary findings of four other studies of reperfusion that incorporated angiography. DATA EXTRACTION: The review emphasizes the findings from multicenter, randomized, controlled trials. DATA SYNTHESIS: Emergency coronary angiography is done primarily in preparation for primary or rescue angioplasty; the value of rescue angioplasty has yet to be assessed in a randomized trial, but technical success and reocclusion improve significantly after therapy with nonspecific plasminogen activators compared with relatively specific agents (success rate, 86% compared with 75%, respectively; P = 0.03; reocclusion rate, 10.9% compared with 26.8%, respectively; P less than 0.001). Urgent coronary angiography has value for treating recurrent ischemia, but patients who develop this complication after thrombolysis are likely to have a suboptimal outcome despite aggressive care. Studies support the use of either selective or routine angiography in uncomplicated patients after thrombolytic therapy; either approach is acceptable, but the former is more practical and may prove to be cost effective. CONCLUSIONS: Optimal follow-up for patients with evolving myocardial infarction who receive thrombolysis may incorporate coronary angiography at various stages. Although our ability to noninvasively detect reperfusion, reocclusion, or viable but ischemic myocardium is limited at present, available data may assist in selecting a catheterization strategy. 
Imaging of vascular complications associated with renal transplants. Vascular complications associated with renal transplants are a significant cause of graft dysfunction. The most common complications are arterial and venous stenoses and thromboses and intrarenal and extrarenal arteriovenous fistulas and pseudoaneurysms. Although angiography is the imaging gold standard for the diagnosis of these disorders, Doppler sonography, scintigraphy, and occasionally CT are capable of detecting them. An awareness of the different imaging appearances of each complication will aid in their early detection and treatment. In this review, we present this information and provide a perspective on the relative roles of these techniques in the detection of vascular complications from renal transplants. 
Acquired immunodeficiency syndrome with disseminated toxoplasmosis presenting as an acute pulmonary and gastrointestinal illness. Encephalitis due to the protozoan Toxoplasma gondii has emerged as a common cause of central nervous system disease in patients with acquired immunodeficiency syndrome. Extraneural disease is less common and more difficult to diagnose. We report a case of widely disseminated toxoplasmosis that presented as acute gastrointestinal and pulmonary disease in a patient without a prior diagnosis of acquired immunodeficiency syndrome. The diagnosis of toxoplasmosis was made only at autopsy. Antemortem diagnosis of disseminated T gondii infection requires a high degree of clinical suspicion and the prompt utilization of appropriate diagnostic testing. Since toxoplasmosis is a potentially treatable opportunistic infection, diagnosis allows the swift institution of anti-Toxoplasma therapy. 
Randomized dose-searching phase ILE/II trials of fractionation in radiation therapy for cancer. This article describes a new design, phase ILE/II dose searching, used in four prospective, randomized, multicenter clinical trials of escalating total doses of hyperfractionated radiation. This design combines an experimental protocol with a statistical application of ranking and selection theory. Its purpose was to identify (within a certain margin of error) a dose that achieved the highest rate of clinical response from a set of doses that were tolerable in terms of both acute (within 90 days) and late (more than 90 days) toxic effects (LE). We calculated the number of patients required to reliably test toxicity under various assumptions. To determine the maximum tolerated total dose for hyperfractionated radiation, we randomly assigned patients with tumors that responded to radiation therapy in a dose-dependent manner from four body sites (lung, upper respiratory and digestive tract, bladder, and brain) to one of three regimens receiving total doses (D1, D2, or D3) differing by increments of 4.8 Gy. All patients received two fractions of 1.2 Gy each (separated by 4-6 hours) daily 5 days a week. The lowest total dose was set at the level considered tolerable with standard once-a-day radiation therapy. We tested tumor responses and late toxic effects of higher doses by assigning patients to these three regimens until acute effects and early estimates of late effects were found to be acceptable for the highest dose D3; thereafter, regimen D1 was closed, and additional patients were assigned to D2, D3, and D4 (an escalated total dose greater than D3 by an increment of 4.8 Gy). The assignment of patients was performed in a weighted manner (1:1:2), so that greater numbers were assigned to the highest dose regimen (whether D3 or D4) to allow rapid evaluation of the feasibility of the highest dose. 
Functional significance of an overlapping consensus binding motif for Sp1 and Zif268 in the murine adenosine deaminase gene promoter. The murine adenosine deaminase (ADA) gene has a (G + C)-rich promoter that can support diverse tissue-specific gene expression. By using deletion and mutation analyses, we have identified a cis-acting "repressor" element located immediately upstream of the proximal Sp1 binding site in the ADA gene promoter. This repressor element was localized to a binding site for the immediate-early, serum-responsive, DNA binding factor Zif268. This Zif268 binding site partially overlaps a binding site for the general transcription activator Sp1. Disruption of the Zif268 binding site without disturbing the Sp1 binding motif abolished Zif268 binding and resulted in significantly elevated promoter function. Conversely, disruption of the proximal consensus Sp1 binding motif without disturbing the Zif268 binding site resulted in a loss of Sp1 binding at that region and greatly reduced promoter activity. Our results suggest that one function of Zif268 may be to down-regulate this type of mammalian gene promoter by competing with Sp1 for binding to the overlapping binding motif. 
N-myc genomic content and DNA ploidy in stage IVS neuroblastoma. DNA ploidy and N-myc genomic content were analyzed in a series of stage IVS neuroblastomas by flow cytometry and Southern blot hybridization, respectively. Of the 12 stage IVS neuroblastomas studied, nine were aneuploid (DNA index [DI] greater than 1), two were diploid (DI = 1), and one was not assessable for DNA content due to insufficient tumor material. N-myc gene amplification was present in two of 12 tumors. None of the aneuploid tumors exhibited N-myc amplification. Among the aneuploid neuroblastomas, the DIs were between 1.27 and 1.60, ie, in the near-triploid range. The follow-up from diagnosis ranged from 1 to 41 months (mean, 20 months). The nine neuroblastomas with near-triploid DNA content were free of disease at the end of the follow-up period. In contrast, a rapid and fatal tumor progression was observed for the three neuroblastomas with N-myc amplification and/or diploidy. Although involving only a limited series, these results strongly suggest that the combined analysis of DNA ploidy and N-myc genomic content could predict clinical outcome in stage IVS neuroblastoma and should help to identify patients for whom a more aggressive therapy is required. 
Report of a hidden case of overfeeding. Nutritional support is essential to the care of the critically ill patient, but complications of overfeeding can occur. Precise metabolic measurement by indirect calorimetry can detect problems of nutrition and allow adjustment in caloric intake. This case study illustrates the complications of carbon dioxide retention and inability to wean from mechanical ventilation with subsequent prevention of further complications. 
Management of renal cell carcinoma with vena caval thrombi via cardiopulmonary bypass and deep hypothermic circulatory arrest. Cardiopulmonary bypass with deep hypothermic circulatory arrest allows safe and effective removal of renal tumors with extensive thrombi involving the vena cava under controlled circumstances without permanent side effects. The technique averts extensive dissection of the inferior vena cava and occlusion of major vessels while providing up to 60 minutes of safe operating time in a bloodless field and complete visibility of the interior of the vena cava. Adjunctive procedures for tumor excision or cardiac revascularization can be performed at the same time without increased operative risk. 
Melanosis coli: a case report in a trauma patient and review of the literature. Melanosis Coli (MC) is a benign pigmentation disorder of the colon occasionally diagnosed at endoscopy. The authors report a case of M. coli in a patient with a gunshot to the abdomen, in whom the entity produced an interesting clinical picture, and a review of the literature on this condition. 
Dental implants placed in a patient with multiple myeloma: report of case A 69-year-old male, under active treatment for multiple myeloma, fractured his left maxillary second premolar palatal abutment tooth and requested treatment because his upper partial denture no longer fit. Several other teeth were deemed hopeless, and construction of a maxillary complete denture presented problems. There are general contraindications regarding dental implant surgery in the terminally ill patient; however, in this case, the patient wished to maximize his quality of life and opted to undergo implant surgery. With close management, the treatment was successful. 
Effects of substance P on norepinephrine release from vascular adrenergic neurons in spontaneously hypertensive rats. This study was performed to investigate the role of substance P in the vascular adrenergic transmission in hypertension. In perfused mesenteric vasculatures prepared from spontaneously hypertensive rats (SHR, 7 to 10 weeks old) and age-matched Wistar-Kyoto rats (WKY), we have examined the effects of substance P on vascular responsiveness as well as on norepinephrine release from the vascular adrenergic neurons. In preliminary studies with normotensive Wistar rats, pressor responses and endogenous norepinephrine release during electrical nerve stimulation were inhibited by substance P in a dose-dependent manner. However, vasoconstrictor responses to exogenous norepinephrine were not affected by the peptide. In SHR, the stimulation-evoked pressor responses and norepinephrine release were enhanced compared with WKY. Alternatively, the suppression of these responses by substance P was significantly less in SHR than in WKY. These results demonstrate that substance P could have a modulatory effect on noradrenergic activity and cause a decrease in stimulation-evoked norepinephrine release from the vascular adrenergic neurons. The attenuated reduction of pressor responses and norepinephrine release by substance P in SHR might suggest insufficient regulation of vascular adrenergic transmission by the peptide in hypertension. 
Control of acute lower respiratory illness in the developing world: an assessment of vaccine intervention. The major bacterial and viral causes of morbidity and death due to acute lower respiratory infection (ALRI) in the developing world are amenable to control by vaccines. Initially, full use of measles, pertussis, and diphtheria vaccines, in appropriately scheduled programs, can make an immediate contribution to the reduction of severe respiratory infection. Emerging technologies offer the promise of vaccines against bacterial and viral respiratory pathogens that are suitable for infants and children in developing countries. These technologic advances include the use of protein-polysaccharide conjugates of endemic serotypes for Haemophilus influenzae and Streptococcus pneumoniae vaccines and new approaches to the use of purified protein components or attenuated live virus with respiratory syncytial virus and paramyxovirus vaccines. Such vaccines should soon be available for evaluation in developing countries. It is timely to embark upon a program of development, evaluation, and worldwide deployment of vaccines for the control of ALRI. 
Electrophysiological effects of left ventricular hypertrophy. Effect of calcium and potassium channel blockade. BACKGROUND. To define the arrhythmogenic effects of left ventricular hypertrophy (LVH) in the intact heart, we carried out a detailed electrophysiological assessment in our previously validated feline aortic-banding model and then tested the effects of agents that blocked either the slow inward calcium or voltage-dependent potassium channel. METHODS AND RESULTS. We measured intraventricular and interventricular conduction times, excitability thresholds, ventricular effective refractory periods, and monophasic action potential duration at several sites in cats with LVH as well as in concurrent control (sham-operated) cats. In addition, we assessed vulnerability to ventricular arrhythmia using direct measurement of ventricular fibrillation (VF) thresholds and by standard techniques of programmed stimulation. Despite finding no difference between LVH and sham-operated cats in mean values for several electrophysiological parameters, the former group was significantly more vulnerable to VF, with more spontaneous VF and lower VF thresholds. Compared with the sham controls, LVH cats also had a greater dispersion of effective refractory period (35 +/- 11 versus 12 +/- 4 msec, p less than 0.01) and monophasic action potential duration at 90% repolarization (69 +/- 25 versus 39 +/- 7 msec, p less than 0.02). Verapamil had no significant effect on these electrophysiological parameters, nor did it affect VF threshold. However, risotilide, an inhibitor of the voltage-dependent potassium channel, narrowed dispersion of the effective refractory period and monophasic action potential duration concomitant with a marked reduction in ventricular vulnerability. CONCLUSIONS. LVH has a pronounced effect on dispersion of refractoriness and repolarization and renders the ventricle more vulnerable to fibrillation. Blockade of the voltage-dependent potassium channel, but not the slow inward calcium channel, narrows the dispersion of recovery of excitability and protects against VF. 
Antihypertensive effects of isradipine and captopril as monotherapy or in combination. The antihypertensive effects of isradipine and captopril were studied in 140 patients (70 men) with mild-to-moderate hypertension, aged 26 to 74 years, in a double-blind, randomized, between-patient comparative trial. Initial treatment started with 1.25 mg isradipine twice daily or 12.5 mg captopril twice daily. If normotension was not achieved after four weeks, doses were increased to 2.5 mg twice daily or 25 mg twice daily, respectively. If the maximum dose as monotherapy did not result in normotension, captopril (12.5 mg or, if necessary, 25 mg twice daily) was added to regimens of the isradipine-treated patients or isradipine (1.25 mg or, if necessary, 2.5 mg twice daily) was given in addition to the captopril-treated patients. After 24 weeks of active treatment, systolic blood pressure was significantly reduced (P less than .001) with isradipine (from 168 +/- 18 to 144 +/- 14 mm Hg) and with captopril (from 168 +/- 20 to 143 +/- 10 mm Hg). Diastolic blood pressure also fell significantly (P less than .001) in both groups (isradipine: from 105 +/- 5 to 84 +/- 5 mm Hg; captopril; from 105 +/- 4 to 85 +/- 4 mm Hg). With isradipine as monotherapy, diastolic blood pressure was normalized in 49% of patients compared with 56% with captopril as monotherapy (P = NS). Combining both drugs resulted in an increased rate of normalization (to 87%). The results indicate that combined treatment with a calcium antagonist and an angiotensin-converting enzyme inhibitor is effective in lowering blood pressure and is well tolerated during long-term therapy. 
Compensatory hypertrophy and adaptation in the cortical collecting duct. The cortical collecting duct (CCD) undergoes hypertrophy and functional adaptation following reduction of renal mass. The nature and mechanisms of these changes have been investigated using microperfusion of isolated CCD from rabbit remnant kidneys. By 1 week after reduction of renal mass, tubule hypertrophy and increased sodium transport are fully developed. The transport adaptations are specific or selective, since bicarbonate transport in these CCD is unchanged. Mineralocorticoids may play an important role in the hypertrophy and increased sodium transport, since plasma aldosterone increases early after reduction of renal mass. Also, adrenalectomy abolishes the changes in size and sodium transport, even with supplementation of aldosterone to unstressed physiologic levels. Epidermal growth factor also has immediate effects on CCD sodium transport; however, the direction of the effect is opposite--an inhibition of transport. 
Perilymph fistula--a diagnostic dilemma. A retrospective series is presented of 51 cases operated on for suspected perilymph fistula. In 26 ears a fistula was identified at surgery. A positive fistula test was found to strongly indicate a perilymph fistula but was more often negative than positive in surgically demonstrated fistula ears. Other vestibular tests were found to be of little value in the pre-operative diagnosis. Ears with a surgically demonstrated fistula and sensorineural hearing loss had either flat or downward-sloping audiograms. Difficulties in diagnosing a perilymph fistula at tympanotomy are discussed. At follow-up, vestibular symptoms were found to be eliminated or improved in 96 per cent of cases with surgically demonstrated fistulae and in 68 per cent of cases in which no fistula was detected at tympanotomy but hearing improved significantly in only one ear (4 per cent) of the former group and in five ears (20 per cent) of the latter group. 
Does the presence of a measurable blood alcohol level in a potential organ donor affect the outcome of liver transplantation? The widespread application of hepatic transplantation has created a tremendous demand for donor organs. An assessment of donor parameters is thought to be important in selecting good donors; however, the criteria utilized have not been standardized. This study was performed to determine the effect of a measurable donor blood alcohol level on graft survival. Fifty-two patients who underwent orthotopic liver transplantation at the University of Pittsburgh were included in the study. Twenty-five patients received liver grafts from donors having a blood alcohol level between 0.04 and 0.4 g/l with a mean of 0.17 g/l. Twenty-seven patients received a liver graft from a donor who had no measurable blood alcohol. There were no differences between these two groups of donors regarding the time of initial hospitalization until the time of donation. Graft failure within the first 30 days was 24% for those receiving an organ from an alcohol-positive donor as compared with 22.2% in those receiving an organ from an alcohol negative donor. The recipient mortality rate was 16% and 11%, respectively. No relationships between the donor blood alcohol level and organ performance, frequency of primary graft nonfunction, or number of episodes of acute cellular rejection were evident. Based upon these data, the presence of a measurable blood alcohol level in a donor should not mitigate against organ donation. 
A novel approach to analysis of transcriptional regulation in human cells: initial application to melanocytes and melanoma cells. An assay system for transcriptional profile analysis of cultured eukaryotic cells has been developed to simultaneously handle multiple samples in a rapid, sensitive, and internally controlled manner. The methodology incorporates a microtiter plate assay system, a rapid cell-harvest enzyme-assay technique, and the bacterial reporter genes beta-glucuronidase and beta-galactosidase. We demonstrate, using beta-actin and SV40 (late) transcription promoting sequences, that this technically refined microtiter-triton-lysate (MTL) assay methodology can readily differentiate between the transcriptional states of human melanocytes before and after pharmacologic stimulation and malignantly transformed versus normal cell environments. Differences in the transcriptional environments are revealed by the relative expression of transcription element probes. The transcriptional activity ratio of the beta-actin compared to the SV40 late transcription promoting sequences was approximately 1:2 in primary cultured melanocytes, 2:1 in 12-0-tetradecanoyl phorbol-13-acetate (TPA)-treated melanocytes and 1:4 in the Tang melanoma cell line. Because this MTL assay methodology can accommodate a panel of transcription element probes, we anticipate that the resultant transcriptional profiles will prove useful in deciphering the diverse transcriptional changes that occur within normally regulated and malignantly transformed cells. 
Intestinal manifestations of invasive diarrheas and their diagnosis. Data from studies of 916 children with diarrhea, including 122 from whom shigellae were isolated, and data on patients affected in an epidemic due to Shigella dysenteriae type I were analyzed to determine whether a diagnostic clinical profile of shigellosis could be identified. Blood and/or mucus in stool, increased frequency of stool, abdominal pain, rectal tenesmus, and fever were noted more frequently in patients with shigellosis. The diagnostic confirmation of shigellosis depends on the isolation of the organism, but in the clinical situation early initiation of appropriate antibiotic therapy can be based on clinical judgment that utilizes local perceptions regarding dysentery. 
Histopathology and immunohistochemistry of the caecum in children with the Trichuris dysentery syndrome. Caecal biopsy specimens from Jamaican children with the Trichuris dysentery syndrome (TDS) and age matched Jamaican controls were investigated by immunohistochemistry and by light microscopy. Biopsy specimens from all children (with TDS and controls) showed a mild to moderate increase in inflammatory cells. Except in the vicinity of the worm, where the epithelium was flattened, there was no other epithelial abnormality. Compared with controls, children with TDS had increased IgM lamina propria plasma cells and decreased intraepithelial T cells. There was also an increase in crypt epithelial cell proliferation. Lamina propria T cells (both activated and non-activated) were no more common in children with the Trichuris syndrome than controls. Epithelial cell HLA-DR and VLA-1 expression (which are increased in other colitides) were the same in both groups. Despite the presence of large worm burdens and chronic dysentery, therefore, only minor changes were seen in the caecal mucosa of children with TDS. 
Analysis of prognostic factors in men with metastatic prostate cancer. Uro-Oncology Group of Northern Alberta. We determined the influence of the extent of disease on bone scan, serum testosterone, patient age, performance status, method of initial diagnosis, Gleason grade, clinical stage at diagnosis, serum acid phosphatase, serum prostate specific antigen (PSA) and primary hormonal treatment on survival. The clinical and hormonal data were obtained when the presence of metastatic disease was established and treatment was to be initiated in 162 men with metastatic prostate cancer. Mean followup was 16 months (range 1 to 105 months). A total of 70 men (43.2%) died of the metastatic disease during the evaluation period. Log rank analysis revealed that only serum testosterone (p = 0.035) and extent of disease on bone scan (p = 0.003) significantly affected over-all survival. A trend (p = 0.068) towards decreased survival was observed with increasing values of PSA. Increasing values of acid phosphatase positively correlated with extent of disease on bone scan but was not a significant independent prognostic factor. Patient age, performance status, clinical stage, method of initial diagnosis, Gleason grade and type of hormonal treatment did not significantly influence survival. Upon using multivariate Cox analysis, only extent of disease on bone scan was significantly correlated with over-all survival (p less than 0.014). PSA may also be influential but longer duration of followup will be necessary. We conclude that extent of disease on bone scan is the most important prognosticator of the analyzed factors and that serum testosterone may be of value. 
Differential effects of transforming growth factor-beta 1 and phorbol myristate acetate on cardiac fibroblasts. Regulation of fibrillar collagen mRNAs and expression of early transcription factors. Cardiac fibroblasts are responsible for synthesis and deposition of fibrillar collagen types I and III. Transforming growth factor-beta 1 (TGF-beta 1) has been proved to increase collagen biosynthesis in various systems, both in vivo and in vitro. We have investigated the effect of TGF-beta 1 on collagen gene expression in cultured cardiac fibroblasts and have compared this effect with that of a mitogenic agent, phorbol myristate acetate (PMA). The regulation of collagen types I and III gene expression was examined by using cDNA probes to rat alpha 2 (I) and mouse alpha 1 (III) procollagens. Quiescent cultured cardiac fibroblasts from rabbit heart were treated with TGF-beta 1 (10-15 ng/ml) and PMA (200 ng/ml). After 24 hours of treatment with TGF-beta 1, the abundance of mRNA for pro-alpha 2 (I) and pro-alpha 1 (III) collagens was increased by 112% (p less than 0.001) and 97% (p = 0.05), respectively, in treated fibroblasts compared with untreated cells. However, PMA-treated cells showed an opposite response: a 42% (p = 0.01) decrease in mRNA levels for pro-alpha 2 (I) collagen was observed. Immunofluorescent staining of cardiac fibroblasts in culture with anti-type I collagen antibody showed that alterations in mRNA levels led to altered collagen synthesis: cellular collagen was relatively increased in TGF-beta 1-treated cells and significantly diminished in PMA-treated cells. The abundance of mRNA for pro-alpha 1 (III) collagen was not affected by PMA treatment. 
Skeletal muscle degradation and nitrogen wasting in rats with chronic metabolic acidosis. 1. Chronic metabolic acidosis is associated with impaired growth and negative nitrogen balance, suggesting that it promotes endogenous protein catabolism. 2. Skeletal muscle is the major repository of body protein and is a potential target for stimuli of protein catabolism. 3. This study in vivo examines the effects of chronic metabolic acidosis on the relationship between growth, nitrogen disposal and skeletal muscle catabolism in the rat. 4. Growth, nitrogen utilization and acquisition of body mass were significantly impaired in acidotic animals compared with pair-fed controls. 5. Total nitrogen excretion was significantly increased in acidotic rats despite decreased urea production. The time course of this response to acidosis was synchronous with that of accelerated protein catabolism in skeletal muscle. 6. It is proposed that metabolic acidosis impairs growth by stimulating skeletal muscle protein catabolism. It is suggested that this forms part of a co-ordinated multi-organ homoeostatic response to acidosis, skeletal muscle and down-regulated urea production supplying the nitrogen required for renal ammoniagenesis. 
Improvement of outcome for infants of birth weight under 1000 g. The Victorian Infant Collaborative Study Group. The two year outcome of extremely low birth-weight (ELBW) infants (birth weight 500 to 999 g), born in the state of Victoria over two distinct eras, 1979-80 and 1985-7, were compared. In the 1979-80 era, 25.4% of the ELBW infants survived to 2 years of age; only 12.5% of liveborn ELBW infants survived to 2 years with no neurological disabilities. In the 1979-80 era, ELBW infants born outside the level III centres in the state were significantly disadvantaged in both mortality and neurological morbidity. By 1985-7, the two year survival rate of ELBW infants rose significantly from 25.4% to 37.9%. By 1985-7, the proportion of ELBW infants who survived to 2 years free of neurological disabilities increased from 12.5% to 26.2%. Despite the improved survival, the absolute number of 2 year old children survivors with severe neurological disabilities remained constant at 8/year in both eras. By 1985-7, fewer ELBW infants were born outside the level III centres, their survival rate remained lower, but the severe neurological disability rate in survivors was no longer significantly higher. There has been a concomitant improvement in both survival and reduction in neurological morbidity. 
CT, MRI, and autopsy findings in brain of a patient with MELAS. Brain autopsy findings in a 14-year-old patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes were compared with those of computed tomography (CT) and magnetic resonance imaging (MRI). Pathologic examinations revealed extensive laminar necrosis bordered by gliotic tissues throughout the cerebral cortices. Moderate losses of myelin and fibrous gliosis were also observed in the subcortical and deep white matter. These lesions were demonstrated as low-density areas on CT and as high-signal areas on T2-weighted MRI. MRI revealed the lesions more distinctively and precisely than CT. Neither CT nor MRI could reveal abnormalities in the basal ganglia, including vascular proliferation and calcium deposits in the blood vessels. 
Effect of hyaluronic acid on postoperative intraperitoneal adhesion formation and reformation in the rat model. The local application of 0.25% or 0.4% HA before the induction of a measured laser injury on the rat uterine horn was associated with a significant reduction (P less than 0.05) in postoperative IP adhesions when compared with the group of animals pretreated with the diluent vehicle PBS or received no pretreatment. However, 0.4% HA, when applied in a similar manner, was ineffective in reducing reformation of adhesions after microsurgical adhesiolysis. 
Gaucher disease: heterologous expression of two alleles associated with neuronopathic phenotypes. To investigate the molecular basis for the distinct neuronopathic phenotypes of Gaucher disease, acid beta-glucosidases expressed from mutant DNAs in Gaucher disease type 2 (acute) and type 3 (subacute) patients were characterized in fibroblasts and with the baculovirus expression system in insect cells. Expression of the mutant DNA encoding a proline-for-leucine substitution at amino acid 444 (L444P) resulted in a catalytically defective, unstable acid beta-glucosidase in either fibroblasts from L444P/L444P homozygotes or in insect cells. This mutation was found to be homoallelic in subacute neuronopathic (type 3) Gaucher disease. In comparison, expression of the mutant cDNA encoding an arginine-for-proline substitution at amino acid 415 (P415R) resulted in an inactive and unstable protein in insect cells. This allele was found only in a type 2 patient with the L444P/P415R genotype. The substantial variation in the type 3 phenotype (L444P homozygotes) suggests the complex nature of the molecular basis of phenotypic variation in Gaucher disease. Yet, the association of neuronopathic phenotypes with alleles producing severely compromised (L444P) or functionally null (P415R) enzymes indicates that the effective level of residual activity at the lysosome is likely to be a major determinant of the severity of Gaucher disease. 
Human papillomavirus type 16 DNA in ocular and cervical swabs of women with genital tract condylomata. Human papillomavirus type 16 is associated with dysplasias and carcinomas of the conjunctiva and of the uterine cervix. To explore the relationship between cervical and ocular human papillomavirus infection, we examined DNA from bilateral limbal swabs and cervical swabs from 17 women (age range, 17 to 46 years; median, 31.7 years) with biopsy-proven human papillomavirus-related cervical dysplasia who had a normal ocular surface. Using polymerase chain reaction, we identified human papillomavirus 16 DNA in one or both eyes of 13 (76.5%) patients, six (46.2%) of whom had demonstrable human papillomavirus 16 DNA in cervical swabs as well. It thus appears that human papillomavirus 16 is present in the conjunctivae of some patients with human papillomavirus-related genital warts who have no ocular manifestations of infection. Although autoinoculation of conjunctiva may be the source of some ocular human papillomavirus, data suggest that other modes of transmission to the eye also exist. Additional study of the epidemiologic characteristics of ocular human papillomavirus, a widely prevalent virus known to be associated with dysplasias/atypias and cancer, is warranted. 
Deglutition syncope with coexistent carotid sinus hypersensitivity. A 63-year-old man had symptomatic deglutition-induced atrioventricular (A-V) block. There was also a coexistent mixed type carotid sinus hypersensitivity presenting as A-V block. No A-V nodal dysfunction was revealed during electrophysiologic studies. The vasodepressor response to carotid massage implies a central vagal hyperresponsiveness, which can also explain the cardioinhibitory responses to swallowing and carotid sinus massage, both possibly unmasked by posterior myocardial infarction. 
Tracking of elevated blood pressure values in adolescent athletes at 1-year follow-up. Resting blood pressures were measured in 467 adolescents during preparticipation physical examinations for high school sports. Fifty-seven of the athletes (12.2%) had significantly elevated blood pressures. Forty-three (79.6%) of 54 subjects demonstrated significantly and persistently elevated blood pressures at 1-year follow-up. A family history of hypertension was positively associated with elevated blood pressures in 46 (80.7%) of 57 subjects compared with controls (23/410 [5.6%]). Consistent with previous studies, subjects with elevated blood pressures had a greater body weight (94.5 +/- 25.7 kg) compared with normotensive subjects (75.2 +/- 14.0 kg). Subjects with elevated blood pressures engaged in heavy resistance weight training (three times a week or more) more often (41/57 [71.9%]) than normotensive subjects (65/410 [15.8%]). These data support the idea that blood pressures measured during routine preparticipation physical examinations for high school sports are a useful tool in screening for elevated blood pressure in adolescents. 
Seminoma of the testis in a patient with 48,XXYY variant of Klinefelter's syndrome. We believe this is the first reported case of seminoma in a patient with the 48,XXYY variant form of Klinefelter's syndrome. Moreover, the seminoma in this patient occurred in a normally descended testis. We report this case because patients with 48,XXYY Klinefelter's syndrome are often confined to institutions, where the diagnosis of testicular tumor may not be recognized as readily. 
From chimney sweeps to oncogenes: the quest for the causes of cancer. Over the past 200 years, a bewildering array of chemical, physical, and viral agents has been identified that can cause cancer, but the mechanisms involved are only now becoming clear. In the leukemias and lymphomas, it appears that the activation of cellular oncogenes is important. The genes involved are present in all normal cells and are often associated with cell growth and regulation. When activated, they act in a dominant fashion to cause a cell to express the malignant phenotype. There is increasing evidence that in solid tumors, a more important mechanism may be the loss of a suppressor gene. The classic example is retinoblastoma, in which the retinoblastoma gene has been cloned and is also found to be associated with several other common cancers including sarcomas and small cell lung cancer. It is likely to be one of a family of such genes. It may well be that the activation of one or more oncogenes or the loss of one or more suppressor genes, or both, is required for a tumor to progress from initiation through promotion to a metastasizing malignancy. 
Influence of changes in arterial carbon dioxide tension on the electroencephalogram and posterior tibial nerve somatosensory cortical evoked potentials during alfentanil/nitrous oxide anesthesia. The effects of variation of arterial CO2 tension (PaCO2) on the electroencephalogram (EEG) and posterior tibial nerve somatosensory cortical evoked potentials (PTN-SCEP) during opioid/N2O anesthesia have not been well documented. We studied the effects of hypocapnia (PaCO2 approximately 23 mmHg) and hypercapnia (PaCO2 approximately 50 mmHg) during steady-state alfentanil/N2O anesthesia in 16 patients. EEG and PTN-SCEP were recorded continuously, while PaCO2 was altered in 15-min intervals by varying the inspired CO2 concentration. Hypocapnia caused significant increases in power in the delta, theta, and beta bands (P less than 0.01), with the greatest increase observed in the alpha band. Relative power increased in the alpha band but remained unchanged in the delta, theta, and beta bands. Median frequency and 95% spectral edge frequency were unaltered during hypocapnia. In contrast, hypercapnia caused a significant decrease of power in the alpha and beta bands, whereas delta and theta power remained unchanged. This was reflected in a significant decrease of the 95% spectral edge frequency, from 8.9 (6.7-11.6) to 7.0 (5.6-8.6) Hz. All EEG parameters returned to normal upon restoration of normocapnia. There was a significant negative correlation between power in the alpha band and end-tidal CO2 in all patients (r = 0.47 to -0.89). PTN-SCEP latencies and amplitudes were not significantly different from control values during hypocapnia and hypercapnia. It is concluded that variations in PaCO2 within the limits 20-50 mmHg produce substantial changes in the EEG power spectrum, especially in the alpha band (8-12 Hz), but do not alter PTN-SCEP. 
Gastric antral vascular ectasia: a problem of recognition and diagnosis. Gastric antral vascular ectasia ('water melon stomach') is a poorly documented cause of occult upper gastrointestinal blood loss. We describe a case which emphasises the clinical and pathological difficulties that can be encountered in making this elusive diagnosis. 
A historic case of visual agnosia revisited after 40 years. In one of the seminal works on visual agnosia, Adler (1944, 1950) presented the case of a 22-yr-old woman who sustained carbon monoxide cerebral toxicity in the Cocoanut Grove nightclub diaster of 1942. We located this patient 40 yrs after injury and performed a detailed reevaluation. The patient demonstrated persistent deficits in visual recognition, characterized most prominently by defective recognition of elemental shape and form, associated with alexia, prosopagnosia, visuospatial disorientation and impaired visual imagery. Visual acuity, colour recognition, writing ability and verbal intelligence were relatively preserved. Isolated bilateral occipital injury was demonstrated by CT and MRI scanning. On comparison with previously reported cases, our results support the hypothesis that carbon monoxide toxicity can induce a visual agnosia of the apperceptive type with well defined characteristics, seldom seen with other types of cerebral injury. Prognosis for long-term recovery is poor. 
Clinical implications of combined hypogastric and profunda femoral artery occlusion. From 1983 to 1990, nine patients with combined hypogastric (HA) and profunda femoral arterial (PFA) occlusive disease presented with five nonhealing hip disarticulations, three nonhealing above-the-knee amputations, perineal necrosis in six patients, buttock necrosis in four patients, visceral ischemia in two patients, and lumbosacral spinal ischemia in one patient. Obviously some patients had more than one regional complication. Five patients died from complications of HA/PFA ischemia. Survivors included two patients who required a hemipelvectomy, one patient who required an axillary-to-hypogastric artery bypass graft for stump salvage, and one patient who survived despite lumbosacral paralysis and complete cystectomy. The 56% mortality and 100% morbidity emphasize the critical significance of combined hypogastric/profunda femoral artery circulatory compromise. Efforts should be made to preserve or re-establish the HA and/or PFA circulation whenever possible. A hemipelvectomy may be required to allow the wounds to finally heal. Furthermore, the certainty of an above-the-knee amputation healing is not present in these patients; therefore, a hemodynamic assessment of the healing potential of an above-the-knee amputation is required. 
Atrial fibrillation associated with autonomic dysreflexia in patients with tetraplegia. Atrial fibrillation is an arrhythmia characterized by disorganized atrial depolarizations and an irregular ventricular response. Most patients with atrial fibrillation have underlying cardiac pathology. This paper presents the cases of three patients with high-level spinal cord injury and symptoms of autonomic dysreflexia who developed atrial fibrillation without any cardiac or metabolic disease that would predispose them to this. The paper proposes that autonomic dysreflexia might predispose a patient to atrial fibrillation by altering the pattern of repolarization of the atria, making the heart susceptible to a reentrant type of arrhythmia. High-level spinal cord injured patients may be at increased risk for the development of atrial fibrillation, an arrhythmia which, if left untreated, can increase the incidence of an embolic cerebrovascular accident that could further impair the patient's functional status. 
Duration of ST segment depression after exercise-induced myocardial ischemia is influenced by body position during recovery but not by type of exercise. To assess whether the duration of ischemic ST segment depression after exercise can be modified by changes in body position during recovery or with different types of exercise, 18 patients with chronic stable angina, positive exercise test results, and documented coronary artery disease were prospectively studied. Every patient underwent testing with three different exercise protocols: (1) Bruce (Bruce-standing recovery), (2) abrupt onset of exercise (abrupt), and (3) modified Bruce protocol preceded by a 10-minute warm-up period (warm-up). After exercise test patients recovered in a sitting position. In addition, all patients performed a fourth exercise (Bruce protocol), but this time they recovered in the supine position (Bruce-supine recovery). Time and heart rate-blood pressure product at 1 mm ST segment depression were similar for Bruce-standing recovery, abrupt, and Bruce-supine recovery protocols (5.1 +/- 2, 4.4 +/- 2, and 5.2 +/- 2 minutes and 20.8 +/- 4, 21.3 +/- 4, and 20.4 +/- 4 beats/min x mm Hg x 10(-3), respectively. Heart rate and heart rate-blood pressure product at peak exercise did not differ in Bruce-standing recovery, abrupt, and Bruce-supine recovery. Maximal ST segment depression was -2.0, -1.9, and -2.0 mm with Bruce-standing recovery, abrupt, and Bruce-supine recovery exercise, respectively, and -1.5 mm with warm-up exercise (p less than 0.05). Duration of ST segment depression into recovery was significantly prolonged after Bruce-supine recovery exercise (9.4 + 5 minutes) compared with Bruce-standing recovery, abrupt, and warm-up protocols (6.8 + 3, 5.9 + 4, and 5.0 + 3 minutes, respectively; p less than 0.05). 
Treatment of experimental suprachoroidal hemorrhage with subconjunctival injection of tissue plasminogen activator: a negative report. Suprachoroidal hemorrhage was created in 10 albino rabbit eyes. Five eyes were treated with subconjunctival injections of 40,000 IU of tissue plasminogen activator (tPA) daily for 6 days; five eyes served as controls. It took approximately the same amount of time for the suprachoroidal hemorrhages to clear in both the control and treatment eyes. We conclude that subconjunctival injection of tPA does not accelerate the clearance of suprachoroidal hemorrhage. 
A phase I study of high-dose ifosfamide and escalating doses of carboplatin with autologous bone marrow support. The dose-limiting toxicity in two separate phase I trials of the high-dose single agents ifosfamide and carboplatin was renal insufficiency at 18 g/m2 and hepatic and ototoxicity at 2,400 mg/m2, respectively. In this phase I study, 16 adults were treated with ifosfamide at 75% of the single-agent maximum-tolerated dose (MTD) (12 g/m2) and escalating doses of carboplatin (400 to 1,600 mg/m2) to determine the nonhematologic dose-limiting toxicity and the maximum-tolerated dose of the combination. Both drugs as well as mesna for uroprotection were given by continuous infusion over 4 days with an additional day of mesna (total dose per course, 15 g/m2). Autologous bone marrow support was stipulated for subsequent dose levels once granulocytes remained less than 500/microL for more than 14 days in two of three to five patients entered at a given dose level. Autologous bone marrow support was used at doses above the 400 mg/m2 carboplatin dose level. At the maximum-tolerated dose level of 1,600 mg/m2 of carboplatin, renal toxicity precluded further dose escalation. Of the five patients entered at this dose level, reversible creatinine elevation greater than 2 mg/dL (median peak, 2.6 mg/dL) was observed in three patients, and irreversible renal failure occurred in an additional patient (peak creatinine, 6.9 mg/dL. Transient gross hematuria appeared more common with the combination than with ifosfamide alone. Two patients developed severe somnolence and confusion associated with a rising creatinine. There were two complete (CRs) and four partial responses (PRs) in 14 heavily pretreated assessable patients (including four partial or complete responses in eight assessable patients with advanced refractory sarcoma, and one CR in two patients with germ cell carcinoma). Carboplatin and ifosfamide appear to have overlapping renal toxicity. Nevertheless, carboplatin and ifosfamide can be combined at 80% and 75% of the single-agent maximum-tolerated doses, respectively, with acceptable nonhematologic toxicity. Ifosfamide and carboplatin are an attractive core combination for further studies in the treatment of sarcoma, germ cell, ovarian, and lung carcinomas. 
New concepts in treatment of chronic persistent asthma. Using a stepwise protocol to control inflammation. Asthma continues to cause unacceptably high rates of disability and death, largely because the severity of disease is underestimated and patients are inadequately educated about their disease. When patients understand what happens during an asthma attack and its aftermath, they are more likely to notice important symptoms and to start or increase self-treatment appropriately. Physicians are responsible for teaching patients how to avoid precipitating factors and for discussing and writing down a self-treatment plan to follow in specific circumstances. The British Thoracic Society has suggested a stepwise protocol for drug treatment of asthma. Each patient must be evaluated individually and started at the appropriate step. 
Allogeneic bone marrow transplantation as therapy for primary induction failure for patients with acute leukemia. The survival of patients with acute leukemia who do not achieve a remission with primary therapy is very poor. High-dose chemoradiotherapy followed by allogeneic bone marrow transplantation (BMT) has been shown to be effective therapy for patients with acute and chronic leukemia. Therefore, we determined the long-term disease-free survival of patients who did not achieve a remission and were then treated with high-dose therapy and bone marrow allografting from matched sibling donors. Twenty-one patients (median age, 28 years) who did not achieve a remission with induction chemotherapy were subsequently treated with allogeneic BMT. After BMT, 90% achieved a complete remission. Six died of complications of the therapy, and six patients relapsed between 27 and 448 days after BMT. Nine patients (43%; median age, 25 years) are alive between 556 and 4,174 days after BMT. The cumulative probability of disease-free survival at 10 years is 43%. This study suggests that allogeneic BMT can be an effective therapy to achieve long-term control of acute leukemia, even in those patients who do not achieve a remission with primary therapy. 
Does tremor pace repetitive voluntary motor behavior in Parkinson's disease? In patients with Parkinson's disease and in normal subjects, the influence of tremor on repetitive voluntary movement was investigated in the index finger by comparing frequency of isometric force tremor with frequency of voluntary alternating isometric contractions. Tremor frequency, measured over the range from 0 to 70% maximum voluntary force, usually increased with force. The tremor frequency band was lower and more often overlapped with the upper voluntary frequency range in patients than in normal subjects. Normal subjects could accurately produce voluntary contractions at all cue frequencies from 1 to 5 Hz. Patients could produce auditory-paced frequencies of 1 and 2 Hz, but at higher cue frequencies, their voluntary contractions were often faster or slower than the cue. The faster or "hastened" voluntary frequencies were within the tremor frequency band, whereas the slowed voluntary frequencies were below it. Maximal voluntary frequency was often greater than the lowest but always less than the highest tremor frequency. It is concluded that parkinsonian tremor may pace voluntary repetitive movements to go faster than intended with the highest tremor frequency being an upper limit for voluntary frequency. Similar mechanisms may underlie the hastened repetitive vocal responses that were also observed in the parkinsonian patients. 
Nonhealing leg ulcers: a manifestation of basal cell carcinoma. Seven patients with basal cell carcinomas presenting as nonhealing ulcers are reported. The importance of considering malignancy and taking biopsy specimens of leg ulcers that fail to respond to treatment is emphasized. 
Potassium depletion exacerbates essential hypertension. OBJECTIVE: To determine the effect of potassium depletion on blood pressure in patients with essential hypertension. DESIGN: Double-blind, randomized, crossover study, with each patient serving as his or her own control. SETTING: Clinical research center at a university hospital. PATIENTS: Twelve patients with hypertension. INTERVENTIONS: Patients were placed on 10-day isocaloric diets providing a daily potassium intake of either 16 mmol or 96 mmol. The intake of sodium (120 mmol/d) and other minerals was kept constant. On day 11 each patient received a 2-litre isotonic saline infusion over 4 hours. MEASUREMENTS: Blood pressure; urinary excretion rates for sodium, potassium, calcium, and phosphorous; glomerular filtration rate; renal plasma flow; and plasma levels of vasoactive hormones. MAIN RESULTS: With low potassium intake, systolic blood pressure increased (P = 0.01) by 7 mm Hg (95% CI, 3 mm Hg to 11 mm Hg) and diastolic pressure increased (P = 0.04) by 6 mm Hg (CI, 1 mm Hg to 11 mm Hg), whereas plasma potassium concentration decreased (P less than 0.001) by 0.8 mmol/L (CI, 0.4 to 1.0 mmol/L). In response to a 2-litre isotonic saline infusion, the mean arterial pressure increased similarly on both diets but reached higher levels on low potassium intake (115 +/- 2 mm Hg compared with 109 +/- 2 mm Hg, P = 0.03). Potassium depletion was associated with a decrease in sodium excretion (83 +/- 6 mmol/d compared with 110 +/- 5 mmol/d, P less than 0.001). Plasma renin activity and plasma aldosterone concentrations also decreased in patients during low potassium intake, but concentrations of arginine vasopressin and atrial natriuretic peptide, glomerular filtration rate, and renal plasma flow were unchanged. Further, low potassium intake increased urinary excretion of calcium and phosphorus and of plasma immunoreactive parathyroid hormone levels. CONCLUSION: Dietary potassium restriction increases blood pressure in patients with essential hypertension. Both sodium retention and calcium depletion may contribute to the increase in blood pressure during potassium depletion. 
Effect of inspiratory muscle fatigue on breathing pattern during inspiratory resistive loading. The purpose of this study was to determine whether induction of either inspiratory muscle fatigue (expt 1) or diaphragmatic fatigue (expt 2) would alter the breathing pattern response to large inspiratory resistive loads. In particular, we wondered whether induction of fatigue would result in rapid shallow breathing during inspiratory resistive loading. The breathing pattern during inspiratory resistive loading was measured for 5 min in the absence of fatigue (control) and immediately after induction of either inspiratory muscle fatigue or diaphragmatic fatigue. Data were separately analyzed for the 1st and 5th min of resistive loading to distinguish between immediate and sustained effects. Fatigue was achieved by having the subjects breathe against an inspiratory threshold load while generating a predetermined fraction of either the maximal mouth pressure or maximal transdiaphragmatic pressure until they could no longer reach the target pressure. Compared with control, there were no significant alterations in breathing pattern after induction of fatigue during either the 1st or 5th min of resistive loading, regardless of whether fatigue was induced in the majority of the inspiratory muscles or just in the diaphragm. We conclude that the development of inspiratory muscle fatigue does not alter the breathing pattern response to large inspiratory resistive loads. 
Benign and malignant tumors in patients with acromegaly. Growth hormone and its principal mediator insulinlike growth factor I are known promoters of normal growth. To determine whether excessive secretion of growth hormone is associated with an increased occurrence of benign and of malignant tumors, we studied records of 87 patients with acromegaly seen in the Lahey Clinic Medical Center (Burlington, Mass) from 1957 to 1988 and compared the rate of tumor occurrence with a control group of patients with pituitary tumors (198) and with findings from a cancer registry. Patients with acromegaly had a 2.45-fold increased rate of malignant tumors (95% confidence interval, 0.98 to 5.04) compared with findings from the tumor registry. Female patients had a higher rate than male patients. The rate of carcinoma of the thyroid was excessive and previously underscribed, but the rate of carcinoma of the colon was not increased as reported by others. Among benign lesions, goiters, predominantly nodular, were seen in 25% of patients in addition to a large number of mesenchymal lesions. 
Superior vena caval obstruction in patients with gut failure receiving home parenteral nutrition. Clinical suspicion and venographic conformation were used to diagnose 15 cases of superior vena caval obstruction (SVCO) in 107 home parenteral nutrition (HPN) patients over 379 cumulative years of HPN (3.9 cases/100 patient-years). Patients with SVCO had been on HPN a mean of 51.5 months and had used 6.2 (range 1-50) central catheters, including short- and long-term, before SVCO was diagnosed. The frequency of inflammatory bowel disease (IBD) with SVCO was approximately the same as that in our general HPN population. Positive blood cultures were present immediately preceding the diagnosis of SVCO in 40% (six of 15) of cases. Atypical line placements were noted in two cases. The most common management strategies employed were conversion to enteral feedings in five patients and placement of a new catheter directly into the right atrium by thoracotomy in another five patients. Two of the five with right atrial catheters experienced a postpericardiotomy syndrome (fever, pericardial rub, and pulmonary infiltrates) that responded promptly to indomethacin. The most significant long-term sequela of SVCO was the need for a left jugular vein to right atrial appendage bypass in one patient with chronic venous congestion from her SVCO. Once the SVCO is confirmed, systemic heparinization provides immediate antithrombotic effect and minimizes the risk of pulmonary embolism. The use of streptokinase may result in rapid thrombolysis. 
Differential diagnosis of cystic neoplasms of the pancreas by fine-needle aspiration. Fine-needle aspiration biopsy of pancreatic lesions is becoming widespread. Pathologists need to be familiar with the cytologic features of pancreatic tumors, of which cystic neoplasms are a distinct subset. Of our 31 pancreatic aspirates diagnostic of neoplasia, six were diagnosed as cystic by radiographic imaging. These cases were compared. Similar symptoms were experienced by all of these patients, although those with malignant tumors lost the most weight. Loss of border definition, ascites, and liver metastases were the only radiologic clues to malignancy. Each entity had distinguishing cytologic features. These cases illustrate the importance of knowing the clinical, radiologic, and cytologic features of pancreatic cystic neoplasms to arrive at a preoperative diagnosis and determine proper treatment. 
Pulmonary dysfunction in advanced liver disease: frequent occurrence of an abnormal diffusing capacity. PURPOSE: Abnormalities in pulmonary function have been reported in association with chronic liver disease of varied etiology. The aim of this study was to better define the frequency and nature of these abnormalities in patients who were being evaluated for liver transplantation. PATIENTS AND METHODS: We performed a battery of pulmonary function tests and chest radiographs in 116 consecutive patients (50 men, 66 women; aged 19 to 70 years, mean 44.6 years) with severe advanced liver disease who were hospitalized specifically for evaluation for possible orthotopic liver transplantation and were able to perform technically satisfactory tests. In 17 patients, quantitative whole-body technetium-99m macroaggregated albumin perfusion scanning was also performed for assessment of possible right-to-left shunting through intrapulmonary vascular dilatations. RESULTS: The most commonly affected test of lung function was the single-breath diffusing capacity for carbon monoxide (DLCO), which was abnormal in 48%, 45%, and 71% of patients who never smoked, former smokers, and current smokers, respectively. Ventilatory restriction was noted in 25% of all patients, airflow obstruction (reduced ratio of forced expiratory volume in 1 second to forced vital expiratory volume in 1 second to forced vital capacity) in only 3%, and a widened alveolar-arterial oxygen gradient in 45%. Diffusion impairment was accompanied by a restrictive defect in only 35% of the patients and by an abnormally widened alveolar-arterial oxygen gradient in 60%. When diffusion impairment was accompanied by an oxygenation defect, it was also associated with a significantly increased right-to-left shunt fraction (mean 24.9%) assessed from quantitative whole-body perfusion imaging. On the other hand, isolated diffusion impairment unaccompanied by significant hypoxemia (noted in approximately a third of the patients with a reduced DLCO) was not associated with evidence of significant intrapulmonary shunting (mean right-to-left shunt fraction 6.7%). CONCLUSIONS: Most patients with advanced liver disease have one or more types of abnormality in lung function, a reduced DLCO being the single most common functional defect. Mechanisms accounting for the abnormality in gas transfer may include intrapulmonary vascular dilatations, diffuse interstitial lung disease, pulmonary vaso-occlusive disease, and/or ventilation-perfusion imbalance. 
Migraine headaches. Once the definitive diagnosis of migraine has been formulated, the physician has many options available for abortive and prophylactic therapy. Nonpharmacologic modalities, including behavioral modification methods such as biofeedback training, may also be considered. Migraine does not necessarily have to disrupt the lives of those afflicted. The patient with mixed headache presents a more difficult diagnostic and therapeutic problem. These patients can also be helped when the disorder is identified, and inpatient therapy for these patients may be required. 
Successful treatment of hepatosplenic candidiasis with a liposomal amphotericin B preparation. The case of a granulocytopenic patient with acute undifferentiated leukaemia and hepatosplenic candidiasis who was refractory to conventional deoxycholate amphotericin B (AmpB) and 5-flucytosine therapy is reported. He experienced severe AmpB-related side-effects, and was subsequently successfully treated with a pharmaceutical preparation of AmpB (5.7 g) entrapped in sonicated liposomes, composed of lecithin, cholesterol and stearylamine in a molar ratio of 4:3:1. Three months later, during maintenance chemotherapy, liposomal AmpB (5.1 g) was reinstituted due to the finding of biopsies positive for Candida albicans at bronchoscopy. After healing of the patient's fungal infection a left upper lobe resection was performed, which showed advanced fibrosis with signs of inflammation, but no evidence of fungal disease. Since no acute side-effects and only moderate hypokalaemia were observed, it appears that liposomal AmpB is superior to conventional AmpB treatment in granulocytopenic patients with hepatosplenic candidiasis and unbearable therapy-related side-effects. 
Incidence of heterotopic ossification after total hip replacement: effect of the type of fixation of the femoral component. The incidence and severity of heterotopic ossification after sixty-five consecutive primary uncemented total hip replacements were compared with those after seventy consecutive primary hybrid total hip replacements (consisting of an uncemented acetabular component and a cemented femoral component). All patients had had the arthroplasty because of osteoarthrosis. The sex distribution, prevalence of bilateral disease of the hip, and frequency of previous operations were similar in both groups. All of the operations were performed by one surgeon who used the same operative approach. Preoperative, immediate postoperative, and six-month follow-up radiographs were reviewed for all patients. For 90 per cent of the hips, radiographs that were made after a minimum follow-up of one year were also reviewed. In the group of patients who had an uncemented femoral component, there was a statistically significant increase in the frequency of heterotopic bone and in its severity. Either none or only class-I ectopic bone developed in 74 per cent of the hips in the hybrid group, compared with 40 per cent of the hips in the uncemented group (p less than 0.005). In contrast, class-III or IV heterotopic ossification was evident in 13 per cent of the hips in the uncemented group (p less than 0.005). None of the patients in the hybrid group needed reoperation for excision of ectopic bone, but four (6 per cent) of the patients in the uncemented group needed such a reoperation because of severe limitation of motion. 
Transduodenal exploration of the common bile duct in patients with nondilated ducts. Exploration of the small common bile duct can be technically difficult and is associated with a significant risk of ductal injury or late stricture, or both. Transduodenal common duct exploration after sphincteroplasty (TCDE/S) is an alternative method of duct exploration that avoids choledochotomy. Cholecystectomy followed by TCDE/S was performed upon 28 patients with nondilated ducts and suspected choledocholithiasis. Common duct stones were retrieved in 17 patients. Failure to retrieve stones in the remaining 11 patients was attributed to either false-positive results of cholangiography, forceful passage of stones into the duodenum during the initial insertion of a Fogarty catheter through the cystic duct or a false-negative finding at duct exploration. There was no perioperative mortality. Two patients had asymptomatic postoperative hyperamylasemia. One patient had postoperative pancreatitis, hyperbilirubinemia and cholangitis that resolved with antibiotic therapy by the eighth postoperative day. Other complications included wound infection, delayed gastric emptying, pneumonia and otitis media. The over-all morbidity rate was 28.6 per cent. Long term follow-up was obtained in all 28 patients. All patients in the follow-up group are free of recurrent biliary tract disease. TCDE/S appears to be a safe and effective method of exploring the nondilated common bile duct. 
Measurements of regional cerebral blood flow and blood flow velocity in experimental intracranial hypertension: infusion via the cisterna magna in rabbits. Cerebral blood flow velocity, as measured in the intracranial segment of the internal carotid artery by transcranial Doppler sonography via the transorbital route, and regional cerebral blood flow and volume in corresponding cortical areas, as measured by the hydrogen clearance technique, were recorded for eight New Zealand White rabbits subjected to infusion via the cisterna magna to elevate intracranial pressure. In the lower range of autoregulation, that is, at perfusion pressures between 80 and 40 mm Hg and even lower, the changes in cerebral blood flow velocity and cerebral blood flow showed a strong correlation (0.86) under conditions of standard pCO2 (PaCO2 = 35 +/- 2 mm Hg). Autoregulation was exhausted at 40 mm Hg, and the cerebrovascular resistance was minimal. Below this perfusion pressure, the cerebral blood flow and volume dropped sharply, whereas the cerebrovascular resistance gradually increased, indicating that, despite the maximally dilated resistance vessels, intracranial hypertension causes vascular resistance to increase, possibly via blocking of the venous outflow. Our results confirmed that noninvasive and easily (even at bedside) applicable measurements of changes in cerebral blood flow velocity could be a substitute for the cumbersome and expensive isotope measurements of cerebral blood flow in patients with intracranial hypertension. 
Endoscopic surgery of the vidian nerve. Preliminary report. The anatomy, surgical technique, and difficulties of endoscopic vidian neurectomy are described. The procedure was carried out on 12 patients: 8 had resistant secretomotor rhinopathy and 4 had recurrent nasal polyposis. This technique is a minor surgical procedure with symptomatic relief and minimal postoperative morbidity. 
Implications for research and policy in the treatment of hypertension. Medical considerations. Hypertension, or high blood pressure, is a disease and a risk factor. Cardiovascular risk is directly proportional to the level of blood pressure. Current therapeutic approaches include the classical medical model of detection, evaluation, and drug treatment of high-risk patients who have elevated blood pressure and also a less-well-studied population approach that seeks to manipulate environmental variables in large groups of subjects to reduce blood pressure and subsequent cardiovascular risk. Future research should center on more precise delineation of cardiovascular risk, evaluation of alternative environmental manipulations to reduce blood pressure, enhanced understanding of the pathophysiological mechanisms of hypertension, better matching of antihypertensive drug therapy to pathophysiology, development of new drugs that not only lower blood pressure but also provide additional benefits with minimal side effects, and finally, investigations to further our understanding of the behavioral aspects of the physician-patient encounter, as well as studies on compliance and other issues that influence therapeutic outcome. 
A randomized trial to evaluate the risk of gastrointestinal disease due to consumption of drinking water meeting current microbiological standards. BACKGROUND: This project directly and empirically measured the level of gastrointestinal (GI) illness related to the consumption of tapwater prepared from sewage-contaminated surface waters and meeting current water quality criteria. METHODS: A randomized intervention trial was carried out; 299 eligible households were supplied with domestic water filters (reverse-osmosis) that eliminate microbial and chemical contaminants from their water, and 307 households were left with their usual tapwater without a filter. The GI symptomatology was evaluated by means of a family health diary maintained prospectively by all study families over a 15-month period. RESULTS: The estimated annual incidence of GI illness was 0.76 among tapwater drinkers compared with 0.50 among filtered water drinkers (p less than 0.01). These findings were consistently observed in all population subgroups. CONCLUSION: It is estimated that 35% of the reported GI illnesses among the tapwater drinkers were water-related and preventable. Our results raise questions about the adequacy of current standards of drinking water quality to prevent water-borne endemic gastrointestinal illness. 
Non-Hodgkin's lymphoma presenting as a primary tumor of the liver: presentation, diagnosis and outcome in eight patients. We report the diagnostic, prognostic and therapeutic features of non-Hodgkin's lymphoma in eight patients in whom the disease was seen as a primary tumor of the liver. This series illustrates the variety of situations in which lymphoma might be diagnosed: (a) abdominal pain and hepatomegaly (three cases), (b) incidental finding at evaluation of a patient with cirrhosis (two cases), (c) secondary neoplasm after treatment for Hodgkin's disease (one case) and (d) complication of AIDS (two cases). In most cases, clinical and/or radiological features were nonspecific. However, the combination of the following features must be considered as suggestive: occurrence of an apparently primary hepatic tumor in an immunocompromised patient, absence of the usual serum tumor markers and increased serum lactic dehydrogenase activity. The final diagnosis was based on histological examination of specimens obtained by ultrasonically guided liver biopsies or at surgery. All cases belonged to unfavorable histological subtypes. Immunohistochemical findings on paraffin-embedded sections demonstrated the B-lymphocyte lineage of the seven tumors available for study. In the three patients without coexisting disease, complete remission was obtained by surgery alone or combined with chemotherapy. In the two patients with coexisting cirrhosis, outcome was rapidly unfavorable, with death occurring less than 3 mo after diagnosis. Among the three immunocompromised patients, two experienced a rapid unfavorable outcome, and the remaining one was in complete remission after surgery and chemotherapy. In conclusion, primary non-Hodgkin's lymphoma of the liver arising in patients without coexisting disease has a slow progression and might be successfully treated by surgery. 
The epidemiologic importance of dysentery in communities. This paper explores the epidemiologic importance of dysentery with use of several community studies that demonstrate its prevalence and incidence as well as its association with pathogens, nutritional status, persistent diarrhea, and death. Results of these studies showed that while watery diarrhea was most prevalent in children aged 6-11 months, the prevalence of dysentery peaked between 18 and 23 months of age. Severely stunted children were found to have significantly prolonged episodes of dysentery. Shigella and persistent diarrhea were more frequent in children with dysentery than in those with nonbloody diarrhea. A striking feature was that watery diarrhea, dysentery, persistent diarrhea, and malnutrition each account for less than 5% of all deaths among children aged less than 5 years. However, persistent diarrhea in association with malnutrition causes 13% of deaths in children aged 0-4 years and 27% of deaths in those aged 1-4 years. These data suggest that a more balanced strategy for diarrheal control is required simply because most diarrheal deaths occur among malnourished children with prolonged diarrhea, which is mainly due to dysentery. Results of the studies also suggest that methods to control dysentery in the community should focus on improved hygiene and antimicrobial treatment with use of appropriate algorithms. Recognition of the synergism between dysentery and persistent diarrhea accompanied by malnutrition is crucial in formulating effective programs for control of diarrhea. 
Embolic abscesses in hereditary hemorrhagic telangiectasia. Hereditary hemorrhagic telangiectasia is an inherited disorder in which patients may have multiple telangiectases and arteriovenous fistulas in the skin and internal organs. Patients can suffer from a variety of serious clinical complications, including abscess formation. We report two patients in whom neurologic symptoms developed from embolic abscesses, one for whom this complication was fatal. The reported incidence and microbiologic features of this complication are similar to that of endocarditis in patients with valvular heart disease. We believe that patients with hereditary hemorrhagic telangiectasia should receive similar antibacterial prophylaxis for procedures placing them at risk for bacteremia. 
Cutaneous T-cell lymphoma in patients with human immunodeficiency virus infection The development of cutaneous T-cell lymphoma is unusual in individuals with human immunodeficiency virus type 1 infection. We present four patients with cutaneous T-cell lymphoma and human immunodeficiency virus type 1 infection. Immunophenotyping of lymph node tissue in three of these patients revealed a predominance of T-suppressor cells. Possible causes for the development of cutaneous T-cell lymphoma in the presence of human immunodeficiency virus type 1 infection are discussed. 
Splenic abscesses due to Mycobacterium tuberculosis in patients with AIDS. Among 60 patients with AIDS seen at our institution, two had splenic abscesses due to Mycobacterium tuberculosis without pulmonary tuberculosis. In both cases splenic abscess was the first manifestation of AIDS; the patients had prolonged fever and had lost weight and experienced malaise; slight hepatomegaly was noted in both instances and peripheral lymphadenopathy in one. Chest radiography gave normal results in one case and showed hilar lymphadenopathy in the other. Ultrasonographic findings were characteristic: homogeneous hepatomegaly and splenomegaly, with multiple filling defects of variable size. Diagnosis required splenectomy in one case and biopsy of cervical lymph nodes in the other. In both cases Ziehl-Neelsen staining gave positive results; M. tuberculosis grew from a culture of splenic tissue of one patient and from a culture of lymph nodal tissue of the other. There was a rapid response to antituberculous therapy. Splenic tuberculosis seems to be a distinct extrapulmonary entity in patients with AIDS. Ultrasonographic images are useful for diagnosis and follow-up. 
The clinical spectrum of hypocalcaemia associated with bone metastases. Malignancy-related hypocalcaemia has received less attention in the literature than the opposite perturbation, hypercalcaemia. Only, scarce and contradictory data exist about hypocalcaemia associated with bone metastases (BMH). We have reviewed the clinical records of 155 patients with bone metastases of solid tumours, 122 of which were followed during the whole course of the disease until death. The frequency of hypocalcaemia ranged from 5 to 13%, depending on the formula used to correct calcium values for protein concentration. BMH was almost exclusively limited to patients with osteoblastic metastases. The frequency of BMH among patients with prostate carcinoma was 13-27%, depending on the formula used. Only two of 60 patients with lytic bone lesions presented hypocalcaemia, and in both cases it was rather mild. The development of hypocalcaemia did not seem to imply a worse prognosis, at least in patients with carcinoma of the prostate. Thus, the prevalence of BMH appears to be higher than is usually considered. Adequate attention should be given to this disorder because of the potentially deleterious effects on several organ systems. 
Thalassaemia trait and myocardial infarction: low infarction incidence in male subjects confirmed. A total of 4401 subjects admitted to the Medical Division of St Camillo Hospital in Comacchio (Ferrara, Italy) over a period of 7 years were prospectively evaluated in order to determine whether the heterozygous beta-thalassaemic (HBT) could be considered as a protective factor against the occurrence of acute myocardial infarction (AMI). Of the total patient sample, 3954 subjects were non beta-thalasaemics (NBTs), and 447 subjects were heterozygous beta-thalassaemics (HBTs). AMI was diagnosed in 384 patients, of whom 17 individuals were HBTs and 367 subjects were NBTs. The prevalence of HBTs in this group was significantly lower than expected (4.43%, P less than 0.0001). Furthermore, an analysis by sex showed that this lower prevalence could be attributed to male patients. Moreover, only in male subjects was a significant negative correlation observed between AMI and HBT. The mean age at which AMI occurred in male HBTs was significantly higher than in male NBTs (72 +/- 2.69 vs. 63 +/- 0.7 years, P less than 0.05), while no differences were found in the mean age at which AMI occurred between HBT and NBT female subjects. This study demonstrates that the thalassaemic trait may afford some protection against the occurrence of AMI in men. 
Regional cerebral blood flow following resuscitation from hemorrhagic shock with hypertonic saline. Influence of a subdural mass. After severe hemorrhage, hypertonic saline restores systemic hemodynamics and decreases intracranial pressure (ICP), but its effects on regional cerebral blood flow (rCBF) when used for resuscitation of experimental animals with combined shock and intracranial hypertension have not been reported. We compared rCBF changes (by radiolabeled microsphere technique) after resuscitation from hemorrhage with either 0.8 or 7.2% saline in animals with and without a right hemispheric subdural mass. We studied 24 mongrel dogs anesthetized with 0.5% halothane and 60% nitrous oxide. In group 1 (n = 12), hemorrhage reduced mean arterial pressure (MAP) to 45 mmHg for 30 min. In group 2 (n = 12), ICP was increased and maintained constant at 15 mmHg, whereas hemorrhage reduced MAP to 55 mmHg for 30 min (cerebral perfusion pressure [CPP] approximately 40 mmHg in each group). After the 30-min shock period, 6 animals in each group received one of two randomly assigned resuscitation fluids over a 5-min interval: 1) 7.2% hypertonic saline (HS; sodium 1,232 mEq.l-1, volume 6.0 ml.kg-1); or 2) 0.8% isotonic saline (SAL; sodium 137 mEq.l-1, volume 54 ml.kg-1). Once fluid resuscitation began, ICP was permitted to vary independently in both groups. Data were collected at baseline (before subdural balloon inflation in group 2), midway through the shock interval (T15), immediately after fluid infusion (T35), and 60 and 90 min later (T95, T155). In groups 1 and 2, ICP was significantly less in animals resuscitated with HS compared to those receiving SAL (P less than 0.05). 
A randomized clinical trial of alprazolam versus progressive muscle relaxation in cancer patients with anxiety and depressive symptoms. A randomized nonblinded study was performed in three cancer centers to test over a 10-day period the efficacy of (1) a triazolobenzodiazepine, alprazolam, 0.5 mg three times a day and (2) use of a behavioral technique in which patients were trained in progressive muscle relaxation at an initial session with a behavioral psychologist and then asked to listen at home to an audiotape of the session three times a day. Of 147 cancer patients who met entry levels of distress and completed the study, uncontrolled for site or disease stage, 70 were randomized to drug, 77 to relaxation. Four measures of anxiety and depression were used: Covi, Raskin, Affects Balance, and Symptoms Checklist-90 (SCL-90). Results showed that both treatment arms resulted in significant (P less than .001) decrease in observer and patient-reported anxious and depressed mood symptoms. Although both treatment arms were effective, patients receiving the drug showed a slightly more rapid decrease in anxiety and greater reduction of depressive symptoms. These findings confirm efficacy of both alprazolam and relaxation to reduce cancer-related anxiety and depression. As safe, inexpensive, and effective interventions, physicians should consider their use in cancer patients experiencing anxiety and depressive symptoms. 
Detection and localization of prolonged epicardial electrograms with 64-lead body surface signal-averaged electrocardiography. BACKGROUND. Prolonged, fractionated ventricular electrograms often are detectable after myocardial infarction and are a marker for an arrhythmia-prone state. QRS late potentials detected on the body surface with signal-averaged electrocardiography (SAECG) are thought to arise from the diseased tissue that generates prolonged ventricular electrograms and as such are also a marker for arrhythmias. A limitation of the current SAECG technique is that recordings are obtained from only three bipolar lead pairs. Because late potentials probably arise from multiple small sources in the heart, more extensive sampling of the body surface may contribute additional information to the SAECG. The present study investigates the additional sensitivity of SAECG using 64 body surface leads in detecting prolonged epicardial electrograms and examines its use in determining the epicardial location of prolonged electrograms. METHODS AND RESULTS. Dogs were studied before and 5-10 days after either lateral left ventricular (n = 13) or right ventricular (n = 8) myocardial infarction. Greater prolongation of signal-averaged QRS duration was detected with 64-lead SAECG (postinfarction QRS duration, 100.3 +/- 16.3 msec) than with three-lead SAECG (postinfarction QRS duration, 89.4 +/- 10.1, p = 0.0005). Nineteen of the 21 dogs (90%) had prolonged epicardial electrograms detected over the infarct. The correlation between epicardial electrogram duration and signal-averaged QRS duration calculated from individual leads was much better for 64-lead SAECG (r = 0.88, p less than 0.0001) than for three-lead SAECG (r = 0.53, p = 0.01), and the difference was most marked in cases with longer electrogram durations (more than 100 msec). Local late potential maxima on the thorax after lateral left ventricular infarction were located to the left and inferior compared with those after right ventricular infarction (p = 0.006). CONCLUSIONS. SAECG with more extensive recording from the body surface using 64 leads detects greater QRS prolongation than three-lead SAECG, and the longer QRS durations detected correspond to the duration of prolonged epicardial electrograms. Body surface location of late potentials corresponds to the epicardial location of the prolonged electrograms. This application of body surface mapping techniques to SAECG may permit more sensitive detection of arrhythmia-prone states and may aid in identifying arrhythmia sources. 
Role of intraoperative enteroscopy in obscure gastrointestinal bleeding of small bowel origin. Intraoperative enteroscopy was performed in 12 patients (median age 68 years) with obscure gastrointestinal bleeding probably of small bowel origin, six of whom were men. All the patients were evaluated by routine haematological, coagulation and biochemical profiles, upper and lower gastrointestinal endoscopies, visceral angiography and/or isotope scanning. All the patients were anaemic. Visceral angiography was useful on three of the 12 occasions on which it was used and isotope scanning was valuable on eight of the 11 occasions it was used. Nine patients had undergone previous laparotomy. Enteroscopy was performed successfully in all cases, with fresh blood and discrete vascular lesions being the chief findings (10 of 12 cases). Segmental resections (n = 8) and local resections (n = 2) were performed in ten patients, with two patients having more than one laparotomy for rebleeding. Five patients developed postoperative complications and there was an operative death and one late death. Three of the ten surviving patients experienced further rebleeding. Intraoperative enteroscopy is now an essential adjunct to laparotomy for gastrointestinal bleeding which has been localized to the small bowel before operation. 
Prevention of stroke and brain damage with calcium antagonists in animals. In a rat model of embolic stroke (permanent occlusion of the left middle cerebral artery [MCAO]), various 1,4-dihydropyridine calcium antagonists have been shown to attenuate brain damage and the resultant functional impairment when administered after MCAO. Dose-response curves reveal that isradipine is one of the most potent and efficacious representatives of this class of compounds, reducing the infarct size by more than 60%. These results suggest that isradipine, when administered shortly after stroke onset, may have beneficial effects in patients suffering from brain ischemia. When isradipine is used to normalize the high blood pressure in spontaneously hypertensive rats, it will, in addition, also protect the brain from damage engendered by a subsequent stroke. This is not the case if blood pressure is controlled with a calcium antagonist which does not cross the blood-brain barrier, suggesting that the brain protection seen with isradipine is not due to blood pressure normalization. Isradipine, when used as an antihypertensive, appears to have an additional beneficial effect within the brain itself. As high blood pressure is a major risk factor for stroke, such an additional benefit with isradipine would be particularly valuable in antihypertensive therapy. 
A prospective genetic study of complete and partial hydatidiform moles. Two hundred two hydatidiform moles were classified by pathologic features and ploidy into partial or complete moles. Further classification was made by using genetic polymorphism, the diagnosis being refined by deoxyribonucleic acid technology. Among 51 partial hydatidiform moles, 44 triploids, two tetraploids, and one diploid were identified. Informative triploid partial hydatidiform moles had one maternal and two paternal sets of chromosomes, the likely origin being dispermy. Among 149 complete hydatidiform moles, one was haploid, one was triploid, and 105 were shown to be diploid or androgenetic; 39 of these were proved homozygous, indicating duplication of the male genome, whereas heterozygous origin by dispermy was likely in 13. The locus-specific minisatellite deoxyribonucleic acid probes were particularly useful for the identification of heterozygous complete hydatidiform moles. None of the patients with partial hydatidiform moles had development of a gestational trophoblastic tumor. No difference was detected in the frequency of requirement for chemotherapy between patients with homozygous or heterozygous complete hydatidiform moles. 
Pharmacokinetics, immune response, and biodistribution of iodine-131-labeled chimeric mouse/human IgG1,k 17-1A monoclonal antibody. Pharmacokinetics, immunogenicity, and biodistribution of a 131I-labeled mouse/human chimeric monoclonal antibody (C-17-1A) was studied in six metastatic colon cancer patients. Pharmacokinetics obtained from serum radioactivity or chimera concentration were identical after 5 mCi of 131I-C-17-1A with mean alpha half-lives of 17.6 +/- 2.3 and 19.7 +/- 2.9 and mean beta half-lives of 100.9 +/- 16.1 and 106.4 +/- 14.1 hr, respectively. HPLC analysis documented the monomeric chimeric 17-1A without evidence of immune complexes or free 131I. None of the patients developed antibody after 131I-chimeric 17-1A exposure. Radiolocalization occurred in known areas of disease greater than 4 cm in all patients. The half-life of total-body radioactivity was 58 +/- 7 hr by whole-body counts and 64 +/- 13 hr by urine measurements. Whole-body and bone marrow dose estimates ranged from 0.75-1.03 and 0.76-1.05 rad/mCi, respectively. These studies confirm the prolonged circulation and reduced immunogenicity of chimeric 17-1A versus murine 17-1A. Marrow radiation exposure using antibodies with prolonged circulation is a critical factor in planning for radioimmunotherapeutic applications. 
Immunogenetic susceptibility for post-schistosomal hepatic fibrosis. In 19 children with hepatic fibrosis as the result of continued schistosomiasis mansoni and 20 children without hepatic fibrosis, the following studies were carried out: HLA antigen typing for 30 antigens, immune response of T lymphocytes to schistosome antigen by measuring DNA synthesis evidenced by 3H-thymidine uptake, and measurement of total OKT3+, OKT4+, and OKT8+ cells using monoclonal antibodies. Patients with hepatic fibrosis were mostly high responders in contrast with those without fibrosis. High immune response and susceptibility to post-schistosomal hepatic fibrosis were associated with a high frequency of A2 and B12 antigens and a lack of DR2 antigens, while low response was associated with the presence of the DR2 antigen. The T4+:T8+ ratio showed increased suppressor proportions in patients with low immune response and/or with no hepatic fibrosis. We suggest an immunogenetic susceptibility for post-schistosomal hepatic fibrosis, probably controlled by HLA-linked genes via the suppressor T cells. 
Predictors of intracranial carotid artery atherosclerosis. Duration of cigarette smoking and hypertension are more powerful than serum lipid levels. The effect of cigarette smoking on intracranial internal carotid artery atherosclerosis (ICAS) was studied by obtaining cigarette smoking histories and data on other potential predictors, including serum lipid estimations, for consecutive patients undergoing carotid arteriography. The duration of cigarette smoking was the most significant independent predictor of the presence of ICAS. Other independently significant predictors of ICAS were hypertension, diabetes mellitus, and current systolic blood pressure. The interaction of diabetes and duration of smoking was a significant negative predictor. In patients for whom serum lipid values were available, lower levels of apolipoprotein A-I were associated with a higher risk of having ICAS. However, the effect of apolipoprotein A-I as a predictor of the presence of ICAS was far outweighted by the effects of duration of smoking and hypertension. 
The influence of contamination of culture medium with hepatitis B virus on the outcome of in vitro fertilization pregnancies. Heat-inactivated human serum is added to the culture medium used for in vitro fertilization and other forms of assisted conception. Because one batch of pooled serum contained hepatitis B virus, an epidemic occurred among women participating in the treatment program. Seventy-nine women had serologic proof of hepatitis B infection. This incident gave the opportunity to study the effect of hepatitis B virus on pregnancy outcome and the newborn. The situation is unique because the preimplantation embryo was exposed to hepatitis B virus or the pregnancy was complicated by a (sub)clinical infection. Twenty-four women were or became pregnant while having an acute hepatitis B infection. Five pregnancies ended in abortion. The remaining 19 pregnancies ended in the birth of 24 children. No evidence for any harmful effect of exposure to hepatitis B virus in the embryonic or fetal period on the newborn could be found. 
Extensive hepatic granulomas associated with peripheral T-cell lymphoma. A case of T-cell lymphoma presenting with marked hepatosplenomegaly and extensive hepatic granulomas is described. A 55-yr-old female experienced long-term liver damage showing histological triaditis with atypical lymphoid cell infiltration and erythrophagocytosis. The patient developed marked hepatosplenomegaly and eventually died of respiratory failure. Neither systemic lymphadenopathy nor hematological disorder was noted until her death. Autopsy revealed small atypical lymphoid cells positive for T-cell marker, as well as extensive infiltration of generalized organs, including the liver, spleen, and lungs. As a result of diffuse proliferation of atypical lymphoid cell admixed with variable reactive cells, mainly at the T-zone, the lymph nodes underwent effacement of normal architecture; however, the peripheral sinuses and the fibrous capsule remained relatively well preserved. These histological features were consistent with a diagnosis of peripheral T-cell lymphoma (PTL). It is interesting to note that there were numerous epithelioid granulomas admixed with a small number of atypical lymphoid cells within the hepatic parenchyma. The atypical lymphoid cells may be responsible for the granulomatous reaction in the liver. To our knowledge, there have been no other reported cases of PTL that presented with numerous epithelioid granulomas confined to the liver. 
Pregnancy and childbearing in a population with biologic valvular prostheses. Long-term performance of biological prostheses and course of pregnancy, labor, and delivery were evaluated in women less than 35 years of age. Between 1975 and 1987, 87 female patients received a porcine (n = 86) or pericardial valve (n = 1); the mean patient age was 26.8 years, with a range of 8 to 35 years. A total of 17 of these patients experienced 37 pregnancies. A total of 25 babies were delivered, of which 19 were babies of normal birth weight born at term and six were born prematurely (two of these were stillborn). There were six spontaneous abortions and five therapeutic abortions. The mean time from primary operation to first delivery was 29 months. Of the 17 pregnant patients, 14 were in normal sinus rhythm and three were in atrial fibrillation. One of those in fibrillation had a therapeutic abortion while receiving warfarin therapy, and another was successfully delivered of her neonate after 7 months of warfarin therapy. The remaining 15 patients were treated through 35 pregnancies without anticoagulants or antiplatelet agents. Of the total population of 87 patients, 32 (36.8%) were treated for valve-related complications. Structural valve deterioration occurred in eight patients (47.1%) of the pregnancy group and 10 patients (14.3%) of the nonpregnancy group (p less than 0.05). The freedom from structural valve deterioration at 10 years was 23.3% +/- 14% for the pregnancy group and 74.2% +/- 8.5% for the nonpregnancy group (p less than 0.05, age as a determinant, p not significant). There were eight valve-related deaths (1.5%/patient-year). Reoperation was performed in 59% of the pregnancy group and 19% of the nonpregnancy group, primarily for structural valve deterioration manifested as valvular obstruction from aggressive calcification (p less than 0.05). The freedom from reoperation at 10 years parallels freedom from structural valve deterioration (20.3% +/- 12.4% and 64.3 +/- 9.1% for the pregnancy and nonpregnancy groups, respectively, with p less than 0.05; with age added as a determinant, p not significant). The overall reoperative mortality was 8.7% (two patients). The biologic prostheses afforded successful pregnancy without fetal wastage or congenital anomalies and without significant maternal morbidity or mortality. 
Mechanisms of platelet activation: thromboxane A2 as an amplifying signal for other agonists. Thromboxane (Tx) A2 is a product of cyclooxygenase catalyzed metabolism of arachidonic acid. It is formed via prostaglandin (PG) endoperoxide intermediates (PGG2 and PGH2) by a specific synthase. PGH2 appears to exert the same biologic effects as TxA2. The cDNA for a TxA2 receptor has been cloned from a human placental library. Although pharmacologic and biochemical studies suggest the presence of multiple isoforms, this remains to be confirmed at the molecular level. A hydropathy plot of the deduced amino acid sequence of the available clone suggests that it has 7 transmembrane spanning domains, typical of a G protein linked receptor. Pharmacologic studies imply that Tx receptors in platelets are linked to phospholipase C activation via pertussis toxin insensitive G proteins. Candidates include the 42 kD Gq and the 60 kD Ge. TxA2 acts as an amplifying signal for platelet agonists and the response to this eicosanoid is tightly regulated. Mechanisms include rapid hydrolysis of the agonist to the inactive TxB2, autoinactivation of Tx synthase, rapid homologous TxA2 receptor desensitization due to receptor-G protein uncoupling, coincidental sensitization to counterregulatory Gs linked receptor systems and stimulation of prostacyclin formation by TxA2. Due to its role as an amplification signal in platelet activation, inhibition of Tx synthesis and action is an effective mechanism for preventing platelet-dependent vascular occlusion. Aspirin is of proven efficacy in this regard. Tx synthase inhibitors and antagonists are under clinical investigation. 
Risk factors for stroke in patients with nonrheumatic atrial fibrillation: a case-control study. PURPOSE: Randomized controlled trials have demonstrated that anticoagulant therapy is very effective at preventing stroke among patients with nonrheumatic atrial fibrillation. However, these trials have reported too few strokes for powerful risk factor analysis. Observational studies may provide additional information. The purpose of this study was to identify risk factors in a larger number of patients with stroke and nonrheumatic atrial fibrillation, using case-control methodology. PATIENTS AND METHODS: We identified all patients discharged from one hospital over an 8-year period who met our case definition of nonrheumatic atrial fibrillation and ischemic stroke (n = 134), and compared them with contemporaneous control subjects who were discharged with nonrheumatic atrial fibrillation without stroke (n = 131). RESULTS: Cases and controls were similar in terms of duration of atrial fibrillation; proportion with paroxysmal atrial fibrillation; percentage with a past medical history of angina, myocardial infarction, congestive heart failure, diabetes, or smoking; and mean left atrial size. In contrast, cases were significantly older than controls (78.5 versus 74.8 years, p = 0.002) and more likely to have a history of hypertension (55% versus 38%, p = 0.0093). The relative odds for stroke was 1.91 for patients with hypertension, 1.73 for patients older than 75 years, and 3.26 for patients with both factors. CONCLUSIONS: Our analysis suggests that age and hypertension should be considered when deciding upon long-term anticoagulant therapy to prevent stroke in patients with nonrheumatic atrial fibrillation. 
The relationship of pain and deformity of the rheumatoid foot to gait and an index of functional ambulation. We evaluated the relationships among pain, structural deformity of the foot, 4 variables of gait, and an index of functional ambulation in 31 patients with rheumatoid arthritis. We saw significant correlations between the ambulation index and all gait variables (p less than 0.005). For the group as a whole, pain in the foot did not correlate with structural deformity. However, when patients were grouped according to the relative preponderance of pain or deformity and duration of disease, we found correlations between the sites of pain and deformity. Pain in the lower extremity, and the knee or hindfoot separately, showed correlations with functional ambulation. Foot deformity did not correlate with functional ambulation at all. Foot pain correlated well with velocity and especially stride length (p less than 0.005), and not as well with cadence and double stance time. Fewer correlations were seen between foot deformity and gait. In general, hindfoot disease was associated with greater impairment of gait and mobility than forefoot disease. 
Effect of intravenous infusion of atriopeptin 3 on immediate renal allograft function. Thirty-eight recipients of nineteen pairs of cadaveric kidneys were entered into a double-blind randomized study in which one recipient received a 12-hour intravenous infusion of Atriopeptin III (AP-3), a synthetic analogue of atrial natriuretic factor, commencing at release of the vascular clamps, and the other received a placebo infusion. In an initial dose ranging study, successive groups of six kidneys (3 pairs) were randomized to receive each of 0.0125, 0.025, 0.05 micrograms/kg/min AP-3 or placebo. Thereafter 20 kidneys (10 pairs) received 0.1 micrograms/kg/min or placebo. There was no discernable effect of AP-3 on allograft creatinine clearance or sodium excretion either when the highest dose of AP-3 was considered alone or when all doses were considered together. Averaged creatinine clearance over the period 0 to 24 hours after transplantation was 20.1 +/- 14.7 ml/min in patients receiving active treatment and 18.2 +/- 13.7 ml/min in those receiving placebo. Thus, despite the documentation of a protective effect of atrial natriuretic factor in animal models of renal ischemia, it is unlikely that intravenous infusion of AP-3 in this dose range will be of benefit in improving immediate renal allograft graft function. 
Effect of dietary ethanol on gallbladder absorption and cholesterol gallstone formation in the prairie dog. Dietary ethanol has been reported to protect against cholesterol gallstone formation. Because enhanced gallbladder absorption of water is important in cholesterol cholelithiasis, we examined the hypothesis that ethanol acts by inhibiting the absorptive function of the gallbladder. Eighteen adult male prairie dogs were fed a lithogenic liquid diet containing 0.4% cholesterol. Half of the animals received 30% of total calories as ethanol, whereas their pair-fed controls received equicaloric amounts of maltose-dextrin. After 3 months, the gallbladders were inspected for gallstones and crystals, and gallbladder and hepatic bile were analyzed. Cholesterol stones and crystals were present in all nine controls. None of the alcohol-fed animals had stones, but four had cholesterol crystals. Gallbladder cholesterol, phospholipids, and total calcium were significantly decreased in alcohol-fed animals. In both gallbladder and hepatic bile, the cholesterol saturation index was significantly lower in alcohol-fed animals, as was the ratio of trihydroxy to dihydroxy bile salts. The ethanol-supplemented diet produced a significant decrease in the absorption of water by the gallbladder as indicated by changes in the gallbladder bile to hepatic bile ratios of the total bile salt concentration (7.29 +/- 1.25 versus 3.84 +/- 0.56; p less than 0.05) and the total calcium (3.37 +/- 0.24 versus 2.43 +/- 0.29; p less than 0.05). These findings indicate that the protective effect of ethanol may be related to its ability both to inhibit gallbladder absorption of water and to alter the composition of biliary lipids. 
High protein intake promotes the growth of hepatic preneoplastic foci in Fischer #344 rats: evidence that early remodeled foci retain the potential for future growth. The effects of successive administration, withdrawal and readministration of high protein diets (20% casein) on the promotional growth, remodeling and regrowth of aflatoxin B1-induced preneoplastic liver lesions (foci) were examined. Weanling male Fischer 344 rats were given 10 intragastric doses of aflatoxin B1 at a level of 250 micrograms/kg body weight over a 2-wk dosing period (initiation). The subsequent 12-wk period was subdivided into four feeding periods, each lasting 3 wk (promotion). Two groups of rats were fed either a 20 or 5% casein diet during all four periods; additional groups were alternately fed these diets in different sequences. Switching from the high protein diet to a low protein diet (5% casein) resulted in marked remodeling (regression) of the growing lesions to a response level similar to that in animals that did not receive the initial promotional stimulus of high protein feeding. However, refeeding the high protein diet caused significant reappearance of these lesions. The restimulated development of these remodeled lesions far exceeded lesion growth in animals receiving only the late promotional stimulus of high dietary protein. Thus, these data suggest that a second occurrence of high protein feeding promotes the growth of remodeled foci, thus demonstrating their potential for future promotional growth. 
Difference in mortality between patients treated with captopril or enalapril in the Xamoterol in Severe Heart Failure Study The double-blind, placebo-controlled, multinational trial Xamoterol in Severe Heart Failure randomized 290 patients treated with captopril and 217 treated with enalapril to xamoterol or placebo. At the end of the 100-day follow-up period, the cumulative probability of survival in patients with coronary artery disease or with dilated cardiomyopathy decreased in the captopril group (90.3%) when compared with the enalapril group (97.2%). The excess mortality in the captopril group could not be related to the indexes of the severity of heart failure, such as baseline exercise duration, functional class, cardiothoracic ratio, ejection fraction or dose of diuretic drugs. Furthermore, the excess in mortality was seen in all subsets of patients examined as well as across countries. Examination of the dosing regimen used, however, suggests that insufficient daily dosage of captopril or the inadequate schedule of administration, or both, might be responsible for different degrees of angiotensin-converting enzyme inhibition between the enalapril and captopril groups and hence for the difference in mortality. It is important in future clinical trials to determine to what extent complete circadian angiotensin-converting enzyme inhibition is necessary to provide the full benefit of this therapy in heart failure. 
A comparison of the effects of ipratropium bromide and metaproterenol sulfate in acute exacerbations of COPD. Thirty-two patients presenting with acute exacerbations of chronic obstructive pulmonary disease were entered into the following double-blind, crossover study. First (time 0), patients inhaled either ipratropium bromide (54 micrograms) or metaproterenol sulfate (1.95 mg) via a metered dose inhaler (MDI) attached to a device (Inspirease) (phase 1). After 90 minutes, they inhaled whichever of the two medications they had not received in phase 1. This is referred to as phase 2. Pulmonary function (FEV1 and FVC) was measured at time 0, and at 30, 60, and 90 minutes following phase 1 treatment, and at 30, 60, and 90 minutes following phase 2 treatment (120, 150, and 180 minutes from the start of the study). Arterial blood gas samples (n = 20) were obtained at entry into the study and 30 and 90 minutes after phase 1 medication. The groups did not differ in age, degree of airway obstruction, hypoxemia, or theophylline usage at the start of the study. In phase 1, at 90 minutes, pulmonary function in both groups significantly and similarly improved. For ipratropium, FEV1 improved from 0.62 +/- 0.08 L to 0.88 +/- 0.11 L (p less than 0.01) and for metaproterenol FEV1 improved from 0.69 +/- 0.06 to 0.92 +/- 0.09 L (p less than 0.01). There was no further improvement with phase 2 treatment for either group. Thirty minutes after inhaling ipratropium, there was a small but significant rise in PO2 (5.8 +/- 3.0 mm Hg; p less than 0.05) while metaproterenol inhalation resulted in a 6.2 +/- 1.2 mm Hg decline in PO2 (p less than 0.05). These changes were not sustained at 90 minutes. We concluded that for acute exacerbations of COPD, both ipratropium and metaproterenol are effective medications when administered via an MDI attached to a device (Inspirease). However, ipratropium may be a safer choice as it initially did not cause a decline in blood oxygenation. 
Effect of superoxide dismutase on infarct size and postischemic recovery of myocardial contractility and metabolism in dogs The effects of superoxide dismutase treatment on infarct size, postischemic recovery of contractile function and tissue content of high energy phosphates were examined in a canine model of myocardial ischemia and reperfusion. Ischemia was induced by thrombotic occlusion of a coronary artery and reperfusion was achieved by intravenous thrombolysis. Average duration of ischemia was 90 min. Fifty closed chest anesthetized dogs were randomized to receive either superoxide dismutase (34,000 IU/min intravenously) or placebo, starting approximately 30 min before and continuing for 30 min into the reperfusion phase. Left ventricular ejection fraction and regional segmental shortening of the postischemic area were calculated from contrast angiograms after 4 h, 48 h and 1 week of reperfusion. Tissue content of high energy phosphates was determined from transmural biopsy after 4 h and 1 week. Infarct size was measured by planimetry of dye-stained heart slices. In the superoxide dismutase and placebo-treated groups, respectively, the mortality rate was 25% and 16%, collateral flow 20 +/- 10 and 23 +/- 18 ml/min per 100 g, area at risk 25 +/- 6% and 26 +/- 7% of the left ventricle and infarct size 28 +/- 19% and 36 +/- 27% of the area at risk. Multiple regression analysis failed to show any beneficial effect of superoxide dismutase treatment on infarct size. Left ventricular ejection fraction, regional segmental shortening of the postischemic area and tissue content of high energy phosphates recovered to a similar extent and at a similar rate in both treated and placebo groups up to 1 week after reperfusion. Thus, in this model of coronary occlusion and reperfusion superoxide dismutase treatment is of no benefit. 
Endoscopic therapy for early colon cancer: the strip biopsy resection technique. Strip biopsy is an endoscopic tissue resection technique in which a lesion and its surrounding tissues are first elevated using physiological saline. The saline solution is injected into the submucosa at the site of the lesion with the help of needle forceps. A snare is placed around the elevated tissue, which is then resected endoscopically by electrocoagulation. The specimen obtained includes both submucosal and mucosal tissues. The authors used this technique to resect a total of 71 lesions of the colon. They were classified histologically as 21 adenocarcinomas, 46 adenomas, 3 metaplastic polyps, and 1 juvenile polyp. All lesions were confirmed to be entirely intramucosal by histological examination. The strip biopsy technique permits resection of tissue down to the submucosal layer regardless of the morphological type of the lesion. This suggests that strip biopsy is an effective new form of endoscopic treatment for early colon cancer. 
Millipore analysis of valvular fluid in sterile valve malfunctions. Malfunctions of sterile shunts may result from valvular dysfunction. The cerebrospinal fluid shunt valves of 14 patients were excised during surgery for sterile shunt malfunctions. In 6 patients, the malfunction was due specifically to a valve malfunction. Cerebrospinal fluid from each valve was passed through a millipore filter, which was then stained using either hematoxylin and eosin or periodic acid-Schiff. The stained millipore filters were examined by a neuropathologist who was unaware of the cause of the shunt malfunction. Although inflammatory cells were detected in all cases, the patients with valve malfunctions were found to have numerous macrophages and giant multinucleated reactive cells within their valves, while cerebrospinal fluid from valves that had been removed during shunt revisions for reasons other than a malfunctioning valve contained only rare mononuclear cells or macrophages. No valve contained erythrocytes, fibrinous matter, neural or glial tissue, or choroid plexus. The possible causes of valve malfunction, including infection and allergic reactions, are discussed. All patients did well after simple replacement of the valve. 
Comparison of long-term survival of 1986 consecutive patients with breast cancer treated at the National Cancer Institute of Milano, Italy (1971 to 1972 and 1977 to 1978). Long-term survival of 1986 consecutive patients with infiltrating duct carcinoma of the breast treated at the National Cancer Institute of Milano (Italy) in two periods of time (1971 to 1972 and 1977 to 1978) was comparatively evaluated to verify if the evolving concepts in the management of breast cancer had an impact on survival. The authors found that 10-year survival of our patients increased from 59.4% of the first period of time to 65% of the second (P = 0.005). Both node-negative (N-) and node-positive (N+) patients had an improvement of survival rates at 10 years of the same magnitude: 6.8% and 5.9% respectively. Taking into consideration both the maximum diameter of the primary tumor and the status of axillary nodes it was found that in (1) both N- and N+ patients with a primary tumor of no more than 2 cm in greatest diameter, the improvement of survival was not statistically significant; and (2) both N- and N+ patients with a primary greater than 2 cm in maximum diameter had a better chance of survival in the second time period. 
Intravascular stents in the management of superior vena cava syndrome. Superior vena cava syndrome can be effectively palliated with the use of intravascular stents. Adjunctive modalities which may be utilized prior to stent placement are thrombolytic therapy and balloon angioplasty. Six patients with an underlying malignancy were treated with these modalities. Complete resolution of symptoms occurred in five patients, and partial resolution occurred in the sixth. Two of the patients who had initial, complete resolution of symptoms had recurrences. One involved rethrombosis of the superior vena cava which occurred twice and required percutaneous thrombectomy, and the second involved restenosis requiring a percutaneous transluminal angioplasty of the SVC just distal to the stent. Both of these patients with second procedures, again, had complete resolution of symptoms. Intravascular stents are a valuable additional treatment of superior vena cava syndrome. 
Grading diabetic retinopathy from stereoscopic color fundus photographs--an extension of the modified Airlie House classification. ETDRS report number 10. Early Treatment Diabetic Retinopathy Study Research Group. The modified Airlie House classification of diabetic retinopathy has been extended for use in the Early Treatment Diabetic Retinopathy Study (ETDRS). The revised classification provides additional steps in the grading scale for some characteristics, separates other characteristics previously combined, expands the section on macular edema, and adds several characteristics not previously graded. The classification is described and illustrated and its reproducibility between graders is assessed by calculating percentages of agreement and kappa statistics for duplicate gradings of baseline color nonsimultaneous stereoscopic fundus photographs. For retinal hemorrhages and/or microaneurysms, hard exudates, new vessels, fibrous proliferations, and macular edema, agreement was substantial (weighted kappa, 0.61 to 0.80). For soft exudates, intraretinal microvascular abnormalities, and venous beading, agreement was moderate (weighted kappa, 0.41 to 0.60). A double grading system, with adjudication of disagreements of two or more steps between duplicate gradings, led to some improvement in reproducibility for most characteristics. 
Linkage of a gene causing familial amyotrophic lateral sclerosis to chromosome 21 and evidence of genetic-locus heterogeneity [published errata appear in N Engl J Med 1991 Jul 4;325(1):71 and 1991 Aug 15;325(7):524] BACKGROUND. Amyotrophic lateral sclerosis is a progressive neurologic disorder that commonly results in paralysis and death. Despite more than a century of research, no cause of, cure for, or means of preventing this disorder has been found. In a minority of cases, it is familial and inherited as an autosomal dominant trait with age-dependent penetrance. In contrast to the sporadic form of amyotrophic lateral sclerosis, the familial form provides the opportunity to use molecular genetic techniques to localize an inherited defect. Furthermore, such studies have the potential to discover the basic molecular defect causing motor-neuron degeneration. METHODS AND RESULTS. We evaluated 23 families with familial amyotrophic lateral sclerosis for linkage of the gene causing this disease to four DNA markers on the long arm of chromosome 21. Multipoint linkage analyses demonstrated linkage between the gene and these markers. The maximum lod score--5.03--was obtained 10 centimorgans distal (telomeric) to the DNA marker D21S58. There was a significant probability (P less than 0.0001) of genetic-locus heterogeneity in the families. CONCLUSIONS. The localization of a gene causing familial amyotrophic lateral sclerosis provides a means of isolating this gene and studying its function. Insight gained from understanding the function of this gene may be applicable to the design of rational therapy for both the familial and sporadic forms of the disease. 
Syndrome of inappropriate antidiuretic hormone secretion in cancer of the head and neck. The syndrome of inappropriate secretion of arginine vasopressin (AVP) known as the syndrome of inappropriate antidiuretic hormone secretion (SIADH) is characterized by hyponatremia that results from water retention attributable to persistent AVP release. It may occur in a variety of malignant and nonmalignant lesions, with small cell or oat cell carcinoma of the lung by far responsible for the largest number of these cases. Cancer of the head and neck may be a rare cause of SIADH, and only a few such cases have been reported. We describe four patients with advanced cancer of the head and neck region with coexisting SIADH. Diagnosis and treatment are reported and the literature is reviewed. The possible occurrence of SIADH in the head and neck surgical practice should be kept in mind. Since SIADH is usually transient, water restriction and parenteral sodium chloride may be sufficient in overcoming the acute phase. 
Spontaneous contrast in the pericardial sac caused by gas-forming organisms. Purulent pericarditis is a life-threatening disease associated with a variety of microorganisms. The case presented herein has unusual manifestations of contrast echoes on two-dimensional echocardiography. To our knowledge, this is the first reported case of pericarditis caused by gas-forming group D Streptococcus and Klebsiella pneumoniae with pyopericardium, resulting in contrast echoes on the two-dimensional echocardiographic image. 
Validating studies for panic disorder in patients with angiographically normal coronary arteries. This article describes validating studies for diagnosing panic disorder in some patients with angiographically normal coronary arteries (NCA) and chest pain. Psychiatric interviews of 94 such patients showed that 34% met the diagnostic criteria for panic disorder. Further studies showed that NCA patients with panic disorder were more disabled at 3.5-year follow-up, had more relatives with panic disorder, were more likely to suffer from major depression, and were more likely to respond to 35% CO2 challenge with panic symptoms. Because panic disorder is highly disabling but responds well to psychological and pharmacologic treatments, screening NCA patients in the cardiology population for this disorder is recommended. 
Recurrence and treatment of urinary bladder cancer after failure in radiotherapy. One hundred fifty-five patients with urinary bladder cancer who were not suitable for radical surgery were treated with full-course radiotherapy, 6600 cGy in 9 weeks, split-course. After the treatment recurrences were observed in 94 patients (60%), 49 (53%) were treated with transurethral surgery and intravesical cytostatics, local surgery, systemic cytostatics, or palliative radiotherapy. The median survivals for the patients were 33, 10, 4, and 2.4 months, respectively. The outcome of treatment for radiotherapy failures was related to the nature of the failure, ureteric obstruction, the recurrence rate, and the mode of treatment. Shrinkage of the bladder was observed in 15 patients (16%). The occurrence of bladder shrinkage was related to the increase in frequency of recurrences and of different types of treatments. 
Immunohistochemical evaluation of uveal melanocytic tumors. Expression of HMB-45, S-100 protein, and neuron-specific enolase. The authors compared the immunohistochemical reactivity of 13 uveal nevi and 20 uveal melanomas for HMB-45, S-100 protein, and neuron-specific enolase (NSE) in formalin-fixed, paraffin-embedded sections. All 33 of the lesions were positive for HMB-45. The false-negative rates for S-100 protein and NSE were 21% and 18%, respectively. If only strongly positive reactions were considered, more than 50% of the tumors would be interpreted as negative for S-100 protein and NSE. Nevi stained with less intensity than melanomas using all three antibodies. The expression of HMB-45 appeared to be greater in active nevi than in inactive nevi. There was a weak association between S-100 protein reactivity and the ability of the uveal melanomas to metastasize (P = 0.1); however, the standard deviation of nucleolar area was a much better predictor (P = 0.02). These results indicate that pathologists will find HMB-45 to be a useful tool in differentiating uveal melanoma from nonmelanocytic tumors. 
Prevention of thromboembolic disease following total knee arthroplasty. Epidural versus general anesthesia. Seventy-two patients were randomized into a prospective clinical trial to evaluate the effects of epidural (EA) versus general anesthesia (GA) on the incidence of thromboembolic disease (TED) following total knee arthroplasty (TKA). Males received aspirin 650 mg po bid and females low-dose warfarin daily to maintain the prothrombin time at 15 to 16 seconds for pharmacologic prophylaxis against TED. Thirty-four patients had EA and 38 GA for their primary TKA. Contrast venography and ventilation-perfusion scanning were performed on the sixth, seventh, and eighth postoperative days, and these were interpreted in a blinded fashion. The mean age of the 45 males and 27 females was 64 years (range, 42-84 years). There were no significant differences between the two groups with respect to hematocrit, operative time, blood loss, number of units transfused, or hospital stay. Twelve of the 34 patients (35%) receiving an EA and 10 of the 38 patients (26%) receiving GA developed TED, an overall incidence of 31% (p greater than 0.05) Fifty-three percent of the clots were located in the popliteal vein above the trifurcation or more proximal. However, the incidence of proximal vein thrombosis was significantly less in patients receiving an EA (46%) rather than a GA (64%). The incidence and distribution of clots was not affected by the type of pharmacologic prophylaxis, gender, or use of methylmethacrylate. Ten percent of the patients had a positive scan by strict criteria and were thought to have a pulmonary embolism (PE). In patients with a femoral vein clot, the incidence of PE was 67%. One bleeding complication occurred in a patient who took double the appropriate warfarin dose. 
Management of bleeding liver tumours in Hong Kong. A retrospective study was undertaken of 41 patients diagnosed as having suffered spontaneous liver rupture over a 4-year period to identify the clinical features, treatment and outcome of this complication in an area in which hepatocellular carcinoma is endemic. Two patients were excluded with a revised diagnosis of haemorrhagic malignant ascites. Of the remaining 39 patients, 37 bled from ruptured hepatocellular carcinoma, one from peliosis hepatis and multiple liver cell adenomas, and one from a malignant hepatic epithelioid haemangioendothelioma. Analysis showed that 59 per cent of patients were in shock on admission and that all but two of the 37 patients with ruptured hepatocellular carcinoma were men with cirrhosis. The association with cirrhosis was significantly higher than in a series of 45 patients with hepatocellular carcinoma undergoing elective resection during the same period (P less than 0.05). Treatment consisted of supportive care only in two patients, angiographic embolization in four, emergency liver resection in 11 of whom six died, hepatic artery ligation in 12 of whom eight died, and suture and/or packing in eight of whom six died. One patient died at laparotomy and in another patient bleeding was successfully arrested by intratumoural injection of absolute alcohol. Because of the high operative mortality of emergency surgery in these poor risk patients, prospective evaluation of emergency angiographic embolization is required. 
Autonomic dysfunction in alcoholic cirrhosis: relationship to indicators of synthetic activation and the occurrence of renal sodium retention. We investigated the occurrence of alcoholic autonomic dysfunction in patients with alcoholic cirrhosis in order to define its prevalence and relationship to renal sodium retention. Forty-seven alcoholics and 16 age-matched normal subjects were evaluated. Thirty-seven patients had liver disease (13 with and 24 without ascites), and 10 patients had normal hepatic function. Autonomic nervous system function was ascertained by skin sudomotor responses and the response of blood pressure and plasma norepinephrine concentration to upright tilt (sympathetic nervous system function), and by heart rate responses to deep breathing, Valsalva maneuver, and upright tilt (parasympathetic and sympathetic nervous system function). Heart rate responses to deep breathing and Valsalva maneuver were diminished, and skin sudomotor responses were significantly worse, in alcoholics than in control subjects. Alcoholic patients also had significantly lower supine mean arterial pressure (93 +/- 10 vs. 116 +/- 8 mm Hg, p less than or equal to 0.0001), and significantly greater increases in arterial pressure during passive upright tilt, than control subjects (mean increase 6.5 +/- 6.6 vs. 0.1 +/- 1.6 mm Hg, p = 0.0003). All of these findings were present to similar degrees in patients with and without liver disease and in cirrhotic patients with and without ascites. Supine heart rates, however, differed among the groups evaluated. Heart rate was significantly greater in patients with cirrhosis than in alcoholic patients without liver disease (83 +/- 11 vs. 71 +/- 13 bpm, p = 0.006), and in patients with ascites than in patients without ascites (88 +/- 12 vs. 80 +/- 10 bpm, p = 0.04). Plasma norepinephrine concentration was elevated in most patients with cirrhosis and was significantly higher in patients with ascites than in patients without ascites (789 +/- 238 vs. 388 +/- 185 pg/ml, p less than 0.0001; nl range: 65-320 pg/ml). Autonomic nervous system function is similarly impaired in alcoholics with and without liver disease. Patients with cirrhosis also have increased heart rate and elevated plasma norepinephrine concentration, abnormalities that are most pronounced in patients with sodium retention. Their is uncertainty as to the stimulus for norepinephrine release, and its source, in these patients. However, the similarity of supine blood pressure in patients with and without ascites and the occurrence of orthostatic hypertension rather than orthostatic hypotension following upright tilt suggest that arterial underfilling is not responsible. 
Hypogonadotropic hypogonadism and temporal lobe epilepsy. The concomitant finding of hypogonadotropic hypogonadism and temporal lobe epilepsy raises the issue of whether or not these entities are related. The case presented herein is one such example. The possible pathophysiologic basis of infertility and temporal lobe epilepsy is reviewed. 
Atrial fibrillation associated with autonomic dysreflexia in patients with tetraplegia. Atrial fibrillation is an arrhythmia characterized by disorganized atrial depolarizations and an irregular ventricular response. Most patients with atrial fibrillation have underlying cardiac pathology. This paper presents the cases of three patients with high-level spinal cord injury and symptoms of autonomic dysreflexia who developed atrial fibrillation without any cardiac or metabolic disease that would predispose them to this. The paper proposes that autonomic dysreflexia might predispose a patient to atrial fibrillation by altering the pattern of repolarization of the atria, making the heart susceptible to a reentrant type of arrhythmia. High-level spinal cord injured patients may be at increased risk for the development of atrial fibrillation, an arrhythmia which, if left untreated, can increase the incidence of an embolic cerebrovascular accident that could further impair the patient's functional status. 
Reaction of human non-collagenous polypeptides with coeliac disease autoantibodies. We identified and purified six human noncollagenous protein molecules that specifically bind to serum IgA from patients with coeliac disease, and which as a combination can act as true antigen to reticulin antibodies. In affinity chromatography, the purified human protein molecules removed antibodies against reticulin and endomysium from serum samples of coeliac disease patients. We postulate that an autoimmune mechanism operates in generating the jejunal damage in gluten-sensitive enteropathy and that the human protein molecules described here act as self-antigens in the disease. 
Stress-induced elevations of gamma-aminobutyric acid type A receptor-active steroids in the rat brain. A 3 alpha-hydroxy A-ring-reduced metabolite of progesterone, 3 alpha-hydroxy-5 alpha-pregnan-20-one (allopregnanolone), and one of deoxycorticosterone (DOC), 3 alpha,21-dihydroxy-5 alpha-pregnan-20- one (allotetrahydroDOC), are among the most potent known ligands of gamma-aminobutyric acid (GABA) receptors designated GABAA in the central nervous system. With specific radioimmunoassays, rapid (less than 5 min) and robust (4- to 20-fold) increases of allopregnanolone and allotetrahydroDOC were detected in the brain (cerebral cortex and hypothalamus) and in plasma of rats after exposure to ambient temperature swin stress. Neither steroid was detectable in the plasma of adrenalectomized rats either before or after swim stress. However, allopregnanolone, but not allotetrahydroDOC, was still present in the cerebral cortex (greater than 3 ng/g) after adrenalectomy. These data demonstrate the presence of allopregnanolone and allotetrahydroDOC in brain and show that acute stress results in a rapid increase of these neuroactive steroids to levels known to modulate GABAA receptor function. 
Granulomatous peritonitis and appendicitis of food starch origin. Two patients with food starch granulomatous reactions, one a necrotising granulomatous peritonitis after the perforation of a gastric ulcer and the other a non-necrotising granulomatous appendicitis, are described. The possibility of food starch induced inflammation must be considered in the differential diagnosis of granulomatous diseases of the gastrointestinal tract. 
Early spontaneous hematoma in cerebral infarct: is primary cerebral hemorrhage overdiagnosed? We identified 15 patients (63 +/- 8 years) in whom CT showed no bleeding within 6 hours of stroke onset but showed ganglionic or lobar hemorrhage less than 18 hours later, without visible underlying infarct (early spontaneous intra-infarct hematoma [ESIH]). No patient had antithrombotic therapy or a coagulation disorder, but eight had hypertension. The second CT was prompted by rapid worsening (in 10) or because the first CT was not available (in five). Prior transient ischemic attacks, silent infarcts on CT, and a potential cardiac source of embolism were more common in patients with ESIH than in 200 patients with primary cerebral hemorrhage (PCH) admitted during the same period. Distal occlusions were present in four of five patients who underwent intracranial studies within the first 2 days. Most of these patients probably had embolism with early and extensive bleeding in the ischemic area. Our findings suggest that ESIH may be under-recognized, while PCH may be overdiagnosed. 
Temper tantrums. Temper tantrums are a normal response to anger and occur commonly in the child between one and four years of age. They arise from the child's thwarted efforts to exercise mastery and autonomy. Tantrums occur more frequently in the active, determined child who has abundant energy. Parenting practices that may encourage tantrums include inconsistency, unreasonable expectations, excessive strictness, overprotectiveness and overindulgence. Boredom, fatigue, hunger or illness may reduce the child's tolerance for frustration. Management consists of teaching the parents to understand the underlying meaning of tantrums and to modify parental behaviors that may perpetuate or accentuate the problem. Temper tantrums are best handled by ignoring the outburst, offering nurturance to the child after the tantrum has subsided and helping the child learn to express negative feelings in more acceptable ways. 
Importance of bile acid structure in amelioration of griseofulvin-induced murine protoporphyric hepatopathy. This study investigated the effects of bile acid structure on griseofulvin-induced murine hepatopathy and explored the mechanism(s) of cholestasis in this model of protoporphyria. Mice were fed pulverized chow with cholate, chenodeoxycholate, or ursodeoxycholate, with or without griseofulvin. After 1 to 4 weeks, bile flow, bile acid excretion and composition, biliary protoporphyrin excretion, hepatic protoporphyrin contents, liver histology, and griseofulvin plasma concentrations were determined. Additionally, bile acid absorption was measured. Griseofulvin induced a progressive increase in liver weight, hepatic protoporphyrin content, and histopathologic evidence of cholestasis. Biliary protoporphyrin excretion increased and pigmented gallbladder microliths developed. Bile flow and bile acid excretion fell in relation to liver weight but not in relation to body weight. Cholic acid augmented biliary protoporphyrin excretion, markedly reduced hepatic protoporphyrin content, and obviated the development of intrahepatic biliary thrombi. Ursodeoxycholate and chenodeoxycholate both reduced biliary protoporphyrin excretion. This was associated with bile acid compositional changes, particularly a fall in cholic acid. Although histopathologic abnormalities were not altered, these bile acids reduced hepatic protoporphyrin contents. Bile acid treatments with griseofulvin all increased bile flow and bile acid excretion relative to controls, but differences in the relationship of bile flow to bile acid structure on protoporphyrin disposition. They document biliary excretion as the principal mode of cholic acid amelioration of griseofulvin-induced hepatopathy. They also suggest distinctive roles for griseofulvin and protoporphyrin in the generation of the cholestasis. 
The hypotensive activity of Crotalus atrox (western diamondback rattlesnake) venom: identification of its origin. Viperidae snakes belonging to the genus Crotalus, subfamily Crotalinae, include the species durissus terrificus, durissus durissus, adamanteus, atrox, cerastes, horridus, molossus, scutulatus, viridis and others. All of them, except for the first 2, are found in North America. Crotalus atrox, or diamondback rattlesnakes, live in the southwest United States and in Mexico. This paper describes the fractionation of C. atrox venom in order to isolate and identify its hypotensive agents. 
A controlled trial comparing foscarnet with vidarabine for acyclovir-resistant mucocutaneous herpes simplex in the acquired immunodeficiency syndrome. The AIDS Clinical Trials Group. BACKGROUND AND METHODS. Most strains of herpes simplex virus that are resistant to acyclovir are susceptible in vitro to both foscarnet and vidarabine. We conducted a randomized trial to compare foscarnet with vidarabine in 14 patients with the acquired immunodeficiency syndrome (AIDS) and mucocutaneous herpetic lesions that had been unresponsive to intravenous therapy with acyclovir for a minimum of 10 days. The patients were randomly assigned to receive either foscarnet (40 mg per kilogram of body weight intravenously every 8 hours) or vidarabine (15 mg per kilogram per day intravenously) for 10 to 42 days. In the isolates of herpes simplex virus we documented in vitro resistance to acyclovir and susceptibility to foscarnet and vidarabine. RESULTS. The lesions in all eight patients assigned to foscarnet healed completely after 10 to 24 days of therapy. In contrast, vidarabine was discontinued because of failure in all six patients assigned to receive it. The time to complete healing (P = 0.01), time to 50 percent reductions in the size of the lesions (P = 0.01) and the pain score (P = 0.004), and time to the end of viral shedding (P = 0.006) were all significantly shorter in the patients assigned to foscarnet. Three patients had new neurologic abnormalities while receiving vidarabine. No patient discontinued foscarnet because of toxicity. Although initial recurrences of herpes simplex infection after the index lesion had healed tended to be susceptible to acyclovir, acyclovir-resistant infection eventually recurred in every healed patient, a median of 42.5 days (range, 14 to 191) after foscarnet was discontinued. CONCLUSIONS. For the treatment of acyclovir-resistant herpes simplex infection in patients with AIDS, foscarnet has superior efficacy and less frequent serious toxicity than vidarabine. Once the treatment is stopped, however; there is a high frequency of relapse. 
Rapid localization of indium-111-labeled inhibited recombinant tissue plasminogen activator in a rabbit thrombosis model. The thrombus localizing properties of indium-111-recombinant tissue plasminogen activator (111In-rt-PA) have been investigated in an effort to achieve prompt and accurate detection of thrombi. Unlike previous studies with rt-PA, the active plasminogen catalytic site was permanently inhibited with peptides of chloromethyl ketone so that the radiotracer binds to fibrin without causing fibrinolysis. Thrombi were created in the external jugular vein of 14 male New Zealand white rabbits followed by injection of 111In-rt-PA. The agent cleared rapidly in vivo with a half-time of 4.6 min. The thrombus: blood ratio in nonheparinized rabbits (n = 7) was 6.39 +/- 0.86. The ratio in heparinized rabbits (n = 4) was 3.11 +/- 0.23. Thrombi were clearly visible in the planar images of both groups 1 hr postinjection. The combination of rapid thrombus localization and positive images, especially in the presence of anticoagulation, suggests that further work is warranted with rt-PA thrombus imaging. 
Occurrence of resting tremor in Parkinson's disease. Several previous studies have noted that resting tremor (RT) is absent in 10% to 30% of idiopathic Parkinson's disease (IPD) patients. We report our 22-year observations in 47 pathologically verified parkinsonian patients. In all the IPD cases with median follow-up of 3.7 years, RT was noted on at least one evaluation. Among other parkinsonian syndrome variants characterized by widespread subcortical pathology with median follow-up of 2.86 years, RT was seen in 31% of the cases. Our data indicate that the sites typically involved in IPD are sufficient to produce RT. 
Diagnosis and management of purulent pericarditis. Experience with pericardiectomy. Twelve cases of purulent pericarditis seen over 6 years are described. Staphylococcus aureus was the most common causative organism (six patients), and a respiratory infection was the most common preceding illness. The chest radiograph and echocardiogram were useful pointers to the diagnosis, but the electrocardiogram was not reliable. Antibiotics, surgical drainage, and pericardiectomy were used in all 12 cases. There was one death (8.3%), which occurred in a patient who was seen late. A review of the literature dealing with the diagnosis and management of this condition is presented. The importance of early diagnosis before a significant degree of cardiac tamponade occurs is noted. Although there is general agreement that surgical drainage is mandatory, the approach, methods of drainage, and extent of pericardial resection have been the subject of some discussion, and at least seven techniques are available. We conclude that pericardiectomy has a definite place in the management of purulent pericarditis. 
Recurrence of hepatitis C virus infection after orthotopic liver transplantation. Identification of the hepatitis C virus--the main cause of posttransfusion and sporadic non-A, non-B hepatitis--and the development of a diagnostic serological test have allowed us to study possible recurrence of this type of hepatitis after liver transplantation. Six of 34 consecutive transplant recipients were found to have had antibodies to hepatitis C before transplantation. All six patients had possible exposure to hepatitis C through blood transfusion or intravenous drug use. Five of the six patients were positive for antibodies to hepatitis C after 1 yr of follow-up. Two of these patients had clinical and histological evidence of acute viral hepatitis in their allografts. In one patient this led to hepatic injury and dysfunction of two successive grafts. In contrast, none of the twenty-eight patients who were seronegative for hepatitis C virus antibodies before transplantation has converted to seropositivity after transplantation despite perioperative blood transfusions. These results suggest that hepatitis C diagnosed serologically recurs in a minority of transplant recipients and that de novo seroconversion must be uncommon. 
Fingerstick glucose determination in shock. OBJECTIVE: To evaluate the accuracy of fingerstick glucose measurements in severely hypotensive patients. DESIGN: Prospective, nonrandomized comparison study. SETTING: Emergency department in a university hospital. PATIENTS: Twenty-five severely hypotensive patients (systolic blood pressure less than or equal to 80 mm Hg) and 39 normotensive patients. MEASUREMENTS: Simultaneous fingerstick reagent strip glucose, venous reagent strip glucose, and laboratory glucose values were compared. Data were analyzed using error-grid analysis. RESULTS: In hypotensive patients, the mean fingerstick glucose values were significantly lower than the values obtained either by venous reagent strip or laboratory glucose measurements. Fingerstick glucose values in the hypotensive group were 67.5% of laboratory glucose values, and were significantly lower than the values obtained in the normotensive group (91.8%, P less than 0.001). Only 36% of the hypotensive patients had fingerstick glucose values within the acceptable range of 20% of the laboratory glucose value. Thirty-two percent of hypotensive patients were incorrectly diagnosed as hypoglycemic (glucose less than 3.89 mmol/L [70 mg/dL]); 2 of these patients were actually hyperglycemic (glucose greater than 11.10 mmol/L [200 mg/dL]). Venous reagent strip measurements accurately reflected laboratory glucose values in both hypotensive and normotensive patients. CONCLUSIONS: Fingerstick glucose testing does not accurately represent venous glucose levels in severely hypotensive patients. If fingerstick glucose testing is relied on for these patients, errors in clinical management may be made. Venous reagent strip glucose testing correlates well with laboratory glucose measurements and should be the preferred method for rapid assessment of glucose level in critically ill patients with severe hypotension. 
Tinnitus suppression by cochlear implants. The beneficial effects of cochlear implants on tinnitus have been noted in several studies, but few detailed appraisals of the phenomenon have been made. Six patients fitted with the UCSF/Storz cochlear implant device were studied. The effects of use of the implant device on tinnitus were monitored, and suppression of tinnitus was tracked throughout periods of stimulation and poststimulation. Tinnitus was effectively suppressed in five of six patients with the device on and with noise input, and reduction of perceived tinnitus loudness occurred in four of six with the device on but without acoustic input to the speech processor. Unilateral stimulation frequently resulted in bilateral tinnitus suppression. These studies reveal that profound tinnitus suppression is obtained by patients using their cochlear implants. Further work is required to quantify the optimal mode of stimulation, but these findings suggest that tinnitus sufferers may ultimately benefit from development of electrical stimulation tinnitus suppression devices. 
Successful treatment of hepatosplenic candidiasis with a liposomal amphotericin B preparation. The case of a granulocytopenic patient with acute undifferentiated leukaemia and hepatosplenic candidiasis who was refractory to conventional deoxycholate amphotericin B (AmpB) and 5-flucytosine therapy is reported. He experienced severe AmpB-related side-effects, and was subsequently successfully treated with a pharmaceutical preparation of AmpB (5.7 g) entrapped in sonicated liposomes, composed of lecithin, cholesterol and stearylamine in a molar ratio of 4:3:1. Three months later, during maintenance chemotherapy, liposomal AmpB (5.1 g) was reinstituted due to the finding of biopsies positive for Candida albicans at bronchoscopy. After healing of the patient's fungal infection a left upper lobe resection was performed, which showed advanced fibrosis with signs of inflammation, but no evidence of fungal disease. Since no acute side-effects and only moderate hypokalaemia were observed, it appears that liposomal AmpB is superior to conventional AmpB treatment in granulocytopenic patients with hepatosplenic candidiasis and unbearable therapy-related side-effects. 
Localization of metallothionein in hair follicles of normal skin and the basal cell layer of hyperplastic epidermis: possible association with cell proliferation. Metallothionein is a low-molecular-weight metal-binding protein. Although it is inducible by a variety of agents and ubiquitously present in many tissues, its physiologic functions are still not clear. The present study was undertaken to determine the possible functions of metallothionein in both the proliferation and differentiation of epidermal keratinocytes. Metallothionein was detected immunohistochemically in hair matrix cells of the bulb and cells of the outer root sheath of anagen hair follicles, but not in dermal papillae in normal skin in the back of mice. In hyperplastic epidermal tissue, induced by either a phorbol ester tumor promoter or cholera toxin, the basal cells of the interfollicular epidermis stained strongly for metallothionein. Elevated expression of mRNA of the metallothionein gene was also demonstrated when the skin was stimulated by agents that induced hyperplasia. Papillomas produced by two-stage carcinogenesis protocols also stained for metallothionein. These observations suggest that metallothionein is involved in the proliferation of epidermal keratinocytes. 
Syndrome X and hyperventilation. The cardiorespiratory responses to exercise and forced hyperventilation were measured in 17 unselected patients with syndrome X (angina, positive exercise test, normal coronary arteriogram, no other cardiovascular disease) and compared with those in 15 healthy subjects. Forced hyperventilation produced hypocapnia and metabolic alkalosis but no chest pain or electrocardiographic change. Patients with syndrome X showed reduced maximum oxygen consumption with an increased respiratory exchange ratio at peak exercise, confirming that exercise was limited by skeletal muscle perfusion--and thus that the increase in cardiac output with exercise is limited in syndrome X as in heart failure. Arterial carbon dioxide tension (PCO2) homoeostasis during exercise was normal but the ventilatory cost of carbon dioxide excretion was increased in syndrome X (as in heart failure). End tidal PCO2 measurements correlated only poorly with arterial PCO2 in individual patients with syndrome X, providing a possible explanation for previous reports, based on end tidal PCO2 of inappropriate hyperventilation. Patients with syndrome X did not show inappropriate hyperventilation but they did show hyperventilation that was appropriate to maintain normal arterial PCO2 in the face of reduced cardiac reserve. 
Postoperative sepsis: reexplore or observe? Accurate indication from diagnostic abdominal paracentesis. OBJECTIVE: To determine if postoperative diagnostic abdominal paracentesis is a useful clinical tool in the abdominal evaluation of the critically ill septic patient. DESIGN: Retrospective review. SETTING: Surgical ICU patients in a Veterans Administration medical center. PATIENTS: Ten patients were studied from a total of 1,053 patients admitted to the surgical ICU between September 1985 and May 1989. INTERVENTIONS: Diagnostic abdominal paracentesis performed by the open or closed approaches. MEASUREMENTS AND MAIN RESULTS: Results are presented in three patient groups (A, B, and C): Group A (n = 4) had positive diagnostic abdominal paracentesis. Abdominal causes for the sepsis were found at reexploration. One of these four patients survived. Group B (n = 3) had negative diagnostic abdominal paracentesis. No abdominal septic source was found at reexploration; all three patients died. In group C (n = 3), diagnostic abdominal paracentesis was negative, patients were not reexplored, and all survived. Diagnostic accuracy correlated with three variables: a) the gross appearance and smell of the fluid, b) WBC count greater than 5000 or less than 500/mm3, and c) Gram stain demonstrating bacterial organisms. CONCLUSIONS: Diagnostic abdominal paracentesis proved accurate, reliable, simple, safe, and rapid in evaluating the abdomen in the postoperative septic patient. The use of this procedure should be considered in postoperative septic patients in whom an abdominal source for the sepsis needs to be excluded. 
A single intravenous infusion of gamma globulin as compared with four infusions in the treatment of acute Kawasaki syndrome BACKGROUND. Treatment of acute Kawasaki syndrome with a four-day course of intravenous gamma globulin, together with aspirin, has been demonstrated to be safe and effective in preventing coronary-artery lesions and reducing systemic inflammation. We hypothesized that therapy with a single, very high dose of gamma globulin would be at least as effective as the standard regimen. METHODS. We conducted a multicenter, randomized, controlled trial involving 549 children with acute Kawasaki syndrome. The children were assigned to receive gamma globulin either as a single infusion of 2 g per kilogram of body weight over 10 hours or as daily infusions of 400 mg per kilogram for four consecutive days. Both treatment groups received aspirin (100 mg per kilogram per day through the 14th day of illness, then 3 to 5 mg per kilogram per day). RESULTS. The relative prevalence of coronary abnormalities, adjusted for age and sex, among patients treated with the four-day regimen, as compared with those treated with the single-infusion regimen, was 1.94 (95 percent confidence limits, 1.01 and 3.71) two weeks after enrollment and 1.84 (95 percent confidence limits, 0.89 and 3.82) seven weeks after enrollment. Children treated with the single-infusion regimen had lower mean temperatures while hospitalized (day 2, P less than 0.001; day 3, P = 0.004), as well as a shorter mean duration of fever (P = 0.028). Furthermore, in the single-infusion group the laboratory indexes of acute inflammation moved more rapidly toward normal, including the adjusted serum albumin level (P = 0.004), alpha 1-antitrypsin level (P = 0.007), and C-reactive protein level (P = 0.017). Lower IgG levels on day 4 were associated with a higher prevalence of coronary lesions (P = 0.005) and with a greater degree of systemic inflammation. The two groups had a similar incidence of adverse effects (including new or worsening congestive heart failure in nine children), which occurred in 2.7 percent of the children overall. All the adverse effects were transient. CONCLUSIONS. In children with acute Kawasaki disease, a single large dose of intravenous gamma globulin is more effective than the conventional regimen of four smaller daily doses and is equally safe. 
Natural history and effectiveness of aspirin in asymptomatic patient with cervical bruits. The Asymptomatic Cervical Bruit Study Group. We report a multicenter study in progress involving a prospective follow-up of asymptomatic patients with cervical bruits. The project consists of two components. All patients meeting clinical criteria for eligibility undergo duplex ultrasonography at the time of entry into the study. Those with a carotid stenosis of 50% or greater are enrolled in a randomized placebo-controlled trial of aspirin. All other patients are followed up in a natural history study, also involving biannual clinical and duplex ultrasonographic examinations. Both clinical and anatomic outcomes are assessed. The project consists of a 3-year accrual phase and a 3-year follow-up phase with completion planned for May 1994. Total anticipated enrollment is 588 patients. 
Severe late postsplenectomy infection. In all, 1490 patients underwent splenectomy in Western Australia between 1971 and 1983, giving 7825 person years exposure. Thirty-three patients developed severe late postsplenectomy infection (septicaemia, meningitis or pneumococcal pneumonia requiring hospitalization) and three developed overwhelming postsplenectomy infection. The incidence and mortality rates of severe late postsplenectomy infection were 0.42 and 0.08 per 100 person years exposure respectively and for overwhelming postsplenectomy infection the incidence and mortality rates were 0.04 per 100 person years exposure. There were 628 splenectomies after trauma, giving 3922 person years exposure. Eight patients developed severe late postsplenectomy infection of whom one had overwhelming postsplenectomy infection. Following trauma, the incidence of severe late postsplenectomy infection was 0.21 per 100 person years exposure, with the incidence and mortality rates of overwhelming postsplenectomy infection being 0.03 per 100 person years exposure. Patients undergoing splenectomy have a 12.6-fold increased risk of developing late septicaemia compared with the general population. Splenectomy following trauma gives an 8.6-fold increased risk of late septicaemia. The majority of severe late postsplenectomy infections did not occur within the first 2 years and 42 per cent of severe late postsplenectomy infections occurred greater than 5 years after splenectomy. The low incidence of severe late postsplenectomy infection and overwhelming postsplenectomy infection makes statistical evaluation of the effectiveness of prophylactic antibiotics, vaccination and splenic repair most difficult. 
Risk of neoplasia and malignancy in "dominant" thyroid swellings. OBJECTIVE--To determine the risk of neoplasia and malignancy in "dominant" thyroid swellings. DESIGN--Prospective analysis during six years. SETTING--Thyroid clinic serving the Grampian region. PATIENTS--574 consecutive patients presenting with a discrete thyroid swelling, of whom 179 (31%) were classified clinically as having a dominant area of enlargement within a multinodular gland. RESULTS--After clinical and cytological assessment 77 dominant swellings were excised. Of the excised swellings, 45 were non-neoplastic and 32 neoplastic, including 11 malignant lesions. The minimum incidence of neoplasia and malignancy in all 179 dominant swellings was therefore 18% and 6% respectively. CONCLUSION--Dominant thyroid swellings should be regarded with greater clinical suspicion than has been traditional. 
Idazoxan treatment in progressive supranuclear palsy. To confirm the preliminary report that increases in norepinephrine neurotransmission improve motor performance, we administered the investigational drug idazoxan (IDA) to nine patients with progressive supranuclear palsy (PSP) according to a double-blind crossover protocol. There were seven women and two men, whose mean age was 70 years and mean duration of illness 4 years. All had an advanced parkinsonian syndrome, supranuclear ocular motor palsies, and poor responses to dopaminergic drugs. During administration of 40 mg tid of IDA, the total score and the motor subscale score of the United Parkinson's Disease Rating Scale significantly decreased. Features that improved most included mobility, balance, gait, and measures of digital dexterity. There were no significant changes in any measure during placebo administration. Corticobulbar manifestations and eye movements were not significantly improved during treatment. Side effects of IDA included transient hypertension, tachycardia, action tremor, flushing, and sweating, but none was so severe that any patient withdrew from the study. Among the few attempted treatments of PSP, IDA is the first medication shown in a double-blind study to improve aspects of motor function. 
Clinical characteristics of acromegalic patients whose pituitary tumors contain mutant Gs protein. Activating mutations in the gene for the alpha-chain of Gs, the stimulatory regulator of adenylyl cyclase, have been identified in human GH-secreting pituitary tumors. Using the polymerase chain reaction and allele-specific oligonucleotide hybridization, we screened 25 GH-secreting tumors for the presence of the activating mutations. We also reviewed the clinical charts of the patients from whom the tumors were removed. Of 25 tumors, 10 (40%) contained activating mutations. Patients in the mutation-positive group came to surgery with smaller tumors and had lower GH levels. The activating mutations identify a subgroup of GH-secreting pituitary tumors that probably arise from a shared oncogenic mechanism. 
Peak expiratory flow rate and the acute chest syndrome in homozygous sickle cell disease. The peak expiratory flow rate (PEFR) was studied in 20 matched pairs of children with homozygous sickle cell disease with either no episodes or six or more episodes of acute chest syndrome. The pairs were carefully matched for height and a highly significant reduction in PEFR was observed in children with multiple episodes of acute chest syndrome. Lateral and anteroposterior chest diameters and chest circumference correlated with PEFR but did not differ between index and control cases. The most likely cause of the reduced PEFR in children with multiple episodes of acute chest syndrome is an accumulating pulmonary fibrosis that decreases lung compliance. 
Induction of the protooncogene c-fos and recovery of cytosolic adenosine triphosphate in reperfused liver after transient warm ischemia: effect of nitrone free-radical spin-trap agents. Ischemia and reperfusion stimulate several adenosine triphosphate (ATP)-dependent processes involving release of substances including free radicals. This cellular response is mediated through receptors responsive to transcriptional products of gene expression; c-fos acts as a transcriptional factor involved in the regulation of genes associated with cellular proliferation and differentiation. We hypothesized that nitrone free-radical spin traps promote restoration of cytosolic ATP during reperfusion and prevent c-fos induction. Four control rats had no ischemia. Global hepatic ischemia was induced in 19 rats in four groups: saline solution, phenyl-N-tert-butyl nitrone (PBN), alpha 1-pyridyl-N-oxide N-tert-butyl nitrone (POBN), and 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). ATP and intracellular pH were measured at intervals before, during, and after ischemia. At 90 minutes of reperfusion, liver c-fos mRNA was measured. A fourfold elevation of c-fos occurred in the saline-treated group (p less than 0.001). PBN and POBN groups did not differ from the saline group. DMPO resulted in significantly less induction of c-fos than did NS. ATP depletion and recovery in all treatment groups was similar to that of the saline group. We conclude that (1) nitrone spin traps do not prevent c-fos induction or alter the pattern of ATP recovery after hepatic ischemia and reperfusion and (2) c-fos induction is not necessary for restoration of ATP, but the rate of ATP restoration is inversely related to c-fos induction. 
Anaesthesia-free extracorporeal shock wave lithotripsy in patients with renal calculi. Modern extracorporeal shock wave lithotripsy can be performed with combined ECG and respiratory triggered shock wave release. Disconnecting the ECG triggering increases the risk of ventricular arrhythmias, including potentially malignant ones. The aim of this study was to assess the relationship of any sympatho-adrenal excitation as a possible explanation for the occurrence of cardiac arrhythmia. Plasma catecholamine levels were assessed in 5 patients during and after 50 min of anaesthesia-free extracorporeal shock wave lithotripsy for the treatment of calculi in the upper pole of the left kidney. Venous blood sampling showed no significant increase in catecholamines (epinephrine, norepinephrine and dopamine) during or after treatment. The heart rate and arterial blood pressure were measured simultaneously and showed no significant increase when shock waves were released during ECG triggering. However, when disconnecting the ECG-triggering mode, the incidence of ventricular extrasystoles on Holter monitoring became more apparent during respiratory triggered shock wave release only, although there was no rise in plasma catecholamine levels. These data suggest that cardiac arrhythmias are related to direct and accidental mechanical stimulation of the heart rather than to any sympatho-adrenal discharge during shock wave release. 
Intracisternal recombinant tissue plasminogen activator after aneurysmal subarachnoid hemorrhage. Fifteen patients undergoing surgery within 48 hours of aneurysm rupture were administered recombinant tissue plasminogen activator (rt-PA) directly into the basal subarachnoid cisterns after minimal surgical clot removal and aneurysm clipping. Preoperatively, 13 patients had diffuse or localized thick subarachnoid blood clots on computerized tomography (CT), and two had diffuse thin clots. The rt-PA was given as a single intraoperative injection of 7.5 mg (one patient), 10 mg (nine patients), or 15 mg (five patients). Postoperative cisternal drainage was employed in three patients. All patients except one demonstrated partial to complete cisternal clot clearance on CT scans within 24 hours after surgery. The patient who showed no clot reduction was the only patient in this series to develop symptomatic vasospasm and was the only fatality, dying 8 days after rupture. No vasospasm was seen on follow-up cerebral angiography in six of the 14 responding patients, and mild-to-moderate arterial narrowing was seen in at least one major cerebral artery in the remaining eight patients. Severe angiographic vasospasm was not seen, although the patient who died did not undergo repeat angiography. There was one major complication early in the series which seemed clearly related to treatment, and that was a large extradural hematoma occurring within several hours of craniotomy. Intrathecal fibrinolytic treatment appears effective in clearing subarachnoid clot and reducing vasospasm, and may be associated with acceptable risks if given to patients with large-volume subarachnoid hemorrhages at high risk for severe vasospasm. 
Coronary atherosclerotic plaques with and without thrombus in ischemic heart syndromes: a morphologic, immunohistochemical, and biochemical study. We investigated incidence, severity, and distribution of coronary atherosclerosis, acute thrombosis, and plaque fissuring in ischemic heart disease (both unstable-acute syndromes and chronic ischemia) and in nonischemic controls. We also studied the structural, immunohistochemical, and biochemical profile of plaques, with and without thrombus, including morphometry, immunophenotyping of inflammatory infiltrates, cytokine presence, and ultrastructural features. Critical coronary stenosis was almost the rule in both acute and chronic ischemic series (greater than 90%) whereas it reached 50% in control subjects. Thrombosis was principally characteristic of unstable-acute ischemic syndromes (unstable angina, 32%; acute myocardial infarction, 52%; cardiac sudden death, 26%) but was also found in chronic ischemia (stable angina, 12%; ischemic cardiomyopathy, 14%) and in control subjects (4%). Plaque fissuring without thrombus occurred in low percentages in lipid-rich, severe eccentric plaques in most series. Major differences were found between pultaceous-rich versus fibrous plaques rather than between plaques with or without thrombus. Pultaceous-rich plaques were frequent in sites of critical stenosis, thrombosis, and ulceration. Inflammatory infiltrates, i.e., T cells, macrophages, and a few beta cells, mostly occurred in lipid-rich, plaques unrelated to thrombus. In adventitia, infiltrates were a common finding unrelated to any syndrome. Necrotizing cytokines such as alpha-TNF were immunohistochemically detected in macrophages, smooth muscle, and intimal cells and detected by immunoblotting in 67% of pultaceous-rich plaques, either with or without thrombus. Immune response mediators such as IL-2 were also expressed in analogous plaques but in a minor percentage (50%-40%). Media were extensively damaged in severely diseased vessels with and without thrombus. Ultrastructural study showed that the fibrous cap was either highly cellular or densely fibrillar. Intimal injury with collagen exposure was often associated with platelet adhesion, whereas foamy cell exposure was not. In conclusion, investigated parameters were essentially similar in plaques, both with and without thrombus, whereas major differences were found between pultaceous-rich and fibrous plaques. Since platelets adhere to exposed collagen and not to foam cells, the type of exposed substrates could play a major role in thrombosis. 
Gastroesophageal reflux, as measured by 24-hour pH monitoring, in 509 healthy infants screened for risk of sudden infant death syndrome. Continuous long-term esophageal pH monitoring has become the preferred test to quantify acid gastroesophageal reflux. Because reflux to a limited extent is physiologic, the determination of optimal thresholds to separate normal from abnormal reflux is mandatory. Esophageal pH was measured during 24 hours in 509 healthy thriving infants, aged 3 days to 1 year, using a glass microelectrode with an external reference electrode connected to a portable recorder. Percentiles of the four parameters studied (reflux index or percent of the investigation time with a pH less than 4, number of episodes with a pH less than 4 during 24 hours, number of episodes lasting greater than 5 minutes, the duration of the longest episode (in minutes) are presented. A percentile curve of the reflux index regarding the age distribution shows that the normal range for the reflux index during the first 12 months of life is about 10% (95 percentile), decreasing from 13% at birth to 8% at 12 months. Application of an age-related percentile curve offers a close-to-reality possibility of data interpretation and illustrates that there is inevitably an overlap of data between normal and abnormal populations, because reflux is a phenomenon occurring to some extent in every human being. 
Role of nitric oxide in renal medullary oxygenation. Studies in isolated and intact rat kidneys. We investigated the role of the endothelial-derived relaxing factor nitric oxide (NO) in the homeostasis of O2 supply to the renal medulla, a region normally operating on the verge of hypoxia. Sensitive Clark-type O2 microelectrodes were inserted into renal cortex and medulla of anesthetized rats. The inhibitor of NO formation, L-NG-monomethylarginine (LNMMA), while increasing blood pressure and reducing renal blood flow, decreased medullary pO2 from 23 +/- 3 mmHg to 12 +/- 3 (P less than 0.001), with no change in the cortex. These responses were promptly reversed by L-arginine, which bypasses the LNMMA blockade. In isolated rat kidneys, LNMMA reduced perfusion flow without altering glomerular filtration rate, and augmented deep medullary hypoxic injury to thick ascending limbs from 68 to 90% of the tubules (P less than 0.02). These changes were prevented by L-arginine. Nitroprusside had a protective effect upon thick limb injury. Finally, in a previously reported model of radiocontrast nephropathy (1988. J. Clin. Invest. 82:401), LNMMA increased the severity of renal failure (final plasma creatinine from 2.3 +/- 2 mg% to 3.4 +/- 3, P less than 0.005) and the proportion of damaged thick limbs (from 24 +/- 6% to 53 +/- 9, P less than 0.01). Nitrovasodilatation may participate in the balance of renal medullary oxygenation and play an important role in the prevention of medullary hypoxic injury. 
Intrarenal hemodynamics in patients with essential hypertension. Intrarenal hemodynamics were estimated clinically in essential hypertension. Two-week studies were performed in 30 patients with essential hypertension who were given a regular sodium diet in the first week and a sodium-restricted diet in the second week. Intrarenal hemodynamic parameters such as afferent arteriolar (preglomerular) resistance, efferent arteriolar resistance, and glomerular hydrostatic pressure were calculated from renal clearances and plasma total protein concentration measured on the last day of the regular sodium diet. Calculations were based on Gomez's equations with the assumption that the gross filtration coefficient of glomerular capillaries was normal. The increase in afferent arteriolar resistance (8,100 +/- 500 dyne.sec.cm-5) was significantly correlated with an elevation in mean arterial pressure (120 +/- 2 mm Hg), whereas glomerular pressure (56 +/- 1 mm Hg) and efferent arteriolar resistance (2,500 +/- 100 dyne.sec.cm-5) remained normal. The renal function curve (pressure-natriuresis relation) was drawn by plotting urinary sodium excretion on the y axis as a function of mean arterial pressure on the x axis, both of which were measured on the last 3 days of each week. The extrapolated x intercept (107 +/- 2 mm Hg) of the renal function curve was strongly correlated in a 1:1 fashion with the sum of the arterial pressure drop from the aorta to the renal glomeruli plus the opposing pressures against glomerular filtration at glomeruli (r = 0.7, p less than 0.001) on the regular sodium diet, suggesting that the difference between mean arterial pressure on the regular sodium diet and the extrapolated x intercept represented the effective filtration pressure across the glomerular capillaries on the regular sodium diet. 
Identity of rearranged LINE/c-MYC junction sequences specific for the canine transmissible venereal tumor. The canine transmissible venereal tumor is a naturally occurring neoplastic disease that affects the external genitalia of both sexes and is transmitted during coitus. Cytogenetic and immunologic studies demonstrated that tumors from different parts of the world are very similar, suggesting that they are transferred from one animal to another by the transplantation of viable cells. We found that the c-MYC oncogene was rearranged in this tumor by the insertion of a transposable genetic element sequence (known as LINE, long interspersed element) 5' to the first exon. The amplification of a DNA segment located in the junction of the LINE genome and c-MYC upstream sequences enabled the testing of the similarity of transmissible venereal tumor samples collected independently in different parts of the world. Oligonucleotide primers flanking the LINE/c-MYC junction were used to amplify a 340-base-pair segment and nested primers amplified a 280-base-pair segment. A fifth oligonucleotide used as a probe contained the actual junction sequence. All of the tumors analyzed revealed the existence of the specific bands, which were absent in normal canine DNA samples. The amplified segments obtained from all of the tumors analyzed were identical in size and nucleotide sequence, suggesting transmission of the original rearranged cell itself, as opposed to independent events of LINE insertion in a "hot spot.". 
Short-term oral zinc supplementation does not improve chronic hepatic encephalopathy. Results of a double-blind crossover trial. The effect of short-term oral zinc supplementation (zinc sulfate 600 mg/day) on hepatic encephalopathy, was assessed in a double-blind, crossover trial. Fifteen cirrhotic patients with stable, chronic hepatic encephalopathy were randomized to receive either oral zinc or a placebo for 10 days. Following a two-week washout period, these were crossed over to the alternate treatment. Conn's index, which comprises the evaluation of the mental state, asterixis, number connection test, EEG record, and plasma ammonia, was used to score the degree of hepatic encephalopathy, both at the beginning and end of each treatment period. Serum zinc was significantly raised after oral zinc administration and reached the levels observed in cirrhotics without hepatic encephalopathy. Despite this, however, no modification in the parameters included in Conn's index were observed. In conclusion, this study failed to confirm that short-term oral zinc supplementation improves chronic hepatic encephalopathy. 
Lymphoepithelioma-like carcinoma of the lung. Historically lymphoepithelioma was a term used to describe an undifferentiated mucosal carcinoma with a lymphocytic component arising only from the nasopharynx, although recently, lymphoepithelioma-like carcinoma has been found to occur as a primary tumor of the lung. Thus far, five patients have been documented as having this rare anatomical presentation. The patient that is being presented is the latest case of lymphoepithelioma-like carcinoma of the lung and will be compared clinically and histologically with the other four cases. The case is presented in order to discuss optimal methods of diagnoses and treatment for this condition. 
Helicopter transport of the patient with acute burns. Helicopter transportation of acutely injured or ill patients has become common practice at most major medical centers. However, its specific effectiveness in the transportation of acute-condition patients with burns has never been critically assessed. This study, for the period 1984 through 1988, evaluated the use of the helicopter for transportation of acute-condition patients with burns to a regional burn center for a rural area. It is concluded that helicopter transport within a 180-mile radius in a non-hospital-based system is not appreciably faster than is ambulance transport, and does not clinically benefit most burned patients. Consideration such as safety, cost, and working space are discussed. It is recommended that at least one of three criteria be met before helicopter transfer is considered for patients with burns: the surface area involved should be enough to require a formal fluid resuscitation, an inhalation injury should be present or suspected, or there should be a possible need for an escharotomy. 
Chemotherapy with 5-fluorouracil (5-FU) and cisplatin or 5-FU, cisplatin, and vinblastine for advanced non-small cell lung cancer. A randomized phase II study of the cancer and leukemia group B. Two hundred forty-seven patients with previously untreated nonresectable non-small cell lung cancer (NSCLC) were entered in a prospective, randomized Phase II trial. Response assessment was possible in 232 patients, and 237 patients were evaluable for survival. Thirteen partial responses (11%) and 5 regressions (4%) of evaluable disease were obtained for the 116 patients treated with 5-fluorouracil (5-FU) and cisplatin (C) (95% confidence interval [CI], 8.5% to 21.5%). The median time to progression was 2.2 months and the median survival time was 4.6 months for 5-FU plus C. Twenty-three partial responses (20%) and 4 regressions (3%) of evaluable disease were obtained for the 116 patients treated with 5-FU, C, and vinblastine (V) (95% CI, 15.3% to 30.7%). The median time to progression was 2.8 months and the median survival time was 5.6 months for 5-FU, C, and V. The 5-FU and C doses were equivalent in the two treatment regimens. Sixteen of 85 patients (19%) with a performance status of 0 and 18 of 103 patients (17%) with a performance status of 1 responded, whereas only 2 of 44 patients (5%) with a performance status of 2 or greater responded (P = 0.009). Patients who had received locoregional radiation therapy had a lower overall response rate then those in the no prior radiation therapy group (P = 0.028). The median survival time for patients with a performance status of 0 or 1 was 6.3 months compared with 1.9 months for patients with a performance status of 2 or greater (P less than 0.001). Performance status also appeared to be a significant factor for time to progression. More frequent and severe leukopenia, fever, genitourinary (GU) toxicity, and pulmonary toxicity was reported with 5-FU, C, and V. There were three treatment-related deaths with 5-FU, C, and V and one treatment-related death with 5-FU plus C. Grade III/VI myelotoxicity was not influenced by prior radiation therapy or performance status. Neither regimen is active enough to be considered as standard therapy for advanced NSCLC. 
Type I human T cell leukemia virus tax protein transforms rat fibroblasts through the cyclic adenosine monophosphate response element binding protein/activating transcription factor pathway. The Tax oncoprotein of the type I human T cell leukemia virus (HTLV-I) activates transcription of cellular and viral genes through at least two different transcription factor pathways. Tax activates transcription of the c-fos proto-oncogene by a mechanism that appears to involve members of the cAMP response element binding protein (CREB) and activating transcription factor (ATF) family of DNA-binding proteins. Tax also induces the nuclear expression of the NF-kappa B family of rel oncogene-related enhancer-binding proteins. We have investigated the potential role of these CREB/ATF and NF-kappa B/Rel transcription factors in Tax-mediated transformation by analyzing the oncogenic potential of Tax mutants that functionally segregate these two pathways of transactivation. Rat fibroblasts (Rat2) stably expressing either the wild-type Tax protein or a Tax mutant selectively deficient in the ability to induce NF-kappa B/Rel demonstrated marked changes in morphology and growth characteristics including the ability to form tumors in athymic mice. In contrast, Rat2 cells stably expressing a Tax mutant selectively deficient in the ability to activate transcription through CREB/ATF demonstrated no detectable changes in morphology or growth characteristics. These results suggest that transcriptional activation through the CREB/ATF pathway may play an important role in Tax-mediated cellular transformation. 
Management of persistent or recurrent urinary incontinence after placement of artificial urinary sphincter. A rational systematic approach is presented in the evaluation of 14 men with persistent or recurrent urinary incontinence after placement of the AMS800 artificial urinary sphincter. Mechanical malfunctions, including device leaks and control assembly malfunctions, may often be discovered with physical examination and radiographic evaluations. Nonmechanical malfunctions, such as cuff erosion, inadequate cuff compression and functional urethral atrophy, can be diagnosed with perfusion sphincterometry, urethroscopy and a filling cystometrogram, all combined in 1 simplified technique. With the presented algorithm the over-all success rate after 1 revision was 82%. Mechanical malfunctions appear to have a better revision rate of success than nonmechanical malfunctions (100% versus 71.5%, respectively). 
A phase II study of mitoxantrone, etoposide, and thiotepa with autologous marrow support for patients with relapsed breast cancer. To further improve the effect of high-dose chemotherapy in the treatment of locally advanced and metastatic breast cancer, we sought to develop a second active high-dose noncross-resistant regimen to use in tandem with our customary high-dose regimen of cyclophosphamide, etoposide, and cisplatin (CVP). We performed a phase II trial of high-dose mitoxantrone 30 mg/m2, etoposide 200 mg/m2 every 12 hours x 6, and thiotepa 250 mg/m2 x 3 days (MVT) in 31 patients with heavily pretreated metastatic breast cancer and one with locally advanced chemotherapy-refractory breast cancer. These patients were ineligible for high-dose CVP chemotherapy because of the amount of prior treatment and poor-response status. Of the 32 patients, 14 responded to cycle 1, did not experience any grade 4 toxicity, and received a second cycle of MVT. Overall, seven of 31 patients achieved a complete response (CR; 23%). Four of the 14, who were partial responders to the first cycle, achieved a CR after the second cycle. The overall response rate was 19 of 31 (61%) with an overall median freedom from progression of 4 to 5 months and an overall median survival of 9 months. Toxicity consisted primarily of mucositis (grade 3 or 4 in 69%). The results indicate that high-dose MVT produces significant activity, even in heavily pretreated patients. Administration of a second cycle of high-dose therapy with MVT increased the CR rate, and the morbidity and mortality from the second cycle were not greater than that for the first cycle. Because of the high incidence of grade 3 or 4 mucositis with this regimen, we are currently completing a follow-up study of high-dose mitoxantrone and thiotepa alone. 
Ibopamine in chronic congestive heart failure: hemodynamic and neurohumoral effects. Ibopamine is a dopamine-like drug that shows mainly vasoactive properties, predominantly acting on dopamine1-(DA1-) and DA2-adrenoceptors. Ibopamine increases cardiac output, reduces peripheral vascular resistance, and increases renal blood flow, exerting a lesser effect on preload parameters. This hemodynamic improvement is also present even after relatively long-term treatment. There is no evidence of pharmacologic tolerance. In relation to DA2-activation, ibopamine modulates the neurohumoral consequences of heart failure with decreases in plasma renin activity and aldosterone and norepinephrine plasma levels, an effect that can be beneficial in the long-term treatment of heart failure patients. 
Paroxysmal kinesigenic choreoathetosis with abnormal electroencephalogram during attacks. An 18-year-old man with paroxysmal kinesigenic choreoathetosis (PKC) showed rhythmic electroencephalographic (EEG) discharges of 5-Hz spikes over the entire scalp during episodes. The EEG findings in this case suggest that PKC may have an epileptogenic basis. 
Quantitation of vascular outflow by measurement of impedance. One of the most important determinants of graft patency is the degree and character of vascular outflow. This study was designed to evaluate input impedance as a functional assessment of the outflow bed of vascular grafts. Four distinct outflow environments were created for external jugular vein conduits in 42 New Zealand white rabbits. Vein grafts (n = 14) were fashioned as end-to-side common carotid interposition bypass grafts. Arteriovenous fistulas (n = 15) were created by side-to-side anastomosis of the distal common carotid artery and linguofacial vein. Arteriovenous fistulas with outflow obstruction (n = 7) were fistulas with a metal clip partially obstructing the distal outflow channel (1 mm lumen). Vein graft/arteriovenous fistula combinations (n = 6) consisted of a vein graft and arteriovenous fistula in series. Pressure and flow in the external jugular vein were measured, and input impedance spectra were calculated by Fourier methods. By use of a PC-based acquisition and processing system, impedance results for 20 cardiac cycles could be obtained in approximately 10 minutes. The results revealed that vein grafts typically demonstrated high resistance to steady state flow (Rin = 235 +/- 50 x 10(3) dyne . sec/cm-5) and steadily decreasing impedance to pulsatile flow resulting in a characteristic impedance (Z0; average of fourth to tenth harmonics) of 35.5 +/- 8.0 x 10(3) dyne . sec/cm-5. Phase angle values were usually negative, especially at low harmonics (first harmonic phase angle = -1.11 +/- 0.10 radians) indicating that flow led pressure. In contrast, arteriovenous fistula Rin was minimal (6.3 +/- 1.4 x 10(3) dyne . sec/cm-5; p less than 0.05 compared to vein graft, and the impedance was flat across the frequency spectrum (Z0 = 8.5 +/- 1.5 x 10(3) dyne . sec/cm-5; p less than 0.05) with pressure and flow nearly in phase (first harmonic phase angle = -0.05 +/- 0.10 radians). Creation of outflow obstruction in arteriovenous fistulas resulted in significantly elevated Rin (136 +/- 41 x 10(3) dyne/sec . cm-5; p less than 0.05 compared to arteriovenous fistula and Z0 (23 +/- 9 x 10(3) dyne . sec/cm-5, p less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS). 
Serum concentrations of tumour necrosis factor alpha in childhood chronic inflammatory bowel disease. Serum tumour necrosis factor alpha (TNF alpha) concentrations were measured by enzyme linked immunoadsorbent assay in 31 normal children and during 65 episodes of clinical remission and 54 episodes of relapse in 92 children with chronic inflammatory bowel disease. An appreciable rise in TNF alpha was found only in children in relapse of ulcerative colitis and colonic Crohn's disease. The group of children with small bowel Crohn's disease in relapse did not show increases of TNF alpha above control concentrations, despite an equivalent rise in disease indices. Height velocity was depressed in children with relapse of large bowel Crohn's disease and ulcerative colitis compared with the equivalent condition in remission. The impairment of growth velocity was significantly greater in relapse of large bowel Crohn's disease and ulcerative colitis than in small bowel Crohn's disease alone, although for the subgroups in stage 1 puberty (prepubertal) the differences were not significant. Inadequate growth in chronic inflammatory bowel disease is currently ascribed to inadequate nutrition and TNF alpha may contribute to this through its cachexia inducing effects. It may, in addition, diminish pituitary growth hormone release. These results suggest that production of TNF alpha may be associated with growth failure in relapse of colonic inflammatory bowel disease. 
Three-dimensional characterization of human ventricular myofiber architecture by ultrasonic backscatter. Normal human left ventricular architecture comprises a highly aligned array of cardiac myofibers whose orientation depends on transmural location. This study was designed to determine whether measurement of integrated backscatter could be used detect the progressive transmural shift of myofiber alignment that occurs from epicardium to endocardium in human ventricular wall segments. Integrated backscatter was measured at 32 transmural levels in seven cylindrical biopsy specimens (1.4 cm diam) sampled from normal regions of six explanted fixed human hearts by insonification of samples at 180 independent angles in 2 degrees steps around their entire circumference with a 5-MHz broadband piezoelectric transducer. Histologic analysis was performed to determine fiber orientation. Integrated backscatter varied approximately as a sinusoidal function of the angle of insonification at each transmural level. Greater integrated backscatter was observed for insonification perpendicular as compared with parallel to fibers (difference = 14.5 +/- 0.6 dB). Ultrasonic analysis revealed a progressive transmural shift in fiber orientation of approximately 9.2 +/- 0.7 degrees/mm of tissue. Histologic analysis revealed a concordant shift in fiber orientation of 7.9 +/- 0.8 degrees/mm of tissue. Thus, human myocardium manifests anisotropy of ultrasonic scattering that may be useful for characterization of the intramural fiber alignment and overall three-dimensional organization of cardiac myofibers. 
Plasma catecholamines in patients with presinusoidal portal hypertension: comparison with cirrhotic patients and nonportal hypertensive subjects. During a hemodynamic study, plasma catecholamine concentrations were measured in the pulmonary artery and in the hepatic vein in 18 presinusoidal portal hypertensive patients. Results were compared with those in 15 nonportal hypertensive subjects and in 24 cirrhotic patients in good condition (grade A, according to Pugh's classification). Plasma norepinephrine concentrations in the pulmonary artery or in the hepatic vein were not significantly different between nonportal hypertensive subjects (mean +/- S.E.M.: 271 +/- 36 and 83 +/- 11 pg/ml, respectively) and presinusoidal portal hypertensive patients (273 +/- 33 and 84 +/- 11 pg/ml, respectively). These concentrations were, however, elevated in cirrhotic patients (408 +/- 47 and 256 +/- 45 pg/ml, p less than 0.05 in comparison with the two other groups). These differences suggest that increased sympathetic nervous activity in cirrhosis is associated with the presence of liver disease or increase in sinusoidal pressure. Differences in plasma epinephrine concentrations were not significant among the three groups of patients. However, the existence of a significant correlation between pulmonary artery plasma epinephrine concentration and cardiac index (r2 = 0.46, p less than 0.01) in patients with presinusoidal portal hypertension suggests that the adrenal medulla could play a role in the pathophysiology of the hyperkinetic syndrome of these patients. 
MRC European Carotid Surgery Trial: interim results for symptomatic patients with severe (70-99%) or with mild (0-29%) carotid stenosis. European Carotid Surgery Trialists' Collaborative Group The European Carotid Surgery Trial is a multicentre trial of carotid endarterectomy for patients who, after a carotid territory non-disabling ischaemic stroke, transient ischaemic attack, or retinal infarct, are found to have a stenotic lesion in the relevant (ipsilateral) carotid artery. Over the past 10 years 2518 patients have been randomised, and the mean follow-up is now almost 3 years among the 2200 thus far available for analysis of the incidence of strokes that lasted more than 7 days. For the patients with "moderate" (30-69%) stenosis on their prerandomisation angiogram the balance of surgical risk and eventual benefit remains uncertain, and full recruitment continues. For 374 patients with only "mild" (0-29%) stenosis there was little 3-year risk of ipsilateral ischaemic stroke, even in the absence of surgery, so any 3-year benefits of surgery were small, and were outweighed by its early risks. For 778 patients with "severe" (70-99%) stenosis, however, the risks of surgery were significantly outweighed by the later benefits: although 7.5% had a stroke (or died) within 30 days of surgery, during the next 3 years the risks of ipsilateral ischaemic stroke were (by life-table analysis) an extra 2.8% for surgery-allocated and 16.8% for control patients (a sixfold reduction, p less than 0.0001). There was also a small reduction in other strokes, and at 3 years the total risk of surgical death, surgical stroke, ipsilateral ischaemic stroke, or any other stroke was 12.3% for surgery and 21.9% for control (difference 9.6% SD 3.3, 2p less than 0.01). The main concern was to avoid disabling or fatal events, and, among severe stenosis patients, 3.7% had a disabling stroke (or died) within 30 days of surgery, an extra 1.1% surgery versus 8.4% control (p less than 0.0001) had a disabling or fatal ipsilateral ischaemic stroke by 3 years, and the total 3-year risk of any disabling or fatal stroke (or surgical death) was 6.0% surgery versus 11.0% control (overall difference 5.0% SD 2.3, 2p less than 0.05); but, for disabling or fatal stroke the control risks seemed to diminish after the first year, so delay of surgery by just a few months after clinical presentation might make this overall difference non-significant. 
Management of advanced retinopathy of prematurity in the older patient. The authors studied 11 eyes of 10 patients who complained of a recent decrease in vision and whose eyes had the clinical appearance of stage 5 retinopathy of prematurity (ROP) as diagnosed by the presence of a dense, opaque retrolenticular membrane. Patients ranged in age from 4 to 33 years, and birth weights ranged from 680 to 1077 g. All eyes underwent vitrectomy, lensectomy, and membrane peeling and were found intraoperatively to have areas of retina that were attached (stage 4B). Preoperatively, a reproducible visual-evoked potential waveform appeared to better predict this retinal configuration and potential retinal function than did the contact B scan ultrasound of the globe. Postoperatively, seven (63.6%) eyes demonstrated an improvement in vision. Vitreous surgery may be beneficial in selected eyes of older patients with advanced ROP to clear media opacities and to uncover areas of functional, attached retina, which may allow these patients to more effectively use the vision they possess. 
Pharmacologic elevation of blood inorganic phosphate in hypoxemic patients with COPD. We have shown that in patients with COPD, myocardial efficiency during exercise is enhanced following acute elevations of plasma phosphate (Pi). A decrease in Hb-O2 affinity (increase in P50) was not responsible for the improvement. We postulated that the physiologic benefit was due to the acute reversal of a subclinical myocardial Pi depletion. To further test this hypothesis in a chronic state, we studied nine stable hypoxemic (PaO2 = 64 +/- 2 mm Hg [+/- SEM]) patients with COPD over five weeks: two weeks at normal plasma Pi; and three weeks at elevated plasma Pi, induced by etidronate disodium (Didronel; 750 mg orally daily). Administration of etidronate disodium increased (p less than 0.05) plasma level of Pi (4.4 +/- 0.2 to 5.8 +/- 0.1 mg/dl), RBC level of Pi (3.1 +/- 0.2 to 4.1 +/- 0.2 mg/dl), RBC level of 2,3-DPG (16.2 +/- 1.1 to 21.3 g+/- 1.3 mumol/g of Hb) and P50 (23.7 +/- 0.5 to 26.0 +/- 0.8 mm Hg). At the end of the treatment, the widening of the C(a-v)O2 with exercise (7.1 +/- 0.8 to 8.9 +/- 0.6 ml/dl) was less pronounced than under control conditions (6.9 +/- 0.4 to 10.1 +/- 0.6 ml/dl; p less than 0.02); concomitantly, the crossover point (COP; the PaO2 below which a rightward-shifted Hb-O2 curve causes the C(a-v)O2 to become narrower rather than wider) increased (37 +/- 2 to 49 +/- 1 mm Hg). Indicators of myocardial work efficiency were not affected by etidronate disodium at rest or during exercise. We postulate that during exercise the potential beneficial effect of the rightward shift of the Hb-O2 curve upon cardiac function was negated by the fall of PaO2 to or below the COP level, a situation which would limit increases in tissue O2 extraction. 
Methods to diminish intraoperative blood loss. With the subcutaneous injection of a saline-vasopressor solution under donor sites and debrided areas, a significant reduction in intraoperative blood transfusions was accomplished. No problems in healing of donor sites or skin grafts were encountered. Vasodilating anesthetics and ketamine can overcome the local vasopressor action. Discontinuing or reducing the concentration of these agents results in less bleeding from the wound. 
Facial dystonia, essential blepharospasm and hemifacial spasm. Movement disorders, or dyskinesias, in the facial region may be categorized in several ways. Dystonic movement disorders in the cranial-cervical region, including essential blepharospasm, Meige syndrome and spasmodic torticollis, are characterized by uncontrollable squeezing movements in the face and neck. These disorders typically present in the fifth and sixth decades of life. Essential blepharospasm is particularly debilitating, as the involuntary eyelid closure that accompanies this condition may result in functional blindness with an otherwise normal visual pathway. Hemifacial spasm is an intermittent, unilateral, spasmodic contraction of the muscles innervated by the facial nerve. This disorder usually presents in the third or fourth decade and has a different underlying pathophysiology than the dystonias. Botulinum A toxin therapy has largely supplanted surgical intervention in the treatment of essential blepharospasm and hemifacial spasm. 
Metastatic angiosarcoma of the brain. Two patients with metastatic angiosarcoma of the brain are described. In one, a 17-year-old man, the tumor was located at the pineal region and exhibited significant vascularity. It was sensitive to radiation therapy and disappeared after radiation of 50 Gy; however, it recurred after 1 year and a new lesion was found in the liver. The other patient is a 31-year-old woman who experienced sudden onset of headache. Computed tomography scan revealed three separate masses in the brain. One tumor was surgically removed. The other two were sensitive to radiation therapy and disappeared after radiation of 40 Gy. A new lesion was found in the femur 16 months after the operation. Brain metastasis from angiosarcoma is exceedingly rare. Both patients developed symptoms with intracranial hemorrhage. The diagnosis of the metastatic lesions preceded diagnosis of the primary lesion by 12 and 16 months, respectively. Ulex europaeus 1 lectin and factor VIII were very useful in establishing the diagnosis of angiosarcoma. 
Production of transforming growth factor alpha by hamster eosinophils. Previously it was demonstrated that malignant transformation of the Syrian hamster cheek pouch mucosa is associated with the expression of TGF-alpha. Therefore in situ hybridization and immunohistochemistry was used to investigate the cellular sources of TGF-alpha production in this model system. Surprisingly one cell type in the inflammatory infiltrate present in the connective tissue adjacent to the transformed epithelium represented a major source of TGF-alpha mRNA. Detailed analysis of these cells revealed that they were eosinophils. In addition to TGF-alpha mRNA, about 40% of the eosinophils associated with the oral tumors exhibited TGF-alpha product reactive with a monoclonal antibody against the C terminus of the mature TGF-alpha peptide. Normal hamster bone marrow eosinophils also exhibited TGF-alpha mRNA and product by in situ hybridization and immunohistochemistry. These results suggest that the eosinophil represents a biologically significant source of TGF-alpha. 
General moderate hypothermia in the surgical treatment of descending thoracic aortic aneurysms. The diagnosis and surgical treatment of aneurysms of the descending thoracic aorta is difficult and some aspects of management remain controversial. We report 53 patients treated in the period 1983-1988; 25.9% of them had previously been erroneously diagnosed as having mediastinal cysts or tumours. Duplex scanning and computerised tomography were valuable adjuncts in establishing the correct diagnosis, which was confirmed by aortography in 52 patients. Of 49 patients operated upon electively three died with a mortality rate of 6.1%; of the 4 patients operated upon as emergencies 2 died. Fifty patients survived the operative procedure and of the 3 operated upon under normothermia 1 developed paraplegia, whereas of the 47 patients operated upon under moderate hypothermia (30 degrees-31 degrees C) only 1 developed paraplegia. 
HBx gene of hepatitis B virus induces liver cancer in transgenic mice. The exact role of hepatitis B virus in the development of liver cancer is not known. The recent identification of a viral regulatory gene HBx suggests a possible direct involvement of the virus whereby the HBx protein, acting as a transcriptional transactivator of viral genes, may alter host gene expression and lead to the development of hepatocellular carcinoma. We have tested this possibility of placing the entire HBx gene under its own regulatory elements directly into the germline of mice. Transgenic animals harbouring this viral gene succumbed to progressive histopathological changes specifically in the liver, beginning with multifocal areas of altered hepatocytes, followed by the appearance of benign adenomas, and proceeding to the development of malignant carcinomas. Male mice developed disease and died much earlier than females. This transgenic animal model appears ideal for defining the molecular events that follow the expression of the viral HBx gene and are responsible for the development of liver cancer. 
Long-latency neurodegenerative disease in the western Pacific. The western Pacific parkinsonism-dementia and amyotrophic lateral sclerosis complex is a prototypical neurodegenerative disorder found among inhabitants of Guam, New Guinea (Irian Jaya, Indonesia) and Japan (Kii Peninsula, Honshu). Nonviral environmental factors peculiar to the affected populations seem to play a prominent etiologic role. Although cause-effect relationships cannot be established by epidemiologic studies alone, we have shown in all three affected population groups that individuals develop the amyotrophic lateral sclerosis variant of this disorder after heavy exposure to the raw or incompletely detoxified seed of neurotoxic cycad plants. Since long periods may elapse between cycad exposure and the appearance of neurological disease in humans, cycads may harbor a "slow toxin" that causes the postmitotic neuron to undergo slow irreversible degeneration. Two cycad neurotoxins are recognized, one of which (cycasin) is known to have long-latency effects (tumorigenesis) on mitotic neurons and replicating cells in other tissues. This paper explores the possible relationship between tumorigenesis and long-latency neurotoxicity, and discusses possible biologic markers of cycad exposure and subclinical neurodegenerative disease. 
Chronic posttraumatic aortic pseudoaneurysm. Recognition before rupture. Few patients survive transection of the aorta caused by blunt trauma. However, among those who do are a small number who go on to live with an unrecognized pseudoaneurysm that may rupture at any time. Because these aneurysms may be mistaken for more common disease processes, such as hilar adenopathy, atherosclerotic aneurysm, or neoplasia, the authors describe radiographic findings that suggest the correct diagnosis. 
Experimental therapy of human glioma by means of a genetically engineered virus mutant. Malignant gliomas are the most common malignant brain tumors and are almost always fatal. A thymidine kinase-negative mutant of herpes simplex virus-1 (dlsptk) that is attenuated for neurovirulence was tested as a possible treatment for gliomas. In cell culture, dlsptk killed two long-term human glioma lines and three short-term human glioma cell populations. In nude mice with implanted subcutaneous and subrenal U87 human gliomas, intraneoplastic inoculation of dlsptk caused growth inhibition. In nude mice with intracranial U87 gliomas, intraneoplastic inoculation of dlsptk prolonged survival. Genetically engineered viruses such as dlsptk merit further evaluation as novel antineoplastic agents. 
Oral cancer screening in the elderly. Oral cancers represent approximately 3% of all cancers diagnosed in the United States. Oral cancer is one-fifth as common as cancer of the breast, colon, and lung but more than twice as common as cervical cancer. Incidence rates for oral cancer are highest among older men. Epidemiologic data identify alcohol and tobacco as major risk factors associated with the disease. Screening for oral cancer is a simple, non-invasive procedure which can be easily incorporated into the comprehensive assessment of older patients. Oral cancer screening can detect early, localized lesions which are associated with an improved prognosis. Five-year survival rates are more than four times greater in individuals with localized lesions than those with distant metastases. Since older Americans visit their physician more often than their dentist, the physician's medical examination provides an excellent opportunity to screen for oral cancers. 
A prion protein missense variant is integrated in kuru plaque cores in patients with Gerstmann-Straussler syndrome. Kuru plaques are the pathologic hallmark in Gerstmann-Straussler syndrome (GSS). To demonstrate that prion protein (PrP) is a component of kuru plaque cores, we fractionated and sequenced kuru plaque core derived peptides, following digestion with Achromobacter lyticus protease I. We identified 3 PrP-derived peptides by reverse-phase high-performance liquid chromatography and found a fragment of digests derived from a missense variant of PrP. The variant PrP was also present in the prion rod fraction in patients with GSS. This substitution may play a major role in cerebral amyloidogenesis. 
Maternal reporting of behaviour following very severe blunt head injury. Mothers of 40 very severely head injured male subjects rated their son's behaviour on the Current Behaviour Scale and their ratings were compared with mothers' ratings of 40 control male subjects. The scale was able to discriminate the two groups, by utilising two factors--loss of emotional control and loss of motivation. The mothers' level of emotional distress was closely related to their reporting of loss of emotional control in their sons, but reporting of loss of motivation, or lowered arousal, was strongly predicted by the functional disability of the son. The utility of refining the measurement of post-trauma behaviour is discussed. 
Sonographic visualization of the ureter in pregnancy. We describe a method of differentiating physiological from pathological dilatation of the renal collecting system in pregnant patients. In physiological hydronephrosis the dilated ureter extends down only to the level of the common iliac artery. In 2 patients with distal ureteral stones a dilated ureter was visualized past the vessels. To determine the frequency and reliability of visualizing the ureters in pregnant patients 105 consecutive asymptomatic pregnant patients were examined. Hydronephrosis was found in 83 kidneys in 59 of the patients. The dilated ureter was visualized in 64 of the renal units. The anatomy was well demonstrated by color flow Doppler scanning and in all of these cases the dilated ureter was seen to taper where it crossed the common iliac artery. These results suggest that the presence of a dilated ureter past the iliac artery is strong evidence for pathological distal ureteral obstruction in pregnancy. 
Lymphangiosarcoma associated with lymphedema in a man with Maffucci's syndrome. A man with Maffucci's syndrome and lifelong lymphedema in the right lower extremity had a lymphangiosarcoma in the same extremity. Despite amputation of the limb and radiotherapy, he died several months later of pulmonary metastases. Malignancies of vascular origin rarely have been reported in this syndrome. Our patient's features suggest that lymphedema may predispose patients with Maffucci's syndrome to the development of lymphangiosarcoma. 
Transient retrocochlear low-frequency sensorineural hearing loss: a new clinical entity. Sensorineural hearing loss (SNHL) of varying types and extent developed in a number of the 963 patients who underwent microvascular decompression for hemifacial spasm. Fourteen of the patients with hearing loss had transient low-frequency SNHL. Low-frequency SNHL is seldom noted in patients with retrocochlear hearing loss, but five of these patients had Horner's syndrome or bulbar palsy. The results of Bekesy audiometry, auditory brainstem response, and electrocochleography in the patients were also suggestive of brainstem pathology. Surgical records revealed that all of them had excessively short perforating arteries surrounding the entry zone of nerves VII and VIII, so that they had to be stretched during surgery. Occlusion of perforating arteries is suspected to have caused lateral brainstem infarction around the entry zone of nerves VII and VIII, and resulted in low-frequency SNHL. 
A novel vitamin D3 analog, 22-oxa-1,25-dihydroxyvitamin D3, inhibits the growth of human breast cancer in vitro and in vivo without causing hypercalcemia. Although 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] has been shown to inhibit the growth of certain malignant cells, its hypercalcemic effect has prevented clinical application. We have recently developed a novel vitamin D3 analog, 22-oxa-1,25-(OH)2D3 (OCT), that is capable of promoting differentiation and inhibiting proliferation without inducing hypercalcemia. The present study was undertaken to determine whether OCT could be applied for the treatment of breast cancer with or without estrogen receptor (ER). OCT inhibited the proliferation of both ER-positive (MCF-7, T-47D, and ZR-75-1) and ER-negative breast cancer cells (MDA-MB-231 and BT-20) in vitro in a time- and dose-dependent manner, as determined by cell number and [3H]thymidine uptake. The antiproliferative effect was observed with a concentration as low as 10(-11) M OCT, and treatment of MCF-7 cells with 10(-8) M OCT for 8 days caused more than a 50% reduction in cell number compared with that of vehicle-treated cells. OCT was approximately 1 order of magnitude more potent than 1,25-(OH)2D3 in inhibiting the proliferation of MCF-7 cells. The in vivo effect of OCT was examined in athymic mice implanted with ER-negative MX-1 tumor, which was established as the xenograft derived from human breast carcinoma. Intratumor administration of OCT three times a week remarkably delayed the growth of MX-1 tumor in a time- and dose-dependent manner. The antitumor effect of 1 microgram/kg BW OCT was greater than that of 500 microgram/kg BW adriamycin, and the relative tumor weights in each group on day 26 were 29.7% and 50.5% of that in the vehicle-treated group, respectively. The effects of OCT and adriamycin were additive, and the relative tumor weight after 26 days of combined treatment was 21.7% of that in the vehicle-treated group. Oral administration of OCT was also effective, and the relative tumor weight in the OCT-treated group (1 microgram/kg BW) was 54.6 +/- 0.1% (mean +/- SEM) of that in the vehicle-treated group. Neither intratumor nor oral administration of OCT raised the serum calcium level in these animals. These results demonstrate that OCT is a potent inhibitor of the proliferation of breast cancer cells with or without ER and that OCT inhibits the growth of breast cancer in vivo without inducing hypercalcemia. We suggest that OCT may provide a new strategy for the treatment of breast carcinoma regardless of ER status. 
PEG ileus. A new cause of small bowel obstruction. A case of small bowel obstruction due to a lodged percutaneous endoscopic gastrostomy tube inner bumper is described. Most probably inner bumper lodgement in the terminal ileum is related to its size. Laparotomy was required to remove the bumper and relieve the obstruction. We suggest that all percutaneous endoscopic gastrostomy bumpers be retrieved endoscopically when the PEG tube is removed or replaced unless a collapsible inner bumper is used. 
A phase II study of the combination of carboplatin and ifosfamide in previously untreated metastatic small cell lung carcinoma. This Phase II study evaluated the combination of two active agents in small cell lung carcinoma (SCLC): carboplatin and ifosfamide. Thirty previously untreated patients (27 men and 3 women) with a median age of 59 years were included in this study. Twelve patients had one metastatic site and 18 had two or more metastatic sites. The median performance status was 80%. The chemotherapy (CT) regimen administered during the course of this study consisted of carboplatin (300 mg/m2) and ifosfamide (4 g/m2) plus mesna every 4 weeks. All 30 patients were evaluable: 1 achieved a complete remission (CR) and 18 achieved a partial remission (PR) (objective response rate, 63%). The median response time was 3 months and the median survival time was 8 months (range, 1 to 25+ months). Bone marrow toxicity was Grade III in three patients and Grade IV in four patients. The carboplatin and ifosfamide combination was well tolerated. No cross-resistance with the doxorubicin and etoposide regimen was established because 4 of 11 patients responded to this combination (+/- cisplatin) after failing to respond to the ifosfamide and carboplatin regimen. The ifosfamide and carboplatin combination may be considered for inclusion in non-cross-resistant alternating CT schedules. 
A simple method for biliary-enteric anastomosis and chronic bile diversion in the rat. A simple method of biliary-enteric anastomosis, without the use of surgical microscopy, is described. There were no signs of cholestasis after 3 mo of follow-up. A modified procedure using a silicone elastomer catheter as a stent for the biliary-enteric anastomosis resulted in biliary obstruction within 3 wk after surgery. Our experimental bile duct implantation technique is a simple and useful experimental method for the investigation of chronic biliary diversion and biliary physiology. Additionally, it can be performed safely and easily in a rodent model without sophisticated microscopic techniques. 
Unwashed filtered shed blood collected after knee and hip arthroplasties. A source of autologous red blood cells. We evaluated the results of twelve hematological and plasma protein determinations in 450 to 500-milliliter volumes of shed blood that had been collected with or without acid-citrate-dextrose anticoagulant (National Institutes of Health Formula A) from knees and hips during the first twelve hours after arthroplasty. We also evaluated the effects on the recipients when the blood was used for reinfusion. The findings in the units that had been obtained in less than four hours, in between four and six hours, and in more than six hours after the arthroplasty were similar whether or not the acid-citrate-dextrose anticoagulant had been used. The mean values for the collected units were: in the blood, a concentration of hemoglobin of 115 grams per liter, a hematocrit of 0.34, a white blood-cell count of 4.8 x 10(9) per liter, and a red blood-cell count of 3.7 x 10(12) per liter, and, in the plasma, a level of hemoglobin of 160 grams per liter, a level of fibrinogen of less than 0.2 gram per liter, a level of factor-V clotting protein of less than 10 per cent of normal, a level of factor-VIII clotting protein that was 45 per cent of normal, a level of antithrombin III that was 45 per cent of normal, a level of plasminogen that was 55 per cent of normal, a level of protein C that was 100 per cent of normal, and a level of fibrin-degradation products of 1000 micrograms per milliliter of plasma. The clinical response of the patient was assessed after the reinfusion of a total of 205 units of unwashed shed blood into 153 patients. In addition, in 126 of the 153 patients, hematological and plasma-protein measurements were analyzed before the autotransfusion and one and twenty-four hours afterward. Each of these patients had received one to four units of shed blood that had been filtered but not washed. Only two (2 per cent) of the ninety-nine patients who received shed blood that had been collected six hours or less after the operation had a febrile reaction, whereas twelve (22 per cent) of the fifty-four patients who received blood that had been collected six to twelve hours after the operation had such a reaction.(ABSTRACT TRUNCATED AT 400 WORDS). 
Percutaneous intra-aortic balloon pump: emphasis on complications. In a review of our 5-year experience with intra-aortic balloon pump (IABP) insertion I examined the complications of percutaneous IABP placement in 93 patients, and compared them with those reported in other studies in the literature. I analyzed several variables that may affect the complication rate. Of 78 patients in our series who had percutaneous IABP cardiac assist, 15 (19%) had complications, which falls into the acceptable range reported by others. Among 15 patients who had surgical placement of an IABP, the complication rate was similar at 20%. The complication rate after IABP insertions done by surgeons primarily in the operating room was compared with that from insertions done by cardiologists in the catheterization laboratory. The overall complication rate was found to be higher in the second group, 28.0% compared with 12.8%. The application of the IABP in cardiogenic shock was associated with a high complication rate (46%). On the other hand, its insertion before cardiac surgery was associated with a relatively low complication rate (9.5%). 
Motor inhibition from the brainstem is normal in torsion dystonia during REM sleep. The maintenance of axial atonia during REM sleep was monitored in 14 patients with primary torsion dystonia, 10 patients with secondary torsion dystonia, and 10 normal subjects using submental EMG and video EEG telemetry. The excitability of the corticospinal tract during REM sleep was also assessed using scalp magnetic stimulation in seven patients and three controls. During REM sleep dystonic patients had well maintained atonia evidenced by infrequent bursts of submental activity, no episodes of complex semi-purposeful behaviour and reduced motor responses to magnetic stimulation. These findings suggest that the inhibitory centres in the region of the locus coeruleus and their descending pathways to the spinal alpha motor neurons are intact in torsion dystonia. 
Lateral parascapular extrapleural approach to the upper thoracic spine. The upper thoracic vertebrae are difficult to approach surgically because of the narrowing of the thoracic inlet, the proximity of the brachial plexus, and the parascapular shoulder musculature. A novel lateral parascapular extrapleural approach to the upper thoracic vertebrae is described. The parascapular shoulder musculature (trapezius, levator scapulae, and rhomboid muscles) is reflected off the spinous processes to the scapula as a musculocutaneous flap, preserving the neurovascular supply. The paraspinal musculature is mobilized and retracted, and the upper dorsal ribs are removed with caution to avoid injury to the C-8 and T-1 nerve roots. The rami communicantes are transected, and the sympathetic chain is displaced anterolaterally. The T2-4 vertebrae can be approached unobstructed. The T-1 nerve root obstructs posterolateral access to the T-1 vertebra, necessitating an inferolateral approach underneath the T-1 nerve root axilla. Four patients with compressive myelopathy from upper thoracic vertebral metastases underwent neural decompression, vertebral reconstruction, and posterior spinal fixation with this approach. Their postoperative neurological status was either unchanged or improved. Complications included radiographic pleural effusion and superficial wound dehiscence; one patient required posterior spinal reinstrumentation for progressive kyphosis. One patient developed pneumonia 7 days postoperatively which was unresponsive to appropriate treatment. It is believed that the anatomical limitations to this region have been overcome, and that excellent exposure of the T1-4 vertebrae for neural decompression and vertebral reconstruction can be performed safely. A major advantage is that posterior spinal fixation can be carried out simultaneously. 
Disulfiram implant: a double-blind placebo controlled follow-up on treatment outcome. Seventy-six alcohol-dependent patients participated in a study of the clinical effect of implanted disulfiram (DS). The patients were randomized to a DS group (n = 40), receiving a subcutaneous abdominal implantation of 10 x 100 mg DS tablets and a placebo group (PL group) receiving an implantation of 9 x 100 mg calcium phosphate tablets together with one calcium phosphate tablet containing 1 mg DS. Both groups believed they were receiving DS. At admission there was no significant difference between the DS and PL groups with regard to demographic characteristics, psychosocial adjustment, drinking variables, medical disorders, or laboratory results. After a study period of approximately 300 days, 63 patients (33 DS; 30 PL) were assessed using a battery of tests. There was no significant difference between the groups with regard to reduction in average alcohol consumption, number of days to the first alcohol intake after implantation, or level of psychosocial function. Nevertheless, both groups reduced their ethanol consumption significantly, probably due to the psychological deterrent effect. The DS implant did result in a significantly higher incidence of wound complications. This study does not support the idea that a 1-g DS implant has any significant clinical effect different from the implant containing only 1 mg DS (placebo). 
Effect of cardiopulmonary support on regional and global left ventricular function during transient coronary occlusion. The ability of extracorporeal cardiopulmonary support (CPS) to unload the left ventricle and reduce ischemic dysfunction during transient coronary occlusion was studied in 10 anesthetized dogs. Three serial 60-second circumflex coronary artery occlusions were performed with CPS initiated only during the second occlusion. CPS significantly reduced preocclusion systolic blood pressure, blood pressure x heart rate double-product, circumflex blood flow, left ventricular end-diastolic pressure (LVEDP), peak negative dP/dt, and left ventricular systolic thickening. Circumflex occlusion caused changes in LVEDP and left ventricular wall thickening that were similar regardless of the presence or absence of CPS. These data suggest that CPS unloads the left ventricle during myocardial ischemia but does not prevent regional or global myocardial dysfunction. 
Clinical features and results of therapy for children with paraspinal soft tissue sarcoma: a report of the Intergroup Rhabdomyosarcoma Study. Soft tissue sarcomas of the paraspinal region comprised 3.3% (56 of 1,688) of the patients entered and eligible on Intergroup Rhabdomyosarcoma Studies I (IRS-I) and II (IRS-II) (1972 to 1984). These lesions tended to be greater than 5 cm in diameter at diagnosis, invaded the spinal extradural space, and were of the extraosseous Ewing's sarcoma or undifferentiated sarcoma subtype in 55% (30 of 56) of the cases. Patients with tumors in clinical groups II, III, and IV were treated with radiotherapy (XRT) and vincristine-dactinomycin (VA) or VA plus cyclophosphamide (VAC) +/- doxorubicin. Clinical group I patients treated on IRS-II did not receive XRT, while those on IRS-I were randomized to receive VAC +/- XRT. Forty-four of the paraspinal patients (79%) achieved a complete response (CR) compared with 77% (1,260 of 1,632) for patients with disease in other sites. Twenty-seven patients (55%) subsequently relapsed (five local, three regional, four local and distant, and 14 distant). The proportion of patients surviving 5 years by clinical group (stage) from I to IV were 50%, 50%, 62%, and 27%, respectively. Paraspinal patients had somewhat poorer survival than patients with disease in other sites, both in IRS-I and IRS-II; the percentage of paraspinal patients surviving 5 years was 50% and 52% for IRS-I and IRS-II, respectively, whereas these percentages were 55% and 63% for patients with disease in other sites. Histology did not influence the CR rate, but unexpectedly, patients who had embryonal rhabdomyosarcoma (RMS) had the poorest overall survival rate. We concluded that patients with paraspinal lesions may require extended-field radiation therapy to reduce the high local failure rate and more intensive chemotherapy to achieve better local and systemic tumor control. 
Pacemaker failure on induction of anaesthesia. A patient with a permanent pacemaker presented for repair of a strangulated hernia. During induction of anaesthesia, the pacemaker generator stopped discharging, thus causing cardiac arrest. The likely cause of the generator failure was inhibition by suxamethonium-induced muscle fasciculations. Following defibrillation, and increase in stimulation threshold necessitated urgent insertion of a transvenous pacing system. It is suggested that, when suxamethonium is to be used in a patient with a permanent pacemaker, consideration should be given to reprogramming the pacemaker to asynchronous mode before induction of anaesthesia. If a patient with a pacemaker requires defibrillation, an acute increase in stimulation threshold may result and cause loss of capture. Rapid insertion of a transvenous pacing system may be necessary. 
Etiology of autism: genetic influences. In summary, there are a few specific genetic conditions that can be associated with autism. Among cases of unknown etiology, there is ample evidence for a higher genetic liability to autism in siblings of autistic probands than expected from the population prevalence. It appears likely that both parents and siblings have a higher liability for social and cognitive deficits that are milder but conceptually similar to those found in autism. Others factors may alter this underlying genetic liability such as sex, IQ, and prenatal and perinatal injury. In the future, genetic analyses and genetic linkage studies will need to consider using a broader definition of the autism phenotype to include not only autism but severe cognitive and social deficits. The exact genetic mechanisms and genes involved are the subject of current investigations by several research groups. Investigations in this area are likely to continue to provide important information about the causes of autism. 
Renovascular hypertension: predicting surgical cure with exercise renography. Renal artery stenosis with resultant renovascular hypertension has attracted clinical attention because the disease is potentially curable and because numerous diagnostic and therapeutic modalities compete for clinical acceptance. An exercise-mediated disturbance of renal hippurate transport was recently described, and has been implicated as having a role in nephrogenic fixed hypertension. To predict the final course of renovascular hypertension before operation we carried out a prospective study with the goal of verifying the predictive value of exercise hippurate scintigraphy. The study was to test the hypothesis that patients with disturbance of renal hippurate transport (pathologic renogram) induced by exercise would have stabilized hypertension and would continue to be hypertensive after operation. Thirty-one patients with hypertension who had unilateral or bilateral renovascular stenosis documented on angiography were referred to rest and exercise hippurate scintigrams before operation. The results of the examinations at rest served as standard and were compared with the exercise scintigrams. In 19 of the 31 (61%) patients a disturbance of transrenal hippurate transport evolved during exercise, whereas 12 (39%) patients failed to respond to exercise with altered hippurate kinetics. Twenty-six patients went on to renovascular operations; five had percutaneous transluminal angioplasty. Revascularization results differed markedly when the blood pressure response of patients with positive results on exercise (abnormal) and patients with negative results on exercise (normal) were compared. Ten of 12 patients with hypertension who had normal exercise renograms were cured. In comparison, blood pressure values were little influenced by therapy in patients with an abnormal response, where 17 of 19 patients continued to have hypertensive disease after therapy. 
Report of the Council on Scientific Affairs: ultrasonic imaging of the heart: report of the Ultrasonography Task Force. The use of ultrasonography in cardiology has progressed so dramatically that not only is anatomic information available but information can also be derived about cardiac hemodynamics. Applications range from intravascular ultrasonic imaging of coronary atherosclerosis to predictions of the severity of fetal valvular pulmonic stenosis detected in utero. We reviewed cardiac ultrasonography as utilized in B-mode imaging, pulsed and continuous-wave spectral Doppler, and Doppler color flow mapping. We reviewed specialized areas, including stress echo for wall motion analysis, valvular and congenital heart disease applications, and new applications in intraoperative, transesophageal, contrast echography, coronary imaging, and fetal echocardiography. Finally, future applications of quantitative flow mapping and intraluminal and interventional ultrasonography were considered along with the required technological advances. 
Unproven methods of cancer management. Livingston-Wheeler therapy. Livingston-Wheeler's cancer treatment is based on the belief that cancer is caused by a bacterium she has named Progenitor cryptocides. Careful research using modern techniques, however, has shown that there is no such organism and that Livingston-Wheeler has apparently mistaken several different types of bacteria, both rare and common, for a unique microbe. In spite of diligent research to isolate a cancer-causing microorganism, none has been found. Similarly, Livingston-Wheeler's autologous vaccine cannot be considered an effective treatment for cancer. While many oncologists have expressed the hope that someday a vaccine will be developed against cancer, the cause(s) of cancer must be determined before research can be directed toward developing a vaccine. The rationale for other facets of the Livingston-Wheeler cancer therapy is similarly faulty. No evidence supports her contention that cancer results from a defective immune system, that a whole-foods diet restores immune system deficiencies, that abscisic acid slows tumor growth, or that cancer is transmitted to humans by chickens. 
Tube feeding-related diarrhea in acutely Ill patients. Acutely ill patients received tube feeding for an average of 15.8 days and, on average, 35% of those days were spent in the intensive care unit (ICU). Patients were prospectively assigned either a fiber-free formula (FFF-OSMOLITE HN, Ross; n = 50) or a fiber-supplemented (soy polysaccharide 14.4 g/L) formula (FSF = JEVITY, Ross; n = 50). Diarrhea was defined as three or more loose or watery stools per day and occurred in 30% of all patients. Diarrhea developed in 29 (41%) of the 71 patients who received antibiotics during, or within 2 weeks prior to, the feeding period, whereas only 1 (3%) of the 29 patients not receiving antibiotics developed diarrhea (p less than 0.005); and this patient developed diarrhea on the day of death. Among the 30 patients with diarrhea, stool Clostridium difficile (CD) toxin was positive in 15 (50%), negative in 11 (37%), and was not measured in four. The mean serum albumin was significantly lower in patients with diarrhea (2.43) than in those without diarrhea (2.75) (p = 0.043). There were no significant differences in age, sex, diagnoses, number of feeding days, and percent ICU days between patients with and without diarrhea. While not statistically significant, patients who received FSF were observed to have a lower incidence of diarrhea, a lower percentage of diarrhea days per total feeding days, and a lower frequency of positive CD toxin assays than patients who received FFF. In this patient population, antibiotic usage was the factor most strongly associated with diarrhea during tube feedings. 
Factors affecting decisions to institutionalize demented elderly. This study followed 321 community-based patients with documented dementias, 22% of whom were institutionalized after 1 year. Multivariate analyses indicated that none of the patient characteristics, such as level of cognitive, psychiatric, or neurological impairment, predicted institutionalization. Social psychological characteristics, type and number of caregivers, and subjective caregiver distress did predict which patients were ultimately institutionalized. Implications for treatment planning are discussed. 
Low back pain: review of diagnosis and therapy. Low back pain is a patient complaint frequently encountered in the emergency department setting. The disease entity is often a diagnostic challenge with a subtle presentation, but can be accompanied by significant neurovascular complications. Current topics of controversy include the utility of radiologic evaluation, pharmacologic and holistic treatment strategies, as well as guidelines for urgent referral of patients with lumbar pain. 
Hyperfractionated radiation therapy in brain stem tumors. Results of treatment at the 7020 cGy dose level of Pediatric Oncology Group study #8495. Between May 1986 and February 1988, 57 patients were accrued to the second dose level of a Phase I/II Pediatric Oncology Group (POG) study exploring the use of hyperfractionated radiation therapy (HRT) in children with high-risk brain stem tumors. Local fields were treated with fraction sizes of 117 cGy given twice daily, with a minimum interfraction interval of 6 hours, to a total dose of 7020 cGy in 60 fractions over 6 weeks. Information regarding clinical status during HRT was available for 55 patients (44 [80%] improved, 6 remained stable, and 5 deteriorated). Results of initial and follow-up computed tomography (CT) scan and/or magnetic resonance imaging (MRI) were available for review for 52 patients. One patient had a complete response (CR) to treatment, 3 had a partial response (PR) (more than 50% response), and 40 remained stable, for a total response rate (CR + PR + stable) of 77%. Median time to disease progression was 6 months. Median survival time was 10 months. Survival rate was 39.6% (standard error [SE] = 6.6%) at 1 year and 23% (SE = 5.8%) at 2 years. Complications of treatment included an enhanced skin reaction in six patients and otitis media and/or externa in nine. One patient bled into tumor shortly after completion of HRT, and three had intralesional necrosis. Five patients continued taking steroids for protracted periods in the face of improved clinical and/or radiologic findings. Complications related to the use of steroids included opportunistic infections, impaired glucose tolerance, hypertension, osteoporosis, and significant mood changes. In no patient was there evidence of any late injury attributable to HRT. When compared with results of treatment with HRT at a lower dose level (6600 cGy), there appears to be a trend toward improved survival at 7020 cGy despite a less favorable patient population at the higher dose level. A second dose escalation to 7560 cGy in 60 fractions over 6 weeks has been implemented as planned. 
Sleep apnea in acromegaly. OBJECTIVE: To provide information on the nature, prevalence, and severity of sleep apnea in patients with acromegaly. DESIGN: Consecutive case series. SETTING: Tertiary referral hospital. PATIENTS: Fifty-three patients with acromegaly were consecutively referred: 33 patients were referred because of clinical suspicion of sleep apnea and 20 patients were referred without suspected apnea. MEASUREMENTS: Sleep studies as well as growth hormone and insulin-like growth factor 1 (IGF-1) measurements were done. MAIN RESULTS: Thirty-one patients (93%; 95% Cl, 85% to 100%) referred because of suspicion of sleep apnea had sleep apnea compared with 12 patients (60%; Cl, 37% to 83%) referred without suspected sleep apnea. Patients with sleep apnea did not have biochemical evidence of increased disease activity (random growth hormone, 12.7 +/- 4.4 micrograms/L; mean growth hormone at 24-hour sampling, 10.8 +/- 8.4 micrograms/L; IGF-1, 90.0 +/- 7.5 nmol/L) compared with patients without sleep apnea (random growth hormone, 14.2 +/- 4.9 micrograms/L, P greater than 0.2; mean growth hormone, 12.4 +/- 3.5 micrograms/L, P greater than 0.2; IGF-1, 90.0 +/- 10.0 nmol/L, P greater than 0.2). Central sleep apnea was the predominant type of apnea in 33% (Cl, 18% to 47%) of patients and was associated with higher random growth hormone and IGF-1 levels than was obstructive apnea (random growth hormone, 23.4 +/- 3.9 compared with 8.8 +/- 3.1 micrograms/L, P less than 0.001; IGF-1, 126 +/- 17.5 compared with 72.5 +/- 7.5 nmol/L, P less than 0.01). CONCLUSIONS: Sleep apnea is common in acromegaly. The rate of central sleep apnea was unexpectedly high in patients with acromegaly, and biochemical evidence of increased disease activity was associated with the presence of central apnea rather than with the degree of sleep apnea. Altered respiratory control is a possible mechanism producing sleep apnea in acromegaly. 
Aortic valve replacement for aortic stenosis in persons aged 80 years and over. Seventy-one patients aged greater than or equal to 80 years (mean +/- standard deviation 82 +/- 2) with aortic stenosis or mixed stenosis and regurgitation underwent aortic valve replacement alone (n = 35, group 1) or in combination with a coronary artery bypass procedure without any other valve procedure (n = 36, group 2). Preoperatively, 91% had severe cardiac limitations (New York Heart Association class III or IV). Hospital mortality was 12.7% overall (9 of 71), 5.7% (2 of 35) for group 1 and 19.4% (7 of 36) for group 2. Perioperatively, 1 patient (1.4%) had a stroke. Survival from late cardiac death at 1 and 3 years was 98.2 and 95.5%, respectively, for all patients, 100% for patients who underwent isolated aortic valve replacement, and 96.3 and 91.2%, respectively, for patients who underwent aortic valve replacement plus coronary artery bypass. Eighty-three percent of surviving patients had marked symptomatic improvement. Freedom from all valve-related complications (thromboembolism, anticoagulant, endocarditis, reoperation or prosthetic failure) was 93.3 and 80.4% at 1 and 3 years, respectively. Thus, short- and long-term morbidity and mortality after aortic valve replacement for aortic stenosis in patients aged greater than or equal to 80 years are encouragingly low, although the addition of coronary artery bypass grafting increases short- and long-term mortality. 
Recognizing and naming tunes: memory impairment in the elderly. Subjects over the age of 50 listened to theme tunes of remote, recent, and frequent television programs. If they recognized the tune, they were asked for the name of the program and for as much information about the program as possible. From the responses to a subsequent questionnaire, it was possible to divide the data according to whether or not the subjects watched the programs. There was no effect of age on the recognition and naming of programs subjects never watched. For programs they watched (a true test of memory), older subjects recognized fewer tunes as familiar and were less able than younger subjects to name the programs with familiar tunes. Neither the amount of exposure nor the delay since exposure had a significant influence on the recognition and naming impairments with age. Older subjects reported less information about programs they watched than younger subjects. In multiple regression analyses, age was a better predictor of performance than measures of current cognitive ability. The results are compared with the effects of age on the recognition and naming of famous faces (Maylor, 1990a). It is argued that the studies together support the view that the information processing rate decreases with age; therefore the elderly are poor at speeded tasks, the most dramatic effects appearing for later components of sequential processes. 
Late cardiac tamponade after open-heart surgery. Late cardiac tamponade occurred in 74 patients 5-287 (median 16) days after open-heart surgery and was treated with pericardiocentesis or surgery. The overall incidence of late cardiac tamponade was 1.3%. After valve operations it was 2.6% and after isolated coronary surgery 0.7% (53/2,028 vs. 18/2,661, p less than 0.002). The diagnosis was assessed by echocardiography in 93% of cases. Pericardiocentesis, attempted in 65 cases (88%), was curative in 80% but failed in 20%. Eight of the latter 13 underwent emergency surgery and five were medically treated. Failure of pericardiocentesis was associated with posterior location of fluid, clots, echo-free space less than 20 mm or myocardial insufficiency. The subxiphoid part of the wound was surgically re-entered in ten cases and the entire sternotomy in seven. Four patients (5%) died within 30 days of the primary intervention. All hospital survivors were observed for a median of 44 (range 11-115) months. Three (4%) had recurrent pericardial effusion requiring repeat pericardiocentesis, but none had pericardial constriction. The 5-year survival rate was 73%. 
Manometric and radiologic investigations and biofeedback treatment of chronic idiopathic anal pain. In 12 patients suffering from chronic idiopathic anal pain, the rectosphincteric function was studied using manometric and x-ray techniques. The results of manometric investigations were compared with those obtained in 12 healthy volunteers. In all patients, the resting pressure in the anal canal was significantly higher than in control subjects. In 10 patients, defecography revealed abnormalities of the pelvic muscles. We treated the patients by using biofeedback techniques, consisting of voluntary modifications of the state of contraction of the external sphincter. In all cases, pain disappeared after a mean of eight biofeedback training sessions. When noxious manifestations had disappeared, manometry showed a significant decrease in the anal canal resting pressure. Our results indicate 1) that chronic idiopathic anal pain is associated with abnormal anorectal manometric profiles, probably resulting from a dysfunctioning of the striated external anal sphincter, and 2) that biofeedback training is an effective treatment for chronic idiopathic anal pain. 
In vitro balloon dilatation of mitral valve stenosis: the importance of subvalvar involvement as a cause of mitral valve insufficiency. To investigate the mechanism that increases the orifice area of the mitral valve during balloon dilatation 43 surgically excised intact rheumatic mitral valves were studied. The main pathological features were (a) fibrosis of mitral valve leaflets and commissures (10 valves); (b) fibrosis with calcification of one commissure (eight anterolateral, seven posteromedial); (c) fibrosis with calcification of both commissures (seven valves); and (d) predominant involvement of the subvalvar apparatus (11 valves). The valves were assessed by photography and radiography before and after balloon dilatation (balloons up to 38 mm (bifoil 2 x 19 mm) and pressures up to 4 atmospheres). The valve was dilated in stages under direct visual control by balloons of increasing diameter. Splitting of the fused commissures was the most common mode of widening the orifice. However, the mitral valve leaflets were torn in two fibrotic valves and in six valves with extensive involvement of the subvalvar apparatus. In the fibrotic valves (group (a] the tear originated near the valve perimeter, at the thinnest part of the remaining valve leaflet. In the valves with subvalvar involvement splitting started at the apex of spaces between the fused chordal columns and proceeded upward. Where there is extensive involvement of the subvalvar apparatus in rheumatic mitral valve disease the risk of tearing of the valve leaflets by balloon dilatation is increased and this is likely to predispose to the development of acute valvar insufficiency. 
Comparison of sucralfate and ranitidine in the treatment of duodenal ulcers. Ninety patients with endoscopically proven duodenal ulcers, enrolled in this prospective, single-blind study, were randomized to sucralfate, 1 g q.i.d., 0.5 hour before meals on an empty stomach or at bedtime, or ranitidine, 150 mg b.i.d., for 4-8 weeks (phase I). Patients who healed during the treatment period were invited to participate in a maintenance therapy follow-up covering 1 year (phase II), during which they were treated with sucralfate, 1 g b.i.d. (before breakfast and at bedtime) or 150 mg of ranitidine at bedtime. After 4 weeks of treatment, healing rates were 30/40 (75.0%) with sucralfate and 36/42 (85.7%) with ranitidine, and healing rates were 39/40 (97.6%) and 40/42 (95.2%) respectively, after 8 weeks of treatment. At the end of the 6th and 12th months of phase II, respectively, relapse rates were 3/33 (9.4%) and 10/32 (31.3%) in the sucralfate group and 5/33 (15.2%) and 10/29 (34.5%) in the ranitidine group. Differences between sucralfate- and ranitidine-treated groups were not significant. Both treatments were well tolerated. We conclude that sucralfate is as effective and safe as ranitidine in the short-term treatment and prevention of relapse in patients with ulcer disease. 
Hepatocarcinoma in cirrhosis. Is antithrombin III a neoplastic marker? It has been reported that hepatoma (HCC) cells produce abnormal proteins such as erytropietin, fibrinogen, prothrombin, and, recently, antithrombin III (AT III). In a preliminary report, we reported increased AT III levels in patients bearing HCC independent of their clinical liver status. The present study was performed to assess antithrombin III levels and other serological data present in patients with cirrhosis and in patients with cirrhosis and clinical findings of neoplastic disease. In 70 well-matched patients (47 with cirrhosis and 23 with cirrhosis and proven HCC) serum total cholesterol, albumin, prothrombin, alkaline phosphatase, AFP, aminotransferases, and AT III were determined. Together with AFP and alkaline phosphatase, patients with HCC had higher values of AT III (88 +/- 7%) and total cholesterol (184 +/- 17 mg/100 ml), as compared with cirrhotic patients (AT III 56 +/- 3.6%; total cholesterol 113 +/- 5 mg/100 ml) (P less than 0.001). No difference was observed between these two groups for albumin, prothrombin, and aminotransferases. In HCC patients, AT III levels were related to the total cholesterol level (R2 = 0.317), whereas in the cirrhotic patients it correlated with the prothrombin level (R2 = 0.274). These data suggest that in HCC patients a greater rate of synthesis of AT III occurs, whereas in cirrhotic patients lower levels of AT III occur due to impaired synthesis or increased catabolism of the protein. The serial determination of AT III in cirrhotic patients as a means of detecting neoplastic transformation is suggested. 
Scintigraphic studies of inflammation in diffuse lung disease. 67Ga lung scintigraphy is an established means to assess alveolar inflammation in a wide variety of diffuse lung diseases. It can be used to monitor the extent and activity of the alveolitis during the course of the disease and as a follow-up evaluation to therapy. Although the mechanism of 67Ga localization is not established firmly, the isotope appears to act as a tracer for disturbed protein and cellular fluxes within the interstitium and alveolar spaces. The radiolabeled aerosol study may also be applied to the study of these fluxes as a reflection of inflammation and injury. Although Tc-DTPA clearance studies are highly sensitive to lung injury, they may be too nonspecific to separate lung injury from other physiologic processes effectively. 
Effect of dobutamine on oxygen consumption and fluid and protein losses after endotoxemia. OBJECTIVE: To determine the effect of a dobutamine infusion on the relationship between oxygen consumption (VO2) and oxygen delivery (DO2) after endotoxin administration, as well as the rate of fluid and protein loss from permeability-injured tissue. METHODS: Unanesthetized adult sheep with lung and soft-tissue lymph fistulas were given 5 micrograms/kg Escherichia coli endotoxin alone, or E. coli endotoxin plus a continuous infusion of dobutamine (10 to 15 micrograms/kg.min) beginning at 3 hrs. Lymph flow reflected the vascular permeability and surface area perfused. Data were compared with dobutamine alone and with controls. Filling pressures were maintained at baseline. RESULTS: Dobutamine alone produced a 75% increase in DO2, a transient 10 +/- 4% increase in VO2, but no increase in lung or soft-tissue lymph flow. Beginning at 3 hrs after endotoxin alone, a significant increase in protein-rich lung and soft-tissue lymph flow was noted, but only a transient 14 +/- 5% increase in VO2. Plasma proteins were slightly decreased. With the addition of dobutamine at 3 hrs postendotoxin, DO2 increased by greater than 50% for the 3-hr infusion period, while VO2 increased for a 30-min period by 25 +/- 8%, which was not different than endotoxin alone. Lung and soft-tissue lymph flow did not increase further, but plasma proteins did decrease significantly compared with controls and with endotoxin alone. CONCLUSION: Increasing DO2 with dobutamine postendotoxin does not increase the surface area perfused or the edema process, at least in lung and soft tissue. Therefore, no microvessels in these tissues are reopened with dobutamine when normal filling pressures are present. Dobutamine administration does not increase VO2 more than the increase seen with endotoxin alone. 
Ischaemic spinal cord lesion following percutaneous radiofrequency spinal rhizotomy. Two patients are presented in whom percutaneous radiofrequency spinal rhizotomy was complicated by contralateral paresis. Both patients were elderly and suffered from cardiac failure, chronic obstructive respiratory disease, and generalized vascular disease. Investigation of the paresis indicated a contralateral ischaemic cord lesion. It is suggested that local haemodynamic changes induced by heat-mediated rhizotomy may compromise oxygen delivery to the adjacent cord, especially in the presence of pre-existent cardiovascular disease. 
Advances in pediatric emergency department procedures. Pediatric procedures in the Emergency Department typically involve techniques for stabilization, evaluation, and treatment of the child. This article considers indications and techniques for vascular access, lumbar puncture, arterial lines, pulse oximetry, and urine collection. Multiple routes of medication administration and pain management modalities also are reviewed. 
Yersinia enterocolitica infection with ileal perforation associated with iron overload and deferoxamine therapy. Despite the frequency of gastrointestinal disease caused by Yersinia enterocolitica, intestinal perforation is a rare complication of this infection and to date only eight cases have been reported in the English literature. We describe a case of this unusual condition in a 17-year-old male patient with thalassemia intermedia requiring transfusion, who was also taking deferoxamine. The severity of the clinical picture is probably due to the increased virulence of Yersinia enterocolitica in the presence of deferoxamine and iron. 
Increased all-cause and cardiac morbidity and mortality associated with the diagonal earlobe crease: a prospective cohort study. PURPOSE: To ascertain whether the diagonal earlobe crease (ELC) is associated prospectively with future death or cardiac events over 8 years of follow-up in two sets of patients: those with known coronary artery disease (CAD) and those without evidence for CAD. PATIENTS AND METHODS: We performed a prospective, observational study of 108 patients in four cohorts (each matched for age, sex, and race, but differing in the presence or absence of both a diagonal ELC and CAD in 1979 to 1982). Follow-up information was gathered by telephone interviews, and dates and causes of death were determined by reference to death certificates (n = 48), hospital records (n = 9), or attending physician statements (n = 1). RESULTS: During 8 to 10 years of follow-up, 58 of the patients had died. Patients with ELCs had poorer survival rates than those without creases, by stratified log-rank test (p = 0.006 for the cohorts thought not to have CAD, and p = 0.058 for those with CAD). Cardiac death rates (due to acute myocardial infarction, "sudden cardiac death," or heart failure) were also higher for patients with ELCs: 8.0 versus 0.9 cardiac deaths per 100 patient-years (p less than 0.001) in patients without CAD at entry, and 11.7 versus 3.7 cardiac deaths per 100 patient-years (p = 0.008) in patients with CAD in 1979 to 1982. Cardiac event rates (cardiac death, nonfatal myocardial infarction, or coronary artery bypass surgery) were also higher in those with ELCs: 10.4 versus 1.4 events per 100 patient-years (p less than 0.001) for those without known CAD, and 15.8 versus 5.7 events per 100 patient-years (p = 0.009) for those with CAD. CONCLUSION: These results suggest that a diagonal ELC is associated with increased all-cause and cardiac morbidity and mortality. Patients with ELCs may be at higher risk for coronary events, and might be especially cautioned to control or reduce other cardiac risk factors, even if currently without diagnostic evidence of CAD. 
Goiter and hypothyroidism during re-treatment with amiodarone in a patient who previously experienced amiodarone-induced thyrotoxicosis. A 55-year-old woman who had been receiving treatment with amiodarone for recurrent supraventricular tachyarrhythmias became thyrotoxic after 30 months of treatment. The thyroid gland was not enlarged or tender. Amiodarone was discontinued, and thyrotoxicosis gradually abated. A thyroid scan performed at that time revealed a gland of normal size and texture. Six months later, amiodarone treatment was reinstated due to life-threatening tachyarrhythmia; however, the patient remained euthyroid. Three years later, multinodular goiter began to develop, and 5 years after that, the patient became hypothyroid. Tests for thyroid autoantibodies, as well as inhibitory and stimulatory antibodies, were negative, and fine needle aspiration biopsy revealed an adenomatous goiter. Treatment with amiodarone was continued; however, therapy with L-thyroxin was initiated, followed by a complete regression of the goiter. The patient has since required a maintenance dose of L-thyroxin. The possible mechanisms by which iodine-containing drugs induce thyroid disfunction are reviewed, suggesting this case was caused by an alteration in the sensitivity of the intrinsic autoregulation of the thyroid gland to iodine. 
Maintenance therapy in peptic ulcer disease. The maxim "once an ulcer, always an ulcer" is still an appropriate description for the chronic nature of peptic ulcer disease. The goals for treating patients with ulcer disease are to relieve symptoms, heal the acute ulcer, reduce the risk of ulcer recurrence and complications, and decrease the economic impact of this chronic disease while maintaining the patient's quality of life. Patients with documented peptic ulcer disease should be carefully evaluated and a treatment plan devised that takes into account the possible need for maintenance therapy. Risk factors that seem to reflect a high likelihood of ulcer recurrence should be identified early in all ulcer patients and attempts made to minimize or correct them in the future. Assuming that a diagnosis of peptic ulcer disease has been firmly established and an adequate period of drug treatment makes complete ulcer healing likely, a reasonable way to proceed is outlined in Figure 4. If the patient is young and generally healthy, has an uncomplicated ulcer and few risk factors favoring ulcer relapse, either no treatment or symptomatic selfcare would be reasonable. If one chooses the latter course, the patient can be given a prescription for 3 to 6 months of medication and told to take full therapy for any recurrent symptoms, continuing the treatment until symptoms are relieved. The failure of such treatment to relieve symptoms after 2 to 3 weeks, the onset of alarming symptoms such as intense pain, vomiting, or melena, or possibly the exhaustion of the 6-month supply of medication with continued mild symptoms should lead to reevaluation. Alternatively, such a patient could be managed with no therapy and seen again if ulcer symptoms recur and reevaluated for further diagnosis and treatment. Obviously, patients who are candidates for these approaches to postulcer healing management are those with a low risk for ulcer recurrence and who are likely to be compliant with follow-up advice. Accordingly, careful patient selection seems most important in prescribing symptomatic self-care or intermittent full-dose maintenance treatment. On the other hand, if the patient has had a complicated course of ulcer disease, such as bleeding, or has a significant number of risk factors that would make early ulcer relapse highly likely, it would be prudent to institute continuous maintenance therapy while working to reduce or eliminate the adverse risk factors. Any relapse of symptomatic ulcer disease during noncontinuous maintenance therapy should indicate the need for return to a continuous dosing program.(ABSTRACT TRUNCATED AT 400 WORDS). 
The role of leukotriene antagonists and inhibitors in the treatment of airway disease. Since the early recognition that leukotrienes are generated in response to allergen exposure, a role for these multipurpose mediators has been sought. The pharmacologic actions of the leukotrienes and their cell sources were strong evidence that they should contribute to allergic airway disease. That promise is now being fulfilled. Potent leukotriene receptor antagonists and enzyme inhibitors of leukotriene generation are now being investigated. With the availability of these new compounds, not only will greater insight to leukotrienes in asthma become apparent, but possibly newer, more effective therapeutics. Of additional interest and relevance is the potential role of leukotrienes in other nonrespiratory inflammatory diseases such as inflammatory bowel disease, rheumatoid arthritis, and psoriasis. Therefore, the role of leukotrienes in inflammation is not limited to the respiratory system but are more universal in their ability to cause tissue injury. Consequently, studies that have shown benefit from inhibition of leukotriene synthesis and antagonism of the LTD4 receptor in respiratory diseases are suggestive that such an approach will also be beneficial in other inflammatory diseases. For example, a study of 72 patients with A-64077 (zileuton) has demonstrated that 5-lipoxygenase inhibitors are efficacious in the treatment of inflammatory bowel disease. Therefore, the contribution of leukotrienes to inflammation is likely to be a global phenomenon, and the introduction of leukotriene antagonists and 5-lipoxygenase inhibitors may represent the beginning of a new era for the treatment of many inflammatory diseases. 
Waterborne outbreak of Norwalk virus gastroenteritis at a southwest US resort: role of geological formations in contamination of well water. From April 17 to May 1, 1989, gastroenteritis developed in about 900 people during a visit to a new resort in Arizona, USA. Of 240 guests surveyed, 110 had a gastrointestinal illness that was significantly associated with the drinking of tap water from the resort's well (relative risk = 16.1, 95% confidence interval 14.5 to 17.8) and this risk increased significantly with the number of glasses of water consumed (p less than 0.005). Three of seven paired sera tested for antibodies to the Norwalk agent had a four-fold or greater rise in titre. Water contaminated with faecal coliforms was traced back to the deep water well, which remained contaminated even after prolonged pumping. Effluent from the resort's sewage treatment facility seeped through fractures in the subsurface rock (with little filtration) directly into the resort's deep well. Although the latest technology was used to design the resort's water and sewage treatment plants, the region's unique geological conditions posed unexpected problems that may trouble developers faced with similar subsurface geological formations and arid climatic conditions in many parts of the world. In these areas, novel solutions are needed to provide adequate facilities for the treatment of sewage and supply of pure drinking water. 
Prospective hospital based study on persistent diarrhoea. A total of 383 children aged less than 5 years suffering from acute watery diarrhoea or dysentery were studied in hospital to determine the rate of persistent diarrhoea. Altogether 335 (87.5%) recovered within 13 days. Only in 48 (12.5%) did the diarrhoea continue for 14 days or more, and they were considered as having persistent diarrhoea. Children aged between 7 and 18 months had a significantly increased incidence of persistent diarrhoea. Children suffering from grade II-IV malnutrition constituted the majority (70.8%) of those with persistent diarrhoea. Higher rates of isolation of Shigella flexneri, Shigella dysenteriae 1, and Salmonella typhimurium were observed among patients with persistent diarrhoea than in those with diarrhoea of shorter duration. No positive correlations were observed between the clinical severity of disease at hospital admission and measles. Breast fed babies were not prone to persistent diarrhoea. 
Antihypertensive drug use. Trends in the United States from 1973 to 1985. Hypertension, a major public health problem, often requires drug therapy. We examined trends in outpatient antihypertensive drug use in the United States from 1973 to 1985. The numbers of prescriptions and the diagnostic and drug treatment information were obtained from the National Prescription Audit (Ambler, Pa, IMS America, 1985) the National Disease and Therapeutic Index (Ambler, Pa, IMS America, 1985), ongoing surveys of pharmacies, and office-based physicians. We adjusted drug-use data for the fact that several antihypertensive drugs also have other uses. During the study period, the annual numbers of prescriptions for treatment of hypertension progressively increased from 128.1 to 208.6 million, an average change of 5% per year. In 1973, the three leading classes of antihypertensive drugs were thiazide diuretic agents, peripheral neuronal inhibitors, and central alpha-adrenergic receptor stimulators. By 1985, the thiazide drugs were still the leader, followed by beta-adrenergic receptor blockers and potassium-sparing diuretic drugs. The use trends presented are consistent with surveys indicating increased drug therapy of hypertension from 1960 to the present. 
Cerebral akinetopsia (visual motion blindness). A review. Cerebral akinetopsia is a syndrome in which a patient loses specifically the ability to perceive visual motion following cortical lesions outside the striate cortex. There has been only one good case of akinetopsia in the published literature. Yet that case was immediately accepted by the neurological world. In this, cerebral akinetopsia differs markedly from cerebral achromatopsia, the evidence for which was strongly contested for the better part of a century (Zeki, 1990). This article complements the one on cerebral achromatopsia, traces the history of akinetopsia and enquires into why it was so much more readily acceptable than achromatopsia. 
Low-dose cyclopenthiazide in the treatment of hypertension: a one-year community-based study. After an 8-week placebo period, 73 patients whose diastolic blood pressures were between 90 and 110 mmHg were randomly assigned to receive 125 micrograms (low dose) or 500 micrograms of cyclopenthiazide (standard dose) for a period of one year. Blood pressure was measured in the patient's home by the same observer at two-weekly intervals during an 8-week placebo run-in period, every 4 weeks for a further 12 weeks and at 24, 36 and 52 weeks thereafter. Serum potassium, urate, glucose, glycosylated haemoglobin, total and HDL cholesterol, and apolipoproteins were measured at the end of the placebo period and at 4, 8, 24 and 52 weeks of active treatment. Twelve of the 73 patients had an inadequate antihypertensive response--five on the higher dose and seven on the lower dose. One patient receiving 500 micrograms was withdrawn because of adverse effects. In the remaining 60 patients, systolic and diastolic blood pressures were significantly reduced when compared with pretreatment values in both treatment groups throughout the one year period. The decreases in blood pressure were not significantly different from each other (p greater than 0.65). Three patients on 500 micrograms required potassium supplements. Maximum decreases in the serum potassium of 0.52 mmol/l (500 micrograms dose) and 0.14 mmol/l (125 micrograms dose) were observed at 24 weeks of treatment in the remaining 57 patients. The differences between the two doses at this time were statistically significant (p less than 0.05), as were the increases in serum urate observed at 4, 8 and 24 weeks (p less than 0.05). 
Ossified mucin-secreting choroid plexus adenoma: case report. This is the first report of a fully documented case of an ossified mucin-producing benign choroid plexus tumor. This was a chance finding in a man who complained only of posttraumatic low back discomfort. The ossification of the tumor appears to have been therapeutic. Mucin production may be a defense mechanism. 
Androscopy for anogenital HPV BACKGROUND. Strong evidence now links anogenital intraepithelial neoplasia to the transmission of the human papillomavirus (HPV) through sexual intercourse. While there is increasing research on women with this disease, less is known about their male sexual partners. METHODS. Male patients whose female sexual partners had been diagnosed as having anogenital intraepithelial neoplasia were recruited for the study. The genital regions of the male patients were examined and biopsied with the aid of a colposcope after application of a 5% acetic acid solution. Treatment was based on the specific findings in each patient. RESULTS. Genital lesions were found on 65% of the male patients examined, even though no disease had been detected by the individual. Seventy-nine percent of patients who were compliant with the prescribed treatment protocol had no detectable HPV-related lesions at the time of their last androscopic examination. CONCLUSIONS. Magnified examination of the male genitalia using an androscope following the application of 5% acetic acid solution is an effective method by which the primary care physician can detect and treat male HPV-related anogenital lesions. 
An animal model for colon cancer metastatic cell line with enhanced metastasizing ability. Establishment and characterization. We have developed an animal model for colon cancer metastasis and produced a metastasizing tumor after using a microinjection technique to inject SW480 cells into the cecal wall of athymic nude mice during "minilaparotomy." After the metastatic foci formed in murine lung, an in vitro primary culture was performed and a new metastatic cancer cell line, which was designated as CC-ML3, was established. The studies included: 1) the comparison between SW 480 and CC-ML3 in morphology, growth kinetics, seeding and plating efficiency, and karyotype; and 2) carcino-embryonic antigen determination, origination, and metastatic ability of CC-ML3. The results showed that CC-ML3 was significantly different from SW480 in vitro and possessed a high metastatic potential in vivo. This newly developed animal model may thus be useful for studying the biology and pathogenesis of metastasis of human colonic cancer. 
Intravascular ultrasound guidance for catheter-based coronary interventions. Intravascular ultrasound is a new method for visualizing the details of vascular pathology, providing high resolution images of plaque and thrombus. This review summarizes the potential applications of ultrasound imaging in the guidance of balloon angioplasty, atherectomy, laser ablation and stenting. Ultrasound differs from angiography and angioscopy in its ability to penetrate below the surface of the vessel lumen, demonstrating specific aspects about the distribution and composition of plaque. Because the different layers of the arterial wall have different acoustic properties, ultrasound catheters are able to define the layers of normal wall in comparison with plaque. Particularly in combination with therapeutic techniques designed to remove or ablate plaque, ultrasound may prove useful in maximizing the amount of plaque treated and minimizing trauma to normal vessel wall components. Combined imaging/therapeutic devices are in the pilot phase of development and show promise for enhancing the safety and efficacy of the catheter devices. 
Clinical experience with the Palmaz-Schatz coronary stent. Complications that occurred in 247 patients who underwent successful elective stenting to native coronary arteries with the Palmaz-Schatz balloon expandable stent included subacute thrombosis in 7 patients (2.8%), myocardial infarction in 3 (1.2%), death 3 (1.2%), urgent bypass surgery in 4 (1.6%) and major bleeding events in 24 (9.7%). Angiographic restenosis occurred in 21 (20%) of 103 patients who received a single stent. Subgroup analysis, however, revealed that restenosis of a single stent occurred in 3 (7%) of 45 patients without prior angioplasty compared with 25 (27%) of 91 patients with prior angioplasty. Patients with "suboptimal" angioplasty results (dis-section) who received a single stent seemed to have a higher thrombosis rate perioperatively (4 [4%] of 98), but no higher incidence of restenosis (7 [15%] of 46) than that of the total group of patients who received a single stent. Coronary stenting may be a valuable adjunct to coronary angioplasty in carefully selected patients. Complication rates are similar to those of routine angioplasty; however, angiographic restenosis may be reduced in certain subsets of patients. 
Pulmonary hypertension associated with long-standing thrombocytosis. A case of thromboembolic pulmonary hypertension associated with long-standing thrombocytosis is presented. In this patient we found a significant local pulmonary platelet activation and thrombin generation as indicated by the existence of a transpulmonary gradient for thromboxane A2, beta thromboglobulin and fibrinopeptide A. Prolonged heparin and acetylsalicylic acid treatment resulted in improvement of clinical and hemodynamic conditions. These findings support the usefulness of anticoagulating and antiaggregating therapy in selected cases of pulmonary hypertension. 
Targeting cancer chemotherapeutic agents by use of lipiodol contrast medium. Arterially administered Lipiodol Ultrafluid contrast medium selectively remained in various malignant solid tumors because of the difference in time required for the removal of Lipiodol contrast medium from normal capillaries and tumor neovasculature. Although blood flow was maintained in the tumor, even immediately after injection Lipiodol contrast medium remained in the neovasculature of the tumor. To target anti-cancer agents to tumors by using Lipiodol contrast medium as a carrier, the characteristics of the agents were examined. Anti-cancer agents had to be soluble in Lipiodol, be stable in it, and separate gradually from it so that the anti-cancer agents would selectively remain in the tumor. These conditions were found to be necessary on the basis of the measurement of radioactivity in VX2 tumors implanted in the liver of 16 rabbits that received arterial injections of 14C-labeled doxorubicin. Antitumor activities and side effects of arterial injections of two types of anti-cancer agents were compared in 76 rabbits with VX2 tumors. Oily anti-cancer agents that had characteristics essential for targeting were compared with simple mixtures of anti-cancer agents with Lipiodol contrast medium that did not have these essential characteristics. Groups of rabbits that received oily anti-cancer agents responded significantly better than groups that received simple mixtures, and side effects were observed more frequently in the groups that received the simple mixtures. These results suggest that targeting of the anti-cancer agent to the tumor is important for treatment of solid malignant tumors. 
Antithrombin III supplementation reduces heparin requirement and platelet loss during hemodialysis of patients with fulminant hepatic failure. Previous studies have shown that antithrombin III levels are low in fulminant hepatic failure, and heparin kinetics are abnormal, making control of heparinization difficult during hemodialysis of these patients who are at risk of bleeding. In this study, we have performed a controlled, randomized trial of antithrombin III supplementation on heparin activity, occurrence of bleeding and the platelet count and activation during hemodialysis in 24 patients with fulminant hepatic failure. The treated group of 12 patients was given 3,000 units of antithrombin III before hemodialysis. Antithrombin III supplementation was shown to normalize antithrombin III levels during hemodialysis (prelevels: 0.22 +/- 0.03 U/ml S.E.; at 1 hr 0.99 +/- 0.06 U/ml; p less than 0.001; control prelevels: 0.24 +/- 0.03 U/ml; at 1 hr 0.23 +/- 0.04 U/ml). Total heparin usage was significantly decreased by antithrombin III supplementation (median 5,200 U; range = 2,000 to 13,000) as compared with the control group (median 10,200 U; range = 5,000 to 16,500; p less than 0.005). Blood heparin level (antifactor Xa activity) after the initial bolus was significantly greater in the antithrombin III-supplemented subjects (0.40 +/- 0.07 U/ml compared with 0.22 +/- 0.05 U/ml in the control group; p less than 0.05). The significant reduction in platelet count observed in the control patients (18% +/- 6% at 1 hr; p less than 0.05) did not occur in antithrombin III patients (6% +/- 4% at 1 hr), which was reflected by a lower release of the platelet-specific protein beta-thromboglobulin. Two of 12 patients in both groups showed minor bleeding around vascular access sites during the first hemodialysis. 
Prevalence and malignant potential of colorectal polyps in asymptomatic, average-risk men. Screening colonoscopy was performed on 119 asymptomatic elderly men with no other risk factors for colonic neoplasms. Ninety adenomas were detected in 49 (41%) subjects. Mean adenoma size was 6.5 mm, with 83 (92%) less than or equal to 10 mm. Forty-nine (54%) adenomas were located proximal to the splenic flexure, and 17 (19%) were classified as tubulovillous or villous. Moderate- to high-grade dysplasia was found in 29 (32%) adenomas and was associated with larger size (p less than 0.0001) and villous architecture (p = 0.0038). Two subjects harbored adenomas with invasive cancer. Seventy-one hyperplastic polyps were found in 40 (34%) subjects. The mean size of hyperplastic polyps was 3.4 mm, and 64 (90%) were located in the left colon. We conclude that, in this population, adenomas are common lesions that are frequently small. However, substantial proportions of these adenomas may be at risk for malignant degeneration due to the presence of villous architecture and higher grades of dysplasia. Because adenomas and hyperplastic polyps are endoscopically indistinguishable, all polyps found at endoscopy should be removed or ablated. 
Conditions not attributable to a mental disorder: an epidemiological study of family problems. OBJECTIVE: The objective of this research was to identify and measure the differences among three groups of psychiatric outpatients: those with family problems but without mental disorders, those with both family problems and mental disorders, and those with a mental disorder but without family problems. DSM-III V code conditions (conditions not attributable to a mental disorder) other than family problems do occur, but family problems were chosen because of their importance. METHOD: All patients admitted to an outpatient psychiatric clinic during a 2-year period were studied (N = 382). Of these, 92 had V code conditions unrelated to family problems and were excluded. Data are presented on the remaining 290 patients. Sociodemographic variables, DSM-III diagnoses, source of referral, previous and subsequent use of outpatient services, and type of family problem were examined. Patients were from a low-income population and came from three ethnic groups (white, black, and Hispanic). RESULTS: Among whites, more men than women had family problems without mental disorders; among blacks, more women than men had family problems with and without mental disorders. Marital problems occurred most frequently in the group with family problems without mental disorders, and married subjects were more likely to have a V code condition. Professional referrals were more common than other referral sources in all three groups. However, family problems without mental disorders were more likely to occur among those who were referred by their families and had never had psychiatric treatment; patients with family problems and mental disorders were more likely to be self-referred and to have been previously treated; those with a mental disorder but without family problems were usually referred by professionals and almost always had been previously treated. There appeared to be underreporting of family problems among those with family problems and mental disorders and among black men with family problems with and without mental disorders. CONCLUSIONS: More research is needed on the patterns of use of outpatient psychiatric services by individuals with family problems and other V code conditions. 
Ultrasonographic findings in thalamus and basal ganglia in term asphyxiated infants. Three severely asphyxiated term neonates demonstrated bilateral hyperechogenicity in the thalamus and basal ganglia. During evolution, areas of attenuated echogenicity appeared in these structures at the same time as periventricular cysts were evident in 2 patients with coexistent periventricular leukomalacia. All 3 patients developed ventricular dilatation; in the 2 patients with periventricular leukomalacia, the ventricular border was irregular in the outer (dorsal) margin, and interhemispheric fissures were widened as a manifestation of cerebral atrophy. Furthermore, the thalamic inner (ventral) margins of the lateral ventricles were irregular in all 3 patients. This previously unrecognized finding points to a particular form of cerebral atrophy localized in the gangliothalamic region that contributes to the development of ventriculomegaly. The reported sonographic sequence implies profound damage in the thalamus and basal ganglia in asphyxiated infants which undoubtedly has contributed to the poor outcomes of our patients. 
Diastolic disease in left ventricular hypertrophy: comparison of M mode and Doppler echocardiography for the assessment of rapid ventricular filling. OBJECTIVE--To investigate possible discrepancies between M mode and Doppler echocardiography in assessing early diastolic filling. DESIGN--Forty seven patients with left ventricular hypertrophy due to aortic stenosis and 26 healthy controls with a similar age range were studied by M mode, Doppler, apexcardiography, and phonocardiography. The patients also underwent cardiac catheterisation. M mode echograms were digitised by a computer. Early diastolic filling in both groups as assessed by the two techniques was compared. SETTING--A tertiary cardiac referral centre with facilities for non-invasive and invasive investigations. SUBJECTS--Patients referred for assessment of aortic stenosis who had left ventricular hypertrophy. MAIN OUTCOME MEASURES--Filling velocities on Doppler and rates of wall thinning and dimension increase on M mode. RESULTS--Digitised M mode indices of diastolic filling (peak wall thinning rate 6.4 (3.0) v 10.0 (3.0) cm/s and peak rate of dimension increase 9.3 (3.3) v 16 (4.5) cm/s) in the patients and controls were consistently different. In contrast, the Doppler A/E ratio and peak E wave velocity were not; they varied widely among patients with left ventricular hypertrophy. In part, this variability was because the Doppler A/E ratio, but not the digitised M mode indices, was very sensitive to the abnormalities of isovolumic relaxation frequently present in left ventricular hypertrophy. The Doppler A/E ratio varied similarly with age in both normal and hypertrophied hearts; in the patients with ventricular hypertrophy the peak rate of dimension increase depended on age only, whereas the thinning rate was independent of age in both the patients and controls. Neither the A/E ratio nor the M mode indices could be related to the left ventricular end diastolic pressure or the peak aortic pressure difference. CONCLUSIONS--When Doppler and M mode techniques are used to assess rapid filling in patients with left ventricular hypertrophy the M mode indices are more consistently abnormal. The two methods measure different aspects of left ventricular diastolic function and should be regarded as complementary rather than interchangeable. 
The feeding pharyngostomy: an alternative approach to enteral feeding. We present a six-year retrospective review of feeding pharyngostomies as performed in this department. The indications, technique and complications of this procedure are discussed. 
Plasma profiles of adrenocorticotropic hormone, cortisol, growth hormone and prolactin in patients with untreated Parkinson's disease. Plasma profiles of prolactin, growth hormone, adrenocorticotropic hormone (ACTH) and cortisol were evaluated in a group of untreated patients with idiopathic Parkinson's disease and a group of healthy age-matched controls. Plasma integrated concentrations of all hormones except prolactin were significantly lower in the patients as compared with the controls; however, prolactin nocturnal peak concentration was significantly elevated in the patients; nocturnal growth hormone levels were significantly reduced in the Parkinson group; ACTH and cortisol plasma concentrations were also consistently lower during most of the day in the patients with Parkinson's disease. These data confirm the presence of a hypothalamic disturbance in patients with idiopathic Parkinson's disease, which can affect pituitary function. 
Plasma concentrations of bupivacaine following combined sciatic and femoral 3 in 1 nerve blocks in open knee surgery. We administered combined femoral 3 in 1 and sciatic nerve blocks to provide postoperative pain relief in 22 consecutive patients undergoing elective knee replacement surgery under spinal anaesthesia. The patients were allocated randomly to two groups. In group A (n = 11) the blocks were performed with 0.5% bupivacaine (with adrenaline) 3 mg/kg body weight and in group B (n = 11) 0.5% plain bupivacaine in the same dose was used. Serial plasma concentrations of bupivacaine were measured for up to 2 h and the duration of postoperative analgesia was measured in both groups. No significant differences were found between the two groups. There were no clinical signs or symptoms of bupivacaine toxicity in each group. This study demonstrated that, after combined sciatic and 3 in 1 femoral block, concentrations of bupivacaine associated with toxicity were not reached, even though the dose of bupivacaine administered exceeded the manufacturer's recommended dose by 50%. 
Immunoglobulin response to intravenous streptokinase in acute myocardial infarction. OBJECTIVE--To devise assays to assess and follow the specific antibody response in patients treated with streptokinase for acute myocardial infarction. DESIGN--Venous blood samples were collected before treatment with streptokinase started and subsequently at regular intervals over one year. Specific IgG and subclass IgG1 were assessed by an enzyme linked immunosorbent assay. SETTING--Coronary care unit in a general hospital. PATIENTS--48 patients with acute myocardial infarction: 22 patients had venous blood samples taken at presentation only; serial blood samples were taken from 20 patients who then received thrombolytic therapy with streptokinase and six patients who were unsuitable for thrombolytic therapy. RESULTS--Titres of antibodies to streptokinase were low at presentation in 36 (75%) of the 48 patients. Serial measurements made in 20 patients showed the virtual disappearance of antibody within the first 24 hours. This was followed by a steady increase in the specific IgG1 titre, which peaked at day 14 before gradually declining. Values at one year remained significantly higher than baseline values. There was no evidence of an IgM response in the patients studied. CONCLUSION--Low titres of antibodies to streptokinase were widespread in the population. Antibody was consumed after treatment and the subsequent immunoglobulin rise suggested a secondary immune responses; the recently described neutralising capacity to streptokinase is probably related to this antibody. 
Mesonephric rest hyperplasia. A potential diagnostic pitfall. A case of mesonephric rest hyperplasia, an incidental finding in the hysterectomy specimen of a 48-year-old woman, was initially misdiagnosed as a well-differentiated cervical adenocarcinoma. We highlight the histologic, histochemical, and immunohistochemical features of this potential diagnostic pitfall and review the relevant literature. 
Shoulder disorders in the elderly: a community survey. A community survey of identifiable symptomatic shoulder disorders in a sample of 644 elderly people over age 70 (318 male and 326 female) revealed a prevalence of 21%. Shoulder disorders were more common in women (25%, versus 17% in men). Approximately 70% of the cases of shoulder pain involved the rotator cuff. Fewer than 40% of the subjects sought medical attention for these symptoms. Increased medical awareness is needed, since the elderly often do not volunteer information about such symptoms. 
Follow-up bronchoalveolar lavage in AIDS patients with Pneumocystis carinii pneumonia. Pneumocystis carinii burden predicts early relapse. We performed an analysis of the value of repeat bronchoalveolar lavage (BAL) at 21 days to identify patients at risk for early relapse with Pneumocystis carinii pneumonia. Patients with P. carinii pneumonia and the acquired immunodeficiency syndrome (AIDS) were asked to participate in this study. All patients had P. carinii identified on methenamine silver stain of BAL fluid. BAL fluid was also stained with a modified Wright-Giemsa technique. The Wright-Giemsa stain was done to determine the cell differential count, and the number of P. carinii clusters associated with 500 nucleated cells was used as an estimate of P. carinii burden in the BAL. Initial and follow-up lavage was performed in 56 patients. Patients were classified based on their clinical response to anti-P. carinii therapy at 21 days. Nonresponders were patients with persistent or worsening symptoms. Responders were patients who improved and had therapy discontinued. Responders were further classified as responders with relapse if P. carinii pneumonia recurred within 6 months of the initial episode or responders without relapse if they remained disease free during the follow-up period. Responders without relapse reduced P. carinii cluster counts more than 50% in 24 of 25 cases. In responders with relapse P. carinii cluster counts were unchanged. The responders as a group had a significant decrease in the percentage of neutrophils in the BAL, with only 2 of 32 still having increased neutrophils in the follow-up lavage compared to 17 of 24 nonresponders (p less than 0.0001). 
Antral choanal polyp presenting as obstructive sleep apnea syndrome. Obstructive sleep apnea syndrome (OSAS) in children is commonly caused by adenotonsillar hypertrophy. The diagnostic criteria of OSAS in children are not so well delineated as in adults. We report the first case of antral choanal polyp presenting as OSAS in a 10-year-old boy that initially presented to the child psychiatry service for behavior disturbance, enuresis, and daytime somnolence. Overnight electroencephalogram sleep study revealed events consistent with OSAS. Multiple inhalant allergies, chronic maxillary sinusitis, and obstructive adenoid hypertrophy were diagnosed by the allergy and otolaryngology services. The child was scheduled for adenoidectomy when his sleep apnea symptoms persisted following antimicrobial therapy. Examination under anesthesia revealed a normal adenoid bed and a large left antral choanal polyp. Polypectomy was performed as dictated by parental consent. Postoperatively treatment with an intranasal steroid was begun. However, polypoid nasal mucosa recurred in 2 months and a Caldwell-Luc procedure was performed. Subjective reports following surgery indicated improvement in daytime irritability, attention, and mood. A follow-up overnight electroencephalogram sleep study confirmed resolution of OSAS. 
Acquisition of protease resistance by prion proteins in scrapie-infected cells does not require asparagine-linked glycosylation. The scrapie and cellular isoforms of the prion protein (PrPSc and PrPC) differ strikingly in a number of their biochemical and metabolic properties. The structural features underlying these differences are unknown, but they are thought to result from a posttranslational process. Both PrP isoforms contain complex type oligosaccharides, raising the possibility that differences in the asparagine-linked glycosylation account for the properties that distinguish PrPC and PrPSc. ScN2a and ScHaB cells in culture produce several PrP molecules with relative molecular masses of 26-35 kDa and proteinase K-resistant cores of 19-29 kDa. When the cells were treated with tunicamycin, this heterogeneity was eliminated and a single PrP species of 26 kDa was observed. Several hours after its synthesis, a fraction of this protein became insoluble in detergents and acquired a proteinase K-resistant core, thus displaying two of the biochemical hallmarks of PrPSc. Synthesis in the presence of tunicamycin restricted the proteinase K-resistant cores of PrP to a single species of 19 kDa. No proteinase K-resistant PrP was found in uninfected cells. Expression of a mutated PrP gene lacking both asparagine-linked glycosylation sites in ScN2a cells resulted in the synthesis of 19-kDa proteinase K-resistant PrP molecules. We conclude that asparagine-linked glycosylation is not essential for the synthesis of proteinase K-resistant PrP and that structural differences unrelated to asparagine-linked oligosaccharides must exist between PrPC and PrPSc. Whether unglycosylated PrPSc molecules are associated with scrapie prion infectivity remains to be established. 
Sensitive detection of clonal antigen receptor gene rearrangements for the diagnosis and monitoring of lymphoid neoplasms by a polymerase chain reaction-mediated ribonuclease protection assay. This report describes a novel assay involving the polymerase chain reaction (PCR) and RNase protection for the rapid and sensitive detection of malignant lymphoid cells by nucleotide sequences within their individual rearranged gamma T-cell receptor (TCRG) genes. In this assay, clonal rearrangements are amplified from the DNA of diagnostic tumor specimens using a consensus V segment primer and a consensus J segment primer to which the promoter for T7 RNA polymerase has been appended. The PCR product from this amplification is transcribed into a radiolabeled RNA probe. Test RNA transcribed from the opposite DNA strand is synthesized by similar methods from TCRG genes of a subsequent biopsy specimen. The test RNA is hybridized with the probe, and mismatched nucleotide sequences in the RNA hybrids are digested by RNase A. Detection of fully protected probe by means of polyacrylamide gel electrophoresis and autoradiography indicates the presence of malignant cells in the test specimen. Dilution experiments with DNA of cell lines from acute lymphoblastic leukemias (ALLs) show that detection of one tumor cell among 10(5) normal bone marrow cells is usually possible. Residual disease was also successfully detected in several cases of ALL during clinical remission, including detection in one case at the 10(-5) level. The procedure described here may provide a simplified and rapid method for the sensitive diagnosis and monitoring of lymphoid malignancies. This procedure should be applicable to most antigen receptor genes, and unlike most comparable methods, requires neither analysis of nucleotide sequence nor synthesis of tumor-specific oligonucleotide probes or primers. 
Red cell membrane sodium transport: possible genetic role and use in identifying patients at risk of essential hypertension. To investigate the influence of a family history of essential hypertension on abnormalities of red cell membrane sodium transport, 28 hypertensive children and their families were studied. In 15 families one or both parents had either essential hypertension or a strong family history. In 13 families neither parent had essential hypertension or a positive family history. There were significant differences between the children with a positive family history of essential hypertension compared with those without. Values are expressed as mean (SD): intracellular sodium concentration (mmol/l cells) 8.19 (2.18) compared with 6.41 (0.98); sodium efflux rate constant 0.4873 (0.1379) compared with 0.5831 (0.1104); and numbers of sodium-potassium ATPase pump sites (BMax) (nmol/l cells) 7.96 (1.71) compared with 9.56 (1.7). Significant differences were also found when the index hypertensive children were excluded and the normotensive siblings with and without hypertensive family histories were compared. These data suggest that abnormal red cell membrane sodium transport has a familial component, and although it is not caused by the hypertension it may be the earliest pathophysiological step in its development, perhaps allowing the identification of children at risk of essential hypertension. 
Nerve growth factor receptor expression in peripheral and central neuroectodermal tumors, other pediatric brain tumors, and during development of the adrenal gland. Nerve growth factor (NGF) is important to the survival, development, and differentiation of neurons. Its action is mediated by a specific cell surface transmembrane glycoprotein, nerve growth factor receptor (NGFR). In this study, NGFR expression by human fetal and adult adrenal medullary tissue, peripheral nervous system (PNS) neuroectodermal tumors (neuroblastoma, ganglioneuroblastoma, ganglioneuroma), pediatric primitive neuroectodermal tumors (PNETs) of the central nervous system (CNS), and CNS gliomas was examined by an immunohistochemical technique. Sixty-nine tumors in total were probed in this manner. Nerve growth factor receptor immunoreactivity was confined to nerve fibers and clusters of primitive-appearing cells in the fetal adrenal, and to nerve fibers and ganglion cells of the adult adrenal medulla; adrenal chromaffin cells were negative. In PNS neuroectodermal tumors, there was NGFR expression in tumor cells of 6 of 11 neuroblastomas and 6 of 6 ganglioneuroblastomas or ganglioneuromas. Thirteen of thirty-five CNS PNETs showed NGFR positivity. In most CNS PNETs, NGFR was restricted to scattered single or small groups of cells, but two tumors with astroglial differentiation showed much more extensive immunoreactivity. Most astrocytomas (11 of 14) and all ependymomas (3 of 3) were intensely NGFR positive. 
Childhood cancers--New Jersey, 1979-1985. In New Jersey, cancers among children aged 0-14 years account for fewer than 1% of all cancers diagnosed annually; however, childhood cancers account for the greatest number of years of potential life lost from cancer. This report summarizes a study by the New Jersey State Department of Health (NJSDH) that determined the incidence and death rates for the most frequent cancers among children aged 0-14 years in New Jersey during 1979-1985; these rates are compared with those for the United States for a comparable period. 
Risk factors for benign oesophageal disease in a random population sample. The association of sex, age, relative weight, smoking and drinking habits, chronic obstructive pulmonary disease (COPD) and economic and marital status, with benign oesophageal disease (BOD) was investigated by means of a point-prevalence study of BOD in a Danish population. A total of 346 individuals, representing subjects who gave positive responses to the discriminating questions pertaining to BOD and risk factors in a previously described questionnaire, as well as control subjects, were invited to participate in a clinical examination. Invasive investigation was accepted by 175 subjects, 114 of whom were diagnosed as having BOD. A statistically significant relationship between BOD and COPD was demonstrated by univariate analysis, and later confirmed by multivariate analysis (P less than 0.01). Odds ratios suggested a non-significant association between BOD and smoking at least 20 g tobacco a day and consuming greater than or equal to 50 alcoholic drinks per week. Obesity, sex, age, marital and economic status were not risk factors for BOD. 
The clinical course of perimesencephalic nonaneurysmal subarachnoid hemorrhage We studied the early clinical course of 65 patients with perimesencephalic (nonaneurysmal) subarachnoid hemorrhage. None of the patients rebled; none had delayed cerebral ischemia; and only 3 patients (5%) developed clinical signs of acute hydrocephalus, 2 requiring ventricular shunting. Hyponatremia and electrocardiographic changes were found in the same proportions as in patients with aneurysmal rupture. All patients had a good outcome after 3 months. To control for the influence of the relatively small amount of cisternal blood in perimesencephalic hemorrhage on the absence of delayed cerebral ischemia, we compared these 65 patients with 49 patients who had aneurysmal subarachnoid hemorrhage. This control group with aneurysms was selected according to a similar amount of cisternal blood, a comparable level of consciousness on admission, and absence of other factors known to increase the risk for delayed cerebral ischemia. We found that 4 of the 49 patients with aneurysmal hemorrhage developed delayed cerebral ischemia (Fisher's exact test, p = 0.03); therefore the relatively small amount of blood does not account for the absence of delayed cerebral ischemia in perimesencephalic hemorrhage. Patients with a perimesencephalic pattern of hemorrhage and a normal angiogram should be considered to have a distinct subset of subarachnoid hemorrhage and should be excluded from future treatment trials of patients with subarachnoid hemorrhage. 
Allografts of tumor nuclear transplantation embryos: differentiation competence. The developmental potential of nuclei can be studied by nuclear transplantation. Although amphibian blastula nuclei and other early embryonic nuclei are totipotent, to our knowledge no nucleus from an adult cell has ever been shown to be totipotent by this procedure. Transfer of Lucke renal carcinoma nuclei into enucleated eggs results in prefeeding swimming tadpoles. Inasmuch as these tadpoles die, rescue of this pluripotential tissue was attempted by grafting fragments of triploid tumor nuclear transplant tadpoles to the tails of normal diploid Rana pipiens hosts. Grafts of tumor nuclear transplant tadpole tissue were histologically indistinguishable from grafts of normally fertilized embryos and developed normal-appearing structures such as complete eyes, well-differentiated neural tissues, kidney tubules, and gut epithelium. Moreover, histological differentiation in tumor nuclear transplant grafts was comparable to that observed in 50-day-old normal larvae. Grafting enhanced the survival of tumor nuclear transplant tissue from no more than 14 days as part of the donor tadpole to 40 days at which time the grafts were harvested as healthy tissue. Thus, both differentiation and survival of tumor nuclear transplant tissue were augmented with the grafting procedure. Cytophotometric analysis of ploidy was used to confirm the tumor origin of the donor tissue. 
Selective pulmonary vasodilation by low-dose infusion of adenosine triphosphate in newborn lambs. The systemic and pulmonary vascular effects of adenosine 5'-triphosphate (ATP) were investigated in 12 newborn lambs during normoxia and during alveolar hypoxia (10% oxygen, 5% carbon dioxide, and 85% nitrogen). Lambs had catheters in the descending aorta, main pulmonary artery, and were studied after a 3-day recovery. We infused ATP or an equal volume of saline solution (control) into the right atrial line in doses ranging from 0.01 to 2.5 mumol/kg per minute. In normoxic lambs, ATP caused a significant decrease in pulmonary vascular resistance in doses of 0.08 to 2.5 mumol/kg per minute, and in systemic vascular resistance in doses of 0.3 to 2.5 mumol/kg per minute. Infusion of ATP in hypoxic lambs caused decreases in pulmonary artery pressure and pulmonary vascular resistance in all the doses tested. Systemic vascular resistance decreased, and cardiac output and heart rate increased in doses greater than 0.3 mumol/kg per minute in hypoxic lambs during ATP infusion. The effects of ATP in hypoxic lambs were not blocked by propranolol, indomethacin, or theophylline. Plasma ATP levels in left atrial blood samples did not change significantly during the infusion of ATP. We conclude that ATP is a vasodilator in lambs, and its effects are specific for pulmonary circulation at doses of less than or equal to 0.15 mumol/kg per minute. The vasodilator effects of ATP appear to be independent of P1 purinergic and beta-adrenergic mechanisms, and of prostacyclin synthesis. 
The use of intravenous milrinone in chronic symptomatic ischemic heart disease. To evaluate the antiischemic effects of intravenous milrinone, 20 patients with angiographically proved coronary artery disease and stable angina were studied at rest and during exercise under control conditions and after an intravenous loading injection of milrinone (50 micrograms/kg/10 min) followed by an infusion with 0.5 micrograms/kg/min. Hemodynamic parameters, epinephrine, norepinephrine, and atrial natriuretic factor were assessed. Control ergometry revealed ischemia; however, during exercise with intravenous milrinone, ischemia was eliminated. Because of unloading effects, there was also a significant decrease in ST segment depression (p less than 0.001). Heart rate increased significantly (p less than 0.001) at rest but increased significantly less after exercise testing (p less than 0.001). The changes in mean arterial pressure, cardiac output, and myocardial oxygen consumption during exercise were not significantly different between the milrinone and control phase. Intravenous milrinone delayed the onset of angina (p less than 0.001) and significantly shortened the duration of anginal attacks (p less than 0.05); exercise duration in the milrinone phase was longer than in the control phase (p = 0.051). Because of vasodilatation, a mild secondary increase in norepinephrine was observed during the milrinone phase, and there was a significantly smaller increase in atrial natriuretic factor during exercise while receiving milrinone as a result of preload reduction (p less than 0.05). Intravenous milrinone produced beneficial hemodynamic and antiischemic effects in patients with coronary artery disease, stable angina, and reproducible ST segment depression probably by enhancing myocardial contractility and reducing preload and afterload. 
Carcinoma of the rectum: a 10-year experience. A consecutive series of 303 patients with carcinoma of the rectum and distal sigmoid colon treated by a single surgeon over a 10-year period are reported. Of these, 202 underwent an anterior resection, 85 an abdominoperineal excision of the rectum and 16 a coloanal anastomosis. Surgery was considered palliative in 52 patients undergoing anterior resection and 24 undergoing abdominoperineal resection. The 30-day hospital mortality rate was six patients (3 per cent) for anterior resection and two patients (2 per cent) for abdominoperineal resection. Peroperative anastomotic testing demonstrated leakage in five stapled anastomoses; these were rectified and no clinical sequelae occurred. Two patients (1 per cent) developed a clinical anastomotic leak, one of which proved fatal; in each case the intraoperative test was negative. The overall 5-year survival rate was 64 per cent after anterior resection and 52 per cent after abdominoperineal resection; the median follow-up was 64 months. The incidence of local pelvic recurrence was 6.4 per cent after anterior resection and 14 per cent after abdominoperineal (not significant). These results confirm the success of sphincter-saving anterior resection combined with total mesorectal excision, routine full mobilization of the splenic flexure and cancercidal lavage of the distal rectum in the treatment of low rectal carcinomas; morbidity, local recurrence and survival are not compromised. 
Pontine myelinolysis after correction of hyponatremia during burn resuscitation. Central pontine myelinolysis is a neurologic disease produced by the rapid correction of hyponatremia. This report describes the occurrence of central pontine myelinolysis in a patient with burns. The natural history of this paralyzing condition and suggestions for its prevention are discussed. Severely burned and hyponatremic patients are at risk for this disorder because a large amount of sodium ion is typically required for the treatment of burn shock. Awareness of this phenomenon and avoidance of rapid correction of hyponatremia are essential to its prevention. 
Aortoesophageal fistula: a comprehensive review of the literature. Aortoesophageal fistula (AEF) is a relatively rare but life-threatening cause of upper gastro-intestinal bleeding. The clinical characteristics of AEF are so unique that a presumptive bedside diagnosis can be made at the time of presentation. In the past decade, surgical management has improved to the point that cure is now possible. For these reasons, we have reviewed the literature. We summarize our findings with respect to the etiology and clinical characteristics of AEF. Further, we discuss the diagnostic modalities that may be used to confirm the diagnosis, and the therapeutic modalities available to slow the hemorrhage, so as to allow time to correct the anatomic defect. 
Antihypertensive drug treatment. Potential, expected, and observed effects on stroke and on coronary heart disease. The effects of prolonged differences in diastolic blood pressure (DBP) on the risks of stroke and of coronary heart disease (CHD) were estimated from nine major prospective observational studies involving about 420,000 men and women who were followed up for intervals of 6-25 years. The results indicate that a prolonged difference of about 6 mm Hg in DBP was associated with approximately 37% fewer strokes and 23% fewer CHD deaths and nonfatal myocardial infarctions. The effects of equivalent reductions in DBP produced by antihypertensive drug treatment but maintained for only a few years have been estimated in several overviews of randomized trials involving a total of 30,000-40,000 patients. The results of the overviews indicate that treatment reduced the risk of stroke by about 40%, suggesting that most or all the long-term potential benefits for stroke due to lower DBP were achieved within about 3 years of beginning treatment. The risks of nonfatal myocardial infarction and CHD death may have been reduced by about 10% among patients allocated to active treatment; the 95% confidence limits for the difference ranged from about zero to about 20%. Whatever the true effect of treatment on CHD, it would appear somewhat less than the difference in risk estimated from the observational studies for a prolonged difference in DBP of the same size. This apparent shortfall in benefit may reflect a long time-course for changes in DBP to have their full effects on CHD, possible adverse side effects of the principal trial treatments, or both. 
Cardiac rupture secondary to blunt trauma: a rapidly diagnosable entity with two-dimensional echocardiography. A 58-year-old woman involved in a single automobile accident sustained an isolated rupture of the right ventricle without any other obvious form of external trauma. On presentation to an outlying hospital, hypotension was the only apparent clinical finding suggestive of injury. After several hours of delay, the patient was transferred to a tertiary medical center. The diagnosis of cardiac rupture was made by two-dimensional echocardiography. The patient underwent successful surgical repair and was discharged home in good condition eight days after sustaining this potentially fatal injury. 
Nonprescription drugs and hypertension. Which ones affect blood pressure? Hypertensive patients should be aware of the possible effects of nonprescription medications on blood pressure control. For absolute safety, no adrenergic agents should be used. Nasal phenylephrine hydrochloride is probably the safest of these agents, and pseudoephedrine hydrochloride may also be safe. Phenylpropanolamine hydrochloride and ephedrine sulfate are probably best avoided. The effects of other adrenergic agents (eg, epinephrine) on blood pressure have not been clinically evaluated. Ibuprofen may elevate blood pressure if taken in maximum over-the-counter doses for more than a few days. The ethanol and sodium chloride content of nonprescription drugs taken in recommended doses does not appear to pose a great hazard. 
Fire hydrant play: injuries and their prevention. A total of 86 children treated for injuries that occurred while playing in water from fire hydrants are described. Patients were urban (100%), minority (97%) children with few alternative means for keeping cool. Injuries occurred on extremely hot summer days (mean maximum temperature 36.3 degrees C [97.5 degrees F]). Laceration of the foot on broken glass was the most common injury and was prevented by wearing footwear (P less than .001). Motor vehicles caused all serious injuries. Sprinkler attachments on the hydrants were associated with significantly fewer motor vehicle-related injuries (P less than .001) and water pressure-related injuries (P = .02). Adults were present at more than 90% of injury scenes, but had no effect on the safety of fire hydrant play. Public policy should be directed toward increasing the availability of alternative means for keeping cool, increasing the number of hydrants equipped with sprinklers, and reducing the amount of broken glass in the streets. Public education targeting adults to remove glass from the street, insist that children wear footwear, and open only those hydrants that have sprinklers could further reduce injuries to urban children who play in water from fire hydrants. 
Improved tumor imaging with radiolabeled monoclonal antibodies by plasma clearance of unbound antibody with anti-antibody column. Imaging of tumors by using radiolabeled monoclonal antibodies (MoAs) is hindered by the presence of background activity. To reduce this problem, the authors investigated the process of removing labeled MoAs from plasma at selected times by means of extracorporeal immunoadsorption. In seven patients with either lung or breast carcinoma, an indium-111-labeled murine antibody was intravenously administered. Six to 24 hours later, immunoadsorption was performed by passing the patients' plasma through a goat anti-mouse antibody column connected to a plasma separator. Whole-body computer images were obtained before and after the treatment. Blood pool activity in the images was reduced by an average of 59%, while tumor activity dropped by only 10%. Tumor-to-blood activity ratios therefore more than doubled, improving by an average of 121% between the pre- and posttreatment image sets. Eight of 12 areas of known disease and three areas of unknown but later documented disease were detected after the immunoadsorption process, while the three areas of unknown disease and three of the areas of known disease were not detected in the preclearance images. Thus, the feasibility of using extracorporeal immunoadsorption to improve MoA imaging of tumors was demonstrated. 
Electrophysiologic recording and thermodynamic modeling demonstrate that helium-neon laser irradiation does not affect peripheral Adelta- or C-fiber nociceptors. The effect of helium-neon laser irradiation (632.5 nm) on A delta- and C-fiber sensory afferents was investigated in the rabbit cornea, to determine the physiologic basis for reports that low power (0.1-5 mW) helium-neon (He-Ne) lasers produce acute analgesia and alleviate chronic pain. Multiple and single unit extracellular recordings from nociceptive corneal afferent nerves (C-fiber cold, C-fiber chemical, A delta mechanical and A delta bimodal) were used to study the effects of He-Ne laser radiation upon the electrophysiologic responses to mechanical, thermal, chemical and electrical stimulation of the cornea. Action potentials were analyzed for latency, amplitude, rise time, duration and frequency. Exposure of the neural receptive field and/or nerve bundle to a 4-mm diameter He-Ne laser (0-5 mW; 0-1800 sec) did not alter spontaneous or evoked neural activity. In addition, single unit action potential parameters were not altered by laser irradiation. Modeling of thermal changes produced by He-Ne radiation on corneal nerves indicated that effects predicted for receptor and axonal depths in both skin and cornea were minimal (less than 0.15 degrees C) and unlikely to alter sensory transduction or transmission. 
Submucous resection of the nasal septum as an outpatient procedure. We report our experience of submucous resection of the nasal septum under local anaesthesia as an outpatient procedure. We have audited 50 consecutive cases and compared the results with a similar group of patients in whom the operation was carried out in the usual way under general anaesthesia. We have found the procedure to be safe, effective and economically advantageous. 
Newborn behavioral performance in colic and noncolic infants. The specific purpose of this investigation was to examine the newborn performance of colic and noncolic infants on the Brazelton Neonatal Behavior Assessment Scale (BNBAS). The sample was composed of 119 firstborn infants from healthy, married, white couples. Data were collected prenatally, during the perinatal period, and postnatally from birth through four months of infant age. A total of 38 infants (32%) were believed to have colic. Colicky infants differed significantly from noncolicky infants on one of the seven item clusters, labeled the BNBAS Orientation cluster (p less than .05). 
Histological changes in free jejunal grafts used in pharyngeal reconstruction. A histological study was performed of biopsies taken from jejunal free grafts used in pharyngeal reconstruction. The main findings were a decreased crypt/villi ratio and a mild chronic inflammatory infiltrate. There was no evidence of metaplastic or dysplastic transformation. 
Very late recurrence of renal vasculitis. We report a case of renal vasculitis with a relapse occurring 9 and a half years after the original presentation. The plasma creatinine six months before relapse was only 118 mumol/l. During the initial illness there was histological evidence of glomerular damage but at the time of relapse renal biopsy showed the remaining glomeruli to be normal with the destructive process causing fibrinoid necrosis of arteries. 
Cardiovascular collapse following orthoclone OKT3 administration: a case report. Orthoclone OKT3 has been described to have significant adverse effects on the cardiovascular system, including pulmonary edema, angina, dysrhythmias, hypertension, and hypotension, usually following the first or second doses of the drug. We describe a case of cardiopulmonary arrest in a patient 1 minute after the initial injection of OKT3. Two subsequent doses were successfully administered with the guidance of hemodynamic monitoring, which showed profound, immediate effects of OKT3 on the cardiovascular system. Potential mechanisms of these effects are discussed. 
Small bowel obstruction after colon resection for benign and malignant diseases. To determine the etiology and outcome of patients with small bowel obstruction after a colon resection for benign and malignant diseases, the medical records of 118 patients who underwent 120 laparotomies for small bowel obstruction were reviewed. Contrary to previous reports, benign adhesions were responsible for the obstruction in all patients with a history of benign colon disease, 82.6 percent of patients with a history of adenocarcinoma of the colon without known recurrence, and 30.1 percent of patients with known recurrent malignancy. The morbidity and mortality was more related to the etiology of the obstruction rather than the preoperative delay or operative procedure performed. Considering the high likelihood of adhesive obstruction in patients with a history of, or known, metastatic colorectal carcinoma, it is suggested that these not deter surgeons from aggressive early surgical intervention in these patients who develop small bowel obstruction. 
Cytochrome c oxidase deficiency with acute onset and rapid recovery. A 7-year-old girl with cytochrome c oxidase deficiency who had no neurologic deficits in infancy suddenly developed ophthalmoplegia, ptosis, and respiratory arrest. She recovered almost completely 80 days after onset, suggesting that acute onset and rapid remission are observed in patients with cytochrome c oxidase deficiency. It is also possible that early initiation of therapy in cytochrome c oxidase deficiency with coenzyme Q10 may hasten and enhance the therapeutic effect. 
Treatment of fulminant viral hepatic failure with prostaglandin E. A preliminary report. The effect of prostaglandins (PG) in patients with fulminant and subfulminant viral hepatitis was studied. Seventeen patients presented with FHF secondary to hepatitis A (N = 3), hepatitis B (N = 6) and non-A, non-B (NANB) hepatitis (N = 8). Fourteen of the 17 patients had stage III or IV hepatic encephalopathy (HE). At presentation, the mean AST was 1844 +/- 1246 units/liter, bilirubin 232 +/- 135 mumol/liter, PT 34 +/- 18 and PTT 73 +/- 26 sec, and coagulation factors V and VII were 8 +/- 4 and 9 +/- 51%, respectively. Twelve of 17 patients responded to PGE1 rapidly, with a decrease in AST from 1540 +/- 833 to 188 +/- 324 units/liter, a decrease in prothrombin time from 27 +/- 7 sec to 12 +/- 1 sec, PTT from 61 +/- 10 sec to 31 +/- 2 sec, and an increase in factor V from 9 +/- 4% to 69 +/- 18% and factor VII from 11 +/- 5% to 71 +/- 20%. Five responders with NANB hepatitis relapsed upon discontinuation of therapy, with recurrence of HE and increases in AST and PT but improvement was observed upon retreatment. After four weeks of intravenous therapy, oral PGE2 was substituted. Two patients have recovered completely and remain in remission six and 12 months following cessation of therapy. Two additional patients continue in remission after two and six months of PGE2. No relapses have been seen in patients with hepatitis A virus (HAV) or hepatitis B virus (HBV) infection. Liver biopsies in the 12 surviving patients have returned to normal. These results suggest efficacy of PGE for FHF. Further investigation is warranted. 
Complete atrioventricular block complicating inferior wall acute myocardial infarction treated with reperfusion therapy. TAMI Study Group. Previous studies report larger myocardial infarcts and increased in-hospital mortality rates in patients with inferior wall acute myocardial infarction (AMI) and complete atrioventricular block (AV), but the clinical implications of these complications in patients treated with reperfusion therapy have not been addressed. The clinical course of 373 patients--50 (13%) of whom developed complete AV block--admitted with inferior wall AMI and given thrombolytic therapy within 6 hours of symptom onset was studied. Acute patency rates of the infarct artery after thrombolytic therapy were similar in patients with or without AV block. Ventricular function measured at baseline and before discharge in patients with complete AV block showed a decrement in median ejection fraction (-3.5 vs -0.4%, p = 0.03) and in median regional wall motion (-0.14 vs +0.24 standard deviations/chord, p = 0.05). The reocclusion rate was higher in patients with complete AV block (29 vs 16%, p = 0.03). Patients with complete AV block had more episodes of ventricular fibrillation or tachycardia (36 vs 14%, p less than 0.001), sustained hypotension (36 vs 10%, p less than 0.001), pulmonary edema (12 vs 4%, p = 0.02) and a higher in-hospital mortality rate (20 vs 4%, p less than 0.001), although the mortality rate after hospital discharge was identical (2%) in the 2 groups. Multivariable logistic regression analysis revealed that complete AV block was a strong independent predictor of in-hospital mortality (p = 0.0006). Thus, despite initial successful reperfusion, patients with inferior wall AMI and complete AV block have higher rates of in-hospital complications and mortality. 
Hypothalamic peptides modulate cytosolic free Ca2+ levels and adenylyl cyclase activity in human nonfunctioning pituitary adenomas. The effects of hypothalamic peptides (TRH, GnRH, arginine vasopressin, vasoactive intestinal peptide, GHRH, CRH, and SRIH) on cytosolic free calcium concentrations ([Ca2+]i) and adenylyl cyclase (AC) activity were evaluated in 12 nonfunctioning pituitary adenomas. TRH, GnRH, and arginine vasopressin induced a marked [Ca2+]i rise in 10/12, 4/12, and 2/5 tumors, respectively. The transients induced by these peptides were due to both Ca2+ mobilization from the intracellular stores and Ca2+ influx from the extracellular medium. AC activity was evaluated in 10 adenomas; 1 microM vasoactive intestinal peptide induced a 2- to 6-fold stimulation of the enzyme activity in all tumors, while neither GHRH nor CRH were effective. Moreover, in 5/10 tumors 1 microM SRIH reduced both AC activity and [Ca2+]i, while in 2/10 the peptide caused a significant rise in [Ca2+]i despite the AC inhibition and in 3/10 SRIH did not modify either AC activity or [Ca2+]i. This study indicates that in nonfunctioning pituitary adenomas a wide spectrum of hypothalamic peptides modulate [Ca2+]i and AC activity. Moreover, the presence of biologically active receptors may offer a possible target for therapeutic intervention. 
Effects of interleukin-4 and interleukin-6 on the proliferation of CD34+ and CD34- blasts from acute myelogenous leukemia. We studied the effects of interleukin-4 (IL-4) and IL-6 on the growth of leukemic blasts from 40 patients with acute myelogenous leukemia (AML). Patients were selected on the basis of negativity for a series of B-cell antigens including CD10 and CD19. Twenty-one cases were CD34-positive (CD34+) (greater than 15% of blasts) and the remaining 19 were CD34-negative (CD34-) (less than 3% of blasts). IL-4 alone (100 U/ml) could stimulate either DNA synthesis (with greater than 2.0 stimulation index) or leukemic blast colony formation in 24 of 40 AML patients. In the presence of other growth factors, IL-4 showed divergent effects on IL-3-, granulocyte-macrophage colony-stimulating factor-, granulocyte colony-stimulating factor-, or erythropoietin-dependent colony formation. These effects of IL-4 were observed in both CD34+ and CD34- AML cases. IL-6 (100 U/mL) alone could not stimulate DNA synthesis and blast colony formation except for one CD34+ case. On the other hand, IL-6 showed synergistic effects on IL-3- and IL-4-dependent blast colony formation in 10 of 12 and 7 of 9 CD34+ AML cases, respectively. Among CD34- AML cases, such synergism was seen only in 1 of 12 cases for IL-3-dependent colony formation and in 3 of 7 cases for IL-4-dependent colony formation. The divergent effect of IL-4 and the synergistic effect of IL-6 were also observed in purified CD34+ leukemic blast populations, indicating that these phenomena are not mediated by accessory cells. The present study suggests that IL-4, alone or in combination with other growth factors, has divergent effects on the growth of AML progenitors irrespective of the CD34 expression, and that IL-6 acts synergistically with IL-3 or IL-4 on the growth of leukemic progenitors preferentially in CD34+ AML. 
Is pulsed Doppler velocimetry useful in the management of multiple-gestation pregnancies? Few studies have addressed the significance of umbilical artery pulsed Doppler velocimetry in multiple gestation. Level II ultrasonography and pulsed Doppler studies were performed in 94 twin pairs and seven sets of triplets, which yielded data on 207 fetuses. A systolic/diastolic ratio was calculated for each fetus; abnormal pulsed Doppler velocimetry showed high correlation with adverse pregnancy events. Those with abnormal Doppler findings tended to be born 3 to 4 weeks earlier and to exhibit a greater number of stillbirths and structural malformations, as well as greater morbidity, when compared with fetuses without abnormal Doppler results. Fifteen of 17 infants with abnormal antenatal waveforms suffered serious morbidity. Seven were small for gestational age, and two were borderline for small for gestational age. An additional five infants with abnormal waveforms were appropriate for gestational age but were either recipient or donor in the twin transfusion syndrome. Eleven fetuses with this syndrome are described. Donor twins tended to be severely small for gestational age, with 7 of the 11 infants showing elevated systolic/diastolic ratios. Amniotic fluid volume tended to be diminished in the donor's sac but normal or increased in the recipient's sac. The observations in the study correlate with suspected physiologic changes of this syndrome. Because present findings suggest that fetuses with abnormal velocimetry suffer increased morbidity and mortality, a more rational method of management that uses Doppler data is suggested for multiple gestations. 
Percutaneous biopsy of left adrenal masses: prevalence of pancreatitis after anterior approach. Acute pancreatitis is an unusual but recognized complication of percutaneous aspiration biopsy of the pancreas. As the pancreatic tail is located anterior to the left adrenal gland, percutaneous biopsy of a left adrenal mass via the anterior approach may result in needle passage through the tail of the pancreas with subsequent potential development of pancreatitis. To evaluate this risk, we retrospectively reviewed 48 CT-directed percutaneous aspiration biopsies of left adrenal masses done between 1984 and 1989 at two institutions. Positioning of the patient, the course of the needle, the number of needle passes, and the size of the needle were analyzed. Thirty-three (69%) of 48 biopsies of a left adrenal mass were performed by using the anterior approach. The pancreas was traversed by one or more needles in 32 of 33 cases. Biopsies were performed with 20- to 22-gauge needles, and the number of needle passes varied widely. The medical records of the 33 patients in whom the anterior approach was used also were reviewed for complications. Acute pancreatitis, which required 11-13 days of hospitalization, developed in two patients (6%). None of the other 31 patients suffered a complication. We conclude that the pancreatic tail is routinely traversed by the biopsy needle when biopsy of a left adrenal mass is done via the anterior approach and that severe acute pancreatitis can occur as a result. 
Variability in physicians' decisions on caring for chronically ill elderly patients: an international study. OBJECTIVES: To determine what treatment decisions physicians will make when faced with an incompetent elderly patient with life-threatening gastrointestinal bleeding and to identify the factors that affect their decisions. DESIGN: Survey. SETTING: Family practice, medical and geriatrics rounds in academic medical centres and community hospitals in seven countries. PARTICIPANTS: Physicians who regularly cared for incompetent elderly patients. OUTCOME MEASURE: A self-administered questionnaire containing three case vignettes. Each provided the same details on an incompetent elderly patient; however, one gave no information about the wishes of the patient and his family (no directive), the second provided a do-not-resuscitate (DNR) request, and the third included a detailed therapeutic and resuscitative effort chart (DTREC) requesting maximum therapeutic care without admission to the intensive care unit (ICU). The four treatment options were supportive care only, limited therapeutic care, maximum therapeutic care without admission to the ICU and maximum care with admission to the ICU. MAIN RESULTS: Treatment decisions varied and were systematically related to age, level of training and country (p less than 0.001). The older physicians and those in family medicine were less likely than the others to choose aggressive treatment options. Brazilian and US physicians were the most aggressive; Australian physicians were the most conservative. The DNR request resulted in a significant decrease in the number of physicians choosing aggressive options (p less than 0.001). The DTREC resulted in a move toward more aggressive treatment, as outlined in the directive (p less than 0.001). Overall, however, about 40% of the physicians chose a level of care different from what had been requested. Furthermore, over 10% would have tried cardiopulmonary resuscitation despite the DNR request. CONCLUSION: Treatment of incompetent elderly patients with life-threatening illness varies widely within and between countries. Uniform standards should be developed on the basis of societal values and be communicated to physicians. 
Intracranial neurenteric cysts. Report of two cases. Two cases of intracranial neurenteric cysts are reported and the literature is reviewed. Neurenteric cysts are rare congenital lesions that tend to occur in the spinal intradural space. An intracranial location is exceptional. 
Proton-pump inhibition for acid-related disease. Omeprazole and lansoprazole are the forerunners of a group of substituted benzimidazole compounds that block the gastric proton pump. These drugs exert a potent antisecretory effect by blocking the final common pathway of acid secretion. Prolonged, potent reduction of acid secretion using omeprazole has resulted in significant therapeutic advantage over existing antisecretory medication, such as H2 receptor antagonists (H2RAs). Research experience with lansoprazole indicates that it has treatment properties for acid-related disease that are similar to those of omeprazole. Omeprazole has been used successfully in the treatment of reflux esophagitis and the Zollinger-Ellison syndrome in the United States over the past year and has received approval recently as first-line therapy for duodenal ulcer disease. Research involving more than 20,000 individuals, postmarketing surveillance studies, and thorough safety studies in man and animals have shown omeprazole to be well tolerated, with an incidence and spectrum of adverse events in clinical trials similar to those observed with H2RAs. 
Epidural lipomatosis as a cause of spinal cord compression in polymyalgia rheumatica. Polymyalgia rheumatica (PMR) is a common rheumatologic disorder in older individuals that usually requires chronic, low dose corticosteroid therapy for adequate control of symptoms. Epidural lipomatosis is a rare complication of chronic corticosteroid use in which neurologic deficits occur due to extradural fat compression of the spinal cord. The author describes the first reported case of epidural lipomatosis occurring as a complication of corticosteroid therapy in a patient with PMR. 
The child with spells. The purpose of this article was to discuss paroxysms, both neurologic and non-neurologic, that can mimic seizures. This is summarized in Table 4. It should be clear that the evaluation of any spell in a child should begin with a detailed and complete history. Historical features should focus on all aspects of the event--length of time, situation, appearance, quantity, as well as other features not directly pertaining to the event. Physical and neurologic examinations are frequently normal. Ancillary testing that may prove valuable include routine and video EEG monitoring as well as home video recording. 
Controlled trial of hypnotherapy in the treatment of refractory fibromyalgia. In a controlled study, 40 patients with refractory fibromyalgia were randomly allocated to treatment with either hypnotherapy or physical therapy for 12 weeks with followup at 24 weeks. Compared with the patients in the physical therapy group, the patients in the hypnotherapy group showed a significantly better outcome with respect to their pain experience, fatigue on awakening, sleep pattern and global assessment at 12 and 24 weeks, but this was not reflected in an improvement of the total myalgic score measured by a dolorimeter. At baseline most patients in both groups had strong feelings of somatic and psychic discomfort as measured by the Hopkins Symptom Checklist. These feelings showed a significant decrease in patients treated by hypnotherapy compared with physical therapy, but they remained abnormally strong in many cases. We conclude hypnotherapy may be useful in relieving symptoms in patients with refractory fibromyalgia. 
Changes in portal blood flow consequent to partial hepatectomy: Doppler estimation. Hemodynamic changes in portal blood flow were investigated in 56 patients with hepatic tumors who underwent partial hepatectomy. Portal flow was measured with a Doppler ultrasound system before, during, and after surgery. The portal flow of patients who underwent massive hepatectomy decreased intraoperatively. The portal flow per unit of cardiac output decreased in patients who underwent massive or major hepatectomy, patients with a cirrhotic liver, and patients who had a satisfactory postoperative course. Postoperatively, the portal flow in patients with a poor clinical outcome (multiple organ failure, hepatic failure, and cardiorespiratory failure) decreased significantly. Monitoring portal hemodynamic values appears to be useful in providing an index of "hepatic functional reserve." Adequate portal flow is essential for postoperative hepatic regeneration; changes in portal hemodynamic values may be directly related to the patient's ability to survive surgery and to regain or maintain normal liver function. 
Aneurysms of the intracavernous carotid artery: a multidisciplinary approach to treatment. Of 43 cavernous sinus aneurysms diagnosed over 6 1/2 years, 23 fulfilled indications for treatment; of these 19 were treated, eight surgically and 11 with interventional radiological techniques. Six small and two giant aneurysms were treated surgically: four were clipped, two were repaired primarily, and two were trapped with placement of a saphenous-vein bypass graft. Seven large and four giant aneurysms were treated with interventional radiological techniques: in five cases the proximal internal carotid artery (ICA) was sacrificed; one aneurysm was trapped with detachable balloons; and five were embolized with preservation of the ICA lumen. The mean follow-up period was 25 months. At follow-up examination, three patients in the surgical group were asymptomatic, two had improved, and three had worsened. Three of these patients had asymptomatic infarctions apparent on computerized tomography (CT) scans. At follow-up examination, four radiologically treated patients were asymptomatic, five had improved, two were unchanged, and none had worsened. One patient had asymptomatic and one minimally symptomatic infarction apparent on CT scans; both lesions were embolic foci after aneurysm embolization with preservation of the ICA. It is concluded that treatment risk depends more on the adequacy of collateral circulation than on the size of the aneurysm. A multidisciplinary treatment protocol for these aneurysms is described, dividing patients into high-, moderate-, and low-risk groups based on pretreatment evaluation of the risk of temporary or permanent ICA occlusion using a clinical balloon test occlusion coupled with an ICA-occluded stable xenon/CT cerebral blood flow study. Radiological techniques are suggested for most low-risk patients, while direct surgical techniques are proposed for most moderate- and high-risk patients. 
Assessment of exercise tolerance in chronic congestive heart failure. In patients with chronic heart failure, exercise capacity is poorly related to cardiac hemodynamics, and peripheral circulation is an important determinant of exercise tolerance. The ability of the muscle vasculature to dilate is markedly impaired, in part, because of exaggerated neurohumoral activity increasing vascular wall stiffness. For this reason, increasing cardiac output is not sufficient to increase exercise capacity if not accompanied by improving vascular reactivity. The poor reliability and reproducibility of exercise tolerance assessed by maximal exercise duration or maximal attained work load (particularly on a treadmill) has led to widespread measurement of respiratory gas during exercise. Peak oxygen consumption (peak VO2), even if it is symptom-limited, has been shown to be a very reproducible criterion of exercise tolerance; moreover, because VO2 is the product of cardiac output and arteriovenous oxygen difference, it also has a qualitative hemodynamic significance. Ventilatory threshold can be determined before maximal exercise; however, problems of determination limit the practical value of this criterion. Unfortunately, peak VO2 lacks sensitivity to detect minor improvement or impairment of symptoms during daily life, although these are significant to the patient. Submaximal exercises have been proposed for this purpose and are currently being evaluated. 
Percutaneous balloon pericardial window for patients with malignant pericardial effusion and tamponade. We performed percutaneous balloon pericardial window (PBPW) in 8 patients (age 40 to 70 yrs; 4 men, 4 women) with malignant pericardial effusion and tamponade. Pericardial window was indicated because they continued to drain greater than 100 ml/day of pericardial fluid through the pigtail catheter for greater than or equal to 3 days. A 0.038 inch guidewire was advanced through the pigtail catheter into the pericardial space and then the catheter was removed. A 20 mm diameter, 3 cm long balloon dilating catheter was advanced to straddle the parietal pericardium. Manual inflations were performed until the waist produced by the pericardium disappeared. All patients tolerated the procedure well with minimal discomfort and with no complications. A left or bilateral pleural effusion occurred in all patients after PBPW. No patient developed recurrent pericardial tamponade at a mean follow-up of 6 +/- 2 months. Thus, PBPW is a useful and safe technique to avoid surgery in patients with malignant pericardial effusion and tamponade. 
Three-dimensional x-ray computed tomography of the temporal bone as an aid to surgical planning. Three-dimensional x-ray computed tomography (3DCT) has been useful in planning surgical procedures involving craniofacial reconstruction, the pelvis, hip, spine, knee and shoulder. The clinical use of 3DCT in temporal bone surgery has not been evaluated. We used 3DCT to assess temporal bone anatomy in 9 patients. These cases evaluated two encephaloceles, two postinflammatory dehiscences, two temporal bone fractures, one glomus jugulare tumor, one acoustic neuroma, and one meningioma. We found 3DCT useful in these temporal bone applications as a supplement to standard two-dimensional CT scanning (2DCT). While 3DCT provided a better preoperative understanding of the underlying anatomy, no treatment was modified solely on the basis of the information derived from the 3-D presentation of data. We conclude that, although 3DCT images have some qualitative advantages over 2DCT techniques, their value in further defining temporal bone morphology must be evaluated against the cost entailed by their use. 
The analgesic effects of caffeine in headache. Caffeine is frequently added to mild analgesic preparations but its effect when used alone on pain has never been studied in humans. Using a double-blind placebo-controlled multiple crossover design, 53 patients with non-migrainous headaches were given placebo, acetaminophen, 2 doses of caffeine and 2 combinations of caffeine with acetaminophen. Caffeine appeared to have independent analgesic effects that were equivalent to acetaminophen and were still significant when statistical adjustments were made for prior caffeine consumption and caffeine's effects on mood. 
Molecular biology of prion diseases. Prions cause transmissible and genetic neurodegenerative diseases, including scrapie and bovine spongiform encephalopathy of animals and Creutzfeldt-Jakob and Gerstmann-Straussler-Scheinker diseases of humans. Infectious prion particles are composed largely, if not entirely, of an abnormal isoform of the prion protein, which is encoded by a chromosomal gene. A posttranslational process, as yet unidentified, converts the cellular prion protein into an abnormal isoform. Scrapie incubation times, neuropathology, and prion synthesis in transgenic mice are controlled by the prion protein gene. Point mutations in the prion protein genes of animals and humans are genetically linked to development of neuro-degeneration. Transgenic mice expressing mutant prion proteins spontaneously develop neurologic dysfunction and spongiform neuropathology. Understanding prion diseases may advance investigations of other neurodegenerative disorders and of the processes by which neurons differentiate, function for decades, and then grow senescent. 
Anterior transpetrosal-transtentorial approach for sphenopetroclival meningiomas: surgical method and results in 10 patients. This report presents a new surgical method and the results in 10 patients with petroclival meningiomas extending into the parasellar region (sphenopetroclival meningiomas). Minimal but effective extradural resection of the anterior petrous bone via a middle fossa craniotomy offered a direct view of the clival area with preservation of the temporal bridging veins and cochlear organs. The dural incision was extended anteriorly to Meckel's cave, and in cases with invasion of the cavernous sinus, Parkinson's triangle was enlarged by mobilization of the trigeminal nerve. This approach offered an excellent view from the mid-clivus to the cavernous sinus. Extra-as well as intradural tumor masses and dural attachments could be cleared under direct view of the pontine surface. The risk of injury to the lower cranial nerve and of retraction damage to the temporal lobe and brain stem were kept minimal by this approach. Total tumor resection was achieved in 7 patients, with no resultant mortality. Eight patients had a satisfactory postsurgical course, extraocular paresis being their main complaint. The extent of tumor resection depended on the degree of tumor adhesion to the carotid artery, and operative morbidity on the degree of tumor invasion of the brain stem. Of the 3 patients in whom subtotal tumor removal was achieved, only one experienced regrowth of the tumor and underwent a second operation during the follow-up period (6 months-6 years). 
Native right atrial tamponade with the Jarvik total artificial heart. Following a massive myocardial infarction culminating in cardiogenic shock, a 61-year-old man underwent implantation of the Jarvik 70-ml total artificial heart. On the fifth postoperative day, hemodynamic instability coupled with subtle radiographic changes and impaired mechanical right ventricular diastolic inflow were instrumental in establishing the diagnosis of localized native right atrial tamponade. To our knowledge, this report is the first detailed discussion of this phenomenon. 
High density lipoprotein turnover in patients with hypertension. Although hyperinsulinemia and decreased high density lipoprotein cholesterol concentration can occur in patients with hypertension, there is no information available concerning the dynamic state of high density lipoprotein metabolism. To address this issue, we quantified high density lipoprotein turnover in 12 patients with mild hypertension and 11 matched subjects with normal blood pressure. Patients with high blood pressure had lower high density lipoprotein cholesterol concentrations. Fractional catabolic rates of 125I-apolipoprotein AI (apoAI)/high density lipoprotein were faster in patients with hypertension (0.36 +/- 0.02 versus 0.26 +/- 0.02 l/day, p less than 0.001). Total synthetic rates of apoAI were also significantly greater in patients with high blood pressure (17.4 +/- 1.1 versus 13.2 +/- 0.6 mg/kg/day, p less than 0.001). Although significant correlation was observed between blood pressure and fractional catabolic rate of 125I-apoAI/high density lipoprotein in the experimental population (r = 0.52, p less than 0.01), no relation was found when patients with normal blood pressure or hypertension were considered separately. However, a highly significant positive correlation was found between 125I-apoAI/high density lipoprotein fractional catabolic rate and insulin concentration in the entire population (r = 0.72, p less than 0.001). In conclusion, the patients with mild hypertension studied were hyperinsulinemic, had a faster fractional catabolic rate of 125I-apoAI/high density lipoprotein, and a lower high density lipoprotein-cholesterol concentration. It is suggested that the changes seen in high density lipoprotein-cholesterol concentration and 125I-apoAI/high density lipoprotein fractional catabolic rates were secondary to the hyperinsulinemia and not due to the high blood pressure per se. 
Cold-induced brain edema and infarction are reduced in transgenic mice overexpressing CuZn-superoxide dismutase. It has been proposed that oxygen-derived radicals, superoxide in particular, are involved in the alteration of blood-brain barrier permeability and the pathogenesis of brain edema following trauma, ischemia, and reperfusion injury. Using transgenic mice that overexpress the human gene for copper-zinc-superoxide dismutase, we studied the role of superoxide radicals in the blood-brain permeability changes, edema development, and delayed infarction resulting from cold-trauma brain injury. At 2 hours after a 30-second cold injury, cerebral water and Evans blue contents were reduced, respectively, from 80 +/- 0.2% and 132.7 +/- 12.9 micrograms/gm of dry weight for nontransgenic mice to 78.5 +/- 0.3% and 87.1 +/- 9.9 micrograms/gm of dry weight for transgenic mice. Infarction, as measured by 2,3,5-triphenyltetrazolium chloride staining, was reduced by 52% in transgenic brains. These data indicate that an increased level of superoxide dismutase activity in the brain reduces the development of vasogenic brain edema and infarction. Superoxide radicals play an important role in the pathogenesis of these lesions in cold-traumatized brain. 
Constitutive expression and role in growth regulation of interleukin-1 and multiple cytokine receptors in a biphenotypic leukemic cell line. A cell line (B1) was established from the bone marrow of a patient with a relapse of acute leukemia characterized by a 4;11 chromosomal translocation and biphenotypic features of early B and myeloid lineages. Analysis of the growth requirements of this cell line showed density-dependent growth and secretion of an autostimulatory growth factor, suggesting an autocrine mechanism. Several lines of evidence implicate the participation of interleukin-1 (IL-1) in the autocrine growth regulation of B1 cells. These cells constitutively express the messenger RNA (mRNA) for IL-1 and IL-1 receptor and secrete IL-1; recombinant IL-1 stimulated the growth of colonies when cells were seeded at low density, and anti-IL-1 antibodies inhibited the growth of colonies with cells seeded at higher density. B1 cells do not express detectable levels of mRNA for any of the other cytokines tested, and other cytokines failed to support the growth of B1 cells at low density. In addition, B1 cells express multiple cytokine receptor genes, including the receptors for IL-6, IL-7, tumor necrosis factor and gamma-interferon. Addition of the respective cytokines to the B1 cells resulted in inhibition of the growth of leukemic cells in vitro. The multiplicity of growth-inhibitory cytokine receptors on this leukemic cell line might be due to its biphenotypic lineage and may suggest new therapeutic possibilities in controlling leukemic cell proliferation. 
Technical considerations for prophylactic mastectomy in patients at high risk for breast cancer. A study of 5 patients and 10 mastectomy specimens was performed to identify the extent of surgery necessary to completely remove all breast tissue in patients having prophylactic mastectomies. A standard total mastectomy performed for breast cancer was shown to frequently leave breast tissue within the superficial pectoralis major muscle and the lower skin flap. Frozen section analysis of margins was found to be essential to clear the axillary extension of the breast and lower skin flap in particular. The value of more extensive surgery to remove all glandular elements of the breast in the high-risk patient remains to be demonstrated. 
Automated procedure for dewaxing and rehydration of paraffin-embedded tissue sections for DNA flow cytometric analysis of breast tumors. Flow cytometric DNA analysis of paraffin-embedded tumors is an important diagnostic and prognostic tool in clinical pathology. The technique is limited, however, by the time-consuming multistep procedure for dewaxing and rehydrating tissue. The authors developed an automated procedure to complete the dewaxing and rehydration of tissue using a routine histologic tissue processor with a 24-hour timer. This technique provided excellent tissue recovery and reproducible DNA histograms comparable to those obtained by manual methods. Subsequently, the authors analyzed the DNA content of 93 paraffin-embedded breast cancer tissues. The automation of a significant portion of the routine processing required for paraffin-embedded tissue makes cytometric DNA analysis a more practical procedure in the laboratory. 
Late complications involving the ascending aorta after cardiac surgery: recognition and management. Pseudoaneurysms and dissecting aneurysms of the ascending aorta after cardiac surgery are uncommon but important complications. Pseudoaneurysms, which result from extravasation of blood into the mediastinum, most commonly occur at the site of aortotomy or aortic cannulation. Infection may play an important role. Dissecting aneurysms after cardiac surgery usually occur at the site of aortic incision or cross clamping, especially in atherosclerotic aortas. Both conditions may be clinically silent but more frequently are seen with significant symptoms. Noninvasive techniques including CT scan, MRI, and echocardiography are very useful in the diagnosis of both complications, with contrast aortography remaining the definitive method. Surgical repair is necessary for dissecting aneurysms and for enlarging and symptomatic pseudoaneurysms, with improving morbidity and mortality. 
Recurrence of hepatitis C virus infection after orthotopic liver transplantation. Identification of the hepatitis C virus--the main cause of posttransfusion and sporadic non-A, non-B hepatitis--and the development of a diagnostic serological test have allowed us to study possible recurrence of this type of hepatitis after liver transplantation. Six of 34 consecutive transplant recipients were found to have had antibodies to hepatitis C before transplantation. All six patients had possible exposure to hepatitis C through blood transfusion or intravenous drug use. Five of the six patients were positive for antibodies to hepatitis C after 1 yr of follow-up. Two of these patients had clinical and histological evidence of acute viral hepatitis in their allografts. In one patient this led to hepatic injury and dysfunction of two successive grafts. In contrast, none of the twenty-eight patients who were seronegative for hepatitis C virus antibodies before transplantation has converted to seropositivity after transplantation despite perioperative blood transfusions. These results suggest that hepatitis C diagnosed serologically recurs in a minority of transplant recipients and that de novo seroconversion must be uncommon. 
Nutritional aspects and swallowing function of patients with Parkinson's disease. Seven patients with Parkinson's disease and three patients with progressive supranuclear palsy underwent adrenal medullary transplant to the caudate nucleus for treatment of their neurologic disease. Preoperative nutritional assessment demonstrated that a significant number of the Parkinson's patients had mild to moderate nutritional depletion. Motility problems, manifest by dysphagia and delayed gastric emptying causing problems over a number of years, were probably responsible. Of the 10 patients studied, 6 were studied by videofluoroscopy. All patients had variable dysphagia of variable servility with or without aspiration. Etiologic factors included the basic underlying neurologic disease, delay in resumption of anti-parkinsonian medications, use of metoclopramide, and postoperative medical complications leading to a debilitated clinical state. 
Acute basophilic leukemia. A clinical, morphologic, and cytogenetic study of eight cases. The authors describe eight cases of acute basophilic leukemia. In six of the eight cases, basophilic involvement was not apparent by light microscopic examination. The cases were identified on the basis of ultrastructural evidence for basophil/mast cell differentiation of the blasts with little or no differentiation into other lineages. Ultrastructural analysis revealed immature basophil granules in blasts in all eight cases and theta granules in blasts in four cases. In three cases, ultrastructural evidence of mast cell differentiation also was present, with rare cells showing evidence for both basophil and mast cell differentiation. No clinical features distinguished this group of patients from others with acute myeloid leukemia. Cytogenetically, the cases were heterogeneous. Three had a Philadelphia chromosome; none had a t(6;9). The authors conclude that ultrastructural analysis usually must be used to diagnose acute basophilic leukemia, that acute basophilic leukemia is associated frequently with the Philadelphia chromosome, and that the ultrastructural findings provide evidence for a common origin of basophils and mast cells. 
Autoimmune enteropathy and nephropathy with circulating anti-epithelial cell antibodies. We describe a child with circulating anti-epithelial cell antibodies, autoimmune enteropathy with intestinal villous atrophy, and membranous glomerulonephritis. The patient had persistent diarrhea at 6 months of age, and a small bowel biopsy showed active enteritis, villous atrophy, and crypt hyperplasia. When the patient was, 10 months of age, nephrotic syndrome developed because of membranous glomerulonephritis. Results of tests for circulating immune complexes were negative. Indirect immunofluorescence studies revealed a circulating antibody directed against renal epithelial cells. Circulating antibodies directed against normal small intestine epithelial cells were also detected by the immunoperoxidase technique. Western blot and immunoprecipitation identified a 55-kd antigen, in both small bowel and kidney, that reacted with an antibody in the patient's serum. High-dose prednisone therapy induced a clinical remission, resolution of the small bowel injury, and diminished serum anti-epithelial cell antibodies; after dose reduction, clinical relapse occurred with villous atrophy and reappearance of anti-epithelial cell antibodies. When the patient was 45 months of age, persistent diarrhea recurred despite intravenous administration of corticosteroids, cyclosporine, and total parenteral nutrition. Autoantibodies to a 55-kd epithelial cell protein are temporally related to the development of enteropathy and nephropathy. Study of similar patients is needed to determine the role of such antibodies in this disorder. 
Burning pain in an extremity. Breaking the destructive cycle of reflex sympathetic dystrophy. The pathogenesis of reflex sympathetic dystrophy is controversial, but the condition can result from a major or seemingly minor injury to a limb, or even an insult to an organ, such as stroke or myocardial infarction. Onset can be sudden or insidious. The syndrome is characterized primarily by localized, deep, burning pain in a limb--pain that may not follow any logical distribution. Nonpitting edema, skin hyperesthesia, and guarding of the limb usually accompany the pain. If treatment is not instituted, deformity, contracture, and wasting of the limb can eventually occur. With appropriate therapy, the process can be stopped and often reversed. The keys are a high index of suspicion, early diagnosis, and aggressive treatment. 
Effects of nitroglycerin and diltiazem on well-developed coronary collateral circulation in conscious dogs. The purpose of the present study was to compare the effects of nitroglycerin and diltiazem on coronary collateral circulation. Studies were conducted in 8 conscious dogs instrumented for the measurement of left circumflex coronary artery (LCCA) flow, subendocardial segment lengths in areas perfused by the LCCA, and left anterior descending coronary artery (LAD). Brief, repeated LCCA occlusions sufficiently developed collateral vessels for the resting metabolic requirement in the LCCA region. One week following the cessation of repeated LCCA occlusions, two-minute coronary occlusions with and without drug pretreatment were performed on separate days. The ischemic responses to coronary occlusions were not altered by diltiazem (50 micrograms/kg, IV), but nitroglycerin (5 micrograms/kg, IV) attenuated myocardial ischemia definitely. The authors conclude that nitroglycerin produces greater effects than diltiazem in attenuating myocardial ischemia in the collateral dependent zone when effects of each drug on systemic and coronary circulation were minimized by pretreatment with small doses. 
Comparative evaluation of carcinoembryonic antigen, secretory component, and mucins in index and metachronous adenomas of the colorectum. Of 124 patients who underwent endoscopic polypectomy, 70 were colonoscopically reevaluated during a mean period of 10 years. On the basis of the clinical outcome, the patients were divided into three groups: group 1, 31 patients who had a colon still with no adenomas or cancer; group 2, 35 patients in whom one or more metachronous adenomatous polyps developed; and group 3, 4 patients in whom a carcinoma of the colon subsequently developed. In addition to the clinical and pathological features, the pattern of the immunohistologic staining for carcinoembryonic antigen and secretory component was studied. Moreover, the mucin histochemical staining intensity of neutral mucins, sulfomucins, and sialomucins was evaluated. The features of the 40 index adenomas obtained from patients in group 1 were compared with the features of the 51 index adenomas from patients in group 2. Furthermore, these characteristics of the index adenomas were compared with those in the 69 metachronous adenomas of the group 2 patients. It was found that male sex (P less than 0.005) and a history of colorectal neoplasia (P less than 0.02) are main factors for the development of new adenomas. The neutral mucins were less abundant in the group 2 index adenomas (r = -0.21; P less than 0.05). The expression of the other evaluated markers was not significantly different between both groups, although the group 2 index adenomas were significantly smaller (r = -0.22; P less than 0.05) and showed a trend toward a more pronounced cytoplasmic expression of carcinoembryonic antigen than the index adenomas from group 1 (22% vs. 12.5%). Moreover, it was found that in comparison with the index adenomas, metachronous adenomas were significantly smaller (r = -0.24; P less than 0.01) and more sessile (r = 0.20; P less than 0.002). Significant negative correlations, i.e., decrease, were also found in the expression of carcinoembryonic antigen (surface P less than 0.001; cytoplasmic P less than 0.05) and neutral mucins (P less than 0.005) between the index adenomas and the metachronous adenomas, whereas positive correlations were found for secretory component (P = 0.0001) and sulfomucins (P less than 0.05). These findings suggest that a limited production of neutral mucins in the goblet cells of a small index adenoma from a male patient with a history of colorectal neoplasia is indicative of an increased risk for the development of new colorectal adenomas. Furthermore, the clinical, mucin histochemical, and immunohistochemical findings of the metachronous adenomas show less malignancy-associated features than those of the index adenomas. 
Comparison of enteral nutrition and drug treatment in active Crohn's disease. Results of the European Cooperative Crohn's Disease Study. IV This study compared the effect of enteral nutrition as the sole therapy of active Crohn's disease with drug treatment. Patients with active Crohn's disease (Crohn's Disease Activity Index greater than 200) were randomized to receive either enteral nutrition with a liquid oligopeptide diet (n = 55) or a combination of 6-methylprednisolone, 48 mg daily, subsequently tapered, and sulfasalazine, 3 g daily (n = 52). The two groups were not different with respect to age, sex, body weight, location of disease, or treatment before the study. The severity of disease was similar at the beginning of the study in both groups [Crohn's Disease Activity Index (mean +/- SEM), 323 +/- 12 vs. 316 +/- 11]. Remission was defined as a decrease of the initial Crohn's Disease Activity Index by 40% or at least 100 points. Twenty-nine patients in the diet group and 41 patients in the drug group reached remission within 6 weeks of therapy (chi 2 test, P less than 0.01). The median elapsed time to remission was 30.7 days in the diet group compared with 8.2 days in the drug group (Mantel Cox, P less than 0.01). To determine whether one of these treatments was more beneficial for a subgroup of patients, the effectiveness of both treatments was analyzed separately in patients with very severe disease (initial Crohn's Disease Activity Index greater than 300) and less severe disease (initial Crohn's Disease Activity Index less than 300), and in patients with different disease location. However, no influence of initial disease activity or disease location on the effect of either treatment could be shown. These data show that enteral nutrition is less effective than a combination of 6-methylprednisolone and sulfasalazine in treating active Crohn's disease. 
Abnormalities of pathways of fibrin turnover in the human pleural space. The potential importance of pleural fibrin deposition in the pathogenesis of pleural injury is supported by both clinical and experimental observations. We hypothesized that the local equilibrium between procoagulant and fibrinolytic activities is disrupted to favor fibrin deposition in exudative pleuritis. To test this hypothesis, we characterized procoagulant and fibrinolytic activities in pleural exudates from patients with pneumonia, lung cancer, or empyema and transudates from patients with congestive heart failure. Procoagulant activity was generally increased in exudative processes and was due mainly to tissue factor. All effusions contained antithrombin III and inhibited factor Xa and thrombin, but endogenous prothrombinase or thrombin activities were variably detected. Pleural fluid fibrinolytic activity was increased in congestive heart failure and was due to both tissue plasminogen activator and urokinase. Depressed fibrinolytic activity was found in pleural exudates despite increased concentrations of plasminogen, mainly glu-1-plasminogen, and was due to inhibition of plasminogen activation by plasminogen activator inhibitors 1 and 2 and of plasmin, in part by alpha 2-antiplasmin. Concentrations of PAI-1 in exudative pleural fluids were increased up to 913-fold, compared with normal pooled plasma. Exudative pleural effusions are characterized by increased procoagulant and depressed fibrinolytic activity, favoring fibrin deposition in the pleural space. The balance of these activities is reversed and favors fibrin clearance in congestive heart failure. 
Adenine arabinoside monophosphate and acyclovir monophosphate coupled to lactosaminated albumin reduce woodchuck hepatitis virus viremia at doses lower than do the unconjugated drugs. The woodchuck was selected to study the efficacy of liver-targeted antiviral drugs on hepadnavirus replication. Nineteen woodchucks chronically infected with woodchuck hepatitis virus were treated with adenine arabinoside monophosphate or acyclovir monophosphate, either free or conjugated with the liver-targeting molecule lactosaminated human serum albumin. Circulating woodchuck hepatitis virus DNA levels remained unchanged in untreated animals and in those receiving the carrier lactosaminated human serum albumin alone; in contrast, they were consistently lower after 5 days of treatment with the antiviral drugs. Free and conjugated adenine arabinoside monophosphate were active at doses of 10 and 0.75 mg/kg, respectively, and free and coupled ACVMP were active at doses of 20 and 2.6 mg/kg, respectively. These results indicate that the dosages of adenine arabinoside monophosphate and acyclovir monophosphate required to inhibit hepadnavirus growth can be sharply reduced by coupling the drugs to lactosaminated human serum albumin. 
The epidemiologic importance of dysentery in communities. This paper explores the epidemiologic importance of dysentery with use of several community studies that demonstrate its prevalence and incidence as well as its association with pathogens, nutritional status, persistent diarrhea, and death. Results of these studies showed that while watery diarrhea was most prevalent in children aged 6-11 months, the prevalence of dysentery peaked between 18 and 23 months of age. Severely stunted children were found to have significantly prolonged episodes of dysentery. Shigella and persistent diarrhea were more frequent in children with dysentery than in those with nonbloody diarrhea. A striking feature was that watery diarrhea, dysentery, persistent diarrhea, and malnutrition each account for less than 5% of all deaths among children aged less than 5 years. However, persistent diarrhea in association with malnutrition causes 13% of deaths in children aged 0-4 years and 27% of deaths in those aged 1-4 years. These data suggest that a more balanced strategy for diarrheal control is required simply because most diarrheal deaths occur among malnourished children with prolonged diarrhea, which is mainly due to dysentery. Results of the studies also suggest that methods to control dysentery in the community should focus on improved hygiene and antimicrobial treatment with use of appropriate algorithms. Recognition of the synergism between dysentery and persistent diarrhea accompanied by malnutrition is crucial in formulating effective programs for control of diarrhea. 
The significance of portal vein thrombosis after distal splenorenal shunt. The aims of this study were to determine the incidence of portal vein thrombosis after the distal splenorenal shunt, to identify any predictive factors, and to assess the clinical significance of this complication. Preoperative and postoperative angiograms and clinical evaluation were reviewed in 124 patients who underwent distal splenorenal shunts. Total and partial portal vein thrombosis were seen on 13 (10.5%) and 22 (17.7%) postoperative angiograms, respectively. The only preoperative variable correlating with development of portal vein thrombosis was portal venous perfusion, which was significantly lower in patients with than in those without portal vein thrombosis. In six of 10 patients with postoperative pancreatitis, portal vein thrombosis developed. The frequency of early postoperative complications was significantly greater in patients with total portal vein thrombosis than in those with partial or no thrombosis. Long-term follow-up has shown no significant effects of portal vein thrombosis on late ascites, encephalopathy, or survival. 
Chronic calcific pancreatitis in a patient with Waldenstrom's macroglobulinemia. We report on a patient with chronic calcific pancreatitis associated with Waldenstrom's macroglobulinemia, and we have hypothesized a possible relationship between these two entities. The hyperviscosity of serum in Waldenstrom's macroglobulinemia may be associated with a viscous pancreatic juice that leads to stone formation. 
Comparative aspects of osteosarcoma. Dog versus man. Canine osteosarcoma bears striking resemblance to osteosarcoma in humans. Similarities include the following: male sex predilection, large patient size, 75% or more affecting the appendicular site, metaphyseal location, generally unknown etiology, less than 10% of patients have documented metastasis at presentation, over 90% of tumors show high-grade histology, 75% of tumors show aneuploidy, the metastatic rate is 80% or more with amputation alone, the lung is the most common site of metastasis, and there is improved survival with adjuvant chemotherapy. The major differences are age of onset, with dogs being affected in middle age; greater frequency in the dog, with over 8000 new cases per year; and time to metastasis being faster in the dog than man. Canine osteosarcoma is a readily available and highly comparable spontaneously occurring cancer that should be useful in a better understanding of the same disease in humans. 
Effect of weight loss on upper airway collapsibility in obstructive sleep apnea. Previous investigators have demonstrated in patients with obstructive sleep apnea that weight reduction results in a decrease in apnea severity. Although the mechanism for this decrease is not clear, we hypothesize that decreases in upper airway collapsibility account for decreases in apnea severity with weight loss. To determine whether weight loss causes decreases in collapsibility, we measured the upper airway critical pressure (Pcrit) before and after a 17.4 +/- 3.4% (mean +/- SD) reduction in body mass index in 13 patients with obstructive sleep apnea. Thirteen weight-stable control subjects matched for age, body mass index, gender (all men), and non-REM disordered breathing rate (DBR) also were studied before and after usual care intervention. During non-REM sleep, maximal inspiratory airflow was measured by varying the level of nasal pressure and Pcrit was determined by the level of nasal pressure below which maximal inspiratory airflow ceased. In the weight loss group, a significant decrease in DBR from 83.3 +/- 31.0 to 32.5 +/- 35.9 episodes/h and in Pcrit from 3.1 +/- 4.2 to -2.4 +/- 4.4 cm H2O (p less than 0.00001) was demonstrated. Moreover, decreases in Pcrit were associated with nearly complete elimination of apnea in each patient whose Pcrit fell below -4 cm H2O. In contrast, no significant change in DBR and a minimal reduction in Pcrit from 5.2 +/- 2.3 to 4.2 +/- 1.8 cm H2O (p = 0.031) was observed in the "usual care" group. We conclude that (1) weight loss is associated with decreases in upper airway collapsibility in obstructive sleep apnea, and that (2) the resolution of sleep apnea depends on the absolute level to which Pcrit falls. 
Cavernomas of the central nervous system: clinical and neuroimaging manifestations in 47 patients. Forty seven cases of central nervous system cavernous angioma (21 males and 26 females) are described. The main clinical signs were epilepsy and brainstem syndromes. Digital subtraction intra-arterial angiography, when used, failed to reveal cavernoma. CT detected many of the lesions, but the most successful supplementary diagnostic procedure was MRI which produces highly characteristic images of cavernous angioma. The diagnosis of cavernous angioma was confirmed in the 18 cases in which the tumour was removed surgically. 
Upper airway collapsibility in snorers and in patients with obstructive hypopnea and apnea. During sleep, mild reduction in inspiratory airflow is associated with snoring, whereas obstructive hypopneas and apneas are associated with more marked reductions in airflow. We determined whether the degree of inspiratory airflow reduction was associated with differences in the collapsibility of the upper airway during sleep. Upper airway collapsibility was defined by the critical pressure (Pcrit) derived from the relationship between maximal inspiratory airflow and nasal pressure. In 10 asymptomatic snorers, six patients with obstructive hypopneas, and 10 patients with obstructive apneas, during nonrapid eye movement sleep, Pcrit ranged from -6.5 +/- 2.7 cm H2O to -1.6 +/- 1.4 and 2.5 +/- 1.5 cm H2O, respectively (mean +/- SD, p less than 0.001). Moreover, higher levels of Pcrit were associated with lower levels of maximal inspiratory airflow during tidal breathing during sleep (p less than 0.005). We conclude that differences in upper airway collapsibility distinguish among groups of normal subjects who snore and patients with periodic hypopneas and apneas. Moreover, the findings suggest that small differences in collapsibility (Pcrit) along a continuum are associated with reduced airflow and altered changes in pattern of breathing. 
Adhesiolysis. Lysis of adhesions improves pregnancy rates. Results of laparoscopic lysis are not different from those of laparotomy. Since laparoscopy is more convenient to the patient, less expensive, saves hospital beds, and involves low morbidity, it should be the preferred surgical approach to the diagnosis and treatment of pelvic adhesions whenever possible. The use of a sharp dissection combined with electrocautery seems, at this time, to be equally effective to the use of lasers of different kinds. Adjuvants presently available, especially Hyskon or INTERCEED, have an added benefit to surgery alone. Even with the best surgical technique, adhesions tend to re-form. Although SLL will identify the extent of adhesion re-formation, the therapeutic advantage of lysing re-formed adhesions is yet to be proved. 
Coronary artery stenting after angioplasty with self-expanding parallel wire metallic stents. Parallel wire stents were implanted over exchange guide wires at percutaneous transluminal coronary angioplasty sites in 27 canine coronary arteries that were predilated with slightly oversized balloons. Stents were stainless steel, self-expandable, 3.5 to 4.5 mm in diameter, 9 to 12 mm in length, and were made of 10 wires that were longitudinally laser-welded in a zig-zag design. The compressible stent was delivered by the withdrawal of a Teflon outer catheter (4.2 to 4.9F) and the push of a polyethylene inner catheter. Aspirin, 80 mg per day, was given from the day before the study began, and heparin (150 U/kg) was administered during implantation. Quantitative angiography and pathologic examinations were performed at day 0 and at weeks 2, 4, 12, 26 and 52. The coronary angiographic diameter at the stent site immediately after stenting marginally increased from diameter before stenting: 3.22 +/- 0.40 mm versus 3.14 +/- 0.37 mm (p = 0.03), and during a mean of 14 weeks of follow-up, remained unaltered from immediate post-stenting: 3.29 +/- 0.43 mm versus 3.22 +/- 0.40 mm (p = NS) with no stent displacement. Comparisons of patency and thrombosis between heparin-coated and uncoated stents, between left anterior descending and circumflex arteries, and among the three different diameters of stents showed uniformly good results. At microscopy, the wires were oriented perfectly and embedded in the arterial wall, and by 2 weeks they were covered by mucopolysaccharide ground substance, smooth muscle cells, and an almost complete monolayer of neoendothelial cells. 
Eight-year outcome in infants with birth weight of 500 to 999 grams: continuing regional study of 1979 and 1980 births. Victorian Infant Collaborative Study Group. The outcome at a mean age of 8.3 years was determined for 88 of 89 surviving children with birth weights of 500 to 999 gm who were born in Victoria in 1979 and 1980; the condition of the untraced child, severely disabled at 5 years of age, was assumed to be unchanged at 8 years. Principal impairments in the children at 8 years of age were cerebral palsy 8 (9%); bilateral blindness 6 (6.7%) and poor vision in another 4 (4.5%); bilateral deafness requiring amplification 5 (5.6%); and epilepsy 2 (2.2%). The Full Scale score of the Weschler Intelligence Scales for Children--Revised was available for 77 children: 5 scores (6.5%) were less than 71 (low IQ), and 9 (11.7%) were between 71 and 85 (borderline IQ). Severe disability in 16 children (18%) was due to severe cerebral palsy, bilateral blindness, or low IQ. Mild or moderate disability was present in another 18 children (20.2%) with borderline IQ, mild or moderate cerebral palsy, poor vision, deafness, or epilepsy. Significantly more outborn children (10/18, 55.6%) than inborn children (24/71, 33.8%) were disabled. Ten children required special schooling; reading accuracy or comprehension was at least 18 months behind chronologic age in 17 (23%) of 75 children in normal school who were tested. The 2-year assessment correctly estimated the category of disability at 8 years of age in 55 (62%), overestimated it in 24 (27%), and underestimated it in 10 (11%). For the 82 children also seen at 5 years age, the category of disability at 8 years of age was correctly identified in 69 children (84%), overestimated in 4 (5%), and underestimated in 9 (11%). Change in psychologic test scores was the principal reason for reclassifying children. We conclude that the 2-yar assessment was valuable in the early identification of most of the severely disabled children, but developmental delay at 2 years of age did not always portend intellectual impairment at 8 years of age. 
Sun protection in childhood. There is compelling evidence that childhood is a particularly vulnerable time for the photocarcinogenic effects of sun exposure on the skin. Studies indicate that excessive sun exposure during the first 10-20 years of life greatly increases the risk of skin cancer. Nonmelanoma skin cancer (basal cell and squamous cell carcinoma) has been associated with cumulative sun exposure, whereas melanoma has been associated with short, intense sun exposure or blistering sunburn. Under normal circumstances, children receive three times the annual sun exposure of adults; most of one's lifetime sun exposure occurs in childhood. Depletion of the earth's protective ozone layer adds to the photodamage problem. It is clear that sun protection is most vital in the early years. Those with fair skin are at highest risk. Photoprotective measures including sunscreen, clothing, and sun avoidance in childhood may significantly reduce the occurrence of melanoma and other skin cancer in later life. Regular use of sunscreen with a sun protection factor of 15 during the first 18 years of life could reduce the lifetime incidence of nonmelanoma skin cancer by 78%. Pediatricians can play a major role in educating parents and children. 
Sacrospinous fixation--should this be performed at the time of vaginal hysterectomy? A sensible individualized approach should be applied to every patient undergoing transvaginal surgery for benign disease. This approach should attempt to correct every defect present in the pelvic supports. Uterovaginal prolapse is the result rather than the cause of genital prolapse. Not every vaginal hysterectomy should be treated like a cystocele-rectocele repair. Instead, every defect of the endopelvic fascial support should be evaluated in a patient both before and during surgery. As a result of these evaluations, more than just a hysterectomy and an anterior and posterior colporrhaphy may be performed. In a case in which a patient is found to have more than one defect at the time of examination, sacrospinous fixation of the vaginal apex at the time of transvaginal hysterectomy may be indicated. In the office, the patient can be examined in the supine and standing positions, both with and without Valsalva's maneuver, to determine if moderate to severe uterovaginal prolapse exists. Sacrospinous fixation should be performed in those cases as an adjunct to other steps taken to prevent postthysterectomy prolapse. 
Animal models for arterial thrombolysis and prevention of reocclusion. Erythrocyte-rich versus platelet-rich thrombus. Experimental animal models for erythrocyte-rich (ER) and platelet-rich (PR) arterial thrombosis were developed in dogs and rabbits and used for the evaluation of the effect of antithrombin and antiplatelet agents on thrombolysis with recombinant tissue-type plasminogen activators (rt-PA). The canine models consist of a whole blood clot produced in the left anterior descending coronary artery (ER thrombus) or a 1-cm everted (inside-out) segment graft in the circumflex coronary artery that predisposes to occlusion with PR material (PR thrombus). The rabbit models consist of a femoral arterial whole blood clot (ER thrombus) or a femoral arterial eversion graft (PR thrombus). The whole blood clot models are sensitive to recanalization with rt-PA but are consistently associated with reocclusion, notwithstanding the concomitant use of heparin and/or aspirin. Clot lysis is accelerated and reocclusion is prevented by the administration of F(ab')2 fragments of a monoclonal antibody 7E3 directed against the platelet glycoprotein IIb/IIIa receptor; of Argatroban, a synthetic thrombin inhibitor; or of kistrin, a glycoprotein IIb/IIIa-blocking polypeptide from the Malayan pit viper venom. The PR thrombus models are very resistant to recanalization with rt-PA, but this resistance can be overcome by the concomitant use of the platelet glycoprotein IIb/IIIa-blocking antibody. Thus, selective platelet glycoprotein IIb/IIIa inhibitors are more effective than aspirin, heparin, or both in accelerating arterial thrombolysis with rt-PA; in preventing reocclusion after clot lysis; and in overcoming the resistance of PR thrombus to dispersion with rt-PA. These experimental animal models may be useful in the development of improved thrombolytic strategies using plasminogen activators in conjunction with specifically targeted antiplatelet and anticoagulant agents. 
Is fiber mitochondrial volume density a good indicator of muscle fatigability to isometric exercise? The relationship between the ratio of interfibrillar mitochondrial volume density (Vvmit) to myofibrillar volume density (Vvmyo) and isometric fatigue characteristics of the human triceps surae was determined in six bodybuilders, six endurance athletes, and six active controls before and after 16 wk of isometric training at 30 or 100% maximal voluntary contraction (MVC) in six sedentary subjects in a unilateral exercise model. Time to fatigue at 30% MVC was significantly less in sedentary subjects before training than in the other subject groups, but it was similar to the other groups posttraining. Stereological analyses of type I fibers indicated that Vvmit/Vvmyo was less in bodybuilders than in other subjects. Training at 30% MVC increased type I fiber Vvmit/Vvmyo of the soleus by 11% but did not affect the gastrocnemii. Training at 100% MVC did not alter Vvmit/Vvmyo in any muscle, nor was this ratio changed in type II fibers by either training program. Despite the morphological differences, both training protocols increased relative endurance, although greater fatigue resistance was seen after training at 30% MVC. Correlation analyses indicated that isometric endurance and improvements in muscle endurance by isometric exercise were not dependent on increasing interfibrillar Vvmit or Vvmit/Vvmyo in either fiber type. 
Electromechanical dissociation in newborns treated with extracorporeal membrane oxygenation: an extreme form of cardiac stun syndrome. OBJECTIVE: To recognize cardiac stun syndrome and electromechanical dissociation in patients receiving extracorporeal membrane oxygenation (ECMO), and to define patients at risk. DESIGN: Retrospective review. SETTING: Tertiary neonatal ICU. PATIENTS: Four newborn patients with cardiorespiratory failure who developed signs of cardiac stun syndrome and electromechanical dissociation early in the ECMO course. MEASUREMENTS AND MAIN RESULTS: Initially, these patients had metabolic acidosis, chest roentgenograms showing pulmonary granularity and moderate cardiomegaly, and symptoms of severe respiratory distress. Cardiac dysfunction was apparent after ECMO was begun, with poor perfusion, pale color, narrow pulse pressure, and tachycardia despite normovolemia. Within 1 to 2 hrs, electromechanical dissociation occurred manifested by the absence of pulse pressure, palpable pulse, cardiac sounds, and apical impulse while on 50% to 70% bypass. All patients survived. INTERVENTIONS: Patients received ECMO, calcium gluconate, sodium bicarbonate, and dobutamine. CONCLUSIONS: Patients with cardiac stun syndrome have symptoms similar to severe respiratory distress syndrome, and may require ECMO support. In the ECMO patient, cardiac stun syndrome and electromechanical dissociation can be confused with low circuit volume, pneumothorax, or cardiac tamponade. Early recognition of electromechanical dissociation may improve care and outcome. Cardiac stun syndrome can be treated successfully with ECMO. 
Complete infarction of the eye complicating a choroidal malignant melanoma. Infarction of malignant melanoma of the choroid has been previously reported, but infarction of the whole eye in association with infarction of melanoma is a rare event that has not been previously described. We present such a case and discuss the possible pathogenesis. 
Management of hypertensive emergencies: changing therapeutic options. Rapid lowering of severe hypertension is essential to prevent irreversible damage to vital organs. The patient's clinical status should be evaluated, noting particularly cardiac, neurologic, and renal functions. Choice of treatment should be based on speed and efficacy of action and on hemodynamic, vascular, and renal consequences. It is also important to preserve circulatory homeostasis and vital organ function. Sodium nitroprusside, labetalol, diazoxide, and hydralazine have been used parenterally for rapid control of severe hypertension, but they do not always produce optimal, balanced hemodynamic effects. Calcium antagonists have been advocated because of their beneficial circulatory effects. Nicardipine, a new dihydropyridine calcium antagonist, produces significant antihypertensive effects, and when given intravenously, results in a rapid fall in blood pressure. Studies have confirmed that nicardipine is effective and safe in the management of severe hypertension and hypertensive crises. Because the aim of rapidly controlling severe hypertension is to prevent target organ dysfunction, nicardipine therapy offers a useful additional option in the clinical management of severe hypertension and hypertensive crises. 
Clinical characteristics and surgical management of vascular complications in patients undergoing cardiac catheterization: interventional versus diagnostic procedures. The purpose of this report is to define the clinical characteristics and outcome of surgical management of vascular complications after interventional cardiac catheterization and to contrast them to those after diagnostic cardiac catheterization. From October 1985 to December 1989, 101 patients were treated for 106 vascular complications after 1866 interventional and 5046 diagnostic cardiac catheterizations at the University of Michigan Medical Center. Interventional catheterizations resulted in 69 vascular complications in 64 patients (frequency 3.4%). The most common interventions included coronary angioplasty (34), of which 10 required percutaneous partial cardiopulmonary bypass, intraaortic balloon pump placement (14), and aortic valvuloplasty (11). Interventional catheter-related complications included hemorrhage (33), arterial thrombosis (18), pseudoaneurysm formation (12), catheter embolization (2), thromboembolism (2), as well as arteriovenous fistula, pseudoaneurysm, and arterial dissection (1 each). Fifteen of these 69 patients (24%) had suffered acute myocardial infarction just before their catheterization. Surgical repair was performed under local anesthesia in 70% of patients. Major vascular reconstructions were required in 9% of patients. Three percent of the involved lower extremities had to be amputated because of complications occurring after arterial puncture. Eight percent of the patients incurring vascular complications after interventional procedures died after operation. Diagnostic catheterizations resulted in 37 vascular complications in 37 patients (frequency 0.7%). In contrast to diagnostic cardiac catheterization, vascular complications after interventional cardiac catheterization occurred more frequently, were most often due to hemorrhage at the vascular access site, and occurred in high-risk, critically ill patients. 
Staving off acute otitis media. When is prophylaxis with antibiotics desirable? Acute otitis media affects most young children and is the condition for which children are most frequently treated with antibiotics. A pattern of recurrent acute ear infections develops in some children and is a source of frustration for parents and physicians. Recurrent episodes can exacerbate asthma or other underlying medical problems, and long-term effects can include chronic otitis media with permanent middle-ear injury and, possibly, delay in psychomotor and language development. Antibiotic prophylaxis can reduce the number of episodes of acute otitis media in children at high risk for recurrent infection. There is no perfect antibiotic to prevent acute otitis media. However, the risks associated with the drugs described in this article are low. Prophylaxis with antibiotics does not prevent all episodes of acute otitis media but can reduce the number of episodes by 50%. 
The mechanism responsible for diminished neutrophil production in neonates delivered of women with pregnancy-induced hypertension. The neonatal neutropenia after pregnancy-induced hypertension is a function of diminished neutrophil production. These studies test the hypothesis that this diminution is due to decreased production of neutrophilic growth factors, reduced responsiveness of neutrophil progenitors to these factors, or the presence of an inhibitor. While the concentrations of placentally derived colony-stimulating factors were similar in normotensive and hypertensive gestations, bioassay demonstrated less colony-stimulating activity in placental conditioned media from hypertensive gestations. Evaluation of the responsiveness of progenitors to recombinant factors revealed no differences between those from normotensive and hypertensive gestations. However, neutrophilic colony formation in vitro was significantly inhibited after the addition of conditioned media or sera from hypertensive gestations, whereas the addition of these from normotensive gestations had no inhibitory effect. Thus this common maternal-fetal disorder is associated with an inhibitor of neutrophil production, which is elaborated by the placenta and present in cord blood serum. 
Transient white matter changes on MR images in children undergoing chemotherapy for acute lymphocytic leukemia: correlation with neuropsychologic deficiencies. The cranial magnetic resonance (MR) images of 25 children with acute lymphocytic leukemia (ALL) who were undergoing chemotherapy were retrospectively studied to determine the frequency of white matter changes and to analyze the significance of these observed changes in predicting subsequent neuropsychologic deficiencies. MR images showed transient white matter abnormalities in 17 of the 25 patients during consolidation therapy. Twelve of 20 children showed neuropsychologic deficits. There was no correlation between white matter changes and neuropsychologic deficits. In the subgroup of children under age 5 years at the time of diagnosis, 10 of 11 showed neuropsychologic deficits, and eight of 11 had white matter changes. Children under age 5 who undergo chemotherapy for ALL are at high risk to develop neuropsychologic deficiencies. Age at diagnosis is a reliable predictor of subsequent neuropsychologic deficits. 
The risk of axillofemoral bypass grafting for acute vascular occlusion. The hypothesis of the present study is that axillofemoral bypass grafting for acute vascular occlusion has results significantly inferior to an elective procedure. We reviewed 53 patients undergoing primary axillofemoral bypass grafting at the University of Virginia from 1984 to 1989. We found that patients who were admitted with acute vascular occlusion had a higher incidence of perioperative complications (63% vs 26%, p = 0.001), perioperative mortality (26% vs 3%, p less than 0.05), lower graft patency at 1 year (60% vs 90%, p less than 0.05), lower rate of freedom from reoperation in first year (50% vs 82%, p less than 0.01), and lower rates of limb salvage (76% vs 94%, p less than 0.05) than patients undergoing axillofemoral bypass grafting for chronic symptoms or conditions. These two groups did not differ in any of the other risk factors or perioperative characteristics examined. We conclude axillofemoral bypass grafting performed for indications other than acute vascular occlusion is associated with acceptable morbidity, mortality, graft patency, and limb salvage rates. 
Na+, K(+)-ATPase inhibition and intracellular electrolyte content in essential and secondary hypertension. A crucial role of humoral factors in the pathogenesis of primary hypertension is discussed. In 1982 Hamlyn et al demonstrated the presence of a Na+, K(+)-ATPase inhibitor in the plasma of essential hypertensives and showed a significant correlation of the Na+, K(+)-ATPase inhibition with the blood pressure. In this study we examined whether an Na+, K(+)-ATPase inhibitor could be found in the blood of essential hypertensives as compared to patients with secondary hypertension (renal hypertension, renal artery stenosis, pheochromocytoma). Second, the possible correlation between an inhibition of Na+, K(+)-ATPase and the intracellular electrolyte composition was examined. The results demonstrate a similar reduction of Na+, K(+)-ATPase inhibition in both essential hypertensives and secondary hypertensives as compared to normotensive controls. Further, the intracellular electrolyte composition (Na+, Na; K+, Ca) does not show a significant correlation to the degree of Na+, K(+)-ATPase inhibition, whereas a significant correlation between the degree of Na+, K(+)-ATPase inhibition and intracellular Cl- concentration could be demonstrated. The present study shows that an endogenous Na+, K(+)-ATPase inhibitor is also present in secondary forms of hypertension, thus implying that a specific role in the pathogenesis of primary hypertension for an Na+, K(+)-inhibitor is unlikely. 
Oral rehydration therapy for invasive diarrhea. Current guidelines for the management of diarrheal diseases focus on the use of oral rehydration therapy (ORT). Clinically evident dehydration of a moderate degree is not uncommon with invasive diarrhea, and when it occurs, the response to ORT is satisfactory. Studies from hospitals and the community each document the effectiveness of ORT for rehydration of patients with invasive diarrhea. This has been confirmed in a clinical trial of oral rehydration solution (ORS) for the treatment of diarrheal diseases in children less than 5 years of age. Children with moderate dehydration benefited most from ORS, especially those who had culture-proven invasive diarrhea. Significant early weight gain was observed for this group of patients alone after rehydration with ORS. In developing countries, there is no reason to withhold ORT at the first signs of watery or dysenteric diarrhea regardless of the cause and independent of the decision to treat the patient with antimicrobial agents. 
Prior poliomyelitis-reduced capillary supply and metabolic enzyme content in hypertrophic slow-twitch (type I) muscle fibres. Capillary supply and oxidative and glycolytic enzyme activities were determined in muscle biopsies from the tibialis anterior muscle in six prior polio patients and a control group. The polio patients, who had paresis and atrophy, but were able to walk normally by making maximal use of all remaining anterior tibial motor units, showed type I (slow-twitch) muscle fibre predominance with a mean (SD) of 98 (2%) type I fibres versus 81 (8)% in the controls (p less than 0.01) and muscle fibre hypertrophy, the average type I fibre cross-sectional area being 108% (p less than 0.005) larger than in the controls. The number of capillaries per muscle fibre was not significantly different from that in the control group, but with the increased muscle fibre area in the polio patients, the capillary density was significantly lower. The number of capillaries in contact with type I fibres relative to fibre area was 40% lower in the patients than in the controls (p less than 0.005). The levels of citrate synthase and phosphofructokinase were significantly lower (38% and 33%, respectively, p less than 0.05) in the patients than in the controls, indicating decreased oxidative and glycolytic potentials in the muscle fibres of the polio patients. It is proposed that the abnormal high-frequency activation of all remaining motor units during each step cycle recorded in these patients constitutes a stimulus for type I muscle fibre predominance and hypertrophy but that the overall low muscle usage results in a decreased stimulation of capillary proliferation and mitochondrial enzyme synthesis. 
The herpes simplex virus 1 segment inversion site is specifically cleaved by a virus-induced nuclear endonuclease. Nuclear extracts from several tissue culture cell lines (human, primate, and murine) contain an endonuclease that specifically cleaves sequences at the herpes simplex virus 1 (HSV-1) segment inversion site. Mapping studies identified the preferential site of cleavage as a set of tandemly repeated dodecamers, the DR2 repeats. Endonuclease levels vary according to the proliferative state of the cell; little or no activity is detectable in extracts from quiescent cells, whereas high levels are expressed in dividing cells. Also, infection of density-arrested BSC-1 cells with HSV-1 induces a substantial increase (at least 35-fold) in endonucleolytic activity, which is first detectable at about 1 hr after infection at 32 degrees C. The elevated levels of enzyme activity then persist throughout the viral life cycle. In addition to the HSV-1 DR2 repeats, certain other G+C-rich sequences with an asymmetric distribution of purines and pyrimidines on the DNA strands and with appropriate sequences and lengths are substrates for the nuclease. These data indicate that target site recognition by the enzyme is conformation specific rather than sequence specific. 
Adrenal cortical carcinoma with vena cava tumor thrombus requiring cardiopulmonary bypass for resection. We believe this is the fifteenth case report of adrenal cortical carcinoma with tumor thrombus to the vena cava, and the fourth reported case of a left-side tumor propagating thrombus to the vena cava. The patient underwent successful resection which required cardiopulmonary bypass. The caval tumor thrombus was very friable and gelatinous, unlike many renal cell thrombi, and required special surgical considerations. 
Bleeding after endoscopic sphincterotomy as an underestimated entity. Hemorrhage is the most frequent complication of endoscopic sphincterotomy, with a reported incidence of 2 to 9 per cent. Previous reports have generally defined this complication clinically, leaving the issue of occult bleeding after sphincterotomy essentially unaddressed. Seventy-five serial sphincterotomies were reviewed to further assess this complication. Nine patients had clinically evident hemorrhage and 27 patients had occult bleeding manifested only by a decrement in hematologic parameters, for a total postsphincterotomy bleeding rate of 48 per cent. No statistically significant risk factors for bleeding were delineated. Endoscopically recognized bleeding at the time of the sphincterotomy was 47 per cent sensitive and 85 per cent specific in predicting postprocedural bleeding. Significant delayed hemorrhage was manifest in three patients, one of whom had clinically occult bleeding. We conclude that bleeding complicates endoscopic sphincterotomy much more frequently than previously reported, although often in a clinically occult manner. Significant delayed bleeding can occur, and may not be clinically apparent. Bleeding recognized endoscopically at the time of sphincterotomy is an insensitive but relatively specific predictor of postprocedural bleeding. As use of endoscopic sphincterotomy increases, careful surveillance for hemorrhagic complications, as well as efforts to identify factors predisposing to the same, will be of increasing importance. 
Blood-brain barrier disruption after cardiopulmonary resuscitation in immature swine. We investigated blood-brain barrier permeability in 2-3-week-old anesthetized pigs during and after cardiopulmonary resuscitation. We assessed permeability by tissue uptake of radiolabeled aminoisobutyric acid, after correcting for plasma counts in tissue with radiolabeled inulin. Among 14 regions examined, the transfer coefficient of aminoisobutyric acid in nonischemic control animals ranged from 0.0018 +/- 0.0001 ml/g/min in diencephalon to 0.0049 +/- 0.0003 ml/g/min in cervical spinal cord. After 8 minutes of cardiac arrest followed by either 10 or 40 minutes of continuous sternal compression, there was no increase in the transfer coefficient. Likewise, during the immediate period after ventricular defibrillation, there was no increase in transfer coefficient despite the brief, transient hypertension. However, after 8 minutes of arrest, 6 minutes of cardiopulmonary resuscitation, and 4 hours of spontaneous circulation, the transfer coefficient was significantly increased by 59-107% in 10 of 11 regions rostral to the pons. Plasma volume in tissue measured by inulin was not elevated, suggesting that the increased transfer coefficient was not due to increased surface area. Thus, after an 8-minute period of complete ischemia, the blood-brain barrier remains intact during and immediately after resuscitation despite large vascular pressure fluctuations. However, in contrast to previous work on adult dogs, immature pigs are prone to a delayed increase in permeability, thereby allowing circulating substances greater access to the brain. 
Ankle arthrodesis. A comparison of internal and external fixation. The authors reviewed the results of ankle arthrodesis in 68 ankles in 66 patients. The average follow-up period of the patients was five years (range, two to ten years). There were 40 ankles in which internal fixation was used and 28 ankles in which external fixation was used. The two groups were compared to determine the effect of mode of stabilization on outcome. Outcome was measured by time to union, development of complications, and clinical follow-up result. The groups were similar in regards to gender, age, and preoperative diagnosis. The external fixation group had a significantly higher prevalence of complications, including non-union, delayed union, and infection, than the internal fixation group. It was concluded that ankle arthrodesis with internal fixation is better tolerated and has fewer complications than techniques that use external fixation. 
Double-blind controlled study of botulinum toxin in adductor spasmodic dysphonia. The treatment of adductor spasmodic dysphonia using botulinum toxin A was conducted in 13 patients as a double-blind, placebo-controlled study. Patients were diagnosed independently by an interdisciplinary team consisting of speech pathologists, an otolaryngologist, and a neurologist. The toxin or saline was injected into each thyroarytenoid muscle under electromyographic and laryngoscopic guidance. Botulinum toxin A markedly reduced perturbation, decreased fundamental frequency range, and improved the spectrographic characteristics of the voice. Fundamental frequency and phonation time remained unchanged. Patients injected with botulinum toxin A noticed significant improvement in their voices in comparison with the placebo-treated group. Excessive breathiness of the voice occurred in two patients, and mild bleeding in one patient in the botulinum toxin A-treated group. Injection with saline resulted in edema of the vocal cord in one patient. Botulinum toxin A proved to be an effective and safe treatment of adductor spasmodic dysphonia. 
Usefulness of the nude mouse model in mesothelioma based on a direct patient-xenograft comparison. A patient with malignant mesothelioma experienced tumor recurrence 3 months after pleuropneumonectomy. Samples of the tumor were transplanted into nude mice to assess chemosensitivity. There was close concordance between the results in xenografts and the clinical outcome in this patient. Both mitomycin and to a lesser extent cisplatin were effective as single agents against the nude mouse xenografts, and the combination of these two drugs produced a complete response both in the patient and in the xenografts. The patient survived 18 months from onset of chemotherapy and 24 months from diagnosis. The duration of clinical complete response to chemotherapy was 14 months, despite the fact that mitomycin, the most effective agent against the xenografts, was discontinued after only two cycles because the patient developed pulmonary toxicity. This direct patient-xenograft correlation further validates the usefulness of the nude mouse model in the search for effective therapies for malignant mesothelioma, a tumor characterized by frequent refractoriness to most available agents. 
Combination antimicrobial therapy in the treatment of acute pelvic inflammatory disease. We compared the clinical and microbiologic efficacy of two broad-spectrum combination antimicrobial regimens in the treatment of 148 patients with acute pelvic inflammatory disease. Patients were randomized to inpatient treatment with either cefoxitin and doxycycline (n = 75) or clindamycin and tobramycin (n = 73). These antibiotics were administered intravenously for at least 4 days, and up to 48 hours beyond defervescence. Patients were discharged on a regimen of oral doxycycline or clindamycin in accordance with the intravenous regimen to complete a total duration of therapy of 2 weeks. Neisseria gonorrhoeae (53%) and Chlamydia trachomatis (31%) were the microorganisms that were isolated most frequently from the genital tract of enrolled patients. At follow-up, N. gonorrhoeae was isolated in two patients, and C. trachomatis was isolated in none. The overall initial favorable response rate to combination antimicrobial therapy was 98.5% (130/132) in patients with uncomplicated pelvic inflammatory disease and 81% (13/16) in patients with pelvic inflammatory disease that was complicated by tuboovarian abscess. A greater than 70% decrease in abdominal tenderness score occurred in 89% of 111 patients within 6 weeks of hospital discharge. There were no significant differences between antibiotic treatment groups in any response categories or in toxicity. During the initial hospitalization, five patients (three with tuboovarian abscess; one with a pyosalpinx, and one with intractable acute and chronic pelvic inflammatory disease) required surgical intervention. These results support the recommendation to use broad-spectrum combination antimicrobial therapy for the treatment of acute pelvic inflammatory disease. 
Psychological changes accompanying non-pharmacological treatment of chronic headache: the effects of outcome. Several prior studies suggest that non-drug treatment for chronic headache is accompanied by concomitant reductions in patients' anxiety, depression and somatization. It is currently unclear, however, whether such beneficial side effects are a function of degree of headache relief or are due simply to receiving treatment. Most work to date in this area has treated outcome as a dichotomous variable. The present report employed a regression approach which treats outcome (degree of headache relief) as a continuous variable in the study of 149 chronic headache patients and their accompanying psychological changes. Anxiety and depression were significantly reduced for headache patients regardless of degree of headache relief. With somatization, however, degree of headache relief had a significant effect; the greater the reduction in headache, the fewer somatic concerns were expressed, especially for mixed headache. 
Subcutaneous metoclopramide in the treatment of symptomatic gastroparesis: clinical efficacy and pharmacokinetics. We investigated the safety and efficacy of short-term s.c. administration of metoclopramide in the treatment of symptomatic gastric stasis. Ten patients with gastroparesis, documented by abnormal solid phase radionuclide gastric emptying study, were treated with 10 mg (2 ml) of s.c. metoclopramide every 6 hr for 3 days. Patients gave themselves the injections as outpatients. Questionnaires were then completed concerning symptom relief, local side effects and adverse reactions. A repeat gastric emptying study was obtained immediately after the last dose of metoclopramide. Serum metoclopramide concentrations were obtained at trough, 1, 2, 3, 4 and 5 hr postadministration and serum prolactin levels at trough, 1 and 3 hr. Pharmacokinetic analysis showed mean peak metoclopramide concentration at 30 min of 99.7 +/- 47.1 ng/ml with measured levels of 93.9 +/- 106.83 ng/ml at 60 min and return to trough values by 4 hr; trough prolactins remained elevated above normal values. Gastric stasis improved from a base-line retention of 78.7% of radioisotope at 2 hr to 72.5% after 3 days of therapy (P = .65). Eight patients reported significant improvement in symptomology and two patients reported lessening of symptoms such as nausea, vomiting, bloating, abdominal pain, heartburn and vomiting. The side effects were minimal and did not interfere with completion of the protocol. We demonstrated that s.c. administration of metoclopramide was well accepted by patients and resulted in subjective and objective improvement of gastric stasis. In addition, serum metoclopramide concentrations were comparable with other parenteral routes of administration. Furthermore, serum prolactin levels may provide both a bioassay of efficacy and a marker for monitoring compliance. 
Disseminated histoplasmosis in a renal transplant patient: a cause of renal failure several years following transplantation. A 49-year-old man developed disseminated histoplasmosis 6 1/2 years after transplantation. The organism was initially present in the urine and in a tongue lesion. Treatment with itraconazole was instituted. However, there was further dissemination of the disease and worsening of renal function. Allograft biopsy showed extensive involvement with the organism. Amphotericin B was started, resulting in a rapid resolution of the disease. However, renal function deteriorated, leading to permanent hemodialysis. 
Dietary risk factors associated with acute and persistent diarrhea in children in Karachi, Pakistan. Feeding practices may have an important impact on diarrheal diseases in developing countries. This study evaluated feeding practices in three groups of male children aged 6-36 mo: 100 with persistent diarrhea (PD), 79 with acute diarrhea (AD), and 86 in a comparison group (CG). The children came from comparably poor socioeconomic settings in Karachi, Pakistan, except that the literacy rates were higher in mothers of the CG (P = 0.0001). Although greater than 95% of all infants were breast-fed, delayed initiation of breast-feeding was more common in the diarrhea groups. Children with diarrhea were also more likely to receive supplemental milk (PD = 92%, AD = 87%) than were children in the CG (69%, P less than 0.05). Feedings were not withheld during diarrhea but changes were made in the nature of foods given. These results indicate that several feeding practices may be important risk factors for diarrhea in Pakistan. 
Adenocarcinoma of urinary bladder: classification and management. Adenocarcinoma of the urinary bladder is an uncommon, often aggressive urologic cancer. In an attempt to classify and define management of this tumor, 28 patients with vesical adenocarcinoma were studied. Excluded were patients with mixed transitional cell carcinoma and adenocarcinoma. Three major classes of tumor were identified: primary vesical adenocarcinoma, urachal adenocarcinoma, and extravesical adenocarcinoma involving the bladder. Signet ring cell tumors appeared to behave more aggressively than other cell types. Radical surgery was the most effective treatment. 
The role of platelets, thrombin and hyperplasia in restenosis after coronary angioplasty. Coronary angioplasty has become a successful and widely used treatment for patients with coronary artery disease since its first clinical application in 1977. The primary success rate has improved despite the increase in procedure and case complexity. However, acute reocclusion and late restenosis, which constitute the most important problems after successful angioplasty, continue to occur in about 5% and 35% of patients within 3 to 6 months, respectively. Angioscopic and pathologic observations have suggested that a multifactorial pathophysiologic process accounts for acute reocclusion, involving marked thrombosis, intimal dissection, medial and subintimal hemorrhage, vascular recoil and vasocontriction. In contrast, chronic restenosis involves the development of fibrocellular intimal hyperplasia within a milieu created by vascular injury, platelet activation, thrombin generation and the release of mitogens. Although current pharmacologic approaches, which involve antithrombotic and anticoagulant therapy, have been largely ineffective in eliminating acute reocclusion and chronic restenosis, recent advances in the research in thrombosis, platelet receptors and smooth muscle growth regulation have allowed new therapeutic options to be tested in the experimental setting, with subsequent potential clinical applications in patients. 
The Washington University-Barnes Hospital experience with lung transplantation. Washington University Lung Transplantation Group OBJECTIVE.--To review our experience with lung transplantation, emphasizing recipient selection, choice of procedure, functional results, and outcome. DESIGN.--Retrospective review of patients who received lung transplants at Barnes Hospital, St Louis, Mo, between July 1, 1988, and January 31, 1991. SETTING.--Washington University School of Medicine, St Louis, Mo, and Barnes Hospital, a medical school and its affiliated referral hospital, respectively. PATIENTS.--Sixty-nine lung transplant procedures were performed in 66 recipients. Patients with clinically and physiologically severe lung disease were selected according to predetermined guidelines. Underlying diseases in the recipients included chronic obstructive pulmonary disease, alpha 1-antitrypsin deficiency emphysema, cystic fibrosis, pulmonary fibrosis, primary pulmonary hypertension, Eisenmenger's syndrome associated with an atrial septal defect, bronchiectasis, eosinophilic granuloma, and lymphangiomyomatosis. INTERVENTION.--Double-lung, bilateral sequential, and single-lung transplantations were performed. Eight patients underwent en bloc double-lung transplantations or a modification of this procedure with separate bronchial anastomoses. Thereafter, the bilateral sequential approach to replacement of both lungs was performed in 26 patients. Thirty-two patients underwent single-lung transplantations. MAIN OUTCOME MEASURES.--Pulmonary function tests, arterial blood gas levels, pulmonary artery pressure, pulmonary vascular resistance, and actuarial survival. RESULTS.--Actuarial survival at 1 year for the 66 lung transplant recipients was 79%. Actuarial survival at 1 year was 82% for the bilateral lung transplant recipients and was 90% for the single-lung transplant recipients. In patients with either restrictive or obstructive lung disease, pulmonary function tests and arterial blood gas levels improved markedly after lung transplantation. In patients with primary pulmonary hypertension or Eisenmenger's syndrome, the pulmonary artery pressure decreased and the cardiac index increased into the normal range after single-lung transplantation. CONCLUSIONS.--In carefully selected patients with end-stage lung disease, single-lung and bilateral lung transplantations can significantly improve functional capacity, with promising early actuarial survival statistics after 1 year. 
Endothoracic endoesophageal pull-through operation. A new approach to cancers of the esophagus and proximal stomach. Many thoracic surgeons have expressed concern about the complications inherent in transhiatal esophagectomy without thoracotomy. The technique of endothoracic endoesophageal pull-through uses a mucosal coring of normal esophagus beyond the tumor and leaves a muscular tube through which the substitute organ is passed. Mediastinal hemorrhage, tracheal injury, and chylothorax are eliminated. 
Pellagra in a patient with an eating disorder. A case of pellagra is described that occurred in a patient with an eating disorder and who presented with marked photosensitivity and diarrhoea. We found urinary 5-hydroxy-indole-acetic acid to be low and suggest that this may be a useful screening test. To our knowledge this is only the second reported case of pellagra associated with an eating disorder. 
Perioperative stroke. Part II: Cardiac surgery and cardiogenic embolic stroke. The major mechanism of stroke in cardiac surgery is embolization. The risk is higher in intracardiac than in extracardiac surgery. The incidence of stoke associated with CABG is about 5%. The cerebral protective properties of isoflurane and thiopentone, acid-base management, and monitoring of cerebral perfusion during cardiopulmonary bypass are discussed. Prophylactic carotid endarterectomy for patients with asymptomatic carotid disease before cardiac surgery is not necessary. Symptomatic carotid disease increases the risk of stroke, and the management of patients who have both symptomatic coronary and carotid artery diseases is discussed. Cardiogenic embolism is probably responsible for many perioperative strokes. Patients with atrial fibrillation, valvular disease, and prosthetic heart valves are at high risk of cardiogenic embolism. Strokes associated with cardioversion, pacemaker insertion, coronary arteriography and angioplasty are explored. 
Desirability of immediate surgical standby for coronary angioplasty. OBJECTIVE--To assess the value of emergency surgical standby for percutaneous transluminal coronary angioplasty. DESIGN--Retrospective review of the major complications of coronary angioplasty in a regional cardiac centre. SETTING--All angioplasties were performed in the cardiac catheterisation laboratory of Wythenshawe Hospital with surgical standby in an adjoining operating theatre. PATIENTS--1262 vessels were dilated in 1032 patients (mean age 53 years) between 1984 and 1989. MAIN OUTCOME MEASURES--In-hospital mortality from emergency surgical revascularisation after angioplasty; the rate of myocardial infarction and overall morbidity. RESULTS--Coronary angioplasty achieved primary success in 90% of cases. Thirty eight (3.7%) patients (five women (mean age 55.8) and 33 men (mean age 53.0] were referred for urgent surgical revascularisation--36 direct to operation and two within 24 hours. All patients survived surgery. Five of the 38 had had a previous angioplasty to the same vessel and one had had previous coronary artery grafts. Four of the 38 had an angioplasty for unstable angina. Eighteen had single, 13 double, and seven triple vessel coronary artery disease. The target vessel was the left anterior descending in 25, right coronary artery in nine, circumflex in three, and the left anterior descending and circumflex coronary arteries in one. Five required external cardiac massage on the way to the operating theatre; two of them had a left main stem occlusion. Four internal mammary artery and 60 reversed saphenous vein grafts were implanted (1.6 per patient). Complete revascularisation was achieved in 36 (94.7%) patients. Q wave myocardial infarction occurred in six (15.8%). The final outcome was: none dead, three patients with angina, one late death, one cerebrovascular accident, one late operation for a new left anterior descending lesion, two patients on diuretics with or without an angiotensin converting enzyme inhibitor. One orthotopic transplant was performed in a patient in whom cardiogenic shock developed after the left anterior descending coronary artery became occluded 72 hours after angioplasty. CONCLUSION--There was no surgical mortality and low morbidity among patients for whom immediate surgical cover was requested. 
Recurrent adnexal torsion and cystadenoma of aberrant ovarian tissue. Torsion of the adnexa is rare, and diagnosis is difficult because of the sparse clinical findings. I describe a patient with recurrent torsion of the right adnexa, involving a cystadenoma of aberrant ovarian tissue. Her only symptom was recurrent right-sided pelvic pain. 
Limitations of ultrasonography in surveillance of small abdominal aortic aneurysms. The repeatability, observer bias and instrument bias of aortic diameter measurement by ultrasonography, were investigated in ten patients with small (3-6 cm by computed tomography) infrarenal abdominal aortic aneurysm. The repeatability of maximum aortic diameter measurement by ultrasonography was much better for anterior-posterior than transverse diameter, with coefficients of repeatability 3.0-7.5 mm and 10-15 mm respectively. The repeatability of suprarenal aortic diameter measurement was poor. Surprisingly, maximum diameter using ultrasonography was larger than that using computed tomography, the difference being least for anterior-posterior measurements. At best a single, experienced observer, using the same instrument may provide aortic diameters using ultrasonography accurate to within 5 mm, but more commonly such aortic diameter is only accurate to within 8 mm. 
Argon beam coagulation is superior to conventional techniques in repair of experimental splenic injury. Present management of splenic trauma focuses on splenic preservation. However, conventional operative techniques for splenic salvage are time consuming and frequently ineffective. The purpose of this study was to assess the efficacy of the argon beam coagulator (ABC) in the management of experimental splenic injury. Ten adult miniature pigs were randomized to treatment with either conventional surgical techniques (topical Surgicel, electrocautery, suture-ligation, digital pressure) or splenic repair with the ABC. Three standard splenic injuries were made in each pig: capsular avulsion, splenic laceration, and hemisplenectomy. The ABC was more effective in treating all three types of splenic injury. The time required to achieve hemostasis and total operative time were significantly less in the group treated with the ABC for all three types of splenic injuries (p less than 0.05, Student's t-test, two sided). Operative blood loss was significantly less in the group treated with ABC for avulsion and hemisplenectomy (p less than 0.05, Student's t-test, two sided). Recurrent bleeding was significantly higher in the group treated with conventional techniques (p less than 0.001, Fisher's exact test, two-sided). We conclude that the argon beam coagulator is more effective than conventional techniques in treating experimental splenic injuries. The ABC provides more rapid and reliable hemostasis. Clinical trials using the ABC for splenic injury are warranted. 
Factors relevant to preventing embolic stroke in patients with non-rheumatic atrial fibrillation. Whether or not to treat patients with non-rheumatic atrial fibrillation with anticoagulants to prevent embolic stroke is a dilemma for physicians. If randomized trials, currently underway, demonstrate a beneficial effect, the dilemma will not be solved because not all of the relevant factors can be addressed by trials. We used current knowledge about non-rheumatic atrial fibrillation and a method of obtaining patient-derived weights for avoiding stroke from eight medically trained subjects, to determine the overall benefit of anticoagulants and to see what factors were relevant and what effect each might have in deciding whether to use anticoagulant therapy. Using standard assumptions, anticoagulants gave an expected benefit for all subjects. The expected benefit (expressed in terms of lives per 1000 saved due to anticoagulants) varied between 5.4 and 46.7. This benefit remained for all subjects when we did a sensitivity analysis for different rates of stroke prevented by anticoagulants and different rates of intracranial hemorrhage caused by anticoagulants. When we used different baseline rates of stroke and different impacts of major hemorrhagic complications the benefit disappeared for 3 and 4 subjects respectively. We found the factors that were most crucial to the decision will not be included in randomized trials; the weight that an individual would place on avoiding embolic stroke vs the risk of intracranial bleeding from anticoagulant therapy; and the rate of embolic stroke that could be expected for the subject at risk. Factors which will be measured in randomized trials, will change results less substantially: the increased risk of major hemorrhages; the proportion of strokes that could be prevented by treatment; the increase in risk of intracranial hemorrhage. This method of analysis suggests that for most patients anticoagulants are beneficial and that the most important factor in determining this result is the value that subjects put on different outcomes. 
Sarcoplasmic reticulum-associated cyclic adenosine 5'-monophosphate phosphodiesterase activity in normal and failing human hearts. Sarcoplasmic reticulum-associated cAMP phosphodiesterase activity was examined in microsomes prepared from the left ventricular myocardium of eight heart transplant recipients with end-stage idiopathic dilated cardiomyopathy and six unmatched organ donors with normal cardiac function. At cAMP concentrations less than or equal to 1.0 microM, sarcoplasmic reticulum-associated cAMP phosphodiesterase activity was functionally homogeneous. cAMP phosphodiesterase activity was inhibited competitively by cGMP (Ki = 0.031 +/- 0.008 microM) and the cilostamide derivative OPC 3911 (Ki = 0.018 +/- 0.004 microM), but was essentially insensitive to rolipram. Vmax and Km were 781.7 +/- 109.2 nmol/mg per min and 0.188 +/- 0.031 microM, respectively, in microsomes prepared from nonfailing hearts and 793.9 +/- 68.9 nmol/mg per min and 0.150 +/- 0.027 microM in microsomes prepared from failing hearts. Microsomes prepared from nonfailing and failing hearts did not differ with respect to either the ratio of cAMP phosphodiesterase activity to ATP-dependent Ca2+ accumulation activity or the sensitivity of cAMP phosphodiesterase activity to inhibition by OPC 3911. These data suggest that the diminished inotropic efficacy of phosphodiesterase inhibitors in failing human hearts does not result from changes in the level, kinetic properties, or pharmacologic sensitivity of sarcoplasmic reticulum-associated cAMP phosphodiesterase activity. 
Erythropoietin deficiency in acute crescentic glomerulonephritis and in total bilateral renal cortical necrosis. Six patients with acute renal failure, in five cases due to acute crescentic glomerulonephritis and in one case due to total bilateral renal cortical necrosis, were studied. All had serum erythropoietin (EPO) concentrations in the normal range, despite a relatively severe anaemia. Half-life and plasma clearance of intravenously injected recombinant human erythropoietin (rhEPO) were determined. The results indicate that the lack of compensatory increase in serum EPO to the anaemic stimulus is not due to increased catabolism, but to decreased synthesis of the renal hormone. Two patients were treated with rhEPO (Eprex). In marked contrast to untreated controls, both patients responded with vigorous reticulocytosis and normalization of haemoglobin levels while they were still in severe renal failure. These results are similar to our previous findings in patients with acute renal failure due to tubular necrosis. Under all three conditions the defective EPO synthesis is probably the dominant pathogenetic factor for the largely aregeneratory anaemia of prolonged cases, and for the sluggish restoration of red cell mass during recovery of renal function. It is concluded that defective synthesis of EPO is not only a permanent and irreversible feature of severe chronic renal failure, but that it is also present, usually in a transient and reversible form, in different types of acute renal failure. 
Chronic sialadenitis with psammoma bodies mimicking neoplasia in a fine-needle aspiration specimen from the submandibular gland. A 65-year-old woman with a submandibular gland nodule had a fine-needle aspiration specimen that contained groups of duct-type cells and a psammoma body, suggestive of adenocarcinoma. The resected gland showed chronic sialadenitis with sialolithiasis and psammoma bodies. In a series of 81 resected nonneoplastic submandibular glands from 72 patients, psammoma bodies, nonlaminated microcalcifications, or both were found in 46 (57%). They were located most commonly just outside of striated or intercalated ducts. When examining fine-needle aspiration specimens from the submandibular gland, it is important that one be aware that psammoma bodies may occur in normal, inflamed, irradiated, and neoplastic conditions. 
Deficits in strategy application following frontal lobe damage in man. A quantitative investigation of the ability to carry out a variety of cognitive tasks was performed in 3 patients who had sustained traumatic injuries which involved prefrontal structures. All 3 had severe difficulties in 2 tests which required them to carry out a number of fairly simple but open-ended tasks over a 15-30 min period. They typically spent too long on individual tasks. All patients scored well on tests of perception, language and intelligence and 2 performed well on a variety of other tests of frontal lobe function. Explanations for their difficulty on the multiple subgoal tasks in terms of memory or motivational problems could be excluded. It is argued that the problem arose from an inability to reactivate after a delay previously-generated intentions when they are not directly signalled by the stimulus situation. 
Descending thoracic aortofemoral bypass as an alternative for aortoiliac revascularization. We performed descending thoracic aorta to femoral bypass in six selected patients over the past four years. An alternative inflow source was selected because the standard transabdominal approach was contraindicated or considered hazardous. The inflow consisted of a single Dacron tube from the descending thoracic aorta to the left groin, and a femorofemoral bypass to the right groin. There was no operative mortality or major morbidity related to the surgical procedure. After an average follow-up of 17.1 months (range 6 to 23 months), all thoracofemoral grafts remained patent. One patient had repeated occlusions of the femorofemoral graft related to right lower extremity outflow disease, while the remaining five crossover grafts are patent. One patient died 22 months postoperatively from a myocardial infarct, with a patent bypass. Although this series represents a small group of patients, we feel that descending thoracic aortofemoral bypass offers excellent inflow and reliable patency, and is a good alternative when reoperation on the abdominal aorta is undesirable. This procedure may also be considered for conversion of an axillofemoral bypass that has failed repeatedly. 
The European Stroke Prevention Study (ESPS): results by arterial distribution. The European Stroke Prevention Study was a multicenter study comparing the effect of the combination of dipyridamole, 75 mg, and acetylsalicylic acid, 330 mg, three times a day, to that of placebo in 2,500 patients in the secondary prevention of stroke or death after one or more transient ischemic attacks, reversible ischemic neurological deficits, or strokes of atherothrombotic origin. The patients with vertebrobasilar events at entry comprised one-third of the whole patient population. The overall total incidence of stroke or death (the end points) during the 2-year follow-up in the placebo group was lower in the vertebrobasilar group compared to the carotid group (14% versus 24%, respectively). The combination therapy of dipyridamole and acetylsalicylic acid caused a marked reduction in the incidence of stroke or death in patients with vertebrobasilar (51%) and carotid (30%) events. When only stroke was considered as the end point, dipyridamole and acetylsalicylic acid seemed to be more effective in reducing the risk of transient ischemic attacks than stroke, and more effective in men than in women. 
Intravenous adenosine: continuous infusion and low dose bolus administration for determination of coronary vasodilator reserve in patients with and without coronary artery disease. To assess the use of adenosine as an alternative agent for determination of coronary vasodilator reserve, hemodynamics and coronary blood flow velocity were measured at rest and during peak hyperemic responses to continuous intravenous adenosine infusion (50, 100 and 150 micrograms/kg per min for 3 min) and intracoronary papaverine (10 mg) in 34 patients (17 without [group 1] and 17 with [group 2] significant left coronary artery disease), and in 17 patients (11 without and 6 with left coronary artery disease) after low dose (2.5 mg) intravenous bolus injection of adenosine. The maximal adenosine dose did not change mean arterial pressure (-10 +/- 14% and -6 +/- 12% for groups 1 and 2, respectively) but increased the heart rate (15 +/- 18% and 13 +/- 16, respectively). For continuous adenosine infusions, mean coronary flow velocity increased 64 +/- 104%, 122 +/- 94% and 198 +/- 59% and 15 +/- 51%, 110 +/- 95% and 109 +/- 86% in groups 1 and 2, respectively for each of the three doses. Mean coronary flow velocity increased significantly after 100 and 150 micrograms/kg of adenosine and 10 mg of intracoronary papaverine (48 +/- 25, 52 +/- 19 and 54 +/- 21 cm/s, respectively; all p less than 0.05 vs. baseline) and was significantly higher than in group 2 (37 +/- 24, 32 +/- 16, 41 +/- 23 cm/s; all p less than 0.05 vs. group 1). The coronary vasodilator reserve ratio (calculated as the ratio of hyperemic to basal mean flow velocity) for adenosine and papaverine was 2.94 +/- 1.50 and 2.94 +/- 1.00, respectively, in group 1 and was significantly and similarly reduced in group 2 (2.16 +/- 0.81 and 2.38 +/- 0.78, respectively; both p less than 0.05 vs. group 1). Low dose bolus injection of adenosine increased mean velocity equivalently to that after continuous infusion of 100 micrograms/kg, but less than after papaverine. There was a strong correlation between adenosine infusion and papaverine for both mean coronary flow velocity and coronary vasodilator reserve ratio (r2 = 0.871 and 0.325; SEE = 0.068 and 0.189, respectively; both p less than 0.0005). No patient had significant arrhythmias or prolongation of the corrected QT (QTc) interval with adenosine, but papaverine increased the QT (QTc) interval from 445 +/- 44 to 501 +/- 43 ms (p less than 0.001 vs. both maximal adenosine and baseline) and produced nonsustained ventricular tachycardia in one patient.(ABSTRACT TRUNCATED AT 400 WORDS). 
Continuous vectorcardiography in cardiac surgery: natural course of vector changes and relationship to myocardial oxygen uptake. Continuous vectorcardiography was registered before and during the first 18 hours after cardiac surgery in 53 patients. QRS vector changes (QRS-VD) occurred during the operation, but no further changes were observed postoperatively. The ST vector (ST-VM) increased during the operation, and a further slight increase occurred postoperatively. Perioperative myocardial infarction occurred in three patients. Their ST-VM was higher than the average in patients without myocardial infarction, while QRS-VD did not differ from the average pattern. Twelve other patients were studied in pacemaker-induced moderate tachycardia. QRS-VD increased in proportion to heart-rate changes (rs median = 0.93, p less than 0.01). QRS-VD also correlated with myocardial oxygen uptake (rs median = 0.62, p less than 0.05). The ST-VM responses were not uniform. The data suggest that vectorcardiogram variables can provide information related to myocardial energy metabolism. 
Value of electrocardiographic leads MCL1, MCL6 and other selected leads in the diagnosis of wide QRS complex tachycardia. To compare the modified precordial leads MCL1 and MCL6 with the conventional precordial leads V1 and V6 and assess the diagnostic accuracy of selected leads for continuous bedside electrocardiographic (ECG) monitoring, 121 wide QRS complex tachycardias were recorded from 92 patients during cardiac electrophysiologic study. As ascertained from intracardiac recordings, 86 tachycardias were ventricular and 35 were supraventricular with aberrant conduction. Early or late peaking of the predominant QRS deflection in lead MCL6 or V6 proved valuable in diagnosing wide complex tachycardia. An interval of less than or equal to 50 ms from the onset of the QRS complex to the predominant peak (or nadir) indicated supraventricular tachycardia; an interval of greater than or equal to 70 ms indicated ventricular tachycardia. The QRS complexes in leads MCL1 and MCL6 were comparable to those in leads V1 and V6 during sinus rhythm. Significant discrepancies in QRS configuration occurred between the modified and conventional precordial leads during ventricular tachycardia, especially between leads MCL1 and V1; however. these differences did not affect diagnostic accuracy. A single MCL1, V1, MCL6 or V6 lead was equally valuable in the diagnosis of wide complex tachycardia and far superior to a single lead II. A combination of leads (MCL1 + MCL6), (V1 + V6), (V1 + I + aVF) or (V1 + V6 + I + aVF) was superior to a single lead or the routinely monitored lead V1 + II combination. 
Multiple luteinizing hormone/chorionic gonadotropin receptor messenger ribonucleic acid transcripts. It has previously been shown that multiple messenger RNA (mRNA) species can be identified in gonadal tissues by probes specific for the LH/CG receptor. Here we show that the sizes and relative abundancies of gonadal LH/CG receptor transcripts are quite variable between such closely related species as rat and mouse. These patterns of LH/CG receptor mRNAs are yet different from that observed in human embryonic kidney 293 cells that have been transfected with a cDNA encoding for the rat luteal LH/CG receptor. In spite of the diversity in the number and sizes of LH/CG receptor mRNA transcripts, however, our data also show that the size of the cell surface receptor expressed in these three cells/tissues is identical. We further show that the most abundant LH/CG receptor mRNA present in MA-10 cells, a clonal strain of cultured Leydig tumor cells, is a 1.2 kilobase transcript which encodes for a truncated version of the LH/CG receptor corresponding to the extracellular hormone-binding domain. It does not appear, however, that this transcript is translated into a functional protein. 
Cytomegalovirus infection of the appendix in patient with the acquired immunodeficiency syndrome. Disseminated cytomegalovirus infection occurs predominantly in immunocompromised hosts. Involvement of the gastrointestinal tract in the acquired immunodeficiency syndrome is frequent, but to our knowledge there is only one report of involvement of the appendix. In this study, a patient with a history of the acquired immunodeficiency syndrome who presented with fever and an acute abdomen is described. At surgery, appendicitis was found. In the surgical specimen, appendicitis and cytomegalovirus infection were found. Cytomegalovirus should be considered as a possible cause of appendicitis in the acquired immunodeficiency syndrome. 
Echo Doppler duplex scanner and color in the study of portal hypertension. In the present state of the art, the Doppler duplex scanner provides much information about portal hypertension and its associated pathology, liver cirrhosis, hepatic malformations, vascular or avascular structures, hepatic transplants, and ascites. Its usefulness for experimental studies, providing new insight into the pathophysiology of this disease, has been proven. It is limited by the subjectivity of the conclusions, and by its poor feasibility in fat patients and those with excessive abdominal gas. However, the noninvasive nature of Doppler and its relative low cost make it a useful first step in the evaluation of portal hypertension. 
Anismus in patients with normal and slow transit constipation. This study examined differences in anorectal function, with particular reference to anismus, which might explain why some patients with intractable constipation have slow and others have normal whole gut transit times. Twenty-four patients were studied; 13 with slow transit (all female, median age 32 years, range 16-52 years) and 11 with normal transit (eight women, three men, median age 37 years, range 21-60 years). Videoproctography with synchronous sphincteric electromyography and anorectal manometry was performed. There were no differences between the two groups, suggesting that slow transit constipation is not secondary to any abnormality in anorectal function and may therefore be a primary disorder of colonic motility. There was no correlation between electromyographic evidence of anismus (pelvic floor contraction on defaecation) and the ability of the patient to evacute the rectum or symptoms of obstructed defaecation. Electromyography findings alone can be misleading and should be related to proctographic evidence of incomplete rectal evacuation before functional anismus can be said to be present. 
Informing schools about children's chronic illnesses: parents' opinions. Parents of 217 chronically ill children and adolescents were surveyed concerning their opinions about disclosing medical information to schools. The sample consisted of parents of more than one third of the children and adolescents meeting inclusion criteria who were seen at a university-based pediatric clinic during a 10-week period. Parents were asked (1) whether schools need information about 16 health items, (2) who in the school should know, and (3) who should provide this information. Parents' willingness to disclose information was compared with family and child demographic data. Parents strongly believed that (1) teachers need to be informed and (2) parents should be the primary informers. The consensus that schools need information did not vary with family and child demographics. However, parents of children with poor illness prognosis, greater likelihood of emergencies, and visible illnesses were more supportive of disclosure. Most parents indicated that physicians should provide information on 10 of the 16 items. Physicians were viewed as particularly appropriate informers about recognizing emergencies and medication effects. Only 21% of the parents were aware of any prior contact between the medical care giver and the school concerning their child's illness. Thus, parents want schools informed and believe physicians should be involved in providing information. 
Dipyridamole echocardiography. A new diagnostic window on coronary artery disease. Dipyridamole echocardiography testing is a highly feasible, inexpensive, and safe diagnostic tool, with excellent specificity and good sensitivity--especially in patients with multivessel disease and/or resting dyssynergy--for the diagnosis of coronary artery disease. The test does not offer an "all or none" binary result but rather a complex stratification of the ischemic response along the coordinates of time and space, accurately identifying the degree of physiological impairment of coronary reserve, the severity and extent of coronary disease, the geographic location of the area at risk, and the prognostic outlook. It offers highly competitive diagnostic information versus more sophisticated, time-consuming, and costly radionuclide techniques; in comparison with other stress echocardiography techniques, it is more feasible than exercise and less invasive and better tolerated than pacing. The electrocardiogram usefully integrates the information provided by the mechanical marker of ischemia during dipyridamole testing. The finding of echocardiographically silent ST segment depression represents a clue to the identification of angiographically normal coronary arteries. On the basis of this evidence, dipyridamole testing with two-dimensional echocardiography and 12-lead electrocardiography can be considered a reasonable choice for the exercise-independent diagnosis of coronary artery disease. 
Cefixime compared with amoxicillin for treatment of acute otitis media. Cefixime was compared with amoxicillin for treatment of acute otitis media in a randomized trial. Results of tympanocentesis on day 3 to 5 of therapy were used as the major outcome. Total daily doses were 8 mg/kg of cefixime and 40 mg/kg of amoxicillin. One hundred twenty-six patients were randomly assigned to receive treatment; 64 cultures grew pathogens. Pathogens were eradicated from the middle ear after 3 to 5 days of therapy in 27 (79.4%) of 34 children given amoxicillin and 26 (86.7%) of 30 children given cefixime (p = 0.47). When Streptococcus pneumoniae cases were analyzed, bacteriologic cure occurred in 14 (93.3%) of 15 children given amoxicillin and 12 (75%) of 16 given cefixime (p = 0.333). When cases of Haemophilus influenzae infection were analyzed, significantly more cures occurred with cefixime (10/10, 100%) than amoxicillin (8/13, 62%) (p = 0.046). Pathogens associated with failure of amoxicillin therapy were H. influenzae (five cases, two beta-lactamase-positive), S. pneumoniae (one case), and Moraxella catarrhalis (one case, beta-lactamase-positive). The four failures with cefixime therapy were all in patients infected with S. pneumoniae. Rates of rash, diarrhea, and vomiting were the same in both groups and did not necessitate stopping therapy. We conclude the following: (1) Cefixime and amoxicillin were equivalent in overall clinical and bacteriologic efficacy for otitis media. (2) Cefixime was more efficacious than amoxicillin in treating H. influenzae otitis media and should be preferred when H. influenzae is the suspected etiologic agent. (3) Side effects of both drugs were mild and equivalent. 
Factors influencing postoperative urinary retention in patients undergoing elective inguinal herniorrhaphy. We retrospectively studied 295 men who had undergone herniorrhaphy under spinal or general endotracheal anesthesia to determine the incidence of postoperative urinary retention and to assess factors influencing it. The type and location of hernia had no effect on retention. In contrast, the use of general anesthesia, patient age above 53 years, and perioperative administration of more than 1,200 mL of fluid were significantly associated with an increase in retention. Our results suggest that urinary retention after herniorrhaphy may be prevented by limiting the amount of fluid given perioperatively and by using a spinal anesthetic, especially in older patients. 
Improved survival at 2 and 5 years in the LMCE1 unselected group of 72 children with stage IV neuroblastoma older than 1 year of age at diagnosis: is cure possible in a small subgroup? The objectives of this study were to determine (1) the role of selection before bone marrow transplantation (BMT), (2) the role of vincristine, melphalan, and total body irradiation (TBI) as consolidation of induction therapy for stage IV over 12 months at diagnosis, and (3) the role of immunomagnetic purging in metastatic neuroblastoma. Among 72 consecutive unselected patients, 10 were not grafted (four died at induction: two in complete remission [CR], two in partial remission [PR]); three had bone marrow progression before harvest; one had uncontrolled progression; and two had parental refusal). Sixty-two patients were grafted (23 in CR/very good PR [VGPR] and 39 in PR). Among the 62, 33 were consolidated with at least 90% excision of their initial tumor excised (53.2%), 15 with catecholamine secretions (24.2%), 22 with minor bone marrow involvement (35.5%), and 31 with positive bone scan (50%). Median observation time is 59 months. Progression-free survival (PFS) for the 10 excluded patients was 20% at 2 years and 0% at 4 years. PFS for the grafted population (n = 62) is 40% at 2 years, 20% at 4 years, and 13% at 7 years. No difference was observed between patients grafted in CR/VGPR or in PR. However, a group of 19 children was grafted resulting in complete normalization of metastasis (regardless of primary-site tumor status). In this group, PFS at 59 months was 38% with no relapses up to 7 years post-BMT. A group of 31 patients with no bone involvement at BMT was also identified. PFS at 5 years is 30% compared with 12% for bone-positive patients at BMT. Moreover, the 11 children presenting at diagnosis with no bone involvement (Evans stage IVS or stage C Memphis) and consolidated with BMT had PFS at 5 years of 50% with no late relapses. A subgroup of stage IV neuroblastoma patients older than 1 year of age at diagnosis may be curable with this therapeutic approach, and the use of multivariate analyses to search for prognostic factors is warranted in currently existing international registries. 
Implications of the uptake of 131I-radiolabelled meta-iodobenzylguanidine (mIBG) for the targeted radiotherapy of neuroblastoma. Selective uptake of radiolabelled meta-iodobenzylguanidine (mIBG) in neuroblastoma provides a possible approach to biologically targeted radiotherapy of this disease. A mathematical model was used to predict absorbed doses to tumours of varying size from therapeutic 131I-mIBG, based on measurements of 125I-mIBG uptake in surgically excised tumours from six patients. Two size categories of tumour target were considered: bulk tumour and microscopic disease. The predicted absorbed doses were compared with doses calculated to achieve a 50% probability of tumour cure. The analysis shows that the probability of tumour cure depends strongly on mIBG uptake, effective half-life of mIBG in tumour and tumour diameter. Small microtumours may be relatively resistant to mIBG treatment owing to the limited absorption of 131I beta-energy. The product of patient mass and percentage uptake per unit mass of tumour may be a useful indicator of therapeutic outcome when targeted radiotherapy is used for the treatment of paediatric tumours. 
Transcranial magnetic stimulation in patients with epilepsy. We studied the effects of transcranial magnetic stimulation (TMS) applied in trains of 8- to 25-Hz stimuli on electroencephalographic epileptiform activity on eight patients being evaluated for epilepsy surgery. We performed the stimulation with a round water-cooled stimulation coil held flat on the scalp and centered over different positions of the International 10-20 System. We were unable to trigger seizures or induce epileptiform discharges arising from the epileptic focus in any of the eight patients with any of the stimulation protocols. However, we induced a partial motor seizure from the contralateral hemisphere to the exclusive temporal focus in the only patient stimulated with 100% maximal intensity. Precautions have to be taken when applying rapid TMS to patients because of the risk of seizure induction. Our results do not support the view that TMS specifically activates the epileptic foci. 
Venous gangrene (phlegmasia caerulea dolens) complicating heart failure from severe mitral stenosis--a case history. Gangrene of the left upper limb was found to complicate severe mitral stenosis presenting with heart failure in a sixty-eight-year-old woman with a documented left atrial thrombus. Arterial obstruction as the cause of gangrene was excluded by Doppler-assisted assessment of the peripheral pulses. Venous gangrene can complicate severe mitral stenosis and must be distinguished from arterial embolization, in which urgent surgical treatment is imperative. 
Heterotopic heart transplantation and native heart ventricular arrhythmias. Heterotopic heart transplantation has been said to be contraindicated in patients with serious native heart arrhythmias that produce hemodynamic instability. Placement of heterotopic allografts, however, can theoretically act as a biological biventricular assist device to provide hemodynamic support during these unstable rhythms. Further, this operation might beneficially alter the hemodynamic milieu of heart failure such that the arrhythmias are ameliorated. Described is our experience with 4 patients with heart failure receiving heterotopic cardiac allografts, documenting changes in native heart arrhythmia that occurred. These cases demonstrate that heterotopic grafts can adequately sustain hemodynamics during malignant native heart dysrhythmia. We believe native heart ventricular arrhythmias are not a contraindication to heterotopic heart transplantation. 
Transperineurial vessel constriction in an edematous neuropathy. The hypothesis that the accumulation of endoneurial edema can exert forces sufficient to occlude transperineurial vessels was tested using light microscopy and computer-assisted morphometry in rat sciatic nerve. Experimental nerves were exposed to a concentration of 10% procaine HCl, which from previous studies has been demonstrated to routinely produce an edematous neuropathy. For each vessel, a "constriction ratio" was defined by dividing its minimum intraperineurial lumen area by the average for minimum endoneurial and epineurial lumen cross-sectional areas. Constriction ratios were 0.91 +/- 0.26 (mean +/- SD) for control vessels and 0.28 +/- 0.25 for vessels in the procaine group (p less than 0.005). In addition, a strong negative correlation was observed between the morphologic demonstration of nerve edema and the transperineurial vessel constriction ratio (r = -0.85; p less than 0.002). It is concluded that in neuropathies characterized by widespread edema and increased endoneurial fluid pressures, the concomitant constriction of transperineurial vessels could diminish nerve blood flow and facilitate nerve injury. 
The role of radical surgery in the management of radiation recurrent and large volume prostate cancer. Twenty-two patients seen between 1975 and 1988 were analyzed who had surgical attempts to cure locally advanced prostate cancer by exenterative procedures or salvage surgery for radiation recurrent disease. Twelve patients (Group I) underwent either a salvage cystoprostatectomy or perineal prostatectomy for radiorecurrent disease, including three patients with a Kock continent urinary diversion done in combination with the salvage operation. Five of the 12 (41.7%) recurrent disease confined to the surgical specimen and 11 of 12 (91.7%) are alive at a mean follow-up of 49 months, including four patients (25%) with a completely negative serum prostate-specific antigen (PSA) value (less than 0.2 ng/dl). All perineal prostatectomy patients are continent, and two of the three Kock pouch patients are continent. Ten of the 22 patients (Group II) had a cystoprostatectomy or exenteration for locally advanced disease that the surgeon did not think was amenable to standard radical prostatectomy. Only one of these ten patients had negative surgical margins, capsule, and seminal vesicles. Nine are alive (although only one patient has no evidence of disease) at a mean follow-up of 59 months. Morbidity was substantial with a 50% major complication rate including four patients requiring reoperation because of bleeding, abscess, bowel obstruction, or colostomy closure. Salvage procedures for radiorecurrent disease can be done safely, even with the inclusion of a continent diversion, and may be curative or provide survival benefit to carefully selected patients. Cystoprostatectomy or exenteration for locally advanced disease does not appear to be a curative endeavor for most patients and may be accompanied by significant morbidity. 
Full-field electroretinograms in patients with the carbohydrate-deficient glycoprotein syndrome. We examined five patients who had carbohydrate-deficient glycoprotein syndrome with full-field electroretinograms. Only two of the patients showed fundus changes typical for retinitis pigmentosa, whereas abnormal electroretinograms were seen in all patients. There was no recordable rod response; however, a delay in the cone b-wave implicit time was noted. All patients had nyctalopia. These observations suggest that patients with the carbohydrate-deficient glycoprotein syndrome have a progressive tapetoretinal degenerative disorder of the retinitis pigmentosa type with defined alterations in the electroretinogram. 
Treatment of adenomyosis with long-term GnRH analogues: a case report. Presented here is the first reported case of biopsy-proved adenomyosis treated medically with long-term GnRH analogue. Uterine volume, as calculated by serial ultrasound measurements, was reduced by 65% after 4 months and remained small several months after discontinuation of therapy. Size reduction was accompanied by amenorrhea and relief of severe dysmenorrhea. Though not proposed as a substitute for surgery, GnRH analogue may be useful as a surgical adjuvant or for temporary reduction of symptoms. 
The representation of the visual field in human striate cortex. A revision of the classic Holmes map. We have tested the accuracy of Gordon Holmes' retinotopic map of human striate cortex by correlating magnetic resonance scans with homonymous field defects in patients with clearly defined occipital lobe lesions. Our findings indicate that Holmes underestimated the cortical magnification of central vision. In a revised map of the human striate cortex, we expand the area subserving central vision and reduce the area devoted to peripheral vision. These changes bring the map of human striate cortex into agreement with data reported for closely related nonhuman primate species. 
Equivalent total doses for different fractionation schemes, based on the linear quadratic model. A majority of patients receiving radical radiation therapy are treated with 1.8-2.0-Gy fractions, a dose that has evolved from clinical experience. However, other fractionation schemes can be advantageous. When fractionation is altered, the total dose prescribed should lead to equivalent or higher tumor control with the same or less tissue toxicity. To facilitate the use of different fractionation schemes, the authors compiled tables for equivalent biologic doses for late toxicity in normal tissues and tumoricidal doses for epithelial tumors, for various fraction sizes. The linear quadratic model according to Fowler was used. It is shown how these tables should be modified for proliferation of tumors during the course of radiation therapy. The tables make the use of different fractionation schemes easy. They also allow adjustment of total dose if fractionation needs to be changed during the course of treatment. 
Myocardial echinococcosis with perforation into the pericardium. Though rare, cardiac echinococcosis should be included in the differential diagnosis of cardiac tumors, particularly in patients originating from endemic areas or with manifestation of hydatid disease in other organs. Diagnosis and localisation of the cysts is best accomplished with non-invasive methods such as 2-D transthoracic and transesophageal echocardiography, computed tomography and NMR. Excision of the cardiac cyst from the interventricular septum in a 21 year old patient with polyvisceral echinococcosis was performed with cardiopulmonary bypass. Adjunctive medical therapy with mebendazol is being continued for 24 months postoperatively. Twelve months after surgery the patient is asymptomatic without echocardiographic signs of recurrence. 
Gastro-oesophageal reflux and respiratory function in infants with respiratory symptoms. This study aimed to define the incidence and severity of gastro-oesophageal reflux (GOR), as measured using 24 hour oesophageal pH monitoring, in 38 infants with recurrent respiratory symptoms and to relate these findings to measures of respiratory function. Twenty one infants had a pH under 4 for more than 5% of the time (one definition of abnormal GOR) and nine had GOR exceeding age related normal values. Maximum expiratory flow at functional residual capacity was reduced in 37 infants, airways resistance was raised in 19 infants, and thoracic gas volume was abnormal in 11 infants. There was no association between indices of GOR and measures of lung function whether assessed by correlation or by chi 2 analysis for normal versus abnormal values. However, individual infants appeared to have respiratory symptoms produced by GOR. This suggests that host responsiveness to GOR may be of greater relevance than the amount of GOR. 
Results of the pelvic-pouch procedure in patients with Crohn's disease. The pelvic-pouch procedure has become a standard operation for selected patients with ulcerative colitis, but is contraindicated in patients with Crohn's disease at our institution. However, the distinction between ulcerative colitis and Crohn's colitis can sometimes be difficult, if not impossible. Between January 1982, and March 1989, 272 patients with ulcerative colitis underwent pelvic-pouch procedures at our institution. Nine (3.5 percent) of these patients eventually were found to have Crohn's disease. The records of these patients were examined to assess their clinical outcome and complication rate. There were five females and four males with a mean age of 28.8 years. In five patients (Group I) the diagnosis of Crohn's disease was made postoperatively on histologic examination of the rectum. The ileostomy was closed in all patients. Two developed complications necessitating excision of the pouch. Three patients are well. In the other four cases (Group II) the mean time to diagnosis was 2.5 years after the pouch procedure. Three patients developed pouch-vaginal fistula, and one multiple anal fissures and stenosis. Two required excision of the pouch whereas two have a functioning pouch but with a persistent pouch-vaginal fistula (n = 1) or anal fissures (n = 1). Overall, four patients have had their pouches removed, and five patients have functioning pouches: three with no complications and two with persistent perianal disease. Thus, we would conclude that the pelvic-pouch procedure should not knowingly be performed in patients with Crohn's disease because of the high associated complication rate. 
Identification of colon cancer-predisposed individuals: a cytogenetic analysis. Peripheral blood lymphocyte cultures from 23 individuals with polyps and 10 age-matched controls were cytogenetically studied. Of 23 individuals with polyps, 13 were males and 10 females. The age distribution of these patients was between 22 and 84 yr, with a medium age of 49.6 yr. Chromosome 5 was involved in structural rearrangements in 10 of the 18 patients with adenomatous polyps (55.5%). All those who showed involvement of chromosome 5 alterations had either adenomatous polyps or Gardner's syndrome, and two had colon adenocarcinoma. Of the remainder who did not show involvement of chromosome 5, eight had adenomatous polyps and five had hyerplastic polyps (non-neoplastic). Of the 10 control samples, only one showed alteration of chromosome 5. Of the 10 adenomatous polyp subjects that showed chromosome 5 defects, two had translocations of chromosome 5 and the short arm of 17. Chromosome 5 was broken 13 times (5 times in the q arm and 8 times in the p arm). Based on our present cytogenetic data, we tentatively conclude that lymphocyte metaphases may be used to identify colon cancer-predisposed individuals. 
AIDS-associated non-Hodgkin lymphoma. Non-Hodgkin lymphoma is associated with HIV infection. We investigated the epidemiology and aetiology of AIDS-related non-Hodgkin lymphoma by analysing data from cases reported to the Centers for Disease Control, Atlanta, USA, up to June 30, 1989. During this period 97,258 AIDS cases were reported, of whom 2824 (2.9%) had non-Hodgkin lymphoma. The condition was about 60 times more common in AIDS patients than in the general US population. 1686 cases were immunoblastic lymphoma, 548 primary lymphoma of the brain, and 590 Burkitt's lymphoma, a condition which is not normally associated with immunosuppression. The proportion of AIDS patients with immunoblastic lymphoma increased from 0% in those under 1 year old to 3.5% in those aged 50 or more. Primary lymphoma of the brain was constant at 0.6% for all ages. The frequency of Burkitt's lymphoma increased from zero in infants to a peak at 10-19 years of age (1.8%). Each type of lymphoma was twice as common in whites as in blacks and in men as in women. Lymphoma was most common in patients with haemophilia or clotting disorders and least common in those born in the Caribbean or Africa who had acquired HIV by heterosexual contact. Epidemiological data suggested that whilst infectious agents (eg, Epstein-Barr virus) may be associated with development of non-Hodgkin lymphomas in AIDS patients there was probably no single cause for all the types of lymphoma. Perhaps the most puzzling question is why Burkitt's lymphoma is commonly associated with HIV infection but not with other types of immunosuppression. 
Inhaled nitric oxide. A selective pulmonary vasodilator reversing hypoxic pulmonary vasoconstriction. BACKGROUND. We examined the effects of inhalation of 5-80 ppm nitric oxide (NO) gas on the normal and acutely constricted pulmonary circulation in awake lambs. METHODS AND RESULTS. Spontaneous breathing of nitric oxide (an endothelium-derived relaxing factor) at 40 ppm or more reversed acute pulmonary vasoconstriction within 3 minutes either because of infusion of the stable thromboxane endoperoxide analogue U46619 or because of pulmonary hypertension due to breathing a hypoxic gas mixture. Systemic vasodilation did not occur. Pulmonary vasodilation by NO inhalation was produced during infusion of U46619 for periods of 1 hour without observing evidence of short-term tolerance. Pulmonary hypertension resumed within 3-6 minutes of ceasing NO inhalation. In the normal lamb, the pulmonary vascular resistance, systemic vascular resistance, cardiac output, left atrial and central venous pressures were unaltered by NO inhalation. CONCLUSION. Breathing 80 ppm NO for 3 hours did not increase either methemoglobin or extravascular lung water levels or modify lung histology compared with those in control lambs. 
Diagnosis and treatment of headache in the elderly. The diagnosis and management of some causes of headache in the elderly are reviewed. Etiologic theories have been presented for each condition. Treatment modalities include pharmacologic, nonpharmacologic, and surgical therapies. The treatment course set forth in this article can help the clinician provide proper relief for the patient in pain. 
Failure of MR imaging to detect reflex sympathetic dystrophy of the extremities. Reflex sympathetic dystrophy of the extremities is a disease with a wide spectrum of clinical manifestations. It is characterized by pain, hyperthermia, and cutaneous changes and has been linked to an abnormality of regional blood flow. The disease is associated with previous injury or trauma including surgery, but also has been found in association with myocardial infarctions and tumors. The final diagnosis can be made only on the basis of the clinical course, which is characterized either by regression without sequel or the appearance of aponeurotic and tendinous retractions including bony sclerosis in the affected region occurring over many months to years. The literature and our own results show that MR imaging has high sensitivity for diagnosing transient osteoporosis of the hip, which is generally thought to be a form of reflex sympathetic dystrophy. Therefore we investigated the usefulness of MR imaging for diagnosing sympathetic dystrophy of the extremities. Twenty-five patients underwent T1- and T2-weighted MR imaging of the affected body region. They were selected on the basis of the initial clinical findings and positive findings on scintigraphy, which is known to be a sensitive, but not very specific, imaging method for sympathetic dystrophy. The final diagnosis was established on the basis of the clinical course in 17 of the 25 patients. In 10 of these, findings on MR images were completely normal, in six the MR images showed only nonspecific soft-tissue changes or bone marrow sclerosis, and in one patient they showed changes in bone marrow signal. Of the remaining eight patients without a final diagnosis of sympathetic dystrophy, MR showed soft-tissue or bone marrow alterations in six. MR imaging appears to be of little value in establishing the diagnosis of sympathetic dystrophy, but it may improve diagnostic specificity when used in conjunction with scintigraphy. 
Endoscopic sinus surgery: outcome in 155 cases. For this retrospective study of endoscopic sinus surgery, charts of 22 patients from a medical center and 133 patients from a private practice (N = 155) were reviewed. Preoperative complaints, clinical findings, computed tomographic evidence of extent of sinus disease, surgical outcome, possible predictors of success, and complications were considered. Indications for endoscopic surgery were persistence of symptoms despite aggressive medical therapy and radiologic evidence of a significant sinus abnormality. Median followup was 12 months. Hemorrhage occurred postoperatively in two patients (1.5%); 17 patients required additional endoscopic surgery. Overall, 140 (91%) patients believed that the surgery was beneficial. Patients with facial pain preoperatively showed the greatest improvement. All patients having simultaneous septoplasty (N = 64) had successful outcome. The total number of opacified sinuses was not a predictor of outcome, but opacificaiton of the sphenoid sinus correlated with a poorer outcome. The patients seen at the medical center had poorer results, but had a larger number of opacified sinuses, were more likely to have had previous sinus surgery, and were more likely to have underlying medical conditions contributing to their sinus disease. 
Experience with 225 hepatic resections for hepatocellular carcinoma over a 4-year period. During the past 4 1/2 years, we have performed hepatic resection on 225 patients with hepatocellular carcinoma (HCC). These patients included 171 men and 54 women, whose ages ranged from 29 to 84 years with an average of 60 years. Underlying cirrhosis of the liver was found in 67% of the patients and chronic hepatitis in 27%. Patients undergoing hepatic resection were classified into five groups according to curability as follows: Group A, resection of the tumor-bearing segment and one additional segment; Group B, complete resection of the tumor with more than 1.0 cm free surgical margin; Group C, complete resection of the tumor with less than 1.0 cm free surgical margin; Group D, incomplete resection of the tumor; Group E, surgical approach for advanced HCC with tumor thrombi in the main trunk or the first branch of the portal vein and/or the inferior vena cava, with multiple daughter nodules in both lobes and with tumor recurrence. The number of patients in Groups A, B, C, D, and E was 12 (5%), 83 (37%), 58 (26%), 14 (6%) and 58, (26%), respectively. There were 4 deaths (2.4%) among the 167 patients in Groups A to D within 30 days after operation and 12 deaths (20.7%) in Group E. The 3-year survival rate of Groups A, B, C, D, and E was 100%, 74%, 21%, 0%, and 35%, respectively. 
Altered antigen receptor signaling in anergic T cells from self-tolerant T-cell receptor beta-chain transgenic mice. T-cell tolerance to the minor lymphocyte-stimulating antigen Mls-1a in a T-cell receptor (TcR) V beta 8.1 transgenic line of mice is maintained by both clonal deletion and clonal anergy. Approximately 20-50% of peripheral CD4+ (but not CD8+) T cells isolated from these mice are anergic and fail to proliferate following TcR ligation. We have examined key events in T-cell signaling in peripheral T cells isolated from these mice. In this report, we show that the anergic CD4+ T cells did not mobilize calcium or express receptors for interleukin 2 (IL-2) following TcR ligation. However, the cells retained viability and functional potential because stimulation with phorbol 12-myristate 13-acetate and ionomycin bypassed the block in receptor-mediated signaling and induced IL-2 receptor expression and proliferation of the anergic cells. 
Reducing postischemic paraplegia using conjugated superoxide dismutase. Paraplegia after thoracic aortic aneurysm repair has an incidence of 2.2% to 24%. Oxygen-derived free radicals after reperfusion of an ischemic spinal cord may be partly responsible for neuronal destruction. We studied the effects of polyethylene glycol-conjugated superoxide dismutase (PEG-SOD), a free radical scavenger, as a way of increasing spinal cord tolerance to ischemia. Thirty rabbits underwent 40 minutes of aortic occlusion (a known model of paraplegia). Ten of these animals received 25,000 U/kg of PEG-SOD 24 hours before aortic occlusion and two additional doses of 10,000 U/kg, one before and one subsequent to spinal ischemia. Ten animals received superoxide dismutase in the same dosages as those receiving PEG-SOD. Ten control animals received placebo. All animals were studied for 96 hours, at which time a final neurological examination was performed and the results were recorded. Of the 10 animals treated with PEG-SOD, 2 were completely paralyzed whereas 8 had less (7) or no (1) neurological impairment. Eight of the 10 control animals and 9 of the 10 animals receiving superoxide dismutase were completely paralyzed. None of the control animals or animals receiving superoxide dismutase had a normal neurological examination (p less than or equal to 0.05). Treatment with PEG-SOD before and during occlusion increased the rabbit spinal cord tolerance to a 40-minute ischemic insult. Scavenging free radicals may lessen experimental spinal cord injury. 
Infusional carboplatin. Phase I studies of 5-day and 14-day infusions. Twenty-two courses of carboplatin (Paraplatin; Bristol-Meyers, Evansville, IN) (CBDCA) were administered to 15 patients with advanced cancer on a continuous 24-hour per day infusion schedule for either 5 days or 14 days. The objective of the trial was to establish the optimal dose rate and cumulative dose for this treatment schedule. The dose-limiting toxicity was myelosuppression, with leukopenia and thrombocytopenia observed. The optimal dose rate for the 5-day infusion was 75 mg/m2/d or a total cumulative dose of 375 mg/m2/d. The optimal dose rate for the 14-day infusion was 25 mg/m2/d or a total cumulative dose of 350 mg/m2/d. The times to nadir levels of leukocyte and platelet counts were 34 days and 25 days, respectively, with a median time to recovery of 14 days and 7 days, respectively, in patients with Grade 3 or greater marrow suppression. The pattern of hematologic toxicity with infusional CBDCA is comparable to that seen with bolus schedules. There is, therefore, no clinical advantage of the infusional schedule for CBDCA in terms of toxicity and the dose delivered per cycle, and the dose intensity is slightly less than with a bolus schedule. If there is a therapeutic advantage for the infusional schedule, a prospective comparative trial against the standard bolus schedule will be required to establish it. Bolus and infusional schedules for CBDCA are associated with a delayed pattern of thrombocytopenia and prolonged leukopenia, necessitating 5 or more weeks between treatment cycles. 
Selective gene expression in failing human heart. Quantification of steady-state levels of messenger RNA in endomyocardial biopsies using the polymerase chain reaction. BACKGROUND. Evaluation of gene expression in failing human heart has been limited by the availability of cardiac tissue. METHODS AND RESULTS. We used the polymerase chain reaction (PCR) to assess gene expression in small quantities of failing and nonfailing human heart. PCR is a powerful new molecular biological tool that allows a small quantity of DNA to be amplified as much as 1 million-fold. Total RNA was extracted from 3-5 mg samples of human heart and reverse-transcribed to complementary DNA (cDNA). With selected oligonucleotide primers, we used PCR to amplify cDNAs encoding atrial natriuretic peptide, beta-myosin heavy chain, phospholamban, and cytoskeletal beta-actin. To quantify the relative levels of messenger RNA (mRNA) in human heart, a known amount of a control RNA was present in the reverse transcription and PCR reactions. The amount of mRNA in the sample could therefore be assessed in relation to the amount of control product. The control RNA was transcribed from a synthetic DNA template containing primers complementary to those used to amplify the cDNAs of interest. Atrial natriuretic factor mRNA could not be detected in nonfailing human heart but was abundant in ventricular myocardium from failing human heart. In contrast, steady-state levels of phospholamban mRNA decreased, whereas levels of beta-myosin heavy-chain mRNA were unchanged with heart failure. CONCLUSIONS. Alterations in gene expression in the failing human heart appear to be selective. In addition, the present study suggests that PCR provides a rapid and economical way to quantify the expression of multiple genes of interest in endomyocardial biopsy specimens and may therefore be used to advance our understanding of heart muscle disease. 
Iatrogenic pneumomediastinum after endodontic therapy. An unusual case of pneumomediastinum caused by subcutaneous emphysema occurring after the use of hydrogen peroxide solution during root canal treatment is described in a 30-year-old man. A thorough search of the available literature failed to reveal similar cases. A review of the literature, including pathogenesis, clinical and radiographic features, and management of this condition, is presented. 
Surgical versus percutaneous drainage of intra-abdominal abscesses. The records of 83 patients with intra-abdominal abscesses treated between 1986 and 1990 were reviewed to determine if there were significant differences in the outcome of patients treated by surgical drainage (n = 41) or percutaneous drainage (n = 42). The two groups were matched for age, abscess location, and etiology. Parametric statistical evaluations included the Student's t test as well as analysis of variance; nonparametric statistics used were chi-square and Wilcoxon rank sums. No significant difference was found in mortality (surgical 14% versus percutaneous 12%) or morbidity (surgical 26% versus percutaneous 29%). The duration of hospital stay was similar. Although there was no significant difference between the two groups in severity of illness as measured by APACHE II scores, these scores were significant in determining prognosis. APACHE II scores were significantly higher in non-survivors of both groups (23 versus 13) and also higher in those developing complications. A subgroup of patients with diverticular abscess was identified in whom percutaneous drainage enabled later resection with primary anastomosis without complication. This study indicates that percutaneous drainage of an intra-abdominal abscess is as efficacious as surgical drainage and that APACHE II scores are prognostic of both potential mortality and morbidity. 
Childhood haemangiomas of the head and neck. Haemangiomas of the head and neck in children may be of several histological types, the clinical course depending on the group to which the haemangioma belongs. Treatment may be required if the haemangioma interferes with the airway, as in the subglottic group, or if the lesion becomes ulcerated with subsequent haemorrhage, as in capillary cavernous haemangiomas. Most haemangiomas require no immediate treatment as they involute spontaneously, though parental reassurance will be of paramount importance. Those lesions which persist may be amenable to treatment at a later date, the laser probably offering the best long-term results in terms of cosmesis as in the case of port-wine stains. Superselective embolization is becoming the treatment of choice for arterial haemangiomas. This paper is designed to clarify the histological and clinical features of these tumours and their management in view of considerable confusion in the literature encountered in our study. 
Resolution of microsporidial epithelial keratopathy in a patient with AIDS. A patient with a positive human immunodeficiency virus (HIV) titer and cryptococcal meningitis suffered bilateral epithelial keratopathy caused by Encephalitozoon, which did not respond to sulfas, erythromycin, bacitracin, tobramycin, neomycin, polymyxin B, or fluconazole. Eventual administration of itraconazole for the meningitis apparently produced resolution of the long-lasting (2-month) ocular infection. This new oral triazole antifungal may be valuable against the increasingly prevalent microsporidial infections in patients with acquired immune deficiency syndrome. Debulking of the infection by corneal scraping may have contributed to the authors' success. 
Epidemiology of chronic venous ulcers. A metropolitan population of 238,000 in Perth, Western Australia, was screened for chronic ulceration of the leg. Patients with a chronic leg ulcer and a venous abnormality comprised 57 per cent of all patients with a chronic leg ulcer, giving a prevalence of 0.62 per 1000 population. There was an increasing prevalence with age; 90 per cent of patients were 60 years and older. This group comprised 16.7 per cent of the population, and had a prevalence of 3.3 per 1000. Although chronic venous ulcers were more common in women there was no difference in age related prevalence. In 36 per cent of patients with a venous abnormality, there was at least one other aetiological factor contributing to chronic ulceration of the leg; 96 per cent had either a history of deep venous thrombosis or a condition known to predispose to deep venous thrombosis. 
Biliary pancreatitis. Operative outcome with a selective approach. To evaluate the efficacy of a selective approach to biliary pancreatitis, we reviewed the outcomes in 276 consecutive patients undergoing operations for this diagnosis during a 7-year period. Initial conservative therapy resulted in elective operations in 63% and urgent operations in 37%. Only 10 patients (3.6%) required primary pancreatic operations, 50% of them as emergencies. The proportion of common duct surgical explorations fell from 70% of those operated immediately after hospital admission to 20% by the third hospital day. Overall mortality was 1.8% but was increased to 30% in patients having an initial pancreatic operation. We conclude that a selective approach to biliary pancreatitis allows the operation to be performed electively in most patients and is associated with a low mortality and an acceptable length of stay. Most common duct stones pass spontaneously permitting cholecystectomy alone. 
Diagnosing and managing oral lichen planus. Lichen planus is a chronic and recurrent inflammatory disease characterized by unpredictable exacerbations and remissions. It affects the skin and/or mucous membrane in nearly 2 percent of the adult population. The symptoms are transient, but clinical evidence of oral disease is more persistent. 
Induction of transformational changes in normal endothelial cells by cultured human astrocytoma cells. Endothelial cell proliferation is a significant biological feature of malignant astrocytomas. The ability of the cells of these tumors to elaborate mitogenic angiogenesis factors has been well documented. However, less is known about the transformational effects that neoplastic astrocytes may have on the endothelial cells within malignant astrocytomas. In this study, the hypothesis that humoral factors elaborated by cells derived from malignant astrocytomas induce transformational changes in normal endothelial cells in vitro is investigated. Conditioned medium (CM) was prepared from exponentially growing cultures of a human glioblastoma cell line (UW18) and from two rat brain-tumor cell lines: an anaplastic astrocytoma (R175A) and a glioblastoma with sarcomatous elements (9L). Subconfluent target bovine aortic arch endothelial cells (BAEC's) were exposed for 48 hours to varying concentrations of CM prepared from each of these tumors, and then evaluated for transformational changes. Different molecular weight (MW) fractions of UW18 CM were prepared by molecular ultrafiltration, and each fraction was tested for transforming activity. Transformation endpoints included changes in cellular deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) content and distribution (measured by differential flow cytometry) and changes in de novo DNA synthesis determined by 3H-thymidine incorporation. Significant changes in the amount and distribution of DNA and RNA were observed in the BAEC's treated with UW18 CM compared to untreated BAEC's. At 10% concentrations of UW18 CM, changes in the RNA profile of target BAEC's were evident, and at 30% concentrations of UW18 CM, an irregular bimodal distribution was well established. Patterns of DNA were also altered in a concentration-dependent manner, with significant aneuploidy developing at UW18 CM concentrations of 20%. The DNA synthesis in BAEC's increased with increasing CM concentrations, up to a maximum of about 250% of control values at 30% concentrations of UW18 CM. The transformational changes induced after exposure of BAEC's to CM prepared from R175A and 9L were significantly less than those observed with UW18 CM. Molecular ultrafiltration was used to prepare UW18 CM fractions with MW cutoffs of less than 10 kD, 10 to 30 kD, and greater than 30 kD. Transformational activity was significant only in CM's with an MW of 10 to 30 kD. It is concluded that the UW18 human glioblastoma cell line elaborates a soluble factor, or group of factors, with an MW in the 10- to 30-kD range, capable of inducing transformational alterations in target normal endothelial cells, and that such transformation may account for some of the abnormal endothelial cell changes associated with malignant astrocytomas. 
Clinical decision making of critical care nurses managing computer-simulated tachydysrhythmias. The purposes of this study were to describe the clinical decision making of critical care nurses managing computer-simulated tachydysrhythmias and to assess the major sources of error related to the management of two tachydysrhythmias: atrial flutter and ventricular tachycardia. In this descriptive study, 142 critical care nurses each completed four computerized clinical simulations (two atrial flutter and two ventricular tachycardia). Simulation performance was measured by proficiency score (comparison with expert performance), patient outcome (cure or die), and amount of data collected before the first intervention. Mean proficiency scores were 51% for atrial flutter and 35% for ventricular tachycardia. Thirteen percent of the atrial flutter and 35% of the ventricular tachycardia simulations ended in patient death. Failure to recognize ventricular tachycardia and unfamiliarity with second- and third-line treatments were major sources of error. Medication errors were the cause of death in 87% of the simulations ending in patient death. These results document the need for emphasis on dysrhythmia management in the critical care curriculum. 
Homologous desensitization of the insulinotropic glucagon-like peptide-I (7-37) receptor on insulinoma (HIT-T15) cells. Glucagon-like peptide-I(7-37) [GLP-I(7-37)] is an intestinal peptide with potent insulinotropic activities on pancreatic beta-cells in vivo and in vitro. In earlier studies elevated concentrations GLP-I(7-37) inhibited insulin release and cAMP generation in beta-cells. We now show that the GLP-I(7-37) receptor in the glucose-responsive B-cell line HIT-T15 undergoes rapid and reversible homologous desensitization in response to supraphysiological concentrations of GLP-I(7-37). GLP-I(7-37) stimulated insulin release and cAMP generation in a glucose-dependent biphasic manner with a maximum stimulation at 10 nmol/liter. The first-phase insulin secretory response was reduced by 41% at doses of GLP-I(7-37) of 100 nmol/liter and higher. Preperifusion of B-cells with 100 nmol/liter GLP-I(7-37) for 5 or 10 min reduced a subsequent insulin secretory response to 10 nmol/liter GLP-I(7-37) after hormone washout and recovery periods of 10 min (52% and 55% reduction) or 30 min (33% reduction or full recovery). Preperifusion of HIT-T15 cells with 100 nmol/liter glucagon (10 min) or 100 nmol/liter gastric inhibitory peptide (GIP) (10 min) had no effect on the insulin secretory response to 10 nmol/liter GLP-(7-37). Prior exposure of cells to 100 nmol/liter GLP-(7-37) (10 min) did not alter the GIP-induced (10 nmol/liter) insulin release, but 100 nmol/liter GIP (10 min) reduced the insulin secretion during stimulation with 10 nmol/liter GIP by 56%. These data indicate that: 1) the GLP-I(7-37) receptor is subject to rapid and reversible homologous desensitization and, 2) the GLP-I(7-37) receptor on beta-cells is distinct from that of GIP. The recent finding of elevated GLP-I(7-36)amide levels in subjects with noninsulin-dependent diabetes suggest the possibility that a homologous desensitization of the GLP-I(7-37) receptor might contribute to the impaired insulin secretion in this disorder. 
The interaction of vasodilating drugs and sympathetic blockade in normal and ischemic canine hindlimbs. The purpose of this study was to determine if intraarterial vasodilating drugs could augment the vasodilation produced by sympathetic blockade, such as occurs during epidural anesthesia. Papaverine (2 mg/min), nitroglycerin (1 microgram/kg/min), aand saline were infused into the femoral artery before and after lumbar sympathectomy in six arterially isolated canine hindlimbs. Femoral blood flow was controlled with a perfusion circuit at baseline (80 ml/min), half-baseline (40 ml/min), and low (5 ml/min) flow rates so that hindlimb mean arterial pressure served as an index of peripheral vasodilation. At low flow, hindlimb arteriovenous oxygen content difference increased from 1.4 (baseline) to 6.2 ml O2/dl, consistent with peripheral ischemia. At baseline flow before sympathectomy, papaverine and nitroglycerin caused a decrease in hindlimb mean arterial pressure of 30% and 18%, respectively (p less than 0.01 vs saline control), equivalent to the decreases of 31% and 16% after sympathectomy (p less than 0.01). At half-baseline, papaverine and nitroglycerin reduced hindlimb mean arterial pressure by 22% and 12%, respectively (p less than 0.01), and caused comparable vasodilation after sympathectomy. Neither drug significantly changed hindlimb mean arterial pressure at low flow. Sympathectomy itself reduced hindlimb mean arterial pressure by 23% at baseline flow (p less than 0.01), by 18% at half-baseline flow (p less than 0.01), but had no effect at low flow. We conclude that intraarterial papaverine and nitroglycerin cause peripheral vasodilation that is synergistic with sympathectomy-induced adrenergic blockade, but they cannot augment vasodilation caused by peripheral ischemia. 
Positive and negative exercise test results with and without exercise-induced angina in patients with one healed myocardial infarction: analysis of baseline variables and long-term prognosis. The prognostic implications of exercise test results with and without exercised-induced angina are not completely understood. In the Program On the Surgical Control Of the Hyperlipidemias (POSCH), 838 subjects with hyperlipidemia who had one healed myocardial infarction were studied and followed for 6 to 13 years (mean 8.6). Of the 417 control subjects, 279 had a treadmill exercise test result that was definitely positive or negative. Angina was also induced by exercise in 30% (45/150) and 8% (10/129) of those with a positive and a negative test result, respectively (p less than 0.0001). The data showed no difference between subjects with a positive or a negative test result with or without angina as regards levels of blood lipids, type of myocardial infarction (Q or non-Q wave), left ventricular function, or prognosis as defined by death, atherosclerotic coronary heart disease death, or myocardial infarction. 
Prostatic occurrence of transitional cell carcinoma after intravesical chemotherapy. Thirteen patients with Stage Tis, Ta, or T1 transitional cell carcinoma (TCC) of the bladder treated by transurethral resections and intravesical chemotherapy developed TCC of the prostate. Among the 13 cases, cytology specimens were obtained from 10 at the time prostatic disease was diagnosed; 9 demonstrated TCC. One was treated successfully by transurethral resection of a Ta lesion involving the prostatic urethra only. One of 2 patients declining radical surgery is alive with residual disease at twenty-four months, and the other died of progressive disease at nineteen months. Of the 10 patients who underwent radical cystoprostatectomy, 7 are alive with no evidence of disease eight to forty-two months postoperatively, with 2 of these 7 having received 4 courses of systemic methotrexate, vincristine, Adriamycin, and cisplatinum (MVAC) for metastatic disease. Two of the 10 died of metastatic disease six and thirteen months postoperatively, and one frail patient died of surgical complications. When treating patients with intravesical chemotherapy for superficial TCC, biopsy of the prostate should be done during follow-up examinations, especially in the presence of cytologic or palpable prostatic abnormalities. 
Gene transfer into vascular cells. The goal of gene therapy is to introduce foreign deoxyribonucleic acid (DNA) into somatic cells to correct or prevent disorders caused by the malfunction of genes within a diseased individual. Overexpression of recombinant genes at specific sites within the vasculature can provide insights into vascular biology and potential treatments for various cardiovascular disorders such as restenosis. Methods for the introduction of foreign DNA into endothelial and vascular smooth muscle cells have been developed recently. These include the genetic modification of endothelium in vitro and implantation in vivo on arterial segments, direct infection of the arterial wall in vivo with a replication-defective retroviral vector expressing a recombinant gene and direct transfer of genes into vascular cells in vivo with use of liposomes. Although still in its formative stages, gene transfer into the vasculature holds promise as a potential treatment for vascular diseases, including atherosclerosis and restenosis. This approach may also provide insight into the role of specific gene products in the development of pathologic lesions. 
Prospective blinded trial of the colonoscopic miss-rate of large colorectal polyps. We prospectively studied the colonoscopic miss-rate of large colorectal polyps in a blinded trial featuring tandem colonoscopy. Sixty-three lesions greater than or equal to 1 cm in size were discovered and none were missed. Confidence intervals of 95% are a miss-rate of 0 to 4.6%. We conclude that less than 5% of large colorectal polyps are missed during the index colonoscopic examination in a well-prepared colon. 
Acalculous biliary pain: cholecystectomy alleviates symptoms in patients with abnormal cholescintigraphy. A 45-minute infusion of an octapeptide of cholecystokinin (Kinevac; Squibb Diagnostics, New Brunswick, NJ) was used to measure the gallbladder ejection fraction during cholescintigraphy in 40 normal volunteers. Cholecystokinin cholescintigraphy was shown to be a reproducible test. The maximum mean gallbladder ejection fraction occurred 15 minutes after cholecystokinin infusion and was 74.5% +/- 1.9% (mean +/- SEM). A gallbladder ejection fraction greater than 40% (mean -3SD) was arbitrarily defined to be normal. The gallbladder ejection fraction test was then used to identify patients with acalculous biliary symptoms who may respond to cholecystectomy. A total of 103 patients was tested; 21 had abnormal gallbladder ejection fractions and were randomized into two groups, cholecystectomy or no operation. These patients were followed up symptomatically at 3-month intervals for 13-54 months (mean, 34 months). Of the 11 patients who underwent cholecystectomy, 10 (91%) lost their symptoms and 1 improved. Of the 10 patients in the group that did not undergo surgery, all continued to be symptomatic, 2 of whom requested cholecystectomy after 13 and 24 months, respectively. Of the 13 gallbladders obtained from surgery, 12 showed evidence of chronic cholecystitis, muscle hypertrophy, and/or narrowed cystic duct. A normal gallbladder ejection fraction was recorded in 82 patients, and further treatment was left to the discretion of their referring clinician. On follow-up, 50 patients were asymptomatic and 10 were symptomatic without specific treatment of the biliary tract; 14 underwent cholecystectomy, 8 of whom were asymptomatic. Pathological abnormalities were recorded in 6 of the removed gallbladders. It is concluded that the gallbladder ejection fraction obtained after a 45-minute infusion of cholecystokinin during cholescintigraphy is a reproducible measure of gallbladder emptying, and that cholecystectomy alleviates the biliary-type pain of patients with a reduced gallbladder ejection fraction. 
Electroencephalogram patterns during sleep reflux in infants. Twenty-four infants, 3-35 months of age, with histories of apnea or chronic lung disease underwent nighttime polysomnography and esophageal pH monitoring. Fifteen infants had pathological levels of gastroesophageal reflux on esophageal pH monitoring, and 9 had normal study results (symptomatic controls). Partition of sleep stages, sleep efficiency, and frequency of arousals to electroencephalographic stage 0 were the same in both groups. During sleeping reflux episodes, defined as reflux starting during sleep stages 1-5 or reflux episodes consisting of greater than 50% of sleep stages 1-5, there was a 50% decrease in the amount of stage 0 electroencephalogram pattern compared with nonreflux sleep, and a compensatory increase in the non-rapid eye movement sleep stages. Reflux onsets in patients with pathological reflux were evenly divided between stages 0, 1/2, and 5. Onset of reflux occurred rarely during sleep stages 3 and 4. Slight body movement accompanied the onset of 62.5% of sleep reflux episodes in symptomatic controls and 64.7% in patients with pathological gastroesophageal reflux. Arousals to stage 0 electroencephalogram occurred with equal frequency in sleep reflux episodes of symptomatic controls and patients, and frequency did not increase over the observed value for nonreflux time. There were no differences between the sleep patterns of infants with and without pathological gastroesophageal reflux; nor were there decreases in arousals from sleep in infants with pathological reflux. However, reflux occurring during sleep in all infants studied was characterized by a significant decrease in stage 0 (waking) electroencephalogram. 
Intraoperative cardiovascular collapse secondary to latex allergy. An apparent allergic reaction has been noted in children undergoing open urological surgery. This condition is characterized by precipitous hypotension, tachycardia and upper body flushing, and it often causes termination of the procedure. Latex allergy has been identified as the possible inciting event. Contact of latex rubber gloves with intra-abdominal structures (handling bowel) appears to be the most dramatic trigger mechanism for this reaction. We report on 10 patients with latex allergy, 6 of whom have myelomeningocele, who have undergone reconstructive surgery. Severe anaphylactic shock developed intraoperatively in 5 patients and during a barium enema performed with a latex catheter in 1 patient. These 6 patients had previous allergic reactions to latex material, which was not detected preoperatively. In the remaining 4 patients latex allergy was diagnosed preoperatively. A total of 6 patients agreed to a skin prick test to liquid latex. Three patients reacted with a wheal size greater than or equal to a histamine control at a dilution of 1:1,000 and 3 patients at 1:100. In contrast, none of the 5 normal controls reacted to any of the concentrations including full strength latex. A history of exposure to latex products (balloons, surgical gloves, catheters, condoms and so forth) with allergic reactions should heighten surgeon awareness of a potentially severe intraoperative reaction. Furthermore, a skin prick test may be used to screen high risk patients such as those with myelomeningocele. A protocol involving preoperative corticosteroid and antihistamine therapy is recommended. 
Necrosis of the small intestine after resection of an abdominal aortic aneurysm. Small bowel infarction following abdominal aortic reconstruction is extremely rare, and the prognosis remains poor. This report describes a 65-year-old man with small bowel infarction after resection of an abdominal aortic aneurysm. He was successfully treated with resection of the ischemic segment from the distal duodenum to the mid-small bowel and construction of a duodenoileostomy. The postoperative course was uneventful. 
Localization of HeLa cell tumor-suppressor gene to the long arm of chromosome II. Cytogenetic and molecular genetic analyses of human intraspecific HeLa x fibroblast hybrids have provided evidence for the presence of a tumor-suppressor gene(s) on chromosome 11 of normal cells. In the present study, we have carried out extensive RFLP analysis of various nontumorigenic and tumorigenic hybrids with at least 50 different chromosome 11-specific probes to determine the precise location of this tumor-suppressor gene(s). Two different hybrid systems, (1) microcell hybrids derived by the transfer of a normal chromosome 11 into a tumorigenic HeLa-derived hybrid cell and (2) somatic cell hybrids derived by the fusion of the HeLa (D98OR) cells to a retinoblastoma (Y79) cell line, were particularly informative. The analysis showed that all but one of the nontumorigenic hybrid cell lines contained a complete copy of the normal chromosome 11. This variant hybrid contained a segment of the long arm but had lost the entire short arm of the chromosome. The tumorigenic microcell and somatic cell hybrids had retained the short arm of the chromosome but had lost at least the q13-23 region of the chromosome. Thus, these results showed a perfect correlation between the presence of the long arm of chromosome 11 and the suppression of the tumorigenic phenotype. We conclude therefore that the gene(s) involved in the suppression of the HeLa cell tumors is localized to the long arm (q arm) of chromosome 11. 
Teratogenic effect of carbamazepine. A girl was born to a mother who had undergone treatment for epilepsy with carbamazepine during pregnancy. The infant had dysmorphic features and was physically and mentally retarded. We consider that the malformations were the result of the maternal treatment with carbamazepine. 
The value of estrogen and progesterone receptor determinations in advanced breast cancer. Estrogen receptor level but not progesterone receptor level correlates with response to tamoxifen. Four hundred fifteen patients with metastatic breast cancer with known hormone receptor status received primary treatment with tamoxifen. Measured values for the estrogen receptor (ER, i.e., with estrogen binding) followed a continuous distribution (range, 3 to 1000 fmol/mg of protein). These values correlated positively with age. The response to treatment with tamoxifen correlated with the ER level, with response rates of approximately 80% when the ER level was greater than 30.1 fmol/mg of protein. Two hundred eighteen (218 of 415, 52%) patients had progesterone receptor (PR) values greater than 10 fmol/mg. The PR positivity correlated with the ER level. Patients with PR levels greater than 10 fmol/mg of protein (124 of 226, 55%) had a significantly higher response rate than those with values less than 10 fmol/mg of protein (45 of 189, 24%). However, in a multivariate analysis including both receptor levels, age, site, and number of metastases, only the ER level was significant in predicting the response to treatment with tamoxifen. A quantitative estimation of the ER level thus is the best predictor of response to hormonal treatment with tamoxifen for advanced breast cancer. 
Hypercapnic and hypoxic ventilatory responses in parents and siblings of children with congenital central hypoventilation syndrome. Children with congenital central hypoventilation syndrome (CCHS) have abnormal ventilatory responses to metabolic stimuli. As there is a genetically determined component of chemoreceptor sensitivity, parents and siblings of children with CCHS may also have blunted ventilatory responses to hypercapnea and hypoxia. To test this, we studied hypercapnic ventilatory responses and hypoxic ventilatory responses in six mothers, four fathers, and five siblings (6 to 49 yr of age) of seven children with CCHS and compared them with 15 age- and sex-matched control subjects (5 to 47 yr of age). Pulmonary function tests were not different between relatives of children with CCHS and control subjects. To measure hypercapnic ventilatory responses, subjects rebreathed 5% CO2/95% O2 until PACO2 reached 60 to 70 mm Hg. To measure hypoxic ventilatory responses (L/min/% SaO2), subjects rebreathed 14% O2/7% CO2/balance N2 at mixed venous PCO2 until SaO2 fell to 75%. All tests were completed in less than 4 min. Instantaneous minute ventilation, mean inspiratory flow (tidal volume/inspiratory time), and respiratory timing (inspiratory timing/total respiratory cycle timing) were calculated on a breath-by-breath basis. Hypercapnic ventilatory responses were 1.97 +/- 0.32 L/min/mm Hg PACO2 in children with CCHS relatives and 2.23 +/- 0.23 L/min/mm Hg PACO2 in control subjects. Hypoxic ventilatory responses were -1.99 +/- 0.37 L/min/% SaO2 in the relatives and -1.54 +/- 0.25 L/min/% SaO2 in the control subjects. 
Mediators, initiating the inflammatory response, released in organ culture by full-thickness human skin explants exposed to the irritant, sulfur mustard. Mediators released from injured human skin that initiate the inflammatory response have not been adequately identified. Organ culture of full-thickness skin explants enables us to do so, because injury to the skin can be made in vitro, eliminating the rapid leakage of serum and infiltration of leukocytes that occur in vivo. In our studies, the military vesicant sulfur mustard (SM) (10 microliters of a 0.01 to 1.0% dilution) was topically applied to injure the epidermis of the explant. Then, the explants were cultured in small Petri dishes, usually for 18 h at 36 degrees C, and the organ-culture fluids were assayed for various inflammatory mediators. We found that the culture fluids from SM-exposed and control explants contained similar amounts of angiotensin-converting enzyme, trypsin-like and chymotrypsin-like proteases, acid phosphatase, beta-glucuronidase, beta-galactosidase, lysozyme, deoxyribonuclease, ribonuclease, interleukin 1, and lactic dehydrogenase. However, the culture fluids from SM-exposed explants contained increased amounts of histamine and plasminogen-activating activity, and often prostaglandin E2, when compared to culture fluids from control explants. After 3 to 4 d in culture, full-thickness human skin explants, when exposed to 0.2% SM (but not when exposed to 1.0% SM), sometimes showed separation of the epidermis and increased collagenase activity (i.e., hydroxyproline release). Thus, histamine (from local mast cells), and prostaglandin E2 and plasminogen-activating activity (probably from both mast cells and epidermal cells) are apparently involved in early mediation of the inflammatory response. 
Comparison of ondansetron and ondansetron plus dexamethasone as antiemetic prophylaxis during cisplatin-containing chemotherapy. Ondansetron, a serotonin antagonist, is effective in controlling the emesis associated with cancer chemotherapy; however, emesis in patients receiving high-dose cisplatin is poorly controlled by ondansetron alone. Dexamethasone is an effective antiemetic with no known interaction with serotonin receptors and was thus chosen for study in combination with ondansetron. 31 patients (30 male, 1 female; median age 28.5 years, range 18-49) receiving a 4-day course of a chemotherapy regimen containing cisplatin (100-120 mg/m2) for metastatic germ-cell tumours were entered in a randomised, double-blind, cross-over trial comparing oral ondansetron plus placebo with oral ondansetron plus dexamethasone as antiemetic prophylaxis. Ondansetron (8 mg every 8 h) was given to all patients for 8 days from the start of chemotherapy. Patients were given 8 mg of dexamethasone or placebo every 8 h starting 2 h before cisplatin (on day 4) and continuing for six doses (ie, for 2 days only). A second course of chemotherapy began 14 days after the start of the first, during which patients crossed over to the alternative antiemetic regimen. Results were available from 27 patients. In the 24-48 h after cisplatin 78% of patients taking ondansetron plus dexamethasone reported complete or major control of emesis compared with 30% of those taking ondansetron plus placebo (p = 0.001). Cross-over analysis showed a significant advantage for ondansetron plus dexamethasone in the control of nausea (p = 0.013) and emesis (p less than 0.001) over the 8-day study. 24 of 26 patients expressed a preference for the combination therapy (p less than 0.001). Ondansetron plus dexamethasone is effective antiemetic prophylaxis for high-dose cisplatin chemotherapy, has few side effects, and is active when given orally. 
Torsades de pointes ventricular tachycardia and terodiline. We report five patients (four women, one man; mean age 74 years, range 55-87) taking terodiline who had torsades de pointes ventricular tachycardia associated with prolongation of the QT interval. The QT interval was normal before the introduction of terodiline in three patients and returned to normal after terodiline withdrawal in four. Atrioventricular conduction disturbance or bradycardia were evident in all patients. Terodiline should be prescribed with caution to elderly patients. 
Psychosis following temporal lobe surgery: a report of six cases. Six consecutive patients who had had temporal lobe surgery for epilepsy, and been referred for psychiatric assessment of psychotic symptoms, are reported. Their symptoms (a delusional depression, four schizophrenia-like illnesses, and a case of Capgras' syndrome) are discussed in relation to the possible role of their operations, all of which were on the right hemisphere. 
The hemodynamic response to hemorrhage in tumor-bearing animals. Tumor-bearing rats submitted to hypovolemia have higher mortality rates than have non-tumor-bearing control rats. To determine the mechanisms underlying this sensitivity to hemorrhage, we studied Fischer-344 rats with subcutaneous methylcholanthrene-induced sarcoma (tumor burden, 10% body weight) to determine hematologic and blood volume alterations. Subsequently we used the same animal model in an unanesthetized condition to determine the sensitivity to hemorrhage and resuscitation, as well as vascular responsiveness to vasoactive agents. The rats were separated into two groups: control and tumor-bearing rats (TBR). Sensitivity to hemorrhage and resuscitation was determined by bleeding the conscious rats (15 ml/kg) and resuscitating them with 0.9% NaCl (45 ml/kg). Vascular responsiveness was determined after injection of varying doses of phenylephrine and nitroglycerin, with continuous measurement of mean arterial pressure (MAP). Rate of increase of MAP, maximum MAP, relative increase in MAP (maximum minus baseline), rate of recovery toward baseline MAP, and duration of the response were determined. There was a significant anemia in TBR, but blood volume was similar in both groups. Baseline MAP was significantly higher in control rats (125.3 +/- 8.1 mm Hg) compared with TBR (107.5 +/- 6.0 mm Hg). After hemorrhage, MAP in TBR reached significantly lower levels than in control rats. In addition, after saline resuscitation, MAP in TBR did not return to baseline levels, whereas MAP in control rats returned to prehemorrhage MAP. With nitroglycerin, MAP decreased to lower levels in TBR than in control rats. With phenylephrine, the maximum MAP reached was significantly higher, and the response to phenylephrine was maintained for a significantly longer period in control rats compared with TBR. We conclude that TBR are more sensitive to hypovolemic events in association with decreased oxygen-carrying capacity, profound hypotension, and altered overall vascular responsiveness to sympathetic stimuli. 
Gangrene of the fingers secondary to myeloproliferative disease. The myeloproliferative disorders comprise a group of related diseases, including polycythemia vera, essential thrombocythemia, chronic myelogenous leukemia, myelofibrosis, and myeloid metaplasia. An increase in circulating platelets is associated with thrombotic phenomena affecting the arterial and venous circulation. In this article, the authors describe a case in which the initial manifestation of myeloproliferative disease was gangrene of the fingers. 
Effects of enflurane on inducibility of ventricular tachycardia. The effects of enflurane on cardiac electrophysiologic parameters and on inducibility of ventricular tachycardia (VT) by programmed stimulation were studied in 12 patients (11 men, 1 woman, mean age +/- standard deviation 55 +/- 8 years) with drug refractory sustained monomorphic VT who underwent transcatheter ablation with high-energy direct-current shocks. One catheter ablation procedure was performed in 10 patients, whereas 2 ablation sessions were necessary in 2 patients. Programmed ventricular stimulation was performed on 2 separate days (mean interval 19). There were 2 baseline studies, 1 several days before ("baseline study I") and the second at the beginning of the ablation procedure ("baseline study II") while the patient was awake and nonsedated. The third programmed stimulation study was done 15 to 30 minutes after administration of anesthesia with enflurane, oxygen and nitrous oxide ("enflurane study"). Rate of sinus rhythm, QRS duration, PQ interval and ventricular effective refractory period were unaltered, whereas QTc interval increased significantly after initiation of anesthesia. Before and after induction of general anesthesia, clinical VT was inducible in all patients. However, in 1 patient, induction of VT was only possible by pacing in the left ventricle after enflurane administration. Based on these data, it is concluded that general anesthesia with enflurane, oxygen and nitrous oxide has no marked influence on inducibility of clinical VTs. Therefore, this type of anesthesia may be useful for nonpharmacologic, ablative procedures requiring general anesthesia. 
A randomized comparison of multipolar electrocoagulation and injection sclerosis for the treatment of bleeding peptic ulcer. Several options are available to the gastroenterologist for the endoscopic control of peptic ulcer hemorrhage. Sixty men (mean age, 62 years) were stratified into those with actively bleeding ulcers or ulcers with stigmata of recent hemorrhage, and then randomized to treatment with injection sclerosis or the multipolar probe until bleeding ceased. There were no significant differences between the randomized groups in terms of age, ulcer size, or transfusion requirements. We achieved hemostasis in 95% of all patients. Re-bleeding rates were 25% and 23% in patients treated with the multipolar probe and injection sclerosis, respectively. There was no significant difference in mortality (14% multipolar probe, 7% injection sclerosis). Patients over the age of 70, those whose onset of bleeding was while an inpatient, and those with an ulcer larger than 2 cm were more likely to have a poor outcome, regardless of the type of endoscopic therapy. Injection sclerosis and multipolar electrocoagulation are equally effective in controlling bleeding from peptic ulcer. 
Response of osteosarcoma and Ewing sarcoma to chemotherapy: imaging evaluation. The importance of diagnostic imaging in evaluating therapeutic response of bone sarcomas has increased with the use of chemotherapy administered before radiation therapy or surgery. The information provided by imaging studies is used to estimate prognosis; modify preoperative chemotherapy; and plan radiation therapy, surgery, and postoperative chemotherapy. This review examines the value and illustrates some pitfalls of traditional imaging methods, including conventional radiography, angiography, CT, and radionuclide scintigraphy, and discusses recent efforts to monitor therapy by using MR imaging and MR spectroscopy. 
Sucralfate retention enemas in solitary rectal ulcer. The conservative treatment of solitary rectal ulcer is generally unsatisfactory. Six patients, aged 27-54 years, with recurrent solitary rectal ulcer were treated with topical administration of sucralfate in a daily dose of 2 g twice a day for 6 weeks. Four patients experienced complete relief of symptoms and the remaining two patients had marked improvement. Although macroscopic healing of the ulcer was apparent in all, histologic improvement was not appreciable. Five of the six patients remain in remission during a follow-up period of 4-14 months (mean, 8 +/- 1.5 months). Recurrence was observed in one patient at 5 months, which satisfactorily resolved with sucralfate enemas. From these preliminary observations we infer that solitary rectal ulcer can be effectively treated with topical application of sucralfate. 
Clinical anatomic study of pure dysarthria. Nine patients with pure dysarthria underwent computed tomography or magnetic resonance imaging. Eight patients had infarcts of lacunar or larger size in the internal capsule: four in the superior portion of the anterior limb or adjacent corona radiata and four in the superior portion of the genu or the adjacent corona radiata. In one patient, there was a small infarct in the bulbar motor cortex. Dysarthria was transient and characterized by poor articulation in all cases. Five patients also had contralateral facial weakness, and three patients with lesions in the genu had minimal and transient involvement of the contralateral fingers. These three cases appeared to be variants of the dysarthria-clumsy hand syndrome. We submit that this syndrome should sometimes be regarded as a stroke syndrome rather than always as a lacunar syndrome. 
Effect of isradipine and atenolol on lung function in patients with mild essential hypertension. Twenty-six hypertensive patients took part in an open, randomized, parallel-group pilot study of the effects of a nine-week treatment period with the calcium antagonist isradipine and the beta 1-blocking agent atenolol. The mean dosage in the isradipine group was 7.9 +/- 3.5 mg/day, and 69.2 +/- 43.5 mg/day in the atenolol group. A significant reduction of the arterial blood pressure was seen with both treatment regimens. Lung volumes and airways resistance remained unchanged, but, in the atenolol-treated group, the linear relationship between alveolar pressure and airways resistance at the lower lung volumes during forced expiration at 25% of forced vital capacity was affected by a shift to higher airways resistance. This change can be interpreted as an early sign of altered air-flow behavior in the small airways in subjects susceptible to beta-adrenoceptor blockade. The calcium antagonist isradipine did not produce changes in any parameters of lung function in this group of patients. 
A technique for needle localization in paraspinal muscles with cadaveric confirmation. Invasive electromyography (EMG) of the paraspinal muscles is useful in clinical and research settings. No technique for localization of the needle in specific fascicles has been validated. Recent descriptions of the segmented innervation of the multifidus imply that such a technique would add greatly to the EMG determination of root level of a radiculopathy. We have developed a technique for localization which relies on palpation of bony structures and needle insertion at certain angles and depths. The technique was evaluated by injecting latex dye in 199 locations in 13 cadavers. Dissection demonstrated that the technique was accurate in 91 of 112 injections into specific fascicles of the multifidus (originating from different spinous processes), 39 of 43 injections into the longissimus, and 35 of 44 injections into the iliocostalis. Certain types of errors would not have occurred with the aid of EMG in vivo. When these are added to the correct injections, accuracy improves 97%, 93%, and 82%, respectively. The technique described here should be useful for kinesiological studies, biopsies and injections, as well as for the EMG confirmation of a radiculopathy. 
Use of oligonucleotide probes directed against T cell antigen receptor gamma delta variable-(diversity)-joining junctional sequences as a general method for detecting minimal residual disease in acute lymphoblastic leukemias. To provide a sensitive and generally applicable method to detect clonal cells in acute lymphoblastic leukemias (ALL), we have designed a new strategy based on the polymerase chain reaction (PCR) amplification of the T cell receptor gamma delta gene rearrangements found in most T and B lineage ALLs. PCR allows rapid sequencing of variable-(diversity)-joining (V-[D]-J) junctions from tumor DNA and construction of anti-junctional oligonucleotides (AJOs) used as probes to detect clonal cells in the same patient. We have defined oligonucleotides suitable for all T cell receptor (TCR) rearrangements involving functional V gamma segments. Oligonucleotides corresponding to preferential TCR delta rearrangements in T and B lineage ALLs were also used. By analysis of the nucleotide sequence of 52 V gamma-V gamma junctions from 30 cases of B and T ALLs, we demonstrate that V-J junctional sequences are clone specific in both lineages and at all stages of differentiation examined despite the frequent presence of the recently described P nucleotides. Experiments performed with TCR gamma delta AJOs on DNA from tumor cells and polyclonal T cells show that AJOs can be used to differentiate clonal cells from polyclonal T cells, distinguish between different T cell clones, and detect residual clonal populations at 10(-4)/10(-5) dilution. AJOs were also used to detect residual disease in samples from patients in clinical and morphological complete remission. Finally, rearrangement patterns were studied by classical Southern analysis in selected cases at both presentation and subsequent relapse showing absence of clonal evolution in most cases. V-(D)-J nucleotide sequences of rearrangements with an identical pattern of rearrangement at presentation and relapse were identical in all cases analyzed. We therefore describe a new, specific, and clinically useful strategy for the detection of minor clonal populations applicable in the majority of cases of ALL. 
Hypertension in young patients. Hypertension is often unrecognized in infants and children. Primary care physicians need the equipment necessary to measure blood pressure in young patients and tables or graphs showing normal values for age and sex. Children should have a blood pressure measurement and preventive counseling at each yearly checkup. Significant hypertension should never be dismissed as a temporary problem but rather should be carefully investigated, treated, and followed up. 
Tuberculous pericarditis. Tuberculosis is responsible for approximately 4% of cases of acute pericarditis, 7% of cases of cardiac tamponade, and, in older studies, 6% of instances of constrictive pericarditis. However, in some nonindustrialized countries, tuberculosis is a leading cause of pericarditis. The diagnosis is based on demonstration of tubercle bacilli in pericardial fluid or on histologic section of the pericardium, or proof of tuberculosis elsewhere in a patient with otherwise unexplained pericarditis. Treatment consists of triple drug therapy for at least 9 months (isoniazid, rifampin, and streptomycin or ethambutol). Pyrazinamide can be used for the first 2 months, and the total therapeutic period can then be shortened to 6 months after culture conversion. Three months of corticosteroid therapy may be useful in patients in whom pericardial effusion persists or recurs despite the use of antituberculous drugs. Surgical resection of the pericardium is indicated for recurrent or life-threatening tamponade, or when there is persistent elevation of systemic venous pressure unrelieved by pericardiocentesis. As many as one third to one half of patients will eventually require pericardiectomy despite adequate drug therapy. 
Sequential high-dose methotrexate and fluorouracil combined with doxorubicin--a step ahead in the treatment of advanced gastric cancer: a trial of the European Organization for Research and Treatment of Cancer Gastrointestinal Tract Cooperative Group. In a prospective phase III multicenter trial, 213 patients with advanced measurable or nonmeasurable gastric cancer were randomized to receive methotrexate (MTX), fluorouracil (5-FU), and Adriamycin (doxorubicin; Farmitalia Carlo Erba, Milan, Italy) (FAMTX) or 5-FU, Adriamycin, and mitomycin (FAM). The results show a significantly superior response rate (41% v 9% [P less than .0001]), and survival (median, 42 weeks v 29 weeks [P = .004]) for FAMTX. There was a cumulative thrombocytopenia in FAM and not in FAMTX. The FAMTX protocol should be the reference treatment in future clinical trials that seek to improve the therapeutic outcome in advanced gastric cancer. 
Genitourinary rhabdomyosarcoma in children. The survival rates for childhood rhabdomyosarcomas have risen from 20% to 50% with the institution of a multidisciplinary approach involving the pediatric oncologist, radiation therapist, and surgeon. Increased survival has been particularly striking in the case of genitourinary rhabdomyosarcomas, which have a more favorable prognosis than rhabdomyosarcomas occurring in other anatomic sites. By stratifying genitourinary rhabdomyosarcomas by anatomic subgroup, i.e., paratesticular, bladder or bladder-prostate, and gynecologic, insight into specific predictors of failure can be obtained. Patients judged to be high risk at diagnosis can then be selected for more intensive or novel forms of therapy. 
Increment-threshold spectral sensitivity in blindsight. Evidence for colour opponency. In the circumscribed visual field defects of 3 patients, increment-threshold spectral sensitivity was measured with a guessing paradigm. Nine 116', 200 ms narrowband stimuli with maximum transmission between 450 and 660 nm were presented on a white background of photopic or scotopic luminance. Sensitivity measured in the blind field was compared with that at matched positions in the patients' normal hemifield, and with that at corresponding positions in 2 control subjects. Results show that spectral sensitivity in the blind field, albeit reduced by up to 1 log unit, shows normal dependence on adaptation level, reflecting rod activity under scotopic, and cone activity under photopic conditions. Characteristic discontinuities in the spectral sensitivity curve seen under light adaptation are evidence for colour-opponent processes, presumably involving primate beta retinal ganglion cells. 
Effect of lung hyperinflation and endotracheal suctioning on heart rate and rhythm in patients after coronary artery bypass graft surgery. We examined the effect of lung hyperinflation and suction on PaO2, heart rate, and rhythm in patients after coronary artery bypass graft surgery (N = 26). Three lung hyperinflation breaths, at one of five randomly ordered volumes (tidal volume, 12 cc/kg, 14 cc/kg, 16 cc/kg, or 18 cc/kg of lean body weight) were delivered, by a ventilator (fraction of inspired oxygen 1.0), followed by 10 seconds of continuous suction. Lung hyperinflation and suctioning were repeated three times. Repeated-measures analysis of variance revealed a statistically significant increase (p = 0.000) in PaO2 immediately after the third suction pass, which was volume dependent (p = 0.009). A statistically significant (p less than 0.001) increase in heart rate from baseline occurred over the three lung hyperinflation-suctioning sequences that was not volume dependent. The mean increase in heart rate was 6.8 beats/min. The majority of rhythm changes for lung hyperinflation and suctioning were from normal sinus rhythm to sinus tachycardia. Suction was associated with a greater incidence of rhythm (53.9%) and arrhythmia (80.8%) changes. The most frequent arrhythmia was premature atrial contraction. 
Pathogenesis of nephrolithiasis post-partial ileal bypass surgery: case-control study. The POSCH Group. Between 1975 and 1983, 838 patients were randomized into the Program on the Surgical Control of Hyperlipidemias (POSCH) trial: 417 to standard medical care and 421 to partial ileal bypass (PIB) surgery. During the course of the trial, an increased incidence of kidney stone formation was found in the surgery group (4%/year) as compared to the control group (0.4%/year). A matched triplet case-control study was conducted to assess the possible causes for the increased incidence of kidney stones. Three groups were studied: PIB stone-formers (S); PIB non-stone formers (N); and non-PIB, non-stone formers in the control group (C). Initially, 162 patients (54 triplets) were selected. Ten percent of the patients declined to participate which resulted in a sample size of 146 patients. The PIB patients had statistically significant (P less than 0.05) lower levels of serum vitamin D metabolites; lower urine volume, pH, citrate, magnesium, carbon dioxide, and sulfate, and higher urinary oxalate, ammonia and relative supersaturation for calcium oxalate and uric acid than the control patients. Although S and N had similar results, those S with no prior history of stones had a higher calcium oxalate supersaturation than similar N with a negative prior history of stones (P less than 0.025). Based on these results, all PIB patients appear to be at risk for kidney stone formation. The combination of reduced urinary volume and calcium oxalate precipitation inhibitor substance with increased calcium oxalate relative supersaturation produced an increase in nephrolithiasis risk in the PIB groups. 
Catabolic illness. Strategies for enhancing recovery. After injury, infection, extensive chemotherapy, and other critical illnesses, both protein and fat are lost from the body. Although minor alterations in body composition are probably of little clinical importance, losses of body protein of 10 percent or more contribute to morbidity and debility. This catabolic response can be modified and recovery can be accelerated by a variety of approaches. First, the inflammatory response can be reduced; second, specific nutrients can be provided to support the patient's tissue requirements during catabolic illness; and third, growth factors can be used to enhance protein synthesis and tissue repair. These approaches, whether used alone or in combination, will reduce the loss of body protein, which should accelerate recovery, shorten the length of hospitalization, and reduce convalescence. 
Nonarteritic anterior ischemic optic neuropathy and intraocular pressure. Several reports have suggested that nonarteritic anterior ischemic optic neuropathy (AION) may be related to increased intraocular pressure. We reviewed the records of 45 patients aged 48 through 86 years with nonarteritic AION (10 patients had bilateral AION) for intraocular pressure measurements and the diagnosis of glaucoma or suspected glaucoma. This group was compared with 45 age- and sex-matched patients with normal eye examination results. The mean +/- SD intraocular pressures were 16.3 +/- 3.3 mm Hg for 45 eyes of the 45 patients with AION and 16.1 +/- 2.8 mm Hg for 45 eyes of the 45 control patients (paired t test, P = .70). Among patients with unilateral AION, intraocular pressure was not greater in the involved eye than in the uninvolved eye. Three patients with AION had a previous diagnosis of glaucoma, while three of the control patients were being followed up with suspected glaucoma. We found no evidence in our series to support the hypothesis that AION is associated with increased intraocular pressure. 
Application and results of the AO internal fixation system in nontraumatic indications. The AO internal skeletal fixation system (ISFS) permits posterior spine fixation to be restricted to the vertebrae immediately adjacent to the lesion and allows manipulation of each instrumented vertebra in three planes. In a prospective study to assess the value of this fixation for adult spinal disorders, 68 patients were reviewed. The device was used in spondylolisthesis, postlaminectomy instability, post-traumatic kyphosis, degenerative scoliosis, spinal stenosis, tumors, and infections. A total of 322 transpedicular screws have been inserted without neurologic complication. Satisfactory results were achieved in 88% of the patients, and only four pseudarthroses (6%) occurred. The ISFS provides rigid stabilization to enhance bone graft consolidation and to allow rapid postoperative mobilization in a light external orthosis. 
Anomalous papillary muscle producing dynamic left ventricular outflow tract obstruction. A patient with a dynamic left ventricular outflow murmur was shown to have an anomalous anterolateral papillary muscle by transthoracic and transesophageal two-dimensional Doppler echocardiography. High late systolic outflow velocity and systolic anterior motion were demonstrated in the lateral outflow tract near the anomalous muscle, suggesting a role for the Venturi effect. This is the first confirmation by Doppler echocardiography of an anomalous papillary muscle contributing to abnormal left ventricular hemodynamics. 
Complex partial status epilepticus of extratemporal origin: report of a case. A 28-year-old woman with no history of seizure was 7 months pregnant when she developed a prolonged complex partial status epilepticus (CPSE) organized in recurrent complex partial seizures of occipital origin, which was ascertained by the presence of elementary visual hallucinations and nystagmus heralding the attacks. EEG demonstrated recurrent seizures starting from the right occipital area. This especially refractory case of CPSE resolved after treatment with antiepileptic drugs and termination of pregnancy by cesarean section. 
Cranial nerve involvement and base of the skull erosion in nasopharyngeal carcinoma. In a prospective study of 262 consecutive patients with nasopharyngeal carcinoma (NPC), using computed tomography (CT) as their baseline evaluation, erosion of the base of the skull and intracranial extension into the middle cranial fossa were found in 31.3% and 12.2% of patients, respectively. Thirty-four of these patients had cranial nerve involvement at presentation; 30 of them had involvement of one or more of the third to sixth cranial nerves. Most cases of intracranial extension of tumor were accompanied by erosion of the base of the skull, but the reverse was not true. All patients with cranial nerve palsy involving the third to sixth cranial nerves had associated erosion of the ipsilateral base of the skull. The CT evaluation of patients with cranial nerve involvement who are believed to harbor NPC should include thin cuts of the base of the skull for detection of subtle bone erosion. This may be the only clue to the presence of a small NPC. The prognostic significance of cranial nerve involvement, base of the skull erosion, and intracranial extension of the tumor on the survival of the group of 84 patients who had T4 tumors was evaluated with regression analysis using the Cox model. Only cranial nerve involvement was found to be a significant factor influencing survival. 
Comparison of the generation of albumin-associated cytotoxic activity in supernatants from ethanol-containing cultures of human blood monocyte-derived macrophages and of two human hepatoma cell lines. The rates of oxidation of ethanol to acetate by human blood monocyte-derived macrophages and the two human hepatoma cell lines PLC/PRF/5 and Hep G2 were studied. The average rates obtained were, respectively, 621, 447 and 596 nmol/h/mg cellular protein. Cultures of these three cell types, containing known quantities of cellular protein per flask, were incubated with 0 or 2 mg ethanol/ml for 72 h and the culture supernatants subjected to affinity chromatography on blue sepharose CL-6B. Pure albumin fractions obtained in this way were adjusted to the same optical density and tested for cytotoxicity against A9 cells. The data showed that the albumin fractions obtained from ethanol-containing macrophage cultures were considerably more cytotoxic than those obtained from ethanol-containing cultures of PLC/PRF/5 and Hep G2 cells. It appeared that, for a given quantity of ethanol metabolised, considerably more acetaldehyde was released extracellularly by macrophages than by the two hepatoma cell lines and that this acetaldehyde bound to albumin to form cytotoxic acetaldehyde-albumin complexes. The data raise the possibility that macrophages are an important source of extracellular acetaldehyde and circulating acetaldehyde-albumin complexes in vivo. 
The endocrine effects of long-term treatment with mifepristone (RU 486). Mifepristone (RU 486) is a compound with progesterone as well as cortisol-blocking activities. We investigated the endocrine effects of long-term therapy of 10 patients with meningiomas with 200 mg mifepristone daily for 1 yr. Most patients initially complained of nausea, vomiting, and/or tiredness. In four patients prednisone (7.5 mg/day) had to be given simultaneously in order to overcome these side-effects. In retrospect those patients who presented with the most severe side-effects showed the most rapidly occurring activation of the hypothalamo-pituitary-adrenal-axis, as measured by an increase of circulating cortisol levels as well as of urinary cortisol excretion. Therapy with RU 486 activated the hypothalamo-pituitary-adrenal axis, resulting in a resetting of this system at a higher level at which the diurnal rhythm and the responsiveness to CRH stimulation were maintained, whereas the sensitivity to dexamethasone had diminished. Secondarily the production of androstenedione and estradiol increased considerably. These endocrine changes were caused by the induction of partial cortisol receptor resistance during therapy with RU 486. The compensatory overproduction of androgens and consequently of estrogens during long-term RU 486 therapy might limit its use as a single treatment in the treatment of estrogen-dependent cancer. 
Detection of hepatitis B virus DNA in paraffin-embedded liver tissues in chronic hepatitis B or non-A, non-B, hepatitis using the polymerase chain reaction. We developed a polymerase chain reaction assay for the direct detection of hepatitis B virus in paraffin-embedded liver tissue and applied this assay to determine whether hepatitis B virus DNA exists in livers with chronic hepatitis non-A, non-B. Fifty five liver biopsy samples were studied: 11 from patients with HBeAg-positive chronic hepatitis (paraffin-embedded) and 44 from patients with chronic hepatitis non-A, non-B (21 paraffin-embedded; 25 fresh frozen). Thirty three (75%) of the non-A, non-B cases were positive for hepatitis C virus antibodies. Approximately 1 to 10 ng of DNA was extracted from the paraffin-embedded tissue and amplified using oligonucleotide (23-mer) primers specific for the S gene (positions 261 to 692). The beta-globin gene was used as an internal control for sensitivity because this is a single copy gene and allows for relative quantification. In each of the chronic hepatitis B livers, the expected 432-base-pair amplification product for hepatitis B virus DNA and beta-globin gene product were both detected. On the other hand, in the 21 paraffin-embedded chronic hepatitis non-A, non-B livers, no hepatitis B virus DNA was detected, although beta-globin gene was observed in all. Furthermore, in all 25 frozen non-A, non-B livers, beta-globin gene was observed, but no hepatitis B virus band was seen. The limit of detection of hepatitis B virus DNA by this method was estimated to be one genomic copy of hepatitis B virus DNA per cell. 
Varicella zoster virus DNA in throat swabs. Eighty-one throat swabs from 18 patients infected with varicella were tested for varicella zoster virus DNA by the polymerase chain reaction. The positive rates were 26.2% (11/42) during the incubation period and 89.7% (35/39) after clinical onset. The results indicate the pharynx is a site for early replication of the virus. 
Content and boundaries of medicine in long-term care: physicians talk about stroke. Twenty physicians were interviewed about roles, treatments, goals, and relationships with older patients, especially stroke patients. Findings from this descriptive, anthropological investigation address the problem of congruence between needs and existing services, and in doing so, recast the ongoing debate about the medicalization of long-term care. This study emphasized the nonmedical features of geriatric medicine in general and stroke care in particular. In many instances, these physicians attempt to bridge gaps between medical and emotional needs and clinical and social services with social and psychotherapeutic as well as biomedical interventions. Because we found physicians' activities with stroke patients to be so broadly construed, treatment and management of stroke may be seen as paradigmatic for the role of physicians in long-term care. 
The risk of seizure recurrence following a first unprovoked seizure: a quantitative review. Knowledge of the recurrence risk following a first unprovoked seizure and the predictors of that risk are necessary for rational treatment decisions. Published estimates of recurrence risk range from 23% to 71%. In a meta-analysis of 16 reports, three methodologic factors explained much of the reported variation: (1) study inclusion criteria, ie, whether patients were enrolled at the time of their first seizure or if patients with prior seizures were included; (2) retrospective versus prospective ascertainment of patients; (3) the interval between the first seizure and the time at which risk was assessed. The average recurrence risk across the 16 studies was 51%. The risk was 40% and 52% in prospective and retrospective studies that employed first-seizure methods and 67% in non-first seizure studies. At or near 2 years following the first seizure, the recurrence risk was 36% and 47% in prospective and retrospective first-seizure studies. The distribution of prognostic factors was also important. Seizure etiology and the EEG were the strongest predictors of recurrence distinguishing between patient subgroups, with recurrence risks as low as 24% and as high as 65%. Partial seizures were associated with an increased recurrence risk, but not consistently. There is considerable agreement among studies concerning the recurrence risk following a first seizure, and much of the discrepancies among studies can be explained by differences in study methods and distributions of important prognostic factors. 
Pathological features of Crohn's disease determining perforation. Even if Crohn's disease (CD) stenoses are related to perforating complications, such as abscess or fistula, it remains unclear why only some stenoses lead to such complications. We have studied the surgical specimens in 94 cases of CD to characterize the anatomical features of stenosis. We found no differences between group A (patients with perforation) and group B (noncomplicated patients) as far as extent of lesion, number of stenoses, and the caliber of the stenotic bowel. In CD of the ileum, the wall thickness of the stenoses was significantly different: 12.0 +/- 3.4 mm in group A and 7.6 +/- 3.1 mm in group B (p less than 0.001). In colonic CD, the length of stenosis was significantly greater in patients with perforation. Duration of symptoms, age at surgery, and sex did not correlate with the increased thickness or with perforating complications. These observations suggest that the fibrotic gastrointestinal tract, poorly distensible, may increase the intraluminal pressure above the stenosis and in this way squeeze bowel content through mucosal fissures of the inflamed bowel. Evaluation and monitoring of wall thickness may help in prompting surgery before the disease is complicated by perforation. 
Prevalence and prognostic significance of silent and symptomatic ischemia after coronary bypass surgery: a report from the Coronary Artery Surgery Study (CASS) randomized population. The prevalence and prognostic significance of postoperative myocardial ischemia, as detected by exercise testing, were prospectively assessed in 174 patients from the Coronary Artery Surgery Study (CASS) randomized surgical population who had exercise testing before and 6 months after coronary artery bypass graft surgery. Whereas the prevalence of symptomatic ischemia significantly decreased postoperatively (52% vs. 6%, p less than 0.001), the frequency of silent myocardial ischemia did not change (30% vs. 29%). Survival at 12 years after bypass surgery based on the 6-month postoperative exercise test results was significantly better for the 112 patients with no ischemia (80%) than for the 51 patients with silent ischemia (68%) or the 11 patients with symptomatic ischemia (45%). These data show that coronary artery bypass graft surgery diminishes the overall prevalence of symptomatic but not silent ischemia and that both silent and symptomatic ischemia adversely affect the postoperative prognosis of these patients. 
Subrenal capsule assay using nude mice as a predictor of the response of the gastric cancer to chemotherapy. Feasibility of utilizing human gastric cancers as first transplant generation xenografts in nude mice for determining tumor sensitivity to chemotherapeutic agents was demonstrated by applying subrenal capsule (SRC) assay. A total of 55 human gastric tumors from patients were tested in this assay. Mitomycin-C (MMC) and hexycarbamyl-5-FU (HCFU, 5-FU derivative) were selected for the treatment of these patients after surgery and also for this assay as first transplant. Evaluable rate of MMC in this assay was 92.7% and that of HCFU was 90.9%. Sensitivity of tumors to MMC was 25% and to HCFU was 32%. Correlation between response to chemotherapy of human tumors in patients and in nude mice was 78.6%. These results indicate that this assay could predict effective drugs for patients with gastric cancer. 
Preclinical markers in studies of Parkinson's disease. The development of reliable preclinical detection procedures for idiopathic Parkinson's disease may be the fundamental advance required for the establishment of the cause, the natural history, and ultimately, the prevention of this neurodegenerative disorder. The usefulness of these preclinical markers in efforts to better understand the etiology and development of this disorder will relate to whether they are direct measures of dopamine production or indirect measures such as metabolic changes or comorbidity, whether they can be used in the first or later decades of life, whether they are invasive, and whether they are expensive and sophisticated or simple and cheap. An overview of the criteria for evaluation of the utility of specific markers, as well as an assessment of the importance of early markers in future research, is presented. 
Rapid growth of untreated esophageal squamous-cell carcinoma in 10 patients. We documented the natural history of esophageal carcinoma and its rapid growth by measuring the change in tumor diameter radiographically in 10 patients during an observation period because the diagnosis had been missed. Nine men and one woman (age range, 48-74 years; mean, 60 years) were included in the study. Eight patients had undergone esophagography for gastrointestinal complaints and had lesions missed on the initial interpretation that were apparent on retrospective review after the patient had returned with more severe complaints and undergone repeat studies; two patients had refused treatment. The tumor was squamous-cell carcinoma in all. The treatment-free retrospective observation period ranged from 4 to 19 months (mean, 12.2 months) and was shorter for elevated (mean, 9.2 months) than for depressed lesions (mean, 16.8 months). The longitudinal diameter increased from 10-100 mm initially (mean, 30.5 mm) to 32-150 mm (mean, 74.9 mm). No correlation existed between the increase in size and histologic features. This documentation of the rapid increase in the size of esophageal carcinoma involving at least the submucosa confirms clinical impressions of the aggressive nature of this lesion and offers an explanation of why this disease is seldom detected at an early stage and long-term survival is so poor after the early stage of disease. 
Primary intrasellar coccidioidomycosis simulating a pituitary adenoma. The case of a 68-year-old woman who had relatively acute, unilateral ophthalmoplegia is reported. Radiological studies indicated a mass lesion involving the pituitary gland and left cavernous sinus. Pathological tissue obtained by the transsphenoidal approach revealed the presence of a Coccidioides granuloma. This pathological entity should be considered when evaluating patients with a pituitary mass and ophthalmoplegia. 
Mapping of DNA instability at the fragile X to a trinucleotide repeat sequence p(CCG)n. The sequence of a Pst I restriction fragment was determined that demonstrate instability in fragile X syndrome pedigrees. The region of instability was localized to a trinucleotide repeat p(CCG)n. The sequence flanking this repeat were identical in normal and affected individuals. The breakpoints in two somatic cell hybrids constructed to break at the fragile site also mapped to this repeat sequence. The repeat exhibits instability both when cloned in a nonhomologous host and after amplification by the polymerase chain reaction. These results suggest variation in the trinucleotide repeat copy number as the molecular basis for the instability and possibly the fragile site. This would account for the observed properties of this region in vivo and in vitro. 
Correlation of the blind spot size to the area of the optic disk and parapapillary atrophy. We evaluated the relationship between the optic disk and the blind spot area. Using kinetic Goldmann perimetry in 23 patients with open-angle glaucoma and 19 normal subjects, the blind spot size was correlated significantly with the total area of the optic disk, peripapillary scleral ring, and parapapillary chorioretinal atrophy. Zone beta of the parapapillary atrophy with a visible sclera was attributed to an absolute scotoma, and zone alpha with irregular pigmentation was attributed to a relative scotoma. The blind spot was significantly larger in the glaucomatous eyes than in the normal eyes, which corresponded with a larger zone beta in the glaucomatous eyes. The intrapapillary and parapapillary region of the optic nerve head correlated to the size of the blind spot, which included the parapapillary chorioretinal atrophy and a significant size difference between normal and glaucomatous eyes. 
Gastroenteritis associated with consumption of raw shellfish--Hawaii, 1991. On January 2, 1991, 12 of 24 persons who attended one or more of three New Year's celebrations in Honolulu, Hawaii, had onset of gastrointestinal illness. An investigation by the Epidemiology Branch of the Hawaii Department of Health (HDOH) determined that the only common foods shared by participants were oysters and clams provided by one distributor. 
Familial juvenile polyposis coli and colorectal cancer. A 40-year-old mother and her 7-year-old son underwent colectomy for polyposis coli. Both colectomy specimens contained predominantly juvenile polyps. The mother's specimen also had numerous tubular adenomas and one 5-cm severely dysplastic villous adenoma without invasive carcinoma. Foci of adenomatous change in juvenile polyps were present in the son's specimen. The histologic features of both cases suggest a sequence of change from juvenile polyps to adenomatous polyps to cancer. 
Mesenteric infarction secondary to tumor emboli from primary aortic sarcoma. Guidelines for diagnosis and management. Primary aortic tumors are rare, difficult to diagnose, and often fatal. This case and a review of the literature identified aortic tumors as a potential source of emboli leading to acute mesenteric insufficiency. The case showed the efficacy of magnetic resonance imaging in diagnosing and determining the extent and location of an aortic tumor. 
MDR1 gene expression and treatment outcome in acute myeloid leukemia To prospectively assess the role of MDR1 gene expression in patients with de novo acute myeloid leukemia (AML), levels of MDR1 RNA in blast cells were determined at diagnosis and correlated with treatment outcome in 63 patients. MDR1 RNA levels were negative in 29% and positive in 71% of the patients. The complete remission rate in response to induction chemotherapy was 89% for MDR1 RNA-negative patients and 53% for MDR1 RNA-positive patients (P = .008). Expression of the MDR1 gene was observed in most patients who died early or had resistant disease. Kaplan-Meier curves revealed a decrease in both disease-free survival and overall survival of patients with detectable MDR1 gene expression compared with the disease-free survival and overall survival of MDR1 RNA-negative patients (P = .029 and P = .009, respectively). These data indicate that MDR1 gene expression is an unfavorable prognostic factor and suggest that multidrug resistance is important in AML. 
Increased dopamine-induced nephrogenous cAMP formation in hypertension. Low doses of exogenous dopamine (3 micrograms/kg/min) were administered intravenously to nine patients with essential hypertension and to six age-matched healthy volunteers. During infusion with dopamine, mean arterial blood pressure decreased in hypertensive patients whereas it did not change in normotensive subjects. Basal levels of sodium excretion were comparable in hypertensive and normotensive subjects. The natriuretic response to dopamine was significantly greater in hypertensive patients. Urinary and nephrogenous cAMP significantly increased in both normotensive and hypertensive subjects. The increase of nephrogenous cAMP was more pronounced in hypertensive patients than in normotensive controls. A significant correlation was found between nephrogenous cAMP and sodium excretion. The enhanced natriuretic response to dopamine in hypertensive patients may be due to increased cAMP formation in response to tubular dopamine receptor stimulation. This is in agreement with the hypothesis of either up-regulation or affinity changes of renal dopamine receptors in patients with essential hypertension, secondary to a decreased endogenous production of intrarenal dopamine. 
Surveillance for recurrent stenosis after endovascular procedures. A prospective study. Eighty-nine endovascular procedures were performed during a 1-year period. Techniques included balloon angioplasty (n = 50), laser-assisted balloon angioplasty (n = 32), and atherectomy (n = 7). Indications were claudication (65.2%), critical ischemia (30.3%), and failing bypass (4.5%). Preoperative evaluation included a history and physical examination, segmental limb pressures, and color duplex ultrasonography. Postoperative surveillance consisted of a history and physical examination, ankle-arm indexes, and color duplex examinations at 1-week, 1-month, and then 3-month intervals. All levels of aortoiliac and infrainguinal disease were treated. Immediate technical success rate was 89.8%. Recurrence rates by life-table analysis reveal a 9-month patency rate of 45.4%. Early results of this prospective study indicate that endovascular procedures are subject to significant restenosis rates. Restraint is advised concerning general acceptance of endovascular procedures pending critical study. 
Pain and vascular reflexes in man elicited by prolonged noxious mechano-stimulation. Interdigital webs of the hands of human volunteers were pinched for periods of 2 min duration to induce tonic pain perceptions. During stimulation, the subjects gave estimates of their pain level at 10-sec intervals on a visual analogue scale, and the stimulus induced changes of the skin blood flow in the stimulated hand was assessed by photo-plethysmography. Sustained pinching induced a tonic reflex vasoconstriction in the stimulated hand with rather slow adaptation rate and no signs of habituation between trials. Step increases of the pinching force in the course of a stimulus were reflected by a decrease in plethysmogram amplitude as well as by increased pain ratings, although the subjects were usually unaware of these steps. Lowering the stimulus strength induced opposite, albeit much smaller effects in both pain ratings and vascular reactions. It is concluded that the vasomotor responses described in this paper are mediated by nociceptor input and reflect the processing of this input mainly at a spinal level. 
Striking CT scan findings in a case of unilateral moyamoya disease--a case report. The authors report striking CT scan findings in a young woman with unilateral Moyamoya disease. Serial CT scans showed features that paralleled the clinical and pathophysiologic evolution of the disorder, in much the same way as has been reported in studies using serial angiograms. 
Acute delta hepatitis: serological diagnosis with particular reference to hepatitis delta virus RNA. To evaluate serologic diagnosis of hepatitis delta virus, we tested HDV RNA in stored sera from 48 patients with acute delta hepatitis who were identified with anti-HD antibodies. Initial sera were positive for HDV RNA in 27 of 48 (56%) patients. In comparison, isolated IgM anti-HD was present in 18 (38%) patients, although IgM and IgG anti-HD were present concurrently in 16 (33%) additional patients. Overall, either HDV RNA or IgM anti-HD was present in 69% of the initial sera. The HDV infection was self-limiting in all except two patients who died of fulminant hepatitis and nine others in whom chronic delta hepatitis ensued. Patterns of HDV seropositivity during progression to chronicity induced variable persistence, disappearance or recrudescence of either HDV RNA or IgM and IgG anti-HD. Results of HDV RNA and IgM anti-HD tests were concordant in only 40-50% of instances. Our results indicate that serological testing for HDV RNA is direct and will demonstrate HDV replication in a large number of cases with acute delta hepatitis. Testing for IgM anti-HD could provide supplemental evidence for HDV infection. Sequential testing for these markers will facilitate assessment of the outcome of acute HDV infection. 
The endoscopic repair of choanal atresia. Since 1755, when choanal atresia was first described by Roederer, more than 300 papers have appeared in the literature dealing with various aspects of choanal atresia. Today's preferred methods of repair are transnasal and transpalatal. Each method has its advantages, disadvantages, proponents, and opponents. The main disadvantage of the transnasal procedure is limited vision, even with a microscope, especially in newborn infants, and the inability to adequately remove enough vomerine septal bone to prevent restenosis. Endoscopic transnasal repair of choanal atresia provides excellent visualization and the ability to perform exact surgery on patients of all ages. Described are four patients who underwent endoscopic repair of choanal atresia. Three of the four have patent nares, one patient after revision surgery. The technique is discussed along with its advantages and disadvantages relative to other surgical treatment modalities. 
Assessment of left atrial appendage function by transesophageal echocardiography. Implications for the development of thrombus. BACKGROUND. The predilection of the left atrial appendage (LAA) for thrombus formation has long been known. METHODS AND RESULTS. We prospectively studied the two-dimensional echocardiographic and Doppler patterns of LAA function in 82 patients by transesophageal echocardiography. In the 63 patients in sinus rhythm, LAA area was measured during LAA diastole at the onset of the electrocardiographic (ECG) P wave (LAAmax) and after LAA systole at the ECG R wave (LAAmin) and LAA ejection fraction was calculated as (LAAmax-LAAmin)/LAAmax; peak Doppler velocity was recorded from the LAA outlet. The 58 patients in sinus rhythm without LAA thrombus were grouped according to left atrial size on transthoracic echocardiography; 39 patients had a left atrial size of less than 40 mm (group 1) and 19 had a left atrial size of 40 mm or greater (group 2). Five patients in sinus rhythm had LAA thrombus. In the 19 patients with atrial fibrillation or flutter LAAmax was measured independent of the ECG; three of these patients had LAA spontaneous contrast, four had thrombus, and one had both. Patients in sinus rhythm without LAA thrombus demonstrated a characteristic pattern of a contractile LAA apex and a noncontractile base with color flow and pulsed Doppler evidence of LAA emptying that coincided with the P wave. Patients in sinus rhythm with LAA thrombus had a mean +/- SD LAAmax (8.0 +/- 1.5 cm2) larger than that in group 1 (5.0 +/- 1.9 cm2) (p less than 0.01) but not group 2 (6.7 +/- 3.1 cm2), LAAmin (6.5 +/- 1.0 cm2) larger than that in both group 1 (2.3 +/- 1.5 cm2) and group 2 (4.2 +/- 2.7 cm2) (p less than 0.01), and LAA ejection fraction (17 +/- 11%) and LAA velocity (0.24 +/- 0.10 m/sec) less than those in both group 1 (55 +/- 21% and 0.48 +/- 0.24 m/sec, respectively) and group 2 (45 +/- 27% and 0.46 +/- 0.24 m/sec, respectively) (p less than 0.01). Patients with atrial fibrillation or flutter with LAA spontaneous contrast and/or thrombus had LAAmax (10.4 +/- 6.6 cm2) greater than that in patients with atrial fibrillation or flutter without LAA contrast and/or thrombus (6.8 +/- 3.0 cm2) (p less than 0.05). The LAA appeared as a static pouch in seven of eight of the former compared with in two of 11 of the latter. When attempted, Doppler demonstrated a recognizable fibrillatory LAA outflow velocity pattern in none of three in the former versus four of seven in the latter group. CONCLUSIONS. We conclude that the LAA has a characteristic pattern of emptying in sinus rhythm. LAA thrombus formation in sinus rhythm and atrial fibrillation is associated with both poor LAA contraction and LAA dilation. 
Square wave jerks in parkinsonian syndromes. The frequency of square wave jerks (SWJ) was compared in eight patients with progressive supranuclear palsy (PSP), 25 patients with multiple system atrophy or Parkinson's disease plus (MSA/PP), 85 patients with idiopathic Parkinson's disease (PD) and 20 age-matched normal volunteers. In the control group, the mean (SD) SWJ frequency (SWJ larger than 1 degree amplitude) was 2.3 (2.4)/min. Abnormal ocular fixation (SWJ frequency greater than 10/min) was observed in a large proportion of PSP patients (7/8) and of MSA/PP patients (16/25) but in few PD patients (13/85). In the group of PD patients with abnormal ocular fixation, freezing of gait, falls and instability were more severe than in the group of PD patients with normal fixation. The study of ocular fixation may help to differentiate PD clinically from other Parkinsonian syndromes. SWJ are probably not related to the central degeneration of the dopaminergic nigrostriatal pathway observed in PD. 
Consequences of ileal pouch-anal anastomosis for Crohn's colitis. Patients with Crohn's colitis are generally not considered candidates for the ileal pouch-anal anastomosis (IPAA) procedure. We reviewed 362 consecutive patients undergoing IPAA and analyzed the outcome of this procedure on 25 patients with a preoperative diagnosis of mucosal ulcerative colitis who were subsequently proven to have Crohn's disease. The mean follow-up was 38.1 months. Sixteen patients have a functioning pouch, seven have required pouch excision, one is diverted, and one has died. Only one of nine patients in whom there was a preoperative clinical feature suggestive of Crohn's disease has a functioning pouch, with complications uniformly occurring within months of ileostomy closure. In contrast, 15 of 16 patients without preoperative features of Crohn's disease have maintained their pouch, generally with good results. These data suggest that patients in whom there is clinical and pathologic evidence of Crohn's disease do very poorly without meaningful symptom-free intervals. However, patients without any clinical features of Crohn's disease, despite a histopathologic diagnosis of Crohn's colitis, have had a good outcome with IPAA thus far. 
Roles of deoxycholate and arachidonate in pathogenesis of cholesterol gallstones in obese patients during rapid loss of weight. Our aim was to examine the relationship between biliary deoxycholate and arachidonate in obese patients and the relationship of deoxycholate and arachidonate to the stimulation of biliary mucous glycoprotein among obese patients predisposed to cholesterol gallstones. Thirty-four obese patients predisposed to cholesterol gallstones by a weight-reducing diet (520 kcal/day) received placebo, ursodiol (1200 mg/day), or aspirin (1300 mg/day). Duodenal bile was collected prior to beginning the diet and at four weeks. There was no correlation between deoxycholate and arachidonate among the 34 patients before beginning the diet. With placebo, deoxycholate decreased while arachidonate and glycoprotein increased. With ursodiol, deoxycholate decreased while arachidonate decreased and glycoprotein did not change. With aspirin, there was no change in deoxycholate but a decrease in arachidonate and no change in glycoprotein. Our data do not support a role for biliary deoxycholate in the regulation of biliary arachidonate. Our data do support a role for arachidonate, but not deoxycholate, in the regulation of biliary glycoprotein during the formation of cholesterol gallstones. 
Psychiatric illness in patients with chronic fatigue and those with rheumatoid arthritis OBJECTIVES: To identify psychiatric differences between patients with chronic fatigue and those with rheumatoid arthritis and to investigate whether patients meeting Centers for Disease Control (CDC) criteria for chronic fatigue syndrome (CFS) can be differentiated from patients with chronic fatigue on measures of disability and psychosocial distress. DESIGN: Cross-sectional study comparing 98 patients with chronic fatigue with 31 patients with rheumatoid arthritis on structured psychiatric interviews and patient questionnaires. Nineteen patients meeting CDC criteria for CFS were compared with 79 patients with chronic fatigue not meeting CDC criteria on questionnaires measuring disability and psychosocial distress. SETTING: Consecutive patients with chronic fatigue were selected from a chronic fatigue clinic at the University of Washington, and 31 consecutive patients with rheumatoid arthritis were sampled from a private rheumatology practice. MAIN RESULTS: Patients with chronic fatigue had a significantly higher prevalence of lifetime major depression and somatization disorder than did patients with rheumatoid arthritis. Patients with chronic fatigue also had a significantly higher prevalence of current and lifetime psychiatric diagnoses. Only 19 of 98 patients with chronic fatigue met CDC criteria for CFS. Patients meeting CDC criteria for CFS could not be differentiated from the larger group of patients with chronic fatigue on any study variable. CONCLUSIONS: Patients with chronic fatigue have a significantly higher burden of psychiatric illness than do patients with rheumatoid arthritis. The psychiatric illness preceded the development of chronic fatigue in over half the patients. Centers for Disease Control criteria for CFS did not select a subset of chronic fatigue patients who could be differentiated on disability or psychosocial parameters from patients with chronic fatigue who did not meet CDC criteria. 
Ossifying fibromyxoid tumor of soft parts. Additional observations of a distinctive soft tissue tumor. The author studied four subcutaneous soft tissue tumors, similar to those recently described by Enzinger and associates (Am J Surg Pathol 1989;13:817) by the name "ossifying fibromyxoid tumor," by immunohistochemistry and electron microscopy to further understand the cellular nature of this lesion. The four tumors were composed of uniform round cells often surrounded by a lacunar space. The tumors often contained a peripheral zone of metaplastic bone. The cellularity was high, but the mitotic rate was low, suggesting a benign or borderline nature of the lesion. Longer follow-up was available for three cases, showing recurrence-free survival times of 11, 8, and 3 years. Immunohistochemistry studies revealed that all tumors were strongly positive for S-100 protein and focally positive for Leu-7, whereas melanoma-specific marker HMB45 was negative. Vimentin was the main type of intermediate filament protein, and one case also contained scattered glial fibrillary acidic protein-positive cells. Epithelial markers (keratins, epithelial membrane antigen), desmin, and muscle actins were negative. Electron microscopic examination showed partial, sometimes reduplicated, basal lamina surrounding many cells. Complex cell processes were also present. No myofilaments were found. The immunohistochemical and electron microscopic results may suggest that this tumor has Schwann's cell differentiation. 
Mitral valve repair in the extensively calcified mitral valve annulus. Mitral valve replacement in patients with an extensively calcified mitral annulus is associated with an increased risk of ventricular rupture. Until now techniques of mitral valve repair have not been applied to patients with a heavily calcified mitral valve annulus. We present 12 patients who underwent extensive decalcification of the annulus with subsequent mitral valve repair between 1987 and 1990. Ages ranged from 11 to 78 years; 6 patients were in New York Heart Association functional class II, 4 were in class III, and 2 were in class IV. All patients had varying degrees of mitral insufficiency. There were no deaths, reoperations, or thromboembolic events. Postoperative echocardiography revealed minimal residual mitral insufficiency in only 2 of 12 patients. All patients are currently in New York Heart Association class I or II. We believe mitral valve repair can be done safely on patients with an extensively calcified mitral annulus, thus avoiding the risks of left ventricular rupture, thromboembolic events, and hemorrhagic complications associated with mitral valve replacement. 
Intrathecal morphine for postoperative analgesia in children after selective dorsal root rhizotomy. The authors report their experience with low doses (0.007-0.015 mg/kg), moderate doses (0.016-0.025 mg/kg), and high doses (0.026-0.035 mg/kg) of intrathecal morphine for postoperative analgesia after selective dorsal root rhizotomy surgery in 50 children, aged 3 to 12 years. After closure of the dura, a single dose of preservative-free morphine was injected into the subarachnoid space, and patients were assessed for 48 hours for level of comfort and side effects. The three doses of morphine provided equivalent analgesia and similar side effects. The duration of postoperative analgesia ranged from 3 to 48 hours (mean, 12.2 +/- 9.5 h). Common side effects were limited to nausea and vomiting (42%) and mild facial pruritus. No patient experienced late respiratory depression or generalized pruritus. The authors conclude that low doses of intrathecal morphine is as effective as moderate or high doses of morphine for reducing pain in the immediate postoperative period. Intrathecal morphine provides excellent analgesia after selective dorsal rhizotomy. 
A novel technique for the evaluation of mechanical pain and hyperalgesia. We describe a new technique which is useful for the evaluation of mechanically induced pain and hyperalgesia. Light metal cylinders are guided and accelerated in a barrel. On impact against the skin they elicit a brief sensation of pain. This method allows the application of a wide range of controllable innocuous and noxious impact velocities of the cylinder at variable stimulus repetition rates. The system is sufficiently flexible to stimulate perpendicularly any skin area and to move rapidly to adjacent target regions if desired. Psychophysical testing using magnitude estimation techniques revealed that pain thresholds were normally distributed. Over a wide range of stimulation intensities monotonically increasing stimulus response functions were obtained. Repeated testing showed a good intra-individual reproducibility of both threshold and supramaximal pain ratings. The method was also useful in determining the time course of pain and mechanical hyperalgesia following a brief painful stimulus. We conclude that the new technique is useful for evaluating psychophysical stimulus response functions of mechanically induced pain and its changes following tissue injury. This technique may also hold some promise in quantifying altered pain sensitivity in patients. 
Cloning of a leucine-zipper protein recognized by the sera of patients with antibody-associated paraneoplastic cerebellar degeneration. Antibody-associated paraneoplastic cerebellar degeneration (the Yo syndrome) is an uncommon disorder in which an immune response is specifically directed against tumor tissue and the cerebellum. Screening of a lambda expression library has resulted in the isolation of cDNA clones that encode the major antigen recognized by serum from these patients. The fusion protein produced by the cDNA clones provides the basis of a simple diagnostic assay for this neurological syndrome. The occurrence of leucine-zipper and zinc-finger motifs in the predicted open reading frame suggests that this protein plays a role in the regulation of gene expression. 
Emergency management of blunt trauma in children. Apart from the trend to nonoperative treatment of blunt abdominal injuries, based on accurate CT diagnosis, most of the recent and anticipated changes in pediatric trauma are organizational. They include resuscitation and triage before hospitalization, the use of designated trauma centers, resuscitation by trauma teams, noninvasive diagnosis and monitoring, comprehensive pediatric intensive care, the use of objective measures of outcome, and improved rehabilitation programs (Templeton JM: personal communication). The treatment of individual cases is based on simple but well-established principles. The key steps in management are to recognize children with life-threatening injuries (on the basis of the mechanism of injury or a Pediatric Trauma Score less than or equal to 8 or a Revised Trauma Score less than or equal to 11), to support the function of vital organs by establishing and maintaining adequate respiratory gas exchange and circulation, and to identify all important injuries by thorough and ongoing assessment. 
Interpretation and clinical significance of the QRS axis of the electrocardiogram. The frontal plane QRS axis of the standard 12-lead electrocardiogram (ECG) is easily and accurately measured by the clinician. A simple method of estimating this axis is discussed. This axis is age-dependent. We reviewed the literature to determine if evidence exists of an association between an "abnormal" QRS axis and clinically significant myocardial disease. We also examined the literature for clinical correlation of a "normal" QRS axis with the absence of myocardial pathology. We found that although an abnormal QRS axis (falling outside the limits of +30 degrees and +90 degrees) occurs in a small number of normal individuals, its presence should prompt a thorough evaluation of all the parameters of the ECG to look for myocardial disease. 
Explicit memory and repetition priming in depression. Preliminary findings. Explicit memory and repetition priming, a form of implicit memory, were examined in depressed patients and controls. Explicit memory of depressed patients was severely impaired, whereas repetition priming was intact. These results are consistent with the hypothesis that the impairment of memory in depression is linked to a failure of effort-demanding cognitive processes. Repetition priming might be useful in differentiating between depression and dementia. 
Delayed presentation and treatment of popliteal artery embolism. In the course of reviewing a 10-year experience with popliteal artery embolism (PAE), two distinct patterns of clinical presentation were identified. In addition to those patients presenting with typical acute (symptom duration less than 7 days) arterial ischemia, a second group was identified who presented with more chronic symptoms. The present study was conducted to contrast the clinical factors and treatment of these two temporal patterns of presentation with PAE. Sixty PAEs in 58 patients were documented by the combination of angiography and/or exploration of the popliteal artery. Acute presentation (AP) was seen in 41 (68%) of these and delayed presentation (DP) was noted in 19 (32%) patients. Delayed presentation patients typically presented with a history of sudden onset of claudication or rest pain and a median symptom duration of 30 days. Eighty per cent of AP patients presented with immediately threatened limbs. Angiography was generally diagnostic of chronic popliteal embolism. In the acute group, 90% were treated with embolectomy alone, while 20% of the DP group required bypass grafting. However in two thirds of the DP group, embolectomy alone performed through a direct popliteal approach was possible. Current results with overall limb salvage (92%) and mortality (7%) represents a substantial improvement compared to the authors' previous experience with PAE. The current study suggests that as many as one third of patients with popliteal artery embolism may present in delayed fashion with chronic symptoms. Furthermore most of these patients can be treated with direct popliteal embolectomy alone with favorable results. 
A phase IA trial of sequential administration recombinant DNA-produced interferons: combination recombinant interferon gamma and recombinant interferon alfa in patients with metastatic renal cell carcinoma. This study investigated the effects of sequentially administered recombinant interferon gamma (rIFN gamma) and recombinant interferon alfa (rIFN alpha) in 36 patients with metastatic renal cell carcinoma (RCC). rIFN alpha was subcutaneously administered daily for 70 days at dosages that varied (2.5, 5, 10, and 20 x 10(6) U/m2) across four cohorts of patients. Within each cohort of patients receiving a given dose of rIFN alpha, three subsets of patients received either 30, 300, or 1,000 micrograms/m2 rIFN gamma. rIFN gamma was administered intravenously for 5 days every third week, 6 hours prior to administration of rIFN alpha. Dose-limiting toxicity (DLT) included constitutional symptoms, leukopenia, nephrotic syndrome with acute renal failure, hypotension associated with death, and congestive heart failure. DLT was related more often to the rIFN alpha dose level than to rIFN gamma dose level. Maximum-tolerated dose (MTD) was 10 x 10(6) U/m2 rIFN alpha and 1,000 micrograms/m2 rIFN gamma. Six patients failed to complete a minimum of 21 days of therapy due to toxicity or rapid progression of disease. Clinical responses were seen in eight of 30 assessable patients. Two patients experienced complete remission and have remained in complete remission 20+ and 22+ months. An additional six patients have shown partial responses for 4 to 18+ months. One patient in partial remission continues to show slow regression of pulmonary and liver lesions off therapy with rIFNs. Clinical responses have remained durable for patients with complete remissions and patients with partial remissions. The results of this study suggest that toxicities associated with combination rIFN therapy can be reduced by administering these agents sequentially as opposed to simultaneously. 
Radiologic recommendation for breast biopsy on screening mammography reports. Radiologic reports on screening mammography findings often obligate breast biopsy. Ready recommendation for biopsy of nonpalpable lesions imaged by x ray is a conservative radiologic policy but is unsettling for patients and creates an imperative bind for surgeons. Like the decision to send the patient with right lower quadrant abdominal pain home rather than to the operating room, the diagnosis that requires clinical confidence and precision is nonappendicitis. Noncancer of the breast is a similar diagnosis that can usually be made on clinical and mammographic findings rather than passing such patients through to invasive diagnosis. A series of 84 patients was referred for needle localization of nonpalpable mammographically detected lesions called suspicious on screening examination. Of these 84 patients, new radiographic reports reinterpreting the findings without biopsy were written on the original mammogram in 15 patients. This is a cancellation rate of 21 per cent. In 69 patients needle localization was carried out with the finding of cancer in 28 per cent, compared with the national average of 15 per cent. This higher than average yield caused concern whether any unbiopsied cancers had been followed, and a review of these patients was undertaken. In the log of patients referred for needle localization, the prereading by the mammographer performing the needle localization was recorded in advance of biopsy confirmation, and specificity proved to be 94 per cent and sensitivity 96 per cent. Of the cancers that were detected, 39 per cent were proven in patients older than 50 years. 
Overnight studies in severe chronic left heart failure: arrhythmias and oxygen desaturation. Overnight studies were performed in 10 patients with severe chronic left heart failure (New York Heart Association grades III and IV) without pulmonary disease and in eight controls. Transcutaneous oxygen (Po2) and carbon dioxide tensions (Pco2) and oxygen saturation were measured and the electro-cardiogram was recorded. During sleep mean oxygen saturation fell to 92.7% (minimum 86.1%) from 95.1% when awake. During the night oxygen saturation was below 95% for 62% of the time, below 90% for 6% of the time, and below 85% for 1% of the time. In four patients there were oxygen desaturation dips (a fall of greater than 4% in oxygen saturation from a stable baseline that lasted greater than 30 s) with concurrent increases in Pco2. Two patients had bradycardia during the dips: in one there was non-sustained ventricular tachycardia during the dips and in the other there was ST depression (greater than 0.1 mV at 80 ms after the J point) during a dip. In the controls the fall in mean oxygen saturation from 95.4% when they were awake to 94.4% when they were asleep was less than the fall in patients with heart failure and there were no desaturation dips or arrhythmias. Thus patients with severe heart failure had episodes of oxygen desaturation during sleep, some of which were associated with arrhythmia. Such episodes may be related to the increased risk of sudden death in chronic heart failure. 
Potential use of monoclonal antibodies in the diagnostic distinction of gynecomastia from breast carcinoma in men. Immunohistochemical (IHC) assays using the monoclonal antibodies (MoAbs) B72.3 and B6.2, recognizing two distinct and independently expressed breast tumor-associated antigens (BTAAs), recently have been shown to significantly improve the accuracy of cytodiagnosis of breast nodules by fine-needle aspiration (FNA). To evaluate whether the same method may be useful diagnostically in distinguishing gynecomastia from breast cancer in men, a retrospective avidin-biotin immunoperoxidase assay study was performed on 50 cases of gynecomastia and 30 cases of breast carcinoma in men, using a panel of five MoAbs known to recognize different BTAAs. The results of this study demonstrated that MoAbs B1.1, HMFG2, and MBr1 displayed a strong reactivity with gynecomastia and carcinoma, but MoAbs B72.3 and B6.2 separated benign and malignant lesions in a high percentage of cases. When used in combination, the latter two reagents reacted with 96% of the carcinomas that were analyzed but labeled only 67% of gynecomastia cases. Thus, the conjoint use of these two reagents may enhance the use of FNA biopsy as a valuable tool in the presurgical diagnosis of breast nodules in men. 
Corynebacterium parvum versus bacille Calmette-Guerin adjuvant immunotherapy of stage II malignant melanoma. Two separate studies have been reported comparing Corynebacterium parvum and bacille Calmette-Guerin (BCG) as adjuvant immunotherapy for stage II melanoma patients (The Milton S. Hershey Medical Center, 48 patients; Southeastern Cancer Study Group [SECSG], 162 patients). As the criteria for patient selection and drugs used were similar, we have pooled the data to analyze the effects of these two treatments. Both studies used BCG (Tice, Chicago, IL) 3 x 10(8) live organisms per treatment by Tine technique and C parvum (Burroughs-Wellcome, Triangle Park, NC) subcutaneous at a dose of 4 mg/m2 (SECSG) or 5 micrograms/m2 (Hershey) per treatment. The only difference in these studies was the frequency of immunization, with patients in Hershey receiving 22 doses and the SECSG patients receiving 55 doses during the 2-year period of treatment. Kaplan-Meier life-table analysis for the 210 patients shows a prolonged disease-free interval for patients treated with C parvum (P = .02, two-sided Mantel procedure). In similar fashion, patients treated with C parvum had an improved survival rate (from all causes) when compared with BCG-treated patients (P = .012). An analysis of the results for the 170 patients for which the number of positive nodes was available was performed using Cox's model, with nodes as a stratification variable and with covariates of place, treatment, age, and sex. In this analysis, an observed benefit for C parvum on the disease-free interval had a P value of .37 while the benefit of C parvum on the survival times (from all causes) had a P value of .04. When the same analysis was performed using only patients aged younger than 60 years, the observed benefit of C parvum on disease-free interval had a P value of .08 and the benefit of C parvum on survival times (from all causes) had a P value of .008. 
Immunohistochemistry of Terrien's and Mooren's corneal degeneration. Lamellar keratoplasty specimens from a patient with Terrien's marginal degeneration and a patient with Mooren's ulcer were compared using routine histopathologic and immunohistochemical staining with an avidin-biotin-peroxidase complex. Less than 25% of the resident cells in the Terrien's marginal degeneration specimen expressed major histocompatibility class II antigens compared with 75% to 100% of the resident cells in the Mooren's ulcer specimen. The ratio of CD4 cells (T-helper/inducer) to CD8 cells (T-suppressor/cytotoxic cells) in the Terrien's marginal degeneration specimen was almost 1:1 compared with 24:1 in the Mooren's ulcer specimen. In addition, less than 5% of the infiltrating cells from the Terrien's marginal degeneration specimen stained positive for CD22 (B cells), compared with 25% to 50% from the Mooren's ulcer specimen. These data may help explain why Terrien's marginal degeneration runs a more benign course than does Mooren's ulcer and provides a rationale for the use of immunosuppressive drugs to treat Mooren's ulcer. 
Developmental disorders of the pediatric spine. Developmental disorders of the pediatric spine are a group of congenital malformations commonly referred to as spinal dysraphism. These malformations are characterized by incomplete or absent fusion of midline mesenchymal, bony, and neural structures. They can be classified according to the presence or absence of an associated back mass. A detailed analysis of the embryology, clinical findings, and radiologic characteristics of the common forms of spinal dysraphism is outlined. 
Subcutaneous lidocaine for treatment of neuropathic cancer pain. Three patients with terminal malignancy reporting ineffective analgesia using systemic and subsequently spinal opiates were treated with subcutaneous infusion of 10% lidocaine hydrochloride. During the infusion, reasonably stable blood concentrations were achieved and maintained using a subcutaneous infusion at varying dose rates over days to months with improvement of the pain complaints which continued to be refractory to conventional analgesics. Blood lidocaine levels obtained at regular intervals revealed effective concentrations between 2 and 5 micrograms/ml for each patient. 
Mycosis fungoides in childhood: an unusual presentation. Mycosis fungoides, a cutaneous T cell lymphoma, is rare in childhood and adolescence. We report a case of mycosis fungoides in a 9-year-old boy initially at a site of benign reactive lymphoid hyperplasia. 
Late results of two hundred seventeen femoropopliteal bypasses to isolated popliteal artery segments. A 10-year-experience of 217 femoropopliteal bypasses to isolated popliteal artery segments in 207 patients is reported. Thirty-three femoropopliteal bypasses (15%) were performed with reversed saphenous vein and 184 (85%) with polytetrafluoroethylene grafts. Operative indications were gangrene in 121 (56%), nonhealing ulceration in 40 (18%), ischemic rest pain in 51 (24%), and claudication in 5 (2%) cases. The 5-year primary graft patency rate of these bypasses was 59% (reversed saphenous vein, 74%; polytetrafluoroethylene, 55%; p less than 0.05), the secondary 5-year graft patency rate was 61% (reversed saphenous vein, 79%; polytetrafluoroethylene, 56%; p less than 0.05), and the 5-year limb salvage rate was 78% (reversed saphenous vein, 78%; polytetrafluoroethylene, 78%). The 30-day operative mortality rate was 10%, and the 5-year patient survival rate was 38%. Eleven patients (5%) required lower extremity amputation because of progressive gangrene or extensive infection despite a patent bypass to an isolated popliteal artery segment. We conclude that femoropopliteal bypasses to isolated popliteal artery segments (1) have acceptable 5-year graft patency and limb salvage rates; (2) should be performed with reversed saphenous vein grafts when possible; (3) may be performed with polytetrafluoroethylene grafts if necessary, with a resulting limb salvage rate equal to that of reversed saphenous vein grafts; and (4) require sequential extension to an infrapopliteal artery in up to 20% of patients. In addition, the presence of an isolated popliteal artery segment is associated with a high operative mortality rate and limited life expectancy because of coronary artery disease. 
Insights gained from the management of problematical anal fistulae at St. Mark's Hospital, 1984-88. Twenty-four (3.6 percent) patients with problematical anal fistulae out of 671 with anal fistulae were analysed to assess the reasons for their recurrences and ultimate outcome. Thirteen patients (group A) had recurrent fistulae despite two definitive attempts at surgery at this hospital (median number of previous procedures before referral to this hospital was two, range 0-7; median number of definitive procedures at this hospital was three, range 3-4). In five of these patients, the reason for recurrence was missed primary (four cases) or secondary tracks (one case) at earlier operations. Five patients required multiple operations related to the use of setons. Eleven other patients (group B) required colostomy construction, eight because of severe perianal sepsis, two because of complex fistulae, and one for postrectal dermoid. Fistula healing occurred ultimately in all patients in group A after a median of 14 months (range 4-38 months). In group B, fistula healing occurred in eight patients after a median of 7.5 months (range 2-55 months) after colostomy construction. Only one patient has had a proctectomy, and five still have their colostomy. Of the other 18 patients, continence is normal in 14, there is mucus leakage in two, flatus incontinence in one and faecal incontinence in one. In conclusion, persistent attempts to resolve anal fistulae in difficult cases are frequently successful in the long term and result in good continence. 
In situ DNA hybridization analysis of oral papillomas, leukoplakias, and carcinomas for human papillomavirus. Twenty-one papillomas, 23 ordinary benign keratoses, 13 smokeless tobacco keratoses, 10 verrucous hyperplasias, 10 verrucous carcinomas, 17 squamous cell carcinomas, 3 epithelial dysplasias, and 6 lichen planus lesions were evaluated for human papillomavirus (HPV) types 6/11, 16/18, and 31/33/35, with biotinylated double-stranded DNA probes by in situ hybridization. Sixty-two percent (13/21) of oral squamous papillomas were positive for HPV DNA. HPV DNA types 6 and 11 demonstrated the strongest reactivity. Of the 13 cases, 10 also showed some reactivity with HPV-16/18 and -31/33/35. None of the cases of keratoses, epithelial dysplasia, squamous cell carcinoma, verrucous hyperplasia, verrucous carcinoma, or lichen planus were positive for HPV DNA. This study confirms the consistent and frequent finding of HPV DNA in oral squamous cell papillomas and the inconsistency of being able to identify HPV DNA in keratotic, premalignant, or cancerous lesions of the oral mucous membranes. 
Anti-IL-6 monoclonal antibodies protect against lethal Escherichia coli infection and lethal tumor necrosis factor-alpha challenge in mice. Potentially fatal physiologic and metabolic derangements can occur in response to bacterial infection in animals and man. Recently it has been shown that alterations in the levels of circulating cytokines such as IL-6 and TNF-alpha occur shortly after bacterial challenge. To understand better the role of IL-6 in inflammation, we investigated the effects of in vivo anti-mouse IL-6 antibody treatment in a mouse model of septic shock. Rat anti-mouse IL-6 neutralizing mAb was produced from splenocytes of an animal immunized with mouse rIL-6. This mAb, MP5-20F3, was a very potent and specific antagonist of mouse IL-6 in vitro bioactivity, demonstrated using the NFS60 myelomonocytic and KD83 plasmacytoma target cell lines, and also immunoprecipitated radiolabeled IL-6. Anti-IL-6 mAb pretreatment of mice subsequently challenged with lethal doses of i.p. Escherichia coli or i.v. TNF-alpha protected mice from death caused by these treatments. Pretreatment of E. coli-challenged mice with anti-IL-6 led to an increase in serum TNF bioactivity, in comparison to isotype control antibody, implicating IL-6 as a negative modulator of TNF in vivo. Anti-TNF-alpha treatment of mice challenged i.p. with live E. coli resulted in a 70% decrease in serum IL-6 levels, determined by immunoenzymetric assay, compared to control antibody, thereby supporting a role for TNF-alpha as a positive regulator of IL-6 levels. We conclude that IL-6 is a mediator in lethal E. coli infection, and suggest that antagonists of IL-6 may be beneficial therapeutically in life-threatening bacterial infection. 
Imaging of cystic and cavitary lesions of the spinal cord and canal. The value of MR and intraoperative sonography. This article discusses the utility and technique of magnetic resonance imaging and intraoperative spinal sonography in the evaluation of cystic and cavitary lesions of the spinal cord and canal. The pathophysiology and fluid dynamics of these lesions are also discussed. 
Inspiratory muscle relaxation rate after voluntary maximal isocapnic ventilation in humans. We have investigated whether the capacity of the inspiratory muscles to generate pressure and flow during a ventilatory load is related to changes in inspiratory muscle relaxation rate. Five highly motivated normal subjects performed voluntary maximal isocapnic ventilation (MIV) for 2 min. Minute ventilation and esophageal, gastric, and transdiaphragmatic pressures were measured breath by breath. We observed that ventilation, peak inspiratory and expiratory pressures, and inspiratory flow rate declined from the start of the run to reach a plateau at 60 s that was sustained for the remainder of the exercise. In a subsequent series of studies, MIV was performed for variable durations between 15 and 120 s. The normalized maximum relaxation rate of unoccluded inspiratory sniffs (sniff MRR, %pressure loss/10 ms) was determined immediately on stopping MIV. Sniff MRR slowed as the duration of MIV increased and paralleled the decline in inspiratory pressure and ventilation observed during the 2-min exercise. No further slowing in MRR occurred when ventilation became sustainable. We conclude that, during MIV, the progressive loss of ventilation and capacity to generate pressure is associated with the early onset and progression of a peripheral fatiguing process within the inspiratory muscles. 
Clindamycin treatment of chronic pharyngeal carriage of group A streptococci. We previously demonstrated that chronic pharyngeal carriage of group A beta-hemolytic streptococci (GABHS) can be terminated by intramuscular administration of benzathine penicillin plus 4 days of orally administered rifampin. Because an effective oral regimen would be desirable, we compared clindamycin with P + R for treating GABHS carriage. Healthy, symptom-free GABHS carriers were randomly assigned to receive orally administered clindamycin (20 mg/kg per day) three times a day for 10 days or intramuscularly administered benzathine penicillin with oral doses of rifampin (20 mg/kg per day) twice a day for 4 days. Compliance was documented by antibiotic activity in urine. Throat cultures for GABHS were obtained every 3 weeks for up to 9 weeks after treatment. Patients who had positive throat cultures for their original GABHS T type 3 weeks after randomization were crossed over to the other treatment. Treatment success was defined as eradication of the original GABHS T type, with all follow-up cultures negative. Clindamycin eradicated carriage in 24 (92%) of 26 patients; penicillin plus rifampin was effective in 12 (55%) of 22 patients (p less than 0.025). Including patients crossed over 3 weeks after enrollment, clindamycin was effective in 28 (85%) of 33 treatment courses compared with 12 of 22 courses of penicillin plus rifampin (p less than 0.05). We conclude that 10 days of oral clindamycin therapy was significantly more effective than benzathine penicillin plus 4 days of orally administered rifampin for treatment of symptom-free GABHS carriers. 
Linear IgA disease of adults: association with lymphoproliferative malignancy and possible role of other triggering factors. Seventy patients with linear IgA disease of adults were followed up for a mean of 8.5 years and all malignant diseases in this group were ascertained. There were three cases of lymphoproliferative malignancy, which constituted a significant excess over the 0.2 cases that would be expected by comparison with an age- and sex-matched population using National Cancer Registry statistics. In contrast, the non-lymphoid malignancy rate of 13% is almost identical to the expected 14%. A subgroup of 35 of the adult linear IgA disease patients were assessed with respect to the possible precipitating illnesses or drugs, as well as co-existing medical conditions. Almost one-third of patients described an event that was felt could possibly have triggered the linear IgA disease, the most frequent being non-steroidal anti-inflammatory or antibiotic drug therapy, trauma/burns and upper respiratory tract infections. However, it is difficult to determine how often the preceding event is coincidental, and how often, if at all, it is causal. 
Unexplained syncope evaluated by electrophysiologic studies and head-up tilt testing. OBJECTIVE: To determine the clinical characteristics of subgroups of patients with unexplained syncope having electrophysiologic studies and head-up tilt testing and to assess the efficacy of various therapies. DESIGN: Retrospective study. SETTING: Inpatient services of a tertiary referral center. PATIENTS: Eighty-six consecutively referred patients with unexplained syncope. MEASUREMENTS: All patients had electrophysiologic examinations. Patients with negative results subsequently had head-up tilt testing. MAIN RESULTS: Twenty-nine (34%) patients (group 1) had abnormal electrophysiologic results, with sustained monomorphic ventricular tachycardia induced in 72%. Thirty-four (40%) patients (group 2) had syncope provoked by head-up tilt testing. The cause of syncope remained unexplained in 23 (26%) patients (group 3). Structural heart disease was present in 76%, 6%, and 30% of groups 1, 2, and 3, respectively. In group 1, pharmacologic or nonpharmacologic therapy was recommended based on electrophysiologic evaluation. All group 2 patients had negative results on head-up tilt testing while receiving oral beta blockers (27 patients) or disopyramide (7 patients). Group 3 patients did not receive any specific therapy. During a median follow-up period of 18.5 months, syncope recurred in 9 (10%) patients. CONCLUSIONS: The combination of electrophysiologic evaluation and head-up tilt testing can identify the underlying cause of syncope in as many as 74% of patients presenting with unexplained syncope. Therapeutic strategies formulated according to the results of these diagnostic tests appear to prevent syncope effectively in most patients. 
Hepatitis C virus infection in chronic hepatitis B virus carriers. One hundred eighty-four patients with hepatitis B surface antigen-positive chronic hepatitis were evaluated for antibodies to hepatitis C virus (anti-HCV). Only 11 (8%) of 136 patients with hepatitis B virus (HBV) replication (HBV-DNA-positive in serum) while 7 (35%) of 20 positive for antibody to hepatitis B e antigen (anti-HBe) but HBV-DNA-negative were positive for anti-HCV. By contrast, anti-HCV was never found in 30 anti-HBe-positive "healthy" carriers. Anti-HCV was more frequent in hepatitis D virus (HDV)-positive than in HDV-negative cases (32% vs. 12%). During 1-11 years of follow-up, anti-HCV persisted in 90% of cases, who showed continuing alanine aminotransferase elevation. Liver histology deteriorated in 2 of 4 anti-HCV-positive, anti-HBe-positive, HBV-DNA-negative patients. These results demonstrate the existence of a subgroup of patients with anti-HBe-positive, HBV-DNA-negative, HDV-negative chronic hepatitis B, where HCV may play a leading role in causing liver disease. 
Impact of left ventricular hypertrophy on ventricular arrhythmias in the absence of coronary artery disease. Left ventricular hypertrophy has a grave prognosis. Ventricular arrhythmias may account for a large portion of this poor prognosis, but the contribution of coronary artery disease has not been excluded. The occurrence of ventricular arrhythmias was investigated by 24 h ambulatory electrocardiographic (ECG) monitoring in 49 hypertensive patients who had normal findings on coronary arteriography. The presence of left ventricular hypertrophy was assessed by both ECG and echocardiography. The frequency and complexity of ventricular arrhythmias were significantly related to the presence of left ventricular hypertrophy whether it was defined by wall thickness (interventricular septum or posterior wall greater than or equal to 1.2 cm) or by left ventricular mass indexed to height (left ventricular mass/height greater than or equal to 163 g/m in men and greater than or equal to 121 g/m in women). The relation between left ventricular mass or wall thickness to ventricular arrhythmia was graded and continuous; for every 1 mm increase in the thickness of interventricular septum or posterior wall there was an associated two- to threefold increase, respectively, in the occurrence and complexity of ventricular arrhythmias. In conclusion, left ventricular hypertrophy is associated with an increase in the frequency and complexity of ventricular arrhythmias in the absence of coronary artery disease, and the relation is graded and continuous. 
Duplex Doppler sonography of the carotid artery: false-positive results in an artery contralateral to an artery with marked stenosis. Anecdotal reports have described a false-positive "jet effect" or velocity increase in the carotid artery contralateral to an artery with significant stenosis or occlusion when using duplex Doppler sonography. In this study, the frequency, significance, and possible reasons for this finding were evaluated by a retrospective comparison of duplex sonography and angiography. Twenty-three patients with unilateral 81-100% carotid artery stenosis who underwent both duplex sonography (16 Acuson, seven Quantum) and angiography were evaluated. In 14 patients, there was an accurate or slight underestimate (less than 20%) of stenosis present in the internal carotid artery contralateral to an artery with tight stenosis/occlusion. In nine, a velocity increase in the internal carotid artery resulted in overestimation (10-80%) of the actual degree of stenosis. In one of these nine patients, real-time images were sufficient to explain the velocity increase on the basis of vessel tortuosity. In one, falsely elevated velocity resulted from inaccurate assignment of the Doppler angle of incidence in a patient in whom real-time visualization of a distal internal carotid lesion was poor. In four of the nine patients, cross filling via the circle of Willis toward the side of greater stenosis occurred. However, seven of 14 patients in whom there was duplex sonography/angiography agreement or slight duplex sonography underestimation also had cross filling. Vertebral artery patency did not correlate well with the presence of a "jet effect." These findings suggest that an increase in blood flow velocity with duplex Doppler sonography in the internal carotid artery on the side opposite an artery with a tight stenosis is a common source of error and is not readily explained by angiographic evidence of collateral flow. 
Exercise echocardiography in the detection of anthracycline cardiotoxicity. Twenty long-term survivors of childhood cancer underwent exercise echocardiography to evaluate possible late anthracycline-induced cardiac toxicity. Ten patients ages 10 to 20 years had received anthracyclines, and ten patients ages 8 to 27 years had not received anthracyclines as part of their medical regimen. Both groups had normal cardiac function at rest. Patients who had not received anthracyclines had a greater increase in M-mode shortening fraction (P less than 0.005), velocity of circumferential fiber shortening (P = 0.05), and Doppler aortic peak flow velocity (P = 0.01) than patients receiving anthracyclines. There were no significant differences in work performed, or increase in heart rate or blood pressure with exercise between the groups. These results suggest that subtle abnormalities in myocardial function exist which become apparent only after exercise in survivors of childhood cancer who have received anthracyclines and have normal resting cardiac function. 
Blood and liver-infiltrating lymphocytes in primary biliary cirrhosis: increase in activated T and natural killer cells and recruitment of primed memory T cells. We used two-color and three-color flow cytometric analysis to study phenotypical activation and functional subsets of T and natural killer cells in the blood and liver tissue of patients with primary biliary cirrhosis, other chronic liver diseases and the blood of healthy subjects. The changes in blood lymphocyte phenotype in patients with primary biliary cirrhosis and other chronic liver diseases were similar and comprised elevated relative or absolute numbers of activated human leukocyte antigen-DR + T subset (CD4+ and CD8+) cells and DR+ natural killer-like (CD16+) cells. B cell (CD19+) numbers were normal. In primary biliary cirrhosis a selective reduction in T cells of suppressor-inducer (CD45RA + CD4 + ) type was registered. The human leukocyte antigen-DR expression among CD4+ T cell subsets was investigated further in primary biliary cirrhosis and healthy controls using triple antibody flow cytometric analysis. Phenotypical cell activation was confined to helper T cells of the primed, memory (CD45RO + CD4+) type. The decrease in suppressor-inducer T cells in primary biliary cirrhosis was paralleled by a reciprocal increase in primed memory T cells. Several significant differences were observed when blood and liver-infiltrating cells from primary biliary cirrhosis patients were compared. In the liver tissue, the CD4/CD8 ratio was decreased, the relative activation of T-subset cells and NK cells was further increased, the suppressor-inducer T subset was further depressed and the primed memory T subset was increased. The cytotoxic T-cell subset (CD11b-) dominated within the CD8+ population. In liver tissue from other chronic liver disease subjects, a lower CD4/CD8 ratio was found compared with primary biliary cirrhosis. 
Low nm23 protein expression in infiltrating ductal breast carcinomas correlates with reduced patient survival. Protein levels corresponding to nm23 were determined in normal and neoplastic breast tissues by immunoperoxidase staining. Nm23 protein levels were highest in normal breast epithelium, and lower in intraductal carcinomas. Based on nm23 staining, 39 infiltrating ductal carcinomas were separated into two groups: tumors with homogeneously high nm23 protein content, and tumors with low staining in either a homogeneous or heterogeneous pattern. Patients with low nm23 staining tumors, determined by three pathologists independently, had reduced survival times (alpha = 0.034, alpha = 0.012, alpha = 0.052 by the log rank test). Nm23 expression approached significance as an independent predictor of survival in Cox's proportional hazards model. The data provide the first correlation of low nm23 protein expression and reduced breast carcinoma patient survival. 
Effect of chronic D-Ala,2 D-Leu5-enkephalin or pertussis toxin treatment on the high-affinity state of delta opioid receptor in neuroblastoma x glioma NG108-15 hybrid cells. Chronic treatment of neuroblastoma x glioma NG108-15 hybrid cells with the opioid agonist D-Ala,2 D-Leu5-enkephalin (DADLE) induces a homologous desensitization of the delta opioid receptors present in these cells. Since the Kd value of the delta opioid receptor's high-affinity state reflects the potency of the agonist, we examined the effect of receptor desensitization in NG108-15 cells on the percentage of receptor in the high-affinity state. When NG108-15 hybrid cells were treated with 10 or 100 nM DADLE for 4 hr at 24 degrees C, loss of DADLE's ability to inhibit adenylate cyclase was observed. However, when competition binding experiments were carried out with P2P3 membranes isolated from the delta opioid-desensitized hybrid cells, it was determined that 41.7 +/- 3.4% of the total binding sites remained in the high-affinity state, with no apparent alteration in the Kd value of either high- or low-affinity states. Similarly, when NG108-15 cells were treated with 100 ng/ml of pertussis toxin for 3 hr at 37 degrees C, 39.9 +/- 3.6% of the binding sites remained in the high-affinity state. This reduction in the percentage of receptor in high-affinity state was agonist specific, for chronic treatment of hybrid cells with levorphanol, a partial agonist, or the antagonist naloxone did not alter the percentage of opioid receptors in the high-affinity state. Furthermore, the delta opioid receptors remaining in the high-affinity state after chronic DADLE treatment were still sensitive to both Na+ and guanyldylimidodiphosphate, indicating that opioid ligand binding remained coupled to the G-proteins. 
Effects of prolonged inhalation of N-formyl-methionyl-leucyl-phenylalanine in rabbits. On the basis of its potent proinflammatory and spasmogenic effects, N-formyl-methionyl-leucyl-phenylalanine (FMLP), a bacterial oligopeptide, is a putative mediator of bronchoconstriction and airway inflammation during bacterial bronchial infection. However, after an FMLP dose-response curve in rabbits, tachyphylaxis to a second challenge was seen in some rabbits and airway inflammation was absent. This study was designed to reproduce the more prolonged airway exposure to FMLP that may occur during bacterial infection. Two groups of rabbits received FMLP [5 mg/ml in 66% dimethyl sulfoxide- (DMSO) saline] or DMSO diluent alone by nebulization every 15 min for 2 h. Pulmonary resistance (RL) was measured at 1 and 2 h. Recovery from bronchoconstriction was also assessed by measuring RL every 30 min for 2 h after the final FMLP administration. Sections of trachea and large bronchi were prepared and graded by quadrant from 0 to 3 for inflammation, a total score from 0 to 12 being given for each section. There was a progressive increase in RL in FMLP-treated rabbits, reaching 68 +/- 9% above baseline after 120 min, a significantly greater change than after diluent, 8 +/- 12% (P less than 0.01). RL remained elevated above baseline for 90 min after the final FMLP dose. Inflammation scores were greater after FMLP than DMSO: 9.3 +/- 0.5 vs. 4.3 +/- 0.7 (P less than 0.01) in trachea and 5.2 +/- 0.4 vs. 1.7 +/- 0.5 (P less than 0.01) in lobar bronchi. We conclude that prolonged exposure of airways to FMLP produces a sustained increase in RL and airway inflammation, the cardinal features of infective exacerbations of chronic airflow limitation. 
Comparison of transrectal ultrasound and magnetic resonance imaging in the staging of prostate cancer. A group of 32 patients with a histological diagnosis of prostate cancer underwent transrectal ultrasound (TRUS) and magnetic resonance imaging (MRI) to stage the disease. TRUS was more sensitive in the detection of tumour and in the detection of direct extracapsular spread. MRI was more sensitive in the detection of tumour involvement of the seminal vesicles and bladder base. MRI allowed the detection of lymphadenopathy and bone metastases in the lumbosacral spine and pelvis. During MRI the short tau inversion recovery (STIR) sequence was found to be particularly useful for the detection of tumour spread. TRUS and MRI are complementary investigations and for the accurate staging of prostatic malignancy both investigations should be used. 
Preliminary vascular control for renal trauma. Preliminary control of the renal vascular pedicle prior to opening Gerota's fascia is advocated as the standard approach for decreasing the rate of nephrectomy from trauma. This method, however, has not been studied widely. Previous reports failed to grade the severity of the renal injury and involved small patient series and historic control for comparison of nephrectomy rates. We studied 297 patients with renal trauma during a ten year period. Sixty-three of 75 patients with penetrating injuries and 12 of 222 patients with blunt injuries underwent renal exploration. We obtained vascular control prior to opening Gerota's fascia in 32 patients; it was obtained in 43 patients after opening Gerota's fascia. The nephrectomy rate depended on the degree of injury rather than on the type of renal vascular control obtained. Obtaining vascular control after opening Gerota's fascia did not increase the nephrectomy rate and shortened operative time by an average of 58 minutes. We recommend vascular control after opening Gerota's fascia when there is a large hematoma crossing the midline, a rapidly expanding renal hematoma, if the patient is unstable, or if Gerota's fascia has already been opened by the injury. 
Magnesium inhibits the hypertensive but not the cardiotonic actions of low-dose epinephrine. Intravenous magnesium supplementation is often used to control cardiac arrhythmias and coronary artery vasospasm resulting from disturbances of magnesium homeostasis after coronary artery bypass surgery. Many such patients also require inotropic drug support of depressed myocardial function. However, increased serum magnesium concentrations directly depress cardiac contractility in animals and may interfere with catecholamine actions. To determine whether small intravenous doses of magnesium sulfate (MgSO4) interfere with the cardiotonic actions of epinephrine, we examined the hemodynamic effects of MgSO4 and epinephrine infusion in 17 cardiac surgical patients on their 1st postoperative day in a prospective, controlled study. In 11 patients, infusion of MgSO4 (7-mg.kg-1 bolus followed by 10 mg.kg-1.h-1 as a continuous infusion) increased serum magnesium concentrations by 44% (mean +/- standard error of the mean [SEM] of 0.8 +/- 0.1 to 1.2 +/- 0.1 mM; P less than 0.01) but had no significant effect on heart rate; mean arterial, central venous, or pulmonary arterial occlusion pressures; or cardiac output. Epinephrine infusion (30 ng.kg-1.min-1) significantly increased cardiac index (2.7 +/- 0.1 to 3.1 +/- 0.21.min-1.m-2; P less than 0.05); this effect was not altered by MgSO4 administration (n = 11). However, MgSO4 significantly blunted epinephrine's hypertensive action and prevented a significant increase in mean arterial pressure during concurrent MgSO4-epinephrine administration. Six placebo control patients were given two sequential infusions of epinephrine separated by a placebo infusion to rule out an effect of time on the hemodynamic response to epinephrine. Mean arterial pressure and cardiac index responses to epinephrine were identical before and after placebo infusion. 
Combined nasal intermittent positive-pressure ventilation and rocking bed in chronic respiratory insufficiency. Nocturnal ventilatory support of a disabled person at home. The use of intermittent positive-pressure ventilation via nasal mask with a rocking bed provided the necessary ventilatory support for a person with quadriplegia living at home. This option was required to maintain an independent life-style of choice. The combination of techniques and the linkage of devices demonstrated an effective use of simple available technology for respiratory care at home and the adaptation of the respiratory prescription to the total needs of each person: medical, social, and financial. The further use of nasal mask ventilation in selected cases is encouraged by clinical research protocol. 
Evidence for a specific role of vasopressin in sustaining pituitary-adrenocortical stress response in the rat. In the adult male Wistar rat a 2-fold 2-min restraint stress exposure, repeated 15 min apart, activated the adrenocortical secretion more than a single one would have. However, in rats with a pharmacological block of the endogenous CRF release, exogenous CRH (0.3 micrograms/kg iv), administered 15 min after a first similar dose, was unable to stimulate pituitary-adrenocortical activity above the level attained with the first peptide injection. On the contrary, in the same conditions exogenous arginine vasopressin (AVP) (0.3 micrograms/kg iv) administered 15 min after CRH, was able to further stimulate pituitary-adrenocortical activity. Using the same experimental procedure, oxytocin (0.3 micrograms/kg iv) was found to be totally inactive. The physiological import of these findings was investigated in the Brattleboro rat, genetically lacking in endogenous AVP, in which, unlike the control Long-Evans strain, the 2-fold stress exposure did not cause an increase in plasma corticosterone concentration greater than that of a single exposure. These results suggest that endogenous AVP is essential in sustaining adrenocortical activation in circumstances in which pituitary refractoriness towards CRH stimulation intervenes. 
Use of folic acid for prevention of spina bifida and other neural tube defects--1983-1991. Neural tube defects--including spina bifida, anencephaly, and encephalocele--are common, serious birth defects that are important causes of infant mortality and disability. Women in the United States who have had a pregnancy resulting in an infant or fetus with a neural tube defect have a 2%-3% risk for having another pregnancy resulting in an infant or fetus with a neural tube defect (i.e., a recurrence) The British Medical Research Council (MRC) Vitamin Study Group recently reported the results of a randomized prevention trial that indicated that daily oral supplementation with folic acid before conception and during early pregnancy substantially reduces the recurrence of neural tube defects. This report summarizes the findings of that study and provides recommendations for supplementation with folic acid to prevent the recurrence of neural tube defects. 
Low-molecular-weight heparin (enoxaparin) vs dextran 70. The prevention of postoperative deep vein thrombosis after total hip replacement. The Danish Enoxaparin Study Group. A prospective randomized study compared the thromboprophylactic efficacy and safety of a low-molecular-weight heparin (LMWH), enoxaparin (40.6 mg subcutaneously once daily), with a standard regimen of dextran 70 in patients undergoing elective total hip replacement. Deep vein thrombosis was diagnosed by bilateral ascending phlebography 7 to 11 days after operation. Two hundred forty-six patients were included and 219 were eligible for analysis. Deep vein thrombosis was diagnosed in seven of 108 patients in the LMWH group and in 24 of 111 patients in the dextran group. Clinical symptoms of pulmonary embolism did not develop in any patients during the study. In the postoperative period, patients receiving LMWH had a lower blood loss in drains and required fewer blood transfusions than patients receiving dextran, although no significant differences were noted between the groups with respect to the total number of blood transfusions required. Bleeding events and adverse events did not differ between the groups. None of the patients died in hospital during the study. One patient in the LMWH group died at home 15 days after the operation. Three patients receiving dextran had development of symptomatic deep vein thrombosis after hospital discharge. In conclusion, enoxaparin was a more effective thromboprophylactic than a standard regimen of dextran in patients undergoing total hip replacement. The two regimens were equally safe under the clinical conditions. 
Recurrent kidney stones: causes and diagnostic criteria in patients from Campania (southern Italy). A study was carried out on 180 recurrent kidney stone formers from the Campania region of southern Italy. The data showed that this hypercalciuric population was similar to that in previous studies; however, there was no difference in terms of parathyroid activity when compared with normal controls. The slightly depressed serum levels of vitamin D in hypercalciurics indicate that gut calcium absorption is not directly related to vitamin D levels. We found no difference in the prevalence of metabolic abnormalities associated with stone formation between the patients in this series and those in previous studies. 
Increased tumor necrosis factor-alpha receptor number in chronic hepatitis B virus infection. Production of the antiviral cytokine, tumor necrosis factor-alpha is increased in chronic hepatitis B virus infection, and clinical studies of tumor necrosis factor-alpha have indicated a proviral effect at higher doses. To determine whether this might be related to abnormal cell surface tumor necrosis factor-alpha receptor expression, binding characteristics of cell surface tumor necrosis factor-alpha receptor on peripheral blood mononuclear cells in chronic hepatitis B virus carriers were studied using radioiodinated recombinant tumor necrosis factor-alpha. The specific binding curves generated were analyzed according to the method of Scatchard to determine cell surface receptor numbers and dissociation constants. A single class of cell surface tumor necrosis factor-alpha receptor was demonstrated on peripheral blood mononuclear cells and mononuclear subsets. The median number (range) of cell surface tumor necrosis factor-alpha receptors on peripheral blood mononuclear cells from controls (n = 11), chronic hepatitis B virus patients seropositive for hepatitis B virus DNA (n = 8) and seronegative for hepatitis B virus DNA (n = 8) were 2,329 (range = 1,538 to 3,133), 3,375 (range = 2,300 to 6,718) (p less than 0.01) and 3,113 (range = 2,229 to 5,246) (p less than 0.05) sites/cell, respectively. They all had similar dissociation constants of 8.4 x 10(-10) mol/L (range = 4.1 to 16.9), respectively. Further dissection of the peripheral blood mononuclear cells showed that this increase in cell surface receptor number was confined to the monocyte fraction (p less than 0.01). Plasma tumor necrosis factor-alpha levels in five patients with increased monocyte cell surface tumor necrosis factor-alpha receptor numbers were also elevated. 
Intratemporal facial nerve hemangiomas. Facial nerve hemangiomas are benign vascular tumors that arise within the temporal bone and have a histologic appearance similar to both cavernous hemangiomas and vascular malformations. In contrast to facial nerve schwannomas, these are extraneural tumors that cause symptoms by compression and tend to produce deficits when very small in size. We report our experience at the House Ear Clinic with 34 patients having these nonglomus intratemporal vascular tumors. Hemangiomas arising in the internal auditory canal tend to produce a progressive sensorineural hearing loss and are demonstrated with magnetic resonance imaging (MRI), whereas those at the geniculate ganglion are usually first seen with facial nerve symptoms and may require high-resolution computerized tomography (CT) for detection. Facial electromyography is helpful in establishing the diagnosis. Because of their extraneural nature, early diagnosis can permit removal of the tumor with preservation of facial nerves in some patients. 
Cellular ions in hypertension, diabetes, and obesity. A nuclear magnetic resonance spectroscopic study. To investigate the cellular basis linking hypertension, non-insulin-dependent diabetes mellitus (NIDDM), and obesity, we used 31P and 19F nuclear magnetic resonance spectroscopy to measure intracellular pH (pHi), free magnesium (Mgi), and cytosolic free calcium (Cai) in erythrocytes of obese and NIDDM subjects with and without hypertension. Compared with normotensive, nondiabetic controls (Cai, 25.2 +/- 1.4 nM; Mgi, 232 +/- 8 microM), Cai was elevated in both normotensive (36.8 +/- 2.7 nM, sig = 0.005) and hypertensive (43.4 +/- 2.9 nM, sig = 0.001) NIDDM subjects, and Mgi was concomitantly suppressed (normotensive: 206 +/- 11 microM, sig = 0.05; hypertensive: 196 +/- 8 microM, sig = 0.001). Similar but less striking changes were noted in obese subjects. Values of pHi were significantly lower (sig = 0.05) in all hypertensive groups compared with their normotensive controls. Continuous relations were observed for all subjects between Cai and diastolic blood pressure (r = 0.649, p less than 0.001) and body mass index (r = 0.565, p less than 0.001), between Mgi and diastolic blood pressure (r = -0.563, p less than 0.001) and fasting blood glucose (r = -0.580, p less than 0.001), and in diabetics, between pHi and diastolic blood pressure (r = -0.680, p less than 0.001). Thus, the constellation of elevated Cai and suppressed Mgi and pHi levels is characteristic of the hypertensive state. These abnormalities of cellular ion handling in whole or in part common to hypertension, diabetes, and obesity may contribute to the pathophysiology of these syndromes and may help to explain their frequent clinical coexistence. 
Oxygen radicals generated at reflow induce peroxidation of membrane lipids in reperfused hearts. To test whether generation of oxygen radicals during postischemic reperfusion might promote peroxidation of cardiac membrane lipids, four groups of Langendorff-perfused rabbit hearts were processed at the end of (a) control perfusion, (b) 30 min of total global ischemia at 37 degrees C without reperfusion, (c) 30 min of ischemia followed by reperfusion with standard perfusate, (d) 30 min of ischemia followed by reperfusion with the oxygen radical scavenger human recombinant superoxide dismutase (h-SOD). The left ventricle was homogenized and tissue content of malonyldialdehyde (MDA), an end product of lipid peroxidation, was measured on the whole homogenate as well as on various subcellular fractions. Reperfusion was accompanied by a significant increase in MDA content of the whole homogenate and of the fraction enriched in mitochondria and lysosomes. This phenomenon was not observed in hearts subjected to ischemia but not reperfused, and was similarly absent in those hearts which received h-SOD at reflow. Reperfused hearts also had significantly greater levels of conjugated dienes (another marker of lipid peroxidation) in the mitochondrial-lysosomal fraction. Again, this phenomenon did not occur in ischemic hearts or in reperfused hearts treated with h-SOD. Unlike the effect on tissue MDA and conjugated dienes, reperfusion did not significantly stimulate release of MDA in the cardiac effluent. Treatment with h-SOD was also associated with significant improvement in the recovery of cardiac function. In conclusion, these data directly demonstrate that postischemic reperfusion results in enhanced lipid peroxidation of cardiac membranes, which can be blocked by h-SOD, and therefore is most likely secondary to oxygen radical generation at reflow. 
Physician practices in the prevention of venous thromboembolism. OBJECTIVE: To determine the rate of use of prophylaxis for venous thromboembolism in high-risk hospital patients. DESIGN: A retrospective medical record review. SETTING: A community-wide study in 16 short-stay hospitals in central Massachusetts. PATIENTS: A total of 2017 patients with multiple risk factors for venous thromboembolism. MEASUREMENTS AND MAIN RESULTS: On the basis of age, length of hospitalization, and the presence of at least one additional major risk factor, 17% of 151,349 discharges (25,410 patients) were identified as being at high risk for venous thromboembolism. Eight percent of these discharges were randomly selected for medical record review. Prophylaxis for venous thromboembolism was received by 32% of these high-risk patients. Prophylaxis use among the 16 study hospitals varied widely, ranging from 9% to 56%, and was higher in teaching hospitals than in nonteaching hospitals (44% compared with 19%; P less than 0.001). One or more of the following methods of prophylaxis was used: low-dose heparin (78%), intermittent calf compression (13%), warfarin (12%), and inferior vena caval filter (3%). Use of prophylaxis increased with the number of risk factors identified (P less than 0.001). CONCLUSION: Prophylaxis for venous thromboemobolism is underused, particularly in nonteaching hospitals. 
Intra-aortic balloon counterpulsation support in the high-risk cardiac patient undergoing urgent noncardiac surgery. Patients with a recent myocardial infarction, congestive heart failure, sever angina, or uncorrected multivessel coronary artery disease are at increased risk of cardiac complications after major noncardiac surgery. Although invasive hemodynamic monitoring and preoperative optimization of cardiac status may lead to some reduction in the rate of perioperative cardiac events, the mortality from such events remains high. We report our experience with the use of perioperative intra-aortic balloon counterpulsation in eight patients with unstable coronary syndromes or severe coronary artery disease who underwent urgent noncardiac surgery. There were no perioperative cardiac events while the intra-aortic balloon pump (IABP) was in place. There were two postoperative cardiac events (non-fatal myocardial infarction, congestive heart failure) in the first postoperative week after the IABP was removed. One patient required emergent femoral thrombectomy as a result of intra-aortic balloon counterpulsation and subsequently died of a gastrointestinal hemorrhage. Intra-aortic balloon counterpulsation should be considered as an adjunct to maintain hemodynamic stability for the high-risk cardiac patient about to undergo urgent or emergent noncardiac surgery. 
The short test of mental status. Correlations with standardized psychometric testing. The Short Test of Mental Status can be administered to patients in inpatient and outpatient settings in approximately 5 minutes, and it contains items that test orientation, attention, immediate recall, arithmetic, abstraction, construction, information, and delayed (approximately 3 minutes) recall. The test was administered to a group of demented community patients and their age- and sex-matched control subjects. Using an age-adjusted approach, sensitivity of the test to identifying dementia is 86.4, with a specificity of 93.5. The test was compared with standardized tests of cognitive function such as the Wechsler Adult Intelligence Scale, Mattis Dementia Scale, and the Auditory Verbal Learning Test, and showed a high degree of correlation. Group means and standard deviations for subtest items and total score are presented for control subjects (n = 138), demented patients (n = 130), and patients with memory impairment only (n = 20). Percentile scores for subtest items in control subjects are also provided. 
Diagnostic accuracy and clinical utility of thermography for lumbar radiculopathy. A meta-analysis. The role of thermography for diagnosing lumbar radiculopathy was evaluated by literature review and meta-analysis. From 81 relevant citations, 28 studies could be analyzed for diagnostic-accuracy data (sensitivity and specificity) and method. Diagnostic-accuracy data varied significantly between studies; therefore meaningful pooled summary statistics could not be reported. Twenty-seven studies had major methodologic flaws including biased test interpretations, faulty cohort assembly, poor clinical descriptions, and small sample size. The only study of reasonably high quality found no discriminant value for liquid-crystal thermography. The role of thermography remains unclear. Rigorous clinical research is required to establish its diagnostic accuracy and clinical utility. Thermography cannot be recommended currently for routine clinical use in evaluating low-back pain. 
Eosinophilic cystitis in children. Eosinophilic cystitis is an uncommon inflammatory disorder of the urinary bladder which causes irritative voiding symptoms and may mimic rhabdomyosarcoma radiographically. In children, eosinophilic cystitis has been previously reported to be self-limiting and requires no specific therapy. Reported herein is a case of a nine-year-old girl in whom eosinophilic cystitis recurred following antireflux surgery, raising the question of an association of eosinophilic cystitis with local trauma such as bladder surgery. Consideration should be given to pretreatment with steroids and antihistamines prior to surgery in these patients. 
Dysrhythmias and blood pressure changes associated with thrombolysis. Recent technologic advances facilitate salvage of viable myocardium before the process of myocardial infarction is complete. The aim of thrombolytic agents is to restore antegrade flow of blood in occluded coronary arteries. The process of reperfusion may be dysrhythmogenic because of the heterogeneous return of electrical activity in myocardial cells. This study examined the incidence and type of dysrhythmia occurrence and the associated changes in mean arterial blood pressure (MAP) during infusion of tissue-type plasminogen activator (TPA). A retrospective chart review of 41 subjects showed that 80% of subjects experienced dysrhythmias during TPA therapy. The most common dysrhythmia was sinus bradycardia, followed by idioventricular/accelerated idioventricular rhythm, ventricular premature beats, and ventricular tachycardia/fibrillation. There was a significant difference between MAP changes when there were no dysrhythmias and MAP changes when dysrhythmias occurred (p less than 0.05). The largest change in MAP (-22.71 mm Hg) was observed when dysrhythmias occurred in those subjects with blockage of the left anterior descending artery, although there was no statistically significant difference in changes in MAP among the groups of different sites of blockage (p greater than 0.05). 
Cytogenetic abnormalities associated with renal cell carcinoma. Cytogenetic analysis was performed on 23 renal cell carcinomas (21 sporadic and 2 associated with von Hippel-Lindau's disease). Clonal chromosomal abnormalities were found in 19 of 21 of the sporadic tumors. The most frequent abnormalities were a loss or rearrangement of material in 3p (11 of 21 cases) or an extra chromosome 7 (7 of 21 cases). Correlation between specific chromosomal abnormalities and clinical presentation was absent with the exception of trisomy 7 and -Y, which occurred only in patients more than 60 years old. An increasing number of cytogenetic abnormalities were associated with a greater likelihood of renal vein and/or capsule involvement. Both patients with von Hippel-Lindau's disease had tumors with a normal karyotype. 
Common bile duct distensibility after cholecystectomy. To assess the possibility of common bile duct distensibility after cholecystectomy, we made a retrospective study of patients who had ultrasonography and endoscopic retrograde cholangiopancreatography (ERCP). The study comprised 52 patients without extrahepatic biliary obstruction; 19 had had cholecystectomy, 18 of whom complained of biliary colic similar to that they had had originally. The other 33 patients had intact, well visualized gallbladders; 15 of these patients had pain in the right upper quadrant or epigastrium, but none had chronic pancreatitis. The average diameter of the common bile duct at its widest point by ultrasonography was 4.8 mm (range, 4.0 to 9.0 mm) in the 33 patients with intact gallbladders, and 5.7 mm (range, 4.0 to 8.0 mm) in the 19 patients who had had cholecystectomy. The diameter by ERCP was 4.4 mm (range, 2.9 to 6.3 mm) in the patients with intact gallbladders, and 11.17 mm (range, 6.9 to 14.7 mm) in the patients who had had cholecystectomy. In each patient who had had cholecystectomy the diameter as measured by ERCP was larger than it appeared by ultrasonography. The results suggest that the common bile duct is distensible, and that this distensibility may be related to the postcholecystectomy syndrome. 
Long-term efficacy of oral cisapride in symptomatic upper gut dysmotility. We conducted a 12-month trial of cisapride (10 mg three times a day) in 21 patients with gastric stasis due to clinically and manometrically diagnosed gastroparesis (N = 9; seven due to diabetes) or chronic intestinal pseudo-obstruction (N = 12). Radionuclide solid-liquid gastric emptying tests were performed at baseline and at the end of the 12-month period. Symptoms were assessed monthly by diary and every three months by the investigators; frequency and severity of symptoms were scored in a standardized manner. For the whole group of 21 patients, gastric emptying of both solids and liquids improved significantly after one year of cisapride (P less than 0.05). Among chronic intestinal pseudoobstruction patients, there was predominantly an improvement in gastric emptying of solids; in contrast, patients with gastroparesis had a greater improvement in liquid emptying. Total symptom score improved significantly in the gastroparesis group (median score: 8 at baseline vs 6 at one year, P less than 0.05) but not in the chronic intestinal pseudoobstruction patients (median score at baseline 10 vs 9 at one year). Similarly, body weight showed a trend towards improvement in the gastroparesis group. No significant side effects were noted. We conclude that during a 12-month open trial, cisapride was effective in improving gastric emptying in patients with gastric stasis and consistently improved symptoms in those with gastroparesis. 
HELLP syndrome: a case report with guidelines for diagnosis and management. A 25-yr-old patient with a twin pregnancy of 34 weeks gestation developed HELLP syndrome and required urgent delivery by Caesarean section. Before operation, a central venous catheter and urinary catheter were inserted, and fresh frozen plasma and platelets were administered to correct hypovolaemia and severe thrombocytopenia. This case demonstrates the critical condition of these patients before operation and that extensive preoperative preparation and invasive monitoring are necessary for successful management. The choice of anaesthetic is governed by the presence of liver and renal dysfunction and severe thrombocytopenia. 
Expression of natriuretic peptide in ventricular myocardium of failing human hearts and its correlation with the severity of clinical and hemodynamic impairment. Atrial natriuretic peptide (ANP) was immunohistochemically investigated in (1) right ventricular endomyocardial biopsy specimens from 87 apparently healthy donor hearts taken from victims of cerebral accidents; (2) 1 normal heart not suitable for transplantation (HBsAg carrier); (3) right ventricular endomyocardial biopsy specimens from 151 patients with dilated cardiomyopathy (DC); and (4) 57 explanted hearts, 26 with DC and 31 with ischemic heart disease. No ANP immunoreactivity was found in normal ventricles. Failing hearts showed ventricular positivity in 31% of the DC biopsy series, in 61% of the left ventricles, and in 30% of the right ventricles of the explanted heart series. An endoepicardial gradient was observed, because ANP positivity was greater and more extensive in the subendocardial layers. Ultrastructural studies were performed on biopsy specimens from 10 normal hearts and 132 DC biopsy samples. No ANP-storing granules were found in biopsy samples of normal ventricles, whereas ANP granules were seen in 15 of 132 (11.4%) DC cases. In parallel immunoblotting, investigation showed the same 13 kDa band protein in 1 normal atrium as well as in 8 failing atria and ventricles. ANP immunoreactivity was positively correlated with higher New York Heart Association functional classes as well as with higher left ventricular end-diastolic pressure (p less than 0.005), end-diastolic volume (p less than 0.005) and end-diastolic volume index (p less than 0.005). In conclusion, apparently healthy ventricles do not show ANP immunoreactivity, whereas failing ventricles do. ANP expression seems to be independent of the underlying disease, but positively related to the clinical status and the degree of left ventricular impairment and dilatation. 
High-energy proton beam radiation therapy for gynecologic malignancies. Potential of proton beam as an alternative to brachytherapy. Fifteen patients with advanced gynecologic malignancies were treated with high-energy proton beam radiation therapy (RT) at the Particle Radiation Medical Science Center (PARMS), Tsukuba University, Japan, from 1983 to 1987. The potential of proton beam RT as an alternative to conventional brachytherapy was evaluated. Except for one local recurrence, 14 of 15 patients were locoregionally controlled for 15 to 57 months. Two-year local control rate and 2-year survival rate were 92.3% and 93.3%, respectively. Two cases of transient, radiation-induced proctitis (neither of which required surgical treatment) were the only complications despite a target dose that exceeded 8000 cGy in most cases. The results suggest that sharply localized, high-dose proton beam RT can produce an antitumor effect equivalent to that of conventional brachytherapy. 
Propafenone disposition and pharmacodynamics in normal and norepinephrine-induced cardiomyopathic rabbit hearts. The myocardial disposition and pharmacodynamics of propafenone were studied in 10 normal and 10 norepinephrine-induced cardiomyopathic rabbit hearts. The left ventricular propafenone concentrations measured after perfusion of propafenone (0.3 microM) for 150 min were similar in the normal group (18 +/- 8 micrograms/g) compared to the cardiomyopathy group (20 +/- 5 micrograms/g, P = NS). However, the concentration of propafenone in cardiomyopathic left ventricular papillary muscle, which was always extensively involved in the inflammatory process, was significantly lower (11 +/- 2 micrograms/g) compared to normal papillary muscle (19 +/- 4 micrograms/g, P less than .05). During propafenone perfusion a significantly greater increment in ventricular conduction time was observed in the cardiomyopathy group (17 +/- 6 msec) compared to the normal group (12 +/- 3 msec, P less than .05). The propafenone myocardial concentration-effect relationships describing changes in QRS duration were shifted to the left in the cardiomyopathy group. Furthermore, the slopes of these linear concentration-effect relationships were greater in the cardiomyopathy group (1.80 +/- 0.60 msec/micrograms/g) compared to the normal group (1.07 +/- 0.25 msec/micrograms/g, P less than .01). The ventricular effective refractory period was shorter at base line in the cardiomyopathy hearts (156 +/- 21 msec) compared to the normal group (176 +/- 23 msec, P less than .08). However, propafenone effects on changes in the ventricular effective refractory period were similar in the two groups. Thus, the myocardial accumulation of propafenone is reduced in areas of extensive necrosis observed in norepinephrine-induced cardiomyopathy. As well, cardiomyopathic tissue is more responsive to propafenone effects on ventricular conduction time. 
Roles of adenosine and theophylline on the recovery of adenine nucleotides in postischemic cultured renal tubular cells. The effect of adenosine (ADO) on the recovery of cellular adenine nucleotides (AN) was evaluated in the cultured cells deprived of oxygen and substrates (ischemia) and in nonischemic cells (control). The primary cultured cells were obtained from microdissected rabbit proximal straight tubules. Ten-day-old cultured cells were made ischemic for 6 hr, and allowed to recover for 24 hr. At the end of ischemia, cells were incubated with ADO, theophylline (T), dipyridamole (D), coformycin (C) or combined agents for 3 hr. Total AN (TAN) were determined after 3 and 24 hr of recovery. The results, after 3 hr of incubation, suggest that in both control and ischemic cells, ADO is taken up by cultured cells and is preferentially converted to nucleotides. This effect is blocked by D, which inhibits ADO uptake, uninfluenced by C, which inhibits ADO deaminase and potentiated by T, which inhibits 5'-nucleotidase. After 24 hr of recovery, the beneficial effects of ADO alone or combined D, C, or T, on TAN were not seen in control cells. In contrast, in the ischemic cells, after 24 hr of recovery, ADO + T normalized ATP, ADP and TAN to the preischemic levels. T alone significantly increased ATP after 24 hr of recovery. To demonstrate further that the beneficial effect of T is due to inhibition of 5'-nucleotidase, cells were treated with adenosine alpha, beta-methylene diphosphate in the same manner as T. Combined ADO + adenosine alpha, beta-methylene diphosphate normalized ATP, ADP and TAN after 24 hr of recovery. This finding suggests that inhibition of 5'-nucleotidase improves postischemic AN. 
Interactive effects of ST-T wave abnormalities on survival of patients with coronary artery disease. Previous studies have documented a reduced survival time in patients with an electrocardiographic (ECG) ST-T wave abnormality. This study was designed to determine the clinical, hemodynamic and angiographic correlates of this observation. Data from 9,731 patients undergoing cardiac catheterization from 1976 through 1986 were analyzed; 5,531 had severe (greater than 70%) obstruction of at least one major coronary artery, 1,706 had mild (10 to 69%) obstruction and 2,494 had no obstruction. Of the patients with severe obstruction, 2,536 were treated medically and 2,995 were treated by surgical revascularization. Patients with an ST-T abnormality had more clinical risk factors (including older age and greater prevalence of diabetes mellitus, hypertension and prior myocardial infarction) and greater left ventricular dysfunction (including higher end-diastolic pressure and ventricular volume, reduced ejection fraction and greater prevalence of contraction abnormality) than did those without this ECG pattern. Survival time was significantly (p less than 0.01) reduced in subsets of patients with an ST-T abnormality and with severe or mild coronary artery disease; in those without coronary disease, ST-T changes did not correlate with reduced survival. Stepwise regression analysis was applied to each group to determine the independent predictors of 5-year survival. In patients with severe disease or no disease, an ST-T abnormality was not chosen as an independent predictor of 5-year survival; in the group with mild disease, ST-T changes were an independent predictor of reduced survival. Thus, the independent impact of an ST-T abnormality on survival is dependent on the severity of underlying coronary artery disease. 
The effect of preoperative flurbiprofen on miosis produced by acetylcholine during cataract surgery. Sustained pupillary dilation during cataract surgery may be achieved with preoperative noncorticosteroidal anti-inflammatory agents such as flurbiprofen. However, these agents may interfere with miosis after injection of acetylcholine. Thirty patients for extracapsular cataract extraction were randomly assigned in a double-masked fashion to receive either a placebo or preoperative 0.03% flurbiprofen every 30 minutes for four doses. All patients also received three doses of 2.5% phenylephrine and 2% cyclopentolate. Pupillary diameter was measured the day before surgery, immediately before the surgical incision, immediately before and five minutes after acetylcholine injection, and the morning after surgery. The flurbiprofen group had a larger mean pupillary diameter before injection of acetylcholine (P less than .001), five minutes after acetylcholine (P less than .001), and on the first postoperative day (P less than .005). 
Prevalence of asthma in Melbourne schoolchildren: changes over 26 years. OBJECTIVES--To determine the prevalence of asthma in the past 12 months in Melbourne schoolchildren aged 7, 12, and 15 years and to compare the prevalence of a history of asthma with that of 26 years ago. DESIGN--A questionnaire on respiratory symptoms was distributed to children for completion by parents and return to the school. Subjects were selected by a stratified cluster design. SETTING--Government and non-government schools in the greater Melbourne area, Australia. SUBJECTS--10,981 children. Parents completed questionnaires for 3324 children aged 7, 2899 aged 12, and 2968 aged 15. The overall response rate was 90%. MAIN OUTCOME MEASURES--History of wheeze or asthma in the past 12 months and in lifetime. RESULTS--The prevalences of wheeze in the past 12 months were 23.1%, 21.7%, and 18.6% for 7, 12, and 15 year olds respectively. A history of wheeze was more common in boys than in girls at age 7 (443/1711 v 324/1614) and 12 (418/1767 v 322/1718) but not at age 15. Overall, 78% (1548) of those reporting wheeze also reported a history of asthma and 83% (1611) had used a bronchodilator. The prevalence of a history of asthma among 7 year olds was 46% compared with 19.1% in the 1964 survey, an increase of 141%. CONCLUSIONS--The current prevalence of asthma in Melbourne schoolchildren is high and has risen substantially over the past 26 years. 
'Role of bone marrow stromal cells in the growth of human multiple myeloma. We have verified the hypothesis that multiple myeloma (MM) may be disseminated by circulating clonogenic cells that selectively home to the bone marrow (BM) to receive the signal(s) leading to proliferation, terminal differentiation, and production of the osteoclast activating factors. Long-term cultures of stromal cells have been developed from the BM of nine patients with MM. These cells were mostly fibroblast-like elements, interspersed with a proportion of scattered macrophages and rare osteoclasts. BM stromal cells were CD54+, produced high levels of interleukin-6 (IL-6) and measurable amounts of IL-1 beta, and were used as feeder layers for autologous peripheral blood mononuclear cells (PBMC). After 3 weeks of cocultures, monoclonal B lymphocytes and plasma cells, derived from PBMC, developed and the number of osteoclasts significantly increased. Both populations grew tightly adherent to the stromal cell layer and their expansion was matched by a sharp increase of IL-6 and by the appearance of IL-3 in the culture supernatant. These data attribute to BM stromal cells a critical role in supporting the growth of B lymphocytes, plasma cells, and osteoclasts and the in vivo dissemination of MM. 
Irreducible inguinal hernia in children below two years of age Eighty-five cases of irreducible inguinal hernia in children below 2 years of age were reviewed. Non-operative treatment was successful in 71 (84 per cent); 14 children required emergency surgery. The younger the child and the longer the duration of symptoms at presentation, the worse was the outcome of non-operative treatment. In 35 (41 per cent) children the diagnosis of inguinal hernia had been made before irreducibility. There is an increased incidence of postoperative complication associated with irreducibility, especially in preterm infants. Early diagnosis of inguinal hernia in young children and prompt referral for surgery is recommended. 
Rickettsial meningitis and encephalitis. Nine of 72 patients with scrub typhus and three of 137 with murine typhus presented with meningitis and/or encephalitis syndromes. Focal neurologic signs were rare, and cerebrospinal fluid profiles were similar to those of leptospirosis and viral and tuberculous meningitis. One patient had papilledema, and another had cerebellitis. Other major organ involvement (renal, liver, or lungs) occurred in five patients. One patient died and four spontaneously recovered, while the conditions of the rest responded well to either chloramphenicol or doxycycline. Scrub and murine typhus should be included in the differential diagnoses of aseptic meningitis and encephalitis in patients exposed to endemic areas, especially when accompanied by renal insufficiency and/or jaundice. They are treatable forms of virallike meningoencephalitis. 
Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators BACKGROUND. Without strong evidence of benefit, the use of carotid endarterectomy for prophylaxis against stroke rose dramatically until the mid-1980s, then declined. Our investigation sought to determine whether carotid endarterectomy reduces the risk of stroke among patients with a recent adverse cerebrovascular event and ipsilateral carotid stenosis. METHODS. We conducted a randomized trial at 50 clinical centers throughout the United States and Canada, in patients in two predetermined strata based on the severity of carotid stenosis--30 to 69 percent and 70 to 99 percent. We report here the results in the 659 patients in the latter stratum, who had had a hemispheric or retinal transient ischemic attack or a nondisabling stroke within the 120 days before entry and had stenosis of 70 to 99 percent in the symptomatic carotid artery. All patients received optimal medical care, including antiplatelet therapy. Those assigned to surgical treatment underwent carotid endarterectomy performed by neurosurgeons or vascular surgeons. All patients were examined by neurologists 1, 3, 6, 9, and 12 months after entry and then every 4 months. End points were assessed by blinded, independent case review. No patient was lost to follow-up. RESULTS. Life-table estimates of the cumulative risk of any ipsilateral stroke at two years were 26 percent in the 331 medical patients and 9 percent in the 328 surgical patients--an absolute risk reduction (+/- SE) 17 +/- 3.5 percent (P less than 0.001). For a major or fatal ipsilateral stroke, the corresponding estimates were 13.1 percent and 2.5 percent--an absolute risk reduction of 10.6 +/- 2.6 percent (P less than 0.001). Carotid endarterectomy was still found to be beneficial when all strokes and deaths were included in the analysis (P less than 0.001). CONCLUSIONS. Carotid endarterectomy is highly beneficial to patients with recent hemispheric and retinal transient ischemic attacks or nondisabling strokes and ipsilateral high-grade stenosis (70 to 99 percent) of the internal carotid artery. 
Isolated atrial infarction in a patients with single vessel disease of the sinus node artery. Atrial infarction is found in approximately 17 percent of autopsy-proven cases of myocardial infarction, but is a frequently missed clinical diagnosis. The antemortem diagnosis of atrial infarction occurring in the absence of ventricular infarction has not been previously reported. We present a patient with ischemic chest discomfort associated with paroxysmal atrial fibrillation. Electrocardiographic and enzymatic changes were consistent with atrial infarction. Cardiac catheterization demonstrated single vessel critical stenosis at the origin of the sinus node artery. Combined atrial and ventricular infarction occurs frequently and should be considered in the setting of paroxysmal supraventricular arrhythmias occurring early in the course of ventricular myocardial infarction. Lone atrial infarction is a rare but distinct clinical entity. The tetrad of typical ischemic chest discomfort, paroxysmal supraventricular arrhythmia, P-Ta segment shifts, and elevated cardiac enzyme levels without evidence for ventricular infarction strongly suggests isolated atrial infarction. 
Alcohol consumption and risk of coronary heart disease. OBJECTIVE--To investigate the hypothesis that the apparent protective effect of habitual alcohol consumption on coronary heart disease is due to drinkers at high risk of coronary heart disease becoming non-drinkers. DESIGN--Case-control population based study. Data were obtained from interviews with patients with non-fatal myocardial infarction and their controls and with the next of kin of those who had died of coronary heart disease and their controls. SETTING--Auckland, New Zealand. SUBJECTS--Two groups of cases were studied. The first comprised 227 men and 72 women with non-fatal myocardial infarction identified from a population based surveillance programme for coronary heart disease; controls were 525 men and 341 women randomly selected from the same population group and matched for age and sex. The second group comprised 128 men and 30 women who had died of coronary heart disease and had been identified from the surveillance programme; controls were a sample of the previous control group and comprised 330 men and 214 women matched for age and sex. All participants were aged 25-64 years and without diagnosed coronary heart disease. MAIN OUTCOME MEASURES--Regular alcohol consumption; high density lipoprotein cholesterol and low density lipoprotein concentrations. RESULTS--Men with myocardial infarction and men who had died of coronary heart disease were more likely to have been never drinkers (had never drunk more than once a month) than controls (18% v 12% and 23% v 13% respectively). After possible confounding factors had been controlled for, people in all categories of drinking (up to more than 56 drinks per week) had at least a 40% reduction in risk of fatal and non-fatal coronary heart disease compared with never drinkers. Former drinkers also had a lower risk of non-fatal myocardial infarction than never drinkers (relative risks 0.41 and 0.10 in men and women respectively) but a similar risk of death from coronary heart disease. The reduction in risk was consistently greater in women than in men in all drinking categories but there was no clear dose-response effect in either sex. CONCLUSIONS--The results support the hypothesis that light and moderate alcohol consumption reduces the risk of coronary heart disease. This protective effect in this population was not due to the misclassification of former drinkers with a high risk of coronary heart disease as non-drinkers. 
Corticobasal degeneration. A unique pattern of regional cortical oxygen hypometabolism and striatal fluorodopa uptake demonstrated by positron emission tomography. Corticobasal degeneration presents with an asymmetric akinetic-rigid syndrome, apraxia and combinations of supranuclear gaze palsy, myoclonus, and an alien limb. Six patients aged 59-77 yrs, diagnosed on clinical criteria as having corticobasal degeneration, have been studied with positron emission tomography using tracers of dopamine storage capacity and oxygen metabolism. Striatal 18F-6-fluorodopa uptake was reduced in an asymmetric pattern, caudate and putamen being involved in all cases. Uptake into medial frontal cortex was also impaired. Regional cortical oxygen metabolism was most significantly depressed in the superior and posterior temporal, inferior parietal, and occipital associated cortices. Within the frontal lobe, the hypometabolism was chiefly posterior. This unique combination of regional hypometabolism and disruption of the nigrostriatal system is discussed in relation to the clinical features of the disease and is compared with reported findings in other disorders of cognition and movement. 
Trends in use of coronary angiography in subacute phase of myocardial infarction. BACKGROUND. Most patients do not undergo acute reperfusion after myocardial infarction, and which of these patients should undergo coronary angiography is still debated. METHODS AND RESULTS. We analyzed the 1-year clinical outcomes and rates of coronary angiography performed as late as 60 days after myocardial infarction in 3,804 patients admitted between 1979 and 1988 and followed in six different centers. Patients less than 75 years old were classified into low-, medium-, and high-risk groups using a multivariate analysis of historical and clinical variables gathered during the first 8 hospital days. Patients who underwent early reperfusion (17%, all after 1984) were analyzed separately. To analyze time trends, patients were compared before and after mid-1984. Mortalities from day 9 through 1 year were similar for the two time periods in the low- (3.3% versus 2.5%) and medium-risk (7.4% versus 5.6%) groups, but mortality was lower for the high-risk group after 1984 (31.6% versus 20.0%). The proportion of patients undergoing coronary angiography increased dramatically in each group after 1984 (low risk, 18% versus 48%; medium risk, 23% versus 49%; high risk, 10% versus 32%, before and after 1984, respectively). Furthermore, a large percentage of patients (more than 40%) in the low-risk group did not have at least one of the indications for coronary angiography recently recommended by a joint task force. Among patients undergoing coronary angiography, the proportion of patients with three-vessel coronary artery disease decreased after 1984, whereas the proportion undergoing mechanical revascularization in the year after infarction increased in all risk groups. CONCLUSIONS. Despite the recent development of noninvasive techniques with high sensitivity for detecting high-risk patients after myocardial infarction, coronary angiography is being performed increasingly in all patients, including those determined to be at low risk for complications based on clinical data. The economic consequences of such a trend could be considerable, and its impact requires careful analysis. 
Gastric carcinoma in patients with Crohn disease: report of four cases. An association between Crohn disease and gastric carcinoma has not been described before. However, we report four patients with documented Crohn disease in whom gastric carcinoma developed later. In three of the four patients, onset of Crohn disease occurred after the age of 40. All of the patients had nonspecific constitutional symptoms and/or complaints referable to the upper gastrointestinal tract. No clinical evidence of active Crohn disease was present. In each patient, barium examination and CT showed either a mass (two cases) or other radiologic features of malignancy (two cases). Endoscopy with biopsy was performed in three patients and findings were misleading in two patients. The possibility of an increased risk of malignancy in sites remote from inflamed bowel segments has been reported. The findings in this study suggest that patients with Crohn disease, particularly disease of late onset, may be predisposed to the development of gastric carcinoma. 
Use of recombinant human interleukin-2 in conjunction with syngeneic bone marrow transplantation in mice as a model for control of minimal residual disease in malignant hematologic disorders. Unlike allogeneic bone marrow transplantation (BMT), autologous BMT is not accompanied by immune-mediated graft-versus-leukemia (GVL) effects; hence, the relapse rate observed after autologous BMT in malignant hematologic disorders is higher than that observed after allogeneic BMT. Autologous BMT represents a much safer medical procedure available for many patients in need in situations where allogeneic BMT is not feasible or risky. The present experiments were designed to investigate whether it might be possible to combine the therapeutic benefits of autologous BMT with additional immunotherapy after BMT. The tumor model used for investigating GVL effects was the murine B-cell leukemia (BCL1), a spontaneous, nonimmunogenic, highly lethal leukemia of BALB/c origin. BALB/c mice inoculated with 10(3) BCL1 leukemia cells were treated on day-1 with cyclophosphamide 100 mg/kg and transplanted with normal syngeneic BM cells on day 0. High-dose recombinant interleukin-2 (rIL-2) (100,000 Cetus units x 3/day intraperitoneally x 5 consecutive days) was initiated on day +1, +7, or +21 after BMT. Kinetics of lymphocyte reconstitution after syngeneic BMT indicated a steep increase in the absolute number of peripheral blood lymphocytes on days 17 through 24. All experimental groups were observed for relapse. Mice receiving no rIL-2 therapy relapsed and died within 50 days after BMT, whereas mice receiving rIL-2 showed long-term disease-free survival. Optimal time for administration of rIL-2 was noted at 3 weeks post-BMT, with 90% of the mice surviving with no evidence of disease for more than 1 year. Similarly, when 10(4) BCL1 cells were given 1 day after syngeneic BMT to simulate minimal residual disease after syngeneic BMT, rIL-2 therapy administered at 14 days post-BMT seemed effective in prolonging disease-free survival in contrast to the same regimen given at 1 day after BMT. Our data suggest that immunotherapy with rIL-2 should be further investigated as a new immunotherapeutic tool for decreasing the relapse rate after BMT for hematologic malignancies. 
A rare cause of nasal obstruction: a solitary neurofibroma. This case represents a peripheral nerve sheath tumor as a cause of nasal obstruction. Nerve sheath tumors are relatively uncommon; however, most otolaryngologists will encounter them. These tumors develop from cranial and spinal nerve roots and from peripheral nerves. In total, approximately 25% to 44% of nerve sheath tumors occur in the head and neck region. Although the most important are cranial nerve tumors--the majority being acoustic neuromas arising from the vestibular nerve--they may also develop in the nasal cavity. 
Cocaine-induced myocardial infarction. A growing threat to men in their 30s. A clear association has been established between cocaine use and acute myocardial infarction. Because of the continuing rise in cocaine use in the United States, many more young patients have or will have this disorder. Such patients are usually managed conservatively with calcium channel blockade and have an excellent in-hospital prognosis. If chest pain recurs or stress testing reveals evidence of ischemia, cardiac catheterization should be done. If cocaine use is discontinued, the long-term prognosis of a typical patient with cocaine-induced acute myocardial infarction is excellent in the absence of other chronic illnesses. 
Ambulatory stab evulsion phlebectomy for truncal varicose veins. The management of primary varicose veins is evolving. Recovery time, cost, recurrence rate, and cosmesis are critical determinants. Classic "high ligation" and ankle-to-groin stripping is expensive, results in a long convalescence, and may produce unacceptable scarring and possible permanent nerve injury. This report describes the technique of stab evulsion phlebectomy performed in an outpatient setting. Under loco-regional anesthesia, and after high ligation, existing tributary and trunk varicosities are evulsed with specially designed hooks. The multiple stab incisions, 1.5- to 3-mm long, are closed with adhesive strips. Fifty-six patients, with 69 involved limbs, have been operated on during the past 9 months. Postoperative pain and complications were minimal. Convalescence was eliminated and all patients immediately resumed normal daily activities. Cosmesis was excellent. This technique is based on hemodynamically accurate principles. It effectively removes all varicosities, eliminates the proximal source of reflux, and disconnects potentially outflowing perforators, yet leaves in situ undamaged trunk veins, which may be used as potential vein grafts. 
Transcriptional regulation of c-jun gene expression by arabinofuranosylcytosine in human myeloid leukemia cells. Previous studies have demonstrated that 1-beta-D-arabinofuranosylcytosine (ara-C) induces terminal differentiation of human myeloid leukemia cells. Other studies have shown that the c-jun protooncogene is expressed during phorbol ester-induced myeloid differentiation. This work examines the effects of ara-C on c-jun gene expression in human KG-1 myeloid leukemia cells. The results demonstrate that c-jun transcripts are undetectable in uninduced KG-1 cells and that ara-C induces expression of this gene in a concentration- and time-dependent manner. Ara-C treatment was also associated with increases in c-jun transcripts in U-937, THP-1, and HL-60 myeloid leukemia cells. Furthermore, transcriptional run-on analysis has demonstrated that exposure to ara-C increases the rate of c-jun gene transcription. The results also demonstrate that while inhibition of protein synthesis superinduces c-jun mRNA levels in phorbol ester-treated KG-1 cells, cycloheximide had no effect on the induction of c-jun transcripts during ara-C treatment. Moreover, the half-life of c-jun transcripts in ara-C-treated KG-1 cells was 42 min. These findings suggest that the increase in c-jun mRNA observed during ara-C treatment is regulated by a transcriptional mechanism, and that c-jun may be involved in the induction of differentiation and regulation of gene expression by ara-C. 
Proenkephalin A in bone-derived cells. Enkephalins, a group of small peptides with opiate-like activity, have been defined originally as neuropeptides. Recent reports showed, using in situ hybridization, that the enkephalin-encoding gene, proenkephalin A (pEnkA), is expressed in nondifferentiated cells of diverse mesodermal lineages. The transient expression of pEnkA in these tissues during organogenesis suggests that this gene is involved in processes such as differentiation and/or cell proliferation. In situ hybridization revealed that bone and cartilage are among the tissues that express pEnkA most actively during organogenesis. Here we show that pEnkA mRNA is abundant in normal calvaria-derived cells and in osteosarcoma-derived cell lines ROS 17/2.8 and ROS 25/1. In addition, pEnkA-derived peptides are synthesized and secreted by these cells, as revealed by specific RIA. pEnkA expression in ROS cells is decreased by osteogenin, an osteoinductive factor, and by the calcium-regulating hormone, 1,25-dihydroxyvitamin D3, whereas the osteoblastic phenotype marker, alkaline phosphatase, is increased by these factors. These results together with the inhibitory effects of pEnkA-derived peptides on alkaline phosphatase activity in ROS 17/2.8 cells suggest that pEnkA is involved in bone development and provide a model system for further analysis of pEnkA expression during this process. 
Rocker-soled shoes and walking distance in patients with calf claudication. Calf claudication is the major clinical manifestation of peripheral vascular occlusive disease in a significant number of patients. Although claudication causes substantial patient disability, most patients are treated conservatively because of the risks of surgical therapy and the uncertain efficacy of drug therapy. It was hypothesized that rocker-soled shoes would decrease the work of the plantar flexors and therefore increase walking distance in patients with calf claudication. To test this hypothesis, walking distances in patients with calf claudication using rocker-soled shoes and a placebo shoe insert were compared. Rocker-soled shoes significantly increased both the total distance walked and the distance at which patients were initially bothered by symptoms by 77m (37%, p less than .0005) and 89m (91%, p = .003), respectively. It was concluded that rocker-soled shoes may reduce disability in patients with calf claudication by increasing walking distance. 
Sympathetic neural control of vascular muscle in reduced renal mass hypertension. Vascular smooth muscle (VSM) transmembrane potentials (Em) were measured in situ in small branch arteries (150-300-microns o.d.), small branch veins (300-400-microns o.d.), arterioles (90-150-microns o.d.), and venules (80-250-microns o.d.) in the mesenteric and gracilis muscle and the arterioles and venules of cremaster muscle vascular beds in anesthetized rats with reduced renal mass hypertension (HT-RRM) and normotensive sham-operated RRM control rats. All rats were given a 4% NaCl diet for 2 weeks with water ad libitum. Relative to sham, HT-RRM mesenteric and gracilis arterial and venous vessels, but not the microvessels of the cremaster muscle bed, were less polarized during superfusion with normal physiological salt solution. Also relative to sham, hyperpolarization responses to local sympathetic neural (SNS) denervation with 6-hydroxydopamine were greater in mesenteric and gracilis small arteries, arterioles, veins, and venules but not in cremaster microvessels. The immediate (less than 5-minute) electrogenic depolarization response to local blockade of VSM Na(+)-K+ pump activity with 10(-3) M ouabain was similar between each respective HT-RRM and sham vessel pair in each vascular bed. 
Effects of hypothermia and hyperthermia on the reactivity of rat intracerebral arterioles in vitro. The effects of hypothermia and hyperthermia on the cerebral microcirculation were studied using isolated perfused intracerebral (parenchymal) arterioles obtained from rats. In a temperature-dependent manner, hypothermia (20.0 degrees to 35.0 degrees C) dilated the spontaneous tone developed by the arterioles and also diminished their contractile response to potassium and prostaglandin F2 alpha. In contrast, hyperthermia (40.0 degrees to 45.0 degrees C) induced a biphasic response consisting of initial vasoconstriction and secondary vasodilation. Exposure of the vessels to 45.0 degrees C for 30 minutes irreversibly abolished the spontaneous tone and responsiveness of the arterioles when the temperature of the preparation was returned to 37.5 degrees C. In calcium-free solutions, however, the arteriolar diameter was not affected within a temperature range of 20.0 degrees to 45 degrees C. Furthermore, arterioles that had been in a calcium-free solution during exposure to 45 degrees C temperature recovered their viability at 37.5 degrees C. These results suggest that changes in ambient temperature alter calcium-induced contraction in arteriolar smooth muscle, and that the irreversible effects of hyperthermia on the arterioles are dependent upon extracellular calcium. These studies indicate that alterations in brain temperature may affect the pathogenesis of cerebral ischemia by mechanisms that are in part independent of parenchymal metabolism. 
Dynamic tracking of cardiac vulnerability by complex demodulation of the T wave. A link is found between T wave alternans and vulnerability to ventricular fibrillation, and a new approach is provided for quantification of susceptibility to malignant arrhythmias. Complex demodulation reveals that alternation of the electrocardiogram is concentrated during the first half of the T wave, coinciding with the vulnerable period of the cardiac cycle. During myocardial ischemia and reperfusion, there are marked increases in the degree of T wave alternans that parallel the established time course of changes in vulnerability. The influence of the sympathetic nervous system in arrhythmogenesis is also accurately detected. Ultimately, complex demodulation of the electrocardiogram could provide a technique for identification and management of individuals at risk for sudden cardiac death. 
Balloon dilation of postsurgical subaortic obstruction. Two children aged 10 and 5.5 years underwent balloon dilation for postsurgical subaortic obstruction. The outcome and the role of this procedure are discussed. 
Post stenotic aneurysm in popliteal artery entrapment syndrome. In a retrospective review of 74 cases of Popliteal Entrapment Syndrome collected over a 16 year period, 10 cases of aneurysm were found (13.5%). This represents an incidence of 26% of the 38 cases of popliteal aneurysm of any etiology seen during the same period of time. In contrast to atherosclerotic aneurysms, these aneurysms were seen in a young age group (21-30 years of age) and all were associated with popliteal entrapment. Evidence is presented to support our opinion that these aneurysms are post-stenotic in origin. We feel that young adults with symptoms of leg ischaemia and evidence of an aneurysm of the popliteal artery should be investigated for popliteal entrapment and treated before complications occur. We have found a posterior approach to be the most satisfactory method of exploring the popliteal fossa. 
A prospective study of liver function in infants and children exposed to daily isoflurane for several weeks. Eleven infants and children presenting for daily radiotherapy for a period of at least 2 weeks were anaesthetised with isoflurane in 33% oxygen and nitrous oxide. They were unpremedicated and given no other agents to supplement anaesthesia. The average number of exposures was 24 (SD 11; range 10-39) and the total anaesthetic time per exposure varied between 15 and 30 minutes. Liver function was assessed by determining serum total bilirubin, aspartate amino transferase, gamma glutamyl transferase and alkaline phosphatase before the start of treatment and at 5-daily intervals thereafter. There was no measurable change in any of these determinants of liver function. All children accepted daily induction of anaesthesia with isoflurane. Induction, maintenance and recovery from anaesthesia were uncomplicated. 
FK 506 ameliorates the hepatic injury associated with ischemia and reperfusion in rats. The effect of FK 506 on regeneration of the liver was studied in rats after a two-thirds partial hepatectomy after 60 min of ischemia of the unresected liver. The animals were divided into three distinct groups of 10 rats each. Group 1 (controls) received 0.5 ml saline solution intravenously 30 min after the induction of ischemia. Groups 2 and 3 were injected with FK 506 (0.3 mg/kg) intravenously 30 min after and 24 min before the induction of hepatic ischemia, respectively. The hepatic content of ATP and serum levels of ALT and lactate dehydrogenase were determined on each animal. In addition, the histological appearance and mitotic activity of the remnant liver was determined at regular 24-hr intervals after hepatic ischemia. All 10 control animals died within 72 hr. Treatment with FK 506 resulted in improved survival in groups 2 and 3 (30% and 80%, respectively). The improved survival seen in the FK 506-treated animals was reflected by a restoration of hepatic ATP content, a reduction in the serum levels of ALT and lactate dehydrogenase, an amelioration of hepatic necrosis and neutrophilic infiltration and an increase in the mitotic activity of the liver. These results suggest that FK 506 ameliorates the hepatic injury associated with ischemia/reperfusion and has a potent stimulatory effect on liver cell regeneration that may make it valuable as a hepatoprotective agent when administered to organ donors before graft harvesting. 
Synthesis of C1 inhibitor in fibroblasts from patients with type I and type II hereditary angioneurotic edema. Patients with hereditary angioneurotic edema (HANE) have serum levels of functionally active inhibitor of the first component of complement (C1 INH) between 5 and 30% of normal, instead of the 50% expected from the single normal allele. Increases in rates of catabolism have been documented in patients with HANE and certainly account for some of decrease in C1 INH level. A possible role for a decrease in synthesis of C1 INH in producing serum levels of C1 INH below the expected 50% of normal has not been well studied. We studied the synthesis of C1 INH in skin fibroblast lines, which produce easily detectable amounts of C1 INH. In type I HANE cells, C1 INH synthesis was 19.6 +/- 4.0% (mean +/- SD) of normal, much less than the 50% predicted. In type II HANE cells, the total amount of C1 INH synthesis (functional and dysfunctional) was 98.9 +/- 17% of normal; the functional protein comprised 43% of the total. Thus, type II HANE cells synthesized functional C1 INH at a much greater rate than for the type I cells. In both type I and II HANE cells, amounts of steady-state C1 INH mRNA levels paralleled rates of C1 INH synthesis, indicating that control of C1 INH synthesis occurred at pretranslational levels. Both type I and type II fibroblasts synthesized normal amounts of C1r and C1s. These data suggest that the lower than expected amounts of functionally active C1 INH in type I HANE may be due, in part, to a decrease in rate of synthesis of the protein, and that the expressions of the normal C1 INH allele in HANE is influenced by the type of abnormal allele present. 
Orbital exenteration with eyelid sparing: indications, technique, and results. Of 22 orbital exenterations performed from January 1980 to December 1989, 16 were performed by an eyelid-sparing technique, and six were allowed to heal by spontaneous granulation. Reviewing these procedures, we conclude that the eyelid-sparing method is indicated mainly for advanced primary orbital malignancies and for certain secondary orbital malignancies such as orbital extension of uveal melanoma, conjunctival melanoma, and conjunctival squamous cell carcinoma. It is not usually applicable to orbital invasion of malignant eyelid tumors such as basal cell carcinoma and sebaceous gland carcinoma. Advantages of the eyelid-sparing method are more rapid healing and earlier fitting of a prosthesis. 
Carotid cavernous fistula after minimal facial trauma. Report of a case. The carotid cavernous fistula has historically been associated with extensive facial trauma as a result of direct or indirect forces. Most fistulas of traumatic origin develop as a result of a fracture through the base of the skull, which produces a force causing laceration of the internal carotid artery in the region where it approximates the cavernous sinus. We report a case in which apparently minimal head trauma resulted in the development of a carotid cavernous fistula. The rather innocuous presentation of this complication requires particular attention by the caregiver in assessing the patient sustaining maxillofacial trauma. 
Outcome of patients with acute myocardial infarction who are ineligible for thrombolytic therapy. OBJECTIVE: To determine what proportion of patients with acute myocardial infarction are not eligible for thrombolytic therapy and to assess their natural history. DESIGN: Retrospective chart review. SETTING: A large community-based hospital. PATIENTS: All patients with acute myocardial infarction hospitalized during a 27-month period. MEASUREMENTS: Of 1471 patients with acute myocardial infarction, 230 (16%) received thrombolytic therapy according to the protocol and an additional 97 (7%) received nonprotocol thrombolytic therapy, primary coronary balloon angioplasty, or both because of contraindications. The other 1144 patients (78%) did not receive reperfusion therapy. MAIN RESULTS: The patients who did not receive thrombolytic therapy were older, more likely to be women, and more likely to have a history of hypertension, previous myocardial infarction, or chronic angina (all comparisons, P less than 0.002). An average of 1.9 reasons for exclusion were identified per patient among the ineligible patients. Mortality was fivefold higher among ineligible patients (19%; Cl, 16% to 21%) than among protocol-treated patients (4%; Cl, 1% to 6%) (P less than 0.001). In-hospital mortality rates for excluded patients were 28% (Cl, 23% to 32%) in elderly patients (age, greater than 76 years; n = 396); 29% (Cl, 23% to 35%) in patients with stroke or bleeding risk (n = 209); 17% (Cl, 14% to 20%) in patients with delayed presentation (greater than 4 hours after the onset of chest pain; [n = 599]); 14% (Cl, 11% to 16%) in patients with an ineligible electrocardiogram (ECG) (n = 673); and 26% (Cl, 21% to 32%) in patients with a miscellaneous reason for exclusion (n = 243). Independent predictors of increased mortality were: age greater than 76 years, stroke or other bleeding risk, ineligible ECG, or the presence of two or more exclusion criteria. CONCLUSIONS: Thrombolytic therapy is currently used in the United States for only a minority of patients with acute myocardial infarction: those who have low-risk prognostic characteristics. 
Patellofemoral pain caused by overactivity. A prospective study of risk factors in infantry recruits. A prospective study of 390 infantry recruits revealed that the medial tibial intercondylar distance and that the isometric strength of the quadriceps, tested at 85 degrees of flexion of the knee, had a statistically significant correlation with the incidence of patellofemoral pain caused by overactivity. Increased medial tibial intercondylar distance and increased strength of the quadriceps were therefore deemed to be risk factors for this syndrome. 
Effect of intrathoracic pressure on plasma arginine vasopressin levels. Abdominal distention during pneumoperitoneum results in a marked increase in plasma arginine vasopressin levels, which has been ascribed to an increase in intrathoracic pressure. Because of this relationship, tense ascites could contribute to nonosmotic release of antidiuretic hormone, to the development of hyponatremia, and eventually to further ascites formation. The effect of pneumoperitoneum, thoracocentesis, and paracentesis on plasma arginine vasopressin levels was studied in three groups of patients, and the mechanism by which these maneuvers may induce these changes was investigated. Patients with pleural effusion, pneumothorax, or ascites showed a significant increase in plasma arginine vasopressin levels, and thoracocentesis or paracentesis resulted in a decrease in these levels. Plasma vasopressin levels increased significantly during pneumoperitoneum, as did intrathoracic and atrial pressures; the atrial transmural pressure gradient declined. However, no changes in plasma levels of norepinephrine, aldosterone, and renin activity were observed during pneumoperitoneum. Changes in plasma arginine vasopressin levels correlated with the changes in intrathoracic and atrial pressures and transmural pressure gradient. The authors conclude that increased intrathoracic pressure is associated with an increase in plasma arginine vasopressin levels and propose that ascites could be a factor promoting vasopressin release by acting on intrathoracic volume receptors in decompensated cirrhotics. 
Toxic effects of cisplatin alone and in combination with gentamicin in stria vascularis of guinea pigs. The toxic effects on the stria vascularis of treatment with cisplatin alone and combined with the aminoglycoside antibiotic, gentamicin, were studied in guinea pigs. The toxicity induced in albino and pigmented guinea pigs was investigated morphologically with light and transmission electron microscopy, and functionally by brainstem-evoked response audiometry. The results of hearing thresholds were variable, ranging from no change in one ear in some of the animals to a hearing loss of 20 dB in one or both ears when treated with low-dose cisplatin alone or in combination with gentamicin. Bilateral deafness resulted from high-dose cisplatin combined with gentamicin. The combined treatment produced prominent structural damage in the stria vascularis. The results should be considered when aminoglycoside therapy is required in conjunction with cisplatin. 
Malignant melanoma arising in a dermoid cyst of the ovary. Autopsy findings of primary malignant melanoma arising in an ovarian dermoid cyst in an 86-year-old woman are presented. The right ovary was replaced by a dermoid cyst, 14 x 9 x 9 cm in size, in which several nodular tumors with diameters less than 3.2 cm were localized. They comprised diffusely proliferating anaplastic cells with prominent nucleoli. Some of them contained melanin pigments in the cytoplasm. The tumor cells were positive for S-100 protein and ultrastructurally showed melanosomes. In addition, several benign pigmented lesions resembling dermal nevus, pigmented schwannoma, or cellular blue nevus were present in the dermoid cyst, one of which contained a malignant melanomatous component. Histologic transition between benign and malignant components and the presence of another small focus of atypical melanocytes in the benign lesion suggested that the malignant melanoma arose in close association with the previously existing benign pigmented lesions in the dermoid cyst. 
Elective coronary artery bypass surgery without homologous blood transfusion. Early results with an inexpensive blood conservation program. Restriction of donor blood transfusions in cardiac surgery should reduce risks of infective contamination and antigenicity. We report a systemic, simple and inexpensive blood conservation program used for 121 consecutive patients who underwent elective coronary artery bypass surgery without need for homologous blood transfusion. The left internal mammary artery was grafted in all cases, in addition to saphenous vein grafts. Autologous, heparinized blood was removed intraoperatively, pre-bypass, and returned to the patient at conclusion of the extracorporeal circulation. The volume remaining in the oxygenator and the tubing set was returned without cell processing or hemofiltration. Using the hard-shell cardiotomy reservoir from the heart-lung machine, autotransfusion of the shed mediastinal blood was continued hourly up to 18 hours after surgery. The mean postoperative mediastinal bleeding was 551 +/- 206 ml, of which 505 +/- 218 ml was autotransfused. No re-exploration for bleeding was required and no homologous red-cell transfusions were given. Five patients each received 1-2 units of fresh frozen plasma because of prolonged bleeding time. Morbidity was low and mortality nil. At discharge the mean hemoglobin was 12.0 +/- 1.4 g/dl and the hematocrit 36.0 +/- 4.2%. 
Insect paralysis by baculovirus-mediated expression of a mite neurotoxin gene. Female mites of the species Pyemotes tritici inject an extremely potent venom into their insect prey that causes muscle-contraction and paralysis. These mites are able to paralyse insects 150,000 times their size and their venom is effective in a broad range of insect species. A toxin (TxP-I) associated with the mite venom apparatus causes immediate muscle-contractive paralysis when injected into insects but not mice. In this report, we describe the cloning, sequencing and expression of a complementary DNA (Tox-34) encoding TxP-I. Insect cells infected with a recombinant baculovirus (vEV-Tox34) expressing Tox-34 secrete three polypeptides related to TxP-I which cause paralysis on injection. Larvae infected with vEV-Tox34 become paralysed during infection, thus reflecting the potential application of this toxin gene in insect biocontrol methods. The toxin gene expression system will also allow further exploration of the neurophysiological basis of its insect-specific effects. 
Vogt-Koyanagi-Harada syndrome. Clinical course, therapy, and long-term visual outcome. We reviewed data from 26 patients with Vogt-Koyanagi-Harada syndrome who presented at the Bascom Palmer Eye Institute between March 1969 and February 1990. Visual outcomes were good, with final visual acuity of better than 20/30 in 29 (66%) of 44 eyes and of worse than 20/400 in only three (7%) of 44 eyes. A poor prognosis was associated with the development of choroidal neovascular membranes or chronic uveitis. All patients were treated with systemic corticosteroids. Corticosteroid therapy averaged 6 months, but was prolonged (48 months) in patients who developed chronic uveitis. Disease recurred in nine (43%) of 21 patients in the first 3 months, usually in association with a rapid tapering of steroid dosage. We recommend the early, aggressive use of systemic corticosteroids in patients with Vogt-Koyanagi-Harada syndrome and a gradual tapering of drug dosage for 6 months after presentation. 
Splenosis presenting as a left renal mass indistinguishable from renal cell carcinoma. Splenosis following splenic trauma is a common but underdiagnosed entity before surgical exploration. In all previously reported cases the ectopic splenic tissue was distinctly separate from the kidney. To our knowledge we report the first known case in which the splenic tissue was located in direct apposition with the kidney. Using conventional imaging techniques, including renal ultrasonography, abdominal computerized tomography and selective renal arteriography, this ectopic splenic tissue appeared to be part of the left kidney and was indistinguishable from renal cell carcinoma. The pathophysiology, clinical presentation and diagnostic studies of splenosis are reviewed. 
Metabolic consequences of (regional) total pancreatectomy. Little information has been reported on the metabolic characteristics of the totally pancreatectomized patient or the efficacy of medical management after radical pancreatic surgery. The prospective evaluation of 49 such patients, with 31% followed for 48 or more months, forms the basis of this report. The major immediate postoperative challenge is control of diarrhea and weight stabilization. Chronically patients have an increased daily caloric requirement (mean +/- SE, 56 +/- 1 kcal/kg), not wholly explained by moderate steatorrhea (fecal fat excretion, 16% +/- 2% of unrestricted fat intake). Despite persistent malabsorption, deficiencies in fat-soluble vitamin, magnesium, and trace element serum levels can be prevented in most patients. Pancreatogenic diabetes is characterized by (1) absence of the major glucoregulatory hormones insulin and glucagon, (2) instability, and (3) frequent hypoglycemia, with the latter parameters improving with rigorous home glucose monitoring. No patient has developed clinically overt diabetic micro- or macrovascular disease. Performance status in long-term survivors has been reasonable. However adverse chronic sequelae of the operation occur and include an unusual frequency of liver disease, characterized by accelerated fatty infiltration, and osteopenia, with an 18% reduction in radial bone mineral content noted in pancreatectomized patients studied more than 5 years after surgery. 
Correlation of nuclear morphometry and DNA ploidy in rectal cancer. Several investigators have used morphometric measurements to determine differences in the nuclear size and shape of normal and neoplastic colorectal tissue. Changes in nuclear morphometric parameters have also been shown to correlate with prognosis in a variety of noncolorectal cancers. The association of nuclear morphometry with prognostic indicators in rectal cancer has not been well studied. Measurements of the nuclear area, perimeter, longest cord, and circularity factor from 39 primary rectal adenocarcinomas were compared with DNA content, degree of tumor differentiation, Dukes' class, and patient survival. Nuclear circularity was found to correlate with DNA ploidy. Nondiploid tumors with a DNA index greater than 1.3 had significantly more circular nuclei than tumors with diploid or near-diploid DNA content. There was no correlation between nuclear morphometry and Dukes' class or patient survival. Significant increases in DNA content of rectal cancers appear to be reflected by measurable changes in nuclear shape. Nuclear morphometric measurements may provide useful information in the study of the progression of neoplastic changes in colorectal cancer. 
Chondrosarcoma of the parapharyngeal space. Chondrosarcoma is rarely found arising in the head and neck region. An unusual case arising in the parapharyngeal space in a male is reported and the differential diagnosis, pathology and treatment are discussed. 
Coronary angioplasty in single-vessel complex lesions: short- and long-term outcome and factors predicting acute coronary occlusion. Percutaneous transluminal coronary angioplasty (PTCA) of complex coronary lesions (plaque ulceration and/or thrombus) has an increased risk of procedural complications. To assess the influence of these angiographic features on immediate and long-term results of PTCA, we prospectively compared the success rate, incidence of procedural complications, and restenosis rate in two groups of patients selected on the basis of the presence (study group = 30 patients) or absence (control group = 200 patients) of complex morphology at the time of angioplasty. The two groups were similar with regard to extent of coronary artery disease and site of coronary stenosis. Patients in the study group had a higher incidence of periprocedural acute coronary occlusion (47% vs 6%; p less than 0.01), which in 78% of the cases was successfully treated with repeat angioplasty and intracoronary thrombolysis. Univariate correlates of this complication were Canadian Cardiovascular Society class IV (57% vs 19%; p less than 0.05) and recent (less than 30 days) onset of worsening of symptoms (71% vs 31%; p less than 0.05). The incidence of acute myocardial infarction was slightly higher in the study group (6.7% vs 2%; p = NS), and the success rate with redilatation was the same (90%). Clinical and angiographic follow-up data were obtained from all patients in whom the procedure was successful; the restenosis rate was 55% in the study group compared with 36% in the control group (p less than 0.05). 
Intravascular ultrasound imaging of human coronary arteries after percutaneous transluminal angioplasty: morphologic and quantitative assessment. An intravascular ultrasound catheter system was used in patients to assess the effect of percutaneous transluminal coronary angioplasty. In 14 out of 16 patients, the intravascular ultrasound catheter could be successfully advanced to the site of a previous dilatation. Qualitative assessment of the cross-sectional images revealed intimal thickening and an increase of ultrasound reflectance and calcification at atherosclerotic coronary arteries. A disruption of the obstructing plaque and evidence for local dissections (11 of 14 cases) were observed after angioplasty. The quantitative comparison between angiography and the ultrasound measurement showed a close correlation for vessel sites distant to the dilatation (r = 0.91 for vessel diameter; r = 0.86 for luminal area; p less than 0.001). After angioplasty, the quantitative evaluation of the dilated area was possible in 11 cases. The correlation of angiographic and sonographic measurements of these segments was good for the assessment of the vessel diameter (r = 0.82, p less than 0.001), but poor for the determination of the luminal area (r = 0.48, p = 0.10). This difference reflected the complex morphology of the vessel lumen after angioplasty, which would be better assessed by the cross-sectional sonographic technique than by contrast angiography. The intravascular imaging of coronary arteries provides a new and unique method to obtain information on the plaque morphology and composition, and to assess the local effects of interventional procedures and their complications. 
Smoking and mortality among older men and women in three communities. BACKGROUND. Although cigarette smoking is the leading avoidable cause of premature death in middle age, some have claimed that no association is present among older persons. METHODS. We prospectively examined the relation of cigarette-smoking habits with mortality from all causes, cardiovascular causes, and cancer among 7178 persons 65 years of age or older without a history of myocardial infarction, stroke, or cancer who lived in one of three communities: East Boston, Massachusetts; Iowa and Washington counties, Iowa; and New Haven, Connecticut. At the time of the initial interview, prevalence rates of smoking in the three communities ranged from 5.2 to 17.8 percent among women and from 14.2 to 25.8 percent among men. During five years of follow-up there were 1442 deaths, 729 due to cardiovascular disease and 316 due to cancer. RESULTS. In both sexes, rates of total mortality among current smokers were twice what they were among participants who had never smoked. Relative risks, as adjusted for age and community, were 2.1 among the men (95 percent confidence interval, 1.7 to 2.7) and 1.8 among the women (95 percent confidence interval, 1.4 to 2.4). Current smokers had higher rates of cardiovascular mortality than those who had never smoked (as adjusted for age and community, the relative risk was 2.0 [95 percent confidence interval, 1.4 to 2.9] among the men and 1.6 [95 percent confidence interval, 1.1 to 2.3] among the women), as well as increased rates of cancer mortality (relative risk, 2.4 [95 percent confidence interval, 1.4 to 4.1] among the men and 2.4 [95 percent confidence interval, 1.4 to 3.9] among the women). In both sexes, former smokers had rates of cardiovascular mortality similar to those of the participants who had never smoked, regardless of age at cessation, whereas the rates for all cancers, as well as smoking-related cancers, remained elevated among men who had once smoked. CONCLUSIONS. Our prospective findings indicate that the mortality hazards of smoking extend well into later life, and suggest that cessation will continue to improve life expectancy in older people. 
Tissue polypeptide antigen activity in cerebrospinal fluid: a marker of central nervous system metastases of breast cancer. Tissue polypeptide antigen (TPpA) in the cerebrospinal fluid (CSF) was measured in 59 consecutive breast cancer patients with suspected central nervous system (CNS) metastases. Subsequently, we determined that 13 patients had parenchymal brain metastases, 10 had leptomeningeal carcinomatosis, and 36 had no CNS involvement. The concentration of TPpA, which is a nonspecific marker for cell proliferation, was significantly higher in patients with CNS metastases than in those without it (P less than .0001; Mann-Whitney test). A tentative cutoff value for CNS metastases was set at 95 U/L TPpA; the upper limit of values indicating absence of CNS metastases was 89 U/L. Given these cutoff points, the sensitivity of TPpA as a marker for CNS metastases was 74% and the specificity was 100%; the predictive values of positive and negative tests were 100% and 86%, respectively. In 16 patients with CNS metastases, no correlation was found between TPpA activity in corresponding CSF and blood samples (correlation coefficient, Spearman's rho = .4; P greater than .1). In three patients treated for leptomeningeal carcinomatosis, the measurements of CSF TPpA showed correlation between the presence of tumor cells in the CSF and neurological clinical function. TPpA concentrations decreased in parallel with the clinical response and increased prior to CNS disease progression. As a marker for CNS metastases, the level of TPpA in the CSF in breast cancer patients appears to be superior to the level of protein, lactate dehydrogenase, or glucose, which showed very low sensitivity (41%, 47%, and 8%, respectively). For quantitative evaluation of treatment for leptomeningeal carcinomatosis, the TPpA level appears to be valuable and superior to CSF cytology, because tumor cells are not always present in CSF samples from patients with this condition. 
Human papillomavirus type-related DNA and c-myc oncogene alterations in colon cancer cell lines. Although squamous-cell epithelium is the most frequent target site of human papillomavirus (HPV) infection, a similar infection is demonstrated in columnar epithelial cells in this paper. The papillomavirus expression in three cell lines was detected in colorectal adenocarcinoma of Chinese patients. The HPV-16 and HPV-18 DNA sequences were found in colorectal cancer cell lines, which might suggest the correlation of HPV to the etiology of colorectal cancers. In addition, c-myc oncogene was identified by amplification in all three colorectal cancer cell lines, but only normal germ-line fragments were found in control tissue. The correlation between HPV and c-myc, and the implications of these findings in colorectal cancers are also discussed. 
Parathyroiditis associated with hyperparathyroidism and branchial cysts. A 57-year-old man had renal stones, and biochemical investigation led to a diagnosis of primary hyperparathyroidism. Surgical exploration revealed bilateral inferior parathyroid enlargement. Both glands were removed; macroscopically, small cysts were seen on cut sections. Histologic examination showed broad bands of fibrosis, lymphoid follicles, and plasma cells that diffusely effaced the parathyroid architecture. Such features--if seen in the thyroid gland--would be reminiscent of an autoimmune process. The cysts were lined by respiratory and squamous epithelia and contained lymphoid follicles in their walls. Less affected areas of the parathyroid tissue were hyperplastic. It is believed that the inflammatory response in the parathyroid glands that is described in this article may be characteristic. It may result from the cysts or their contents or from an autoimmune reaction. 
Intraoperative ultrasonography: an important surgical adjunct for intramedullary tumors. The echographic characteristics of 186 suspected intramedullary spinal cord tumors were reviewed. Ultrasonography was found to be specific in distinguishing the tumor type, the extent of the lesion, and the presence and type of associated cysts. Ultrasonography greatly facilitates the selection of respective sites for the placement of a myelotomy, and for initiation of the resection. Additionally, this indispensable adjunct provides ongoing images that allow the preoperative plan to be precisely followed in a surgical field where anatomical landmarks are limited and the margin for error is minimal. 
Molecular basis of the enhanced susceptibility of the erythrocytes of paroxysmal nocturnal hemoglobinuria to hemolysis in acidified serum. When incubated in acidified serum, the erythrocytes of paroxysmal nocturnal hemoglobinuria (PNH) are hemolyzed through activation of the alternative pathway of complement (APC), but normal erythrocytes are resistant to this process. PNH cells are deficient in decay-accelerating factor (DAF), a complement regulatory protein that inhibits the activity of both the classical and the alternative pathways. However, deficiency of DAF alone does not account entirely for the aberrant effects of acidified serum on PNH cells. Recently, we have shown that PNH erythrocytes are also deficient in another complement control protein called membrane inhibitor of reactive lysis (MIRL) that restricts complement-mediated lysis by blocking formation of the membrane attack complex (MAC). To determine the effects of the DAF and MIRL on susceptibility to acidified serum lysis, PNH cells were repleted with the purified proteins. DAF partially inhibited acidified serum lysis by blocking the activity of the amplification C3 convertase. MIRL inhibited acidified serum lysis both by blocking the activity of the MAC and by inhibiting the activity the C3 convertase. When DAF function was blocked with antibody, normal erythrocytes became partially susceptible to acidified serum lysis. By blocking MIRL, cells were made completely susceptible to lysis, and control of C3 convertase activity was partially lost. When both DAF and MIRL were blocked, the capacity of normal erythrocytes to control the activity of the APC and the MAC was destroyed, and the cells hemolyzed even in unacidified serum. These studies demonstrate that DAF and MIRL act in concert to control susceptibility to acidified serum lysis; of the two proteins, MIRL is the more important. In addition to its regulatory effects on the MAC, MIRL also influences the activity of the C3 convertase of the APC. Further, in the absence of DAF and MIRL, the plasma regulators (factor H and factor I) lack the capacity to control membrane-associated activation of the APC. 
Prevention of heterotopic ossification in high-risk patients by radiation therapy. Heterotopic ossification (HO) is a frequent occurrence after cemented and cementless total hip arthroplasty (THA). Patients at risk for this complication include those with preexisting ipsilateral or contralateral HO, diffuse idiopathic skeletal hyperostosis, hypertrophic osteoarthrosis, posttraumatic arthritis, and ankylosing spondylitis. Low-dose radiation therapy effectively prevents HO in this high-risk group when treatment is begun early in the postoperative period. A prospective evaluation has established the efficacy of fractionated and single-dose radiation therapy protocols. Limited radiation portals are used in patients receiving cementless prostheses. A rectangular radiation portal obliquely oriented to the prosthesis enables radiation treatment of the periarticular soft tissues while avoiding exposure of the bone-prosthesis interface. Radiation therapy to this interface may inhibit or delay bony ingrowth. Radiation therapy is the only treatment used to prevent HO that is delivered locally and not systemically. Low-dose radiation therapy using a limited radiation portal is the treatment of choice to prevent HO in high-risk patients after cementless THA. 
Long-term inhibition of tumor growth by tumor necrosis factor in the absence of cachexia or T-cell immunity. The relationship between detrimental (cachectic) and beneficial (antitumor) effects of tumor necrosis factor (TNF) was studied in mice bearing murine tumors transfected to secrete human TNF. In vitro, the TNF-producing transfectants were resistant to the secreted TNF and grew at rates similar to those of untransfected cells or transfected cells that did not secrete TNF. However, tumors formed by the TNF-secreting cells in vivo remained much smaller than the nonsecreting (transfected and untransfected) tumors. This inhibition of tumor growth required only relatively low serum levels of TNF, persisted for many weeks, and was independent of T cells since it occurred in nude mice. Growth of the TNF-secreting tumors increased dramatically after treatment with anti-human TNF antibody, indicating that extracellular TNF secreted by the tumor cells was necessary for the tumor inhibition. Severe weight loss characteristic of cachexia only occurred in animals with very high serum TNF levels (250 pg/ml) and could be prevented or reversed by anti-TNF antibody treatment. These data are consistent with the existence of a therapeutic window in which persistent exposure to human TNF can lead to prolonged inhibition of tumor growth in the absence of T-cell immunity or severe weight loss and without development of resistant tumor variants. 
Demonstration of osteonectin mRNA in megakaryocytes: the use of the polymerase chain reaction. Platelets have been shown to release osteonectin on thrombin stimulation. The origin of platelet osteonectin was unclear as it may have been synthesized by megakaryocytes or it may have been endocytosed from plasma as other platelet alpha-granule constituents are. Platelet osteonectin has a larger apparent molecular size than the bone species, although the molecular basis for this difference has not been elucidated. These two issues have been addressed here by (1) examining the potential for osteonectin biosynthesis in human megakaryocytes by demonstrating the presence of osteonectin mRNA in purified megakaryocytes, and (2) comparing the coding portion of osteonectin transcript in megakaryocytes to the size of its bone counterpart. Because of the limitations of cell population purity and in obtaining sufficient numbers of megakaryocyte cells for Northern analysis, we have used the polymerase chain reaction (PCR) to detect the presence of human osteonectin mRNA in megakaryocyte and megakaryocyte-depleted bone marrow cells. Isolation of RNA, cDNA synthesis, and PCR were performed on human osteosarcoma SaOS-2 cells, enriched megakaryocytes, and megakaryocyte-depleted cells. Restriction enzyme analysis of PCR DNA products confirmed the identity of the products as those encoding osteonectin for all three cell populations studied. In addition, the sizes of DNA indicate that osteonectin genomic DNA, nuclear RNA, or altered transcript were not amplified, and that the transcript from megakaryocytes is the same size as that from bone cells. These data suggest that the difference in protein size between platelet and bone osteonectin is due to posttranslational modification. To overcome the possibility that megakaryocyte signal originated from contaminating cells (less than 5% by cell count), all three cell populations were diluted to less than one cell per tube and PCR amplification was performed. Limiting dilution analyses demonstrated the presence of osteonectin mRNA in single megakaryocytes as well as in single cells from the cell population depleted of megakaryocytes, suggesting the capacity for osteonectin biosynthesis in all cells studied. The procedure we describe in this report can be used to examine specific characteristics of mRNA molecules in heterogeneous cell populations and in situations where only small quantities of cells can be obtained. 
The double-balloon and Inoue techniques in percutaneous mitral valvuloplasty: comparative results in a series of 232 cases. Immediate hemodynamic results of percutaneous mitral valvuloplasty were compared in two consecutive series of unselected patients from the same institution undergoing valvuloplasty with the double-balloon (161 patients) or the Inoue balloon (71 patients) technique. Before valvuloplasty, the patient series were comparable with regard to average age, gender repartition and most clinical, electrocardiographic, X-ray and hemodynamic variables. Poor anatomic forms of mitral stenosis were equally distributed in both series (41% vs. 45%, p = NS). The magnitude of mitral valve area increase and of mean mitral gradient decrease during percutaneous mitral valvuloplasty did not differ significantly in the Inoue balloon and double-balloon series (mean +/- SEM 1.1 +/- 0.2 to 1.95 +/- 0.5 and 1.0 +/- 0.2 to 1.97 +/- 0.5 cm2, respectively, for mitral valve area and 12 +/- 3 to 5 +/- 2 and 13 +/- 4 to 5 +/- 2 mm Hg, respectively, for mean mitral gradient). Four cases of 3+ mitral regurgitation occurred in the Inoue balloon series and 7 in the double-balloon series (p = NS). A good immediate result--defined as mitral valve area greater than or equal to 1.5 cm2 with greater than or equal to 25% in mitral valve area gain and mitral regurgitation less than 2+ at the end of the procedure--was observed in 78% of patients in both series. Three cases of tamponade due to chamber perforation and 14 cases of transient air embolism in the right coronary system due to balloon rupture were observed in the double-balloon series. 
Mutational analysis of an archaebacterial promoter: essential role of a TATA box for transcription efficiency and start-site selection in vitro. By using a recently developed in vitro transcription assay, the 16S/23S rRNA-encoding DNA promoter from the archaebacterium Sulfolobus sp. B12 was dissected by deletion and linker substitution mutagenesis. The analysis of 5' and 3' deletion mutants defined a core promoter region between positions -38 and -2 containing all information for efficient and specific transcription. Further characterization of this region by linker substitution mutagenesis indicated two sequence elements important for promoter function--one located between positions -38 and -25 (distal promoter element) and the other one located between positions -11 and -2 (proximal promoter element). The distal promoter element encompassed the TATA-like "box A" element located approximately 26 nucleotides upstream of the majority of transcription start sites in archaebacteria (Archaeobacteria). All mutations within this box A motif virtually abolished promoter function. Complete inactivation of the proximal promoter element was dependent on extensive mutagenesis; this element is not conserved between archaebacterial promoters except for a high A + T content in stable RNA gene promoters from Sulfolobus. Mutants containing insertions or deletions between the distal and proximal promoter elements were only slightly affected in their transcription efficiency but displayed a shift in their major initiation site, retaining an essentially fixed distance between the distal promoter element and the transcription start site. Thus, efficient transcription and start-site selection were dependent on a conserved TATA-like sequence centered approximately 26 nucleotides upstream of the initiation site, a situation unlike that of eubacterial promoters but resembling the core structure of most eukaryotic RNA polymerase II (and some RNA polymerase III) promoters. This finding suggests a common evolutionary origin of these promoters consistent with the known similarities between archaebacterial and eukaryotic RNA polymerases. 
Decreased CD45RA T cells in B-cell chronic lymphatic leukemia patients: correlation with disease stage. T-cell subsets CD4, CD8 and suppressor-inducers (CD45RA) were determined in 20 patients with B-cell chronic lymphatic leukemia (B-CLL). The proportion of CD4 and CD45RA was decreased when compared with T cells from normal subjects. CD8 was markedly increased. The activity of concanavalin A-induced suppressor cells was not significantly different from that of normal controls and was negatively correlated to the percentage of CD4 of B-CLL patients. The selective loss of CD45RA cells was more prominent in patients in advanced Rai stages of the disease (III to IV) than in early stages (0 to II). Six patients of the advanced stages group suffered from autoimmune hemolytic anemia, whereas no patient in the early stages of disease showed an autoimmune phenomenon. Our results may indicate a mechanism of autoimmunity in B-CLL similar to that of patients with autoimmune diseases. 
Role of endoscopic retrograde cholangiopancreatography after orthotopic liver transplantation. Twelve of 178 (7%) liver transplant patients underwent endoscopic retrograde cholangiopancreatography (ERCP) after transplantation. The indications for ERCP were persistent or late onset cholestasis, recurrent cholangitis, and suspected biliary leaks or strictures. The time between transplantation and ERCP ranged from 44 to 330 days (median 153 days). Biliary complications diagnosed by ERCP included biliary sludge in the form of casts, calculi, or debris (n = 7); bile leaks (n = 2); a biliary stricture (n = 1), and complete biliary obstruction (n = 1). One patient had a normal cholangiogram after transplantation. Biliary sludge was detected by ultrasound before ERCP in only one of six patients. Eight patients underwent endoscopic papillotomy, followed by clearance of biliary sludge in four and dilatation of a biliary stricture in one. Two patients bled after papillotomy but neither required surgical intervention. At a median follow up of 1.2 years (range 0.5-2.8 years), nine patients are well and three have died. ERCP provides both accurate diagnosis of biliary complications after liver transplantation and treatment that obviates the need for additional surgery in selected patients. 
The JH/LVOH method in the quantification of aortic regurgitation: how the cardiac sonographer may avoid an important potential pitfall. Color flow Doppler allows for methods in which to quantitate the severity of valvular regurgitation. In particular, the regurgitant jet height/left ventricular outflow tract height (JH/LVOH) method of quantitating the severity of aortic regurgitation has been validated and is routinely used in the adult echocardiography laboratory. A potential pitfall exists in the measurement of the LVOH. This article points out this potential source of error and, in addition, proposes steps that may be taken by the cardiac sonographer to avoid this potential measurement pitfall. 
The double-stapled ileal reservoir and ileoanal anastomosis. A prospective review of sphincter function and clinical outcome. Fifteen consecutive patients (nine males and six females) who underwent construction of a double-stapled ileoanal reservoir (DS-IAR) were prospectively evaluated. Mean and maximal resting pressures preoperatively, before ileostomy closure, and at 12 months, were 53 and 84 mm Hg, 39 and 62 mm Hg, and 62 and 81 mm Hg. Mean and maximal squeeze pressures at those same time periods were 96 and 153 mm Hg, 111 and 173 mm Hg, and 95 and 168 mm Hg. There were no significant decreases in either resting or squeeze pressure between preoperative values and those obtained 12 months after surgery. However, the length of the high pressure zone decreased from 3.8 cm preoperatively to 2.3 cm at 12 months. This reflects the sacrifice of the cephalad 1.5 cm of the internal anal sphincter necessary to effect this anastomosis at a mean of 1.4 cm from the dentate line. However, this maneuver did not result in poor continence. Eleven patients whose ileostomies were closed for a mean of 9 months, ranging from 3 to 15 months, were evaluated regarding functional outcome. Only one patient had any incontinence and this patient had incomplete circular-stapled tissue rings, which necessitated transanal suture repair of the anastomotic defect. Similarly, three of the four patients who sometimes or rarely use a pad at night had transanal-suture reinforcement. Ten of the 11 patients never wear a pad during the day. No pelvic or perianal sepsis occurred. Stratified squamous epithelium was found in 6 of the 13 distal stapler "donuts" that were examined. In addition, 10 patients underwent biopsy of the tissue immediately caudad to the circular staple line at the time of ileostomy closure; in five, only stratified squamous epithelium was noted. The DS-IAR is associated with excellent objective physiologic and subjective functional results. 
Adverse effect of therapeutic vasoconstrictors in experimental acute pancreatitis. Alpha-adrenergic drugs commonly are used to treat hypotension resulting from severe acute pancreatitis. It was shown previously that although systemic arterial pressure is increased by phenylephrine, pancreatic microcirculatory perfusion is decreased. Because inadequate tissue perfusion may be critical in the progression of edematous pancreatitis to parenchymal necrosis, it was hypothesized that vasoconstrictors might be harmful in pancreatitis. Therefore the effect of phenylephrine on cerulein-induced mild pancreatitis were studied. Sprague-Dawley rats (n = 54) were randomly allocated to 6 experimental groups and subjected to the following infusion regimens: (1) cerulein (cae) + phenylephrine (phe), (2) cae + saline (NS), (3) NS + phe, (4) cae + phenoxybenzamine (pbz) + phe, (5) NS + pbz + phe, and (6) NS. Initial and terminal hematocrit, serum amylase activity, and blood ionized calcium concentration were determined. The animals were killed 9 hours after starting the infusion. Macroscopic and histologic changes were scored by a 'blinded' pathologist. Phenylephrine increased the severity of cerulein-induced pancreatitis as manifested by statistically significant adverse changes in serum amylase, hematocrit, ionized calcium, peripancreatitic soap formation, and acinar cell vacuolization. These changes were antagonized by alpha-adrenergic receptor blockade with phenoxybenzamine. It is concluded that phenylephrine is deleterious in acute experimental pancreatitis, the first demonstration of such an effect by a pharmacologic vasoconstrictor, and suggested that microcirculatory changes may be important in the transition of mild to severe pancreatitis. Caution in the use of vasoconstrictor drugs in patients with acute pancreatitis is recommended. 
Clinical effect of continuous gastric cooling for massive GI bleeding in uremia. Continuous gastric cooling (CGC) with dialysate was done in nine hemodiaysis patients with massive gastro-intestinal (GI) bleeding. Eight patients were treated by direct irrigation using a double-lumen naso-gastric (NG) tube without balloon. Four patients with bleeding from the duodenum (B-f-D) had complete hemostasis, and there was only one recurrence. However, two out of four patients with bleeding from the stomach (B-f-S) had complete hemostasis, but all four suffered recurrence. The NG tube had to be reinserted in three patients with B-f-S because of obstruction by clots. The direct irrigation method of CGC thus appears to be more effective for the treatment of B-f-D than B-f-S, so we investigated a three lumen, single-balloon catheter (3L-SBC) with which the bleeding site in the stomach can be cooled and pressed without removing coagula. CGC using the 3L-SBC was done in one patient with B-f-S, and complete hemostasis was obtained without recurrence. 
Preliminary results of left heart bypass in pigs using a heparin-coated centrifugal pump. To assess the feasibility of left ventricular assist without systemic heparinization, we used a commercially available (Sarns 3M) centrifugal pump with tubing set and cannulas, all internally precoated for the purpose of this study with heparin, to bypass the left ventricle in 12 pigs for periods of either 1 or 3 hours. There was no significant activation of clotting and there was no sign of generalized embolization. However, on postmortem studies, 5 kidneys out of 22 examined showed signs of minimal thromboembolism. This experiment shows that artificial left ventricular assist, free of systemic heparinization but using heparin precoating, is feasible and safe, at least for a short period of time. 
Detection of clinically suspected deep vein thrombosis using light reflection rheography. Venography is the current standard for the diagnosis of deep vein thrombosis (DVT). Noninvasive tests have differing sensitivity and specificity, are technically demanding, and may be subject to variability in interpretation. Light reflection rheography (LRR) is a noninvasive method utilizing light-emitting diodes and a sensor to measure light reflected from the skin surface. The intensity of reflected light establishes a graphic pattern that indirectly quantifies parameters of venous function by measuring changes in the microcirculation. Seventy-two patients who underwent contrast venography at our institution were also evaluated with LRR. Twenty-four patients were found to have DVT as demonstrated by venography. Of these, 23 also had DVT detected by LRR. No evidence of thrombus was seen in 45 patients studied by venography; in this group, 35 had normal venous emptying indicated by LRR. Using LRR, a sensitivity of 96% was achieved in the evaluation of clinically suspected DVT. This sensitivity is comparable with other noninvasive tests. In addition, LRR is easy to operate, portable, inexpensive, and not technically demanding. Further investigation is needed to confirm these data and further define the role of LRR in the evaluation of clinically suspected DVT. 
Effect of ischemia on protein synthesis in the septic liver. The effect of ischemia on hepatic protein synthesis during sepsis is not known, but is of clinical relevance, since hepatic blood flow decreases during the late phase of sepsis. In this study, synthesis of acute-phase proteins was measured in perfused livers of rats 16 hours after sham operation or cecal ligation and puncture. Livers from each group had 45 minutes of complete ischemia or control perfusion. Protein synthesis was measured during two hour perfusion after the ischemia or control period, by determining incorporation of 3H-leucine into total secreted trichloracetic acid precipitated proteins, immunoprecipitated complement component C3 and albumin and phosphotungstenate-precipitated alpha 1-acid glycoprotein. Lactate, glutamine-oxalacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) levels in the perfusate were measured during preischemic and postischemic perfusion. Tissue glutathione levels were measured at the end of the perfusion. Synthesis of alpha 1-acid glycoprotein was increased by 100 per cent and albumin synthesis decreased by 46 per cent in septic livers, consistent with an acute-phase response and apparent downregulation of albumin synthesis during early sepsis. Synthesis rates were reduced by 50 to 60 per cent after ischemia in perfused livers from sham operated rats and 70 to 80 per cent in livers from septic rats. Hepatic production of interleukin-1 was not different between the groups during perfusion. GOT and GPT levels increased significantly during ischemia of both nonseptic and septic livers and rapidly returned toward baseline during reperfusion. Lactate levels were higher in perfusate of septic than of nonseptic livers before ischemia and increased further during ischemia. The results suggest that ischemia inhibits production of secreted hepatic proteins similarly in nonseptic and septic livers, but perhaps to a slightly greater extent in septic livers. 
Insulin resistance. A multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes mellitus is commonly associated with systolic/diastolic hypertension, and a wealth of epidemiological data suggest that this association is independent of age and obesity. Much evidence indicates that the link between diabetes and essential hypertension is hyperinsulinemia. Thus, when hypertensive patients, whether obese or of normal body weight, are compared with age- and weight-matched normotensive control subjects, a heightened plasma insulin response to a glucose challenge is consistently found. A state of cellular resistance to insulin action subtends the observed hyperinsulinism. With the insulin/glucose-clamp technique, in combination with tracer glucose infusion and indirect calorimetry, it has been demonstrated that the insulin resistance of essential hypertension is located in peripheral tissues (muscle), is limited to nonoxidative pathways of glucose disposal (glycogen synthesis), and correlates directly with the severity of hypertension. The reasons for the association of insulin resistance and essential hypertension can be sought in at least four general types of mechanisms: Na+ retention, sympathetic nervous system overactivity, disturbed membrane ion transport, and proliferation of vascular smooth muscle cells. Physiological maneuvers, such as calorie restriction (in the overweight patient) and regular physical exercise, can improve tissue sensitivity to insulin; evidence indicates that these maneuvers can also lower blood pressure in both normotensive and hypertensive individuals. Insulin resistance and hyperinsulinemia are also associated with an atherogenic plasma lipid profile. Elevated plasma insulin concentrations enhance very-low-density lipoprotein (VLDL) synthesis, leading to hypertriglyceridemia. Progressive elimination of lipid and apolipoproteins from the VLDL particle leads to an increased formation of intermediate-density and low-density lipoproteins, both of which are atherogenic. Last, insulin, independent of its effects on blood pressure and plasma lipids, is known to be atherogenic. The hormone enhances cholesterol transport into arteriolar smooth muscle cells and increases endogenous lipid synthesis by these cells. Insulin also stimulates the proliferation of arteriolar smooth muscle cells, augments collagen synthesis in the vascular wall, increases the formation of and decreases the regression of lipid plaques, and stimulates the production of various growth factors. In summary, insulin resistance appears to be a syndrome that is associated with a clustering of metabolic disorders, including non-insulin-dependent diabetes mellitus, obesity, hypertension, lipid abnormalities, and atherosclerotic cardiovascular disease. 
Two-dimensional echocardiographic assessment of intracardiac masses in infants and children. We studied six infants and children with intracardiac masses of different causes. The diagnosis was made noninvasively using two-dimensional echocardiography in all six patients. In five patients, surgical excision of the mass was undertaken with good results. Two-dimensional echocardiography is an excellent noninvasive diagnostic tool that allows the clinician to determine the size and location of intracardiac masses in infants and children. 
Toxin production by Bacillus pumilus. Two strains of Bacillus pumilus (M11 and M38) and one strain each of Bacillus cereus (M27), Bacillus subtilis (M67), and Enterobacter agglomerans (M14) were identified from the air of Lancashire cotton mills. These strains were tested for cytopathic effects in Vero cells; B pumilus and B cereus strains were also examined for haemolytic activity, lecithinase production, and proteolytic action on casein. Rounding and clumping of the Vero cells occurred after the addition of supernatants prepared from B pumilus and B cereus strains; finger-like projections developed in the cells treated with B pumilus supernatants. Minimal effects occurred with B subtilis and E agglomerans. After two hours of exposure B pumilus (M11) produced the greatest effect, but treatment with trypan blue showed that most cells exposed to the M11 strain were still alive after 96 hours of exposure; those exposed to the supernatant prepared from the M38 strain of B pumilus were dead. Sheep erythrocytes were lysed more rapidly by B cereus than by B pumilus, B cereus (strongly positive) had a greater effect on lecithin than either of the B pumilus strains (M38 weakly positive, M11 negative). All hydrolised casein but the effect was more rapid with one of the B pumilus (M11) strains. It is concluded that not only do the toxins of B pumilus differ from those of B cereus, but there are also differences between the toxins produced by the two strains of B pumilus (M11 and M38). 
Cardioplegia by way of the coronary sinus for valvular and coronary surgery. Retrograde coronary sinus perfusion has recently reemerged as an attractive means of delivering cardioplegic solutions during open heart procedures. In patients undergoing aortic valve or aortic root surgery, there is no evidence that coronary sinus cardioplegia results in a better myocardial protection than that achieved with the use of standard methods of anterograde cardioplegia delivery. However, the retrograde approach provides distinct technical advantages that might favor its use as an alternative to direct coronary ostial cannulation. In select subgroups of patients undergoing coronary bypass procedures, there is a growing body of evidence that the coronary sinus route may be more effective than the anterograde route because of its superior capacity to ensure homogeneous distribution of cooling and cardioplegia in myocardial areas supplied occluded arteries. The well established safety of coronary sinus cardioplegia in the clinical setting further justifies its inclusion among techniques for ensuring adequate myocardial preservation during surgically induced ischemic arrest. 
Single photon emission computed tomography in patients with acute hydrocephalus or with cerebral ischaemia after subarachnoid haemorrhage. Using single photon emission computed tomography (SPECT), cerebral blood flow was studied in eight patients with gradual deterioration in the level of consciousness after subarachnoid haemorrhage. Four had cerebral ischaemia and four had acute hydrocephalus. In patients with cerebral ischaemia, single photon emission computed tomography scanning showed multiple regions with decreased uptake of technetium-99M labelled d,l-hexamethyl-propylene amine oxime (99mTcHM-PAO) mainly in watershed areas. In patients with acute hydrocephalus, decreased uptake was seen mainly in the basal parts of the brain: around the third ventricle, around the temporal horns of the lateral ventricles, and in the basal part of the frontal lobe. After serial lumbar puncture, there was improvement of the uptake of 99mTc HM-PAO in these basal areas in three (convincingly in two and slightly in the other) of the four patients accompanied by clinical improvement in these three patients. These results suggest that patients with acute hydrocephalus and impaired consciousness after SAH, in contrast to patients with cerebral ischaemia, have decreased cerebral blood flow predominantly in the basal parts of the brain. 
Retroperitoneal fibrosis as host response to papillary renal cell carcinoma. A case of papillary renal cell carcinoma associated with retroperitoneal fibrosis is described. This type of fibrosis has not been previously reported to be associated with renal cell carcinoma. The case is of additional interest in that it implicates an immune phenomenon in the pathogenesis of the fibrosis, involving both putative tumor antigens and antigens associated with tumor growth but unrelated to tumor cells. 
A "twilight period" of coronary perfusion: the risk of intraoperative infarction in surgery for main left coronary obstruction. This study investigates the significance of an intraoperative period of low coronary perfusion pressure which may lead to ischemia, infarction, or both, in patients undergoing coronary bypass surgery for tight left main obstruction. "Twilight Period" (TP) was defined as the time interval from initiation of cardiopulmonary bypass to implementation of cold cardioplegia. Fifty-four patients with main left coronary obstruction (greater than 50%) were divided in three groups: Group I (20), TP less than 5 minutes; Group II (15), TP = 5-15 minutes; and Group III (19), TP greater than 15 minutes. Monitoring parameters included: systemic perfusion pressure during TP, perfusion flows, length of TP, time of ischemia, myocardial temperatures during ischemia, postoperative CK-MB level, EKG-detectable infarction, and postoperative therapeutic support requirements. Results: Intraoperative myocardial infarction by EKG was 0% in Group I, 7% in Group II, and 26.3% in Group III; mortality was 0%, 0%, and 15.7%, respectively. CK-MB values were 18 +/- 3.2 IU, Group I; 18.3 +/- 2.5 IU, Group II; and 49.4 +/- 10.3 IU, Group III. Group I vs. III: P 0.01. Levels of postoperative support: Level A, less than 12 hours; Level B, 12-36 hours; and Level C, greater than 36 hours. Intra-aortic balloon pump (IABP) was considered Level C. In Group I, 75% (15/20) fell in Level A; 15% (3/20) in Level B and 10% (2/20) in Level C. In Group II, 60% (9/15) fell in Level A; 26.7% (4/15) in Level B; and 13% (2/15) in Level C. In Group III, 36.8% (7/19) fell in Level A; 15.8% (3/19) in Level B; and 47.4% (9/19) in Level C. 
Mechanisms of lymphocytotoxicity induced by extracorporeal photochemotherapy for cutaneous T cell lymphoma. Extracorporeal photochemotherapy is an effective treatment for cutaneous T cell lymphoma but its mode of action is uncertain. The reduction in viability of patients' photoirradiated buffy coat lymphocytes was correlated with a 35% increase in DNA single-strand breaks and marked decreases in cellular ATP and NAD levels (to 58 and 34% of control, respectively) immediately after photoirradiation. Complementary in vitro studies were conducted with normal human peripheral blood lymphocytes using a Therakos ultraviolet A (UVA) light box. UVA light was cytotoxic on its own but was potentiated by 8-methoxysporalen. 3-aminobenzamide, a poly (ADP-ribose) synthetase inhibitor, mitigated the cytotoxic effect of ultraviolet A light in the presence of 8-methoxypsoralen in lymphocytes and reduced the amount of nucleotide depletion they caused. 10 J/cm2 of UVA light in the presence of 300 ng/ml 8-methoxypsoralen increased the poly (ADP-ribose) synthetase activity of peripheral blood lymphocytes. Exposing lymphocytes to deoxycoformycin and deoxyadenosine was found to induce biochemical and physical effects similar to those of photochemotherapy. In summary, we have shown that the lymphocytotoxic effect of extracorporeal photochemotherapy for cutaneous T cell lymphoma is apparently mediated by DNA damage, subsequent poly (ADP-ribosyl)ation and adenine nucleotide depletion. It is not known how the DNA damage and resultant biochemical effects relate to the possible immunological mechanism of extracorporeal photochemotherapy; however, it is possible that its effects can be mimicked by other DNA-damaging agents. 
Tumor growth dependent on Kaposi's sarcoma-derived fibroblast growth factor inhibited by pentosan polysulfate. A neoangiogenic response is critical for the unrestricted growth of solid tumors beyond a few millimeters in diameter. Release of adequate growth-stimulating activity from tumor cells is obviously required for the stimulation of blood vessel growth, and blockade of such stimulatory activity should repress tumor growth at the microscopic level. To test this hypothesis and to study appropriate inhibitors, we used a human adrenal cancer cell line (SW-13/K-fgf) engineered to secrete Kaposi's sarcoma-derived fibroblast growth factor (K-FGF), which we previously showed to induce growth of highly vascularized subcutaneous tumors in animals by autocrine and paracrine stimuli. In the present study, we tested different polysulfates for their selective inhibition of proliferation induced by K-FGF versus proliferation independent of K-FGF. Suramin and dextran sulfate showed slight selective inhibition of K-FGF-induced proliferation, ie, inhibition three- and five-fold greater, respectively, than the inhibition of proliferation independent of K-FGF. In contrast, heparin was inactive. The heparin analogue pentosan polysulfate (PPS), however, showed selective inhibition that was more than 2000-fold greater. The inhibitory effects of PPS on growth of SW-13/K-fgf cells, as well as endothelial cells, were fully reversible by an excess of added FGF. Daily intraperitoneal injections of PPS were tolerated well by athymic nude mice and prevented growth of subcutaneous SW-13/K-fgf tumor xenografts. PPS will be a useful tool to elucidate the effects of FGFs in vitro and in vivo and appears to be a prototype for the development of tumoricidal therapy based on targeting of growth factors. 
CT of acute pancreatitis: correlation between lack of contrast enhancement and pancreatic necrosis. This study was performed to determine if a correlation exists between pancreatic parenchymal enhancement or lack thereof on contrast-enhanced CT and surgical evidence of pancreatic necrosis. Accurate CT assessment of pancreatic vascular perfusion would be helpful in preoperative planning before pancreatic debridement and necrosectomy. The CT scans and medical records were blindly and retrospectively reviewed in 13 patients with the operative diagnosis of pancreatic necrosis. In all cases, CT examinations preceded surgery within 72 hr. Surgical and pathologic findings served as the gold standards for the diagnosis of pancreatic necrosis. Seven (54%) of 13 patients had a region or regions of parenchymal necrosis within the head, body, and/or tail of the pancreas seen during surgery. All seven of these patients had no pancreatic enhancement on CT in at least one region of the pancreas (CT sensitivity = 100%). In four of the seven, two regions were found to be necrotic at surgery, but only one of the two segments did not enhance on CT scans. In three of the seven patients, lack of contrast enhancement on CT (no enhancement of the pancreatic head and body in two patients and throughout the gland in another) correlated with necrosis in the same regions at surgery. The remaining six (46%) patients, who had peripancreatic or small, focal, and/or superficial areas of pancreatic necrosis at surgery, had normal pancreatic enhancement on CT. Our results show that regions of pancreatic necrosis found surgically correlate with lack of enhancement of pancreatic parenchyma on CT. Peripancreatic necrosis and minor areas of focal or superficial parenchymal necrosis were not detected on CT. 
Shunt failure caused by valve collapse. Shunt failure due to collapse of the Mini-Holter valve was observed 13 times in 11 out of 179 children with an implanted Mini-Holter ventriculo-peritoneal (VP) or ventriculo-atrial (VA) shunt during a 10 year period. Intussusception of the proximal or distal end of the valve thus caused a shunt failure rate of 6% of the children in this series. Two children experienced this complication twice. All collapsed valves were part of a VP shunt system. Because of this experience use of the mini valve was abandoned and an adult Holter valve was implanted in children over the age of one month. Breakdown of this particular valve has not occurred in 102 children and two hundred adults with the adult Holter shunt system. 
Myocardial ischemia during daily activities: the importance of increased myocardial oxygen demand. The role of increased myocardial oxygen demand in the pathophysiology of myocardial ischemia occurring during daily activities was evaluated in 50 patients with coronary artery disease and exercise-induced ST segment depression. Each patient underwent ambulatory electrocardiographic (ECG) monitoring for ST segment shifts during normal daily activities and symptom-limited bicycle exercise testing with continuous ECG monitoring. All 50 patients had ST depression greater than or equal to 0.1 mV during exercise. A total of 241 episodes of ST depression were noted in the ambulatory setting in 31 patients; only 6% of these were accompanied by angina pectoris. Significant (0.1 mV) ST depression during ambulatory monitoring was preceded by a mean increase in heart rate of 27 +/- 12 beats/min. Patients with ischemia during daily activities developed ST depression earlier during exercise (7.9 +/- 4.4 vs. 14.2 +/- 6.4 min, p less than 0.001) and tended to have significant ECG changes at a lower exercise heart rate and rate-pressure product than did those without ST depression during ambulatory monitoring. In the 31 patients with ischemia during daily activities, the mean heart rate associated with ST depression in the ambulatory setting was closely correlated with the heart rate precipitating ECG changes during exercise testing (r = 0.74, p less than 0.001). 
Renal artery stenosis: preliminary results of treatment with the Strecker stent. Use of the Strecker flexible balloon-expandable tantalum stent for treatment of renal artery stenosis after failed angioplasty or transaortic thromboendarterectomy was evaluated in 10 patients (nine hypertensive, one normotensive). Left (n = 3) and right (n = 5) renal arteries were involved; renal artery stenosis in two patients had developed after kidney transplantation. Indications for stent placement were inadequate immediate postangioplasty response (n = 7), development of considerable restenosis after angioplasty (n = 1), and obstructing intimal flaps following transaortic endarterectomy (n = 2). Stent placement was technically successful (less than 20% residual stenosis) and patency was preserved in eight patients. Of the seven hypertensive patients with successful implantation, two were cured, three had improvement, and two had no change at latest follow-up evaluation (mean, 10.6 months; range, 6-12 months). The Strecker stent may be helpful in treating restenosis after failed revascularization procedures, although the precise indication, true safety, and long-term efficacy of stent placement in renal arteries will not be known until trials with more subjects and longer follow-up periods are completed. 
Transoral decompression evaluated by cine-mode magnetic resonance imaging: a case of basilar impression accompanied by Chiari malformation. Cine-mode magnetic resonance imaging provides simultaneous images of cerebrospinal fluid flow dynamics. A patient with a basilar impression accompanied by a Chiari malformation and von Recklinghausen's disease who underwent transoral decompression is reported. Preoperative cine-mode magnetic resonance imaging visualized an associated obstruction of cerebrospinal fluid pulsatile flow at the level of the foramen magnum. Tonsilar herniation (Chiari I malformation) and hydrocephalus were also present. Postoperatively, the obstruction of cerebrospinal fluid flow was resolved concomitant with the correction of the cervicomedullary angulation. On the basis of observations made by magnetic resonance imaging, the surgical treatment of basilar impression accompanied by Chiari malformation is briefly discussed. 
Atrial natriuretic peptide response to cardioversion of atrial flutter and fibrillation and role of associated heart failure. Plasma atrial natriuretic peptide (ANP) concentrations were measured before and 1 hour after cardioversion in 40 patients (27 with atrial flutter and 13 with atrial fibrillation) admitted for elective cardioversion. Fourteen (11 with atrial flutter and 3 with atrial fibrillation) had clinical evidence of congestive heart failure (CHF). Conversion to sinus rhythm was successful in 39 patients. The mean ANP concentration in the entire group decreased after cardioversion from 38 +/- 4 to 17 +/- 2 pmol/liter (p less than 0.001). In the subgroup with CHF, the ANP level, which was not significantly higher than that in the group without CHF, decreased from 47 +/- 8 to 19 +/- 3 pmol/liter (p less than 0.01). Neither mode of cardioversion (spontaneous 1, pharmacologic 2 and direct-current countershock 36) nor associated CHF influenced ANP response to cardioversion. One patient with atrial flutter and "failed cardioversion" had unchanged ANP level. The decrease after cardioversion in ANP concentration correlated with its control level (r = 0.88, p less than 0.001) but not with the decrease in heart rate. The ANP level in patients with atrial fibrillation was 45 +/- 9 vs 38 +/- 5 pmol/liter in those with atrial flutter (difference not significant). Arrhythmia duration, left atrial size, and ventricular rate or arterial blood pressure did not correlate with ANP concentration in any subgroup. It is concluded that (1) the ANP level is elevated comparably in patients with both atrial flutter and fibrillation regardless of the presence or absence of CHF; and (2) the level decreases, independent of the mode of cardioversion or presence of CHF, promptly after successful cardioversion. 
Quantitation of estrogen and androgen receptors in hepatocellular carcinoma and adjacent normal human liver. Sex hormones have been shown to influence the development and course of several liver diseases. The worldwide predominance of hepatocellular carcinoma (HCC) in males has led to the suggestion that this disease might be hormone-responsive. Therefore, the hepatic estrogen (ER) and androgen receptor (AR) status of liver specimens from such patients was investigated. Samples were obtained from three female and six males patients undergoing liver resection; in each case, a small sample of both the tumor and adjacent normal tissue was collected. All patients had primary hepatocellular carcinoma without cirrhosis. In most cases, the tumor and the normal specimen had an equivalent content of cytosolic ER; however, three of the tumor samples (one female and two male) displayed considerably elevated cytosolic ER levels as compared to that of the normal tissue. In every sample, the tumor contained less nuclear ER than did the normal liver. When AR was measured, tumors of three patients (one female and two male) demonstrated a twofold elevation in cytosolic AR as compared to adjacent normal tissue. In the two male patients, an approximately twofold greater nuclear AR was found. Two other samples from male patients showed a modest elevation of cytosolic AR in the tumors. The patients whose tumors showed elevations in ER were not the same patients as those in whom the AR was elevated. Thus, these studies indicate that certain, but not all, specimens of HCC demonstrate either elevated ER or AR and suggest that a determination of receptor content might be useful prior to initiation of certain antihormone therapies. 
Premenstrual syndrome. Tailoring treatment to symptoms. Despite the interest in premenstrual syndrome (PMS) taken by the media and the public in recent years, some women still do not recognize the cyclic nature of their symptoms. Thus, PMS continues to elude diagnosis. Dr Nader discusses the major categories of symptoms and when they occur, summarizes theories on the cause of PMS, and comments on how well these theories have been substantiated by testing. Choosing agents for treatment on the basis of symptoms to be controlled is also described. 
CHARGE and Joubert syndromes: are they a single disorder? A patient with the CHARGE association (Coloboma of the eye, Heart defect, Atresia of the choana, Retarded growth and development, Genital hypoplasia, and Ear anomalies or deafness) had intermittent hyperpnea and cerebellar hypoplasia; therefore, he had both the CHARGE association and Joubert syndrome. The 2 syndromes have not been previously linked. We discuss their similarities and review the literature. 
Current medical management of cirrhotic ascites. The presence of ascites may indicate a number of hepatic and extra-hepatic disorders. This situation requires comprehensive evaluation to determine the underlying cause. The evaluation and management of ascites in patients with known cirrhosis is very important since this manifestation of portal hypertension has a detrimental effect on the prognosis for such patients. 
Hepatic colorectal metastases: correlation of MR imaging and pathologic appearance. Results of magnetic resonance (MR) imaging examinations for 76 patients with proved colorectal metastases to the liver were retrospectively reviewed. Signal intensity and morphologic patterns of 157 lesions were scored. The morphologic patterns were correlated with the histologic material obtained at segmental hepatic resections or excisional biopsies in 33 patients. In 154 lesions (98%) colorectal metastases to the liver were found to be hyperintense on MR images acquired with a long repetition time/echo time; in 77 lesions (49%) central low-signal-intensity changes were seen. Virtually all larger lesions demonstrated areas of low signal intensity within the tumor. These areas were found to reflect histologic findings of coagulative necrosis and desmoplasia within the tumor. Peripheral hyperintense halos around central hypointense areas encompassed the growing tumor margin and variable degrees of cell necrosis. Hypointense peripheral rims, which correspond to abnormalities of surrounding hepatic parenchyma, were seen in 40 lesions (25%). This sign should not be assumed to represent the fibrous pseudocapsule of primary hepatic malignancy. No correlation between tumor grade (differentiation) and tumor morphology was observed. 
Alterations of the nailfold capillary morphology associated with Raynaud phenomenon in patients with systemic lupus erythematosus. Quantitative analysis of nailfold capillary morphology was performed in age and sex matched groups of 29 patients with systemic lupus erythematosus (SLE) presenting Raynaud phenomenon (RP), 29 RP negative patients with SLE with the same duration of the disease, and 29 healthy controls. Percentages of tortuous, meandering and bushy capillaries were significantly increased in both groups of patients without influence of RP. Capillary density was lower, mean diameters of the capillary loops were higher in patients, especially when RP was present (at the venular branch in microns, mean +/- SD: controls: 15.0 +/- 2.0, RP negative patients with SLE: 17.6 +/- 3.6, RP positive patients with SLE: 20.5 +/- 6.3). In a subgroup of 13 patients with frequent Raynaud's attacks (more than 1/week), diameters were still higher (22.1 +/- 7.1, p to controls less than 0.0005; p to RP negative patients less than 0.05). In patients with SLE, the prevalence of RP seems not to be associated with the increased number of abnormal capillaries but with capillary enlargement, correlating with the frequency of attacks. 
A review of 32 cases of tardive dystonia. OBJECTIVE: Tardive dystonia, historically combined with tardive dyskinesia, is now viewed as probably having a different pathophysiology, course, outcome, and treatment response than tardive dyskinesia. In addition, patients with tardive dystonia are reported to be younger, and most are men. This study evaluates characteristics of 32 patients with tardive dystonia and compares results to other reports. METHOD: Twenty-four patients had been referred for research purposes and were videotaped, while eight had been followed clinically. Two of the authors reviewed all available videotapes and clinical reports to assess the course of symptoms over time. For global ratings and ratings of affected body parts, two scales were used: the Abnormal Involuntary Movement Scale (AIMS) for tardive dyskinesia and a similar scale for tardive dystonia. The method of case finding does not provide incidence or prevalence data for tardive dystonia. RESULTS: Fifty-nine percent of the patients experienced onset of tardive dystonia symptoms within 6 years of antipsychotic drug exposure; women had a shorter exposure time. No patient had complete remission of tardive dystonia symptoms, and 22 were moderately or severely impaired when their movements were most prominent. CONCLUSIONS: While epidemiological studies of tardive dystonia have yet to be performed, these results support the observations of others that most patients with tardive dystonia are men, have a short history of exposure to antipsychotic drugs, and may initially present with blepharospasm. Tardive dystonia rarely remits completely, can cause notable disability, and may partially respond to anticholinergic agents. 
The use of magnetic resonance imaging in the study of edema. A method of studying edema using magnetic resonance imaging (MRI) is presented. Three patients with lower extremity edema due to congestive heart failure were imaged with a 0.6 tesla system before and after diuresis. Edge detection algorithms were utilized to precisely outline regions of interest for quantification. Water and nonwater elements were separated within the region of interest to quantify water content. The results show that: (1) Edema can be quantified by use of MRI. (2) Subcutaneous edema is distributed along defined planes (ie, nonuniformly). (3) Increased water content is present not only in the subcutaneous tissue but also in deeper lying muscle. 
Hypertension and coronary artery disease. Can the chain be broken? Hypertension is an established risk factor for all the clinical sequelae of coronary artery disease. Despite this, individual therapeutic trials of antihypertensive therapy have not demonstrated the expected reduction in coronary morbidity and mortality. This apparent failure is perhaps not surprising when one considers the multifactorial nature of coronary artery disease and the different ways in which hypertension may affect the coronary circulation. Much debate has also centered on the antihypertensive therapy used in major trials in that it may in some way prevent the reduction in coronary mortality. However, thus far no clear evidence of a harmful effect has emerged. Reducing coronary mortality in hypertensive patients is a major challenge but one that can be effectively surmounted by approaching these different factors in a concerted manner. The ultimate goal must be to prevent the development of hypertension and left ventricular hypertrophy, but until such time as that can be achieved, the early detection of hypertension is mandatory. The optimal levels of systolic and diastolic blood pressures must be established. Studies on the more recent antihypertensive agents hold promise for a more specific effect on the atherosclerotic process as well as sustained control of arterial blood pressure. In this regard, it would seem essential to develop more precise ways of quantifying atherosclerosis and thus clarifying the nature of its relation to hypertension. Finally, management of hypertension must include precise assessment of the patient's overall cardiovascular risk status and appropriate and aggressive management of all risk factors for coronary artery disease. 
Platelet-activating factor produces shock, in vivo complement activation, and tissue injury in mice. We previously showed that TNF and endotoxin (LPS) synergize to activate the complement system and produce shock and bowel injury in normal mice. However, C5-deficient mice were protected from these adverse effects. In this study, we show that in mice, platelet-activating factor (PAF) antagonist prevents TNF- and LPS-induced complement activation, bowel injury, and death, indicating that PAF mediates the actions of TNF and LPS. We then examined the role of the complement system in PAF-induced shock and tissue injury. We found that 1) PAF (3 micrograms/kg) induces shock, hemoconcentration, bowel necrosis, and death in normal mice, whereas C5-deficient mice are protected from these effects. (Protection was abrogated when the dose of PAF was raised to 5 micrograms/kg.) Furthermore, when C5-deficient mice were reconstituted with normal serum, they also developed shock, bowel injury, and death in response to PAF. Thus, C5 is required for PAF to induce injury. 2) PAF activates the complement system in vivo, but not in vitro. The mechanism of complement activation by PAF is unclear. Inasmuch as PAF stimulates neutrophils to release protease that may activate the complement system, we examined the effect of neutrophil depletion on PAF-induced injury and complement activation. We found that neutrophil depletion fails to prevent PAF-induced complement activation, although PAF-induced lethality is much reduced. We conclude that PAF causes complement activation, and acts in synergy with active complement fragments to produce shock and tissue injury. Neutrophils probably do not play the pivotal role in PAF-induced complement activation. 
Leiomyosarcoma arising in atypical fibromuscular hyperplasia (phyllodes tumor) of the prostate with distant metastasis. An extremely rare neoplasm of the prostate, commonly known as phyllodes type of atypical prostatic hyperplasia, is described in a 57-year-old man. Over a 2-year period, the atypical smooth muscle component has transformed into leiomyosarcoma, and eventually metastasized to the bones and the lungs. Such an evolution has never been documented for this tumor. 
Rationale for development of low-molecular-weight heparins and their clinical potential in the prevention of postoperative venous thrombosis. Interest in low-molecular-weight heparins (LMWHs) as potential antithrombotic agents was stimulated by two observations in the mid-1970s and early 1980s. The first was finding that LMWH fractions prepared from unfractionated heparin (UFH) progressively lost their ability to prolong the activated partial thromboplastin time (APTT) while retaining their ability to inhibit Factor Xa. The second was the observation that LMWHs prepared by chemical depolarization of UFH are antithrombotic in experimental animal models but produce less microvascular bleeding in experimental models for an equivalent antithrombotic effect than the UFH from which they are derived. Subsequently, it was shown that LMWHs inhibit platelet function and impair vascular permeability less than standard heparin and that LMWHs have a longer biological half-life than standard heparin. A number of LMWHs have been evaluated in clinical trials in general and orthopedic surgery and in the treatment of venous thrombosis. LMWHs are highly effective in orthopedic surgery, where they appear to be more effective than standard heparin. LMWHs have also been shown to be either as effective or more effective than UFH in preventing postoperative thrombosis following general surgery. In preliminary studies, LMWHs appear to be as effective as standard heparin in the treatment of venous thrombosis, but larger studies are required using clinically relevant outcome measures. 
Cortical blindness and residual vision: is the "second" visual system in humans capable of more than rudimentary visual perception? We studied 12 patients with static cortical blindness to evaluate residual vision after destruction of area 17 and to assess the visual capacity of the subcortical "second" visual system in humans. In each case, the cause was bilateral infarction of the occipital lobes. Five patients had total blindness, and four had residual rudimentary vision (RRV), characterized by homonymous areas of light perception in the peripheral field and ability to detect moving objects. Only three patients had the ability to read; two of these had spared macular vision, and the other had spared left homonymous hemimaculae and spared temporal crescent. Neuroimaging and visual evoked potentials (VEPs) correlated with the extent of the visual dysfunction. Total destruction of area 17 bilaterally was associated with total permanent visual loss. The larger the amount of spared visual cortex, the better the vision. Positron emission tomography (PET) or single photon emission computed tomography (SPECT) demonstrated retained metabolic activity in islands of preserved area 17 in patients with some residual vision. VEPs were present in totally blind individuals. We conclude that, in humans, useful visual function is preserved only when a critical amount of area 17 is spared. The subcortical second system may participate in the generation of VEPs, but is incapable of conscious visual perception. 
Estramustine binding protein in human brain-tumor tissue. Estramustine, an estradiol-17 beta and nornitrogen mustard complex, is used in the treatment of advanced prostatic carcinoma. A specific estramustine binding protein (EMBP) is important for its cytotoxic action, and the presence of EMBP has previously been demonstrated in rat and human prostatic cancer tissue. Significant levels of EMBP were detected by radioimmunoassay in human brain-tumor tissue. The EMBP concentrations (expressed as ng/mg protein) in 16 astrocytomas (mean 2.6 ng/mg, range 0.5 to 6.2 ng/mg) and seven meningiomas (mean 5.1 ng/mg, range 0.3 to 9.3 ng/mg) were significantly higher than that found in four samples of epileptic brain (mean 0.7 ng/mg, range 0.5 to 1 ng/mg) and 18 samples of normal brain (mean 0.5 ng/mg, range 0.2 to 1.0 ng/mg). The uptake, metabolism, and antiproliferative effects of the prostatic anticancer agent estramustine have been previously demonstrated in cultured glioma cells. The presence of EMBP may suggest a selective binding and effectiveness in human brain-tumor tissue. 
Determination of pulse wave velocities with computerized algorithms. Careful determination of pulse wave velocity is important in the study of arterial viscoelastic properties, wave reflections, and ventricular-arterial interactions. In spite of its increasingly widespread use, there is as yet no standardized method for its determination. Most studies have manually identified the transit time of the pressure wave front as it travels over a known distance in the arterial system, but the issues of accuracy and reproducibility have not been addressed. This study was designed to investigate the efficacy of four computerized algorithms in the determination of pulse wave velocities in invasive as well as in noninvasive pressure determinations. The four methods were the identification of: (1) the point of minimum diastolic pressure, (2) the point at which the first derivative of pressure is maximum, (3) the point at which the second derivative of pressure is maximum, and (4) the point yielded by the intersection of a line tangent to the initial systolic upstroke of the pressure tracing and a horizontal line through the minimum point. High-fidelity aortic pressure recordings were obtained in 26 patients with a multi-sensor micromanometer catheter. Noninvasive brachial and radial pressure waveforms were recorded in 11 volunteers with external piezoelectric transducers. The results show that the first derivative method consistently provided results that were different from the other methods for both the invasive and noninvasive methods because of changes in the structure of the upstroke as the arterial pulse propagates distally. Although the minimum method worked well for the invasive determinations, it was erratic with the noninvasive determinations, probably because of the higher amount of noise and reflection in the latter. Among the four algorithms, the second derivative and the intersecting tangents methods worked well with both invasive and noninvasive determinations with mean variation coefficients of less than 7% and correlation coefficients between the methods of greater than 0.90 for all data. In conclusion, computerized algorithms allow accurate determination of pulse wave velocity in invasively and noninvasively measured arterial pressure waveforms. 
CT of the gastrointestinal tract: principles and interpretation. The experience accumulated in daily abdominal CT scanning and CT evaluation of gastrointestinal lesions has generated helpful technical guidelines and some reliable principles of interpretation. These general principles are briefly discussed in this review, and the importance of performing a CT examination that is adequate for the detection and evaluation of gastrointestinal lesions is stressed. CT features useful in differentiating benign from malignant lesions, limitations and pitfalls in CT interpretation, overlap in the CT appearance, and classical CT features leading to specific diagnoses are described and illustrated. Although CT is established as one of the most important techniques for imaging the gastrointestinal tract, it should be used selectively and only in the context of appropriate clinical and conventional radiologic examination. CT should not be regarded as competing with, but as complementing, barium examination of the gastrointestinal tract. 
Visual field defects in diabetic patients with primary open-angle glaucoma. We reviewed the automated visual field tests of 110 nondiabetic and 87 diabetic patients with primary open-angle glaucoma randomly selected from a large glaucoma practice to investigate a possible qualitative difference in the pattern of visual field defects between nondiabetic and diabetic patients with primary open-angle glaucoma. A single reviewer analyzed, in masked fashion, the visual field tests of each patient and decided whether or not visual field defects were present mainly in the inferior half of the visual field. Of the 110 nondiabetic patients, 40 (36.4%) had visual field defects located mainly in the inferior half of the visual field in one or both eyes, whereas 56 of the 87 (64.4%) diabetic patients had such defects. This difference was statistically significant (P = .0001). We believe that a vascular factor, such as that attributable to diabetes mellitus, may influence glaucomatous optic nerve damage, thus causing a difference in the pattern of visual field loss in patients with primary open-angle glaucoma. 
C6 glioma-astrocytoma cell and fetal astrocyte migration into artificial basement membrane: a permissive substrate for neural tumors but not fetal astrocytes. Cortically homografted C6 glioma-astrocytoma cells both invade the rat host brain as a mass and migrate as individual cells. In contrast, fetal astrocytes derived from homografted whole pieces of fetal cortex migrate only as individual cells throughout the brain of the rat but are not capable of invasion. Our experiment explored the migratory capacity (over 7 days) of cultured purified fetal astrocytes and C6 cells after seeding 10(6) cells on a hydrated artificial basement membrane wafer (Matrigel). The artificial basement membrane wafer was not a suitable substrate for the growth of cultured fetal astrocytes. In contrast, C6 cells migrated as individual cells from the surface of the wafer into the substrate. Individual C6 cells migrated 1.8 mm in the first 4 days and then ceased migration. The C6 cells were observed at the base of a digestion tube that extended from and was open to the surface of the wafer. At 3 days, micropockets were observed to form around each C6 cell at the base of each tube. By 7 days, the majority of pockets observed were large and contained several C6 cells. These multiple cell groups appeared to be progenitors of tumor masses. These data indicate that C6 glioma-astrocytoma cells, which in vivo appear to be a model for glioblastoma multiforme, primarily migrate as individual cells through artificial basement membrane and secondarily form tumor masses. Progenitor tumor masses form by coalescence of individual C6 cell micropockets or the division of a single cell in an individual micropocket. 
Liver metastases: results of percutaneous ethanol injection in 14 patients. Percutaneous ethanol injection (PEI) was performed under ultrasound (US) guidance in the outpatient department in 14 patients with 21 metastases 1.0-3.8 cm in diameter. The primary cancer was colorectal adenocarcinoma (seven patients), adenocarcinoma of the stomach (four patients), abdominal leiomyosarcoma (one patient), gastrinoma of unknown origin (one patient), and bronchial carcinoid (one patient). The indicators of therapeutic efficacy were US, computed tomography, fine-needle biopsy, and serologic markers. No complications occurred after a total of 175 treatment sessions. Complete response was obtained in 11 lesions, nine of which were less than 2 cm in diameter, and in all endocrine metastases (four lesions in two patients) with a maximum, recurrence-free follow-up of 38 months. Carcinoembryonic antigen values decreased in all patients but one for a 2-6-month period. The natural course of metastatic disease strictly limits the applicability of PEI, a local treatment. Single, metachronous, nonoperable metastasis of adenocarcinoma and endocrine metastases seem to be the only indications for PEI. 
Theophylline-associated seizures with "therapeutic" or low toxic serum concentrations: risk factors for serious outcome in adults. We report 12 adults with seizures associated with serum theophylline levels between 14 and 35 mg/l. The seizures were frequently prolonged, and outcome was generally poor with eight deaths. Although we did not identify comparable control groups, possible risk factors for serious outcome in theophylline-associated seizures were age, previous brain injury or disease, severe pulmonary disease, and possibly low serum albumin level. In patients with these risk factors, serum theophylline levels should be maintained below 10 to 15 mg/l. 
Multivessel PTCA using the hugging balloon technique based on single guide catheter and dual balloon-on-a-wire systems. For percutaneous transluminal coronary angioplasty (PTCA) of oversized arteries, often-times a satisfactory dilatation cannot be achieved with conventional balloon systems due to the unavailability of adequately sized balloons. This fact has contributed to a higher restenosis rate for this group of patients. We were able to obtain a satisfactory dilatation result in an oversized right coronary artery with a shepherd's crook configuration and eccentric anatomy at the origin using two balloon-on-a-wire systems and an Amplatz type guiding catheter. Although such favorable dilatation of an oversized artery using this "hugging balloon technique" can be expected, issues do exist such as difficult maneuverability and estimation of the balloon size obtained through simultaneous dual balloon inflation wherein size does not simply equal the sum of the two balloon catheters. It is hoped that there will be further improvements of the technique and development of new systems. At this time, however, it is felt that this is the most effective and reasonable strategy to achieve a high chance of success in oversized vessel lesions. 
Combined interferon alfa and doxorubicin in the treatment of advanced cervical cancer. Interferon alfa and doxorubicin have been shown to have synergistic effects when tested in vitro with cells derived from cervical cancers. A clinical trial was designed, testing interferon alfa plus doxorubicin in patients with advanced or recurrent cervical cancers. Twenty-one patients were given interferon alfa, 10 million units per square meter intramuscularly and 10 million units per square meter intravenously over a 30-minute infusion period. One hour later 20 mg/m2 doxorubicin was given intravenously slowly over a 2-hour period. Treatments were repeated once weekly for 3 weeks. Initial response evaluation was done at week 5, and treatment was continued on an every-other-week schedule for patients showing favorable responses or stable disease. Bone marrow, hepatic, and renal toxicities were minimal. Fever and malaise were the major sources of toxicity. Of the 17 evaluable patients, six had clinical partial responses. Two of the responders have enjoyed more than 5 years' survival. This regimen is well tolerated and does have efficacy in some patients with advanced cervical cancers. 
Repetitive sinoatrial exit block as the major mechanism of drug-provoked long sinus or atrial pause. Prolonged sinus or atrial pause occurred in six patients with paroxysmal supraventricular tachycardia after drug administration. All six patients had normal sinus node function during control electrophysiologic study; the sinus cycle length ranged from 510 to 900 ms (mean 743 +/- 141) and the longest sinus node recovery time ranged from 800 to 1,230 ms (mean 1,018 +/- 168). A long sinus or atrial pause occurring at the termination of tachycardia or cessation of atrial pacing, ranging from 3,100 to 8,200 ms (mean 6,270 +/- 1,674), was provoked by the administration of various drugs. These included an intravenous bolus injection of adenosine triphosphate (5 mg; one patient), intravenous bolus injection of verapamil (5 mg; one patient), a combination of a single oral dose of diltiazem (120 mg) and propranolol (20 to 40 mg; three patients), oral diltiazem (240 mg/day; one patient) and a combination of oral diltiazem (240 mg/day) and propranolol (160 mg/day; one patient). In five patients, low frequency deflections suggestive of sinus node activity with a cycle length between 620 and 3,500 ms were recorded during pauses. These findings suggest that repetitive sinoatrial exit block was responsible for the pause. Sinus slowing with a long arrest suggesting suppression of sinus automaticity was also noted in three of these five patients; the longest sinus arrest in these three patients was 4,160, 4,800 and greater than 4,910 ms, respectively. The remaining patient with a pause of 6,840 ms had no recordable sinus activity, either reflecting suppression of sinus automaticity or technical failure. 
Intracranial aneurysms in sickle-cell anemia: clinical features and pathogenesis. Intracranial aneurysms are an unusual complication of sickle-cell anemia; only 15 patients have been described in the world literature. An additional 15 patients with sickle-cell anemia and subarachnoid hemorrhage (SAH) from ruptured intracranial aneurysms are presented. There was a high incidence of multiple aneurysms (60%); some of which were in unusual locations. The clinical and pathological features of this series of patients have provided a paradigm for acquired aneurysm formation that may be applicable to other intracranial aneurysms. Thirteen patients underwent craniotomy and clip ligation; the perioperative management of these patients is discussed. Of these 13, eight had a good recovery, three were left with moderate disability, one patient died of surgical complications, and one died of complications related to sickle-cell anemia. Two of the 15 patients died of SAH. The authors propose that endothelial injury from the abnormal adherence of sickle erythrocytes to the endothelium is the initiating event in arterial wall injury. Subsequently, there is fragmentation of the internal elastic lamina and degeneration of the smooth-muscle layer. Hemodynamic stress at these loci of arterial wall damage results in aneurysm formation. This hypothesis also explains other cerebrovascular manifestations of sickle-cell anemia, namely vaso-occlusive disease and hemorrhage without aneurysm formation. Pathological material from this series and data from the literature are presented to support this hypothesis. 
Time course of recovery from frostbitten phrenics after coronary artery bypass graft surgery. Bilateral diaphragmatic paralysis developed in a patient after coronary artery bypass graft surgery during which cold cardioplegia was used. The patient's progress and eventual recovery over an 18-month period is described, with particular reference to chest wall motion and respiratory pressure measurements. 
Necrotizing bronchial aspergillosis in a patient receiving neoadjuvant chemotherapy for non-small cell lung carcinoma. We describe a case of necrotizing bronchial aspergillosis which developed after lobectomy following neoadjuvant chemotherapy in a 73-year-old woman with non-small cell lung cancer. The lesion was visualized and biopsied through FBS, which played a useful role for early diagnosis of this disease. Itraconazole therapy was effective and safe. 
Effect of antihypertensive therapy on focal stroke in spontaneously hypertensive rats. Spontaneously hypertensive rats subjected to focal cerebral ischemia develop larger infarcts than normotensive rat strains. To determine whether antihypertensive therapy decreases infarct volume in hypertensive rats, 60 13-week-old animals were treated with 20 mg/kg hydralazine added daily to the drinking water for 1.5, 6, 10, or 16 weeks and then subjected to focal cerebral ischemia by tandem right common carotid artery and middle cerebral artery occlusion. Blood pressure in the treated groups was substantially lower than that in untreated groups after 1 week of hydralazine therapy and remained lower for the entire treatment period in all four experiments. Mean infarct volume in spontaneously hypertensive rats treated for 10 (p = 0.02) or 16 (p = 0.005) weeks, but not 1.5 or 6 weeks, was significantly less than that in the untreated controls. The percentage reduction of infarct volume in animals treated for 10 and 16 weeks was similar. This study demonstrates that antihypertensive therapy decreases infarct volume in hypertensive rats subjected to focal cerebral ischemia. This treatment effect appears to be dependent on the duration of therapy, and the magnitude of the treatment effect seems to plateau by 10 weeks of therapy. 
The effects of resection of the proximal part of the fibula on stability of the knee and on gait. We studied six patients to determine the effects of unilateral marginal resection of the proximal part of the fibula on stability of the knee and on gait. At the time of the operation, the fibular collateral ligament and the tendon of the biceps femoris were reattached, but no attempt was made to stabilize the fibula otherwise. The patients were tested an average of sixty-one months after operation. Stability of the knee was measured with an instrumented system. Gait was evaluated with an optical electronic three-dimensional digitizing system and a multicomponent force-platform. The gait of six healthy control subjects of similar age was also studied, and the reproducibility of measurements of stability of the knee was investigated in four healthy adults. There were significant differences between the side on which an operation had been done and the contralateral side with regard to the extent of anterior translation and of total anterior-posterior translation of the tibia at both 20 and 90 degrees of flexion of the knee, and in total varus and valgus rotation of the knee (the number of degrees from a position of maximum varus to one of maximum valgus angulation) at 20 degrees of flexion. The measurements of gait and of motion of the knee were found to be normal when compared with those in the control subjects. In the ground-reaction measurements, there were some significant differences from normal in the medial-lateral plane, but they were clinically unimportant. Resection of the proximal part of the fibula can lead to instability of the knee. 
Bacterial meningitis following spinal anaesthesia for caesarean section. We report a case of meningitis caused by inadvertent introduction of bacteria following spinal anaesthesia for Caesarean section. The technique of performing the spinal anaesthesia is reviewed. Meningitis may occur, although very rarely, despite meticulous aseptic techniques. It is vital that meningitis should be considered in the differential diagnoses of post-spinal headache when patients present with headaches, pyrexia and meningism in the postoperative or postpartum period. 
The effects of chronic endoscopic variceal sclerotherapy on portal pressure in cirrhotics. The effect of obliterating esophageal varices by endoscopic sclerotherapy on portal pressure was prospectively studied in 11 cirrhotic patients with variceal hemorrhage. Portal venous pressure gradient, determined as the difference between transhepatic portal and hepatic vein pressure, increased by a mean of 31.1% +/- 14.5% in 8 (73%) and decreased by a mean of 30.1% +/- 11.7% in 3 (27%) patients, with no statistically significant change overall (P = 0.1). These changes in portal venous pressure gradient occurred despite an improvement in the laboratory and clinical parameters of hepatic function. Deep abdominal sonography with color flow imaging at variceal obliteration showed patent paraumbilical veins in 6 (55%) patients, 3 of whom had decreases in portal venous pressure gradient (29%, 19%, 42.5%) at variceal obliteration. In 5 (45%) patients without patent paraumbilical veins, a statistically significant increase in portal venous pressure gradient between initial endoscopic variceal sclerotherapy and variceal obliteration was noted (P = 0.008). Rebleeding (single episode in all 4 patients, before obliteration in 3 patients) occurred in those with an increase in portal venous pressure gradient; all patients with portal venous pressure gradient decreases were nonbleeders. No correlation between changes in portal venous pressure gradient and time to variceal obliteration, number of sclerotherapy treatments, or rebleeding episodes was observed. Thus, an increase in portal venous pressure gradient was noted in the majority of patients at variceal obliteration. Although the portal venous pressure gradient decrease may be explained by a patent paraumbilical vein, the mechanism of portal venous pressure gradient increase is not clear. It is speculated that this portal venous pressure gradient increase may be caused by an increase in collateral resistance or flow or a combination of both, resulting from obliteration of esophageal varices by endoscopic sclerotherapy. 
Portal venous system after portosystemic shunts or endoscopic sclerotherapy: evaluation with Doppler sonography. We sought to determine the usefulness of duplex Doppler sonography in the assessment of blood flow and clot formation in the portal vein in 44 patients with portal hypertension and bleeding esophageal varices who had undergone either endoscopic sclerotherapy (28 cases) or portosystemic shunt procedures (16 cases). The main, left, and right portal veins (collectively referred to as intrahepatic portal veins), superior mesenteric vein, splenic vein, and shunt were assessed for flow direction, presence of thrombi, and collaterals. Patent shunts were visualized in 12 (75%) of the 16 cases. Clot was detected in 27 (69%) of 39 intrahepatic portal veins in patients with end-to-side shunts, in six (67%) of nine intrahepatic portal veins in patients with distal splenorenal shunts, and in five (5%) of 92 intrahepatic portal veins in patients who had had endoscopic sclerotherapy. Flow in the main portal vein was hepatopetal in two (15%) of 13 patients with patent shunts (one end-to-side portacaval shunt and one distal splenorenal shunt). Flow in the main portal vein was hepatopetal in 26 (93%) of 28 patients who had had endoscopic sclerotherapy. Our data suggest endoscopic sclerotherapy preserves antegrade portal flow and results in fewer portal vein clots than surgical portosystemic shunts do. Patterns of thrombosis and flow direction vary unpredictably from patient to patient. Shunt patency should not be inferred without direct visualization of the shunt. 
Funic reduction for the management of umbilical cord prolapse. The current management of umbilical cord prolapse centers on attempts to alleviate the pressure of the presenting part on the cord while preparation for cesarean section is being made. A 10-year experience in which there were vigorous attempts to accomplish safe vaginal delivery after the diagnosis of umbilical cord prolapse is presented. Eight cases of umbilical cord prolapse occurred, a frequency of 1 in 277 deliveries (0.37%), all of which had a normal immediate neonatal outcome. Vaginal delivery was accomplished in seven patients (87.5%); diagnosis was made in two of them when delivery was imminent. Five patients were more remote from delivery and had successful funic reduction (manual replacement of the prolapsed cord). Funic reduction is proposed as a potentially beneficial initial step in the management of umbilical cord prolapse. 
Sudden unexpected death due to papillary fibroma of the aortic valve. Report of a case and review of the literature. The case of the sudden unexpected death of a 21-year-old man due to embolization of segments of an aortic valve papillary fibroma to the left main and anterior descending coronary artery is presented. The literature regarding cardiac papillary fibroma is reviewed with particular reference to those cases associated with sudden death. 
Laser balloon angioplasty: potential for reduction of the thrombogenicity of the injured arterial wall and for local application of bioprotective materials. Mitigation of adverse biologic reactivity after balloon angioplasty is necessary before the incidence of restenosis can be appreciably reduced. A brief review of experimental evidence supports the hypothesis that the thrombogenicity of the injured arterial wall can be reduced by a suitable level of thermal denaturation or cross-linking of thrombogenic proteins. In addition, the concept of local pharmacologic therapy, which can be provided with laser balloon angioplasty at the site of arterial injury, is introduced. Preliminary in vitro and in vivo data suggest that guide catheter-injected albumin-heparin conjugates fabricated as water-insoluble microspheres remain adherent to the injured luminal surface and deeper arterial layers after physical trapping by the inflated balloon and subsequent laser/thermal exposure. The combination of initially adequate luminal morphology, reduction of the thrombogenicity of the injured arterial wall and application of local pharmacologic therapy with laser balloon angioplasty may eventually prove helpful in reducing the incidence of restenosis. 
Innominate artery occlusive disease: surgical approach and long-term results. We reviewed our experience with 54 patients who underwent innominate artery revascularization during a 10-year period. Their age range was from 16 to 75 years (mean, 49.8 years). The innominate artery alone was involved in 21 patients (39%); the remaining patients had additional arch vessel obstructions. Before operation, neurologic symptoms occurred in 25 patients (46%), arm ischemia related to claudication and microembolization occurred in 8 patients (14%), a combination of symptoms occurred in 17 patients (32%), and no symptoms were noted in 4 patients (8%). The extrathoracic approach to surgery was used in 16 patients (30%). Eleven of the 38 patients in whom the intrathoracic approach was used had endarterectomy of the innominate artery; in three of those, the procedure was combined with left common carotid endarterectomy. Bypass grafts were used in the other 27 patients undergoing procedures with an intrathoracic approach; in six of those, bypass was combined with carotid endarterectomy. No operative deaths occurred. Perioperative revascularization failure occurred in four cases; all of those patients underwent a second revascularization procedure, with a secondary patency rate of 100%. In four patients, late occlusion was noted at 6 months and at 1, 1.5, and 10 years. One patient had a permanent perioperative neurologic deficit in the distribution of the left carotid artery after a combined common carotid endarterectomy/innominate endarterectomy procedure. No neurologic deficits were directly related to the innominate artery territory. Long-term actuarial survival was 83% at 10 years. Early and late graft failures were related to inadequate inflow in bypass grafts, progression of distal disease in arteritis, and primary closure in endarterectomy. 
Idiotypic cross-reactivity of immunoglobulins expressed in Waldenstrom's macroglobulinemia, chronic lymphocytic leukemia, and mantle zone lymphocytes of secondary B-cell follicles. Monoclonal antibodies (MoAbs) specific for autoantibody-associated cross-reactive idiotypes (CRIs) of Waldenstrom's IgM react frequently with the surface Ig (slg) expressed by leukemia cells of patients with chronic lymphocytic leukemia (CLL). Evaluation of the molecular basis for this cross-reactivity indicates that such CRIs are encoded by conserved antibody variable region genes (V genes) that have undergone little or no somatic hypermutation. We find that such anti-CRI MoAbs stain a subpopulation of cells within the mantle zones surrounding the germinal centers of normal human tonsil. In contrast, MoAbs specific for variable region subgroup determinants react with cells in both the mantle zones and germinal centers of secondary B-cell follicles. To test whether mantle zone B cells not reactive with existing anti-CRI MoAbs may express slg bearing as-yet-unrecognized CRIs present on Igs produced by neoplastic cells of some patients with Waldenstrom's macroglobulinemia or CLL, we immunized mice with purified Waldenstrom's IgM that have been characterized for their variable region subgroups using subgroup-specific antisera raised against synthetic peptides. The supernatants of hybridomas generated from the splenocytes of immunized mice were screened for their ability to stain a subpopulation of mantle zone lymphocytes in human tonsil. With this approach, two new anti-CRI MoAbs were identified, designated OAK1 and VOH3. OAK1 binds to a CRI present on a subset of kappa light chains of the VK1 subgroup. VOH3 recognizes a CRI determinant(s) present on a subset of antibody heavy chains of the VH3 subgroup. Flow cytometric analyses demonstrated that OAK1 specifically binds leukemia cells from 5 to 20 patients (25%) with kappa light chain expressing CLL. In addition, VOH3 reacted with the leukemia cells from 1 of 17 (6%) patients tested. The success of these methods demonstrates that the variable regions of the Igs produced by mantle zone B cells share idiotypic determinants with Igs expressed in B-cell CLL (B-CLL) and Waldenstrom's macroglobulinemia. 
Suturing or stapling in gastrointestinal surgery: a prospective randomized study. West of Scotland and Highland Anastomosis Study Group. A prospective randomized study of 1004 patients is reported, comparing surgical stapling and manual suturing techniques in the construction of gastrointestinal anastomoses. The incidence of clinical leaks was similar between the two groups (sutured 3.2 per cent, stapled 4.7 per cent; P = 0.22), while for radiological leaks the incidence was significantly higher in the sutured group (12.2 per cent versus 4.1 per cent, P less than 0.05). Stapling instruments afforded significantly quicker anastomoses, mean(s.e.m.) 28.1(0.7) versus 14.3(0.5) min (P less than 0.001), and quicker operations, 115.5(2.4) versus 103.8(2.2) min (P less than 0.001). The two groups were found to be comparable in other respects such as operative mortality, requirements for blood transfusion, incidence of infective complications, recovery of gastrointestinal function and postoperative hospital stay. 
Hepatitis C in liver transplant recipients. HCV infection is commonly found in patients with chronic liver disease undergoing liver transplantation. However, the presence of antibody to HCV does not appear to be associated with the development of hepatitis posttransplant. No other risk factors were identified that appear to predispose patients to development of hepatitis in the posttransplant period, including amount of blood product exposure. The role of immunosuppression in the acquisition and expression of liver disease caused by HCV remains to be determined. 
Cholestasis and changes of portal pressure caused by chlorpromazine in the perfused rat liver. Chlorpromazine (10 mumol/L) causes a marked increase in portal pressure in perfused rat liver. Simultaneously, oxygen consumption, hepatic clearance of taurocholate and bile flow are diminished. These effects are prevented by the cyclooxygenase inhibitors indomethacin (15 mumol/L), acetylsalicylate (3 mmol/L) or ibuprofen (200 mumol/L). On addition of chlorpromazine the liver releases increased amounts of prostaglandin D2; this increase does not occur in the presence of indomethacin. At higher concentrations of chlorpromazine (100 mumol/L) the inhibition of taurocholate clearance and bile flow is accompanied by only a moderate increase of portal pressure, and indomethacin is without effect. At this high concentration, substantial cell damage, as indicated by the release of lactate dehydrogenase, is present. We conclude that arachidonic acid-derived metabolites, notably prostanoids, are involved in the inhibition of bile flow and of taurocholate clearance observed at low concentrations of chlorpromazine. The data suggest that changes in the microcirculation are responsible for the impairment of the liver functions. At higher concentrations of chlorpromazine the cell toxicity of the drug becomes prominent. 
Prevention of an air embolism by moderate hypoventilation during surgery in the sitting position. The effect of ventilation (normo-, hypo-, and hyperventilation) on transverse sinus pressure (TSP), central venous pressure (CVP), mean arterial blood pressure (mABP), and heart rate was studied in 15 patients undergoing neurosurgical treatment in the sitting position for tumors of the posterior fossa, and the findings were compared with the influence of positive end expiratory pressure (PEEP) on these parameters. TSP was not influenced significantly by PEEP ranging from 0 to 15 mbar, whereas CVP increased. At the same time, mABP decreased slightly. In contrast, TSP showed characteristic changes with varying ventilation: during normoventilation [end expiratory CO2 pressure (PECO2), 38 mm Hg], TSP was 3 mm Hg and increased to 7 mm Hg on average with hypoventilation (PECO2, 44 mm Hg), whereas hyperventilation (PECO2, 32 mm Hg) caused a reduction in TSP to the atmospheric range. At the same time, CVP remained unchanged, whereas mABP increased with hypoventilation. Presuming that the risk of venous air embolism is closely related to the level of TSP, our results allow the following conclusions. 1) PEEP does not seem to be effective in preventing venous air embolism. 2) Hyperventilation is dangerous in the sitting position, as TSP is reduced to the atmospheric and even subatmospheric range. 3) To prevent air embolism, moderate hypoventilation is recommended during the most critical period of exposing the posterior fossa followed by normoventilation when surgery of the actual lesion has begun. 
Pyruvate dehydrogenase deficiency due to a 20-bp deletion in exon II of the pyruvate dehydrogenase (PDH) E1 alpha gene. A 20-bp deletion in the last exon of the pyruvate dehydrogenase (PDH) E1 alpha gene was found in a severely affected female patient diagnosed with PDH deficiency. PDH-complex activity in the patient's fibroblasts was 22% of that in normal controls. The mutation was characterized using PCR techniques with both patient cDNA and genomic DNA, followed by sequencing of the products. E1 beta cDNA sequence was found to be the same as that in controls. The deletion causes a frameshift and the occurrence of a premature stop codon. Western blot analysis revealed an extra band migrating just above the PDH E1 beta band. Northern blot analysis showed normal levels of both E1 alpha and E1 beta message when probed with the respective cDNAs. However, a larger intermediate-size transcript was observed for this patient in the E1 beta blot. The 20-bp deletion was not found in either parent's genomic DNA, and hence we conclude that the mutation must have occurred de novo, either in the germ-line cells or immediately following fertilization. 
Induction and prevention of radiocontrast-induced nephropathy in dogs with heart failure. Radiocontrast-induced nephropathy (RCIN) is a clinically important cause of acute renal failure with no effective treatment. Recognizing the high incidence of RCIN in humans with severe congestive heart failure (CHF), this study was designed to test the hypotheses that dogs with experimental CHF are at increased risk for RCIN and that pharmacologic renal levels of atrial natriuretic factor (ANF) can prevent RCIN in this model. In chronic experiments, three groups of five conscious dogs received intravenous radiocontrast (7 ml/kg). One group consisted of normal controls, while the two other groups had experimental CHF induced by eight days of ventricular pacing at 250 beats per minute. One of the CHF groups received an infusion of ANF (30 ng/kg/min) into the suprarenal aorta for one hour before, during and after the infusion of radiocontrast to achieve pharmacologic renal plasma levels. Renal function remained stable in the normal controls in contrast to the consistent decreases in daily creatinine clearance during the five days following radiocontrast in experimental CHF. In addition, ANF prevented radiocontrast-induced reductions in creatinine clearance in dogs with experimental CHF. Additional studies performed in two groups of anesthetized dogs with experimental CHF demonstrated that, in this model of RCIN, the reduction in renal function appears biphasic, and the action of ANF may be to increase glomerular filtration rate prior to radiocontrast, thus allowing a maintenance of renal function during and after radiocontrast. 
MR imaging of the portal venous system: value of gradient-echo imaging as an adjunct to spin-echo imaging. We evaluated the use of gradient-echo (GRE) as an adjunct to spin-echo (SE) MR imaging of the portal venous system. GRE imaging was performed in 31 subjects, 15 normal volunteers and 16 patients with documented portal venous disease (15 cases) or suspected disease (one case). Eight of 16 patients had venous thrombosis, five had focal thrombus, and three had complete occlusion. Six patients had extrinsic venous compression by tumor. Of the two other patients, one had an arteriovenous fistula and the other a falsely positive angiogram, suggesting portal vein occlusion. In normal subjects, GRE scans had excellent visualization of the portal venous system with high intravascular signal compared with surrounding tissues. Nine (60%) of 15 normal subjects and three patients had an artifact consisting of a curvilinear area of decreased signal that could mimic clot. In three of five patients with focal thrombus, clot was identified on GRE but not on SE images. In all three patients with occlusion, SE and GRE images demonstrated similar findings. In five of the six patients with extrinsic venous compression by tumor, SE and GRE studies showed similar findings. Of the two patients, an arteriovenous fistula was seen on GRE MR in one, and in the other, patency of the left portal vein was seen on SE and GRE images after angiography had suggested portal vein occlusion. Collateral vessels were seen in nine of 16 patients. In five of nine cases, GRE MR demonstrated more extensive collaterals than did SE MR. In summary, GRE MR provides a useful adjunct to standard SE MR imaging. Benefits include high contrast between vascular structures and surrounding tissues, reduced motion artifact, and rapid scanning within a breath-hold. 
Posttraumatic stress disorder following recent-onset psychosis. An unrecognized postpsychotic syndrome. Clinical experience with psychotic patients early in the course of their illness suggested that symptoms of posttraumatic stress disorder (PTSD) may not be uncommon after recovery from an acute psychotic episode. Thirty-six patients recovering from an acute psychotic episode within 2 to 3 years of onset of their illness were assessed as inpatients and followed up on two occasions during the year after discharge. The prevalence of PTSD was found to be 46% at 4 months and 35% at 11 months, measured by a questionnaire linked to DSM-III criteria. The relationships between negative symptomatology and PTSD symptoms and between depressive symptomatology and PTSD symptoms were also examined; a significant correlation was found only for the latter. The psychopathological, preventive, and therapeutic implications of these findings are discussed, and future research strategies are proposed. 
The effect of quadriceps excision on functional results after distal femoral resection and prosthetic replacement of bone tumors. Although resection and reconstruction with a prosthesis is an accepted form of treatment for tumors of the distal femur, minimal effort has been made to correlate the functional result with the degree of adjacent muscle excision. From 1983 to 1986, 65 patients had distal femoral resection and prosthetic reconstruction. Ten patients had only the vastus intermedius excised (Group A), 30 patients had excision of the vastus intermedius plus either the vastus medialis or lateralis (Group B), nine patients had only the rectus femoris spared (Group C), and 16 patients had the entire quadriceps excised or conversion of the previous arthrodesis (Group D). Based on the rating system of the Musculoskeletal Tumor Society, satisfactory results were obtained in 70% of Group A patients (30% excellent and 40% good), with no poor results. In group B, 80% had good or excellent results and 7% poor results. In Group C, 78% of the patients had good results but no excellent results, whereas Group D had only 50% satisfactory results. The parameters that most often led to functional impairment were restricted motion and inadequate extensor powers. Muscle transfers, however, (flexors to extensors) were effective only in Group C patients. With proper technique and prosthetic design, satisfactory results can be achieved after distal femoral resection and prosthetic reconstruction, even after extensive quadriceps excision. 
Swedish Agency for Research Cooperation with Developing Countries. Prospects for public health benefits in developing countries from new vaccines against enteric infections. The symposium participants concluded that vaccines with even moderate efficacy can be highly useful to prevent large numbers of severe illness episodes and deaths and that the decision of whether to initiate a vaccine program should be based on measures or estimates of public health effectiveness rather than only on protective efficacy. Studies of protective efficacy are of course critical to establish the vaccine's biologic activity, but additional aspects of public health effectiveness are also crucial in making these decisions. First-generation vaccines are available against typhoid, cholera, and soon rotavirus diarrhea, and vaccines against enterotoxigenic E. coli diarrhea and shigellosis are under development. The problems related to enteric diseases are enormous; the vaccines may soon be produced at low cost and promise to be relatively more easy to distribute than most previous vaccines. The number of illnesses and deaths averted from vaccine programs are potentially great. Pilot programs using the new vaccines should urgently be considered in areas where the disease burden is high, and steps should be taken to monitor effectiveness of the intervention in these programs. Such studies of vaccine effectiveness and costs in a "real world" situation are an essential step of the research process and should be used to guide the organization of larger-scale programs. Finally, many of the necessary research and development activities relevant to public health vaccinology must address country-specific problems. Developing countries should consider the role of vaccine-related research among the priorities for their essential national health research and build the necessary capabilities in applied and basic medical sciences and in the social sciences. 
Determination of growth fraction in advanced prostate cancer by Ki-67 immunostaining and its relationship to the time to tumor progression after hormonal therapy. Reliable predictors of response for prostate cancer patients undergoing hormonal therapy are lacking. This study investigates the possibility that tumor proliferation rates might predict tumor behavior for these patients. The growth fraction of metastatic prostate cancer biopsy specimens obtained before androgen withdrawal therapy was evaluated by Ki-67 antibody immunohistochemical study to determine whether a higher tumor growth fraction was associated with a shorter time to tumor progression after therapy. The percentage of Ki-67-positive malignant epithelial nuclei in the primary tumors of 17 patients ranged from 1.7% to 7.5% (median, 2.5%). When patients were divided into two response groups according to the median time to progression, poor responders (time to progression less than 20 months) and good responders (greater than or equal to 20 months) had similar growth fractions (3.5 +/- 0.5% versus 3.1 +/- 0.6% Ki-67-positive nuclei, respectively). However, when patients were divided into two groups based on the median growth fraction, patients with a high growth fraction (greater than 2.5% Ki-67-positive nuclei) tended to have a shorter time to progression (median, 10 months) than patients with a low (less than 2.5%) growth fraction (median time to progression, 25 months), although statistical significance was not reached. Despite this interesting trend, Ki-67 immunostaining was not accurate to predict the time to progression in individual patients undergoing hormonal therapy. Reliable prediction of growth rates may require measurement of both cell proliferation and cell death rates. 
Donor hearts with impaired hemodynamics. Benefit of warm substrate-enriched blood cardioplegic solution for induction of cardioplegia during cardiac harvesting. Brain-dead donors frequently show circulatory deterioration and often require so much inotropic support that the donor heart is of questionable value. This experimental study quantifies the cardiac metabolic consequences of brain death and the role of warm blood cardioplegic solution for induction of cardioplegia to improve the quality of potential donor hearts with impaired hemodynamics. Twelve dogs were subjected to brain death by interrupting cerebral blood flow (ligation of innominate artery, carotid arteries, and superior vena cava) and were followed up for as long as 6 hours. Each showed progressive hemodynamic deterioration, necessitating inotropic support (dopamine, calcium, and epinephrine) and large amounts of volume replacement (hetastarch; Hespan) to support the circulation (maintain mean arterial blood pressure greater than 60 mm Hg). Biopsy specimens were taken after 6 hours, or when irreversible ventricular fibrillation occurred, and were analyzed for adenosine triphosphate, creatine phosphate, glycogen, glutamate, and lactate. In six dogs the aorta was then clamped, and a 10-minute infusion of warm (37 degrees C) substrate-enriched aspartate/glutamate blood cardioplegic solution (with the dog's own blood) was given by roller pump to simulate warm induction during the harvesting process. Biopsies were then repeated. Myocardial metabolism, expressed as percent of control values, during brain death was characterized by the following: (1) moderate energy depletion (adenosine triphosphate fell 25% +/- 8%, creatine phosphate fell 55% +/- 15%; p less than 0.05 versus control: mean +/- standard error of the mean); (2) substrate depletion (tissue glutamate fell 48% +/- 9.5%, glycogen fell 66% +/- 7.5%; p less than 0.05 versus control: mean +/- standard error of the mean); and (3) evidence of anaerobic metabolism (lactate increased 374% +/- 95%; p less than 0.05 versus control: mean +/- standard error of the mean). Warm induction of blood cardioplegia in these energy- and substrate-depleted ischemic hearts showed (1) return of creatine phosphate levels to normal (113% +/- 16.8%), (2) replenishment of glutamate (201% +/- 24% of control; p less than 0.05 versus control: mean +/- standard error of the mean), and (3) 43% +/- 14% reduction in myocardial lactate content; (p less than 0.05 versus brain-dead animals). These data suggest that brain-dead donors requiring inotropic support sustain energy and substrate depletion and ischemic damage that can be reversed by a brief period of induction of cardioplegia with a warm substrate-enriched blood cardioplegic solution before harvesting.(ABSTRACT TRUNCATED AT 400 WORDS). 
Hepatic perfusion index (HPI) in mesenteric angina and following successful revascularization. This is a case report of a 45 year old man who had previously undergone a small bowel resection for acute mesenteric ischaemia. He subsequently suffered from mesenteric angina due to stenosis of the origin of the superior mesenteric artery and intermittent claudication due to aorto-iliac atheroma. The patient underwent a successful aorto-bifemoral Y graft and small bowel revascularization with a saphenous vein graft between the Y graft and the accessible proximal portion of the superior mesenteric artery. Before vascular reconstruction, the hepatic perfusion indices (HPI) in both the fasted and fed states were elevated; after mesenteric revascularization the HPI values were substantially lowered. The hepatic perfusion index may, by demonstrating functional abnormality, be useful in the diagnosis of mesenteric ischaemia and also in the assessment of treatment. Further evaluation of HPI in patients with suspected mesenteric ischaemia is therefore required. 
Treatment with recombinant human tumor necrosis factor-alpha protects rats against the lethality, hypotension, and hypothermia of gram-negative sepsis. Tumor necrosis factor (TNF) is a peptide secreted by macrophages in response to endotoxin that can produce many of the changes seen in septic shock. After cecal ligation and puncture (CLP) rats gradually develop tachycardia, hypotension, tachypnea, and hypothermia. At 5 h post-CLP, rats have a peak in serum levels of endotoxin and 60% of rats have blood cultures that grow Gram-negative rods (Escherichia coli and Klebsiella pneumonia). At 20 h post-CLP all rats develop positive blood cultures. Serum levels of TNF are not reproducibly measurable in rats following CLP. Rats undergoing CLP have a 50-80% mortality with deaths usually occurring 24-72 h postinjury. Repetitive (twice daily x 6 d) i.p. injection of sublethal doses of recombinant human TNF-alpha (100 micrograms/kg) to rats undergoing CLP 1 d after the treatment period resulted in a significant reduction in mortality compared to control rats previously unexposed to rTNF (P less than 0.03). Animals treated with rTNF had no hypotension or hypothermia after CLP and regained normal food intake faster than control rats. 12 h after CLP the gene expression for manganous superoxide dismutase (MnSOD), an inducible mitochondrial metalloenzyme responsible for cellular resistance to injury from toxic reactive oxygen species, was higher in livers of rats treated with rTNF suggesting that the TNF treatment augmented expression of this protective enzyme. Unlike MnSOD, expression of the gene for copper-zinc SOD was not affected by CLP or rTNF treatment. The results suggest that prior treatment with recombinant TNF can ameliorate the lethality, hypotension, hypothermia, and anorexia of Gram-negative sepsis in rats and that the mechanism may be related to enhanced hepatic expression of the gene for MnSOD. Repeated administration of recombinant TNF may be a strategy to minimize mortality and morbidity of Gram-negative sepsis. 
Adequate crystalloid resuscitation restores but fails to maintain the active hepatocellular function following hemorrhagic shock. Studies have shown that active hepatocellular function is depressed early after trauma-hemorrhage and persists despite resuscitation with two or three times (x) the volume of maximum bleedout (MB) with lactated Ringer's solution (LR). However, it is not known if a larger volume of fluid resuscitation corrects this dysfunction. To study this, rats were bled to and maintained at a mean arterial pressure of 40 mm Hg until 40% of the MB volume was returned in the form of LR, and then resuscitated with 4x or 5x the volume of MB with LR. Three doses of indocyanine green (ICG) were given intravenously and [ICG] measured in vivo using an in-vivo hemoreflectometer. The initial velocity of the clearance of ICG was calculated. Maximal velocity of the clearance (Vmax: the number of functional ICG receptors) and kinetic constant (Km: the efficiency of the active transport) were determined from the Lineweaver-Burk plot. Vmax decreased during hemorrhage, was restored to control levels at 0-4 hours after resuscitation, but decreased at 4-8 hours after resuscitation despite restoration of cardiac output following resuscitation with 5x LR. This could be the result of increased TNF release. The Km also decreased during hemorrhage, but increased at 0-1.5 hours and remained at control levels even 4-8 hours after resuscitation. Thus the failure of Vmax to remain at control levels following adequate fluid resuscitation may form the basis of cellular dysfunction and multiple organ failure after severe hemorrhagic shock. 
Analyses of 200 lymphadenectomies in patients with penile carcinoma. From 1972 to 1987, 200 consecutive lymphadenectomies were performed in 112 patients with squamous cell carcinoma of the penis. A Gibson incision provided exposure of the iliac and inguinal lymph nodes with a low morbidity rate (5% flap necrosis, 15% wound infection, 16% lymphedema and 9% lymphocele). The controversy surrounding the necessity of iliac lymphadenectomy is discussed, since 305 iliac lymph nodes examined did not have metastatic invasion. 
Peripheral white blood cell counts and bacterial meningitis: implications regarding diagnostic efficacy in febrile children. In order to investigate the clinical value of peripheral white blood cell variables for the diagnosis of bacterial meningitis among young, febrile children, we compared total peripheral white counts, total segmented neutrophil counts, total band counts, and the ratio of immature-to-total neutrophils (I:T ratio) among 46 children with bacterial meningitis, 130 children with aseptic meningitis, and 56 febrile children with culture confirmed extrameningeal bacterial infection. Children with bacterial meningitis were comparable to those with aseptic meningitis with respect to median total white blood cell counts and median total segmented neutrophil counts but had a significantly higher median total band count (1760/microliters vs 378/microliters, P = 0.0001) and a significantly higher median I:T ratio (0.40 vs 0.09, P less than 0.001). In contrast, children with bacterial meningitis were comparable to those with an extrameningeal bacterial infection with respect to median total band count but had a significantly lower median total peripheral white count (10,650/microliters vs 15,300/microliters, P = 0.0013), a lower median total segmented neutrophil count (4511/microliters vs 6796/microliters, P = 0.023), and a significantly higher median I:T ratio (0.40 vs 0.15, P less than 0.001). Children with meningitis who were bacteremic at presentation had a significantly lower total white cell count (P = 0.001) and significantly higher I:T ratio (P = 0.005) when compared with children who had an extrameningeal infection and concurrent bacteremia at presentation. 
Pancreatic-portal vein fistula with disseminated fat necrosis treated by pancreaticoduodenectomy. I have reported the case of a 62-year-old man with chronic alcoholic pancreatitis and a rare pseudocyst-portal vein fistula. Even though he experienced no abdominal symptoms, he had severe metastatic fat necrosis manifested as subcutaneous fat necrosis, polyarthritis, medullary bone necrosis, and mental status changes. Remote tissue destruction continued until relief was gained by pancreaticoduodenectomy and repair of the necrotic portal vein. Disseminated fat necrosis is a rare syndrome that can be the only presenting feature in patients with pancreatitis and pancreatic cancer. Early recognition and treatment of the underlying pancreatic disease may decrease the high morality rate associated with this syndrome. 
The use of intraaortic balloon pumping as an adjunct to reperfusion therapy in acute myocardial infarction. The Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) Study Group. To assess the risk and possible benefits of use of the percutaneous IABP in patients given thrombolytic therapy as treatment for acute myocardial infarction, we prospectively evaluated 810 consecutive patients entered into the TAMI trials. During hospitalization the 85 patients treated with the IABP had more cardiac risk factors, were slightly older (58 vs 56 years), and more often had anterior infarction (62% vs 38%). At acute cardiac catheterization, patients treated with the IABP also had more multivessel coronary disease (67% vs 43%), more frequent TIMI grade 0 or 1 flow (44% vs 28%), lower global ejection fraction (40% vs 52%), and worse regional infarct (-3.2 vs -2.5 SD/chord) and noninfarct (-0.67 vs +0.36 SD/chord) zone function. Although mortality rates (32% vs 4%) and in-hospital complications were greater in patients treated with the IABP, a greater improvement in global (delta ejection fraction: +1.9% vs +0.7%) and noninfarct zone (delta SD/chord: +0.11 vs -0.09) left ventricular function was observed in patients treated with the IABP at 1-week follow-up angiography. In addition, no reinfarction or reocclusion of the infarct-related artery occurred while patients were being treated with the IABP. These results suggest that the IABP may have a specific role after thrombolytic therapy in treating patients at high risk for reocclusion or at high risk for hemodynamic deterioration because of large infarction or critical stenoses in coronary vessels supplying the noninfarct zone. 
Chronic inflammatory demyelinating polyradiculoneuropathy of childhood: treatment with high-dose intravenous immunoglobulin. We treated four children with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) with high-dose intravenous immunoglobulin (IVIG). All patients received 400 mg/kg of IVIG a day for 5 days during relapses, and one patient received additional periodic infusions of 400 mg/kg. All patients showed excellent recovery of motor strength following each relapse that was treated with IVIG. Compared with plasmapheresis (which was used to treat relapses earlier), recovery of function with IVIG treatments was similar, and in two patients it was superior, to plasmapheresis. There were no side effects with IVIG treatments as compared with plasmapheresis with which two children had infection of central lines with Staphylococcus epidermidis, one had profuse bleeding from accidental extrusion of a central line, and one had multiple episodes of major venous thromboses. High-dose IVIG was a safe and effective adjunctive therapy for childhood CIDP in these four patients. 
Postoperative computed tomography three months after lumbar disc surgery. A prospective single-blind study. In a prospective single-blind study, 60 patients surgically treated for lumbar disc herniation underwent clinical examination and computed tomography preoperatively and 3 months after surgery. At follow-up (58 patients; median, 31 months; range, 21-37 months), 29 patients had an excellent outcome (51%), 20 improved (33%), and 9 were unchanged or worse (16%). Dural or radicular scar tissue was present by computed tomography in 88% of the patients, but the findings could not be correlated with the clinical outcome. Recurrent or persistent disc herniation was found in 9% of the patients. The clinical outcome of patients with abnormal computed tomography did not differ significantly from patients without this finding. A relation between facet joint degeneration and less successful clinical outcome was demonstrated. Computed tomography (without contrast) 3 months after surgery gave little information which could be correlated with the clinical outcome. Patients with an excellent outcome had all degrees of intraspinal scar tissue. 
Fragile X genotype characterized by an unstable region of DNA. DNA sequences have been located at the fragile X site by in situ hybridization and by the mapping of breakpoints in two somatic cell hybrids that were constructed to break at the fragile site. These hybrids were found to have breakpoints in a common 5-kilobase Eco RI restriction fragment. When this fragment was used as a probe on the chromosomal DNA of normal and fragile X genotype individuals, alterations in the mobility of the sequences detected by the probe were found only in fragile X genotype DNA. These sequences were of an increased size in all fragile X individuals and varied within families, indicating that the region was unstable. This probe provides a means with which to analyze fragile X pedigrees and is a diagnostic reagent for the fragile X genotype. 
Treatment of bilateral intrahepatic stones with high duct strictures through selective central hepatic resection. Bilateral intrahepatic duct stones with strictures, more common in the Orient than elsewhere, are difficult to access surgically. The results of surgical procedures have not been generally successful and are attended by a high postoperative complication and recurrence rate. We report the treatment of 30 patients with intrahepatic calculi and high duct strictures by means of selective central hepatic resection without dissection of the major vessels at the hilum. Central hepatic resection provided satisfactory access to the primary and secondary confluences of the intrahepatic ducts, allowed removal of residual stones and ascariasis, and permitted correction of multiple strictures. Twenty-nine patients so treated were followed for a mean of 32 months after operation. No patients developed recurrent fever, biliary colic, or jaundice after the operation. The technique is therefore recommended as an effective alternative to extensive hepatic lobectomy in the treatment of the intrahepatic calculi with multiple strictures. 
Carcinoma and DNA aneuploidy in Crohn's colitis--a histological and flow cytometric study. Twenty four patients with longstanding colonic Crohn's disease were examined prospectively with colonoscopy and multiple biopsy sampling in order to detect histological dysplasia or abnormal aneuploid DNA content, or both. Biopsy specimens were taken from 10 predetermined locations in the colon and rectum. No patient had definite dysplasia but three displayed DNA aneuploidy (12.5%), and one of these subsequently developed a carcinoma (Dukes' C at operation) in the ascending colon. No concomitant dysplasia was detected but the carcinoma as well as other parts of the mucosa were DNA aneuploid. It is concluded that dysplasia is rare in patients with Crohn's colitis, but findings of DNA aneuploidy warrant vigilance in follow up as this may indicate impending carcinoma. Further prospective studies are needed before the predictive value of DNA aneuploidy can be determined and before general recommendations of colonoscopic surveillance, as in longstanding ulcerative colitis, can be made. 
Neonatal schizencephaly: comparison of brain imaging. Schizencephaly is a regional disturbance of cerebral hemisphere formation occurring at 3-5 months gestation; neonatal presentation is uncommon. Three neonates with schizencephaly were evaluated with cranial ultrasonography (US), unenhanced computed tomography (CT), and magnetic resonance imaging (MRI) examinations. Common findings in US, CT, and MRI include parasylvian and midline clefts, size asymmetries of the basal ganglia and thalamus, cerebral parenchymal volume loss, ventriculomegaly, ventricular diverticula, and absence of the septum pellucidum. MRI and CT were superior to US in detecting calcification, gyral and sulcal abnormalities, and parasylvian clefts. MRI alone demonstrated homolateral absence of the sylvian vasculature, small medullary pyramids, low position of the fornix, and the thinning of the corpus callosum. Although US appears adequate as a screening test, MRI best defines the precise pathoanatomic findings of neonatal schizencephaly and allows for the prediction of neurologic outcomes in affected newborns. 
Surgical treatment of peptic ulcer disease. Elective surgery for peptic ulcer disease has diminished significantly over the past 15 years. However, emergency surgery has not shown a decline. Some series have even reported an increase in hospitalizations and operations for hemorrhage. The appropriate surgical procedure for peptic ulcer disease must be tailored to the specific needs of the individual patient. During emergency operations for hemorrhage from duodenal ulcer, we recommend suture ligature of the bleeding vessel and vagotomy-pyloroplasty for high-risk patients, or vagotomy-antrectomy for the lower-risk patient. Bleeding gastric ulcers should be resected, if possible. For massive hemorrhage from stress ulceration requiring surgery, near-total or total gastrectomy should be performed. Perforated duodenal ulcers are best managed by closure and a definitive ulcer operation, such as vagotomy-pyloroplasty. Perforated gastric ulcers are best excised but may be simply closed if conditions do not favor resection. In these situations, biopsy should be performed. We recommend truncal vagotomy-antrectomy for patients presenting with obstruction. Vagotomy (truncal or proximal gastric) with drainage is an acceptable alternative in this situation. For patients with intractable ulcer disease or for those who are noncompliant, proximal gastric vagotomy is the preferred operation. However, other operations may need to be considered, depending on the specific situation. Recurrent ulceration needs appropriate work-up to determine the possible cause. Although patients with ulcer recurrence initially may be placed on medical treatment, about 50% will require reoperation. The most effective procedure for peptic ulcer disease is truncal vagotomy-antrectomy, which has a recurrence rate of less than 1%. The procedure with the least morbidity and the fewest undesirable side effects is proximal gastric vagotomy. Ulcer recurrence after proximal gastric vagotomy or truncal vagotomy-pyloroplasty is in the range of 10% to 15%. 
Interstitial delivery of dexamethasone in the brain for the reduction of peritumoral edema. Controlled-release polymers have facilitated the interstitial delivery of drugs within the central nervous system. In the present study, dexamethasone was incorporated into ethylene-vinyl acetate polymers, which were then implanted adjacent to a 9L gliosarcoma in the brain of Fischer 344 rats. The effect of interstitial delivery of dexamethasone on peritumoral edema was assessed and compared to the effect of dexamethasone delivered systemically. Eighty-five rats underwent intracranial implantation of the 9L gliosarcoma. Five days later, the animals were randomly assigned to one of four treatment groups: Group 1 received intracranial implantation of controlled-release polymers containing dexamethasone; Group 2 received intraperitoneal implantation of controlled-release polymers containing dexamethasone; Group 3 received serial intraperitoneal injections of dexamethasone; and Group 4 received sham treatment. The animals were sacrificed 3 days after initiation of therapy and their brains were removed for measurement of the water content (edema) in the tumor-bearing and contralateral hemispheres. Brain and plasma samples were analyzed by reverse-phase high-performance liquid chromatography to determine the tissue and plasma concentrations of dexamethasone. Measurement of the release kinetics of dexamethasone from the ethylene-vinyl acetate polymers in an in vitro system showed that the drug was released in a controlled, tapering fashion. During the first 3 days of controlled release in vitro, 330 micrograms of a total content of 7.5 mg of dexamethasone was released into the medium. Analysis of tissue for drug levels demonstrated, however, that the interstitial delivery of this fractional amount of dexamethasone within the brain resulted in levels 19 times higher than those achieved by administering the full dose of 7.5 mg systemically over a 3-day period. Conversely, the systemic administration of dexamethasone resulted in plasma levels 16 times higher than those measured in the interstitial delivery of dexamethasone in the brain. Brain-water content determinations showed that the interstitial controlled release of the fractional amount of dexamethasone within the brain was as effective in controlling peritumoral edema as systemic administration of the full dose by serial intraperitoneal injections. The study demonstrates the following: 1) controlled-release polymeric carriers deliver biologically active dexamethasone in a sustained fashion; 2) very high concentrations of dexamethasone in brain tissue can be achieved using interstitial polymer-mediated drug delivery while minimizing plasma concentrations of this drug which are sometimes associated with serious systemic side effects; and 3) peritumoral brain edema can be effectively treated by the interstitial delivery of dexamethasone directly within the tumor bed. 
Thromboprophylaxis in patients with hip fractures: a prospective, randomized, comparative study between Org 10172 and dextran 70. A prospective, randomized, assessor-blind trial has been undertaken to compare the thromboprophylactic effect and safety of the heparinoid Org 10172 (a mixture of low molecular-weight sulfated glycosaminoglycuronides) and dextran 70 in patients operated on for hip fracture. Prestudy biostatistical calculations led to the need for 260 patients. Three hundred eight patients were randomized and 19 were excluded after randomization, the majority because of postponed surgery. Analyses were made on the 289 patients on an intention-to-treat basis, as well as on the 247 patients given correct prophylaxis. Diagnosis of deep vein thrombosis was based on bilateral ascending phlebography on postoperative days 10 through 12. The frequency of deep vein thrombosis on an intention-to-treat basis was 10% in the Org 10172 group and 30% in the dextran 70 group and, on the basis of correct prophylaxis, 12% and 31%, respectively, both differences being significant (p less than 0.001). Two-month mortality rates were equal in the groups. Three fatal pulmonary emboli were seen in the dextran group. Significantly more patients in the dextran group received postoperative transfusions; no other differences in various hemorrhagic parameters were seen. Thus it can be concluded that Org 10172 has a significantly better thromboprophylactic effect than does dextran in patients with hip fractures without significant side effects. 
Early combination of selegiline and low-dose levodopa as initial symptomatic therapy in Parkinson's disease. Experience in 26 patients receiving combined therapy for 26 months. Thirty-eight patients newly diagnosed as having Parkinson's disease (mean age, 57.3 years; mean Parkinson's disease duration, 2.7 years) in the earlier phase of the disease (mean Hoehn/Yahr stage, 2; mean motor scores, 11.4) were given selegiline (Deprenyl), 10 mg daily, and maintained on this drug alone until significant clinical worsening warranted the addition of low-dose levodopa (Sinemet, 25/100 three to four doses per day). Five of these patients were not yet receiving additional levodopa despite some worsening of motor scores. Of the 33 patients now taking combined therapy, seven have been followed up for 6 months or less. Twenty-four (92%) of the 26 patients taking combined therapy for a mean of 26 months (8.5 to 99 months) who have had Parkinson's disease for 6 years showed a dramatic improvement in their parkinsonism shortly after the addition of levodopa, with significant decreases in their rated motor scores, such improvement being maintained at their latest neurologic evaluation. Eighteen (75%) of these 24 patients responded to the combined selegiline/levodopa therapy with degrees of improvement equal to or greater than 50%, compared with their motor status at the start of combined therapy just before the addition of levodopa. This degree of "reversal" of parkinsonism on addition of levodopa (mean carbidopa/levodopa dose, 98/389 mg) was not observed in any of these same patients receiving selegiline alone for an average of 13.8 months. Four patients taking combined therapy developed mild, transient, abnormal involuntary movements, and end-of-dose pattern of response after more than 2 years of combined therapy (24.75 and 33.5 months, respectively). 
Rotavirus surveillance--United States, 1989-1990. Rotavirus infection is the most common cause of dehydrating diarrhea in children in the United States. In January 1989, CDC established a National Rotavirus Surveillance System (NRSS) to monitor national patterns in the epidemiology of rotavirus. This report summarizes findings from the NRSS from January 1989 through November 1990. 
Massive incisional hernia: abdominal wall replacement with Marlex mesh. Marlex (polypropylene) mesh was used to replace the abdominal wall in massive incisional herniation in 50 patients. Seventeen unsuccessful attempts at primary repair had previously been made on nine patients. Patient follow-up ranged from 6 to 120 months (mean = 45 months). There was minor hernia recurrence in four (8 per cent) patients. In each instance it was due to partial detachment of the peripheral fixation of the patch. Complications were: wound infection, four (8 per cent); wound seroma, two (4 per cent); wound haematoma, one (2 per cent); and wound sinus, six (12 per cent). Complications did not necessitate removal of the patch in any case. Inadequate peripheral attachment of the patch has been the only cause of hernia recurrence and should be avoidable. 
Palliation of proximal malignant biliary obstruction by endoscopic endoprosthesis insertion. For four years up to December 1987, 190 patients (median age 73 years) with proximal malignant biliary obstruction were treated by endoscopic endoprosthesis insertion. Altogether 101 had cholangiocarcinoma, 21 gall bladder carcinoma, 20 local spread of pancreatic carcinoma, and 48 metastatic malignancy. Fifty eight patients had type I, 54 type II, and 78 type III proximal biliary strictures (Bismuth classification). All patients were either unfit or unsuitable for an attempt at curative surgical resection. A single endoprosthesis was placed initially, with a further stent being placed only if relief of cholestasis was insufficient or sepsis developed in undrained segments. The combined percutaneous-endoscopic technique was used to place the endoprosthesis when appropriate, after failed endoscopic endoprosthesis insertion or for second endoprosthesis placement. Full follow up was available in 97%.Thirteen patients were still alive at the time of review and all but one had been treated within the past six months. Initial endoprosthesis insertion succeeded technically at the first attempt in 127 patients, at the second in 30, and at a combined procedure in a further 13 (cumulative total success rate 89% - type I: 93%; type II: 94%; and type III: 84%). There was adequate biliary drainage after single endoprosthesis insertion in 152 of the 170 successful placements, giving an overall successful drainage rate of 80%. Three patients had a second stent placed by combined procedure because of insufficient drainage, giving an overall successful drainage rate of 82% (155 of 190). The final overall drainage success rates were type I: 91%; type II: 83%; and type III: 73%. The early complication rates were type I: 7%; type II: 14%; and type III: 31%. 
Reactivity of proximal and distal angiographically normal and stenotic coronary segments in chronic stable angina pectoris. To assess whether vasoreactivity of significant coronary stenosis (greater than 50% intraluminal diameter reduction) and that of angiographically normal coronary segments differs in proximal and distal locations, 53 patients (40 men, 13 women, mean +/- standard deviation age 55 +/- 11 years) with chronic stable angina and angiographically documented coronary artery disease were studied. While abstaining from antianginal therapy, all 53 patients underwent coronary arteriography before and after 1 mg of intracoronary isosorbide dinitrate and 21 of the 53 also before and after 20 to 30 micrograms intracoronary ergonovine. Computerized quantitative angiography was used to assess changes in the intraluminal diameter of 126 normal coronary segments (63 proximal, 63 distal) and 43 significant coronary stenoses. Nitrates dilated proximal normal coronary segments by 7.4 +/- 1.2% and distal normal coronary segments by 15 +/- 1.7% (p less than 0.01). Significant proximal coronary stenoses dilated by 11 +/- 2.5% and distal stenoses by 23 +/- 2.8% (p less than 0.01) after nitrates. Ergonovine reduced the diameter of proximal normal coronary segments by 9.3 +/- 1.7% and that of normal distal segments by 15.5 +/- 1.4% (p less than 0.01). Proximal stenoses constricted by 11 +/- 2.2% and distal stenoses by 18.4 +/- 2.8% (p = 0.06). Analysis of segments showed that nitrates dilated 19 of 63 (30%) proximal normal segments by (greater than or equal to 10%), 31 of 63 (49%) distal (p less than 0.05) and 21 of 43 (49%) stenoses. 
Endometrial thickness after menopause: effect of hormone replacement Ultrasound (US) images of the pelvis were evaluated in 112 asymptomatic postmenopausal women to investigate the normal range of endometrial thickness (double-layer measurement) and the effect of hormone replacement on these measurements. Twenty-one patients (19%) had endometrial thickness greater than 0.8 cm. One patient, with an endometrial thickness of 2.5 cm, had endometrial carcinoma. Consideration of the known actions of estrogen and progestogen on the endometrium led the authors to believe that the clinical significance of an endometrium measuring more than 0.8 cm depends on the patient's hormonal status. Among asymptomatic postmenopausal women with an endometrial thickness between 0.8 and 1.5 cm, those receiving unopposed estrogen or continuous estrogen and progestogen need to undergo dilatation and curettage (D&C) or biopsy and those receiving no hormones or receiving sequential estrogen and progestogen should be encouraged to undergo D&C or biopsy. If a patient in one of the latter two groups is unwilling to undergo an invasive procedure, then US examination at 3-month intervals is acceptable. Any patient with endometrial thickness of at least 1.5 cm should undergo histologic diagnosis, regardless of symptoms or hormone status. 
Lineage-restricted clonality in biphasic solid tumors. Cytogenetic analysis of two pulmonary chondroid hamartomas and nine breast adenofibromas revealed clonal chromosome aberrations in both hamartomas and in four breast tumors. To determine lineage of the cells with chromosome aberrations, a combined immunohistochemical/cytogenetic approach was developed that enabled simultaneous ascertainment of cytogenetic aberrations and immunohistochemical features in individual cells. Immunohistochemical/cytogenetic evaluation of one hamartoma and two adenofibromas demonstrated that neoplastic proliferation, in each case, was confined to the mesenchymal (stromal) component, whereas epithelial cells appeared to be reactive. Cytogenetically abnormal short-term cultures of the remaining hamartoma and another of the breast adenofibromas were composed entirely of mesenchymal elements, indicating mesenchymal clonality in those tumors as well. Our findings support redesignation of pulmonary chondroid hamartomas as 'pulmonary chondromas' and suggest that carcinomas developing within fibroadenomas arise from reactive epithelial proliferation. Combined immunohistochemical/cytogenetic analysis might be useful in the development of novel therapeutic approaches that selectively target neoplastic populations within solid tumors. 
Intravascular streaming during carotid artery infusions. Demonstration in humans and reduction using diastole-phased pulsatile administration. Intra-arterial carotid artery chemotherapy for malignant gliomas is limited by focal injuries to the eye and brain which may be caused by poor mixing of the drug with blood at the infusion site. This inadequate mixing can be eliminated in animal models with diastole-phased pulsatile infusion (DPPI) which creates 1-ml/sec spurts during the slow blood flow phase of diastole. Before treatment with intracarotid cisplatin, 10 patients with malignant gliomas were studied to determine whether intravascular streaming occurs after intracarotid infusion in humans, and if so, if it is reduced with DPPI. Regional cerebral blood flow (rCBF) studies were performed by intravenous injection of H2(15)O and positron emission tomography. This was followed by supra- or infraophthalmic internal carotid artery (ICA) injections of H2(15)O with either continuous infusion or DPPI. Local H2(15)O concentration in the brain was determined and the images of radiotracer distribution in the continuous infusion and DPPI studies were compared to the rCBF images. Intravascular streaming of the infusate was identified by a heterogeneous distribution of the infused H2(15)O in brain compared to rCBF. Extensive and variable intravascular streaming occurred in three patients who received infusions into the supraophthalmic segment of the ICA. Some brain areas received up to 11 times the expected radiotracer delivery, while other regions received as little as one-tenth. This streaming pattern was markedly reduced or eliminated by DPPI. In the five patients who received infraophthalmic infusions, a minimally heterogeneous distribution of the infusate was detected. The authors conclude that extensive intravascular streaming accompanies supraophthalmic ICA infusions in patients. The magnitude of streaming can be substantially reduced or eliminated with DPPI. Those who perform intra-arterial infusion should consider using DPPI to assure uniform drug delivery to brain. 
Experimental superficial siderosis of the central nervous system. I. Morphological observations. Autologous washed red blood cells were injected weekly over a period of three to six months into the cisterna magna of adult New Zealand white rabbits. After three months, the surface of the brain stem, cerebellum, and piriform cortex showed a distinct brown color, and staining of the gross specimens for iron produced an intense blue color which extended for a distance of 1-2 mm into the brain parenchyma. Enhanced iron stains of vibratome sections revealed the accumulation of reaction product in microglia and Bergmann glia of the cerebellar cortex, and in microglia and astrocytes of the piriform cortex. Ferritin immunocytochemistry revealed reaction product in cerebellar microglia and Bergmann glia which strongly resembled that obtained by the enhanced iron stain. In the piriform cortex, only microglia were reactive with anti-ferritin. Electron microscopy confirmed the accumulation of electron-dense ferritin granules only in the cytoplasm of microglia. Bergmann glia in the cerebellum and astrocytic processes in the piriform cortex were replete with intermediate filaments and contained an excess of glycogen. After six months, small granules of hemosiderin began to appear in cerebellar and piriform cortices. The observations support that the sequence of conversion of hemoglobin to ferritin and hemosiderin occurs in brain as in other organs. 
Esophageal obstruction 14 years after treatment for Hodgkin's disease. The incidence of late radiation injury of the esophagus is not precisely determined but, overall, the occurrence of clinically apparent damage is infrequent. The authors report a complete esophageal obstruction in a 21-year-old man, 14 years after chemo-radiation therapy for Hodgkin's lymphoma. Although endoscopy failed to demonstrate a gross morphologic abnormality, an esophagogram detected abnormal peristalsis and stricture, and esophageal manometry coupled with dynamic isotopic study clearly demonstrated a multilevel secondary neuronal damage. Data in the literature suggest that alteration in motility is by far the most frequent radiologic manifestation. Further prospective studies will probably clarify the actual incidence of late esophageal damage after chemo-radiation therapy. 
Renal lesion characterization with gadolinium-enhanced MR imaging: efficacy and safety in patients with renal insufficiency. Five patients with renal insufficiency were studied with T1-weighted magnetic resonance (MR) imaging before and after intravenous administration of gadopentetate dimeglumine (0.1 mmol/kg) to characterize renal lesions that were detected with nonenhanced computed tomography (CT) and were considered indeterminate. Four patients demonstrated renal lesions that enhanced after gadolinium administration. A total of five lesions in these four patients were surgically resected and found to be renal cell carcinoma at pathologic examination. The fifth patient was spared surgery because a hyperattenuated lesion noted at nonenhanced CT did not enhance with intravenous gadolinium, indicating a benign cyst. Five incidentally occurring benign cysts removed at the time of nephrectomy in two of the patients did not demonstrate enhancement with gadolinium on MR images. Serial serum creatine levels were obtained before and after gadolinium administration in all patients; no changes were noted after gadolinium administration. Gadolinium-enhanced MR imaging is an effective method for characterizing renal lesions in patients with renal insufficiency. At the usual dosage, there appears to be no nephrotoxic reaction in these patients. 
Malignant colorectal polyps: venous invasion and successful treatment by endoscopic polypectomy. We reviewed the pathology of 81 malignant colorectal polyps in 80 patients treated by endoscopic polypectomy and assessed the importance of carcinomatous invasion of veins in the stalk (submucosa). All the patients were followed up for at least five years. Venous invasion was present in 30 of the polyps (37%). The histological features of lymphatic invasion were considered too subjective to be of value. Most of the tumours were well or moderately differentiated adenocarcinomas, one was poorly differentiated, and one was a signet ring cell carcinoma. Seventy one patients were treated by polypectomy alone, and 58 of these were alive and well five years later, with no evidence of recurrence. Nine died of unrelated causes within five years, but four died of carcinomatosis: one with recurrent tumour, one with a possible metachronous caecal cancer, and in two patients there was late development of malignancy of uncertain nature. The remaining nine patients underwent surgical resection after initial endoscopic polypectomy because of incompleteness of excision, poor differentiation of the tumour, or a decision by the surgeon. Tumour was not present in the resection specimens apart from a single lymph node deposit in the patient with signet ring cell carcinoma. These nine patients were alive and well without evidence of recurrence five years later. The results reemphasise the necessity of good cooperation between endoscopist and pathologist, meticulous laboratory technique, strict histopathological criteria including examination of resection margins and degree of differentiation of the tumour, and regular endoscopic follow up. 
Cachexia and tumour necrosis factor-alpha in cytomegalovirus infection. Although cachexia is a common feature of cytomegalovirus infection, little is known about its cause. To explore any contributory role that tumour necrosis factor-alpha (TNF) might have the serum concentrations of TNF in eight patients who developed CMV disease after liver transplantation were investigated. All patients exhibited pronounced and long lasting increases in TNF serum concentrations. Increased endogenous TNF concentrations were associated with weight loss and anorexia. In contrast, liver transplant recipients without CMV disease showed no weight loss. 
Transesophageal echocardiographic demonstration of distinct mechanisms for right to left shunting across a patent foramen ovale in the absence of pulmonary hypertension. The optimal visualization of the atrial septum and fossa ovalis by transesophageal echocardiography was utilized to demonstrate saline contrast transit across the atrial septum and to relate it to the motion of the flap valve (septum primum) of the fossa ovalis. In three cases, three distinct mechanisms of right to left interatrial shunting in the absence of right ventricular systolic hypertension were identified: 1) transient spontaneous reversal of the left to right atrial pressure differential with each cardiac cycle; 2) sustained elevation of right atrial pressure above left atrial pressure induced by respiratory maneuvers; and 3) aberrant flow redirection across the foramen ovale due to a large right atrial mass. Any of these three mechanisms may be operative during paradoxic embolism in the absence of elevation of right ventricular pressures. 
Scopolamine patch reduces postoperative emesis in paediatric patients following strabismus surgery. Scopolamine patch was evaluated for the prevention of postoperative emesis in 50 children undergoing strabismus surgery. All subjects were premedicated, with none receiving narcotic premedicants. Anaesthesia included controlled ventilation with the use of muscle relaxants, atropine, and halothane. Before operation, the subjects were randomly assigned to one of two groups: a treatment group received a scopolamine patch at a dose of either 0.75 mg or 0.375 mg, and a control group received no patch. Both the incidence and frequency of vomiting in the scopolamine-treated group were significantly (P less than 0.05) lower than in the control group. 
Enhanced immunoglobulin levels correlate with infectious complications after surgery in esophageal cancer. Severe septic complications account for the high mortality of patients with esophageal cancer. We examined the levels of immunoglobulins and complements together with infection-related complications in a large number of patients. Enhancements of IgG, IgA, C3, C4, and CH50 were evident in patients with esophageal cancer and were more predominant compared to findings in cases of gastric cancer. Average levels of IgG and IgA immediately before surgery were significantly higher in esophageal cancer patients with postoperative septic complications than in those without such problems. Preoperative radiation therapy and total parenteral nutrition did not significantly alter the levels of immunoglobulins and complements. It would thus appear that the enhancement of IgG and IgA is associated with the occurrence of infectious complications following surgery for patients with esophageal cancer. 
Exercise endurance and arterial desaturation in normobaric hypoxia with increased chemosensitivity. We studied whether exercise endurance under normobaric hypoxia can be enhanced by increasing hypoxic ventilatory sensitivity with almitrine bismesylate (ALM). On both ALM and placebo (PL) days, resting subjects breathed a hypoxic gas mixture (an inspired O2 fraction of 10.4-13.2%), which lowered resting arterial O2 saturation (SaO2) to 80%. After 15 min of rest there was a 3-min warm-up period of exercise at 50 W (light) on a cycle ergometer, followed by a step increase in load to 60% of the previously determined maximum power output with room-air breathing (moderate), which was maintained until exhaustion. With PL, SaO2 decreased rapidly with the onset of exercise and continued to fall slowly during moderate exercise, averaging 71.0 +/- 1.8% (SE) at exhaustion. With ALM, saturation did not differ from PL during air breathing but significantly exceeded SaO2 with PL, by 3.4% during resting hypoxia, by 4.0% at the start of exercise, and by 5.9% at exhaustion. Ventilation was not affected by ALM during air breathing and was slightly, although not significantly, increased during hypoxic rest and exercise. ALM was associated with an increased heart rate during room air breathing but not during hypoxia. Endurance time was 20.6 +/- 1.6 min with ALM and 21.3 +/- 0.9 min with PL. During hypoxic exercise, the potential benefit of greater saturation with ALM is apparently offset by other unidentified factors. 
Endoscopic sphincterotomy complications and their management: an attempt at consensus. Despite its relative safety (in comparison with surgery), and undoubted role in many clinical circumstances, biliary sphincterotomy is the most dangerous procedure routinely performed by endoscopists. Complications occur in about 10% of patients; 2 to 3% have a prolonged hospital stay, with a risk of dying. This document is an attempt to provide guidelines for prevention and management of complications, based on a workshop of selected experts, and a comprehensive review of the literature. We emphasize particularly the importance of specialist training, disinfection, drainage, and collaboration with surgical colleagues. 
Athletic participation after myocardial revascularization. Possibilities and benefits. Exercise after open heart operation is not only possible but highly desirable. Training increases the efficiency of exercise and therefore decreases myocardial work for any given level of activity. Even before sternal and incisional healing is complete the patient may become physically active. Almost every patient can improve his or her level of fitness safely by following simple guidelines. Exercise treadmill testing is the basis for assessing exercise capacity in cardiac patients. Upper-body exercise is not adequately emphasized in most exercise programs. 
Roles of muscularis mucosae and myofibroblasts in the healing process of acetic acid-induced ulcer. The changes in the localization of FITC-phalloidin-positive smooth muscle cells and interstitial cells were studied in control and acetic acid-treated rat fundic mucosa. In the control rats, the FITC-phalloidin-positive cells mostly corresponded to the smooth muscle cells of the muscularis mucosae, and the arteriolar and venular smooth muscle cells. On the other hand, 1 week after the acetic acid treatment, the fluorescence of the smooth muscle cells of the muscularis mucosae disappeared and a large number of fluorescent interstitial cells, probably corresponding to myofibroblasts, appeared in the regenerated mucosal layer. Three weeks after the application, severely thickened fluorescent muscularis mucosae were formed and the fluorescence of the interstitial cells was rather decreased. 
Infection of inbred rat strains with Rift Valley fever virus: development of a congenic resistant strain and observations on age-dependence of resistance. A congenic rat strain (WF.LEW) was derived from the susceptible Wistar-Furth (WF) (background strain) and the resistant LEW (donor strain) inbred strains and was used to evaluate the phenotypic expression of a dominant Mendelian gene that confers resistance to fatal hepatic disease caused by the ZH501 strain of Rift Valley fever virus (RVFV). Resistance to hepatic disease developed gradually with age, with full expression at approximately 10 weeks in the WF.LEW and LEW rat strains. The ZH501 strain caused fatal hepatitis in WF rats regardless of age. However, resistance to the SA75 RVFV strain (relatively non-pathogenic for adult rats), was age- and dose-dependent in both WF and LEW rats. The resistance gene transferred to the newly derived WF.LEW congenic rat strain appears to amplify age-dependent resistance of adult rats, resulting in protection against fatal hepatic disease caused by the virulent ZH501 strain. The congenic rat strain will be a valuable asset in elucidating the mechanism of resistance to Rift Valley fever virus governed by the dominant Mendelian gene. 
Diagnosis of cysticercosis in endemic regions. The Cysticercosis Working Group in Peru. Taenia solium cysticercosis is a frequent cause of neurological disease in developing countries. Specific diagnosis of cysticercosis is difficult. We obtained serum and/or CSF samples from 204 consecutive patients admitted to a neurological ward in Lima, Peru, and looked for antibodies specific for T solium with the enzyme-linked immunoelectrotransfer blot (EITB) assay. 21 (12%) of 173 serum samples from these patients were EITB-positive. In contrast, only 2 (1.5%) of 135 patients attending a public endoscopy clinic and 1 (1%) of 88 patients attending a private endoscopy clinic were seropositive. 1 (1%) of 98 pregnant women living in a Lima shanty town was EITB-positive. 15 (58%) of 26 neurology patients diagnosed clinically as having cysticercosis were seronegative. Routine screening by EITB of all patients with neurological symptoms from areas of endemic cysticercosis would avoid misdiagnosis of this common and treatable disease. 
Function of the diabetic retina after panretinal argon laser photocoagulation. Influence of the intensity of the coagulation spots. To investigate the influence of the intensity of coagulation spots on retinal function and the clinical course after panretinal argon laser photocoagulation in diabetic retinopathy, we conducted a prospective study in 24 eyes of 12 diabetics. One eye was treated with moderate spots (average: 300 mW), the fellow eye was coagulated with intense spots (average: 600 mW). The spot size was identical in both eyes. Subjective parameters (visual acuity, perimetry), as well as objective functions (ERG, EOG) and the clinical course, were studied preoperatively and on a regular base with a follow-up of 12 months. Visual acuity and fundus findings deteriorated less often in eyes coagulated with intense spots. Visual field loss, however, was more prevalent in eyes treated with intense spots. Early treatment complications only occurred with high-energy coagulation. For this reason, high-energy spots should not be used even though they might be indicated theoretically. 
Association of a precore genomic variant of hepatitis B virus with fulminant hepatitis. A variant of hepatitis B virus has been described recently in HBsAg+ Mediterranean patients who lack HBeAg and who have an unusual and severe form of chronic hepatitis. This variant is unable to produce HBeAg because of the presence of a novel translational stop codon at the end of the precore region of the genome. By direct sequencing of DNA, generated by the polymerase chain reaction, we have evaluated the association between infection with this variant and the fulminant course of hepatitis B. Eighteen patients with fulminant hepatitis B were studied. Of the 15 cases from whose serum viral DNA could be sequenced, the variant was found in the admission sera of 8 of 9 HBeAg- patients but in none of 6 HBeAg+ patients who had fulminant hepatitis B. Patients harboring the variant progressed more rapidly into hepatic encephalopathy, but those infected with the variant strain alone had a greater likelihood of survival than those infected with the normal strain or a mixture. The mutant strain may emerge spontaneously during fulminant hepatitis as occurs in chronic hepatitis B infection during seroconversion from HBeAg to antibody. Alternately, and perhaps less commonly, patients may be infected with the variant ab initio. 
Infectious and inflammatory processes of the spine. Infectious and inflammatory processes of the spinal column are discussed, including disc space infection, osteomyelitis, epidural abscess, arachnoiditis, and rheumatoid arthritis. The relative sensitivity and specificity of various imaging modalities, as well as the imaging characteristics and utility of these various modalities are given. Emphasis is placed on the use of magnetic resonance imaging. 
Intrathoracic osteosarcoma diagnosed by CT scan and pleural biopsy. Osteosarcoma rarely presents as a primary lesion in the chest, whereas pulmonary metastases are common. The diagnosis of primary intrathoracic osteosarcoma has invariably been by thoracotomy or autopsy. We present a case of a densely calcified, primary intrathoracic osteosarcoma where diagnosis was made antemortem by pleural biopsies and computed tomography scan. 
Diffuse mesangial sclerosis in a fetus. An 18-week fetus was born following termination of pregnancy by prostaglandin induction. Pregnancy was terminated because of elevated maternal serum alpha-fetoprotein and ultrasonographic evidence of severe oligohydramnios, intrauterine growth retardation, non-visualization of the bladder, dolichocephaly and possible mild hydrocephalus. Pathologic examination disclosed diffuse mesangial sclerosis and histologic evidence of the nephrotic syndrome. To our knowledge this is the first reported example of ante-natal diffuse mesangial sclerosis; of fetal congenital nephrosis other than Finnish type; and of fetal congenital nephrosis with prominent glomerular lesions. 
The zinc-reversible antimicrobial activity of neutrophil lysates and abscess fluid supernatants. There is some evidence to suggest that microbial growth inhibition may occur in chronic abscesses. A substance perhaps responsible for this phenomenon is calprotectin, a neutrophil cytoplasmic protein that inhibits microbial growth and that belongs to a class of proteins often having specific binding sites for zinc. In the present study, the suppressive effects of either human or mouse neutrophil lysates on Candida albicans growth were found to be completely reversed by micromolar quantities of zinc but not by iron or other trace elements. Similarly, supernatants of exudates from experimental abscesses in mice or from clinical specimens of abscesses in humans markedly inhibited the proliferation of C. albicans, and this effect was also completely reversed by zinc. A protein complex characteristic of calprotectin was identified in the abscess fluids. Preparations of the neutrophil growth-inhibiting protein, containing predominantly calprotectin, were shown to have zinc-binding activity by a dialysis technique. These findings suggest that the major mechanism of C. albicans growth inhibition by abscess fluids is through competition for zinc by a cytoplasmic protein apparently released from dying neutrophils. 
Acute atraumatic subdural hematoma associated with moyamoya disease in an African-American. A 57-year-old black woman with an atraumatic subdural hematoma was treated for congestive heart failure and was found to have moyamoya disease. The association of these two lesions is rare and has never been described in an African-American. High cerebral venous pressures and changes in cerebral perfusion caused by congestive heart failure and the loss of cerebrovascular autoregulation in moyamoya disease may explain the spontaneous occurrence of a subdural hematoma. Recommendations for management are discussed. 
Management of radionecrosis of the vulva and distal vagina. Twelve patients were seen between January 1983 and June 1989 with the clinical diagnosis of radionecrosis of the vulva or distal vagina. Seven patients received radiation for vulvar cancer, three for distal vaginal cancer, and two for recurrent endometrial cancer. No patient healed spontaneously and the mean delay in surgical therapy was 8.5 months. The radionecrotic site was treated with local therapy, radical local excision (with or without colostomy), or exenteration. The operative defect was closed primarily in three patients and covered with local flaps or myocutaneous flaps in seven patients. The two patients with local care still have radionecrotic ulcers. One of three patients who were closed primarily continues to have an ulcer. All other patients have healed satisfactorily except one who died after two attempts to correct the problem. Radionecrosis of the vulva and distal vagina should generally be treated surgically. 
Primary resection and anastomosis in obstructed descending colon due to cancer. Intraoperative colonic irrigation followed by one-stage resection is gaining popularity as the optimal surgical treatment for left-sided colonic obstruction. However, its efficacy and potential hazards have not been adequately tested in obstruction due to colonic cancer. We analyzed the early results of 23 consecutive patients with obstructive left-sided colonic carcinoma treated by primary resection and anastomosis following intraoperative antegrade colonic lavage. Two patients (8.6%) died, one from complication of anastomotic leakage. The significant postoperative complications were chest infection in three (13%) and wound infection in seven (30.4%). The average hospital stay was 16.5 days. The results of this study suggest that intraoperative bowel irrigation permits one-stage resection and anastomosis to be conducted with reasonable safety provided care is taken in operative techniques. 
Phacoemulsification combined with pars plana vitrectomy. Phacoemulsification combined with pars plana vitrectomy was performed on seven patients with both cataracts and vitreoretinal disease. Six of the seven had a posterior chamber intraocular lens (PC-IOL) placed in the capsular bag following cataract extraction. Visual acuities ranging from light perception to hand movement preoperatively, postoperatively ranged from hand movement to 20/25. There were no perioperative complications. During an average follow-up of more than 6 months, neovascular glaucoma developed in one patient, and a conjunctival cyst in another. The PC-IOLs were well tolerated. The small limbal incision used in phacoemulsification allows better control during the vitrectomy procedure and ensures a water-tight wound. In addition, with the limbal approach, the posterior lens capsule is maintained, with all the attendant advantages. 
A phase I trial of recombinant human interleukin-1 beta alone and in combination with myelosuppressive doses of 5-fluorouracil in patients with gastrointestinal cancer. We studied escalating doses of recombinant human interleukin-1 beta (IL-1 beta) alone and after a myelosuppressive dose of 5-fluorouracil (5-FU) in patients with gastrointestinal cancer. Transient neutropenia, monocytopenia, and lymphocytopenia were observed followed by a 1.3- to 6.0-fold (mean, 3.46-fold) dose-dependent neutrophil leukocytosis (P less than .00001) on the days of IL-1 beta administration. Increases in platelet counts were observed at a median of 14 days (range, 6 to 23) after IL-1 beta administration. Transient hypoglycemia, rebound hyperglycemia, elevations in serum cortisol, and C-reactive protein were observed. Side effects included fever, rigors, and headache in the majority of patients. Hypotension was observed in three of five patients at the highest dose level (0.1 micrograms/kg) and was dose-limiting. Fewer days of neutropenia were noted after 5-FU plus IL-1 beta than after 5-FU alone; however, this difference did not reach statistical significance. These data show that IL-1 beta has stimulatory effects in human hematopoiesis. 
Localization of the gene encoding the GABAA receptor beta 3 subunit to the Angelman/Prader-Willi region of human chromosome 15. Deletions of the proximal long arm of chromosome 15 (bands 15q11q13) are found in the majority of patients with two distinct genetic disorders, Angelman syndrome (AS) and Prader-Willi syndrome (PWS). The deleted regions in the two syndromes, defined cytogenetically and by using cloned DNA probes, are similar. However, deletions in AS occur on the maternally inherited chromosome 15, and deletions in PWS occur on the paternally derived chromosome 15. This observation has led to the suggestion that one or more genes in this region show differential expression dependent on parental origin (genetic imprinting). No genes of known function have previously been mapped to this region. We show here that the gene encoding the GABAA (gamma-aminobutyric acid) receptor beta 3 subunit maps to the AS/PWS region. Deletion of this gene (GABRB3) was found in AS and PWS patients with interstitial cytogenetic deletions. Evidence of beta 3 gene deletion was also found in an AS patient with an unbalanced 13;15 translocation but not in a PWS patient with an unbalanced 9;15 translocation. The localization of this receptor gene to the AS/PWS region suggests a possible role of the inhibitory neurotransmitter GABA in the pathogenesis of one or both of these syndromes. 
Sleep apnea in patients with acute myocardial infarction. OBJECTIVE: To document sleep apnea in the acute phase of myocardial infarction. If apnea occurs in patients with myocardial infarction, hypoxemia induced by apnea might exaggerate insufficiency of oxygen supplied to the damaged myocardium. DESIGN: Prospective controlled study. SETTING: Critical care unit of a teaching hospital. PATIENTS: Forty-nine patients, average age 64 yrs (range 49 to 91). MEASUREMENTS AND MAIN RESULTS: Patient measurements were recorded on a polygraph using an apnea-monitor, pulse oximeter, pulmonary artery pressure monitor, and an ECG. All of the patients observed showed frequent apneic episodes. The apnea was especially frequent when the cardiac index was low. Capillary oxygen saturation of less than 90% (suggesting systemic hypoxia) was observed in 21 patients concomitantly with apnea. Occasionally, arrhythmias followed these episodes (premature supraventricular contractions [n = 10], premature ventricular contraction [n = 4], and ventricular tachycardia [n = 2]). CONCLUSIONS: This study suggests that sleep apnea is common in the setting of acute myocardial infarction. It may be a factor predisposing to, or even causing, sudden death in patients with acute phase of myocardial infarction. 
Choanal atresia and lymphedema. The coexistence of bilateral bony choanal atresia and lower-extremity lymphedema was observed in a family with several consanguineous marriages. The combination of these two rare anomalies, in a hereditary form, has not been described before. 
Clinical overview of management of chronic ischemic heart disease. The outcome of patients with chronic coronary artery disease is dependent on many factors; the most important ones include the severity and extent of coronary artery disease, state of left ventricular function at rest, extent and severity of myocardial ischemia, and the total amount of left ventricular myocardium that is at risk. To use noninvasive tests optimally, the clinician first must define the information needed. The sensitivity, specificity, and predictive accuracy of the test(s) in providing the necessary information, the additive value of the result of a test to the information already available, and the best combination of tests in providing the desired information help determine the choice of various noninvasive tests in a particular clinical circumstance. 
A regional prospective study of in-hospital mortality associated with coronary artery bypass grafting. The Northern New England Cardiovascular Disease Study Group. OBJECTIVE--A prospective regional study was conducted to determine if the observed differences in in-hospital mortality rates associated with coronary artery bypass grafting (CABG) are solely the result of differences in patient case mix. DESIGN-Regional prospective cohort study. Data including patient demographic and historical data, body surface area, cardiac catheterization results, priority of surgery, comorbidity, and status at hospital discharge were collected. This study presents data for 3055 CABG patients between July 1, 1987, and April 15, 1989. SETTING--This study includes data from all surgeons performing cardiothoracic surgery in Maine, New Hampshire, and Vermont; the data were collected from five regional medical centers. PATIENTS--Data were collected from all consecutive isolated CABG surgery patients during the study period. MAIN OUTCOME MEASURES--Crude and adjusted in-hospital mortality rates associated with CABG. MAIN RESULTS--The overall crude in-hospital mortality rate for isolated CABG was 4.3%. The rate varied among centers (range, 3.1% to 6.3%) and among surgeons (range, 1.9% to 9.2%). Predictors of in-hospital mortality included increased age, female gender, small body surface area, greater comorbidity, reoperation, poorer cardiac function as indicated by a lower ejection fraction, increased left ventricular end diastolic pressure and emergent or urgent surgery. After adjusting for the effects of potentially confounding variables, substantial and statistically significant variability was observed among medical centers (P = .021) and among surgeons (P = .025). CONCLUSION--We conclude that the observed differences in in-hospital mortality rates among institutions and among surgeons in northern New England are not solely the result of differences in case mix as described by these variables and may reflect differences in currently unknown aspects of patient care. Understanding this variation requires a detailed understanding of the processes of care. 
Tumor necrosis factor-alpha inhibits 1,25-dihydroxyvitamin D3-stimulated bone Gla protein synthesis in rat osteosarcoma cells (ROS 17/2.8) by a pretranslational mechanism. Tumor necrosis factor-alpha (TNF alpha), a 17,000 mol wt protein, mediates a variety of immunological and inflammatory events. TNF alpha is a potent inhibitor of bone collagen synthesis and stimulator of osteoclastic bone resorption, the net effect of which is to cause bone loss. We have previously reported that TNF alpha inhibits the synthesis of collagen by osteoblastic cells in culture out of proportion to effects on total protein synthesis, suggesting that inhibition of bone formation by TNF alpha may be due to selective inhibition of matrix protein synthesis. To further test this hypothesis and to evaluate the mechanism of TNF alpha action, we studied the effect of TNF alpha on synthesis of the osteoblast-specific bone Gla protein (BGP) by ROS 17/2.8 cells, which have the osteoblast phenotype. Cells were cultured with 10 nM 1,25-dihydroxyvitamin D3 to stimulate BGP secretion, followed by the addition of TNF alpha (1-100 ng/ml) in 1,25-dihydroxyvitamin D3-containing medium. TNF alpha (10 ng/ml) inhibited BGP secretion to 42 +/- 5%, 19 +/- 10%, and 15 +/- 3% of control values after 24, 48, and 72 h of treatment. After 48 h, inhibition of BGP secretion was observed with 2 ng/ml TNF alpha and was maximum with 100 ng/ml. To determine the effect of TNF alpha on total protein synthesis, cells were pulse labeled with [14C]leucine during the last 4 h of TNF alpha treatment, and incorporation of radioactivity into trichloroacetic acid-precipitable protein in cell layer and medium was determined. The TNF alpha inhibition of BGP secretion was independent of changes in [14C]leucine incorporation, suggesting that TNF alpha did not have a general inhibitory effect on total protein synthesis. Cell number was not affected by TNF alpha. Northern analysis of steady state BGP mRNA revealed a dose-dependent decrease in the BGP/cyclophilin mRNA hybridization signal intensity after 24 h of treatment. The maximum inhibitory effect was 41 +/- 5% of the control value with 100 ng/ml TNF alpha. The effect of TNF alpha on steady state BGP mRNA levels was not prevented by treatment of cells with cycloheximide, suggesting that TNF-induced new protein synthesis was not required for TNF alpha action. These results suggest that the mechanism of TNF alpha inhibition of BGP synthesis includes a pretranslational site and support the hypothesis that TNF alpha inhibits bone formation by a selective inhibition of matrix protein production. 
C4A deficiency and poor prognosis in patients with IgA nephropathy. IgA nephropathy (Berger's disease) is an important cause of end-stage renal failure in persons of Asian and European descent. We performed C4 phenotyping on plasma from 123 patients with IgA nephropathy who resided in several different parts of the United States. All of these patients underwent diagnostic renal biopsy in adulthood. Six patients had a total deficiency for the C4A protein and all six had chronic renal insufficiency (serum creatinine concentration higher than 1.4 mg/dl at last follow-up). In contrast, 47% of the patients without C4A deficiency had chronic renal insufficiency (p = 0.001). The C4 gene defect was due to deletion of both C4A genes in only two individuals, whereas three patients were heterozygous for the C4A gene deletion. We speculate that the functional alteration of the complement system related to C4A deficiency might lead to expression of clinically severe disease in an individual with a genetic susceptibility to IgA nephropathy. 
A comparative immunohistochemical study of Kuru and senile plaques with a special reference to glial reactions at various stages of amyloid plaque formation. The authors examined 10 patients with Gerstmann-Straussler syndrome or Creutzfeldt-Jakob disease and 10 with Alzheimer's disease (AD). Immunohistochemistry using anti-prion protein (PrP) and anti-beta/A4 protein (beta/A4) coupled with formic acid pretreatment could detect Congophilic and non-Congophilic deposits. Prion protein deposits were classified into five types and compared with types of beta/A4 deposits. Kuru plaques with multicentric cores and fine granular deposits were a characteristic feature of PrP deposits. Some types of PrP or beta/A4 deposits depend on the anatomic sites. To clarify the relationship of microglia and astrocytes to PrP or beta/A4 deposits, double-immunostaining method was performed. In both kuru and senile plaques, microglia were closely linked to the Congophilic plaques. Astrocytes, however, extended their processes toward the plaques even in the non-Congophilic plaques. These observations strongly suggest that similar glial association with plaque formation may be involved in both kuru and senile plaques, although the amyloid core proteins differ. 
Determinant selection in murine experimental autoimmune myasthenia gravis. Effect of the bm12 mutation on T cell recognition of acetylcholine receptor epitopes. C57BL/6 (B6) mice respond to immunization with acetylcholine receptor (AChR) from Torpedo californica as measured by T cell proliferation, antibody production, and the development of muscle weakness resembling human myasthenia gravis. The congenic strain B6.C-H-2bm12 (bm12), which differs from B6 by three amino acid substitutions in the beta-chain of the MHC class II molecule I-A, develops a T cell proliferative response but does not produce antibody or develop muscle weakness. By examining the fine specificity of the B6 and bm12 T cell responses to AChR by using T cell clones and synthetic AChR peptides, we found key differences between the two strains in T cell epitope recognition. B6 T cells responded predominantly to the peptide representing alpha-subunit residues 146-162; this response was cross-reactive at the clonal level to peptide 111-126. Based on the sequence homology between these peptides and the T cell response to a set of truncated peptides, the major B6 T cell epitope was determined to be residues 148-152. The cross-reactivity of peptides 146-162 and 111-126 could also be demonstrated in vivo. Immunization of B6 mice with either peptide primed for T cell responses to both peptides. In contrast, immunization of bm12 mice with peptide 111-126 primed for an anti-peptide response, which did not cross-react with 146-162. Peptide-reactive T cells were not elicited after immunization of bm12 mice with 146-162. These results define a major T cell fine specificity in experimental autoimmune myasthenia gravis-susceptible B6 mice to be directed at alpha-subunit residues 148-152. T cells from disease-resistant bm12 mice fail to recognize this epitope but do recognize other portions of AChR. We postulate that alpha-148-152 is a disease-related epitope in murine experimental autoimmune myasthenia gravis. In this informative strain combination, MHC class II-associated determinant selection, rather than Ag responsiveness per se, may play a major role in determining disease susceptibility. 
Transesophageal echocardiography in the detection of potential cardiac source of embolism in stroke patients. To compare the diagnostic yields of transesophageal and transthoracic echocardiography in the detection of potential cardiac sources of embolism, 63 patients (mean +/- SD age 63 +/- 15 [range 18-87] years) with transient ischemic attacks or stroke underwent both procedures. Transthoracic echocardiography revealed a potential cardiac source of embolism in 14% (nine) of the patients, all of whom had clinical evidence of heart disease. Transesophageal echocardiography revealed a potential cardiac source of embolism in 41% (26) of the patients; 27% (seven) of these patients had no clinical cardiovascular abnormalities. Abnormalities detected only by transesophageal echocardiography in the patients with unsuspected cardiac disease included atrial septal aneurysm in two, patent foramen ovale in two, left atrial appendage thrombus in one, and myxomatous mitral valve in two. The 26 patients with an identified cardiac source of embolism were older (67.5 versus 59.4 years, p = 0.04), more frequently in atrial fibrillation (62% [16] versus 8% [3], p less than 0.0001), had a larger left atrium (43 versus 37 mm, p = 0.01) and more commonly had left ventricular hypertrophy (62% [16] versus 32% [12], p less than 0.02) than the 37 patients in whom no cardiac source of embolism was identified. Thus, transesophageal echocardiography is more sensitive than transthoracic echocardiography in the detection of potential cardiac sources of embolism in patients with cerebral ischemic events. 
Localization and needle aspiration of breast lesions: complications in 370 cases. A prospective study of the immediate complications of 370 consecutive breast-imaging procedures (203 wire localizations and 167 radiographically or sonographically guided fine-needle aspirations) is reported. Vasovagal reactions occurred in 27 (7%) of 370 cases, ranging in severity from syncope (four of 370, 1%) to mild light-headedness. These vasovagal reactions were independent of procedure type or use of local anesthesia, but were more common in younger patients. Other complications included prolonged (5 min or longer) bleeding (three of 370, 1%) and extreme pain (two of 370, 1%). One patient was found to have malignant hypertension. We conclude that wire localizations and imaging-guided aspirations are generally well tolerated procedures. However, vasovagal reactions are frequent enough to warrant close observation of patients. Radiologists and breast-imaging personnel should be able to recognize and treat vasovagal reactions. 
Response of atrial natriuretic factor to acute and chronic increases of atrial pressures in experimental heart failure in dogs. Role of changes in heart rate, atrial dimension, and cardiac tissue concentration. BACKGROUND. This study evaluated the role of changes in heart rate, atrial pressure, volume, and cardiac tissue atrial natriuretic factor (ANF) concentration in the modulation of plasma ANF concentration in a model of pacing-induced heart failure. METHODS AND RESULTS. The effects of acute right ventricular pacing (250 beats/min), acute volume expansion (35 ml/min), and volume expansion after 1 week of right ventricular pacing on plasma ANF concentration were compared in eight dogs (group 1). As shown during right ventricular pacing previously, volume expansion produced significant increases in cardiac filling pressures and left atrial volume. Right ventricular pacing and volume expansion produced similar increments in plasma ANF concentration: from 32 +/- 12 to 168 +/- 153 pg/ml (p less than 0.05) and from 32 +/- 9 to 137 +/- 113 pg/ml (p less than 0.05), respectively. When pacing was initiated after volume expansion, plasma ANF concentration increased further to 462 +/- 295 pg/ml (p less than 0.05) despite little change in filling pressures and left atrial volume. With repeated volume expansion after 1 week of pacing, there were no significant further increases in left atrial volume and plasma ANF concentrations (from 332 +/- 121 to 407 +/- 113 pg/ml) despite significant increases in filling pressures. Atrial and ventricular tissue samples were also obtained from 21 dogs paced to severe heart failure (group 2) and from 14 normal dogs (controls). In all groups, atrial ANF was higher than ventricular ANF concentration. At 1 week (group 1), left atrial appendage ANF concentration (6.2 +/- 2.5 versus 16.1 +/- 10.3 ng/mg) was reduced, whereas left ventricular free wall ANF concentration (0.62 +/- 0.31 versus 0.24 +/- 0.16 pg/mg) was increased compared with that of controls (both p less than 0.001). At severe heart failure (group 2), atrial ANF remained low, whereas ventricular ANF concentration was similar to that of the controls. CONCLUSIONS. These data indicate that in pacing-induced heart failure, changes in heart rate, atrial pressure, and volume all contribute to the increased plasma ANF concentration. However, by 1 week (early heart failure), ANF release is attenuated, perhaps because of the inability of the atria to be stretched further and because of reduced atrial ANF concentration. In addition, the ventricle may be an additional source of ANF. 
Lymphocytic adenohypophysitis: a pituitary mass lesion occurring in pregnancy. Proposal for medical treatment. Lymphocytic adenohypophysitis is a nonneoplastic, autoimmune cause of pituitary enlargement and insufficiency. Forty-eight of the 50 reported cases have occurred in women, nearly all in association with pregnancy. Left undiagnosed and untreated, it can progress to pituitary insufficiency and death. Histologic studies show characteristic changes of autoimmune disease with lymphocytic infiltration and destruction of anterior pituitary tissue with fibrotic replacement. Lymphocytic adenohypophysitis is currently diagnosed after other pituitary mass lesions are excluded and has been treated with a combination of neurosurgery and end-organ hormone replacement. However, with improved knowledge of the pathophysiologic characteristics and natural history of the disease and with the ability to make a prospective diagnosis, we believe glucocorticoids may suppress the inflammatory response and protect remaining pituitary tissue. Two previously unreported pregnancy-associated cases are described, including one prospectively diagnosed and treated without neurosurgery during pregnancy. Obstetrician-gynecologists must place lymphocytic adenohypophysitis in the differential diagnosis of pituitary enlargement associated with pregnancy, since treatment is available and the sequelae may be life-threatening. 
Hepatocellular carcinoma in Richardson's ground squirrels (Spermophilus richardsonii): evidence for association with hepatitis B-like virus infection. During studies of seasonal obesity, a high frequency of hepatic neoplasms was observed in Richardson's ground squirrels. Of 12 Richardson's ground squirrels examined thoroughly, 7 had mild or moderate degrees of chronic portal hepatitis and 6 (50%) had hepatocellular carcinoma. Serological tests for hepadnavirus surface antigen, anti-core antibody and virion DNA that recognize the ground squirrel hepatitis virus of California ground squirrels (Spermophilus beecheyi) were uniformly negative. Southern blot analyses of EcoRI digests of liver cell DNA demonstrated 3.2 kb fragments that hybridized with a ground squirrel hepatitis virus-specific probe in nontumorous liver tissue from 6 of 10 ground squirrels and in hepatocellular carcinoma specimens from 2 of 5 squirrels indicating infection with a hepadnavirus related to ground squirrel hepatitis virus. Failure, however, to detect serum antibody to ground squirrel hepatitis core antigen suggested probable antigenic differences between the ground squirrel hepatitis virus of California ground squirrels and the putative Richardson's ground squirrel agent. Further studies are required to fully characterize the hepadnavirus of Richardson's ground squirrels and to determine its relationship to hepatocarcinogenesis in this species. 
Experimental induction of heterotopic bone. Heterotopic bone can be induced in experimental animals by trauma to the soft tissues, by induction from living cells, or by extracts from bone and teeth. In the first two types, the mechanism of the inductive process is not known, whereas in the latter, a factor isolated from bone matrix induces bone formation. Mesenchymal cells in bone marrow are determined for development into cartilage and bone cells and only an unspecific stimulus, such as trauma or autotransplantation, is sufficient for the development into mature osteogenic tissue. Mesenchymal cells will not differentiate into bone cells unless stimulated by a specific inductive substance, bone morphogenetic protein (BMP). Implanted to a heterotopic site, BMP induces undifferentiated mesenchymal cells into a bone morphogenetic pathway of development, causing heterotopic bone formation. The quantitative inductive response is dependent on the source of the BMP, and the bone formation is also determined by the recruitment of inducible target cells and by the environment at the implantation site. Hence, the environment at the implantation site is of major importance for the amount of bone formed. BMP initiates a cascade of events that is modulated by endocrine and paracrine factors. The heterotopic bone has all the morphologic and biochemical characteristics of orthotopic bone, is subjected to turnover, and even has the intriguing ability to generate the formation of bone marrow. Experimental induction of heterotopic bone has become a most useful method to study osteoneogenesis and has supplied important information on the prerequisites for new bone formation and on the regulation of bone metabolism. 
Mechanisms of failure of mitral valve repair: an echocardiographic study. Surgical valve repair for mitral regurgitation has significant advantages over valve replacement, but little is known about the mechanisms of its failure. This echocardiographic study examined abnormalities leading to failed mitral valve repair in two populations: "immediate failure" of the valve repair in the operating room requiring a second run of cardiopulmonary bypass and "late failure" of valve repair necessitating reoperation on another occasion. Intraoperative echocardiography (IOE) after cardiopulmonary bypass was performed in 309 patients undergoing valve repair for mitral regurgitation over a 3-year period. Twenty-six (8%) of these patients had immediate failure of the repair demonstrated by IOE, requiring further repair or replacement during the same thoracotomy. The causes of immediate failure were left ventricular outflow tract obstruction (10 patients), incomplete correction (10 patients), and suture dehiscence (six patients). Echocardiography was performed on 17 patients requiring reoperation for recurrent mitral regurgitation who had undergone previous primary valve repair. These late failures resulted from progressive degenerative leaflet or chordal disease (n = 9) or suture dehiscence of the annular ring or the leaflet resection site (n = 6). In only two patients early in the series did the problem originate from inadequate initial surgery. IOE is an effective marker for unsuccessful mitral valve repair, and affords an understanding of the mechanism of the persistent dysfunction. Immediate failure of mitral repair may be reduced by greater attention to the mechanism of valve dysfunction and by changes in valvuloplasty technique to avoid outflow tract obstruction. Late failure after mitral repair occurs predominantly due to progression of disease, particularly in patients with severe myxomatous or annular abnormalities that are prone to progress. 
Sleep apnea and systemic hypertension: a causal association review. OBJECTIVE: To critically examine the causal association between sleep apnea syndrome and hypertension. METHODS: A retrospective systematic critique of five epidemiologic studies published in the English literature during 1978 to 1989 identified on Medline and manual literature searches. The evidence was evaluated using the standard observational criteria for causation: strength of association, consistency, dose-response relationship, temporal sequence, specificity, and biologic plausibility. RESULTS: We found evidence to support a causal association between sleep apnea syndrome and hypertension in consistency and specificity and some evidence to suggest a dose-response relationship. Review of the data dealing with the mechanisms important in the pathogenesis of sleep apnea and hypertension allowed us to advance several theories to provide support for biologic plausibility. CONCLUSION: We concluded that there is a positive association--relative risk estimate between 1.3 and 40--for sleep apnea syndrome and hypertension, but the risk association is unstable. Thus, we believe that there is insufficient data to justify doing polysomnography as part of the routine diagnostic work-up for patients with hypertension. 
Accessory receptors regulate coupling of the T-cell receptor complex to tyrosine kinase activation and mobilization of cytoplasmic calcium in T-lineage acute lymphoblastic leukemia. T-lineage acute lymphoblastic leukemia (T-ALL) cells have abundant cytoplasmic CD3/Ti but express low amounts on the cell surface and are deficient in CD3/Ti-mediated signal transduction. Nevertheless, plating T-ALL cells on dishes containing immobilized anti-CD3 monoclonal antibodies with a source of growth factors induced the expression of CD25 (interleukin-2 receptor alpha chain) and stimulated the formation of blast colonies in 12 of 14 cases studied. The proliferative response to CD3 ligation was modulated by the presence of antibodies to the CD2, CD4, or CD8 accessory T-cell receptors. The effect of these accessory receptors on signal transduction mediated by CD3/Ti was next investigated by monitoring cytoplasmic calcium concentration [( Ca2+]i) and by measuring tyrosine phosphorylation after stimulation. Crosslinking CD3, CD2, CD4, or CD8 alone did not induce cytoplasmic calcium mobilization in T-ALLs, but crosslinking the accessory receptors with CD3/Ti induced calcium responses in three of the T-ALLs and enhanced calcium responses in three of the T-ALL cell lines, including HPB-ALL, MOLT-4, and CEM. Crosslinking CD4 but not CD2 with CD3/Ti greatly enhanced tyrosine phosphorylation of multiple substrates in comparison with crosslinking either CD4 or CD3/Ti separately on both normal mature T cells and the CEM T-ALL cell line. Thus, CD4 regulates CD3/Ti signal transduction in T-ALL cells through the tyrosine phosphorylation of substrates whereas CD2 may regulate [Ca2+]i signal transduction through a separate mechanism. 
Double-inlet ventricle presenting in infancy. II. Results of palliative operations. The influence of palliation on survival was studied in 191 consecutive infants, presenting at under 1 year of age, with double-inlet ventricle (1973 to 1988, median follow-up 8.5 years). Palliative operations were performed on 154 occasions in 121 patients (63%). Survival after a systemic-pulmonary arterial shunt (n = 57) and banding of the pulmonary trunk (n = 35) was comparable (84% and 77% at 1 year, 62% and 45% at 5 years), but those who underwent repair of aortic arch obstruction fared worse (n = 18, 44% and 22% at 1 and 5 years, p less than 0.001). The remainder did not undergo an operation because of balanced physiology (n = 17, 9% of entire group), complex anatomy (n = 32, 15%), or irreversible low output (n = 19, 12%). Palliative surgery, overall, had a deleterious effect on immediate survival (greater than 1 month relative risk 6.6, p less than 0.001), but, in the survivors, medium-term outcome was improved (greater than 6 months, 0.68, p less than 0.05). This effect was most marked for those undergoing a systemic-pulmonary artery shunt (less than 1 month, 2.52; greater than 6 months, 0.43); by contrast, after banding of the pulmonary trunk, with or without additional repair of the aortic arch repair, medium-term risk was not altered (greater than 6 months, 1.13 and 0.91, respectively). These data will assist the clinician in making decisions concerning the management of infants with double-inlet ventricle and in the judicious use of palliative surgery. 
Effect of intraoperative aprotinin administration on postoperative bleeding in patients undergoing cardiopulmonary bypass operation. To study the hemostyptic effect of aprotinin (Trasylol) in patients undergoing extracorporeal circulation for coronary artery bypass operations, we randomized 12 of 24 patients to receive aprotinin in high dosage (about 800 mg) during extracorporeal circulation. From the resulting two groups each, one patient was excluded from the study because of postoperative myocardial infarction (control group) and surgical hemorrhage (aprotinin group) leading to a second operation. Although heparin was used for anticoagulation in all 22 patients, all had a marked increase in plasma levels of thrombin-antithrombin III complexes during extracorporeal circulation, indicating an intravasal activation of coagulation. By monitoring the plasma levels of fibrin degradation products in patients without aprotinin therapy, we recorded a concomitant hyperfibrinolysis significantly less pronounced in patients receiving aprotinin (p less than 0.005). The mean total postoperative blood loss was lower in patients receiving aprotinin (620 ml) than in control patients (1000 ml; p less than 0.03). The results confirm previous reports of a hemostyptic effect of aprotinin in cardiac operations. This effect is probably due to a prevention of hyperfibrinolysis. 
Gout and hyperuricemia. Accurate diagnosis is essential since gout is overdiagnosed by a factor of three. Asymptomatic hyperuricemia is not associated with adverse consequences and should not ordinarily be treated. The acute attack of gout responds to any nonsteroidal anti-inflammatory drug, and antihyperuricemic therapy with allopurinol, probenecid or sulfinpyrazone is effective in lowering uric acid and preventing further attacks. Except for prophylaxis, colchicine is not recommended for the treatment of gout because of unacceptable levels of toxicity. Diet therapy, once a mainstay of treatment, is usually not indicated since drug therapy alone is far more efficacious. 
Reduced cerebral grey matter observed in alcoholics using magnetic resonance imaging. Twenty-eight chronic alcoholics and 36 age- and sex-matched non-alcoholic controls were examined with magnetic resonance imaging and brain morphometric analyses. Results confirmed large increases in subarachnoid cerebrospinal fluid (CSF) volume and mild ventricular enlargement in the alcoholics and revealed associated volume reductions of localized cortical and subcortical cerebral structures. Volume losses in the diencephalon, the caudate nucleus, dorsolateral frontal and parietal cortex, and mesial temporal lobe structures were the most prominent. Significant correlations between increments in cortical and ventricular CSF and decrements in the volume of cortical and subcortical grey matter were noted. Although there was little evidence for relationships between performance on neuropsychological tests and volume of grey matter structures, significant correlations between some cognitive measures and subcortical and cortical fluid volumes were found. The parallels between this pattern of affected structures and recent neuropathological findings are discussed. 
Pathogenesis of edema in constrictive pericarditis. Studies of body water and sodium, renal function, hemodynamics, and plasma hormones before and after pericardiectomy. BACKGROUND. The pathogenesis of sodium and water accumulation in chronic constrictive pericarditis is not well understood and may differ from that in patients with chronic congestive heart failure due to myocardial disease. This study was undertaken to investigate some of the mechanisms. METHODS AND RESULTS. Using standard techniques, the hemodynamics, water and electrolyte spaces, renal function, and plasma concentrations of hormones were measured in 16 patients with untreated constrictive pericarditis and were measured again in eight patients after pericardiectomy. The average hemodynamic measurements were as follows: cardiac output, 1.98 l/min/m2; right atrial pressure, 22.9 mm Hg; pulmonary wedge pressure, 24.2 mm Hg; and mean pulmonary artery pressure 30.2 mm Hg. The systemic and pulmonary vascular resistances (36.3 +/- 2.5 and 3.2 +/- 0.3 mm Hg.min.m2/l, respectively) were increased. Significant increases occurred in total body water (36%), extracellular volume (81%), plasma volume (53%), and exchangeable sodium (63%). The renal plasma flow was only moderately decreased (49%), and the glomerular filtration rate was normal. Significant increases also occurred in plasma concentrations of norepinephrine (3.6 times normal), renin activity (7.2 time normal), aldosterone (3.4 times normal), cortisol (1.4 times normal), growth hormone (21.8 times normal), and atrial natriuretic peptide (5 times normal). The ratio of left atrial to aortic diameter measured by echocardiography was only minimally increased (1.29 +/- 0.04), indicating that in constrictive pericarditis the atria are prevented from expanding. The studies repeated after pericardiectomy in the eight patients showed that all measurements returned toward normal. CONCLUSIONS. The restricted distensibility of the atria, in constrictive pericarditis, limits the secretion of atrial natriuretic factor and, thus, reduces its natriuretic and diuretic effects. This results in retention of water and sodium greater than that occurring in patients with edema from myocardial disease. The arterial pressure is maintained more by the expansion of the blood volume than by an increase in the peripheral vascular resistance. 
Transient penetration of the hip joint during in situ cannulated-screw fixation of slipped capital femoral epiphysis. Before the routine intraoperative use of fluoroscopy at our institution during procedures to stabilize a slipped capital femoral epiphysis, twenty-five patients (thirty hips) had in situ cannulated-screw stabilization of a slipped capital femoral epiphysis with use of biplane radiography. Thus, a permanent record of the procedure was available for review. Fourteen hips in fourteen patients had an intraoperative episode during which the joint was penetrated by the guide-pin assembly or cannulated screw, or both. This penetration was corrected at the time of the operation. Eleven patients were followed for a minimum of two years (mean, thirty-nine months; range, twenty-four to sixty-three months). All physes went on to closure. None of the patients had clinical or radiographic evidence of chondrolysis. Transient penetration of the hip joint did not lead to chondrolysis in this series. This suggests that a single episode of penetration by a pin or screw, with immediate removal from the joint, is not associated with the development of chondrolysis. 
Massive hepatic enlargement with fatty change associated with ketoconazole Several forms of hepatic toxicity have been described with the antifungal agent ketoconazole. We report a case of massive liver enlargement with fatty infiltration presenting as gastric compression. This occurred in a young woman with AIDS taking ketoconazole as maintenance therapy for cryptococcal meningitis. This is the first reported case of ketoconazole causing fatty change in the liver. 
Angelchik prosthesis complicates treatment of adenocarcinoma in Barrett's esophagus. Indications for use of the Angelchik prosthesis remain controversial, and many surgeons actively involved in the treatment of reflux disease have not used the device. We describe a case that illustrates difficulties associated with resection of a tumor in the presence of this prothesis. Such experience suggests that patients known to have Barrett's esophagus might be better treated with standard antireflux procedures. 
Appendicitis: prospective evaluation with high-resolution CT. Computed tomography (CT) was used to prospectively evaluate 100 patients with clinical indications for acute appendicitis. Examinations were performed with the terminal ileum and cecum filled with contrast material. Acute appendicitis was diagnosed when an abnormal appendix or inflammatory changes plus an appendicolith were detected. Failure to visualize an abnormal appendix or appendicolith in the presence of pericecal inflammatory changes was considered suspicious but nonspecific. CT results were correlated with surgical and pathologic results (74 patients) and other radiologic and clinical findings (26 patients). CT helped to diagnose appendicitis (64 patients) and nonspecific right lower quadrant inflammation (five patients) and to rule out appendicitis (31 patients). CT had a 98% sensitivity, an 83% specificity, and a 93% accuracy. In 17 of 31 patients without CT evidence of appendicitis, other conditions explaining their symptoms were detected. When the clinical diagnosis is in doubt, CT can be used successfully to evaluate patients with acute appendicitis. 
Syndrome of the cervical plexus caused by high cervical nerve root compression. Lesions affecting the roots of the cervical plexus can cause a syndrome not previously described. The C3-C4 disc space is the most likely to be involved, but pressure on the C5 root can also produce facial, auricular, or retroauricular pain. Motor innervation to the diaphragm can be affected, and even the uppermost disc space at C2-C3 might be implicated. Findings on examination findings are sparse, although sensory impairment in areas of cervical plexus innervation has been observed. In a series of 1000 cervical decompression cases (both anterior and posterior) for disc disease or similar processes, only 10 instances of this syndrome have been found. Paresthesia or episodic shock-like pain affecting the ear, para-auricular, lower occipital, and mandibular areas prompted by head turning or extension are the most common complaints. 
Fast short-tau inversion-recovery MR imaging. To enhance the versatility of the short-tau inversion-recovery (STIR) sequences, the authors determined a range of repetition time (TR) and inversion time (TI) combinations that suppress signal intensity from fat by study of both patient and phantom images. To make fast STIR images, variations in the following pulsing conditions were studied with use of an interactive computer program: decreasing the TR, limiting the number of excitations, and limiting the number of phase-encoding steps. The authors found that (a) STIR imaging need not be time consuming, (b) fat suppression can be accomplished at shorter TR by using shorter TI, and (c) short-TR fast STIR imaging is sensitive to enhancement with gadopentetate dimeglumine. 
Antibody responses to protein, polysaccharide, and phi X174 antigens in the hyperimmunoglobulinemia E (hyper-IgE) syndrome. To investigate whether an underlying defect in antibody (Ab)-forming capacity could contribute to the infection susceptibility of patients with hyper-IgE syndrome, we evaluated 11 such patients for their responses to bacteriophage phi X174 (phi X174), diphtheria and tetanus toxoids, and pneumococcal (Pneumovax) and Hemophilus influenzae vaccines. Three of nine patients immunized with phi X174 had normal primary and secondary Ab responses, five had accelerated declines in their titers after initially normal primary Ab responses and lower than normal secondary Ab responses, and two of the latter patients failed to switch normally from IgM to IgG Ab production. Only one of 10 patients tested had normal Ab responses to diphtheria toxoid, and postimmunization antitetanus titers were abnormally low in five of the 10 patients tested. Serum Abs to H. influenzae polyribose phosphate were protective in seven of the eight immunized patients. Five of the nine patients administered Pneumovax had poor Ab responses to at least one of the pneumococcal serotypes 7, 9, or 14. Abnormal antipolysaccharide responses did not correlate with IgG2 deficiency. All patients responded with protective Ab levels to type 3. Thus, patients with hyper-IgE syndrome are heterogeneous with respect to their Ab-forming capacities. Ab deficiency may contribute to infection susceptibility in some of these patients. 
Immunohistochemical expression of galactomannan in the cytoplasm of phagocytic cells during invasive aspergillosis. The monoclonal antibody EB-A1 to galactomannan is apparently specific for detecting Aspergillus species and Penicillium marneffei in formalin-fixed, paraffin-embedded tissues. It reveals hyphae, remnants of filaments, and organisms in the cytoplasm of some phagocytic cells. 
Successful transcatheter embolization of pseudoaneurysm associated with pancreatic pseudocyst. Hemorrhage into a pancreatic pseudocyst is a rare event, but is the most rapidly lethal complication of chronic pancreatitis. Visceral-vessel aneurysms are an unexpectedly common finding in arteriography of patients with chronic pancreatitis. This case report describes bleeding from an anterior superior pancreaticoduodenal artery aneurysm, caused by chronic pancreatitis. The aneurysm was successfully treated by embolization with a steel coil. 
Successful operation on a coronary arteriovenous fistula in a 74 year old woman. Coronary arteriovenous fistulas are rare and are usually diagnosed in children or young adults. Most are believed to be congenital. A right coronary arteriovenous fistula was first diagnosed in a patient of 74. Despite her age the fistula was successfully operated on and her symptoms were relieved. 
Antifungal treatment by amphotericin B and 5-fluorocytosine delays the recovery of normal hematopoietic cells after intensive cytostatic therapy for acute myeloid leukemia. Systemic fungal infections are recognized at increasing frequency during the course of intensive therapy for acute leukemias and require parenteral antifungal treatment mostly by amphotericin B (ampho B) alone or in combination with 5-Fluorocytosine (5-FC). Because of the potential myelosuppressive side effects of 5-FC it was the aim of the current study to evaluate the recovery of hematopoietic cells after intensive antileukemic therapy in patients receiving ampho B and 5-FC treatment for proven or suspected systemic fungal infections. The study population comprised 87 patients who were treated by standard chemotherapy for acute myeloid leukemia (AML) at first diagnosis or relapse. Twenty-two patients underwent systemic antifungal therapy consisting of ampho B (3 to 10 mg/kg/d) and 5-FC (150 mg/kg/d) for 3 to 33 days (median, 12 days). The remaining 65 patients served as controls to assess the hematologic recovery time (TR) as defined by the interval between the onset of chemotherapy and the post-treatment rise of granulocyte levels to greater than 500 cmm and thrombocyte levels to greater than 20,000 cmm. In patients receiving antifungal therapy, a significant prolongation of TR was observed with a median TR of 29 days compared with a median TR of 24 days (P = 0.0016) for the control group. No correlation was found between TR and the total dose of either ampho B or 5-FC or the type of antileukemic regimen. A possibly direct myelosuppressive effect of a fungal infection was unlikely to explain the findings because the ampho B/5-FC treatment was started in patients with proven or only suspected fungal infections, causing a similar delay of TR in both groups. The present data strongly suggest a myelosuppressive effect of ampho B/5-FC antifungal treatment in patients after intensive chemotherapy for acute leukemias. 
Postoperative deficits and functional recovery following removal of tumors involving the dominant hemisphere supplementary motor area. The supplementary motor area (SMA) is a region located within each cerebral hemisphere at the posterior mesial border of the frontal lobe adjacent to the falx. The functional significance of this area has been somewhat unclear, and information regarding its influence on motor output has largely been based on evoked responses to direct stimulation in primates and humans. In this series of patients with primary and metastatic tumors involving the dominant hemisphere SMA, a distinct pattern of postoperative deficits and recovery has emerged which emphasizes the role of this critical area in the initiation of motor activity, including speech. Based upon this analysis, ablation of this region after first identifying the primary motor cortex may be accomplished without risk of permanent loss of motor activity or speech function, despite the initial severe deficits. 
A case of photosensitivity and contact allergy to systemic tricyclic drugs, with unusual features. A 43-year-old farmer on tricyclic antidepressive drugs developed a severe photodermatitis with associated liver involvement. The lesions spread to covered areas of the skin, suggesting photoallergy clinically. Patch and photopatch testing revealed photoallergy and contact allergy to clomipramine and contact allergy also to carbamazepine. In addition, the patient had positive patch test reactions to chlorpromazine, balsam of Peru and fragrance-mix, as well as a positive photopatch test to fentichlor. UVA and UVB erythema thresholds were normal. In this patient, an initial episode of photosensitization, probably elicited by clomipramine, was accompanied by contact allergy to this drug and to carbamazepine. The contact sensitivity to clomipramine could also be elicited by oral provocation without UV light. Hypothetically, a photoproduct of clomipramine may have been the original sensitizer, this compound subsequently cross-reacting with clomipramine and, possibly with carbamazepine. 
Hypophosphatemic osteomalacia in von Recklinghausen neurofibromatosis. Skeletal lesions are not uncommon in von Recklinghausen neurofibromatosis. Most of them are considered to be dysplastic in nature. Association of osteomalacia or rickets with neurofibromatosis has been documented only rarely. Reported herein is a 40-year-old woman with known von Recklinghausen neurofibromatosis who presented with bone pain, multiple pseudofractures, marked increase in osteoid by bone biopsy, and hypophosphatemia with renal phosphate wasting. Treatment with oral phosphate and vitamin D was effective. A survey of the literature revealed that 34 similar cases have been reported in the past. Although the exact pathogenetic mechanism remains to be determined, osteomalacia in neurofibromatosis appears to be distinct from more common dysplastic skeletal affections of this disease, being characterized by later onset in adulthood as a rule, renal phosphate loss with hypophosphatemia, multiple pseudofractures in typical cases, and response to treatment with pharmacological dose of vitamin D with or without phosphate supplement. 
Occult metastatic neck disease: detection with US and US-guided fine-needle aspiration cytology. The authors performed a prospective study of the value of ultrasonography (US) and US-guided fine-needle aspiration cytology (FNAC) for assessment of N0 lesions in the neck. Preoperative US was performed in 107 patients with squamous cell carcinoma of the head and neck, who underwent 132 elective neck dissections. During the US examination of the last 54 patients, who underwent 70 elective neck dissections, US-guided FNAC was performed. US alone was found to be an unreliable method for detecting occult lymph node metastasis; the accuracy never exceeded 70% (93 of 132), with a sensitivity of 60% (32 of 53) and a specificity of 77% (61 of 79). In contrast, US-guided FNAC had an accuracy of 89% (62 of 70), a sensitivity of 76% (25 of 33), and a specificity of 100% (37 of 37). Because of the high sensitivity and specificity of US-guided FNAC for the assessment of the N0 neck, this modality may play an important role in directing treatment of these patients in the future. 
Impact of temperature elevation on immunologic defenses. Fever is a common response to infection and to other challenges to host defense. Temperature elevation has been associated with effects on the recognition, recruitment, and effector phases of the immune response. Specific immunologic responses are generally enhanced in the setting of temperature elevation within the physiologic range but not the supraphysiologic range. In contrast, natural immune responses may be unchanged or adversely affected. Temperature elevation appears to affect primarily the phase of recognition and sensitization or activation of mononuclear leukocytes. T lymphocyte responses (and/or the interactions of T lymphocytes with monocytes-macrophages) are enhanced for generation of effector cells. The activities of the effector cells, once generated, are usually not enhanced--or may even be depressed--by temperature elevation, but decreases are more than offset by increased T helper function. Overall, the data suggest that temperature elevations of the febrile response constitute a beneficial component of effective host defense. 
Pericardial mass mimicking constrictive pericarditis. Persistent pericardial hematoma due to blunt chest trauma is extremely rare. We report a case of constricted myocardium resulting from a large, partially organized hematoma in the right cardiophrenic angle. The hematoma was assumed to be caused by an occupational accident 17 years before diagnosis. Constriction could only be controlled by complete removal of the fibrous posterior capsule of the hematoma, which covered the epicardium of the right heart. 
Paediatric haemangiomas: the role of radiotherapy. Radiotherapy currently maintains an occasional place in the therapy of complicated haemangiomas of childhood. Eight such childhood benign lesions have been so treated at St Bartholomew's Hospital in the last 10 years. The case histories are presented before being discussed in the context of other therapies available (no treatment, steroids, embolism and surgery), radiation technique used and radiation dose prescription advised. 
Cavoatrial tumor thrombectomy using cardiopulmonary bypass without circulatory arrest. Of 29 patients with inferior vena caval tumor thrombus, 14 with supradiaphragmatic extension were deemed suitable for operation. Patients (age, 7.5 to 70 years) had renal cell carcinoma (n = 8), Wilms' tumor (n = 2), transitional cell carcinoma (n = 1), and adrenal carcinoma (n = 3). Seven patients had stage III disease, and 7 patients had stage IV disease. Two patients (group A) had unresectable disease at exploratory celiotomy, 4 patients (group B) underwent tumor thrombectomy without cardiopulmonary bypass, and cardiopulmonary bypass was employed in 8 patients (group C). Three of 8 group C patients had Budd-Chiari syndrome at diagnosis. Cardiopulmonary bypass with moderate hypothermia, and inferior vena caval interruption (clip or filter), was employed in all patients. There were no perioperative deaths. Transient neurological impairment was observed postoperatively in 2 patients. Coagulopathy developed in 1 patient who had hepatic encephalopathy and Budd-Chiari syndrome preoperatively and in another patient in whom protamine could not be administered. No patient had acute renal failure requiring hemodialysis. Median survival is 41 and 17 months in groups B and C, respectively. Some authors have advocated profound hypothermia and circulatory arrest in these patients. We find that satisfactory visualization and excision can be performed with cardiopulmonary bypass and moderate hypothermia, avoiding potential renal, hepatic, neurological, and septic complications associated with circulatory arrest. 
Transplantation after first-stage reconstruction for hypoplastic left heart syndrome. The surgical treatment of infants born with hypoplastic left heart syndrome has received considerable attention in recent years. Although this lesion was previously considered uniformly fatal, dramatic successes have been achieved with the use of staged reconstructive and replacement therapies. However, both surgical options have benefits and limitations, and neither has demonstrated clear superiority over the other. As survival for first-stage reconstruction by the Norwood procedure has improved, a greater number of patients are potential candidates for the Fontan operation, but not all will be suitable at an acceptable risk. These patients may be treated by cardiac transplantation. The results of a treatment protocol for 90 patients with classic hypoplastic left heart syndrome or its variants at The University of Michigan are reported, with particular attention given to those patients surviving initial palliation but judged to be unsuitable for a subsequent Fontan procedure. 
Staurosporine facilitates recovery from the basal forebrain-lesion-induced impairment of learning and deficit of cholinergic neuron in rats. Alzheimer's disease is characterized by the loss of cholinergic neurons in the nucleus basalis of Meynert and by a primary loss of memory function. Since staurosporine has been reported to induce differentiation in human neuroblastoma cells in vitro, we studied the effects of staurosporine on the amnesia induced by basal forebrain-lesion in rats. Staurosporine (0.05 and 0.1 mg/kg intraperitoneal) attenuated the impaired performance of water maze and passive avoidance tasks, even though the drug administration began 2 weeks after the lesion. Moreover, staurosporine (0.1 mg/kg) partially reversed the decrease of choline acetyltransferase activity in the fronto-parietal cortex induced by basal forebrain-lesion. These results suggest that staurosporine attenuates impairment of learning through reversal of damage to cholinergic neurons induced by basal forebrain-lesion. This evidence indicates that neurotrophic factor-like substances may be used in novel therapeutic approaches to Alzheimer's disease. 
Perioperative total parenteral nutrition in surgical patients. The Veterans Affairs Total Parenteral Nutrition Cooperative Study Group BACKGROUND. We undertook this study to test the hypothesis that perioperative total parenteral nutrition (TPN) decreases the incidence of serious complications after major abdominal or thoracic surgical procedures in malnourished patients. METHODS. We studied 395 malnourished patients (99 percent of them male) who required laparotomy or noncardiac thoracotomy. They were randomly assigned to receive either TPN for 7 to 15 days before surgery and 3 days afterward (the TPN group) or no perioperative TPN (the control group). The patients were monitored for complications for 90 days after surgery. RESULTS. The rates of major complications during the first 30 days after surgery in the two groups were similar (TPN group, 25.5 percent; control group, 24.6 percent), as were the overall 90-day mortality rates (13.4 percent and 10.5 percent, respectively). There were more infectious complications in the TPN group than in the controls (14.1 vs. 6.4 percent; P = 0.01; relative risk, 2.20; 95 percent confidence interval, 1.19 to 4.05), but slightly more noninfectious complications in the control group (16.7 vs. 22.2 percent; P = 0.20; relative risk, 0.75; 95 percent confidence interval, 0.50 to 1.13). The increased rate of infections was confined to patients categorized as either borderline or mildly malnourished, according to Subjective Global Assessment or an objective nutritional assessment, and these patients had no demonstrable benefit from TPN. In contrast, severely malnourished patients who received TPN had fewer noninfectious complications than controls (5 vs. 43 percent; P = 0.03; relative risk, 0.12; 95 percent confidence interval, 0.02 to 0.91), with no concomitant increase in infectious complications. CONCLUSIONS. The use of preoperative TPN should be limited to patients who are severely malnourished unless there are other specific indications. 
Consequences of queuing for care at a public hospital emergency department OBJECTIVE: To determine whether the length of a queue at a public hospital emergency department was associated with increased likelihood of patients' leaving without being seen by a physician and whether leaving adversely affected patients' health or affected their subsequent use of health care services. DESIGN: Observational cohort. Patients were surveyed during 1 week in July 1990 and received a follow-up survey 7 to 14 days later. The responses of patients who left without being seen by a physician were compared with those who were seen by a physician. SETTING: Emergency department at San Francisco (Calif) General Hospital. PATIENTS: All English-, Spanish-, and Cantonese-speaking adults waiting for emergency care were eligible. Of 882 eligible individuals, 700 agreed to participate; 85% of enrolled subjects saw a physician and 15% left without being seen. Demographic characteristics of patients who were and who were not seen were not significantly different. MAIN OUTCOME MEASURES: Emergency department waiting time and changes in patients' self-reported health. RESULTS: Patients were more likely to leave as waiting times increased. At follow-up, patients who left without being seen were twice as likely as those who were seen to report that their pain or the seriousness of their problem was worse. Only 4% of patients who left required subsequent hospitalization, but 27% returned to an emergency department. CONCLUSION: Many patients can appropriately decide whether their problem is truly urgent and make alternative plans in the face of long waits, but the health of some patients may be jeopardized by long queues for emergency care. 
The hyperekplexias and their relationship to the normal startle reflex. The startle response to unexpected auditory and somaesthetic stimulation was studied in 8 patients with hereditary or symptomatic hyperekplexia. It was abnormal in its resistance to habituation and in its exaggerated motor response. Both noise and taps to the face and head elicited a normal early blink response, separate from the subsequent true startle reflex. The earliest reflex EMG activity recorded after the blink was in sternocleidomastoid. EMG activity in masseter, and trunk and limb muscles followed later. This pattern of muscle recruitment suggests a brainstem origin for the abnormal startle responses. In addition, the abnormal startle responses exhibited disproportionately long latencies to the intrinsic hand and foot muscles and relatively slow recruitment of caudal muscles. The pattern of muscle recruitment was similar between patients, irrespective of the absolute latency of the response, and regardless of whether stimulation was auditory or somaesthetic. This suggests that auditory and somaesthetic afferents converge on a common brainstem efferent system, and that this system forms the final common pathway for abnormal startle responses of differing latency. The characteristics of this efferent system differ from those previously described in brainstem reticular reflex myoclonus, but are similar to those described in the normal auditory startle reflex in man. This suggests that the abnormal startle response in hyperekplexia, and the normal startle reflex represent pathological and physiological activity in the same brainstem efferent system. 
Four years of North American registry home parenteral nutrition outcome data and their implications for patient management. The OASIS Registry started annual collection of longitudinal data on patients on home parenteral nutrition (HPN) in 1984. This report describes outcome profiles on 1594 HPN patients in seven disease categories. Analysis showed clinical outcome was principally a reflection of the underlying diagnosis. Patients with Crohn's disease, ischemic bowel disease, motility disorders, radiation enteritis, and congenital bowel dysfunction all had a fairly long-term clinical outcome, whereas those with active cancer and acquired immunodeficiency syndrome (AIDS) had a short-term outcome. The long-term group had a 3-year survival rate of 65 to 80%, they averaged 2.6 complications requiring hospitalization per year, and 49% experienced complete rehabilitation. The short-term group had a mean survival of 6 months; they averaged 4.6 complications per year and about 15% experienced complete rehabilitation. The registry data also indicated HPN was used for 19,700 patients in 1987 with therapy growth averaging about 8% per year. This growth was chiefly from new cancer patients. The number of new patients with long-term disorders in whom HPN was initiated appeared rather constant. We conclude that these clinical outcome assessments justify HPN for long-term patients, but the utility and appropriateness of HPN for the cancer and AIDS patients remains uncertain and requires further study. Medical, social, and fiscal aspects of HPN management in long-term and short-term patients appear to involve quite separate considerations. 
Can decision analysis help in the management of giant hemangioma of the liver? [editorial] We explore the trade-off between the risk and expected benefits from resection of giant liver hemangioma (GLH), one larger than 4 cm in diameter. We searched the English-language literature for studies of the postoperative mortality after resection of GLH and of the outcome of expectantly treated patients. The results of the data synthesis showed an operative mortality of 1.5% (90% confidence intervals, 0.1-3.0%) and an early surgical morbidity of up to 13%. Mortality among the 37 reported cases with ruptured GLH was 78%. There were no cases of spontaneous or traumatic rupture of unresected GLH during a follow-up of a total of 282 patient years. The main source of ambiguity regarding the management of GLH is the uncertain risk of its rupture. Rough estimates of this risk based on published data suggest that surgical resection is not justified in asymptomatic GLH. Yet, although rare, rupture of GLH does occur with disastrous consequences. Future research may attempt to define patient subsets whose GLHs are at higher risk of rupture, and in whom preventive resection may improve survival. 
Evidence of a selective increase in cardiac sympathetic activity in patients with sustained ventricular arrhythmias BACKGROUND. Although enhanced efferent cardiac sympathetic nervous activity has been proposed as an important factor in the genesis of ventricular arrhythmias and sudden cardiac death, direct clinical evidence has been lacking. METHODS. We measured the rates of total and cardiac norepinephrine spillover into the plasma, which reflect respectively overall and cardiac sympathetic nervous activity, in 12 patients who had recovered from a spontaneous, sustained episode of ventricular tachycardia or ventricular fibrillation outside the hospital 4 to 48 days earlier. The results were compared with those from three age-matched reference groups without a history of ventricular arrhythmias: 12 patients with coronary artery disease, 6 patients with chest pain but normal coronary arteries, and 12 healthy, normal subjects. RESULTS. The patients who had had ventricular arrhythmias had reduced left ventricular ejection fractions, as compared with the patients with coronary artery disease or chest pain (mean [+/- SE], 46 +/- 3 percent vs. 58 +/- 4 percent and 69 +/- 5 percent, respectively; P less than 0.003). The rates of total norepinephrine spillover into the plasma were similar in the three reference groups, but 80 percent higher in the patients with ventricular arrhythmias (P less than 0.005). The rate of cardiac norepinephrine spillover was 450 percent higher in these patients (176 +/- 39 pmol per minute, as compared with 32 +/- 8 pmol per minute in the normal subjects; P less than 0.001), a disproportionate increase relative to the increase in total spillover, which indicated selective activation of the cardiac sympathetic outflow. This increase in cardiac norepinephrine spillover was probably caused by a reduction in left ventricular function. CONCLUSIONS. These results suggest that in some patients major ventricular arrhythmias are associated with and perhaps caused by sustained and selective cardiac sympathetic activation. We speculate that depressed ventricular function was present before the ventricular arrhythmia occurred, and that this resulted in reflex cardiac sympathetic activation, which in turn contributed to the genesis of the arrhythmia. 
Sebaceous carcinoma: an unusual cause of a rapidly enlarging rhinophyma. We describe a patient who developed sebaceous carcinoma within a long-standing rhinophyma with rapid enlargement of the lesion. We believe the development of this tumour was a random occurrence but the possibility of tumour development should be considered in any rhinophyma showing a rapid increase in size. 
End-stage avascular necrosis of bone in renal transplant patients. The natural history. We report the results of conservative treatment of stage III and stage IV avascular necrosis of bone (AVN) affecting the hip or knee in renal transplant patients. Twenty-nine patients were followed for a mean period of five years. Conservative management was successful in controlling symptoms in 40% of those with AVN of the hip and in 70% of those with AVN of the knee. Knowledge of the natural history of AVN is important because of the long survival times after renal transplantation. 
Sigmoid sinus thrombosis diagnosis by contrasted MRI scanning. Septic thrombosis of the transverse-sigmoid sinuses and the jugular bulb is a highly lethal condition. The presenting signs and symptoms of this disease entity are subtle and not in proportion to the magnitude of the problem. Later in the disease course, sudden fulminant findings appear. A high index of suspicion, combined with scanning techniques of either enhanced MRI or CT, allows prompt diagnosis and treatment. MRI enhanced with gadolinium-DTPA (Gd) is a valuable adjunct that confirms the diagnosis and delineates the extent of suspected pathology. 
Epicardial and endocardial mapping of ventricular tachycardia in patients with myocardial infarction. Is the origin of the tachycardia always subendocardially localized? BACKGROUND. Left ventricular endocardial reentry is the conventional concept underlying surgery for ventricular tachycardia (VT). We assessed the incidences of patterns showing complete reentry circuits at either the subendocardial or subepicardial level and of patterns in which left ventricular endocardial mapping could only in part account for a reentrant mechanism. METHODS AND RESULTS. We retrospectively analyzed epicardial and left ventricular endocardial isochronal maps of 47 VTs induced in 28 patients with chronic myocardial infarction (inferior, 14 patients; anteroseptal, 14 patients). Electrograms were recorded intraoperatively from 128 sites with epicardial sock and transatrial left ventricular endocardial balloon electrode arrays. Given the methodology used in this study, the mapping characteristics of the tachycardias suggested five types of activation patterns: 1) complete (90% or more of VT cycle length) subendocardial reentry circuits in seven VTs (15%) and seven patients (25%), 2) complete subepicardial reentry circuits in four VTs (9%) and four patients (14%), 3) incompletely mapped circuits with a left ventricular endocardial breakthrough preceding the epicardial breakthrough in 25 VTs (53%) and 21 patients (75%), 4) incompletely mapped circuits with a left ventricular epicardial breakthrough preceding the endocardial breakthrough in three VTs (6%) and three patients (11%), and 5) a right ventricular epicardial breakthrough preceding the left ventricular endocardial breakthrough in eight VTs (17%) and seven patients (25%). After surgery, one type 3 VT and three type 5 VTs were reinducible. Thus, left ventricular endocardial reentry substrates (types 1 and 3) accounted for 68% of VTs, but substrates involving subepicardial (types 2 and 4) and deep septal layers (type 5) accounted for 32% of VTs. CONCLUSIONS: In a substantial number of VTs, a substrate localization that is at variance with the conventional concept can be detected by simultaneous epicardial and endocardial mapping and may require modification of the surgical approach conventionally aimed at endocardial layers. 
Williams syndrome: masseter spasm during anaesthesia. A 4-year-old boy with Williams syndrome developed masseter spasm after halothane and suxamethonium. He did not develop malignant hyperthermia; the surgery was accomplished with a nontriggering anaesthetic and no further problems. 
Preherpetic neuralgia. We have encountered six zoster patients whose pain preceded rash by 7 to more than 100 days. Pain was severe, burning, and radicular, and located both in dermatomes different from, as well as in, the area of eventual rash. Two patients ultimately developed disseminated zoster with neurologic complications, one of zoster paresis, and the other, a fatal zoster encephalitis; both had been taking long-term, low-dose steroids. A third case of preherpetic neuralgia developed in a patient with prior metastatic carcinoma, and another case in a patient with an earlier episode of brachial neuritis. The final two cases of preherpetic neuralgia developed in individuals with no underlying disease. An extended period of pain before the onset of zoster rash has gone largely unrecognized. 
Clonorchis-associated cholangiocarcinoma: a report of two cases with unusual manifestations. Two cases of Clonorchis-associated cholangiocarcinoma are described along with their cholangiographic features to illustrate the spectrum of pathology ascribed to the injurious effects of the flukes on the bile duct epithelium. This includes adenomatous hyperplasia, extensive fibrosis, and carcinoma. The first case was also complicated by hepatic abscesses, left hepatic lobar atrophy, gastrobiliary and biliarocutaneous fistulae. The second case features an unusually dilated pancreatic duct containing pancreaticoliths that was found later to consist of hyperplastic bile duct epithelium, presumably carried by worm migration in the biliary tree. Liver sections from both patients showed typical features of hepatic clonorchiasis with the cancer. A knowledge of the wide spectrum of clinical presentation of clonorchiasis, particularly cholangiocarcinoma, might aid Western physicians in averting this serious sequela through prompt eradication of the helminthic infection and early recognition and treatment of its complications. 
Biliary lithotripsy: correlation between gallbladder contractility before treatment and the success of treatment. We perform biliary lithotripsy without adjuvant chemolitholytic agents, and therefore fragment clearance depends solely on the gallbladder's ability to evacuate its contents. We studied 205 patients to determine if gallbladder contractility before biliary lithotripsy is a predictor of treatment results and rate of fragment clearance. Percentage gallbladder contraction was calculated from the fractional difference in the sonographically measured gallbladder volumes before and after a fatty meal. Seventy-six patients (37%) were free of stones and fragments, and 129 patients (63%) had residual fragments at comparable follow-up intervals. Statistical analysis showed a significant difference in gallbladder contractility before biliary lithotripsy between the fragment-free group and the residual-fragment group (p = .008). Stone burden before treatment showed no significant difference between the groups (p = .074), but the number of stones was significantly less in the fragment-free group (p = .022). In the fragment-free group, a poor correlation (r = .047) was found between the percentage gallbladder contraction and the rate of fragment clearance. These data indicate that contractility of the gallbladder before treatment correlates with overall success of biliary lithotripsy but is not a predictor of the speed of fragment clearance. 
Long-term follow-up and prognostic factor analysis in advanced ovarian carcinoma: the Gynecologic Oncology Group experience. Long-term follow-up was obtained on 726 women with advanced ovarian carcinoma (suboptimal stage III and stage IV) who had received primary chemotherapy on two Gynecologic Oncology Group (GOG) protocols between 1976 and 1982. The first study compared melphalan alone versus melphalan plus hexamethylmelamine versus cyclophosphamide plus doxorubicin (CA). The second study evaluated the same CA regimen with or without cisplatin. Eligibility for the two studies was the same. At last contact, 76 patients were alive. In a multivariate analysis, cell type other than clear cell or mucinous, cisplatin-based treatment, good performance status, younger age, lower stage, clinically nonmeasurable disease, smaller residual tumor volume, and absence of ascites were favorable characteristics for overall survival (P less than .05). Second-look laparotomy was negative significantly more often among those with endometrioid tumors; there were no negative second-look laparotomies among those with mucinous or clear cell tumors. There were 30 patients with suboptimal stage III disease who had a negative second-look laparotomy; 18 (60%) have experienced recurrence, and 13 (43%) have died. Although cisplatin treatment was beneficial, new treatments are clearly needed. 
Radiolabeled antibody imaging in the management of colorectal cancer. Results of a multicenter clinical study. Presurgical colorectal cancer patients (n = 116) received single intravenous infusions of 1 mg of CYT-103 (OncoScint CR103), an immunoconjugate of monoclonal antibody B72.3, radiolabeled with 111In. Following gamma camera imaging, 103 patients underwent an operative procedure: 92 had primary or recurrent colorectal carcinoma, 1 patient evaluated for recurrence of colorectal cancer had a second primary malignancy (small cell lung), and 10 patients had no demonstrable evidence of malignancy. 111In-CYT-103 immunoscintigraphic findings were consistent with the pathologic diagnoses for 70% of patients with colorectal cancer and 90% of disease-free patients. Antibody imaging contributed to surgical decision making through the detection of occult disease (12% of patients) and the confirmation of localized, potentially resectable disease without regional or metastatic spread. Seven patients (6%) experienced adverse effects, primarily fevers and itching, and 33% of patients developed antibodies to murine immunoglobulin after administration of 111In-CYT-103. The results of this study suggest that 111In-CYT-103 is a useful diagnostic tool for the presurgical evaluation of colorectal cancer patients. 
Management of infected aortoiliac aneurysms. A 30-year retrospective review identified 13 patients treated for infected aneurysms of the abdominal aorta or iliac arteries, for an overall incidence of 0.65%. A constellation of clinical findings led to the correct preoperative diagnosis in 11 (85%) of 13 patients. Treatment methods included resection and in situ replacement grafting in seven patients, resection and extra-anatomic bypass in five patients, and resection-ligation in one patient. Four (31%) of 13 patients died within 30 days of operation, three of whom died of rupture. Overall, good results were achieved in five patients (38%), while poor results were noted in the remaining eight patients (62%). The determinants of outcome were aneurysm location or rupture, the presence of established infection, and the virulence of the infecting organism. In 10 (77%) of the 13 aneurysms, Salmonella species, Bacteroides fragilis, Staphylococcus aureus, and Pseudomonas aeruginosa accounted for all deaths, ruptures, and suprarenal aneurysm infections. These data suggest that patients with primary infections of the abdominal aorta or iliac arteries continue to present with advanced infections or aneurysm rupture that result in a high mortality. 
Reduction in the incidence of acute bronchitis by an oral Haemophilus influenzae vaccine in patients with chronic bronchitis in the highlands of Papua New Guinea. Following the administration of a standardized questionnaire, 62 adult patients with chronic bronchitis were enrolled into a double-blind controlled trial of an oral killed Haemophilus influenzae vaccine in the highlands of Papua New Guinea. A 3-day course of vaccine or placebo was given monthly for 3 consecutive months. Participants were monitored weekly over 12 months for acute exacerbations; early morning sputum specimens were collected monthly and during acute exacerbations. Density of colonization by H. influenzae and H. parainfluenzae was determined by standard quantitative and semiquantitative techniques, and the latter method (quadrant score) was used to determine the density of growth of pneumococci. A total of 30 patients received vaccine and 32 placebo. The incidence rate of acute bronchitis in the vaccine group (0.011 episodes/person-weeks) was significantly lower than that in the placebo group (0.021 episodes/person-weeks), but there was no difference between the two groups in the incidence rates of more severe disease. Vaccine efficacy was maximal at times of peak incidence of disease. There was no evidence of a decline in vaccine efficacy for acute bronchitis over the 12-month follow-up period. The number of viable H. influenzae in the sputum declined in both vaccine and placebo groups over the 12-month follow-up period. The average concentration of H. influenzae in the vaccine group fell below that in the placebo group within 1 to 2 months after first immunization and remained so for 12 months, although the difference between the two groups narrowed during the follow-up period. 
Regenerating nodules in hepatic cirrhosis: MR findings with pathologic correlation. To establish clearly the pathologic basis for small low-intensity nodules seen on MR images of the cirrhotic liver, we obtained MR images in 26 patients with cirrhosis in whom partial hepatectomy for hepatoma (15 patients), laparoscopy for cirrhosis (10 patients), or autopsy (one patient) was subsequently performed. Small low-intensity nodules were seen on gradient-echo images with short TEs (10-13 msec) in 13 of the 26 patients. In 12 of these 13 patients, small low-intensity nodules appeared larger and clearer as the TE was prolonged (14-25 msec). On T2-weighted spin-echo images, small low-intensity nodules were seen in 12 of the 13 patients, but not seen as well as on gradient-echo images. Pathologic correlation in these 13 patients revealed that the nodules on the MR images corresponded to iron deposits in regenerating nodules. Small low-intensity nodules were observed only on T2-weighted spin-echo images in two of the remaining 13 patients, in whom microscopic examination of the liver revealed marked inflammatory cell infiltration in the fibrous septa and no iron deposition. We conclude that small low-intensity nodules observed on MR images are caused by iron deposits in regenerating nodules, and that gradient-echo images with short and prolonged TEs are useful to confirm the presence of iron deposits in regenerating nodules. 
Suture length to wound length ratio and the integrity of midline and lateral paramedian incisions. A total of 349 patients were randomized to undergo laparotomy through a lateral paramedian incision with layered closure (n = 137), a midline incision with mass closure (n = 104) or a midline incision using layered closure (n = 108), endeavouring to close the latter two incisions with a measured suture length to wound length ratio of greater than 4:1. After 18 months follow-up, no patient in the lateral paramedian group had developed an incisional hernia whereas 7 of 104 patients undergoing a midline incision with mass closure and 7 of 108 patients undergoing a midline incision with layered closure had incisional hernias (P less than 0.01). The mean suture length to wound length ratios for the three groups were 2.6 (range 1.3-6.2), 5.0 (range 3.0-8.7) and 3.7 (range 2.0-6.3) respectively (P less than 0.0001). The lateral paramedian incision remains superior to the midline incision closed with the mass technique and its integrity is independent of the suture length to wound length ratio. 
Bilateral coronary ostial stenosis associated with aortitis syndrome. A patient with aortitis syndrome showed severe stenosis of the bilateral coronary ostium. We discuss the coronary angiographic findings and the treatment. 
Spontaneous haematomyelia: a necropsy study. Spontaneous haematomyelia (intramedullary spinal haematoma), is an uncommon event. Predisposing conditions have been reported including syringomyelia, pregnancy and delivery, angioma, spinal artery aneurysm, and haemophilia, but only rarely has a pathological evaluation been performed. Two such cases studied at necropsy are reported. In one case, the haematoma was restricted to the cervical spinal cord, while in the second case it extended from the medulla into the lowest thoracic cord segments. In both cases the haematomyelia was fatal. In the first case the clinical course was subacute, but in the other the course was more acute. Careful neuropathological examination showed no apparent cause for the haemorrhages. 
Cancer occurrence in a cohort of patients surgically treated for peptic ulcer. A cohort of 4107 patients treated surgically for peptic ulcer between 1955 and 1960 was followed up to determine the incidence of cancer by record linkage to the Danish Cancer Registry. A total of 930 cases of cancer were observed during 76,634 person-years. Relative risks of cancer were computed by comparison with the recorded cancer incidence in the Danish population. During the first five years after surgery the relative risk of gastric cancer was slightly increased (RR = 1.43), but 5-15 years after the operation the risk was lower than expected (RR = 0.55). Thereafter, the relative risk of gastric cancer increased steadily and increased more than twofold after 25 years. Lung cancer occurred more frequently in the cohort members than expected (RR = 1.66), but the relative risk was independent of time since surgery. Malignancies other than gastric cancer and cancers related to tobacco smoking were close to the expected numbers. The results do not support the findings of a recent British study of similar size in which increased risks were reported for cancer at other sites. 
Interleukin 4 promotes expression of mast cell ICAM-1 antigen. Cell recognition molecules play a crucial role in the regulation of immune cells. We recently found that mast cells (MCs) express leukocyte recognition molecules, including ICAM-1 antigen, a natural ligand of LFA-1. We here report that interleukin 4 (IL-4), a pleiotropic cytokine and mast cell differentiation factor, selectively promotes expression of surface ICAM-1 antigen and ICAM-1 mRNA in human MCs. IL-4 also up-regulates ICAM-1 antigen in cells of monocyte/macrophage lineage but has no effect on ICAM-1 antigen expressed on basophils, fibroblasts, or lymphocytes. The increase in expression of mast cell/macrophage ICAM-1 antigen induced by IL-4 may contribute to the accumulation of leukocytes and facilitate cell-contact-dependent regulation of immune cells in inflamed tissues. 
Visual and quantitative analysis of interictal SPECT with technetium-99m-HMPAO in temporal lobe epilepsy. Interictal 99mTc-HMPAO SPECT images were compared to ictal EEG localization in 51 patients with intractable temporal lobe epilepsy to determine their usefulness for preoperative seizure focus localization. Both quantified temporal lobe asymmetry and blinded visual detection of temporal lobe hypoperfusion were employed. Visual analysis detected ipsilateral hypoperfusion in 18 (39%) of the 46 patients with a unilateral focus and contralateral hypoperfusion in 3. None of the five patients with bitemporal foci had unilateral hypoperfusion. The positive predictive value of unilateral temporal lobe hypoperfusion was 86% (18/21). Quantified anterior temporal lobe asymmetry, greater than a previously derived normal range, correctly identified the focus in 22 (48%) but gave the wrong side in 5, resulting in a predictive value of 81%. The degree of asymmetry correlated inversely with age of seizure onset, but not with other clinical parameters, histology, or verbal and nonverbal memory. The usefulness of interictal 99mTc-HMPAO SPECT for pre-operative seizure focus localization is limited by low sensitivity when performed with a conventional rotating gamma camera. This suggests that ictal or immediate postictal imaging may be necessary for this purpose. 
Appendicitis in cystic fibrosis. Appendicitis is said to be uncommon and difficult to diagnose in cystic fibrosis. The clinical and radiological features in nine patients with cystic fibrosis who had appendicitis were studied. All but one of the patients had an appendiceal abscess at surgery. Four patients had a delay in diagnosis of greater than three days before the correct diagnosis was made. This delay may have been due to a more indolent presentation or because these patients were initially considered to have distal intestinal obstruction syndrome. Appendicitis should be considered in the differential diagnosis if a contrast enema demonstrates extrinsic compression of the caecum. Ultrasound, computed tomography, and gallium scans were found to be of limited help in our series. 
Vitrectomy for premacular fibroplasia. Prognostic factors, long-term follow-up, and time course of visual improvement. Two hundred seventy eyes with premacular fibroplasia consecutively treated by pars plana vitrectomy and membrane peeling were reviewed. This study is among the largest series with long-term follow-up reported to date. Visual improvement of two or more lines was achieved in 43% of eyes at 6 to 12 months, in 54% at 1 to 2 years, in 60% at 2 to 3 years, and in 58% at 3 to 5 years. Overall, complications occurred in 34 eyes (13%). Cataract progression after vitrectomy was noted in 106 (57%) of phakic eyes at 3 to 5 years, and 43 of these eyes underwent subsequent cataract extraction. Mean time to best visual acuity after vitrectomy was slightly less than 1 year for all eyes unless they had cataract worsening with subsequent cataract extraction (1.9 years). Significant factors affecting visual outcome were: preoperative lens status, visual acuity before vitrectomy, duration of preoperative symptoms of distortion and/or blurred vision, and the occurrence of intraoperative complications. 
Retrolabyrinthine vestibular nerve section: efficacy in disorders other than Meniere's disease. The retrolabyrinthine vestibular nerve section has evolved as an effective treatment for intractable vertigo of peripheral vestibular origin when hearing preservation is desired. This report studies the efficacy of retrolabyrinthine vestibular nerve section for control of vertigo due to causes other than Meniere's disease. This report details our experience with 42 patients with a wide variety of diagnoses. The reduced success rate of retrolabyrinthine vestibular nerve section in these patients is difficult to evaluate, as very few patients have been analyzed with respect to their specific diagnoses. Of patients who underwent retrolabyrinthine vestibular nerve section for control of vertigo, 23 patients had uncompensated vestibular neuritis and 19 others had a wide range of other diagnoses. For patients with uncompensated vestibular neuritis (n = 23), the physician record noted that 39% of patients were cured and 30% improved. This compares to our series of patients with Meniere's disease (n = 48), where 94% were cured and 2% improved. The true vestibular abnormality may be less reliably identified in patients with uncompensated vestibular neuritis, contributing to the less effective results. Since the development of a vestibular rehabilitation program, retrolabyrinthine vestibular nerve section for uncompensated vestibular neuritis has been all but abandoned. Retrolabyrinthine vestibular nerve section appears to achieve a high cure rate in patients with sensorineural hearing loss associated with their vestibular abnormalities. While retrolabyrinthine vestibular nerve section is helpful for control of vertigo in some diagnoses, a substantial incidence of persistent postoperative dysequilibrium was noted. 
Study of experimental pain measures and nociceptive reflex in chronic pain patients and normal subjects. This study evaluates (i) the effect of heterotopic chronic pain on various experimental pain measures, (ii) the relationship between experimental pain measures and chronic pain symptomatology assessment, and (iii) the influence of the various pain aetiologies on experimental pain measures. Fifty-three chronic pain patients were compared to 17 pain-free subjects with the following psychophysical and physiological indices: pain threshold (PTh), pain tolerance (PTol), verbal estimation of intensity and unpleasantness (intensity scale, IS; unpleasantness scale, US), threshold for intensity and unpleasantness (ITh and UTh), lower limb RIII nociceptive reflex (RIIITh and RIII frequency of occurrence). Chronic pain syndromes included neuropathic pain (n = 12), iodopathic pain (n = 12), myofascial syndromes (n = 9), headache (n = 9), and miscellaneous pain (n = 11). Chronic pain symptomatology was assessed with a visual analogue scale (VAS), a French MPQ adaptation (QDSA), Beck Depression Inventory (BDI), Spielberger State Trait Inventory (STAI) and Eysenck Personality Inventory (EPI). No significant difference was observed between chronic pain patients and pain-free control groups and between patient subgroups for PTh, PTol and RIIITh. No significant correlation was found between experimental pain measures and clinical pain, anxiety or depression scores. However, the chronic pain patients had a higher threshold for unpleasantness and judged the suprathreshold stimuli significantly less intense and less unpleasant than the control group. These results are discussed in relation to diffuse noxious inhibitory controls and the adaptation level theory of chronic pain experience. 
Influence of racial origin on admission rates of patients with suspected myocardial infarction in Birmingham. All patients with suspected myocardial infarction admitted to hospital in four Birmingham health districts were studied to test the hypothesis that Asian patients would be overrepresented and Caribbean patients underrepresented compared with the indigenous population. One thousand four hundred and ninety six patients had a final diagnosis of myocardial infarction or severe angina pectoris. The relative risk of admission for Asian men compared with white men aged 45-64 years was 2.65 (95% confidence interval 2.20 to 3.19) and the risk for Asian men was high for both myocardial infarction and ischaemia when analysed separately. The relative risk of admission for Caribbean men compared with white men was 0.53 (95% CI 0.33 to 1.20). The relative risk for Asian women compared with white women in the same age group was 2.58 (95% CI 1.68 to 3.96), but this was due to an excess of admissions diagnosed as ischaemia rather than infarction in the Asian women. For Caribbean and white women the risk of admission was the same, although significantly fewer Caribbean women were admitted with myocardial infarction. The study was undertaken in 1986-87 and population data had to be derived from the 1981 census. The resident population changed in those five years and so the results were recalculated making allowances for these changes in the health districts involved. Based on these data the admission rate for Asian men with suspected myocardial infarction aged 45-64 was nearly twice that for white men (1.8): the relative risk of admission for Asian men compared with white men was 2.04 (95% CI 1.53 to 2.18). 
Biopterin-dependent hyperphenylalaninemia due to deficiency of 6-pyruvoyl tetrahydropterin synthase. We describe the clinical, neurologic, and biochemical findings in 10 patients with 6-pyruvoyl tetrahydropterin synthase (6-PTS) deficiency from seven families, all of whom originate from one large tribe in Saudi Arabia. This deficiency presents with severe, early onset of failure to thrive, neurologic deterioration, and morbidity and mortality secondary to repeated episodes of bronchopneumonia or cardiorespiratory abnormalities. The urinary pterin excretion pattern indicates deficient activity of 6-PTS, which has been confirmed by direct enzyme assay in red blood cells of three patients. We treated our patients with combined use of tetrahydrobiopterin 20 mg/kg/d, L-dihydroxyphenylalanine 15 mg/kg/d, carbidopa 3.75 mg/kg/d, and L-5-hydroxytryptophan 5 mg/kg/d. Neurologic findings improved significantly in all after 5 to 24 months. Although head circumference and weight returned to the lower limit of normal in four, height normalized only in one of seven patients. Despite an unrestricted diet during combined therapy, blood phenylalanine and urinary excretion of neopterin and biopterin returned to normal. 
Alpha 1 antitrypsin phenotypes and alcoholic pancreatitis. Altered frequencies of alpha 1 antitrypsin phenotypes have been reported in patients with chronic pancreatitis, suggesting a possible genetic basis for individual susceptibility to this disease. Alpha 1 antitrypsin phenotypes, with particular regard to alcoholic pancreatitis, were studied. Patients with alcoholic pancreatitis were compared with alcoholic control subjects with no history of pancreatic disease. Serum alpha 1 antitrypsin concentrations were raised in pancreatitis patients sampled within one month of an acute attack of pancreatitis, but otherwise values were similar to those of control subjects. There were no significant differences in alpha 1 antitrypsin phenotypes between alcoholics with pancreatitis and alcoholic control subjects. This study of alpha 1 antitrypsin phenotypes provides no evidence of an inherited susceptibility to alcoholic pancreatitis. 
Percutaneous coronary mid-infra-red laser angioplasty. A pilot study was performed to determine the safety and efficacy of coronary pulsed mid-infra-red laser angioplasty. The laser was coupled with a novel 2.0 mm multifiber catheter consisting of 37 optical fibers of 150 microns each arranged concentrically around a 0.018-inch central lumen and a soft leading tapered distal tip to maintain coaxial alignment and position plaque in front of fibers. The laser was operated at 500 millijoules/pulse, 3.5 Hz, and 250 microseconds/pulse. Twenty-three patients with stenosis or occlusion of the left anterior descending or right coronary artery were selected for laser treatment. In three patients the catheter could not be positioned against the obstruction. In the 20 remaining patients laser angioplasty increased the diameter of the lumen from 0.3 +/- 0.3 mm to 1.4 +/- 0.3 mm and reduced the stenosis from 91 +/- 8% to 57 +/- 10%. In three patients "stand-alone" laser treatment was sufficient. In 17 patients balloon dilatation further reduced the stenosis to 20 +/- 18%. In two patients who had previously undergone unsuccessful balloon angioplasty with high inflation pressure, laser angioplasty allowed subsequent successful dilatation with low inflation pressure. There were no deaths, perforations, dissections, or arrhythmias. One patient had abrupt reclosure 24 hours after the procedure. Spasm occurred in four patients, and six patients had chest sensations during laser emission. Thus mid-infra-red pulsed coronary laser angioplasty is safe and effective for recanalization of stenosed and totally occluded arteries. The efficacy may be sufficient for "stand-alone" laser treatment. The technique may improve the efficacy of balloon angioplasty in cases of unsuccessful primary dilatation. 
Association of hypovolemia after subarachnoid hemorrhage with computed tomographic scan evidence of raised intracranial pressure. Hypovolemic patients are more likely to suffer delayed cerebral ischemia and infarction after a subarachnoid hemorrhage (SAH). Prompt recognition and correction of hypovolemia may improve the outcome. We have identified computed tomographic (CT) scan findings that increase the probability of a patient presenting with hypovolemia soon after an SAH. The plasma volume (PV) of 25 patients admitted within 96 hours of an SAH was measured using radioiodinated serum albumin. The normal PVs were measured in an outpatient setting 6 months later or predicted from their total body water. Nine patients (36%) were found to be hypovolemic, defined as a fall in PV exceeding 10% of the normal PV (mean fall, 18 +/- 2%). Sixteen patients were normovolemic or hypervolemic (mean PV, +9 +/- 2%). The basal cisterns were compressed or obliterated on the CT scans of all hypovolemic patients compared with 12.5% of normovolemic patients (chi-square, 14.52; P less than 0.01). The probabilities of a patient being hypovolemic if the CT scan indicated raised intracranial pressure were high: hydrocephalus, P = 0.80; compression of the basal cisterns, P = 0.82; and compression of the basal cisterns associated with intracerebral hematoma or midline shift, P = 1.00. Patients with an SAH and radiological evidence of raised intracranial pressure should be considered at particular risk for systemic hypovolemia. 
Candidal mediastinitis after surgical repair of esophageal perforation. Candidal mediastinitis, like Boerhaave's syndrome, is uncommon, and both, if treated late or incompletely, frequently result in death. Early recognition and aggressive medical and surgical intervention are the best means to convalescence and cure in both conditions. 
Vaginal and vulvar adenosis. An unsuspected side effect of CO2 laser vaporization. During a 15-month period, September 1984 through January 1986, 10 women who were treated in the Section of Gynecologic Oncology, Department of Obstetrics and Gynecology, Pennsylvania Hospital, Philadelphia, Pennsylvania, developed vaginal or vulvar adenosis after CO2 laser vaporization. The indications for therapy were condylomata of the cervix, vagina and vulva refractory to conservative management in 3 patients, vulvar intraepithelial neoplasia in 3, lichen sclerosus in 1 and cervical intraepithelial neoplasia with condylomata on the cervix and vagina in 3. All the patients underwent treatment of the vagina. Most underwent treatment of the cervix, and some underwent treatment of the vulva at various degrees of intensity and depth. During the posttreatment colposcopic follow-up examination, all the patients demonstrated lesions colposcopically consistent with adenosis of the vagina or vulva within the area treated with the CO2 laser. Biopsies of the lesions were performed, adenosis was confirmed histologically, and endometriosis was ruled out histologically. This entity has not been previously associated with CO2 laser vaporization, and its clinical significance is undetermined. Further follow-up is indicated. 
Incidence of ultrasound-detected intrahepatic hematomas due to Tru-cut needle liver biopsy. This is a prospective study in which 120 patients with diffuse liver disease undergoing liver biopsy were followed by serial ultrasounds to determine the incidence of postbiopsy intrahepatic hematoma formation. Forty-five of the patients had a blind biopsy, while the remaining 75 patients had a biopsy performed during laparoscopy. In both groups a 2.0-mm Tru-cut needle was employed. The overall incidence of postbiopsy hematoma formation was 18.3%, with approximately the same results occurring in blind biopsy patients (20%) and laparoscopy-guided biopsy patients (17%). Only two patients had significant pain associated with the hematoma formation (one from each group), one of whom had evidence of intraperitoneal bleed and rebleed. Our results suggest that postbiopsy asymptomatic hematomas occur more frequently than had been generally thought and that laparoscopy-guided biopsy is not safer than blind biopsy. 
Pulmonary dysfunction in surgical conditions of the newborn infant. OBJECTIVE: To describe the pathophysiology of surgical conditions that are associated with respiratory insufficiency in the newborn infant. DESIGN: Survey. SETTING: Newborn ICU in a children's hospital. PATIENTS: Twenty-four newborn infants (1 to 28 days old) who required endotracheal intubation and mechanical ventilation for operative procedures or postoperative ventilatory support. INTERVENTIONS: Flow-volume curves obtained by manual inflation of the lungs, followed by forced deflation by negative pressure, and by passive expiration, under sedation and pharmacologic paralysis. MEASUREMENTS: Deflation flow-volume curves and passive expiratory curves were measured. Pulmonary function testing before and after bronchodilator administration (n = 11) began midway during the study period. Term and preterm groups served as controls. MAIN RESULTS: Forced vital capacity (FVC) was decreased in all groups with surgical disease as follows: abdominal wall defects and necrotizing enterocolitis groups to 48.3% and 62.1% that of preterm, respectively; pulmonary hypoplasia group to 55.5% that of term (p less than .05). Maximal expiratory flow at 25% of FVC decreased in all groups: abdominal wall defects and necrotizing enterocolitis group, to 36.8% and 37.9% that of preterm, respectively (p less than .05); pulmonary hypoplasia group, 20.0% that of term (p less than .05). The ratio of maximal expiratory flow at 25% of FVC divided by FVC was significantly decreased in necrotizing enterocolitis and pulmonary hypoplasia groups compared with that of preterm and term groups, respectively, but not in the abdominal wall defects group. Maximal expiratory flow at 25% of FVC, but not FVC, increased significantly (36%, p less than .05) after bronchodilator nebulization, indicating the presence of airway reactivity. Respiratory system compliance was decreased significantly (p less than .05) in all surgical disease groups compared with the term group. CONCLUSIONS: Bronchial reactivity contributes to decreased maximal expiratory flow at 25% of FVC, a feature also seen in premature infants with respiratory distress syndrome who later develop bronchopulmonary dysplasia. Babies who require chronic ventilatory support after operation and who have developed reactive airways may benefit from the administration of bronchodilators during postoperative ventilatory management. 
Azathioprine induced liver disease: nodular regenerative hyperplasia of the liver and perivenous fibrosis in a patient treated for multiple sclerosis. Azathioprine hepatotoxicity has been described mainly in renal transplant recipients. Most reported cases are related to lesions of the venous system of the liver: peliosis hepatis, veno-occlusive disease of the liver, perisinusoidal fibrosis, and nodular regenerative hyperplasia of the liver. The most common clinical manifestation of these hepatic vascular lesions is portal hypertension. We present a case of nodular regenerative hyperplasia and perivenous fibrosis in a patient receiving azathioprine for multiple sclerosis. Histological abnormalities were similar to those described in renal transplant patients, and azathioprine was the only potential hepatotoxic agent present. 
Mitochondrial dysfunction in multiple symmetrical lipomatosis. Multiple symmetrical lipomatosis is a striking clinical finding associated with a variety of peripheral and central nervous system abnormalities. We describe 4 unrelated patients with evidence of mitochondrial dysfunction in skeletal muscle. Multiple symmetrical lipomatosis is an additional, albeit unusual, manifestation of the expanding clinical spectrum of mitochondrial diseases. 
Role of endothelium-derived relaxing factor in regulation of vascular tone and remodeling. Update on humoral regulation of vascular tone. In addition to preserving the permselectivity of the vascular wall and providing an antithrombogenic surface, the vascular endothelium contributes importantly to the regulation of vasomotor tone. Indeed, the endothelium participates in the conversion of angiotensin I to angiotensin II; the enzymatic inactivation of several plasma constituents such as bradykinin, norepinephrine, serotonin, and ADP; and the synthesis and release of vasodilator substances such as prostacyclin and the recently discovered endothelium-derived relaxing factor (EDRF). The diffusible EDRF released from the endothelium is nitric oxide or a substance closely related to it such as nitrosothiol. The endothelium also synthesizes and releases vasoconstrictive factors, including products derived from arachidonic acid metabolism and the recently discovered peptide endothelin. An increasing body of evidence from experimental and clinical studies indicates that EDRF and endothelium-derived contracting factors play an important role in vascular physiology and pathology. It has become apparent that the balance of these factors may be a major determinant of systemic and regional hemodynamics. Moreover, through generally opposite effects on growth-related vascular changes, contracting factors such as endothelin and relaxing factors such as EDRF also may be important determinants of the vascular response to injury in various disease states such as atherosclerosis and hypertension. It is clear that the vascular endothelium is a complex and dynamic organ. Understanding endothelium function in normal physiology and disease states is of potential clinical importance and should be the focus of future investigation. 
Comparison of an antiinflammatory dose of ibuprofen, an analgesic dose of ibuprofen, and acetaminophen in the treatment of patients with osteoarthritis of the knee BACKGROUND. The optimal short-term, symptomatic therapy for osteoarthritis of the knee has not been fully determined. Accordingly, we compared the efficacy of a nonsteroidal antiinflammatory drug, ibuprofen, given in either an antiinflammatory dose (high dose) or an analgesic dose (low dose), with that of acetaminophen, a pure analgesic. METHODS. In a randomized, double-blind trial, 184 patients with chronic knee pain due to osteoarthritis were given either 2400 or 1200 mg of ibuprofen per day or 4000 mg of acetaminophen per day. They were evaluated after a washout period of three to seven days before the beginning of the study, and again after four weeks of treatment. The major measures of outcome included scores on the pain and disability scales of the Stanford Health Assessment Questionnaire (range of possible scores, 0 to 3), scores on the visual-analogue scales for pain at rest and pain while walking, the time needed to walk 50 ft (15 m), and the physician's global assessment of the patient's arthritis. RESULTS. Seventy-eight percent of the patients completed four weeks of therapy. No significant differences were noted among the three treatment groups with respect to failure to complete the trial because of noncompliance or adverse events. All three groups had improvement in all major outcome variables, and the groups did not differ significantly in the magnitude of improvement in most variables. The mean improvement (change) in the scores on the pain scale of the Health Assessment Questionnaire was 0.33 with acetaminophen (95 percent confidence interval, 0.14 to 0.52), 0.30 with the low dose of ibuprofen (95 percent confidence interval, 0.09 to 0.51), and 0.35 with the high dose of ibuprofen (95 percent confidence interval, 0.13 to 0.57). Side effects were minor and similar in all three groups. CONCLUSIONS. In short-term, symptomatic treatment of osteoarthritis of the knee, the efficacy of acetaminophen was similar to that of ibuprofen, whether the latter was administered in an analgesic or an antiinflammatory dose. 
Mouse macrophage clones immortalized by retroviruses are functionally heterogeneous. Murine macrophage clones were generated from thymus, spleen, brain, and bone marrow by in vitro immortalization with recombinant retroviruses carrying an avian v-myc oncogene. The cloned cell lines express F4/80 molecules, exert phagocytosis, have nonspecific esterase activity, and express class II molecules after interferon gamma activation. The macrophage clones are diploid and their karyotypes have remained stable for greater than 3 years in culture. After the macrophage clones were activated, their pattern of cytokine production was investigated. Functional heterogeneity in cytokine transcription was demonstrated: one of six liposaccharide-activated macrophages was unable to transcribe interleukin 1 alpha, whereas all of the liposaccharide-activated clones were able to transcribe tumor necrosis factor alpha. Interleukin 6 production was detected in three of six clones. The production of nitrite and tumor necrosis factor alpha as effector molecules of cytotoxicity was detected in all clones, thus showing that a single macrophage can exert more than one cytotoxic mechanism. The results indicate that immortalized and cloned macrophages have a differentially regulated expression of cytokine genes, adding further evidence for the existence of functional heterogeneity among cloned macrophages. This heterogeneity seems to derive from differentiation-related mechanisms rather than from external constraints. 
Does selective decontamination of the gastrointestinal tract prevent multiple organ failure? An experimental study. Gut bacteria have been incriminated as causing or contributing to generalized sepsis with multiple organ failure in severely ill patients, and selective decontamination of the gastrointestinal tract of Enterobacteriaceae has been claimed to decrease septic complications in these patients. We studied the effects of selective decontamination of the gastrointestinal tract on survival and organ function in an experimental model of sepsis with multiple organ failure. Wistar rats were inoculated intraperitoneally with zymosan and randomized into control or treatment groups (trimethoprim or streptomycin sulfate). Selective decontamination effectively prevented bacterial translocation of Enterobacteriaceae. However, only early mortality was decreased, and only so in the streptomycin-treated rats. Selective decontamination did not result in a significantly better condition of the surviving animals on day 12. 
Role of intraoperative ultrasound examination in patients undergoing a Fontan-type procedure. To determine its potential impact on perioperative surgical management intraoperative ultrasound examination (cross sectional imaging, colour flow mapping, pulsed and continuous wave Doppler) was used in 16 consecutive patients undergoing a Fontan-type procedure. Epicardial cross sectional imaging before bypass defined the precise intracardiac morphology in 15 of 16 patients. The preoperative morphological diagnosis was refined in four patients (25%), and this influenced surgical management in two (12%). Epicardial studies after bypass identified seven residual haemodynamic lesions in five patients (three residual intercardiac shunts, one ventricular outflow obstruction, one pulmonary artery obstruction, two mitral valve regurgitation), and led to immediate revision during a second period of bypass in three (18%). In one patient who required early reoperation residual shunting was not detected after bypass by either colour flow mapping or a contrast study. Final intraoperative studies showed a good surgical result in 14 patients (87%). Flow characteristics and flow velocities within the Fontan circulation could be assessed immediately after the patient came off cardiopulmonary bypass by means of combined pulsed wave Doppler and colour flow mapping in 14 of the 16 patients. Cross sectional studies of the left heart after bypass showed no change in ventricular function and allowed monitoring of volume replacement and ventricular filling. Intraoperative ultrasound was a valuable monitoring technique in patients undergoing a Fontan-type procedure. It refined preoperative diagnosis, monitored ventricular function, and identified or excluded residual haemodynamic lesions in most patients. 
Primary cutaneous gamma/delta T-cell lymphoma presenting as disseminated pagetoid reticulosis. The first case of primary gamma/delta cutaneous T-cell lymphoma (CTCL) with a fatal outcome is reported. The patient had the clinical and histopathologic features of disseminated pagetoid reticulosis, a rare form of CTCL characterized by a strong epidermotropic lymphoid infiltrate. Extensive immuno-cytochemical studies showed that the neoplastic cells were almost exclusively localized in the epidermis, expressed the gamma/delta variant of the T-cell receptor (CD3+, TCR-delta-1+) and were CD5+, CD7+, CD27+, CD29+, CD43+, CD44+, CD45+, CD45RA+, CD54+, CD69+, but beta F1-, Ti gamma a-, BB3-, A13-, CD2-, CD4-, CD8-, CD11a-, CD49d-, CD25-, CD30-, and HLA-DR-. A comparison of our results with those of the literature, which have not included gamma/delta T-cell receptor analysis, suggests that some reported cases of pagetoid reticulosis may have phenotypes similar to our case. Electron microscopy studies demonstrated that the gamma/delta T lymphocytes were villous, containing dense and multivesicular bodies, and formed close contacts with the surrounding keratinocytes, suggesting that these cells should have a role in the skin-associated lymphoid tissue. The proliferating cells in our case might represent the neoplastic counterpart of the recently reported CD2- subset of normal human peripheral blood gamma/delta T lymphocytes. 
Efficacy of (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine in various models of herpes simplex virus infection in mice. The phosphonylmethoxyalkyl derivative (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC) was evaluated for its in vivo efficacy in several model infections for herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) and thymidine kinase-deficient (TK-) HSV-1 in mice. In hairless mice infected intracutaneously with HSV-1 or HSV-2, HPMPC completely suppressed all manifestations of the disease (skin lesions, paralysis of the hind legs, and mortality) if it was administered topically at a concentration of as low as 0.1, 0.3, or 1%. Similarly, HPMPC completely suppressed TK- HSV-1 infection in athymic nude mice if it was administered topically at 0.1 or 0.3% or intraperitoneally at 100 or 250 mg/kg/day. HPMPC was also effective against intraperitoneal HSV infection if it was given orally at a dose of 50 mg/kg/day or higher. In mice inoculated intracerebrally with HSV-2, intraperitoneal HPMPC treatment achieved a significant and dose-dependent protection at doses ranging from 5 to 400 mg/kg/day. The protective effect of HPMPC (at 200 mg/kg/day) was accompanied by a complete inhibition of virus multiplication in the brain. In all models of infections studied, the efficacy of HPMPC proved to be superior to that of acyclovir. The most remarkable feature of HPMPC was that a single administration of the compound, even as late as 4 days after infection, conferred significant protection against HSV-1 or HSV-2 infection. Topical or systemic HPMPC treatment is efficacious in murine models of HSV-1, HSV-2, and TK- HSV infections. 
Total excision and extra-anatomic bypass for aortic graft infection. Reports of high mortality and amputation rates following total excision and extra-anatomic bypass for aortic graft infection have prompted the use of alternate approaches including local antibiotics, partial resection, in situ revascularization, and graft excision without revascularization. Experience with aortic graft infection was reviewed to establish current morbidity and mortality rates and evaluate our bias in favor of total excision and extra-anatomic bypass. Aortic graft infection was identified in 32 patients, 8 with aortoenteric fistulas. The mean interval between graft placement and infection was 34 months. History of groin exposure (75%) or multiple prior vascular surgery (50%) was common. Clinical signs included fever and/or leukocytosis (23 patients), false aneurysm (9 patients), graft thrombosis (6 patients), groin infection (11 patients), and gastrointestinal hemorrhage (6 patients). Microbiologic data, available in 26 patients, demonstrated gram-positive organisms in 15 patients and gram-negative in 9. Multiple organisms were seen in 11 patients. Patients were treated by partial removal with (8 patients) or without (4 patients) revascularization or total removal with (18 patients) or without (2 patients) revascularization. Revascularization was by an extra-anatomic route, either simultaneous or staged. Overall morbidity/mortality was less in the revascularized groups (p = 0.01), while late complications were seen only after partial removal (p less than 0.01). The best results were found after total excision with revascularization. No patient in this group experienced late infection or amputation during a mean follow-up of 34 months (range: 1 to 168 months). Complications after total excision and extra-anatomic bypass for aortic graft infection are lower than generally appreciated. This approach should remain the standard to which other approaches are compared. 
Use of life-sustaining care for the elderly. Advanced age has been proposed as one criterion for limiting the use of life-sustaining medical treatment, but very little is known about current practices. We retrospectively studied utilization rates of intensive care (IC) and cardiopulmonary resuscitation (CPR) in admissions to a university hospital over 1 year (n = 9,998), to test whether these treatments are used more selectively for elderly patients. Overall utilization rates did not vary by age. However, among 524 terminal admissions, IC was used for 63% of patients age 35-74 but for only 50% of patients 75 and older (P less than 0.01). Among elderly patients, nursing home residence, diagnosis of advanced malignancy, severe chronic illness, and older age were independent predictors of withholding IC prior to death. Despite more selective use, survival rates were lower for elderly than for younger patients receiving IC (88% vs 78%, P less than 0.001). CPR showed similar but non-significant trends. Intensive care is being used less frequently prior to death for elderly patients, based on diagnosis and functional status as well as chronologic age. 
Paediatric blood pressure and anaesthesia. One percent of children have appreciably and consistently raised arterial blood pressure. A 7-year-old girl admitted for routine tonsillectomy, had unrecognised hypertension which put her at increased risk. Should anaesthetic practice take more note of paediatric blood pressures?. 
Role of intraoperative enteroscopy in obscure gastrointestinal bleeding of small bowel origin. Intraoperative enteroscopy was performed in 12 patients (median age 68 years) with obscure gastrointestinal bleeding probably of small bowel origin, six of whom were men. All the patients were evaluated by routine haematological, coagulation and biochemical profiles, upper and lower gastrointestinal endoscopies, visceral angiography and/or isotope scanning. All the patients were anaemic. Visceral angiography was useful on three of the 12 occasions on which it was used and isotope scanning was valuable on eight of the 11 occasions it was used. Nine patients had undergone previous laparotomy. Enteroscopy was performed successfully in all cases, with fresh blood and discrete vascular lesions being the chief findings (10 of 12 cases). Segmental resections (n = 8) and local resections (n = 2) were performed in ten patients, with two patients having more than one laparotomy for rebleeding. Five patients developed postoperative complications and there was an operative death and one late death. Three of the ten surviving patients experienced further rebleeding. Intraoperative enteroscopy is now an essential adjunct to laparotomy for gastrointestinal bleeding which has been localized to the small bowel before operation. 
Changes in body composition and energy expenditure after six weeks' growth hormone treatment. Changes in body composition and energy expenditure were assessed in 15 children after six weeks of human growth hormone (hGH) treatment. Body composition measurements were made by stable isotope labelled water (H2(18)O) dilution, bioelectrical impedance, and skinfold thickness techniques. Energy expenditure was assessed both by indirect ventilated hood calorimetry (resting energy expenditure) and the stable isotope doubly labelled water (2H2(18)O) technique (free living daily total energy expenditure). Mean increases in weight of 0.96 kg and fat free mass of 1.37 kg and a mean decrease in fat mass of 0.41 kg were observed. Significant increases both in resting energy expenditure and free living daily energy expenditure were detected. Absolute changes in fat mass and resting energy expenditure were correlated. The data suggest (i) that the increase in the fat free mass is the most significant early clinical measure of hGH response and (ii) that hGH increases the metabolic activity of the fat free mass. Monitoring such changes may be predictive of the efficacy of hGH in promoting growth. 
Gastric leiomyosarcoma. Prognostic factors and surgical management. Information on gastric leiomyosarcoma, such as important prognostic factors, patterns of disease recurrence, and optimal methods of treatment, are derived from limited patient experience. We address these questions, with specific focus on whether an advantage could be demonstrated for radical resection compared with wide local excision, by retrospectively investigating 53 patients who underwent surgical treatment at Mayo Clinic, Rochester, Minn. Abdominal pain and/or gastrointestinal bleeding associated with an intramural or exogastric mass were typical features of this disease. Only tumor size and histologic grade were statistically significant prognostic factors. With analysis of survival curves and patterns of recurrence, neither the addition of lymphadenectomy nor the wider tumor-free margins of a radical gastrectomy seemed superior to the more conservative local excision. Therefore, wide local excision remains the preferred treatment when technically feasible. 
Alpha-thalassemia resulting from deletion of regulatory sequences far upstream of the alpha-globin structural genes. We describe an alpha-thalassemia determinant in which alpha-globin expression is silenced by a deletion located 27 kb 5' to the transcription start site of the alpha 2-globin gene. This alpha-thalassemic determinant, (alpha alpha)MM, is a member of a newly described group of thalassemic mutations resulting from deletion of locus-controlling sequences critical to globin gene expression. 
Thrombogenic microballoon for cerebral aneurysms, arteriovenous malformations, and carotid cavernous fistula occlusion. Preliminary technical note. A thrombogenic microballoon was developed to overcome the problems of cerebral aneurysm rupture during microballoon inflation and incomplete aneurysm obliteration by microballoons with subsequent fatal rupture. These complications occur in about 35% of reported series with current microballoon embolization techniques. The wall of the new thrombogenic microballoon allows 80% aneurysm occlusion by inflation, thus avoiding mechanical rupture, and at the same time it produces a blood clot in the space remaining between the microballoon and the aneurysm wall. This clot undergoes fibrosis with firm adherence of the microballoon to the aneurysm wall. Experimental evidence is presented to support these conclusions. This thrombogenic microballoon system is also applicable to carotid-cavernous fistulas and arteriovenous malformations. 
Technetium-99m-d,1-hexamethylpropyleneamine oxime (HMPAO) uptake and glutathione content in brain tumors Technetium-d, HMPAO SPECT was performed in 70 patients suffering from intracerebral tumors of various histologic types (glioma n = 30, meningioma n = 19, metastases n = 10, angioma n = 3, neuroma n = 2, lymphoma n = 2, neurocytoma n = 1, epidermoid n = 1, gliosis n = 1, cholesteatoma n = 1). Tumor classification was histologically verified in all subjects except in two cases with inoperable angiomas. SPECT was performed under resting state conditions with a dual-head rotating camera (SIEMENS ZLC 37) following intravenous injection of 18-25 mCi 99mTc-d, 1-HMPAO. Regional tracer deposit was expressed in terms of a cerebellar index (CBI). Significantly higher regional HMPAO uptake was found in meningiomas when compared with gliomas of different malignancy (ANOVA p less than 0.05). Within gliomas, regional uptake increased with malignancy (n.s.). In 23 patients, a total of 32 tumor specimens were obtained for histochemical analysis of glutathione (GSH) content using high-pressure liquid chromatography. A significant correlation (least square method, p less than 0.001) between CBIs and GSH values was found, supporting the hypothesis that GSH is the predominant factor for the conversion of the lipophilic complex to hydrophilic derivates. 
Doxapram after general anaesthesia. Its role in stopping shivering during recovery. A group of patients who developed postoperative shivering after receiving inhalational anaesthesia were assigned, at random, to receive either doxapram or a placebo under double-blind conditions. A significantly higher proportion of patients stopped shivering after being given doxapram than after the placebo. 
A technique for control of hypertrophic scarring in the central region of the face. Various methods are available for applying pressure to the central portion of the face to reduce hypertrophic scarring after burn injury. Our center uses an elastomer insert with a thermoplastic backing, which is formed over a plaster mold of the patient's face. The insert is worn under a traditional anti-burn scar face mask. We reviewed the records of 26 patients with hypertrophic scarring to the central portion of the face to assess the effectiveness of the insert. Seventeen (65%) of these patients wore the insert until scar maturation. Three of these 17 patients later required reconstructive surgery of the central face. Our findings suggest that pressure to this part of the face may be effective in decreasing hypertrophic scar formation. The insert described in this article is inexpensive and relatively easy to fabricate. 
Normal thymus simulating pericardial disease: diagnostic value of magnetic resonance imaging. Normal enlargement of the thymus in infancy can often lead to erroneous clinical suspicion of cardiomegaly. Roentgenographic differentiation is not always definitive but echocardiography is generally effective in differentiating cardiac pathology from an enlarged thymus. In this patient, magnetic resonance imaging was necessary to differentiate benign thymic hyperplasia from pericardial or mediastinal pathology. Thymic involution with a severe neonatal illness, followed by thymic rebound, which later subsided, added to the interest and initial confusion in this patient. 
Transseptal catheterization in adults: enhanced efficacy and safety by low-volume operators using a "non-standard" technique. Transseptal catheterization is often not performed because of concerns about morbidity and mortality. The authors present several refinements of this technique that have allowed a series of cases to be done with minimal morbidity or mortality. This was possible despite limited previous experience in this technique and a relatively low-volume of cases. 
Association between disturbances in the immune system and hypertension. For many decades evidence has been accumulating which implicates the immune system in the etiology and pathogenesis of hypertension. There appears to be a strong association between hypertension and immunologic dysfunction in humans and in rats. Patients with severe hypertension have significantly higher levels of serum IgG in comparison with normotensive controls. A positive correlation has been found between serum IgG levels and blood pressure in untreated essential hypertensive patients. In some studies it has been demonstrated that autoantibody levels are higher in both untreated and treated hypertensive patients than in normotensive control subjects. Furthermore, in the spontaneously hypertensive rat (SHR), several indices of immune system function have been shown to be depressed. There is also a significant correlation between immune intervention and antihypertensive effects. Short term administration of anti-rat thymocyte serum results in a significant decrease in the arterial pressure of the SHR. Chronic cyclophosphamide treatment prevents the progression of hypertension and significantly reduces its final level in the adult SHR. Neonatal thymic implants from normotensive donor rats delay the development of hypertension and significantly attenuate the level of the hypertensive state in the SHR. Also, thymectomy at an age of 4 weeks delays the development of hypertension in the SHR. The differences in the antihypertensive effectiveness of a variety of immunological manipulations in the SHR may be the result of their different levels of improvement on the severity of the autoimmune process in these rats. 
Klebsiella pneumoniae urinary tract infection complicated by endophthalmitis, perinephric abscess, and ecthyma gangrenosum. We have reported the case of an immunocompromised patient with a K pneumoniae bacteremia admitted with endophthalmitis. The source of the infection was an asymptomatic left renal calculus associated with a perinephric abscess. Persistent bacteremia resulted in the development of ecthyma gangrenosum, which has not previously been associated with Klebsiella spp infection. 
DEGR-factor Xa blocks disseminated intravascular coagulation initiated by Escherichia coli without preventing shock or organ damage. One of the aims of research in the area of thrombosis has been to design an effective anticoagulant that would function in a predictable and direct manner. In evaluating the role of coagulation in sepsis we used factor Xa blocked in the active center with [5-(dimethylamino)1-naphthalenesulfonyl]-glutamylglycylarginyl+ ++ chloromethyl ketone (DEGR-Xa). We infused 1 mg/kg of DEGR-Xa together with LD100 concentrations of Escherichia coli (4 x 10(10) organisms/kg) into five baboons. As controls, we infused E coli alone into five baboons. The inflammatory, coagulant, and cell injury responses to E coli of both the treated and control groups were lethal and were similar in every respect except for the complete inhibition of the consumption of fibrinogen in the DEGR-Xa group. The half life of DEGR-Xa was approximately 10 hours and 2 hours, as determined by isotopic and enzyme-linked immunosorbent assays, respectively. These results for the first time demonstrate that, although coagulation occurs in E coli sepsis, fibrin formation per se did not influence the lethal outcome in this model. These results also show the effectiveness of DEGR-Xa as an anticoagulant and raise the possibility that it could serve as an alternative to anticoagulants currently in use. 
Symptomatic pancreatic heterotopia treated by local excision. Non-ulcer dyspepsia is a continuing problem and in many cases a precise cause is never identified. We present five patients with an allegedly uncommon condition--pancreatic heterotopia. They were managed by local excision of the tumour and after a mean (range) follow up of 42 (9-80) months all remain free of the original symptoms. 
Influence of parenteral nutrition on leg nitrogen exchange in injured patients. Body N balance, 3-methylhistidine (MEH) excretion, amino acid (AA) plasma concentration, and fluxes across the leg were investigated both during fasting and during parenteral nutrition of injured patients in order to better understand protein-sparing mechanisms induced by metabolic support in the whole body and in skeletal muscle. Patients were randomized to receive 15 or 30 kcal/kg.day coupled with 0.30 g of N either with standard or branch-chain (BC)-enriched AA solutions. During fasting, patients were highly catabolic (N balance -14.7 +/- 1.2 g N/m2.day, MEH excretion 422 +/- 25 mumol/m2.day) and showed a high efflux of AA N from the leg (5.08 +/- 2.1 g N/m2.day) without difference between the groups. During treatment, body N balance (-5.55 +/- 0.88, p less than .001) and MEH excretion (284 +/- 20, p less than .001) were significantly reduced without difference among the groups; also, AA N leg efflux (2.64 +/- 0.47, p less than .001) was reduced. Moreover, considering the effect of calorie load, patients receiving 30 kcal/kg.day showed a lower efflux of total AA N and of some AA considered as markers of muscle protein catabolism, such as phe, lys, met, and glu. The main difference between solutions was in the efflux of BCAA; particularly, val and leu efflux was turned into uptake in the BCAA group. No significant difference among the groups was found in N balance and MEH excretion during treatment. In brief, muscle catabolism was reduced in an amount dependent on glucose and insulin load, but it was not influenced by BCAA supply. Whole body net protein catabolism was reduced through different mechanisms, either an increased visceral N retention or a decreased muscle N loss. However, muscle N loss was never abolished even in the high calorie groups. 
Magnetic resonance imaging of temporomandibular joint after surgical treatment of internal derangement. Sagittal and coronal surface coil magnetic resonance imaging was performed on 21 patients who about 2 years earlier had surgery for temporomandibular joint internal derangement. Surgical procedure included disk repositioning (23 joints) and diskectomy (seven joints). At the time of reimaging, 20 joints showed recurrence of pain and 10 joints were asymptomatic. Extensive fibrous tissue was seen in the joint space and in the joint capsule in 13 of the 20 painful joints, whereas minimal fibrous tissue in the lateral capsule wall was seen in 3 of the 10 nonpainful joints. Fibrous tissue was surgically confirmed in 10 of the painful joints. Disk displacement was seen in 11 of the 23 joints that had surgical disk repositioning. Disk displacement was seen in both painful (9/17) and nonpainful joints (2/6). It was concluded that magnetic resonance imaging is an excellent method for postoperative imaging of the temporomandibular joint and that attention should be directed to the presence or absence and extension of the fibrous tissue in the joint space and in the joint capsule. 
Post-laryngectomy stomal recurrence: tumour implantation or paratracheal lymphatic metastasis? In the treatment of obstructing laryngeal cancer, an association has often been noted between emergency tracheotomy for airway relief and subsequent post-laryngectomy stomal recurrence. It is however unclear whether this is due to tumour implantation in the tracheotomy track, or paratracheal lymph node metastasis. To investigate the pathophysiology of stomal recurrence, the recurrence rate and clinical outcome of 26 cases of T3N0M0 glottic cancer treated with emergency tracheotomy and subsequent laryngectomy were analysed, and compared with 65 stage-matched cases treated with laryngectomy alone. Analysis shows the 'emergency tracheotomy' group to have a very poor prognosis with a higher incidence of recurrence at the stoma, and also in the regional lymph nodes. These findings suggest that paratracheal lymph node metastasis is an important mechanism in the development of stomal recurrence and thus has considerable implications for the prevention of such a recurrence following laryngectomy in the patient presenting with malignant airway obstruction. 
Ventricular tachycardia with congenital ventricular diverticulum. A 24-year-old man presented with symptomatic, recurrent, sustained ventricular tachycardia (VT). He was found to have a basal inferior left ventricular diverticulum. His sustained VT was reproduced by programmed electrical stimulation and was unresponsive to procainamide, tocainide, propafenone, and flecainide. Endocardial mapping followed by resection and cryoablative surgery was performed. The patient had only one recurrence after 18 months, with subsequent control with procainamide for over 14 months. 
Mitochondrial encephalomyopathies in childhood. I. Biochemical and morphologic investigations. During a 4-year period (1984 to 1988), 50 children referred with manifestations of central nervous system or neuromuscular disease combined with hyperlactatemia were subjected to investigations that aimed to identify and characterize children with mitochondrial disorders. Biochemical and morphologic investigations of quadriceps muscle biopsy tissue were done, including oximetric and spectrophotometric analysis of the respiratory chain function, enzyme histochemistry, electron microscopy, and analysis of mitochondrial DNA. A diagnosis of mitochondrial disease was based on the presence of at least two of five criteria: (1) abnormal results of oximetry, (2) abnormal results of spectrophotometry, (3) enzyme histochemical evidence of cytochrome x oxidase deficiency, (4) deletions or point mutations of mitochondrial DNA, and (5) abundant ultrastructurally abnormal mitochondria. With the combined biochemical and morphologic investigation, 20 of the children were found to have mitochondrial disorders. In an additional 10 children a mitochondrial disorder was neither excluded nor verified. Mitochondrial disorders are thus an important cause of central nervous system and neuromuscular disease in children with hyperlactatemia. 
Predicting the outcomes of electrophysiologic studies of patients with unexplained syncope: preliminary validation of a derived model. PURPOSE: To develop and validate a predictive model that would allow clinicians to determine whether an electrophysiologic (EP) study is likely to result in useful diagnostic information for a patient who has unexplained syncope. PATIENTS: One hundred seventy-nine consecutive patients with unexplained syncope who underwent EP studies at two university medical centers comprised the training sample. A test sample to validate the model was made up of 138 patients from the clinical literature who had undergone EP studies for syncope. DESIGN: Retrospective analysis of patients undergoing EP studies for syncope. The data collector was blinded to the study hypothesis; the electrophysiologist assessing outcomes was blinded to clinical and historical data. Clinical predictor variables available from the history, the physical examination, electrocardiography (ECG), and Holter monitoring were analyzed via two multivariable predictive modeling strategies (ordinal logistic regression and recursive partitioning) for their abilities to predict the results of EP studies, namely tachyarrhythmic and bradyarrhythmic outcomes. These categories were further divided into full arrhythmia and borderline arrhythmia groups. RESULTS: Important outcomes were 1) sustained monomorphic ventricular tachycardia (VT) and 2) bradyarrhythmias, including sinus node and atrioventricular (AV) conducting disease. The results of the logistic regression (in this study, the superior strategy) showed that the presence of organic heart disease [odds ratio (OR) = 3.0, p less than 0.001] and frequent premature ventricular contractions on ECG (OR = 6.7, p less than 0.004) were associated with VT, while the following abnormal ECG findings were associated with bradyarrhythmias: first-degree heart block (OR = 7.9, p less than 0.001), bundle-branch block (OR = 3.0, p less than 0.02), and sinus bradycardia (OR = 3.5, p less than 0.03). Eighty-seven percent of the 31 patients with important outcomes at EP study had at least one of these clinical risk factors, while 95% of the patients with none of these risk factors had normal or nondiagnostic EP studies. In the validation sample, the presence of one or more risk factors would have correctly identified 88% of the test VT patients and 65% of the test bradyarrhythmia patients as needing EP study. CONCLUSION: These five identified predictive factors, available from the history, the physical examination, and the initial ECG, could be useful to clinicians in selecting those patients with unexplained syncope who will have a serious arrhythmia identified by EP studies. 
Stress erosive gastritis. Bleeding from stress erosive gastritis continues to be a potential problem in critically ill and injured patients, but fortunately its incidence has decreased dramatically over the last decade. The explanation for this circumstance is probably multifactorial, but clearly relates to our increased knowledge of its pathophysiology. This understanding has led to the routine use of measures to reduce intragastric acidity (luminal acid being a prerequisite for stress ulcer to occur), coupled with improved techniques for the treatment of shock and the accompanying gastric mucosal hypoperfusion (another prerequisite for the formation of stress ulcers). A number of measures have been used to lower intragastric acidity with H2 receptor blockers emerging as the agents of choice to accomplish this goal. In the unlikely event that bleeding occurs despite these prophylactic measures, aggressive medical management will result in cessation of hemorrhage in over 80% of patients. In those few individuals requiring surgery to control bleeding, no operation has emerged as the recognized procedure of choice. Thus, we believe that a conservative operative approach is indicated in this setting and recommend vagotomy and pyloroplasty with oversewing of the bleeding erosions as appropriate therapy for most patients requiring surgical intervention. 
First-pass nuclear magnetic resonance imaging studies using gadolinium-DTPA in patients with coronary artery disease. Nuclear magnetic resonance (NMR) imaging has been shown to accurately portray cardiac anatomy and function. To investigate the potential of NMR imaging for the assessment of coronary stenosis in patients with chest pain, ultrafast NMR imaging in conjunction with a T1 (longitudinal relaxation time) contrast agent was performed in 17 patients with chest pain who had undergone cardiac catheterization. These included 12 patients with significant coronary artery stenoses and 4 who underwent repeat NMR study after myocardial revascularization. Cardiac images at rest were obtained during rapid intravenous injection of gadolinium-DTPA (0.04 mM/kg). Electrocardiographic-gated images were acquired over 380 ms, with repetitive images obtained every 3 to 4 s. After contrast injection, there was pronounced signal enhancement in the right ventricular cavity, followed by enhancement in the left ventricular cavity and myocardium. Regional myocardium perfused by a diseased vessel demonstrated a lower peak signal intensity (p = 0.001) and lower rate of signal increase (p = 0.001) than did myocardium perfused by coronary arteries without stenosis. Repeat NMR study after revascularization showed an increase in peak signal intensity (p less than 0.002). These results demonstrate the clinical potential of dynamic gadolinium-DTPA-enhanced NMR imaging for the assessment of coronary artery disease in patients with chest pain. In combination with anatomic and functional NMR imaging, this technique has the potential to provide a comprehensive noninvasive cardiac evaluation of patients with suspected coronary artery disease. 
Plasma atrial natriuretic peptide in young normotensive subjects with a family history of hypertension and in young hypertensive patients. Plasma atrial natriuretic peptide (ANP) behavior was evaluated in 26 untreated essential hypertensives, 21 normotensives, and 20 normotensives with hypertensive heredity under normal sodium intake (120 mEq of Na+/day). All subjects were men, mean age 22.1 +/- 1.9 years. Plasma ANP was evaluated by radioimmunoassay on samples collected in supine position upon waking and again after 1 h of orthostatism. Resulting data showed that ANP in hypertensives (supine = 44.5 +/- 19.4 pg/mL, orthostatism = 24.1 +/- 11.6 pg/mL) was at higher levels than in controls (supine = 38.3 +/- 19.4 pg/mL, orthostatism = 19.9 +/- 10.6 pg/mL) or in normotensives with hypertensive heredity (supine = 42.1 +/- 16.8 pg/mL, orthostatism = 23.2 +/- 10.8 pg/mL). Mean ANP level was higher in the latter group than in the control group (supine = +9%; orthostatism = +14.2%). In conclusion, plasma ANP is raised in young essential hypertensives, resulting in slightly elevated levels in normotensives with hypertensive heredity. 
Birthweight ratio revisited. In order to test the hypothesis suggested in a recent report that the birthweight ratio might be a useful predictor of several important clinical outcome measures in babies of less than 31 weeks' gestation, we examined the association between the birthweight ratio and aspects of both short and long term outcome in 436 Leeds babies of less than 31 weeks' gestation. Unlike the report, and contrary to what we had expected, we were unable to find any significant association between birthweight ratio and length of time on the ventilator, mortality, neurological outcome, or intellectual outcome. 
Dideoxyinosine in children with symptomatic human immunodeficiency virus infection. BACKGROUND. 2',3'-Dideoxyinosine (ddl) is a dideoxynucleoside with potent activity in vitro against the human immunodeficiency virus (HIV). In initial clinical trials in adults, ddl showed evidence of antiretroviral activity with little hematologic toxicity. METHODS. We conducted a phase I-II study in 43 children with symptomatic (CDC class P-2) HIV infection. Of these children, 16 (median age, 10 years) had previously received zidovudine, and 27 (median age, 2.6 years) had not. ddl was administered orally in three divided doses totalling 60, 120, 180, 360, or 540 mg per square meter of body-surface area per day for 24 weeks. Eight of the 43 patients did not complete 24 weeks of ddl: 6 died, 1 was withdrawn because of progressive disease, and the other because of toxicity. RESULTS. After oral administration, ddl was rapidly absorbed, although its bioavailability varied greatly among patients. Pancreatitis developed in two children, one receiving ddl at each of the two highest doses. The median CD4 cell count in 38 patients with paired counts increased from 0.218 x 10(9) per liter (218 per cubic millimeter) at base line to 0.327 x 10(9) per liter (327 per cubic millimeter) after 20 to 24 weeks (P = 0.001). Those with CD4 cell counts above 0.1 x 10(9) per liter (100 per cubic millimeter) at base line were significantly more likely to improve in this respect. The median levels of p24 antigen (in 27 patients with detectable levels at entry) declined from 272 pg per milliliter at base line to 77 pg per milliliter at 20 to 24 weeks (P = 0.005). The plasma concentration of ddl correlated significantly with both the degree of decline in the p24 antigen and the degree of improvement in IQ score. Improvement in clinical and immunologic measures occurred in both the previously untreated patients and in those who had been treated with zidovudine. CONCLUSIONS. Dideoxyinosine was well tolerated and showed promising antiretroviral activity in HIV-infected children. The correlation between the clinical response and the plasma concentration of ddl indicates that bioavailability is an important consideration in the use of ddl to treat HIV infection and that individualized pharmacokinetic monitoring and dose adjustment may be important for optimal activity. 
Dietary risk factors associated with acute and persistent diarrhea in children in Karachi, Pakistan. Feeding practices may have an important impact on diarrheal diseases in developing countries. This study evaluated feeding practices in three groups of male children aged 6-36 mo: 100 with persistent diarrhea (PD), 79 with acute diarrhea (AD), and 86 in a comparison group (CG). The children came from comparably poor socioeconomic settings in Karachi, Pakistan, except that the literacy rates were higher in mothers of the CG (P = 0.0001). Although greater than 95% of all infants were breast-fed, delayed initiation of breast-feeding was more common in the diarrhea groups. Children with diarrhea were also more likely to receive supplemental milk (PD = 92%, AD = 87%) than were children in the CG (69%, P less than 0.05). Feedings were not withheld during diarrhea but changes were made in the nature of foods given. These results indicate that several feeding practices may be important risk factors for diarrhea in Pakistan. 
Optic nerve sheath decompression for the treatment of progressive nonarteritic ischemic optic neuropathy. We performed optic nerve sheath decompression on four patients (five eyes) with visual loss secondary to nonarteritic anterior ischemic optic neuropathy. Four of the five eyes had marked improvement in visual function after the operation. Optic nerve sheath decompression is an effective treatment for patients with nonarteritic ischemic optic neuropathy and progressive visual loss. 
Resection of a granular cell tumor at the hepatic confluence. A precarious location for a benign tumor. Granular cell tumors are lesions that account for less than 10 per cent of benign biliary tumors and only 1 per cent occur in the biliary tract. Since the first description, 45 other cases have been described to which we add a case. In reviewing the literature, a striking predominance in black females is evident. The most frequent location of these tumors in the biliary tree appears to be the common bile duct (50%), followed by the cystic duct (37%), the hepatic ducts (15%), and the gallbladder (4%). Most patients have been treated with resection followed by restoration of biliary continuity using biliary enteric diversion. In the case presented, the tumor was located at the hepatic confluence with extension into the hepatic substance requiring segmental duct cholangiojejunostomy after resection. This resulted in fulminant sepsis and death despite adequate preoperative biliary decompression and the lack of signs or symptoms of infected bile. Alternative forms of management in the treatment of this benign condition at this location are discussed. 
Advantages of an immunohistochemical estrogen receptor assay. Immunohistochemical and biochemical assays for estrogen and progesterone receptors were done on 20 breast carcinomas, and results were correlated with various histologic features. The slide-based immunohistochemical technique demonstrated several distinct advantages relative to the tissue homogenization required by the traditional biochemical assay. With the use of frozen tissue sections, the immunohistochemical technique permitted direct visualization of antireceptor binding to tumor cells. Receptor staining of reactive stroma, necrotic tumor, and intermingled benign parenchyma was easily distinguished from receptor staining of the actual carcinoma. This separation is not possible with the biochemical assay. In addition, in situ and invasive components and different morphologic subtypes were evaluated independently. Receptor content of the most aggressive portion of the neoplasm is likely to have the greatest clinical relevance and prognostic significance. Careful correlation of histochemical scores with biochemical assay concentrations is needed to permit the application of this technique to patients entering cancer treatment protocols. 
Use of adenosine echocardiography for diagnosis of coronary artery disease. Two-dimensional echocardiography combined with exercise is sensitive and specific in the detection of coronary artery disease (CAD) by demonstrating transient abnormalities in wall motion. Frequently, however, patients cannot achieve maximal exercise because of various factors. Pharmacologic stress testing with intravenous adenosine was evaluated as a means of detecting CAD in a noninvasive manner. Patients with suspected CAD underwent echocardiographic imaging and simultaneous thallium 201 single-photon emission computed tomography during the intravenous administration of 140 micrograms/kg/min of adenosine. An increase in heart rate, decrease in blood pressure, and increase in double product were observed during adenosine administration. Initial observations revealed that wall motion abnormalities were induced by adenosine in areas of perfusion defects. The adenosine infusion was well tolerated, and symptoms disappeared within 1 to 2 minutes after termination of the infusion. Therefore preliminary observations suggest that adenosine echocardiography appears to be useful in the assessment of CAD. 
Treatment of pancreatic pseudocysts with octreotide. Pancreatic pseudocysts are a common and painful complication of chronic pancreatitis. Seven patients (six male, one female; mean age 49.9 years) with chronic pancreatitis complicated by pseudocysts and persistent pain were treated with the pancreatic anti-secretory drug octreotide for 2 weeks. Octreotide caused no notable changes in the size of the pseudocysts of three patients. In the remaining four patients, the pseudocysts decreased in size by a mean of 42% (range 29-52%), and pain disappeared completely. These findings suggest a role for octreotide in the treatment of pancreatic pseudocysts. 
An open label study of oral transmucosal fentanyl citrate (OTFC) for the treatment of breakthrough cancer pain. Ten patients with advanced cancer and breakthrough pain between the ages of 39 and 78 received oral transmucosal fentanyl citrate (10-15 micrograms/kg) 4 or 5 times each over 2 days (42 total administrations) in an open study. Baseline vital sign and rating scale results did not vary over administrations, except for heart rate which showed an 8 beats/min decrease over 4 administrations. Heart rate and oxygen saturation did not vary significantly over 120 min of evaluation, and minimal changes in blood pressure and respiration rate were found. Significant reduction in pain scores as measured by a pain descriptive scale, the McGill-Melzack scale, and a numeric (VAS) scale were seen at all evaluations from 5 to 120 min. Average time to onset of pain relief was 9.5 min after administration. Wellbeing was significantly increased at all evaluations. Activity level as recorded by the investigator was significantly reduced from 10 to 30 min after administration, however, activity level as reported by the patient was significantly increased at 5 min and from 60 to 120 min after OTFC administration. There were no significant adverse effects. 
Influence of calcium administration on the short-term hemodynamic and anti-ischemic effects of nifedipine. This prospective study investigated whether pretreatment with intravenously administered calcium would influence the effect of nifedipine on rest hemodynamics and treadmill performance in patients with ischemic heart disease. Seventeen patients were studied after undergoing a qualifying treadmill exercise test that revealed ST segment depression indicative of ischemic heart disease. Study subjects performed three additional treadmill tests as part of the protocol. One treadmill test was obtained from each patient to provide baseline measurements without a preceding intravenous infusion and in the absence of all antianginal drugs including nifedipine; two additional exercise tests were preceded by an infusion and 10 mg of bite-and-swallow nifedipine. The infusions, administered in a randomized, double-blind, crossover fashion, consisted of either 10 ml of 10% calcium chloride (13.6 mEq) in 50 ml of 5% dextrose in water or 5% dextrose in water alone. Rest systolic blood pressure (134 +/- 4.6 mm Hg) was unchanged after placebo infusion (135 +/- 4.6 mm Hg) but decreased to 124 +/- 4.1 mm Hg (p less than 0.01) 25 min after nifedipine administration. Rest systolic blood pressure increased after calcium infusion (from 139 +/- 4.3 to 148 +/- 4.8 mm Hg, p less than 0.01) and then decreased significantly 25 min after nifedipine administration to 135 +/- 4.2 mm Hg (p less than 0.01). Despite a decrease at the time of peak nifedipine effect after either infusion, systolic blood pressure was significantly lower after administration of nifedipine alone than after administration of calcium and nifedipine (124 +/- 4.1 vs. 135 +/- 4.2 mm Hg, p less than 0.01). 
Neurophysiologic assessment of the anal sphincters. One hundred twenty consecutive patients with either fecal incontinence (60 patients), chronic constipation (41 patients), or idiopathic intractable pelvic pain (19 patients) were prospectively assessed. Patients underwent concentric needle electromyography (EMG), bilateral pudendal nerve terminal motor latency evaluation, anorectal manometry, and cinedefecography. The most common EMG finding in patients with fecal incontinence was decreased recruitment of motor units with squeezing and polyphasic motor unit potentials; these are consistent with an injury pattern. The most common EMG finding in the constipated patients was paradoxical puborectalis contraction. This latter abnormality was also a frequent finding in patients with rectal pain, as was prolongation of pudendal nerve latency. Paradoxical puborectalis contraction was diagnosed more frequently with EMG than with cinedefecography. Inter-examination correlation was best in the incontinent group between EMG and manometry. Cinedefecography had poor correlation with EMG in all patient groups but was valuable in the detection of additional pathology such as rectoanal intussusception and anterior rectocele. Electromyography including pudendal nerve terminal motor latency assessment is a valuable adjunct in the evaluation of disorders of evacuation. The information it yields is complementary to that offered by more routine physiologic examinations. 
Prenatal diagnosis of the neurofibromatoses. This article reviews the application of genetic linkage analysis to molecular prenatal diagnosis using the neurofibromatoses as an example. The clinical manifestations and diagnostic criteria for these diseases are reviewed first, followed by a brief description of the principles underlying genetic linkage analysis, the detection of DNA polymorphisms and their application to the cloning of the NF1 gene. The last two sections review the molecular diagnosis and some of the problems in prenatal genetic counseling for NF1. 
Ventriculoatrial intervals during narrow complex reentrant tachycardia in children. Ventriculoatrial (VA) intervals during narrow complex tachycardia were measured in a pediatric population. The VA intervals were similar to those in adults but were slightly shorter. In the pediatric subjects values less than 60 msec excluded the participation of an accessory pathway in the tachycardia circuit. Three out of 11 patients with atrioventricular nodal reentrant tachycardia (AVNRT) had VA values greater than or equal to 70 msec, while 5 of 28 patients with orthodromic reciprocating tachycardia (ORT) had values less than or equal to 70 msec. Using a cut-off value of 70 msec as the sole criteria to distinguish between ORT and AVNRT could lead to errors in classification of the underlying mechanism of the tachycardia. 
A familial coincidence of pseudotumor cerebri and communicating hydrocephalus. A family in which the mother and two of four daughters had a diagnosis of pseudotumor cerebri and one son developed communicating hydrocephalus is described. The other two daughters both have a long history of headaches but no signs of intracranial hypertension. The argument is advanced that there exists a defect of cerebrospinal fluid absorption common to pseudotumor cerebri and communicating hydrocephalus. 
Physical activity and reduced occurrence of non-insulin-dependent diabetes mellitus BACKGROUND. Physical activity is recommended by physicians to patients with non-insulin-dependent diabetes mellitus (NIDDM), because it increases sensitivity to insulin. Whether physical activity is effective in preventing this disease is not known. METHODS. We used questionnaires to examine patterns of physical activity and other personal characteristics in relation to the subsequent development of NIDDM in 5990 male alumni of the University of Pennsylvania. The disease developed in a total of 202 men during 98,524 man-years of follow-up from 1962 to 1976. RESULTS. Leisure-time physical activity, expressed in kilocalories expended per week in walking, stair climbing, and sports, was inversely related to the development of NIDDM. The incidence rates declined as energy expenditure increased from less than 500 kcal to 3500 kcal. For each 500-kcal increment in energy expenditure, the age-adjusted risk of NIDDM was reduced by 6 percent (relative risk, 0.94; 95 percent confidence interval, 0.90 to 0.98). This association remained the same when the data were adjusted for obesity, hypertension, and a parental history of diabetes. The association was weaker when we considered weight gain between the time of college attendance and 1962 (relative risk, 0.95; 95 percent confidence interval, 0.90 to 1.00). The protective effect of physical activity was strongest in persons at highest risk for NIDDM, defined as those with a high body-mass index, a history of hypertension, or a parental history of diabetes. These factors, in addition to weight gain since college, were also independent predictors of the disease. CONCLUSIONS. Increased physical activity is effective in preventing NIDDM, and the protective benefit is especially pronounced in persons at the highest risk for the disease. 
Isolation of a human DNA sequence which spans the fragile X. To identify the sequences involved in the expression of the fragile X and to characterize the molecular basis of the genetic lesion, we have constructed yeast artificial chromosomes (YACs) containing human DNA and have screened them with cloned DNA probes which map close to the fragile site at Xq27.3. We have isolated and partly characterized a YAC containing approximately 270 kb of human DNA from an X chromosome which expresses the fragile X. This sequence in a yeast artificial ring chromosome, XTY26, hybridizes to the two closest DNA markers, VK16 and Do33, which flank the fragile site. The human DNA sequence in XTY26 also spans the fragile site on chromosome in situ hybridization. When a restriction map of XTY26, derived by using infrequently cutting restriction enzymes, is compared with similar YAC maps derived from non-fragile-X patients, no large-scale differences are observed. This YAC, XTY26, may enable (a) the fragile site to be fully characterized at the molecular level and (b) the pathogenetic basis of the fragile-X syndrome to be determined. 
Hepatitis C virus infection and chronic liver disease in children with leukemia in long-term remission. Antibody to the recently identified hepatitis C virus (HCV) was investigated in sera of 50 leukemic children who had chronic liver disease (CLD), observed for 1 to 12.6 years after therapy withdrawal. All patients were tested for anti-HCV at regular intervals: Ortho-enzyme-linked immunosorbent assay (ELISA) test was performed in all cases. Reactive sera were also tested by recombinant immunoblotting assay to define the specificity of the results obtained by ELISA. Twelve cases (24%) were persistently positive (group A), 11 (22%) were transiently anti-HCV+ positive (group B), and 27 (54%) were negative. Mean SGPT peak during follow-up was significantly higher in group A (P = .014, A v B and P less than .00001, A v C). SGPT normalized off-therapy in 1 of 12 cases (group A), 10 of 11 (group B), and 19 of 27 (group C) (P = .0004, A v B and P = .012, A v C). Accordingly, liver histology, available in 37 patients, showed signs of chronic hepatitis in all patients in group A while most patients in group B and C had less severe liver lesions. These results indicate that HCV plays a significant role in the etiology of chronic hepatitis in leukemic patients and that persistent anti-HCV activity correlates with a more severe CLD, which could jeopardize the final prognosis of children cured of leukemia. 
Antihypertensive effect of isradipine on blood pressure at rest and during exercise. After three months of treatment with isradipine, 20 patients with mild hypertension had reduced their resting blood pressure (BP) from 157/103 to 132/85 mm Hg and their BP during isometric exercise from 192/124 to 166/105 mm Hg. The isradipine dose necessary to normalize BP (both at rest and post-exercise) was 1.25 mg twice daily (2 x 1/2 tablet) in 50% of patients and 2.5 mg twice daily (2 x 1 tablet) in 25%. In the remaining 25% of patients, isradipine was combined with 1 mg/day bopindolol. There were virtually no accompanying side effects; in particular, reflex tachycardia was negligible or absent. It is concluded that isradipine is a reliable antihypertensive treatment in mild-to-moderate hypertension. 
Diagnostic imaging of musculoskeletal infection. Roentgenography; gallium, indium-labeled white blood cell, gammaglobulin, bone scintigraphy; and MRI. A great deal of effort has been made to evaluate and define the role of various diagnostic imaging techniques in various clinical settings that complicate the diagnosis of osteomyelitis. Except possibly in neonates, bone scintigraphy remains generally recommended when there has been no previous osseous involvement. In other cases of chronic disease, previous fracture or trauma, prosthesis, and diabetic foot, In-WBC scintigraphy is generally accepted as an appropriate imaging technique. MRI will play an increasingly important role in diagnosing osteomyelitis and may prove to be an important adjunct in these cases. Research continues to improve our current diagnostic armamentarium. In-IgG appears to avoid practical deficiencies encountered with 67Ga and In-WBC; it remains to be seen what role this agent will play in routine clinical practice. All agents to date image inflammation, not infection, and most require delayed imaging sessions, usually at 24 hours. These shortcomings necessitate further research to develop new radiotracers that can provide useful images within several hours and that are specific for infection, perhaps ultimately delineating the particular microorganism involved. 
Meningiomas of the lateral skull base: neurotologic manifestations and patterns of recurrence. The eradication of basicranial meningiomas by traditional surgical techniques is often hindered by neoplastic entanglement with critical neurovascular structures. Apparent, complete tumor resection is frequently followed by extensive, yet clinically silent, recurrent disease with local infiltration of bone, cranial nerves, and brain. Fifty-five cases of sphenoid wing or parasellar meningioma were analyzed to identify clinical manifestations suggestive of early tumor recurrence. Regrowth patterns were then defined according to preoperative radiographic and intraoperative surgical findings. Medial tumor regrowth, involving the cavernous sinus, caused neurapraxia of cranial nerves III, IV, or VI, with associated diplopia or ophthalmoplegia. Inferior (caudal) regrowth of disease involved the infratemporal fossa, pterygomaxillary space, or paranasal sinuses by bony erosion of the middle cranial fossa floor or through natural anatomic foramina and fissures. Such inferior extension was manifested clinically by facial hypesthesia, trismus, and referred otalgia caused by trigeminal nerve involvement and by autophony or serous otitis media related to eustachian tube obstruction. Posterior tumor regrowth occurred along the petrous bone and horizontal carotid canal, resulting in internal auditory meatus erosion and cerebellopontine angle extension with associated tinnitus, hearing loss, unsteadiness, and occasional facial twitching. While the clinical and radiographic evaluations of any patient with a suspected recurrent basicranial meningioma are critical in planning the method and magnitude of reoperation, an understanding of potential recurrence patterns can be used in devising more extensive, combined approaches that may allow complete tumor extirpation at the initial surgical intervention. 
Provocation of transient lower esophageal sphincter relaxations by meals in patients with symptomatic gastroesophageal reflux. The effect of a meal on the rate of transient lower esophageal sphincter (LES) relaxations and patterns of gastroesophageal reflux was investigated in 49 patients referred for evaluation of gastroesophageal reflux. Esophageal motility and pH were recorded concurrently before and after a standard meal. In the patients with symptomatic reflux, the meal induced a four- to sevenfold increase in the gastroesophageal reflux through two mechanisms: a four- to fivefold increase in the rate of transient LES relaxations and an increase in the proportion of transient LES relaxations accompanied by reflux from 47% to 68%. Overall the rate of reflux episodes that occurred by mechanisms other than transient LES relaxation did not increase significantly. An exception to these findings were those in six patients with chronically absent basal LES pressure in whom transient LES relaxations could not be scored. In these patients, reflux increased postprandially through mechanisms other than transient LES relaxation. These findings confirm the pivotal importance of transient LES relaxations in the pathogenesis of gastroesophageal reflux. 
Atrial antitachycardia pacing in children and young adults. Atrial antitachycardia pacing was tested in 23 children and young adults. The majority of these patients had had operative repair of congenital cardiac defects and had both bradycardia and tachycardia. Pacemakers were usually implanted by the transvenous technique using bipolar leads. In each patient it was possible to find a tachycardia termination algorithm that successfully converted the tachycardia. In some patients very complex algorithms were necessary. In each patient it was also possible to find an algorithm that successfully differentiated the abnormal tachycardia from sinus tachycardia. Twelve patients required no antiarrhythmic drugs after pacemaker implantation, while 10 patients required one drug and one patient required two drugs. Eight of 23 patients had symptomatic tachycardias that required reprogramming the pacemaker to a different tachycardia termination sequence. Seven patients required reoperations, five for adapter problems and two for infection or erosion. Cardiac function improved in 15 of the 23 patients. Antitachycardia pacing is a viable option for management of tachycardias in children and young adults. 
Prevalence of Raynaud's phenomenon in Japanese males and females. In order to estimate the prevalence rate of Raynaud's phenomenon in the Japanese population, 1875 males and 1998 females were interviewed by medical doctors, aided by a typical photograph of Raynaud's phenomenon. The prevalence rates were 3.3% in males and 2.5% in females. Approximately 60% of the male cases of Raynaud's phenomenon were presumed to be caused by vibration syndrome or trauma to the fingers. Prevalence rates excluding these two causes were 1.2% in males and 2.2% in females. The male:female ratio of these prevalence rates was 1:1.9. The prevalence rate for males increased with age, while that for females tended to decrease. The male:female ratio for subjects under 50 years old was 1:5.2 and for those 50 years old or older the ratio was 1:1.1. The prevalence rates of symptoms limited to finger whitening, excluding cases caused by vibration syndrome or trauma, were 1.0% in males and 1.8% in females. Both of these prevalence rates were lower than those of male and female Caucasians. 
The physical examination in acute cardiac ischemic syndromes. The physical examination in acute cardiac ischemia remains a valuable tool when done with skill. Ischemia without infarction alters cardiac function, and the physical examination yields findings that reflect these changes. Ischemia with infarction alters structure and function, resulting in physical findings that are usually more dramatic and of longer duration, sometimes permanent. Carefully done, the physical examination provides information that helps in management of the immediate course, predicts prognosis, and allows for better interpretation of cardiovascular tests, both invasive and noninvasive. 
Phase I/II study of cyclophosphamide, doxorubicin, fluorouracil, and leucovorin for treatment of metastatic adenocarcinoma. Leucovorin enhances the cytotoxicity of fluorouracil (5-FU) in patients with colorectal cancer and may increase the efficacy of combination chemotherapy regimens containing 5-FU. To determine the maximum tolerated dose of 5-FU with leucovorin for use in combination with cyclophosphamide and doxorubicin, we conducted a phase I/II trial in 20 patients. The doses of leucovorin (200 mg/m2 on days 1-5), cyclophosphamide (500 mg/m2 on day 1), and doxorubicin (40 mg/m2 on day 1) were held constant, while the dose of 5-FU was escalated in cohorts of patients beginning at 150 mg/m2 on days 1-5. Cycles were repeated every 3 weeks. Significant mucositis, diarrhea, and myelosuppression were infrequently observed in patients receiving up to 250 mg/m2 5-FU on days 1-5. In contrast, at a dose of 300 mg/m2 on days 1-5, three of six patients had granulocyte count nadirs of less than 500/microL during the first cycle of therapy, and two of these three had platelet counts of less than 25,000/microL. In addition, two patients treated at this dose had significant mucosal toxic effects, and three had insufficient recovery to permit a second course by day 22. Among 14 patients with assessable breast cancer, there were one complete and nine partial responses (response rate 71%). Leucovorin modulation of 5-FU can be safely incorporated into combination chemotherapy with cyclophosphamide and doxorubicin and provides a highly active regimen for treatment of metastatic breast cancer. Further study will be required to determine whether the addition of leucovorin significantly enhances the activity of this regimen. 
Deep vein thrombosis: effect of graduated compression stockings on distension of the deep veins of the calf. The mechanisms by which graduated compression stockings prevent deep vein thrombosis are not completely understood. Recent work has suggested that venous distension plays a role in initiating the process. Our previous work has shown that the deep veins of the lower limb distend in patients undergoing surgical procedures. We have investigated 40 patients receiving surgical treatment on the abdomen or neck. A medial gastrocnemius vein was studied using ultrasound imaging during the operations. In half the patients a graduated compression anti-embolism stocking was applied to the limb under study at the start of the operation, immediately after initial measurements of vein diameter. The median vein diameter in both groups was the same at the start of the operative procedures (control, 2.6 mm, interquartile range 2.1-3.3 mm; stocking, 2.6 mm, interquartile range 2.1-3.7 mm). After application of a stocking the median diameter in this group fell to 1.6 mm (interquartile range 1.3-2.8 mm) and then decreased slightly at the end of the operation. In the control group the vein diameter increased to 2.9 mm (interquartile range 2.3-4.0 mm) during the operative procedure. 
Right coronary artery disease. Pathophysiology, clinical relevance, and methods for recognition. Among the clinical manifestations of ischemic heart disease, right coronary artery (RCA) disease offers a wide variety of right and left ventricular ischemic involvement, including prevalent right ventricular dysfunction and severe cardiac failure. Whether the right ventricular impairment is dependent primarily on ischemia of the right ventricle or requires a concomitant left ventricular dysfunction remains debatable. To assess the pathophysiology and clinical relevance of RCA-related ischemia, a systematic study of patients with single RCA disease (either vasospastic angina at rest or typical stable angina) was undertaken by radionuclide ventriculography. A high incidence of ischemia-induced right ventricular dysfunction was observed (93% and 95% in angina at rest and on effort, respectively), either alone or associated with left ventricular impairment. These results were compared with those obtained in a control population with isolated left anterior descending artery disease and either primary or secondary angina pectoris. We infer that the impairment of the right ventricle was related primarily to right ventricular ischemia and that left ventricular dysfunction alone did not cause an important depression of right ventricular systolic function. In conclusion, the clinical manifestations of RCA disease can be protean; the right ventricle can be the target of ischemia, and recognition of its impairment poses diagnostic problems. Radionuclide ventriculography and two-dimensional echocardiography, together with stressors of coronary flow reserve, are reliable techniques for assessing RCA-related ischemia. 
Unrecognized stenosis by angiography documented by intravascular ultrasound imaging. This report documents how intravascular ultrasound imaging was used to diagnose a short "napkin-ring" stenosis that was missed by coronary angiography. Intravascular ultrasound revealed a lumen of 2.6 x 2.5 mm in diameter and 5.0 mm2 in cross-sectional area, with a residual atheroma that occluded 63% of available cross-sectional area at the stenosis. 
Reduction in the frequency of ventricular late potentials after acute myocardial infarction by early thrombolytic therapy. Ventricular late potentials are strong predictors of arrhythmic events after acute myocardial infarction (AMI). To assess the effect of intravenous thrombolysis on the incidence of ventricular late potentials, 223 consecutive patients surviving a first AMI were included in the present study: 59 patients (53 men, 6 women, mean age +/- standard deviation 55 +/- 10 years) received intravenous recombinant tissue-type plasminogen activator (100 mg over 3 hours, group A) and 164 patients (123 men, 41 women, mean age 61 +/- 11 years) received conventional medical treatment (group B). A time-domain signal-averaged electrocardiogram and a high-resolution beat-to-beat recording (gain 10(6), filters 100 to 300 Hz) were performed at 10 +/- 3 days after AMI. There was no difference between group A and B patients in terms of AMI location (anterior in 28 of 59 vs 80 of 164, difference not significant [NS]), mean left ventricular ejection fraction (55 +/- 10 vs 55 +/- 13%, NS), or presence of heart failure (New York Heart Association class III or IV in 12 of 59 vs 40 of 164, NS). The incidence of ventricular late potentials was 10% (6 of 59) in group A and 24% (39 of 164) in group B (p less than 0.05). Among the 146 patients who underwent coronary arteriography, the incidence of ventricular late potentials was 13% (10 of 80) in patients with a patent infarct-related artery and 26% (17 of 66) in patients with an occluded infarct-related artery (p less than 0.05). 
A phase IA trial of sequential administration recombinant DNA-produced interferons: combination recombinant interferon gamma and recombinant interferon alfa in patients with metastatic renal cell carcinoma. This study investigated the effects of sequentially administered recombinant interferon gamma (rIFN gamma) and recombinant interferon alfa (rIFN alpha) in 36 patients with metastatic renal cell carcinoma (RCC). rIFN alpha was subcutaneously administered daily for 70 days at dosages that varied (2.5, 5, 10, and 20 x 10(6) U/m2) across four cohorts of patients. Within each cohort of patients receiving a given dose of rIFN alpha, three subsets of patients received either 30, 300, or 1,000 micrograms/m2 rIFN gamma. rIFN gamma was administered intravenously for 5 days every third week, 6 hours prior to administration of rIFN alpha. Dose-limiting toxicity (DLT) included constitutional symptoms, leukopenia, nephrotic syndrome with acute renal failure, hypotension associated with death, and congestive heart failure. DLT was related more often to the rIFN alpha dose level than to rIFN gamma dose level. Maximum-tolerated dose (MTD) was 10 x 10(6) U/m2 rIFN alpha and 1,000 micrograms/m2 rIFN gamma. Six patients failed to complete a minimum of 21 days of therapy due to toxicity or rapid progression of disease. Clinical responses were seen in eight of 30 assessable patients. Two patients experienced complete remission and have remained in complete remission 20+ and 22+ months. An additional six patients have shown partial responses for 4 to 18+ months. One patient in partial remission continues to show slow regression of pulmonary and liver lesions off therapy with rIFNs. Clinical responses have remained durable for patients with complete remissions and patients with partial remissions. The results of this study suggest that toxicities associated with combination rIFN therapy can be reduced by administering these agents sequentially as opposed to simultaneously. 
Primary cardiac leiomyosarcomas. Two patients with primary cardiac leiomyosarcoma, one of the rarest malignant tumors of the heart, are described. The first patient had a tumor of the pulmonary trunk and was admitted with symptoms suggestive of pulmonary thromboembolism. The second had a tumor of the left atrium and had signs and symptoms of mitral valve obstruction and regurgitation. The 2 patients were operated on and later underwent adjuvant chemotherapy. Both died more than 22 months after operation, having required multiple hospital admissions for treatment of complications related to the pathology or the treatment of the primary cardiac leiomyosarcoma. Nonetheless, aggressive surgical excision followed by chemotherapy appears to have improved survival in these patients with primary cardiac leiomyosarcoma, as they are among the longest survivors reported. 
Regulation of luteinizing hormone-releasing hormone receptor binding by heterologous and autologous receptor-stimulated tyrosine phosphorylation. Pancreatic cancers overexpress tyrosine kinase and luteinizing hormone-releasing hormone (LH-RH) receptor (LH-RHR)-mediated tyrosine phosphatase. LH-RHR is a 60-kDa protein. One of the substrates of epidermal growth factor (EGF)-stimulated tyrosine kinase activity and LH-RH- and somatostatin-stimulated tyrosine phosphatase activity is also a 60-kDa protein. This suggests the possibility that LH-RHR regulation by tyrosine phosphatase and tyrosine kinase is mediated by (de)phosphorylation of existing LH-RHR. To test this hypothesis, membranes of MIA PaCa-2 cells, a human dedifferentiated pancreatic cancer cell line, were incubated without hormone (control) or with 0.1 microM EGF or somatostatin analogue RC-160 for 1 hr at 4 degrees C to phosphorylate the 60-kDa protein. Competition binding experiments with I125-labeled [D-Trp6]LH-RH by displacement with a nonradioactive ligand showed that the LH-RH binding in 69% of the points was increased by EGF and 85% was decreased by RC-160 compared with controls (n = 61; both significant, P less than 0.001). The specific binding was altered, increasing 50-150% after preincubation with EGF and decreasing 60-70% after RC-160. No change was seen in the binding affinity constant after pretreatment with EGF or RC-160. This shows that phosphorylation regulates binding of LH-RH and may explain the up-regulation by EGF and down-regulation by RC-160 and by LH-RH of the LH-RH response. 
Noninvasive diagnosis of deep venous thrombosis. Deep venous thrombosis of the lower extremity poses a diagnostic challenge. Clinical signs and symptoms are often misleading, and sensitive and specific tests are essential for diagnosis. The cost, patient discomfort and risk of morbidity associated with contrast venography have led to the development of noninvasive diagnostic techniques such as Doppler ultrasound, impedance plethysmography and duplex ultrasound scanning. If noninvasive tests unequivocally indicate deep venous thrombosis, treatment may be started without the need for contrast venography. 
Effects of perinatal stroke on striatal amino acid efflux in rats studied with in vivo microdialysis. We used in vivo microdialysis to determine the impact of a focal hypoxic-ischemic insult on striatal amino acid efflux in the immature brain. Microdialysis probes were inserted into the right striatum of postnatal day 7 rats. To induce hypoxic-ischemic injury, the right carotid artery was ligated and the animals were exposed to 8% oxygen for 2.5 hours (n = 22). Rats exposed to ligation alone (n = 10) or hypoxia alone (n = 8) and untreated controls (n = 17) were also studied. Two hours after probe insertion, a 30-minute baseline microdialysis sample was obtained. After arterial ligation, two additional baseline samples were collected. Five more samples were collected over the next 2.5 hours (in 8% oxygen or room air). Eight amino acids (glutamate, aspartate, taurine, glutamine, alanine, serine, glycine, and asparagine) were consistently detected in dialysates using a high-performance liquid chromatography assay with electrochemical detection. In untreated controls, amino acid efflux did not change over 4 hours. During hypoxia-ischemia, efflux values fluctuated widely, with marked intra-animal and interanimal variability. Efflux peaks for each amino acid were defined as values greater than the highest control mean value plus two standard deviations. Glutamate efflux peaks (greater than 7 pmol/min compared with 2 pmol/min at baseline) were detected in no controls and in eight hypoxic-ischemic rats (p = 0.006, Fisher's two-tailed exact test). Taurine efflux peaks (greater than 75 pmol/min compared with 10 pmol/min for controls at baseline) were detected in 10 hypoxic-ischemic rats and one control (p = 0.01) and in seven of the eight animals in which glutamate efflux peaks occurred (p = 0.006). 
Patterns of morbidity and mortality in typhoid fever dependent on age and gender: review of 552 hospitalized patients with diarrhea. Features of typhoid fever were correlated with age and gender through a review of the charts of 552 hospitalized culture-positive patients with diarrhea in Bangladesh. Seizures occurred more frequently in children from birth through 10 years of age (5%-11%) and pneumonia more frequently in children from birth through 5 years of age (8%-15%) than in older age groups (P less than .05), whereas intestinal perforation occurred more frequently in patients greater than or equal to 11 years of age (5%-25%) than in younger age groups (P less than .005). Compared with older age groups, children from birth through 10 years of age were more anemic, those from birth through 5 years of age had a higher mean white blood cell count, and those from birth through 1 year of age had a lower mean blood carbon dioxide content (all P less than .05). Female patients were more severely anemic than male patients (P less than .05). The case-fatality rate was 4.3% overall, with the highest rates for children from birth through 1 year of age (11%) and adults greater than or equal to 31 years of age (10%). Female patients had a higher case-fatality rate (6%) than male patients (3%), although the difference was not significant (P greater than .05). Death was independently associated with seizures, intestinal perforation, pneumonia, and delirium or coma. These results indicated that the patients with typhoid fever who were at highest risk of complications and death were children from birth through 1 year of age and adults greater than or equal to 31 years of age. 
Diurnal blood pressure variation in quadriplegic chronic spinal cord injury patients. 1. Measurement of blood pressure and heart rate over a 24 h period was performed in 10 quadriplegic spinal cord injury patients and 10 immobilized, neurologically intact orthopaedic subjects by using the Spacelabs 90207 automated ambulatory monitoring system. 2. Systolic and diastolic blood pressure fell significantly at night in orthopaedic subjects but not in quadriplegic patients, and night-time blood pressures were similar in both groups. 3. Cumulative summation of differences from a reference value (cusum analysis) confirmed a markedly diminished diurnal blood pressure variation in the quadriplegic patients. 4. These findings could not be accounted for on the basis of blood pressure variations during chronic postural change. 5. Heart rate fell significantly at night in both groups. 6. The findings suggest that the increase in blood pressure during waking hours in neurologically intact subjects is a consequence of a diurnal variation in sympathetic activity (absent in quadriplegic patients with sympathetic decentralization) which is independent of changes in physical activity. 
Postpericardiotomy and postmyocardial infarction syndrome presenting as noncardiac pulmonary edema. Three cases are reported that describe acute pulmonary edema as an early manifestation of a postpericardiotomy or postmyocardial infarction syndrome. Each of these cases occurred in the presence of good left ventricular function. The cases suggest this syndrome occurs in immunologically primed patients who have had prior cardiac injury resulting in readily available heart antibody. The first report followed an acute myocardial infarction that required a temporary pacemaker, and the two other cases occurred following coronary artery bypass surgery. Two of the patients had a history of distant myocardial or pericardial injury, and the third patient had an acute anteroseptal myocardial infarction two to three weeks before cardiac surgery. All three patients with pulmonary edema responded dramatically to corticosteroids, having been resistant to diuretic and pre-load and afterload reduction therapy, suggesting an autoimmune capillary injury process. Early recognition of such a syndrome is important since all three patients were successfully treated, and might otherwise have been confused with other causes of pulmonary edema. 
Splanchnic oxygen consumption in septic and hemorrhagic shock. Oxygen consumption (VO2) is dependent on oxygen delivery (DO2) in septic shock. Local hypoxia with later secondary organ failure may develop, however, despite an often hyperdynamic circulation. The splanchnic organs seem to be of vital importance in this context. In experiments performed in pigs we compared total body VO2 and DO2 with oxygen consumption and delivery in the gastrointestinal organs and the liver in two different shock states: (1) septic shock induced by peritonitis (n = 6) and (2) hemorrhagic shock (n = 6). Another group of six animals not in shock served as controls. Total, gastrointestinal, and liver DO2 decreased in a similar pattern in both septic and hemorrhagic shock. Gastrointestinal and liver VO2 increased in sepsis, whereas it was unchanged in hemorrhage. In the later phase of sepsis, liver VO2, but not gastrointestinal VO2, again decreased, because liver oxygen extraction was almost total and liver DO2 decreased further. The development of flow-dependent liver hypoxia was reflected in a decrease in liver lactate turnover (increased liver lactate release) during late sepsis. Early hypoxia in the splanchnic region is suggested as a plausible mechanism behind the development of secondary organ failure, especially in sepsis. 
Long-term L-carnitine treatment in isovaleric acidemia. A 5-year-old girl with isovaleric acidemia was treated with long-term L-carnitine and no supplemental glycine. Clinical and laboratory data are presented. Following diagnosis and treatment at age 2 years, the frequency of acute exacerbations of metabolic acidosis was reduced and she resumed normal growth and development. L-carnitine supplementation and protein restriction may be sufficient for effective therapy of isovaleric acidemia. 
Wrist movements in able-bodied and brain injured individuals. The purpose of this study was to compare movement velocity characteristics during targeted wrist movements between able-bodied individuals and a sample of individuals with spasticity secondary to closed head injury. Two amplitudes (30 degrees and 60 degrees) of movement were performed at slow and fast velocities, with the forearm either passively supported or actively supported by elbow extension and shoulder flexion. Variables measured were the following: (1) average velocity of entire movement, (2) velocity for 10 degrees increments of a movement, and (3) ratio of average peak 10 degrees increment velocity to average velocity. In addition, qualitative examination of velocity profiles was performed. Slow movements were performed in a discontinuous manner by both groups; however, observable differences in peak/average velocity were noted between groups in the unsupported position during slow and fast movements. Able-bodied individuals performed seven of eight fast movements with greater velocity (p less than .05) than brain injured individuals, and the fast movements of the able-bodied subjects were continuous. 
Recurrent prolonged coma due to basilar artery migraine. A case report. A 25 year old patient presented with recurrent prolonged episodes of life-threatening coma varying from 3 to 10 days. The clinical recovery was slow. The history and technical examinations led to the diagnosis of basilar artery migraine (BAM). The etiology of the coma episodes is thought to be related to ischemic dysfunction of the rostral part of the brainstem due to severe spasm of the basilar artery demonstrated by arteriography. Exceptional are the recurrent prolonged coma episodes of sudden onset, the severe spasm of the basilar artery, and the suppression-burst and FIRDA pattern on the EEG examinations during the coma episodes. 
White sponge naevus and ocular coloboma. White sponge naevus occurred in association with coloboma of the iris in six members of one family, across three generations. The association of these two dominantly inherited conditions has not to our knowledge previously been described. 
Effects of short-term, diet-induced hypercholesterolemia on systemic hemodynamics, myocardial blood flow, and infarct size in awake dogs with acute myocardial infarction. BACKGROUND. Short-term cholesterol feeding has been shown to affect vasomotor tone and increase infarct size in anesthetized rabbits. The purpose of the study was to determine whether acute hypercholesterolemia reduced collateral flow to ischemic myocardium and increased infarct size in the awake dog. METHODS AND RESULTS. Acute myocardial infarction was produced in awake dogs by a 4-hour left anterior descending coronary artery occlusion followed by 6-hour reperfusion after either a cholesterol-supplemented diet (n = 14) or a control diet of dog chow (n = 15) for 10 days. Infarct size was determined using nitroblue tetrazolium staining. In two subgroups, a 15-minute transient occlusion of the left anterior descending coronary artery was produced before the diet treatments and was compared with occlusion after diet treatments, so that the effects of hypercholesterolemia of collateral flow could be determined by paired comparisons. Cholesterol feeding increased plasma cholesterol to 288 +/- 52 mg/dl, which was twofold to threefold that in the control group (127 +/- 35 mg/dl), but had no effects on baseline systemic hemodynamics and myocardial blood flow. Coronary artery occlusion produced similar increases in heart rate, mean aortic pressure, left atrial pressure, and plasma norepinephrine in both groups of animals. However, cholesterol feeding reduced collateral flow to ischemic myocardium and increased infarct size, compared with the control group. The infarct size correlated with ischemic myocardial blood flow in both groups, but the slopes of regression lines relating the two variables did not differ between the two groups. CONCLUSIONS. Short-term, diet-induced hypercholesterolemia increased infarct size in awake dogs. This change results, at least in part, from a decrease in collateral blood flow to ischemic myocardium during coronary artery occlusion. 
Stress incontinence and cystoceles. We studied prospectively 62 women with cystoceles by video-urodynamics before and after operative repair. Of 29 women with grades 1 and 2 cystoceles 8 had residual urine, 14 had urge incontinence and 24 had symptoms of stress urinary incontinence. Of these women 23 had urodynamic evidence of stress incontinence, as did 3 of 5 without stress incontinence symptoms. Of 33 women with large cystoceles 22 had symptoms of stress urinary incontinence but 10 more had urodynamic evidence of stress urinary incontinence. Of these 33 women 18 had significant residual urine and 24 had urge incontinence. Operative repair resolved stress incontinence in 51 of 54 women, urge incontinence in 33 of 38 and residual urine in 24 of 26. Cystoceles recurred in 3 patients, and enteroceles developed in 3 and recurred in 2. These findings indicate that cystoceles may cause voiding dysfunction and lack of symptoms of stress incontinence is unreliable in patients with cystoceles. In addition, cystoceles are associated with other symptoms, most of which actually resolve after operative repair. 
Cardiovascular and catecholamine responses to head-up tilt in the diagnosis of recurrent unexplained syncope in elderly patients. To increase understanding of the mechanisms causing syncope in patients over the age of 60, hemodynamic and hormonal responses to 60 minutes of 60 degree head-up tilt were examined in 10 patients with recurrent syncope of unknown origin and five controls with no history of syncope. Nine of 10 patients and all five controls experienced orthostatic intolerance on the tilt table. Syncope or pre-syncope occurred later in controls than in those syncope patients who had exact reproduction of their clinical symptoms (median time 52 versus 22 minutes, P = 0.05). Three different mechanisms of orthostatic intolerance were identified in the 14 subjects: (1) vasovagal syncope, n = 9 (sudden hypotension +/- bradycardia); (2) dysautonomic syncope, n = 3 (immediate and gradual parallel declines in both systolic and diastolic pressures with blunted increase in heart rate); (3) psychogenic or vestibular reaction, n = 2 (orthostatic intolerance without hemodynamic changes). Vasovagal syncope patients showed a significant increase in plasma norepinephrine from baseline to maximum level during tilt (100 +/- 39% increase, P = 0.03) and a subsequent decrease at the time of syncope (30 +/- 5% decrease, P = 0.01), while plasma epinephrine increased markedly from baseline to the time of syncope (827 +/- 154% increase, P = 0.0003). Dysautonomic syncope patients had lower supine levels of norepinephrine compared to vasovagal syncope patients (182 +/- 30 versus 614 +/- 146 pg/mL, P = 0.008) and no significant change in norepinephrine over time; epinephrine levels increased significantly less than in vasovagal patients (net change 38 +/- 8 versus 189 +/- 56 pg/mL, P = 0.008). 
Cystoscopic suction diathermy for the treatment of superficial bladder tumours. The treatment of superficial bladder tumours (Ta, T1) is a time-consuming exercise for urological surgeons and patients. A method of treating the tumours, whether primary or recurrent, by endoscopic suction diathermy has been developed. The technique significantly reduces the amount of tumour debris within the bladder during treatment as well as the amount of diathermy employed. By removing the free tumour cells in the irrigation fluid the risk of tumour cell implantation may be kept to a minimum. 
The t(1;22) (p13;q13) is nonrandom and restricted to infants with acute megakaryoblastic leukemia: a Pediatric Oncology Group Study. We report the nonrandom occurrence and frequency of the t(1;22)(p13;q13) in acute myeloid leukemia (AML) and its close association with the French-American-British M7 subtype of AML in infants (less than 1 year). This chromosomal abnormality occurred in 6 of 252 (2.4%) children and adolescents with AML (6 of 28 infants, 22%; 6 of 18 M7 AML cases overall, 33%; and 6 of 6 M7 cases in infants). Infants with AML of M7 subtype and the t(1;22) often presented with prominent abdominal masses. Two of these infants were not treated and died early. Three of four treated infants entered complete remission with therapy for AML; the remaining infant died of hemorrhage on day 8. Of the three infants who entered remission, only one remains alive and disease free at 5+ months. The other two infants relapsed in the bone marrow at 5 and 2 months from the start of therapy, respectively. We conclude that M7 AML with the t(1;22) usually presents in infants with extensive infiltration of abdominal organs by leukemic cells and may confer a poor prognosis despite intensive AML-directed treatment. Identification of this nonrandom translocation exclusively in infants with acute megakaryoblastic leukemia (AMkL) implies that it may serve as an additional diagnostic marker for this disease and links it to the pathogenesis of AMkL in infants. 
Pentoxifylline in resuscitation of experimental hemorrhagic shock. BACKGROUND: Pentoxifylline improves survival in animal models of hemorrhagic shock. The purpose of this study was to determine the physiologic effects of pentoxifylline in hemorrhagic shock that may be responsible for improved survival. METHODS: Randomized, prospective, blinded trials in Sprague-Dawley rats subjected to hemorrhage and resuscitation, with or without pentoxifylline. RESULTS: Pentoxifylline had no effect on BP or cardiac output. However, tissue oxygenation and oxygen consumption were increased with pentoxifylline resuscitation. Pentoxifylline resuscitation also significantly decreased polymorphonuclear leukocyte adhesiveness. CONCLUSIONS: Pentoxifylline improves tissue oxygenation and oxygen consumption posthemorrhage and this effect is not due to increased cardiac output. Therefore, it must be due to improved microcirculatory blood flow. This effect may be due to decreased polymorphonuclear leukocyte adhesiveness induced by pentoxifylline resuscitation. 
Alcoholic liver disease: pathologic, pathogenetic and clinical aspects [published erratum appears in Alcohol Clin Exp Res 1991 Mar;15(2):180] Alcoholic liver disease includes steatosis, alcoholic hepatitis and cirrhosis. Other liver diseases of genetic origin, but with a curious association with alcohol intake, are hemochromatosis and porphyria cutanea tarda. The attribution of chronic hepatitis to alcohol intake remains speculative, and the association may reflect hepatitis C infection. Hepatic injury attributed to alcohol includes the changes reported in the fetal alcohol syndrome. Steatosis, the characteristic consequence of excess alcohol intake, is usually macrovesicular and rarely microvesicular. Acute intrahepatic cholestasis, which in rare instances accompanies steatosis, must be distinguished from other causes of intrahepatic cholestasis (e.g., drug-induced) and from mechanical obstruction of the intrahepatic bile ducts (e.g., pancreatitis, choledocholithiasis) before being accepted. Alcoholic hepatitis (steatonecrosis) is characterized by a constellation of lesions: steatosis, Mallory bodies (with or without a neutrophilic inflammatory response), megamitochondria, occlusive lesions of terminal hepatic venules, and a lattice-like pattern of pericellular fibrosis. All these lesions mainly affect zone 3 of the hepatic acinus. Other changes, observed at the ultrastructural level, are of importance in progression of the disease. They include widespread cytoplasmic shedding, and capillarization and defenestration of sinusoids. Progressive fibrosis complicating alcoholic hepatitis eventually leads to cirrhosis that is typically micronodular but can evolve to a mixed or macronodular pattern. Hepatocellular carcinoma occurs in 5 to 15% of patients with alcoholic liver disease. The clinical syndrome of alcoholic liver disease is the result of three factors--parenchymal insufficiency, portal hypertension and the clinical consequences of extrahepatic damage produced by alcohol. At the several phases of the life history of alcoholic liver disease, the individual factors play a different role. The clinical manifestations of alcoholic steatosis are mainly extrahepatic in origin. Those of alcoholic hepatitis reflect mainly parenchymal insufficiency and those of cirrhosis are mainly those of portal hypertension. Alcoholic liver injury appears to be generated by the effects of ethanol metabolism and the toxic effects of acetaldehyde, perhaps the immune responses to alcohol- or acetaldehyde-altered proteins, and questionably enhanced by viral hepatitis. Alcoholic hepatitis may be mimicked histologically, and to a varying degree clinically, by a number of conditions (obesity, diabetes, several drug-induced injuries, jejunoileal bypass, and related "shortcircuiting" of the bowel). Perhaps the most important facet of the hepatotoxicity of alcohol is its enhancement of the effects of a number of other hepatotoxic agents, among which acetaminophen is the prime example. 
Correlation of clinical and histopathologic features in clinically atypical melanocytic nevi. To define better the evolving entity of dysplastic melanocytic nevus (DMN), studies correlating clinical with histologic features of DMN are essential. However, based on a literature search, no previous quantitative analysis was found of the relationship between gross morphologic features and histologic features of DMN. The authors correlated individual clinical features with histopathologic features and histologic diagnosis of the clinically most atypical nevus in 153 melanoma patients. This nevus was identified, evaluated clinically, and removed for histologic evaluation from each patient. Gross morphologic features assessed for nevi included: size (in mm), the presence of a macular component, irregular border, ill-defined border, haphazard coloration, distortion of skin cleavage lines on tangential lighting, asymmetry, and number of colors present (12 features in all). Nineteen histologic features were assessed in each nevus by a single dermatopathologist. These included architectural, nuclear, and cytoplasmic parameters ascribed to dysplastic nevi. Each of these histologic features was correlated with the 12 individual clinical features. Seventeen percent of the nevi fulfilled the criteria for the histologic diagnosis of DMN. Among individual nevus parameters, size (in mm), irregular border, ill-defined border, macular component, and pink color were associated significantly with histologic DMN. Nevus size (in mm) and irregular borders correlated with the greatest number of individual histologic parameters. A comparison of clinicopathologic correlations for two different examiners revealed that certain clinical features are probably more important than others for the recognition of dysplastic nevi and that individual examiners have different thresholds for the perception of some gross morphologic features. These observations are relevant to the development of clinical criteria for dysplastic nevi. 
Acute non-A, non-B hepatitis in a hospital population in Warsaw, Poland: clinical and epidemiological aspects. In the years 1986-1988, 530 consecutive cases of acute viral hepatitis were admitted to an infectious disease hospital in Warsaw. Hepatitis A was diagnosed in 34 cases (6.4%), hepatitis B in 436 (82.3%), CMV infection in five (0.9%), and 55 cases (10.4%) were classified as hepatitis non-A, non-B. In 47 cases (85%) of non-A, non-B hepatitis, there was evidence of parenteral transmission, whereas in eight (15%), the source of infection was unknown. Chronic liver disease developed in 50% of patients with parenteral exposure, but there were no cases with known exposure. Seroconversion to anti-HCV was observed only in patients with parenteral exposure, and 60% of followed up cases developed antibodies within 6 months. 
Pericardial effusion after intravenous recombinant tissue-type plasminogen activator for acute myocardial infarction. The effect of thrombolytic therapy on the frequency, time course and sequelae of pericardial effusion after myocardial infarction are unknown. A prospective, serial, 2-dimensional echocardiographic study of patients with myocardial infarction who received recombinant tissue-type plasminogen activator (rt-PA) was undertaken to address this issue. The study population comprised 52 of the 112 patients enrolled in the first Thrombolysis and Angioplasty in Myocardial Infarction trial at Duke University Medical Center. Enrollment in the serial echocardiography protocol was determined by equipment and support staff availability. Complete echocardiographic studies were performed within 90 minutes after initiation of thrombolytic therapy (day 0), and on days 1, 3 and 6. Patients undergoing serial echocardiography did not differ in demographic or clinical characteristics from those who did not. Pericardial effusion was present in 3 of 38 patients (8%) at day 0, in 2 of 44 (5%) at day 1, in 8 of 43 (19%) at day 3, and in 10 of 42 (24%) at day 6. By day 6, 3 of 10 pericardial effusions were moderate in size, 1 of 10 was large and the remainder were small. No patients developed echocardiographic or hemodynamic signs of cardiac tamponade. The prevalence and time course of pericardial effusion among patients with acute myocardial infarction who received rt-PA in this study are similar to observations reported in earlier studies in which patients did not receive thrombolytic therapy. Adverse sequelae of pericardial effusion after thrombolytic therapy are rare. 
Developing a dysphagia program in an acute care hospital: a needs assessment. A needs assessment for a hospital-based dysphagia program was conducted to determine incidence, management procedures, and outcome for stroke patients with swallowing disorders. Using a chart review of 225 patients, it was found that 28% had documented evidence of dysphagia. When dysphagia co-occurred with stroke, significantly more functional problems and medical complications were reported, as well as increased need for dietary modifications and alternative feeding methods. The dysphagic patients were more often aphasic and dysarthric and less able to communicate. Mental status was more likely to be reduced and the need for staff supervision during mealtime was increased. Dysphagic patients had significantly longer hospital stays, thus increasing the cost of their care. At discharge, almost half of them continued to need feeding modifications, which may have delayed rehabilitation or transfer to facilities with other levels of care. The dysphagia group clearly displayed a wide range of clinical symptoms that would alert staff to their risk for medical complications because of swallowing problems. We believe that this needs assessment clearly showed that a multidisciplinary dysphagia management program has the potential to enhance patient care while decreasing the cost of health care delivery for the hospital. 
Computerized tomography and magnetic resonance imaging following cranial base surgery. The computed tomography scans and magnetic resonance imaging films of 57 patients who underwent anterior or anterolateral cranial base surgery from January 1987 to August 1989 were retrospectively reviewed to ascertain the significance of early and late postoperative intracranial imaging changes. Extra-axial changes (air, blood, cerebrospinal fluid collection) were found in 96% of patients; axial changes (brain edema, contusion) were seen in 30% of patients in the first postoperative period (72 hours). Subsequently, extra-axial changes began to resolve but axial changes became more prevalent. After 6 months, only axial changes persisted (encephalomalacia). It was encouraging to find a low correlation of imaging abnormalities with clinically significant findings. 
Resistant hypertension in a tertiary care clinic. STUDY OBJECTIVE.--To determine the prevalence of resistant hypertension in a tertiary care facility, the frequency of its various causes, and the results of treatment. DESIGN.--Review of clinic records of all patients seen for the first time between January 1, 1986, and December 31, 1988. METHODS.--Patients meeting criteria for resistant hypertension were examined for appropriateness of their medical regimen, presence of secondary causes of hypertension, noncompliance, interfering substances, drug interactions, office resistance (elevated blood pressure in the office only while receiving treatment), and other potential causes of resistance. RESULTS.--Of the 436 charts reviewed, 91 were those of patients who met criteria for resistant hypertension and were seen more than once. The most common cause was a suboptimal medical regimen (39 patients), followed by medication intolerance (13 patients), previously undiagnosed secondary hypertension (10 patients), noncompliance (nine patients), psychiatric causes (seven patients), office resistance (two patients), an interfering substance (two patients), and drug interaction (one patient). Blood pressure control, defined as diastolic blood pressure of 90 mm Hg or less and systolic blood pressure of 140 mm Hg or less for patients aged 50 years or less (less than or equal to 150 mm Hg for those aged 51 to 60 years and less than or equal to 160 mm Hg for those aged greater than 60 years), was achieved in 48 (53%) of those 91 patients. Another 10 had significant improvement in their blood pressure (greater than or equal to 15% decrease in diastolic blood pressure). Of patients whose blood pressure was controlled after they had been on a suboptimal regimen, the two most frequently used therapeutic strategies were to add (50%) or modify (24%) diuretic therapy or to add (50%) or increase the dose of (12%) a newer drug, either a calcium entry blocker or angiotensin-converting enzyme inhibitor. CONCLUSION.--We conclude that resistant hypertension is common in a tertiary care facility and that a suboptimal regimen is the most common reason. Furthermore, in the majority of these patients, the elevated blood pressures can be controlled or significantly improved. 
Percutaneous transluminal angioplasty of aortocoronary venous bypass grafts and effect of the caliber of the grafted coronary artery on graft stenosis. The influence of morphologic parameters on the recurrence of stenosis after percutaneous transluminal coronary angioplasty of 49 stenoses in aortocoronary venous bypass grafts of 41 patients was investigated. Vessel dimensions were measured quantitatively. Angioplasty was successful in 46 stenoses (94%) of 38 patients (93%). In 35 patients (92% of successfully treated patients) with 42 stenoses, control angiography was performed after a mean interval of 189 +/- 186 days. In 9 patients (26%), 9 stenoses (21%) had recurred. The diameter of the grafted coronary artery distal to the anastomosis was significantly smaller in grafted arteries with than without recurrent stenoses (1.92 +/- 0.52 vs 2.45 +/- 0.50 mm; p less than 0.01). Recurrence also correlated with the ratio between graft diameter and coronary artery diameter greater than 1.35 (p less than 0.02) and with the stenosis length greater than 10 mm before angioplasty (p less than 0.01). Graft age, graft diameter and stenosis location in the graft had no significant influence on recurrence. Thus, the diameter of the grafted coronary artery and the length of the critical stenosis are parameters for recurrence after angioplasty of graft stenoses and should be considered in the selection of patients for this intervention. 
Prolonged paralysis after treatment with neuromuscular junction blocking agents. OBJECTIVES: Previous reports have described prolonged paralysis after treatment with neuromuscular junction blocking agents in critically ill patients. The purpose of this study was to further describe a group of patients who developed prolonged weakness after treatment with these agents. DESIGN: Clinical information, electrodiagnostic and muscle pathology results are described in this group of patients. Clinical information includes diagnoses, dosage of neuromuscular junction blocker, other medications affecting the neuromuscular system, and neuromuscular examination and clinical course. SETTING: All patients were seen in the ICUs of three local hospitals. PATIENTS: Included were critically ill patients with a variety of diagnoses, all of whom developed severe weakness after discontinuation of neuromuscular junction blocking agents. INTERVENTIONS: Electrodiagnostic studies and muscle biopsies were performed on several of the patients. MEASUREMENTS AND MAIN RESULTS: All patients had pronounced weakness without sensory loss. Electrodiagnostic and muscle pathology findings were consistent with failed neuromuscular transmission. Although many patients had disorders or were taking medications that can injure the neuromuscular system, no disorder or medication was common to all. Recovery of strength often took several months and most patients were slow to wean from mechanical ventilator support. CONCLUSIONS: Although alternative explanations cannot be excluded with certainty, the use of neuromuscular junction blocking agents may lead to neurogenic atrophy and care must be taken when using them. 
Inflammatory pseudotumor: a gallium-avid mobile mesenteric mass. An 8-yr-old boy with a 1-mo history of culture-negative fever and anemia underwent gallium, ultrasound, and computed tomography studies as part of the evaluation of a fever of unknown origin. These studies revealed a mobile gallium-avid solid abdominal mass subsequently proven to be an inflammatory pseudotumor of the mesentery, a rare benign mass. This report documents the gallium-avid nature of this rare lesion and discusses associated characteristic clinical, pathologic, and radiographic features. 
Radiologic evaluation of aortic dissection. The radiologic assessment of patients suspected of having an aortic dissection must be based on an understanding of the treatment options and how these are to be employed in any clinical setting. The appropriate selection and timing of imaging studies is crucial. The diagnosis of dissection must be quickly confirmed, other diseases that mimic dissection must be excluded, and the type and extent of dissection must be established so that appropriate therapy can be instituted. Although computed tomography, magnetic resonance (MR) imaging, and echocardiography greatly enhanced the ability to evaluate the aorta by noninvasive means, aortography remains the examination of choice for defining the vascular anatomy, especially when surgical intervention is considered. MR imaging may become the primary examination for the initial and subsequent evaluation of acute and chronic dissections as MR angiographic techniques improve and changes are made in monitoring equipment to allow the safe examination of acutely ill patients. 
Genital chlamydial infections: epidemiology and reproductive sequelae. Genital chlamydial infection is increasing and is now more common than gonorrhea. A sizable percentage of chlamydial infections of the lower genital tract in women progress to endometritis and salpingitis. Tubal infertility and ectopic pregnancy are important sequelae. Failure to control chlamydial infections reflects the following four factors: (1) Many cases are mild or asymptomatic; (2) diagnostic tests are expensive and technically demanding; (3) at least 7 days of multiple-dose therapy are currently required; and (4) partner notification is not routinely performed. Thus early identification of infected persons and compliance with curative therapy are less likely than with other sexually transmitted bacterial diseases. 
Detection of hepatitis B virus DNA sequences in liver in HBsAg seronegative patients with liver disease with and without anti-HBc antibodies. Excluding studies from Brechot and co-workers, little support has been found for a role of the hepatitis B virus in the pathogenesis of HBsAg seronegative patients with predominantly chronic liver diseases, including primary liver cancer. In this study liver DNA from 59 predominantly British patients (four cases with paired biopsies, 6-12 months apart) with different, mostly chronic, liver diseases was analysed by molecular hybridization. All were seronegative for HBsAg and serum hepatitis B virus DNA (dot blot hybridization) and their liver diseases were believed to be unrelated to hepatitis B virus infection. Hepatitis B virus DNA was detected in liver of 11 (18.6 per cent) patients; nine had episomal (3.2 Kb) DNA and eight had higher molecular weight bands suggesting integrated forms. Six patients were also seronegative for anti-HBc. Patients of UK and non-UK origin were equally represented. Hepatitis B virus DNA was detected in serum of six of nine patients tested using the polymerase chain reaction. The detection of hepatitis B virus DNA in liver and in serum by this assay in a significant proportion of patients with chronic liver disease, hitherto unsuspected of being hepatitis B virus-related, suggests a possible role for this virus in low- as well as high-prevalence countries. 
Evolution of renal insufficiency in ischemic nephropathy. This retrospective review of data collected during a recent 42-month period from 58 consecutive patients with ischemic nephropathy submitted to operative management in the authors' center was undertaken to report the rate of decline in their renal function during the period before intervention and to examine the impact of operation on their outcome. Based on serum creatinine values, immediate preoperative estimated glomerular filtration rates (EGFR) ranged from 0 to 46 mL/minute (mean, 23.85 +/- 9.76 mL/minute). Eight patients were dialysis dependent or anuric at the time of operation. Patients with at least three sequential measurements for calculations of EGFR changes during the 6 months before operation (n = 50) and the first 12 months after operation (n = 32) were used to describe the preoperative rate of decline in EGFR and the impact of operation on this decrease in the operative survivors. In addition comparative analyses of data from patients with unilateral versus bilateral lesions and patients classified as having improvement in EGFR versus no improvement after operation were performed. Comparison of the immediate preoperative EGFR with the immediate postoperative EGFR for the entire group showed significant improvement in response to operation. Likewise the rate of deterioration in EGFR for the total group was improved after operation. A similar improvement in the rate of deterioration in EGFR was seen in the subgroup of patients who received an immediate improvement in EGFR in response to operation. These data argue that ischemic nephropathy is a rapidly progressive form of renal insufficiency. Although individual responses to operation were heterogeneous, renal revascularization may provide both immediate improvement in renal function and an improvement in its rate of deterioration during follow-up in patients with ischemic nephropathy. 
Metastatic meningioma in the neck. Although meningiomas represent 15 per cent of tumours of the central nervous system, they rarely metastasize. A case is presented in which metastasis to a cervical lymph node occurred, together with local recurrence, nine years after initial diagnosis and treatment. This case serves to illustrate that malignant meningioma is a rare cause of a neck mass. 
Validation of a clinical antisaccadic eye movement test in the assessment of dementia. The ability to generate antisaccades (eye movements deliberately made in the direction opposite to that of a visual stimulus) may be used to assess central nervous system function in a variety of neurologic and psychiatric disorders. However, the usefulness of this paradigm in clinical practice is limited by the need for an oculographic laboratory. We describe a clinical version of such an antisaccadic task and present normative data from 332 subjects. We also examined clinical antisaccades and cognitive performance in 30 patients with Alzheimer's disease, five patients with Huntington's disease, and 12 patients with pseudodementia. In Alzheimer's disease, error rates in the clinical antisaccadic test correlated well with those from a laboratory-based antisaccadic task measured on the same day by infrared oculography, confirming that the clinical antisaccadic test is a valid analog of the more sophisticated laboratory paradigms. Clinical antisaccadic error rates correlated strongly with the severity of dementia in Alzheimer's disease, and correlations with cognitive performance suggested that the clinical antisaccadic test may have some specificity for frontal lobe dysfunction. Patients with pseudodementia had normal clinical antisaccadic error rates, and the test may therefore be of use in differentiating dementia from pseudodementia. This clinical antisaccadic test provides a simple, reliable, and inexpensive quantitative clinical tool that is of value in the assessment of disturbances of higher cortical function. 
Neuromodulatory effects of atrial natriuretic factor are independent of guanylate cyclase in adrenergic neuronal pheochromocytoma cells. This study tests the hypothesis that atrial natriuretic factor (ANF) and C-ANF(4-23)-NH2 (C-ANF) augment cGMP generation and inhibit both cAMP generation and depolarization-induced catecholamine release in nerve growth factor treated pheochromocytoma cells by a pertussis toxin (PTX)-sensitive mechanism. Synthetic rat ANF(99-126) and the clearance receptor antagonist C-ANF (10(-12)-10(-9) M) inhibited basal and 5 microM vasoactive intestinal peptide (VIP)-induced cAMP generation in a concentration-dependent manner. These actions of ANF and C-ANF were blocked by 12-18 h pretreatment with PTX (100 ng/ml), suggesting ANF receptor coupling to adenylate cyclase via an inhibitory guanine nucleotide-binding protein. Both ANF (10(-11)-10(-9) M) and C-ANF (10(-11)-10(-8) M) also inhibited K(+)-induced catecholamine release in a concentration-dependent manner. ANF (10(-11)-10(-8) M) increased cGMP generation in a concentration-dependent manner but C-ANF did not. The accumulation of cGMP in response to ANF was not altered by treatment with PTX. Therefore, PTX dissociated the increased concentrations of cGMP from the ANF-mediated depression of evoked catecholamine release. C-ANF also dissociated elevations in cGMP concentrations from an ANF-mediated attenuation of evoked catecholamine release. The results of this study indicate that ANF inhibits adrenergic neurotransmission independent of guanylate cyclase. 
Leptotrichia buccalis bacteremia in patients with cancer: report of four cases and review. Leptotrichia buccalis, an anaerobic gram-negative rod, is part of the normal oral flora and has rarely been isolated from clinical material. We describe four patients with neutropenia and progressive malignancy who had symptomatic L. buccalis bacteremia, and we review an additional four cases from the literature. The mean age of the patients was 31 years (range, 7-73 years), with an equal number of males and females. The number of positive blood cultures in each case ranged from one to four (mean, two); these cultures became positive after 48-120 hours (median, 54 hours). All tested isolates were sensitive to the beta-lactam agents, clindamycin, tetracycline, and metronidazole; five of seven were sensitive to chloramphenicol; and not one was sensitive to the aminoglycosides, vancomycin, ciprofloxacin, or erythromycin. Seven patients had one or more possible portals of entry for bacteremia, including mucositis (four patients), mucositis plus esophageal lesions (two), and possible mucositis plus diverticulitis (one). L. buccalis should be considered a potential pathogen in neutropenic patients, especially when breaks in the mucosal breaks in the mucosal barriers are present. 
How AIDS forces reappraisal of hepatitis B virus control in sub-Saharan Africa For developing countries the cost-benefit of vaccination in the control of hepatitis B virus (HBV) infection is great since the acute infection is generally subclinical and the benefit is the prevention of small numbers of cases of cirrhosis and hepatocellular carcinoma. Since the pattern of HBV infection in Africa is such that, compared with south-east Asia, infection occurs later in childhood and spread is horizontal rather than vertical, investigation of the method of spread of HBV may result in a means of control other than by vaccination. In the meantime, because of the overlap in the means by which HBV and human immunodeficiency virus (HIV) are spread, it could be worthwhile taking advantage of existing AIDS prevention programmes to educate people about how to avoid both HBV and HIV infections. 
Impending paradoxical embolism: a rare but important diagnosis. A man aged 50 presented with a history of a cerebrovascular accident and arterial embolism at two discrete peripheral sites. Echocardiography showed thrombus trapped in an interatrial site and impending paradoxical embolism was diagnosed. Treatment with heparin was started and the potentially embolic intracardiac material was removed at open heart surgery. The patient was treated with warfarin and made a good recovery. This is only the third case report of impending paradoxical embolism diagnosed in life. 
The low-affinity p75 nerve growth factor (NGF) receptor mediates NGF-induced tyrosine phosphorylation. Protein tyrosine phosphorylation is a potential mechanism for initial signaling in PC12 cells during differentiation in response to nerve growth factor (NGF). NGF-induced tyrosine phosphorylation has been found to be initiated by the trk protooncogene, which participates in the formation of high-affinity NGF binding sites. In contrast to transfection of wild-type low-affinity p75 NGF receptors, transfection of p75NGFR with mutations in the cytoplasmic domain resulted in an inability of NGF to elicit tyrosine phosphorylation of intracellular substrates, indicating that p75NGFR is involved in initiating phosphorylation events by NGF. Even though the p75NGFR receptor does not possess any inherent tyrosine kinase activity, these experiments demonstrate that the p75NGFR has a potential role in NGF-induced tyrosine phosphorylation. 
Effect of a cyclic adenosine monophosphate phosphodiesterase inhibitor, DN-9693, on myocardial reperfusion injury. A new cyclic adenosine monophosphate phosphodiesterase inhibitor, DN-9693, was examined to see whether myocardial reperfusion injury could be reduced in a setting of cardioplegic arrest through its antiaggregation effect on leukocytes. Isolated rabbit heart models with whole blood perfusion were used, and 18 hearts were divided into three groups according to the reperfusion method: control (G-1, n = 5), DN-9693 (G-2, n = 7), and leukocyte depletion (G-3, n = 6). The hearts were subjected to 120 minutes of cold global ischemia under crystalloid cardioplegia followed by 30 minutes of reperfusion. A dose of 20 micrograms.kg-1.min-1 of DN-9693 was administered in G-2, and a leukocyte removal filter was used in G-3 during reperfusion. Ultrastructural changes in mitochondrial injuries, intracellular edema, and capillary injuries of the myocardium showed worse changes in G-1 than in G-2 and G-3. Under microscopic study, the intracapillary leukocyte count was significantly higher in G-1 than in G-2 and G-3. Recovery of rate-pressure product, left ventricular developed pressure, and coronary flow were significantly better in G-2 and G-3 than in G-1. There were no significant differences between G-2 and G-3 for all these indices. These results indicate that reperfusion with leukocyte-depleted blood attenuates reperfusion myocardial injury and DN-9693 has a comparable myocardial protective effect with possible inhibition of leukocyte aggregation. 
The role of contraception in the development of postmolar gestational trophoblastic tumor. From January 1974 to June 1988, 299 evaluable patients were referred to the John I. Brewer Trophoblastic Disease Center of Northwestern University Cancer Center for treatment and/or follow-up of a hydatidiform mole (N = 162) or postmolar gestational trophoblastic tumor (N = 137). The type of contraception and other prognostic factors before and after evacuation were correlated with the development of gestational trophoblastic tumor using both univariate and multivariate analysis. There was no relationship between pre-hydatidiform mole contraception and the development of gestational trophoblastic tumor. Oral contraceptives (OCs) were used by 139 patients (46%), barrier methods by 141 patients (47%), intrauterine devices (IUDs) by two patients (1%), and no contraception by 17 patients (6%). The risk of developing gestational trophoblastic tumor was compared between patients using versus not using: OCs--33 versus 57% (P less than .001), barrier methods--53 versus 40% (P = .30), IUD--100 versus 46% (P = .21), and any contraceptive method--43 versus 88% (P less than .001). The dose of estrogens could be determined in 75 patients taking OCs; 14 of 49 (29%) of the patients taking less than 50 micrograms versus nine of 26 (35%) taking 50 micrograms or more developed gestational trophoblastic tumor (P = .78). Stepwise logistic regression analysis demonstrated that the type of contraceptive used was the most important prognostic factor in gestational trophoblastic tumor development (P less than .0001), followed by the occurrence of theca-lutein cysts (P less than .0001), Asian maternal race (P = .02), lesser time from the last menstrual period (P = .005), and greater maternal age (P = .04). 
Removal of massive right atrial thrombus guided by transesophageal echocardiography. Formation of massive right atrial thrombi around a peritoneovenous shunt is a known complication of these devices. Removal of an obstructive right atrial thrombus requires cardiopulmonary bypass and has been associated with a high morbidity and mortality. Transesophageal echocardiography was used in this case to diagnose and guide the surgical removal of a massive right atrial thrombus. 
Amikacin pharmacokinetics in patients receiving high-dose cancer chemotherapy. We retrospectively analyzed amikacin pharmacokinetics in 28 patients (mean age, 47.4 +/- 13.6 years) who received high-dose chemotherapy during a neutropenic febrile episode. Patients received an experimental protocol of high-dose anticancer chemotherapy. Amikacin pharmacokinetic parameters were calculated from two or more concentrations in serum around a single dose by the method of Sawchuck and Zaske (J. Pharmacokinet. Biopharm. 4:183-195, 1976). Predicted parameters were calculated by using standard methods. The observed amikacin volume of distribution and clearance were significantly greater and the elimination half-life was longer than predicted (0.38 +/- 0.13 versus 0.25 liter/kg [P = 0.0001], 1.51 +/- 0.92 versus 1.17 +/- 0.38 liters/h/kg [P = 0.012], and 3.8 +/- 2.4 versus 2.9 +/- 1.1 h [P = 0.011], respectively). Multivariate analysis revealed that albumin correlated negatively and creatinine correlated positively with the volume of distribution and the elimination half-life. Creatinine and the percentage below the ideal body weight correlated negatively and hematocrit correlated positively with clearance. Administration of dosage regimens based on predicted pharmacokinetic parameters yielded subtherapeutic amikacin concentrations in serum in our patients. Because of the increased dosage requirements and the need for adequate antibiotic treatment in this population, we suggest guidelines for empiric dosing for patients with advanced cancer receiving intensive chemotherapy. 
Autoimmune Addison's disease and thyrotoxic thyroiditis presenting as encephalopathy in twins. An 11 year old boy who presented with neuropsychiatric symptoms including delirium and pronounced agitation was found to have simultaneous onset of autoimmune adrenocortical insufficiency and hyperthyroidism. His identical twin also had hyperthyroidism and six months later developed symptoms of adrenocortical insufficiency. In children presenting with neuropsychiatric symptoms, adrenal (or pituitary) and other endocrine disorders should be considered. 
Treatment of vasospasm with a 480-nm pulsed-dye laser. Laser energy at a wavelength of 480 nm was applied in 1-microseconds pulses of 3 to 10 mJ to two models of vasospasm. Rabbit common carotid arteries (CCA's) were constricted chronically by the application of human blood within a silicone sheath. Peak vasospasm developed 24 to 48 hours later, and persisted for up to 6 days. Endovascular laser treatment was delivered to 40 CCA's via a 200-microns diameter silica quartz fiber introduced through the femoral artery. The CCA caliber increased from 60% of the pre-vasospasm control diameter to a minimum post-laser diameter of 83% of control. No instances of laser-induced perforation or of arterial thrombosis were observed for up to 60 days after treatment. Prophylactic laser application to nine normal vessels was able to attenuate the development of vasospasm if blood was applied immediately thereafter (88% vs. 59% of control diameter, p less than 0.02), but not if blood was applied 7 days later. Studies in 16 normal CCA's established that there was a considerable margin between the laser energy required to induce dilatation and that which caused perforation, providing that the fiber remained relatively central within the artery. Morphological examination demonstrated focal loss of endothelial cells immediately after laser application, followed approximately 7 days later by the development of areas of intimal hyperplasia. Only minimal changes were observed in the medial or adventitial layers. In a second study, the basilar artery of seven dogs was constricted chronically by two intracisternal injections of autologous blood 3 days apart. Five dogs received endovascular laser treatment 7 or 10 days after the first injection, when basilar artery diameter was reduced to a mean of 61% and 77% of control, respectively. Immediately following treatment, basilar artery diameter increased to 104% and 102% of resting diameter, respectively. Both untreated and laser-treated arteries were smaller than the control diameter at 30 days (80% and 82%, respectively), but in each group the vasodilatory response to hypercapnia was preserved. These findings indicate that 1-microsecond laser pulses are well tolerated by systemic and cerebral arteries in two different animal models, and suggest that the 480-nm pulsed-dye laser may have an application for the treatment or prophylaxis of cerebral vasospasm. 
Acute reversible hypoxemia in systemic lupus erythematosus. OBJECTIVE: To determine the frequency of unexplained reversible hypoxemia in patients with systemic lupus erythematosus and to assess the relation between hypoxemia and elevated plasma levels of complement split products. DESIGN: Cohort study. SETTING: Inpatient and outpatient facilities of the New York University Medical Center/Bellevue Hospital and the Hospital for Joint Diseases. PATIENTS: Case patients were 22 patients hospitalized with disease exacerbation and no evidence of parenchymal lung disease on chest roentgenogram. Four patients with stable disease were followed in the outpatient clinic, and five healthy normal volunteers served as controls. MEASUREMENTS: Plasma levels of complement split products (C3a, factor Bb fragment), alveolar-arterial (A-a) Po2 gradients, and pulmonary function were measured. MAIN RESULTS: Nine episodes of hypoxemia or hypocapnia (mean A-a gradient, 30.4 +/- 4.8 mm Hg) or both (despite normal chest roentgenogram results) were noted in six hospitalized patients (group 1). Gas exchange improved within 72 hours of steroid therapy (mean A-a gradient, 11.6 +/- 4.3 mm Hg; P less than 0.01). These patients had an elevated initial mean C3a level (938.4 +/- 246.8 ng/mL) that decreased within 72 hours (407.8 +/- 80.9 ng/mL; P less than 0.01), concomitant with improved oxygenation. Ventilation-perfusion scans, obtained for four of six group 1 patients, excluded pulmonary emboli. Four hospitalized patients (group 2) had a normal A-a gradient (mean, 7.5 +/- 2.7 mm Hg). The mean C3a level of this group (358.3 +/- 39.2 ng/mL) was lower than that of group 1 (P less than 0.05). Four patients with stable disease (group 3) had a mean A-a gradient and a mean C3a level of 3.3 +/- 2.7 mm Hg and 237.8 +/- 105.7 ng/mL, respectively, similar to values found in five normal volunteers, in whom the mean A-a gradient was 3.7 +/- 1.7 mm Hg and the mean C3a level was 124.8 +/- 9.2 ng/mL. CONCLUSION: A syndrome of reversible hypoxemia, unassociated with parenchymal lung disease, is unexpectedly common in acutely ill, hospitalized patients with systemic lupus erythematosus. The pathogenesis of this syndrome is unclear, although the data are compatible with the hypothesis that hypoxemia may be related to pulmonary leukoaggregation. 
Enteral feeding as sole treatment for Crohn's disease: controlled trial of whole protein v amino acid based feed and a case study of dietary challenge. A controlled trial was performed to compare enteral feeding with either an amino acid based feed or a whole protein feed as sole treatment for active Crohn's disease. Twenty four patients were studied (nine with ileal, 11 with ileocolonic, and four with colonic disease). Both feeds proved effective; nine of 13 patients randomised to receive the amino acid based feed were in clinical remission within three weeks as defined by a simple activity index compared with eight of 11 treated with the whole protein feed. Patients in clinical remission were then crossed over onto the other feed. None of the six patients who were changed to the whole protein feed relapsed over the subsequent three week period compared with three of seven patients who were changed to the amino acid based feed. In responders the median serum C reactive protein concentration fell from 21 mg/l (range 9-82) on entry to 6 mg/l (range 3-19) at six weeks. Seven patients relapsed within eight months of starting solid food (mean 3.7 months), while nine were still in remission (follow up period 3-9 months, median six months). Detailed studies of staged reintroduction of food and permitted food additives were carried out over a four year period in a patient with extensive stricturing small bowel Crohn's disease who had been brought into remission by open treatment with enteral feeding. Carrageenan, other permitted emulsifiers, bread, meat, potatoes, oranges, refined sugar, dairy produce, flour, and rice were all reintroduced without any objective ill effect, but green vegetables provoked a clinical and biochemical relapse within one week of introduction. 
An open-label study of high-dose intravenous immunoglobulin in severe childhood asthma. Eight pediatric patients with severe steroid-dependent asthma were enrolled in an open-label trial of high-dose intravenous immunoglobulin (IVIG) in an attempt to decrease their steroid requirements. Monthly therapy with high-dose IVIG resulted in a threefold decrease in both maintenance oral corticosteroid dose and in extra oral corticosteroids needed for control of exacerbations of asthma. This was accompanied by significant improvements in peak expiratory flow rates and in symptom-score rating. An immunomodulatory effect of IVIG was suggested by the changes in immediate skin test reactivity. Seven of the eight patients demonstrated one or more reactions to a panel of allergens before therapy. During the course of the trial, there was a progressive diminution in skin test reactivity with a 100-fold reduction in sensitivity at the completion of 6 months of therapy. In this preliminary study, the reduction in steroid requirements, improvement in symptoms and peak flow measurements, and diminution in immediate skin test reactivity support a potential role for IVIG in the treatment of severe steroid-dependent asthma. A larger, randomized trial now appears warranted. 
Venous thromboembolism after brain tumor surgery: a retrospective review. We retrospectively reviewed the incidence rate of clinical postoperative deep vein thrombosis and/or pulmonary embolism in 1703 patients undergoing initial craniotomy for meningioma, glioma, or cerebral metastasis. The incidence rate of clinical thromboembolic complications was 1.59% for all tumor groups within the first 4 weeks of surgery. Patients undergoing surgery for meningiomas had a statistically significant increased risk of thromboembolism despite fewer overall perioperative risk factors, when compared with the other tumor groups. The tumor-specific incidence rates of deep vein thrombosis and/or pulmonary embolism for meningioma, glioma, and metastasis were 3.09%, 0.97%, and 1.03%, respectively. Whether this difference was a result of increased surgical time or an inherent property of meningiomas could not be ascertained. 
Loss of heterozygosity suggests multiple genetic alterations in pheochromocytomas and medullary thyroid carcinomas. Loss of heterozygosity (LOH) at specific loci may help localize tumor suppressor genes involved in the formation of various familial and sporadic tumors. In addition, the genetic loci for a number of familial tumor syndromes have been mapped by linkage analysis. To explore the possible role of tumor suppressor genes in endocrine tumors, we tested 41 pheochromocytomas (34 sporadic and 7 familial) and 11 medullary thyroid cancers (MTC) (10 sporadic and 1 familial) for LOH near a variety of potentially important genetic loci: (a) the multiple endocrine neoplasia type 2A (MEN 2A) locus on chromosome 10; (b) the von Hippel-Lindau locus on 3p; and (c) the p53 and neurofibromatosis 1 loci on 17. We also examined chromosomes 1p and 22q because previous studies in a small number of pheochromocytomas and MTCs suggested LOH in these regions. Background rates for LOH were assessed using several "random" probes. Finally, we examined a number of clinical and histologic characteristics of these tumors for possible correlations with specific genetic alterations. LOH in the region of the MEN 2A locus was uncommon (0% for MTCs, 5% for pheochromocytomas). However, we found significant allelic losses in pheochromocytomas on chromosomes 1p (42%), 3p (16%), 17p (24%), and 22q (31%). We also noted a correlation between LOH on 1p and urinary excretion of metanephrine by these patients (P = 0.02). LOH on 1p, 3p, and 17p also appeared to be associated with increased tumor volume. Analysis of the smaller number of MTCs demonstrated allelic losses on chromosomes 1p and 22q. Our results suggest that tumor formation and/or progression in pheochromocytomas and MTCs involves multiple genes, analogous with the model proposed for colon carcinoma. 
Anaplastic thyroid carcinoma. Immunocytochemical study of 32 cases. To study the histogenesis of and determine the most useful markers for diagnosing anaplastic thyroid carcinoma (ATC), 32 cases, including 2 with numerous osteoclast-like cells, were stained with a battery of antibodies to epithelial (keratin, epithelial membrane antigen [EMA], carcinoembryonic antigen [CEA]), mesenchymal (vimentin, desmin, muscle-specific actin [MSA], Factor VIII-related antigen [FVIII:RAg]), endocrine (thyroglobulin, calcitonin, chromogranin [Cg]), lymphocytic (leukocyte common antigen [LCA]), histiocytic (alpha-1-antitrypsin [alpha 1AT], alpha-1-antichymotrypsin [alpha 1AChy], KP1), melanocytic (HMB-45), and Schwann cell (S-100 protein) markers. Five tumors were associated with papillary carcinoma. In one of these cases, a morphologic continuum between the well-differentiated carcinoma and the ATC was visualized by their positive immunostaining for both vimentin and keratin, thus supporting the hypothesis that the latter tumor originated from the former. Twenty-five (78.1%) tumors expressed keratin, 10 (31.3%) reacted for EMA, and 3 (9.4%) expressed CEA, confirming the epithelial nature of this neoplasm. Reactivity for thyroglobulin was seen in a small number of cells in five (15.6%) thyroglobulin was seen in a small number of cells in five (15.6%) ATCs. Because all of the cases that expressed keratin also stained positively for EMA, CEA, or thyroglobulin, it is believed that keratin is the most useful epithelial marker for diagnosis of ATC. A lack of reactivity for calcitonin and Cg indicates that these tumors are not derived from C cells, as has been proposed by some authors. Reactivity for KP1 (CD68), a monoclonal antibody that reacts with a macrophage-associated antigen, occurred in the osteoclast-like cells but not in the anaplastic tumor cells. This finding, together with negative keratin staining of the osteoclast-like cells, indicates that these cells are not epithelial in nature and therefore should be considered reactive rather than neoplastic. Thirty tumors (93.8%) expressed vimentin, 15 (46.9%) marked for alpha 1AChy, 11 (34.4%) exhibited alpha 1AT, and 11 (34.4%) expressed S-100 protein. Because all of these markers can be seen in a wide variety of tumors of different histogeneses, they have no value in the diagnosis of ATC. Although immunostaining for FVIII:RAg, desmin, and MSA was negative in all of these tumors, these markers can help to differentiate between ATCs and some soft tissue sarcomas with which they can be confused. 
Acute appendicitis following blunt abdominal trauma. Incidence or coincidence? Inflammation of the appendix is a common cause of acute abdominal pain. The etiology and pathophysiology of appendicitis have been well described. The initiating factor often is obstruction of the appendiceal lumen by inspissated stool, barium, food, parasites, or hyperplastic lymphoid tissue. Two patients have been identified who developed appendicitis temporally related to blunt abdominal trauma, without other clear etiology. Although absolute documentation of trauma as an etiologic factor in these cases is difficult, theoretical mechanisms for the occurrence are discussed. In the setting of right lower quadrant pain following mild to moderate blunt abdominal trauma, acute appendicitis should be considered as a possibility. 
Continuous interleukin-2 and tumor-infiltrating lymphocytes as treatment of advanced melanoma. A national biotherapy study group trial. Melanoma metastases were harvested from 82 patients for the purpose of growing and expanding tumor-infiltrating lymphocytes (TIL). Tumor tissue cell suspensions were incubated with interleukin-2 (IL-2), followed by repeated exposure to tumor antigen with or without OKT3 monoclonal antibody (MoAb). Initial growth success was achieved in 56 of 82 cultures (72%). Efforts were made to expand 26 of these 56 cultures for therapeutic TIL; 23 of 26 early cultures (88%) were successfully expanded for in vivo therapy. It took a mean of 78.5 +/- 25.4 days to grow sufficient TIL for treatment. Therapy included cyclophosphamide (1 g/m2) on day 1, followed by a 96-hour continuous infusion of IL-2 (18 x 10(6) IU/m2/d) on days 2 to 5, and approximately 10(11) (mean 1.49 +/- 0.93 x 10(11)) TIL on day 2. Patients who responded received monthly IL-2 as a 96-hour infusion. Median patient age was 45 years of age. Sixty-seven percent of the patients were men. Performance status was 0 to 1 in 77% of patients. Thirty-four percent of the patients had liver metastases. The usual IL-2 toxicities were seen. Response rate for 21 patients was 24% (95% confidence interval, 10% to 49%). One complete response was achieved with cells 98% CD4+; four partial responses were achieved with cells 80%, 94%, 98%, and 98% CD8+, respectively. Four of eight patients who received TIL, which had never been stimulated with OKT3, had tumor response. The authors conclude that a treatment plan for IL-2/TIL is technically difficult, costly, and effective for only a minority of patients. Overall, clinical results are not clearly superior to those obtained with other IL-2 regimens. 
Somatosensory function following dorsal root entry zone lesions in patients with neurogenic pain or spasticity. The goal of this study was to assess the effects of the dorsal root entry zone (DREZ) lesioning procedure, microsurgical DREZ-otomy (MDT), on spinal cord somatosensory function based on peri- and intraoperative clinical and electrophysiological data. The study was performed prospectively on a series of 20 patients suffering from either chronic neurogenic pain or spasticity. Physiological observations were made of the intraoperative evoked electrospinographic recordings as collected from the surface of the spinal cord. The MDT procedure produced analgesia or severe hypalgesia, moderate hypesthesia, and only slight deficits in proprioception and cutaneous spatial discrimination on the body segments operated on. These clinical data correlated well with evoked electrospinographic recordings, which showed a moderate effect of MDT on presynaptic compound action potentials recorded from the spinal cord (N11 and N21), a partial or even reversible effect on the cortical postcentral N20 wave, a more marked effect on the postsynaptic dorsal horn waves N13 and N24 related to large primary afferent fibers, and a disappearance of dorsal horn waves related to finer afferents (N2 and possibly N3). These data provide evidence for an acceptably selective action of MDT on spinal cord nociceptive mechanisms, and for a partial, often slight, involvement of the other somatosensory domains. The presence of abnormal evoked electrospinographic waves is discussed in relation to the mechanisms of neurogenic pain and spasticity. The hypothesis of a "retuning" of the dorsal horn as the mode of action of MDT is presented. 
A prospective study of aspirin use and primary prevention of cardiovascular disease in women OBJECTIVE. The aim of the study was to examine prospectively the association between regular aspirin use and the risk of a first myocardial infarction and other cardiovascular events in women. DESIGN. Prospective cohort study including 6 years of follow-up. SETTING. Registered nurses residing in 11 US states. PARTICIPANTS. US registered nurses (n = 87,678) aged 34 to 65 years and free of diagnosed coronary heart disease, stroke, and cancer at baseline. Followup was 96.7% of total potential person-years of follow-up. MAIN OUTCOME MEASURES. Incidence of myocardial infarction, stroke, cardiovascular death, and all important vascular events. RESULTS. During 475,265 person-years of follow-up, we documented 240 nonfatal myocardial infarctions, 146 nonfatal strokes, and 130 deaths due to cardiovascular disease (total, 516 important vascular events). Among women who reported taking one through six aspirin per week, the age-adjusted relative risk (RR) of a first myocardial infarction was 0.68 (95% confidence interval [CI], 0.52 to 0.89; P = .005), as compared with those women who took no aspirin. After simultaneous adjustment for risk factors for coronary disease, the RR was 0.75 (95% CI, 0.58 to 0.99; P = .04). For women aged 50 years and older, the age-adjusted RR was 0.61 (95% CI, 0.45 to 0.84; P = .002) and the multivariate RR was 0.68 (95% CI, 0.50 to 0.93; P = .02). We observed no alteration in the risk of stroke (multivariate RR = 0.99; P = .94). The multivariate RR of cardiovascular death was 0.89 (P = .56) and of important vascular events was 0.85 (P = .12). When examined separately, the results were nearly identical for the subgroups who took one through three and four through six aspirin per week. Among women who took seven or more aspirin per week, there were no apparent reductions in risk. CONCLUSIONS. The use of one through six aspirin per week appears to be associated with a reduced risk of a first myocardial infarction among women. A randomized trial in women is necessary, however, to provide conclusive data on the role of aspirin in the primary prevention of cardiovascular disease in women. 
National High Blood Pressure Education Program Working Group Report on High Blood Pressure in Pregnancy This consensus report focuses the presentation, pathophysiology, and management of the hypertensive disorders of pregnancy expanding on recommendations first presented in 1988 by the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. Practicing physicians should determine whether a patient's hypertension during pregnancy falls into the classification of (1) chronic hypertension, (2) preeclampsia, (3) preeclampsia superimposed on chronic hypertension, or (4) transient hypertension. The distinction, for management considerations, is made between hypertension that is present before pregnancy (chronic and preexisting) and that occurring as part of the pregnancy-specific condition preeclampsia. When maternal blood pressure reaches diastolic levels of 100 mm Hg or greater, treatment should be instituted to avoid hypertensive vascular damage. The report includes a discussion of antihypertensive therapy specific to the chronic or acute hypertension occurring concomitantly with pregnancy. The roles of calcium supplementation and low-dose aspirin to prevent preeclampsia and chronic and transient hypertension are under investigation. 
Globoid cell leukodystrophy: a family with both late-infantile and adult type. We present a patient with adult-onset globoid cell leukodystrophy (GBL) who had almost complete deficiency of galactosylceramide beta-galactosidase. A brother of the index patient deteriorated neurologically and died at the age of 4, probably from the late-infantile form of the disease. In this family, two clinical types of GBL are probably different expressions of an identical genotype. 
Elimination of clonogenic breast cancer cells from human bone marrow. A comparison of immunotoxin treatment with chemoimmunoseparation using 4-hydroperoxycyclophosphamide, monoclonal antibodies, and magnetic microspheres. Autologous bone marrow transplantation (ABMT) may aid in the management of breast cancer, but is currently limited to patients without bone marrow metastases. In earlier studies, 5 logs of malignant clonogenic breast cancer cells could be eliminated from human bone marrow using a combination of chemoseparation with 4-hydroperoxycyclophosphamide (4-HC) and immunoseparation with monoclonal antibodies and magnetic microspheres. In this report the authors compare chemoimmunoseparation to treatment with immunotoxins for elimination of tumor cells from human bone marrow and for the preservation of normal precursors. Breast cancer cells from each of five cell lines were mixed with a tenfold excess of irradiated human bone marrow cells. Treatment with a combination of five immunotoxins reduced clonogenic tumor cell growth by 1.8 to 5.5 logs depending upon the cell line. With two of the five cell lines, clonogenic tumor cells were eliminated quantitatively. Using the CAMA-1 breast cancer cell line, treatment with multiple immunotoxins was compared with chemoimmunoseparation with 4-HC, a panel of five unconjugated monoclonal antibodies and magnetic microspheres. Chemoimmunoseparation eliminated 3.5 to 5.4 logs of malignant cells, while preserving 21% of Colony-forming unit-granulocyte-macrophage (CFU-GM) and 37% of burst-forming unit-erythrocyte (BFU-E). No clonogenic breast cancer cells could be detected. Immunotoxin treatment eliminated 2.2 to 5.4 logs of clonogenic breast cancer cells, but had no effect on the bone marrow precursors. In seven of ten experiments, however, clonogenic breast cancer cells remained after immunotoxin treatment. Consequently, treatment with 4-HC, multiple murine monoclonal antibodies and magnetic microspheres provided more consistent elimination of tumor cells than separation with immunotoxins, but was significantly more toxic for marrow precursors. 
Low-back pain in adolescent athletes: detection of stress injury to the pars interarticularis with SPECT. The authors reviewed 1 year of experience with planar and single photon emission computed tomographic (SPECT) bone scintigraphy in 162 young patients with symptoms of low-back pain possibly related to stress injury to the pars interarticularis or spondylolysis. Planar scintigraphy and SPECT revealed no abnormality in 91 patients (56%). All abnormalities detected on planar images were also detectable with SPECT. SPECT showed an abnormal focus of radiotracer uptake in the lumbar spine in 71 patients (44%). In 32 of these 71 patients, these findings were also evident with planar scintigraphy. In 39 of these 71 patients, use of SPECT. Correlation with contemporaneous radiographs was made in 72 cases (including computed tomography in 10 cases). SPECT can be used to detect stress injury not seen with planar bone imaging or radiography and is recommended in evaluation of low-back pain in young athletes. 
Sucralfate retention enemas in solitary rectal ulcer. The conservative treatment of solitary rectal ulcer is generally unsatisfactory. Six patients, aged 27-54 years, with recurrent solitary rectal ulcer were treated with topical administration of sucralfate in a daily dose of 2 g twice a day for 6 weeks. Four patients experienced complete relief of symptoms and the remaining two patients had marked improvement. Although macroscopic healing of the ulcer was apparent in all, histologic improvement was not appreciable. Five of the six patients remain in remission during a follow-up period of 4-14 months (mean, 8 +/- 1.5 months). Recurrence was observed in one patient at 5 months, which satisfactorily resolved with sucralfate enemas. From these preliminary observations we infer that solitary rectal ulcer can be effectively treated with topical application of sucralfate. 
Relation between mixed venous oxygen saturation and cardiac index. Nonlinearity and normalization for oxygen uptake and hemoglobin. The ability of mixed venous oxygen saturation (SvO2) monitoring to reflect changes in cardiac index (CI) with therapy in critically ill patients is unclear. To this end, SvO2 and CI were measured before and during an infusion of enoximone and/or dobutamine in 30 patients with advanced heart failure. A nonlinear relationship was observed between SvO2 and CI with the nonlinear correlation coefficient being 0.52. On normalizing for individual differences in hemoglobin and oxygen consumption, this correlation coefficient became 0.90. Further analysis of individual data was performed using linear regression, and the slopes and correlation coefficients were found to span a wide range slope: -10.0 to 30.9 min-m2/L, r: -0.27 to 0.99). However, the mean slope and correlation coefficient for patients with baseline CI and SvO2 less than 21/min/m2 and less than 55 percent were 18.3 min-m2/L and 0.87, respectively, while those for the remainder of patients were only 3.1 min-m2/L and 0.42, respectively. Thus, the nonlinear correlation coefficient of the SvO2-CI relationship in a group of patients is dependent on the homogeneity of their oxygen consumption and hemoglobin concentration. Furthermore, the ability of SvO2 to serve as a therapeutic indicator in any given patient is dependent on baseline SvO2 and CI. 
Intra-arterial thrombolytic therapy in the management of acute and chronic limb ischaemia. A group of 54 patients with acute or chronic limb ischaemia were initially treated with low dose intra-arterial thrombolytic therapy using streptokinase (10,000 units h-1) or plasminogen activator (0.5 mg h-1). Complete thrombolysis was obtained in 90 per cent of patients with symptoms of less than 1 week duration, and in 50 per cent with symptoms of greater than 1 week (P less than 0.05). Successful lysis in 36 patients was followed by successful bypass surgery in seven, percutaneous angioplasty in 13, no further treatment in 13, repeat thrombolysis in two and amputation in one. Failed therapy was associated with major amputation in 40 per cent. One patient died of haemorrhage and another of stroke as a direct result of thrombolytic treatment. The most common complication was haematoma at the site of cannulation of the vessel. Intra-arterial thrombolytic therapy can be very useful for the management of acute and chronic limb ischaemia, but complications do occur and patients should be carefully selected. 
Comparison of the effects of ureteral calculosis and occlusion on muscular sensitivity to painful stimulation in rats. An animal model of muscular hyperalgesia was developed. In humans, this disorder follows painful crises due to ureteral calculosis. Changes in vocalization thresholds to electrical stimulation of the obliquus externus muscle of both sides were studied in a group of rats with chronically implanted muscles before and after the production of a stone in one ureter. In another group of rats with implanted muscles, it had been verified preliminarily that these thresholds did not vary widely from day to day. On the contrary, a significant lowering in threshold (max 31%) in the muscle ipsilateral to the implanted ureter appeared the day after the production of the stone and persisted for the subsequent 10 days of observation, although less pronounced during the last 5 days. Hypersensitivity to manual pressure was also observed, mainly in the ipsilateral muscle, in most rats during the same period. In order to differentiate between the effects due to the presence of the stone in the ureteral lumen and those due to the spontaneous occlusion which frequently occurred in the implanted ureter, 2 other groups of rats were studied. In one, a unilateral ureteral ligature was performed; in the other, the production of a stone was combined with a ligature (placed distally to the stone). Ligature alone never induced any hyperalgesic effect. Stone plus ligature produced a marked hyperalgesia (max 39%) in the ipsilateral muscle, which lasted for only 5 days. It is concluded that the ureteral stone is the factor responsible for the appearance of muscular hyperalgesia. 
Genetic aspects of admissions to a paediatric intensive care unit. Of 821 consecutive admissions to a paediatric intensive care unit, 47 (5.7%) were for chromosomal or monogenic disorders. These patients had more readmissions, longer mean stays, and a higher mortality rate than the group as a whole. In two of the four cases that died of single gene disorders, failure to store DNA made genetic counseling difficult. 
Late follow-up of carotid endarterectomy with venous patch angioplasty. Ninety carotid endarterectomies with venous patch angioplasty were performed in 83 patients between July 1980 and December 1985. The primary indication for patching was a small-caliber internal carotid artery (ICA) with a diameter less than 3.0 mm in 54 arteriotomies (60%). Patency of the endarterectomy was evaluated by completion arteriography in all instances. Follow-up was conducted after an intermediate postoperative period of 21 +/- 12.5 months in 69 sides by arteriography. A late follow-up was conducted at 55.4 +/- 11.2 months either by arteriography (in 45 sides) or by carotid duplex scanning (in 11 sides). Twenty-one patients with 23 endarterectomies died, only 1 of a cerebral event. Seven patients moved or refused study and five were lost to follow-up. Three recurrent stenoses and five carotid occlusions developed by the time of the intermediate follow-up. By the time of late follow-up, three additional patients developed recurrent stenoses. Our results suggest that recurrent stenosis continues to develop with a longer period of follow-up in patients undergoing venous patch angioplasty with carotid endarterectomy. 
Headaches due to cerebrovascular disease. Subarachnoid hemorrhage causes sudden, severe headache and requires immediate medical and surgical diagnosis and treatment. A CT scan is the first choice for correct diagnosis. In order to prevent rebleeding, delays in treatment should be avoided. Intraparenchymal cerebral hemorrhage is now often recognized by means of CT scanning and sometimes is a cause of headache. Cerebellar hemorrhage commonly causes occipital headache and is an indication for immediate surgical intervention, although small cerebellar hemorrhages can be treated conservatively. Ischemic cerebrovascular disease is frequently accompanied by headache, but its etiology remains uncertain. Thrombosis of the cerebrovenous system is a less frequent cause of head pain than that of the arterial system, but it usually shows characteristic neurologic signs. Following carotid endarterectomy or superficial temporal artery-middle cerebral artery bypass surgery, the patient may have moderate to severe unilateral headaches, probably as a result of platelet aggregation and serotonin release. 
Sodium and volume sensitivity of blood pressure. Age and pressure change over time. Salt sensitivity has been implicated in the age-related increase in blood pressure. We studied the reproducibility of a rapid method for assessing sodium sensitivity and resistance of blood pressure as well as the effect of age on this phenomenon. Blood pressure after volume expansion with 2 l intravenous saline (0.9%) over 4 hours was compared with that after 1 day of 10 mmol sodium chloride intake and 3 and 40 mg oral doses of furosemide. Normal and hypertensive subjects (n = 28) were studied twice within a year. Cross-sectional observations of the effect of age were made from studies in 230 hypertensive and 430 normotensive subjects. Longitudinal observations of blood pressure change over time were made 10 or more years after categorization of sodium responsivity in 31 subjects. The blood pressure response was reproducible in 28 subjects studied twice (r = 0.56, p less than 0.002). Four subjects changed salt-responsiveness status and six were indeterminate on restudy. Sodium sensitivity of blood pressure increased significantly with increasing age in the entire population (n = 660, r = -0.38, p less than 0.001). The relation was more striking in hypertensive subjects (n = 230, r = -0.31, p less than 0.001) in whom a progressive increase in salt sensitivity with decades was seen than in the normotensive group (n = 430, r = -0.19, p less than 0.01) in whom salt sensitivity was not observed until the sixth decade. Salt-sensitive subjects had a significantly greater increase in systolic (p less than 0.001) and diastolic (p less than 0.01) pressure over time than those who were salt-resistant. Salt sensitivity is a reproducible phenomenon that is related to the age-associated increase in blood pressure characteristic of industrialized societies. In addition, salt sensitivity can be shown to be a predictor of subsequent, age-related blood pressure increase. 
Aztreonam in the treatment of gram-negative bacterial meningitis. Aztreonam was administered to 122 patients with presumptive or confirmed gram-negative bacillary meningitis in an open, multinational study. The antibiotic was administered at a dosage of 1-2 g to adults, 50 mg/kg to children greater than 2 years old, and 30 mg/kg to infants three or four times daily. Seventy-seven patients had microbiologically confirmed gram-negative meningitis due to an aztreonam-susceptible organism and received aztreonam for at least 48 hours. Haemophilus influenzae was the most frequently recovered pathogen (40 patients), followed by Enterobacteriaceae (16 patients), Neisseria meningitidis (15 patients), and Pseudomonas species (six patients). All but four patients were microbiologically cured. Microbiologic failure was associated with either a persistent intracerebral abscess (one patient) or a foreshortened course of therapy before microbiologic reevaluation and death (at 48 hours, 48 hours, and 72 hours after initiation of treatment, respectively). These data suggest that aztreonam is effective in the treatment of gram-negative bacillary meningitis caused by susceptible organisms. 
The clinical significance and pathophysiology of stress-related gastric mucosal hemorrhage. Critically ill patients admitted to intensive care units (ICUs) develop a spectrum of gastroduodenal mucosal lesions that may result in mucosal hemorrhage and subsequent morbidity and mortality. Although stress-related mucosal lesions may be detected endoscopically in most critically ill patients, the incidence of clinically significant bleeding from these lesions is difficult to establish because of the heterogeneity in patient populations, the definitions of bleeding, and the methods of monitoring in various studies. Bleeding occurs overall in approximately 16% of patients not receiving prophylaxis, but the incidence of life-threatening hemorrhage appears to be much lower (less than 6%). In light of the increasing use of pharmacologic prophylaxis in ICUs, the clinical impact of stress-related bleeding and its prophylaxis is discussed in terms of bleeding incidence, morbidity and mortality, cost, and potential side effects. The pathophysiology of stress-related mucosal ulceration involves the complex interaction of gastric luminal factors, alterations in blood flow and intramucosal pH, and alterations in numerous factors that are normally responsible for maintaining an intact mucosa. The pathophysiology of stress ulceration is discussed, with an emphasis on cause-and-effect relationships, evolving areas of investigation, and implications for prophylaxis and treatment. 
Cervical paraganglioma with subsequent intracranial and intraspinal metastases. Case report. Paragangliomas, tumors derived from the extra-adrenal paraganglion system, have commonly been found in the retroperitoneum, abdomen, mediastinum, skull base, and neck. Rare intraspinal cases have included involvement of the cauda equina and filum terminale, and a recent case has been reported of thoracic cord paraganglioma with metastasis to the cauda equina. The authors present the case of a patient with a cervical paraganglioma who underwent subtotal resection followed by postoperative irradiation; she subsequently developed multiple intracranial and intraspinal metastases 7 months following the first decompression procedure. 
Comparison of different antibiotic regimens for therapy of 32 cases of Q fever endocarditis. We studied 32 cases of Q fever endocarditis diagnosed in France between January 1985 and December 1989 to evaluate the efficacies of the different regimens of antibiotics used for treatment. Each patient was monitored during the treatment (range, 12 to 60 months), and clinical and biological information was computerized. Various treatments were prescribed, including doxycycline alone (9 cases) or in association with rifampin (4 cases), quinolones (16 cases), or sulfamethoxazole-trimethoprim (1 case). Two patients died before the beginning of the treatment. Nineteen patients had hemodynamic failure and subsequently underwent valve replacement. Nine valve tissue cultures were positive despite previous antibiotic treatment. In terms of their effects on mortality, the difference between doxycycline alone and doxycycline plus quinolones is statistically significant. We conclude that the addition of quinolones to doxycycline is beneficial. On the basis of clinical, serological, and valve tissue culture results, no treatment was able to cure Q fever endocarditis within 2 years, even with a combination of antibiotics. We advise a minimum duration of treatment of 3 years with therapy combining quinolones and doxycycline. 
How prevalent is cancer family syndrome? Based on an established but pragmatic definition of cancer family syndrome as the presence of three or more relatives affected by colorectal cancer in a first degree kinship, the contribution of this syndrome to the total cancer burden in Northern Ireland has been studied by investigating all non-polyposis probands under 55 years old at histological diagnosis between 1976 and 1978. Family interviews were possible for 95% (n = 205) of all non-polyposis probands and verification of vital status or medical history was obtained for 98% of 1811 first degree relatives. The prevalence of cancer family syndrome was between 1 and 2%, a figure some fivefold less than that estimated elsewhere. A proximal tumour excess was not characteristic of the ascertained families. These results may have implications for the identification of susceptible people if screening for high risk groups is considered a worthwhile option for reducing colorectal cancer mortality in the United Kingdom. 
Percutaneous transjugular portosystemic shunt. OBJECTIVE.--To determine the effectiveness of the Palmaz balloon expandable stent for the creation of a transjugular intrahepatic portosystemic shunt. The device is designed to achieve portal decompression in patients with variceal hemorrhage secondary to portal hypertension. DESIGN.--Transjugular intrahepatic portosystemic shunting was performed in eight patients during a 9-month period. Mean follow-up was 5 months. PATIENTS.--All patients had cirrhosis with portal hypertension and varices. Bleeding occurred in seven patients from esophageal varices and in one patient from hemorrhoids. MAIN OUTCOME MEASURES.--Shunt patency and recurrent variceal hemorrhage. RESULTS.--Shunts created from a transjugular approach between a hepatic and a portal vein (diameters of 8 to 12 mm) lowered the average portosystemic pressure gradient from 36 to 11 mm Hg. Mean postoperative hospital stay was 7.7 days. Complete variceal decompression after transjugular intrahepatic portosystemic shunt placement was identified endoscopically in all eight patients. The patient treated for hemorrhoids rebled and was treated successfully by transfemoral balloon expansion of the shunt diameter from 8 to 12 mm. All shunts were patent at 1 to 9 months (mean, 5 months) of follow-up. CONCLUSION.--Initial results suggest that transjugular intrahepatic portosystemic shunt is a safe and effective method of portal decompression for the treatment of variceal hemorrhage. 
Effects of dietary Ca2+ on erythrocyte Na(+)-transport systems in spontaneously hypertensive rats. 1. The purpose of this study was to determine the effect of dietary Ca2+ intake on blood pressure and erythrocyte Na+ transport in spontaneously hypertensive rats. 2. Spontaneously hypertensive rats and Wistar-Kyoto rats were fed diets with three different Ca2+ contents, 0.1% (low-Ca2+ diet), 0.6% (normal-Ca2+ diet) and 4.0% (high-Ca2+ diet), between 6 and 20 weeks of age. At 20 weeks of age, the levels of erythrocyte Na+ efflux, as well as Na+ and K+ contents in erythrocytes, were measured. 3. On the low-Ca2+ diet, spontaneously hypertensive rats showed an enhancement of hypertension. Conversely, on the high-Ca2+ diet, they showed an attenuation of the increase in blood pressure. Spontaneously hypertensive rats had a lower erythrocyte Na+ content and increased activity of the Na+ pump at higher levels of dietary Ca2+. Passive Na+ permeability and Na(+)-K+ co-transport were similar in spontaneously hypertensive rats on the low-, normal- and high-Ca2+ diets. There were no significant differences in blood pressure and in Na+ pump activity in WKY on the three different diets. 4. It is concluded that dietary Ca2+ might affect the regulation of blood pressure in spontaneously hypertensive rats by changing the activity of Na+ pump in the cell membrane. 
Incidence and characteristics of preventable iatrogenic cardiac arrests We studied the contribution of iatrogenic illness to cardiac arrest among patients hospitalized in 1981 in a university teaching hospital. During this 1-year period, 28 (14%) of 203 arrests in which resuscitation was attempted followed an iatrogenic complication. Seventeen (61%) of the 28 patients died. The demographic characteristics of patients with iatrogenic arrest did not differ strikingly from those of other patients who arrested. However, patients with iatrogenic arrest were less likely to be in cardiogenic shock or to have suffered an acute myocardial infarction prior to arrest. They were more likely to survive to discharge from the hospital and to be taking digoxin or antiarrhythmic medication prior to arrest. Among the 28 cases of iatrogenic cardiac arrest, 18 (9% of all arrests) might have been prevented by stricter attention to the patient's history, findings on physical examination, and laboratory data. The most common causes of potentially preventable arrest were medication errors and toxic effects (44%) as well as suboptimal response by physicians to clinical signs and symptoms (28%), most frequently dyspnea and tachypnea. Rapid, appropriate response to abnormal drug levels, to electrocardiographic signs of adverse drug effects, and to signs and symptoms of congestive heart failure or toxic effects from digoxin might decrease the incidence of cardiac arrest among hospitalized patients. 
Nutritional support of patients with cancer of the gastrointestinal tract. Malnutrition is extremely common in patients with malignant disease. Whereas the causes are multifactorial, the predominant factor is the imbalance between nutrient intake and host nutrient requirements. Furthermore, the evidence suggests that cachexia is related to abnormal changes in host intermediary metabolism induced by host-tumor interactions, and endogenous peptides such as TNF may be important mediators. The role of nutritional therapy in cancer patients remains to be defined. Clearly, patients with severe malnutrition benefit from nutritional intervention. However, the benefit of nutritional therapy in less severe cases of malnutrition as an adjuvant to oncologic therapy has yet to be established. 
Age-related normal values of signal-averaged electrocardiographic variables after acute myocardial infarction. The study examined standard time domain variables of a signal-averaged electrocardiogram (SAECG) in 328 survivors of acute myocardial infarction. The correlation of these variables with age and the influence of age on the prediction of postinfarction arrhythmic complication (sudden death [n = 12] or sustained ventricular tachycardia, or both [n = 14]) from the SAECG were investigated. Statistically highly significant correlations (p less than or equal to 0.00002) between age and SAECG variables were found. Compared with patients aged less than 60 years, the SAECG-based stratification of arrhythmic complications after myocardial infarction in patients greater than 60 years had lower sensitivity for the same values of specificity and lower specificity for the same values of sensitivity. 
Factors influencing the outcome of congenital heart disease detected prenatally. The diagnosis of structural heart disease before birth is associated with a poor prognosis. Of 222 continuing pregnancies seen in a 10 year period, there has been a 79% mortality. This is inconsistent with published results and current concepts of the outcome for children with cardiac malformation. Of the 222, death occurred in intrauterine life in 57, 87 died as neonates, and 31 in infancy or childhood. There are 47 survivors of whom only five have survived beyond 4 years. Factors influencing the outcome in these cases were examined further. A high mortality was associated with the presence of extracardiac anomalies in 71 (32%) and prenatal cardiac failure in 28 (13%). As many patients were referred for these reasons, referral methods preferentially select patients with a different range of heart disease from that seen postnatally. In addition, some forms of heart disease progress in severity during fetal life. Those involved in the management and counselling after diagnosis of heart disease in early pregnancy must be aware of the additional prenatal factors influencing prognosis and allow for them in making predictions of outcome. 
Proliferation of endocrine cells in the rat stomach caused by drug-induced achlorhydria. Time-related changes of serum gastrin levels, gastrin cell, and enterochromaffinlike cell densities, and proliferation kinetics of these cells have been examined in rats during treatment with the substituted benzimidazole BY 308 over a period of 73 days. Serum gastrin levels increased very rapidly from 74 +/- 6 pg/mL (controls) to 438 +/- 31 pg/mL (day 1) and 727 +/- 68 pg/mL (day 4). Thereafter, a steady increase was observed until day 70 (2097 +/- 208 pg/mL). Enterochromaffinlike cell density was unchanged until day 10, but then increased progressively without reaching a plateau (144% above control on day 73). The labeling index of these cells was enhanced shortly after drug application and remained on a constant elevated level from day 14 to day 73 (about 10-fold to 12-fold above controls from day 14 to day 70). The number of gastrin cells increased rapidly within the first week and reached a plateau after 17 days (96% increase above controls). In contrast to enterochromaffinlike cells, the labeling index did not change immediately but increased on day 7 by 37% and returned beneath control values after day 28. The results suggest that in drug-induced achlorhydria, the progressive increase of enterochromaffinlike cells is explained by an enhanced mitosis, whereas other factors in addition to proliferation are responsible for the augmentation of gastrin cells. 
Independent risk factors for hepatocellular carcinoma in French drinkers. The aim of this study was to assess whether markers of hepatitis B virus or hepatitis C virus infection are independent risk factors for hepatocellular carcinoma in drinkers after adjustment for three known risk factors: cirrhosis, age and male sex. Among 2,015 consecutive drinkers admitted, hepatitis C virus antibodies were found by sensitive radioimmunoassay in 1,259. The following five factors have been identified and ranked as risk factors for hepatocellular carcinoma in unidimensional and regression analysis: cirrhosis (p less than 0.001), age (p less than 0.001), male sex (p less than 0.001), presence of HBsAg (p less than 0.001) and presence of hepatitis C virus antibodies (p less than 0.03). Among drinkers with cirrhosis, the patients with hepatocellular carcinoma were older (64 +/- 11 yr vs. 56 +/- 9 yr; p less than 0.001), were more often male (93% vs. 65%; p less than 0.0001) and had higher prevalence of HBsAg (9% vs. 2%; p = 0.02) and hepatitis C virus antibodies (41% vs. 26%; p = 0.02). A simple algorithm permitted us to identify a high-risk population of drinkers: the male cirrhotic patient older than 50 yr. The relative risk of hepatocellular carcinoma in this selected population was 17.7 (95% confidence interval = 9.0 to 37.5; p less than 0.0001). From a pragmatic point of view, the detection of HBsAg or hepatitis C virus antibodies, although independently associated with hepatocellular carcinoma, is not useful in increasing the diagnostic value of this algorithm because of the poor sensitivity of these tests. The weak relationships observed between hepatitis C virus antibodies and hepatocellular carcinoma needs confirmation by more accurate tests. 
Antiphospholipid antibodies in cerebral ischemia. In a 2-year prospective study of 146 patients with cerebral ischemia, we compared vascular risk factors for stroke with clinical and laboratory findings, particularly antiphospholipid antibodies. Ten patients (6.8%) were positive for at least one antiphospholipid antibody; one patient had systemic lupus erythematosus, one had rheumatoid arthritis, and the remaining eight fulfilled criteria for the diagnosis of primary antiphospholipid syndrome. These patients were predominantly male, not necessarily young, and 50% of them did not have any other vascular risk factors; there were no significant clinical or paraclinical differences between these patients and those without antiphospholipid antibodies. Outcome in the 10 patients was good, and platelet antiaggregating drugs proved to be useful in preventing further cerebrovascular ischemic events in our patients. 
Rectosigmoid varices and other mucosal changes in patients with portal hypertension. A prospective study was performed to evaluate the prevalence of anorectal varices and their clinical significance as well as to study other proctosigmoidoscopic changes in 75 patients with portal hypertension of diverse etiology. Sixty-seven patients (89.3%) had lower gastrointestinal varices with no significant difference (p greater than 0.05) in prevalence between cirrhosis (92.1%), noncirrhotic portal fibrosis (87%), and extrahepatic portal venous obstruction (85.7%). The rectum was the most common site of lower gastrointestinal varices. External anal and sigmoid colonic varices almost always occurred in the presence of rectal and/or internal anal varices. There was no correlation between the presence of rectosigmoid varices and the severity of esophagogastric mucosal changes or portal hypertension. There was no suggestion that esophageal variceal sclerotherapy influenced the presence of anorectal varices. Seven patients (9.3%) had recent hematochezia, including three patients in whom it occurred in the absence of any upper gastrointestinal hemorrhage. Varices were the cause of bleeding in at least five patients. An abnormal mucosal vascular pattern in the form of telangiectasias or spiders was seen, irrespective of etiology of portal hypertension, in nine patients (12%). Hemorrhoids were present in 31 patients (41.3%) with an age-related difference (p less than 0.05) between patients with cirrhosis (55.3%) and extrahepatic portal venous obstruction (21.4%). 
Revascularization of infarcted myocardium. Effect on myocardial perfusion assessed with quantified Tl-201 SPECT technique. Myocardial perfusion was studied in 21 patients before and after revascularization of all graftable stenotic vessels following post-infarction anteroapical akinesia and minor dyskinesia. At preoperative and late postoperative evaluation, perfusion abnormalities in identified sectors were quantified with two methods, one (Q1) assessing the extent and the other (Q3) the severity of abnormal perfusion. The preoperative scores with both methods indicated permanent myocardial perfusion defects in all 21 patients and reversible defects, indicating myocardial ischemia, in 16 with Q1 and 14 with Q3. After bypass grafting there was overall reduction of myocardial perfusion defect and of abnormality scores: Notably, 13/21 patients (62%) had decreased permanent myocardial defect score, reflecting reactivation of 'hibernating myocardium'. The findings indicated that obstructed but graftable vessels supplying myocardium with loss of contractile function should be bypassed, since flow contribution to distant, viable myocardium is probable via preserved collateral circulation. This should be particularly relevant for the LAD, because of that artery's septal branches. 
Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. The impact of nonrheumatic atrial fibrillation, hypertension, coronary heart disease, and cardiac failure on stroke incidence was examined in 5,070 participants in the Framingham Study after 34 years of follow-up. Compared with subjects free of these conditions, the age-adjusted incidence of stroke was more than doubled in the presence of coronary heart disease (p less than 0.001) and more than trebled in the presence of hypertension (p less than 0.001). There was a more than fourfold excess of stroke in subjects with cardiac failure (p less than 0.001) and a near fivefold excess when atrial fibrillation was present (p less than 0.001). In persons with coronary heart disease or cardiac failure, atrial fibrillation doubled the stroke risk in men and trebled the risk in women. With increasing age the effects of hypertension, coronary heart disease, and cardiac failure on the risk of stroke became progressively weaker (p less than 0.05). Advancing age, however, did not reduce the significant impact of atrial fibrillation. For persons aged 80-89 years, atrial fibrillation was the sole cardiovascular condition to exert an independent effect on stroke incidence (p less than 0.001). The attributable risk of stroke for all cardiovascular contributors decreased with age except for atrial fibrillation, for which the attributable risk increased significantly (p less than 0.01), rising from 1.5% for those aged 50-59 years to 23.5% for those aged 80-89 years. While these findings highlight the impact of each cardiovascular condition on the risk of stroke, the data suggest that the elderly are particularly vulnerable to stroke when atrial fibrillation is present. 
Rubella susceptibility of an infertile population. The recent trend reported by the CDC reaffirms that rubella continues to be a health care issue and should be a concern particularly for those who care for women in the childbearing age group. Immunization of all susceptible women will not only offer them protection but reduce the pool of susceptible individuals that can transmit the disease. 
Analysis of the colonoscopic findings in patients with rectal bleeding according to the pattern of their presenting symptoms. Patients presenting with rectal bleeding were prospectively categorized according to the pattern of their presentation into those with outlet bleeding (n = 115), suspicious bleeding (n = 59), hemorrhage (n = 27), and occult bleeding (n = 68). All patients underwent colonoscopy and this was complete in 94 percent. There were 34 patients with carcinoma and 69 with adenomas greater than 1 cm diameter. The percentage of neoplasms proximal to the splenic flexure was 1 percent in outlet bleeding, 24 percent with suspicious bleeding, 75 percent with hemorrhage, and 73 percent with occult bleeding. Barium enema was available in 78 patients and was falsely positive for neoplasms in 21 percent and falsely negative in 45 percent. Colonoscopy is the investigation of choice in patients with suspicious, occult, or severe rectal bleeding. Bleeding of a typical outlet pattern may be investigated by flexible sigmoidoscopy. 
Long-term (2 year) beneficial effects of beta-adrenergic blockade with bucindolol in patients with idiopathic dilated cardiomyopathy. Beta-adrenergic blockade represents a promising therapeutic approach to idiopathic dilated cardiomyopathy. Bucindolol, a new beta-blocker, showed favorable effects in a short-term (3 month) trial in idiopathic dilated cardiomyopathy. To assess long-term response, 20 study patients (7 of 9 patients previously assigned to the placebo group and 13 of 14 patients previously assigned to bucindolol therapy) received long-term bucindolol therapy and were followed up for a mean of 23 +/- 4 months (range 17 to 30). The mean patient age was 49 years (range 29 to 66) and the median duration of disease was 11 months (range 1 to 190). Ten patients were in functional class II and 10 were in class III; 15 patients were men. At the end of the common follow-up time, all 20 patients were alive, 17 continued to receive bucindolol (mean dose 176 mg/day, range 25 to 200), and 2 underwent cardiac transplantation. Left ventricular ejection fraction increased from a baseline value of 25 +/- 8% to 35 +/- 13% (n = 19 pairs, p less than 0.001). Functional class improved in 12, was unchanged in 5 and deteriorated in 3 (p = 0.056). Exercise time was maintained (9.4 +/- 3.1 versus 9.1 +/- 3.5 min, n = 19, p = NS), as was maximal oxygen uptake (19.2 +/- 4.9 versus 18.8 +/- 5.7 ml/kg per min, n = 19, p = NS). Thus, long-term bucindolol therapy leads to substantial increases in ejection fraction and to improved functional class while stable exercise performance is maintained. 
Free-tissue transfer in elderly patients. A retrospective survey was undertaken to evaluate the success of free-tissue transfer (free flap) in the elderly. During a 70-month period, 199 free flaps were performed in 151 patients at the Western Pennsylvania Hospital, 60 of these involving 47 patients over the age of 60. Primary coverage rates differed significantly between the elderly and younger age groups (68.5 versus 85.3 percent, respectively); however, eventual coverage rates (92.6 versus 96.3 percent), minor complication rates (34.0 versus 34.6 percent), mortality rates (2.1 versus 1.0 percent), flap revision rates (32 percent of patients versus 30 percent), and length of postoperative hospitalization (18.7 versus 18.8 days) were not significantly different in the two groups. Among the elderly, significant increases in flap loss rates were noted with the use of end-to-side arterial anastomosis, placement of the anastomosis within a zone of injury, and the use of the gracilis muscle donor site. Our data suggest that the primary cause of free-flap failure is construction of the anastomosis within a zone of injury. Free-tissue transfer is a valuable option in the repair of tissue defects in the elderly and should not be denied as a treatment because of patient age. 
Efficacy and toxicity of thromboxane synthetase inhibitor for cerebral vasospasm after subarachnoid hemorrhage. The efficacy and possible side effects of thromboxane A2 (TXA2) synthetase inhibitor in the treatment of cerebral vasospasm after subarachnoid hemorrhage (SAH) were assessed for 24 patients who presented with grades I to IV of the Hunt and Hess classification. All patients underwent aneurysmal clipping within 48 hours after SAH. Postoperatively, TXA2 synthetase inhibitor, Cataclot [sodium (E)-3-[p-(1H-imidazol-1-ylmethyl)phenyl]-2-propenoate] was administered to 13 patients by continuous drip infusion at a dose of 1 microgram/kg/min for 8 to 14 days (group A). The remaining 11 patients did not receive this drug (group B). Of the 13 patients in group A, seven patients (54%) showed no symptomatic vasospasm after SAH. Four patients (31%) developed a transient deterioration of consciousness and/or motor disturbance. Three of these patients fully recovered, while one of them showed a mild neurological deficit on discharge. One patient (8%) developed permanent dysphasia and hemiparesis as a result of ischemic brain damage due to vasospasm. One patient (8%) died of the side effect. On the other hand, of the 11 patients in group B, only three (27%) showed no symptomatic vasospasm. One (9%) patient presented a transient neurological deficit but fully recovered upon discharge. Four patients (36%) showed permanent neurological deficits, although they all could lead an independent life after discharge. The three remaining patients developed a severe disturbance of consciousness caused by ischemia due to vasospasm, and two of them died within 1 month after the onset of SAH. In the group treated with Cataclot, two patients developed an epidural hematoma late during the administration of the drug. Of these two, one patient died of increased intracranial pressure that was accelerated by the complication. These results indicate that TXA2 synthetase inhibitor is effective in not only decreasing the occurrence of symptomatic vasospasm but also reducing the neurological deterioration due to vasospasm after SAH. However, this drug has a hazardous side effect in that it may promote a tendency to bleed, which caused death in one of our patients. 
The incidence of postoperative nausea and vomiting in women undergoing laparoscopy is influenced by the day of menstrual cycle. Postoperative nausea and vomiting is a major cause of postoperative morbidity. It can lead to increased recovery time, delaying patient discharge and an increase in hospital costs. Past studies have shown that postoperative nausea and vomiting is more frequent in women than men, appears to elevate around the time of menarche and is reduced around the time of menopause. This retrospective review of a one-year experience of laparoscopic tubal ligation at our institute examined the effect of menstrual cycle on postoperative nausea and vomiting. The anaesthetic and surgical techniques were consistent for all patients. Patient data included age, weight, last day of menstrual cycle, the length of anaesthetic, the dose of inhalational agent, the dose of narcotic, emesis on emergence and whether or not droperidol was used. Of the the 235 patients in the study, the incidence of nausea and vomiting was 28%. One hundred fifty-eight had had no preoperative antiemetic and 77 had received droperidol. These two groups were analyzed separately. The incidence in the group not receiving droperidol was 33.5% and in the droperidol group, 16.9% (P less than 0.01). The incidence of nausea and vomiting was higher on the first eight menstrual days (51.6 vs 21.6, P less than 0.001), was highest on day five of the menstrual cycle and lowest on days 18, 19, and 20 where there was no nausea and vomiting. Droperidol reduced the incidence of postoperative nausea and vomiting but the variation in postoperative nausea and vomiting during the cycle persisted. 
Tunneled central venous catheter sepsis: risk factors in a pediatric hospital. All tunnelled central venous catheters (TCVC) placed at the Alberta Children's Hospital in Calgary, Alberta, between November 1984 and July 1987, were retrospectively reviewed to study the association of catheter infection with a number of factors including age, diagnosis, catheter use, and areas caring for children. One hundred children received 130 silastic catheters placed for a total of 17,861 days. Each catheter survived a median of 100 days. Thirty-one episodes of catheter sepsis were identified (one episode for each 576 days of catheter use). Children under 2 years of age had more than two times the risk of catheter infection (p less than 0.01). Children with malabsorption had a greater risk (45.7%) than did those with infection (25.0%) or cancer (15.5%). The use of catheters for total parenteral nutrition (TPN) or for multiple purposes markedly increased the risk of catheter infection. The risk of infection of TCVC appears to be great in the young child, in particular, in those requiring TPN or multiple intravenous infusions. Use of TCVC in these children should be avoided if possible. 
Spinal intramedullary ependymal cyst. Report of three cases. Three cases of spinal intramedullary ependymal cyst, two at the thoracolumbar junction and one in the cervical spinal cord, are reported in women in their fifth to seventh decades. Neurological signs and symptoms were extremity dysesthesias, paresthesias, and weakness. Plain cervical and lumbothoracic x-ray films were normal for the patients' age. Magnetic resonance (MR) imaging demonstrated a rounded cystic intramedullary mass at the thoracolumbar junction in two cases and at C3-7 in one case. The signal intensity of the cyst contents approximated that of cerebrospinal fluid on T1- and T2-weighted images. Upon administration of gadolinium-diethylenetriaminepenta-acetic acid (Gd-DTPA), MR imaging showed no enhancement in the cyst wall or cavity. Myelotomy and cyst drainage were performed in each case, and the neurological status of each patient improved. The lining of the cyst was biopsied in one of the three patients undergoing surgery and was composed of a single layer of cuboidal cells supported by glial tissue. Periodic acid-Schiff staining of the tissue did not reveal a basement membrane. The findings in these cases suggest that the Gd-DTPA-enhanced MR imaging appearance of intramedullary spinal ependymal cyst is consistent and allows for accurate preoperative diagnosis with or without biopsy. 
Incidence of abnormal RNA studies and dysrhythmias in patients with blunt chest trauma. The incidence and significance of myocardial contusion and subsequent cardiac complications have recently been debated. A prospective study of patients with blunt chest trauma was undertaken at a Regional Trauma Unit between January 1, 1989 and March 31, 1990. One hundred ninety-one patients were entered into the study; 72-hour Holter monitoring was performed in 183 patients, and radionuclide angiography (RNA) was performed on 163 patients. All patients had CPK levels (with CPK-mb fractions) measured, and serial electrocardiographs. There were seven patients with abnormal RNA studies; five of the seven abnormal studies were attributable to previously undiagnosed coronary artery disease or myocardial infarction. Nine patients were diagnosed as having atrial fibrillation, seven of whom were in atrial fibrillation on admission. Ventricular dysrhythmias were classified by the number of premature ventricular contractions (PVCs) per hour or the presence of ventricular tachycardia. Twelve patients developed short runs of ventricular tachycardia, and clinically insignificant PVCs were common. Only one patient with ventricular dysrhythmias (frequent PVCs) was treated and there were no hemodynamically significant dysrhythmias. The incidence of clinically significant dysrhythmias or hemodynamically significant myocardial contusion appears to be low in this patient population. Aggressive investigation and monitoring solely for cardiac complications may not be indicated. 
Irreversible drop of systemic vascular resistances in patients implanted with a Jarvik total artificial heart. Maintenance of the body's perfusion by a total artificial heart (TAH) may result in physiological alterations to the circulatory system. Little has been said about modifications to systemic vascular resistances (SVR) during TAH assistance. This paper reports on two patients implanted with a Jarvik - 70 cc TAH, who died after 1 and 3 days, both with an irreversible drop of SVR related to a complete loss of vascular tone but not related to sepsis. Activation of multiple cascades of inflammation, triggered by the extracorporeal circulation (ECC), is maintained during TAH support. Desperately sick patients might not be able to face the vaso-active situations created by the inflammatory response. 
Phosphodiesterase III inhibition or adrenoreceptor stimulation: milrinone as an alternative to dobutamine in the treatment of severe heart failure. High levels of endogenous plasma catecholamines in patients with severe congestive heart failure induce a down-regulation of the myocardial beta-adrenoreceptors and thus cause adrenoreceptor agonists, such as dobutamine, to be less effective in the treatment of these patients. Phosphodiesterase III inhibitors work independent of adrenoreceptor activity and plasma catecholamine levels; thus these agents are likely to be more effective in the treatment of severe heart failure. The present study compares both the initial and late hemodynamic effects of dobutamine and milrinone during sequentially administered 24-hour infusions. Twenty patients with severe heart failure (New York Heart Association class III, n = 4; New York Heart Association class IV, n = 16) were investigated. Dobutamine could be administered at the prescribed maximum dose of 15 micrograms/kg/min for 24 hours in only 15 of 20 patients. In three patients the dose was reduced or dobutamine infusion completely stopped because of a drug-related increase in heart rate greater than 140 beats/min. Another 2 of 20 patients showed no hemodynamic improvement over 3 hours at the maximum dose of 15 micrograms/kg/min. Dobutamine administration was also discontinued in these patients on account of the existing unfavorable hemodynamic condition, and therapy with intravenous milrinone was started. All 20 patients responded to milrinone without side effects, although comparison of the hemodynamic effects during a 24-hour infusion was possible in only 15 patients. The 15 patients studied over both observation periods experienced an increase in heart rate from 88.8 to 105.6 beats/min (+ 1 hour; p less than or equal to 0.001) when receiving dobutamine but had no increase with milrinone. Stroke volume increased during dobutamine infusion from 19.3 to 28.9 ml/m2 (+49.6%) after 1 hour and then fell continuously to 25.2 ml/m2 after 12 hours; during milrinone therapy, stroke volume increased from 18.8 to 31.2 ml/m2 (+66%; p less than or equal to 0.001) and remained at this level until the end of the infusion (30.2 ml/m2). Pulmonary capillary wedge pressure (PCWP) decreased (p less than or equal to 0.001) immediately during milrinone therapy from 26.5 to 16.2 mm Hg after 30 minutes and stabilized at 20.1 mm Hg after 24 hours. During dobutamine infusion PCWP showed a delayed decrease from 27.8 to 19.0 mm Hg after 6 hours and subsequently rose to 22.7 mm Hg after 24 hours.(ABSTRACT TRUNCATED AT 400 WORDS). 
Prognostic indices of survival in patients supported with temporary devices (TAH, VAD). In an attempt to identify current indications and patient selection criteria for the use of mechanical circulatory support, we reviewed our experience in 83 patients who received a total artificial heart (TAH; n = 43), ventricular assist device (VAD) (n = 13), centrifugal pump (n = 17) or extracorporeal membrane oxigenation (ECMO) (n = 8) as a bridge to transplantation (Group I, n = 50) or for recovery from heart failure (Group II, n = 33). Comparing patients successfully transplanted (n = 20) or weaned (n = 9) who survived initial hospitalization, and those who died on mechanical support, there were no differences in preoperative renal, hepatic or pulmonary functions. Postoperative urinary output and bilirubin levels were the earliest variables affecting survival, and urinary output 24 hours after implant was discriminative in patients who survived (p less than 0.01). Age (above or below 40 years) and modality of terminal heart failure (acute versus chronic) were the most important factors affecting survival in the bridge to transplant group: 82% of young patients with acute decompensation were transplanted and 63% are long-term survivors while all patients over 40 years with chronic heart failure died on mechanical support (MS). In postcardiotomy patients, duration of cardiopulmonary by-pass (CPB) was significantly different comparing survivors with those who died in either bridge or recovery groups and all patients who had a CPB greater than 4 hours died on MS or after transplantation or weaning. In conclusion, preoperative indices indicating reversibility of multiple organ dysfunction remain to be identified. 
Two closely linked Drosophila POU domain genes are expressed in neuroblasts and sensory elements. We have characterized two Drosophila POU genes designated dPOU-19 and dPOU-28. These genes are transcribed as 3.1- and 2.2-kilobase mRNAs, respectively, which accumulate maximally during the first 12 hr of embryogenesis. The mRNAs encode 601- and 475-amino acid deduced proteins; their POU domains are most related to those of the human OCT1 and OCT2. Both genes give similar nervous system expression patterns and map to an indistinguishable site at 33F on the cytological map. Transcription of the genes is first observed in the cellular blastoderm. In the course of embryonic development, expression is observed in the neuroectoderm, with subsets of neuroblasts in the procephalic and germband central nervous system as well as a subset of peripheral nervous system elements. The expression patterns of the two POU genes suggest a possible functional role for these putative transcription factors in neurogenesis and neurospecification. 
5-Hydroxtryptamine1D receptor agonism predicts antimigraine efficacy. The interactions of four abortive anti-migraine agents and four prophylactic anti-migraine agents with 5-HT1D receptors in bovine brain were analyzed using radioligand binding techniques and adenylate cyclase assays. In bovine caudate, the affinities of abortive anti-migraine agents (i.e. 5-hydroxytryptamine, ergotamine, dihydroergotamine, sumatriptan) for 5-HT1D receptors range from 4.0-34 nM while the affinities of prophylactic anti-migraine agents (i.e. methysergide, amitriptyline, (-)propranolol, verapamil) range from 46-11,000 nM. In adenylate cyclase studies in bovine substantia nigra, all four abortive anti-migraine agents dose-dependently inhibit forskolin-stimulated adenylate cyclase activity, a biochemical effect mediated by 5-HT1D receptors. No agonist effect on cyclase activity is observed with the four prophylactic anti-migraine agents. These data support the hypothesis that abortive anti-migraine agents are 5-HT1D receptor agonists and that this effect may underlie their anti-migraine efficacy. 
Serum bioactive and immunoreactive luteinizing hormone and follicle-stimulating hormone levels in women with cycle abnormalities, with or without polycystic ovarian disease. Serum steroid, gonadotropin, and alpha-subunit levels were assessed in 35 women with cycle abnormalities [11 with and 24 without polycystic ovarian disease (PCOD) according to strict clinical and biochemical criteria] and 8 regularly cycling women in the early (cycle day 3 or 4) and mid (cycle day 7 or 8) follicular phase. LH and FSH levels were estimated using two immunological techniques [RIA and immunoradiometric assay (IRMA)] and in vitro bioassays (BIO), using mouse Leydig cells and rat granulosa cells, respectively. In PCOD patients mean alpha-subunit, free androgen index [FAI; testosterone x 100/sex hormone-binding globulin (SHBG)], androstenedione, estrone, and estradiol (E2) were significantly elevated compared to levels in the early follicular phase of control cycles and non-PCOD patients. In addition, in PCOD patients mean IRMA-LH and RIA-LH levels were distinctly increased (2.8- to 3.6 fold, respectively; both comparisons, P less than 0.001) compared to control values, but in the same order of magnitude (1.3- to 1.4-fold increments) as that in non-PCOD patients. However, the median BIO-LH level in PCOD patients was 5.9-fold higher than that in non-PCOD patients and 4.0-fold higher than the BIO-LH in the early follicular phase of control women. Consequently, the median BIO/IRMA-LH ratio was 4.8-fold higher in PCOD patients compared to non-PCOD patients. In women with cycle abnormalities, individual BIO/IRMA-LH ratios correlated with BIO-LH (rs = 0.48), FAI (rs = 0.39), free estrogens (E2/SHBG ratios; rs = 0 0.47), and dehydroepiandrosterone sulfate (rs = 0.60) concentrations. Mean IRMA-, RIA-, and BIO-FSH levels and BIO/IRMA-FSH ratios were not significantly different when various groups were compared. Although RIA- and IRMA-LH levels showed good correlation (rs = 0.88), RIA-LH levels were consistently higher, resulting in distinctly higher RIA-LH/FSH ratios (mean, 4.5) compared to IRMA-LH/FSH ratios (median, 1.8) in PCOD patients.(ABSTRACT TRUNCATED AT 400 WORDS). 
Splenic vein aneurysm: MR appearance--a case report. A presumed pancreatic head mass by non-contrast CT examination, was proven to be a splenic vein aneurysm by enhanced CT, MRI, sonography and arteriography. Dangerous percutaneous aspiration was avoided. 
Study of experimental pain measures and nociceptive reflex in chronic pain patients and normal subjects. This study evaluates (i) the effect of heterotopic chronic pain on various experimental pain measures, (ii) the relationship between experimental pain measures and chronic pain symptomatology assessment, and (iii) the influence of the various pain aetiologies on experimental pain measures. Fifty-three chronic pain patients were compared to 17 pain-free subjects with the following psychophysical and physiological indices: pain threshold (PTh), pain tolerance (PTol), verbal estimation of intensity and unpleasantness (intensity scale, IS; unpleasantness scale, US), threshold for intensity and unpleasantness (ITh and UTh), lower limb RIII nociceptive reflex (RIIITh and RIII frequency of occurrence). Chronic pain syndromes included neuropathic pain (n = 12), iodopathic pain (n = 12), myofascial syndromes (n = 9), headache (n = 9), and miscellaneous pain (n = 11). Chronic pain symptomatology was assessed with a visual analogue scale (VAS), a French MPQ adaptation (QDSA), Beck Depression Inventory (BDI), Spielberger State Trait Inventory (STAI) and Eysenck Personality Inventory (EPI). No significant difference was observed between chronic pain patients and pain-free control groups and between patient subgroups for PTh, PTol and RIIITh. No significant correlation was found between experimental pain measures and clinical pain, anxiety or depression scores. However, the chronic pain patients had a higher threshold for unpleasantness and judged the suprathreshold stimuli significantly less intense and less unpleasant than the control group. These results are discussed in relation to diffuse noxious inhibitory controls and the adaptation level theory of chronic pain experience. 
Not all that moves is tardive dyskinesia. OBJECTIVE: Because tardive dyskinesia and spontaneous dyskinesia appear the same, it is difficult to determine whether an individual patient's abnormal movements are induced by medication or have developed spontaneously. Therefore, estimates of the prevalence of tardive dyskinesia that are based on observations not adjusted for spontaneous dyskinesia are inflated. In addition, age is thought to be an important risk factor in the development of both tardive and spontaneous dyskinesias. The authors estimate the prevalence of both disorders for specific age groups. METHOD: The authors reviewed nine reports on dyskinesia prevalence that included history of neuroleptic treatment and related prevalence to age. A rating of 2 or more on the Abnormal Involuntary Movement Scale or an equivalent score on another scale was considered an indication of dyskinesia. If the subject had taken neuroleptics for more than 3 months, the movement disorder was classified as neuroleptic-associated dyskinesia; other dyskinesias were considered spontaneous. The prevalence of tardive dyskinesia was defined as the rate of neuroleptic-associated dyskinesia minus the rate of spontaneous dyskinesia. RESULTS: The true rate of tardive dyskinesia was below 20% for all age groups except 70-79 years. The correlation between the rate of neuroleptic-associated dyskinesia and the rate of spontaneous dyskinesia was low. CONCLUSIONS: After age 40 the prevalence of spontaneous dyskinesia is sufficiently high to conclude that many patients with diagnoses of tardive dyskinesia have abnormal movements attributable to causes other than neuroleptics. 
Primary bile acid diarrhoea without an ileal carrier defect: quantification of active bile acid transport across the ileal brush border membrane. Unexplained bile acid malabsorption associated with diarrhoea that responds to cholestyramine was first described in 1973 but convincing evidence of the proposed mechanism--a defective active ileal bile acid transport--has never been substantiated. Active bile acid transport was quantified in vitro using brush border membrane vesicles prepared from terminal ileal biopsy specimens from 10 patients who fulfilled the criteria of idiopathic bile acid diarrhoea. They were recruited from 181 patients with bile acid malabsorption of various causes. Transport was quantified as in vitro Na+ dependent bile acid transport (INBAT), expressed as pmol taurocholate/mg brush border membrane protein/15 seconds, and in vitro Na+ dependent bile acid local transport capacity (INBALTC), expressed as pmol taurocholate/g ileal biopsy tissue/15 seconds. The lowest INBAT and INBALTC values in the 10 patients with idiopathic bile acid diarrhoea were well above the 10th centile values of a control group of 132 patients. Both INBAT (mean (range) 88 (30-136)) and INBALTC (158 (85-268)) values were significantly higher in the 10 patients than in the control group (INBAT: mean (range) 63 (1-244), INBALTC: mean (range) 98 (1-408)). Quantification of active ileal bile acid transport in these 10 patients with idiopathic bile acid malabsorption suggests that a genetic (carrier) defect is rare in adults. 
Significance of ipsilateral breast tumour recurrence after lumpectomy. Breast cancer treatment trials from the US National Surgical Adjuvant Breast and Bowel Project have established breast-conserving operations as a replacement for radical mastectomy (NSABP B-04), and have shown that in terms of survival free from distant disease there was no significant difference between lumpectomy, lumpectomy plus breast irradiation, and total mastectomy (NSABP B-06). 9-year follow-up data from B-06 are used here to address the issue of ipsilateral breast tumour recurrence (IBTR) and the development of distant disease, a question with important clinical and biological implications. A Cox regression model on fixed co-variates (ie, features such as tumour type or size present at surgery and not subsequently alterable) and on IBTR, which is time dependent and not fixed, revealed that the risk of distant disease was 3.41 times greater after adjustment for co-variates in patients in whom an IBTR developed. IBTR proved to be a powerful independent predictor of distant disease. However, it is a marker of risk for, not a cause of, distant metastasis. While mastectomy or breast irradiation following lumpectomy prevent expression of the marker they do not lower the risk of distant disease. These findings further justify the use of lumpectomy. 
Use of the argon-pumped tunable dye laser for port-wine stains in children. The authors reported previously a new technique using a low power argon-pumped tunable dye laser at a wave-length of 577nm (yellow light) to treat port-wine stains in adults. The authors report their results using this same technique as a form of treatment for 92 children with facial port-wine stains. 
Histological grading of squamous cell carcinoma of the penis: a new scoring system. A system of histological grading based on retrospective analysis of 239 patients with squamous cell carcinoma of the penis is presented. A new scoring system with 4 histological grades was used. The results of this study confirm previous reports that penile cancer is usually a highly (50%) or moderately (29%) differentiated squamous cell carcinoma. Poorly differentiated carcinomas and cancers of other types are very rare. The new grading system was found to be practical and a correlation between histological grade, clinical findings and prognosis was established. Patients with grade 1 tumours had an exceptionally favourable prognosis, with more than 80% being long-term survivors; for these patients, treatment with delayed side effects should be avoided and new forms of treatment should be explored. 
Left ventricular diastolic collapse. An echocardiographic sign of regional cardiac tamponade. BACKGROUND. Cardiac tamponade after cardiac surgical procedures is often associated with hemodynamically significant localized pericardial effusions. The localized collection of pericardial effusion in the postoperative period and the atypical presentation of cardiac tamponade limit the use of conventional clinical and echocardiographic signs usually seen with a circumferential pericardial effusion. Observation of left ventricular diastolic collapse in the echocardiogram of a patient with postoperative regional cardiac tamponade prompted us to explore the frequency of this sign in regional cardiac tamponade. METHODS AND RESULTS. We retrospectively analyzed the echocardiograms of 18 patients with postoperative cardiac tamponade for the following echocardiographic findings: right atrial collapse, right ventricular diastolic collapse, left atrial collapse, and left ventricular diastolic collapse. Three of the 18 patients had circumferential pericardial effusion, and 15 had loculated pericardial effusion; in 10, the effusion was predominantly posterior, and in the other five, it extended laterally or inferiorly. The conventional echocardiographic signs of cardiac tamponade such as right atrial collapse, right ventricular diastolic collapse, and left atrial collapse were present in only 3, 1, and 3 of these 15 patients, respectively, but all exhibited left ventricular diastolic collapse. Increasing pressure within the compartment of a loculated pericardial effusion reaching the limit of pericardial distensibility and consequent transient reversal of transmural left ventricular pressure during diastole are most likely the basis for diastolic collapse of the thick-walled ventricle in a setting of regional cardiac tamponade. CONCLUSIONS. We conclude that left ventricular diastolic collapse is a frequent sign of regional cardiac tamponade and could be a useful marker of tamponade in postoperative patients. 
Effect of diphtheria-tetanus-pertussis immunization on prolonged apnea or bradycardia in siblings of sudden infant death syndrome victims. To determine whether the incidence of apnea or bradycardia increased after the first diphtheria-tetanus-pertussis (DTP) immunization in 100 subsequent siblings of victims of sudden infant death syndrome, we examined data obtained from floppy disk recordings attached to apnea-bradycardia monitors for episodes of apnea lasting 15 seconds or longer and episodes of bradycardia lasting 10 seconds or longer. The data were divided into three periods: (1) 10 days before the first DTP immunization was received (pre-DTP period), (2) 10 days immediately after the DTP (DTP period), and (3) 10 days after the DTP period (post-DTP period). Seventeen infants had at least one episode of prolonged apnea or prolonged bradycardia either before or after the 30-day study period (eight before only, eight after only, and one before and after). None of the infants had episodes of apnea lasting 15 seconds or more or bradycardia lasting 10 seconds or more during the pre-DTP or DTP period. One episode of apnea, 16 seconds long, and one episode of bradycardia lasting 11 seconds occurred in the post-DTP period. These results failed to confirm the clinical impression that DTP immunizations are associated with an increased frequency and severity of prolonged apnea. They also place in question the utility of assessing an infant's response to a DTP immunization to determine continued risk of apnea and bradycardia before home monitoring is discontinued. 
A phase II trial of high-dose cisplatin and dacarbazine. Lack of efficacy of high-dose, cisplatin-based therapy for metastatic melanoma. Cisplatin and dacarbazine are used widely in the treatment of metastatic melanoma. To evaluate high-dose cisplatin and dacarbazine, 32 patients with metastatic melanoma were treated with cisplatin 50 mg/m2 and dacarbazine 350 mg/m2 daily for three days repeated at 28-day intervals. Their median age was 43.5 years (range, 25 to 73 years), and their median Karnofsky performance status was 80% (range, 70% to 100%). Measurable and evaluable disease sites (number of patients) included lymph nodes (22), lung (17), soft tissue (16), liver (13), bone (seven), spleen (four), adrenal gland (three), skin (three), and other sites (five). Patients received a median of two cycles of therapy (range, one to eight cycles). Thirty patients were evaluable for response. No complete responses were observed. Five patients had a partial response (17%; 95% confidence interval, 3% to 30%) for 16+, 12+, 7, 6.5, and 3 months. Responding sites of disease included lymph nodes (five of 22), lung (three of 17), and soft tissue (two of 16). Hematologic toxicity (Grade greater than or equal to 3) included neutropenia (16 of 32 patients, 30 of 90 cycles), thrombocytopenia (eight of 32 patients, 12 of 90 cycles), and anemia (five patients). Nine episodes of neutropenia and fever were seen in four patients; two had bacteremia. Nonhematologic toxicity (Grade greater than or equal to 3) included hypotension (two patients), nausea and vomiting (four), neuropathy (two), ototoxicity (four), and hypomagnesemia (nine). The low objective response rate and severe toxicity of this regimen preclude its standard use in patients with metastatic melanoma. A review of cisplatin-based therapy in metastatic melanoma suggests that there is no dose-response relationship. The use of high-dose cisplatin (greater than 100 mg/m2) in the treatment of metastatic melanoma is not recommended. 
Circulatory abnormalities and compensatory mechanisms in heart failure. Knowledge of the basic alterations of central hemodynamics in congestive heart failure has failed to explain many aspects of this important syndrome. Increasing attention has recently been paid to compensatory and adaptive mechanisms occurring after the initial insult. Thus, new insights have been gained into the pathophysiology of contraction of hypertrophied myocardium and changes of adrenergic receptors in the myocardium due to chronically increased cardiac sympathetic tone. The role of the renin-angiotensin-aldosterone system in early and advanced congestive heart failure has been further elucidated, and the role of the vasodilating atrial natriuretic peptide is undergoing further definition. New results further clarify the mechanisms leading to breathlessness and muscular fatigue in congestive heart failure, with emphasis shifting from the traditional concept of the importance of increased filling pressures to changes to the peripheral circulation and exercising muscles. Although progress has been made in understanding of the pathophysiology of congestive heart failure, many aspects are still poorly understood and await clarification. 
The eyes of child abuse victims: autopsy findings. The authors studied 77 pairs of eyes removed from children who had died of suspected child abuse. Forty-seven of the cases had retinal hemorrhages. Those showing retinal hemorrhages were younger children and had fewer other stigmata of child abuse. Hemorrhages are more likely to occur in cases where the child was shaken or swung than in those with severe direct head trauma. The authors recommend that examination of the eyes be included in the autopsies of all small children who died without an obvious cause of death. Experience in both processing and reading of ocular material is necessary for reliable results. 
Crossing failure in PTCA: mind the deflated balloon profile! An attempt to reposition an Integra PTCA balloon-on-a-wire failed although the whole stenosed segment could be crossed before inflation. After careful removal the device showed a grossly altered shape. Deflated balloon profiles, quite different from the initial shape, can determine the outcome both in dissections and in multilesion cases. 
Suprascapular nerve lesions at the spinoglenoid notch: report of three cases and review of the literature. Lesions of the suprascapular nerve can occur at the supraspinatus notch (SSN) or at the spinoglenoid notch (SGN). Electromyographic (EMG), evaluation of the infraspinatus, and especially the supraspinatus muscles distinguishes SGN from SSN lesions. Three cases of SGN lesions, which are more common than SSN lesions, are presented. 
Ifosfamide continuous infusion without mesna. A phase I trial of a 14-day cycle. Twenty patients received 27 courses of ifosfamide administered as a 24-hour continuous infusion for 14 days without Mesna. The goal of the study was to deliver a dose rate and total cumulative dose of ifosfamide that would be comparable to standard bolus or short-term infusions administered with Mesna. Dose escalations proceeded from 200 to 300, 400, 450, 500, and 550 mg/m2/d. Four patients developed transient microscopic hematuria at 400, 450, and 500 mg/m2/d. There were no instances of macroscopic hematuria. At 550 mg/m2/d, three patients experienced nonurologic toxicity; confusion (1), nausea (1), and Grade 2 leukopenia (1). The recommended dose of 500 mg/m2/d delivers a total dose of 7 g/m2 per cycle, which is comparable to that delivered in clinical practice for bolus or short-term infusion. Because few patients received multiple courses over time, the cumulative effects are indeterminate in the present trial. The frequency and predictability of hematuria are not precise, and at least daily monitoring by urine Hematest is essential, adding Mesna to the infusate in patients with persistent hematuria. The protracted infusion schedule for ifosfamide permits convenient outpatient administration without Mesna and reduces the drug cost of clinical usage of this agent by up to $890 per cycle. Clinical activity was demonstrated in a single patient, but a comparative trial of standard bolus schedules with the protracted infusion schedule will be necessary to determine if the clinical effectiveness of the drug is maintained. 
VpreB gene expression in hematopoietic malignancies: a lineage- and stage-restricted marker for B-cell precursor leukemias. We show here that analysis of VpreB gene transcription can be a specific way to identify acute leukemias of cells at very early stages of B-cell development. Northern blot analysis of RNAs from 63 leukemia samples showed that VpreB RNA was present in malignancies of precursor B cells, the expression being a feature of both common acute lymphoblastic leukemia (ALL) (CD10+) and null ALL (CD10-). It was absent from malignancies of mature B cells (surface Ig positive), from acute leukemias of the T-cell lineage and granulocyte-macrophage lineages, and from normal tonsil B and T lymphocytes. Chronic myeloid leukemia blast crises of the B-precursor-cell type expressed the VpreB gene while myeloid blast crises did not. VpreB RNA was also expressed in the neoplastic cells of one of three patients with acute undifferentiated leukemias. These data show that VpreB RNA expression is a marker of the malignant forms of precursor B cells, and that it appears at least as early as cytoplasmic CD22 and CD19 in tumors of the B-cell lineage. 
Argon laser photocoagulation for neovascular maculopathy. Five-year results from randomized clinical trials. Macular Photocoagulation Study Group. With completion of follow-up of all patients enrolled in three randomized clinical trials of argon laser photocoagulation of extrafoveal choroidal neovascular membranes secondary to senile (age-related) macular degeneration, ocular histoplasmosis, or idiopathic causes, the Macular Photocoagulation Study Group has demonstrated that laser treatment of such lesions is beneficial in preventing or delaying large losses of visual acuity for at least 5 years. In eyes with senile (age-related) macular degeneration as the underlying cause, the relative risk of losing six or more lines of visual acuity from the baseline level among untreated eyes (n = 117) compared with laser-treated eyes (n = 119) was 1.5 from 6 months through 5 years after entry (P = .001). In addition, after 5 years, untreated eyes had lost a mean of 7.1 lines of visual acuity, while laser-treated eyes had lost 5.2 lines. Recurrent neovascularization had been observed in 54% of laser-treated eyes by the end of the 5-year follow-up period. Among eyes with ocular histoplasmosis, untreated eyes (n = 130) had 3.6 times the risk of laser-treated eyes (n = 132) of losing six or more lines of visual acuity (P less than .0001). Also, untreated eyes had lost a mean of 4.4 lines of visual acuity after 5 years, compared with only 0.9 lines lost by laser-treated eyes. Among laser-treated eyes, recurrent neovascularization had been observed in 26% by 5 years after enrollment. 
Classical conditioning of ventilatory responses in humans. A classical conditioning experiment, in which an auditory stimulus was paired with a hypoxic stimulus, was carried out on 34 normal subjects assigned to two groups (experimental and control). Each subject took part in one session divided into two phases, acquisition and test. In the acquisition phase, eight hypoxic and eight auditory stimuli were paired in the experimental group and unpaired in the control group. In the test phase, which was identical for the two groups, the hypoxic stimuli were suppressed and three purely auditory stimuli were presented. Significant differences between the two groups in ventilatory response to these auditory stimuli provided evidence for conditioning. In the control group, no significant changes were elicited by the auditory stimuli, whereas a conditioned increase in total cycle duration was observed in the experimental group. The conditioned response closely resembled the first component of the hypoxic response. Analysis of the pattern of the conditioned response, along with postexperimental interviews, strongly suggests that this response was not mediated by volitional factors. 
Peritoneal adhesion formation after lysis: inhibition by polyethylene glycol 4000. Peritoneal adhesions cause much long-term postoperative morbidity. This study evaluates the efficacy of polyethylene glycol (PEG) 4000 in reducing adhesion reformation after lysis. Adhesions were induced, by abrasion, in 111 Sprague-Dawley rats at a first laparotomy. At a second operation, 10 days later, these adhesions were graded and lysed, after which the animals received one of the following solutions intraperitoneally: 5 per cent PEG 4000 (n = 21), 25 per cent PEG 4000 (n = 23), 32 per cent dextran 70 (n = 22) or isotonic saline (n = 25), or were left as an untreated control group (n = 20). When the reformed adhesions were graded after a further 10 days 5 per cent PEG 4000 was found to be the only solution that inhibited adhesion reformation. The adhesions that reformed in the other four test groups were significantly worse than when they were first graded (P less than or equal to 0.033 for all groups). Therefore 5 per cent PEG 4000 may be useful in clinical practice for the reduction of adhesion formation after lysis. 
The effect of preoperative therapy on the histologic features of Wilms' tumor. An analysis of cases from the Third National Wilms' Tumor Study. Preoperative chemotherapy is being used with increasing frequency in the US for the management of selected children with Wilms' tumor, despite relatively limited knowledge as to the effects of such therapy on tumor histologic features. The authors reviewed pathologic material from all preoperatively treated unilateral Wilms' tumors registered on the third National Wilms' Tumor Study. Preoperative therapy was associated with increased ambiguity of tumor stage. The prevalence of anaplasia in the 83 evaluable specimens was similar to, although slightly increased over, that in comparable high-stage untreated Wilms' tumors (11% versus 5% to 8%), and it appeared to retain its adverse connotations. These data also suggest that alterations of tumor character and distribution by therapy provide useful prognostic information. All 17 children whose residual viable tumor was limited to intrarenal sites at the time of resection were alive and disease-free at last follow-up. Extensive (greater than 90%) tumor necrosis, low mitotic activity, and high degrees of differentiation of residual tumor were also associated with favorable outcomes. Although careful utilization of preoperative chemotherapy can be of value in children with otherwise difficult-to-manage Wilms' tumors, the potential benefits of preoperative tumor bulk reduction must be weighed against the risk of overtreatment or undertreatment as a result of increased ambiguity of tumor stage. 
Efficacy of ampicillin versus trimethoprim-sulfamethoxazole in a mouse model of lethal enterococcal peritonitis. Lethal enterococcal peritonitis in mice was used to compare trimethoprim-sulfamethoxazole (TMP-SMX) therapy with ampicillin therapy. Peritoneal fluid showed a 10(3)-CFU decrease in enterococci with ampicillin compared with TMP-SMX. Mortality of the untreated mice was 100%, compared with 40% for ampicillin and 95% for TMP-SMX, despite adequately measured levels in serum and peritoneal fluid. 
Respiratory complications and hypoxic episodes during inhalation induction with isoflurane in children. We have studied the incidence of respiratory complications and hypoxic episodes during inhalation induction with isoflurane in 75 healthy unpremedicated children. Problems occurred less frequently when 4% isoflurane in oxygen was used from the outset than with traditional techniques using nitrous oxide and a gradually increasing inspired vapour concentration. The improved results observed with the former method may be secondary to more rapid uptake of vapour so that the second stage of anaesthesia characteristic of anaesthetic ethers is shortened considerably. 
Resection and reconstruction of the carotid bifurcation with polytetrafluoroethylene grafts; operative technique. Preliminary results in 25 procedures and indications. Although carotid endarterectomy is the standard procedure, the purpose of this paper is to describe a new surgical technique and indicate its role in the surgery of cervical cerebrovascular disease. The technique consists of resection of the pathologic carotid artery bifurcation followed by its total replacement with a bifurcated thin-wall polytetrafluoroethylene (PTFE) graft constructed by the surgeon. Prosthetic graft reconstruction of the carotid bifurcation (PGRCB) was performed in 21 patients (25 procedures) from November 1984 to May 1987. Many patients were over 70 years old. The indications for surgery were transient ischemic attacks (TIA)'s in 10 patients (high-grade stenosis), established stroke with mild deficit in 3 patients (high-grade stenosis). Eight patients (high-grade stenosis) were asymptomatic and 4 had vertebro-basilar symptoms. In 11 procedures the indications were the same as for standard carotid endarterectomy (significant stenosis and/or ulcerated plaque). In 14 cases, the procedure was justified by extensive lesions involving a long segment of the internal carotid artery (2 restenoses, 12 calcified lesions). In the perioperative period, there were no deaths and no TIA's. The 25 procedures were assessed one month postoperatively by ultrasonic imaging and venous substraction angiography. All the grafts were patent with perfect restoration of the carotid bifurcation anatomy. Systematic follow-up study was carried out in 1987. Three patients had died of non-neurologic causes and one was lost to study. The remaining 19 procedures were evaluated with an average follow-up of 19 months (range 7 to 32 months). The patients were asymptomatic and all the grafts remained patent including one stenosis (greater than 50%) at the common carotid artery anastomosis. Because recent studies have documented a much higher rate of technical defects or recurrent stenosis after carotid endarterectomy, we believe that PGRCB merits consideration, particularly in difficult endarterectomies, and in recurrent carotid stenosis. Furthermore it seems acceptable to advocate PGRCB in aneurysms of the internal carotid artery and in post-irradiation arteritis. 
Effects of antiarrhythmic drugs on canine atrial flutter due to reentry: role of prolongation of refractory period and depression of conduction to excitable gap. Antiarrhythmic drugs prolong the effective refractory period and depress conduction. To determine the exact role played by these two electrophysiologic effects in the termination of reentry, the effects of disopyramide, flecainide, propafenone and E-4031, a new class III drug, were examined in a canine model of atrial flutter (cycle length 120 +/- 4 to 131 +/- 3 ms) caused by reentry. Atrial flutter was induced in 32 anesthetized open chest dogs after placement of an intercaval crush. The excitable gap ranged from 9 +/- 2% to 11 +/- 4% of the basic flutter cycle length. The effective refractory period in the reentrant circuit during atrial flutter was estimated by subtracting the excitable gap from the basic flutter cycle length. Prolongation of flutter cycle length by the test drugs was proportional to the interatrial conduction time (r = 0.87, p less than 0.001). Atrial flutter was terminated by each test drug in all dogs except for flecainide and propafenone in one dog each. E-4031 prolonged the refractory period during atrial flutter to 129 +/- 6 ms, which did not differ significantly from the flutter cycle length immediately before termination (134 +/- 4 ms). The refractory period during atrial flutter after injection of the other drugs was shorter than the flutter cycle length before termination of atrial flutter (for example, flecainide 126 +/- 5 vs. 179 +/- 11 ms, p less than 0.01). 
Phantom-related phenomena after rectal amputation: prevalence and clinical characteristics. Phantom sensations are well known and almost inevitable sequels to limb amputation, whereas similar phenomena are only rarely described after rectum amputation (phantom rectum). Our study attempted to assess the frequency and character of phantom rectum. All surviving patients (n = 22), who had undergone abdominoperineal surgical resection of the rectum in the period 1980-1986 at our clinic, were interviewed by a standard questionnaire and underwent a physical examination. Sixty-eight per cent of the patients experienced a sensation of a missing rectum (phantom rectum), and in 27% of these or 18% of all patients this sensation was painful (phantom pain). The most common symptoms were sensations of flatus and/or faeces in a normal rectum, phantom flatus or phantom faeces. The phantom pains were described as either pricking and shooting or like haemorrhoids or hard stools that would rupture the rectum. Neither age, sex, preoperative pain, the Duke classification of the tumour nor the healing of the perineal wound seemed related to the likelihood of phantom rectum. The pathophysiological mechanisms underlying phantom-related phenomena following amputation have not yet been elucidated. This study describes a relatively unknown phantom-related clinical entity after amputation and may thus contribute to the understanding of this phenomenon. 
Induction of apoptosis during normal and neoplastic B-cell development in the bursa of Fabricius. The lymphoid cells of embryonic bursal follicles are engaged in rapid growth and preimmune diversification of immunoglobulin genes. Disruption of follicular architecture by mechanical dispersion of these cells in short-term tissue culture was accompanied by continued cell division and extensive cell death by apoptosis. Apoptosis was suppressed in parallel cultures of intact follicles. gamma Radiation also triggered extensive apoptosis in embryonic bursal follicles within a few hours. Preneoplastic bursal stem cell populations induced by a v-myc oncogene were hypersensitive to induction of apoptosis by follicular dispersion and radiation. In contrast, tumor progression in v-myc- and v-rel-initiated bursal neoplasms was accompanied by development of resistance to induction of apoptosis. A programmed cell death pathway can be activated during normal B-cell development in the bursa, and alterations in the expression of this pathway accompany neoplastic change in this system. 
Operations for Wolff-Parkinson-White syndrome. Forty-six patients with symptomatic tachycardia underwent operations to divide 55 atrioventricular accessory pathways. Mean age was 29 years (range 11 to 63). Ten patients (22%) had associated cardiac disease, including two with a congenital diverticulum of the coronary sinus and six (13%) who had concomitant surgical procedures. A bipolar hand-held electrode was used in 22 operations, and simultaneous multisite mapping in the last 24 operations. Ten patients (22%) had multiple accessory pathways. A modified endocardial approach was used. The overall patient success rate was 93% with 91% to 93% of accessory pathways successfully divided. The perioperative morbidity was 17%. There were two reoperations. There were no early or late deaths. Patients have been followed up for a mean of 16 months. There were five recurrences of preexcitation (two early, three late). Two of these patients (both with a congenital diverticulum of the coronary sinus) had reoperation. One patient had late recurrence of atrial fibrillation. Operation for the Wolff-Parkinson-White syndrome has a high probability of success with a low operative risk. 
Chronic perineal pain related to sacral meningeal cysts. Chronic perineal pain is an often encountered problem that is difficult to evaluate. Based on a series of 17 patients in whom urological, gynecological, and anorectal pathology was excluded, the authors compared magnetic resonance imaging (MRI) with computed tomographic (CT) scan with myelography in the investigation of chronic perineal pain. After a clinical neurological examination, patients underwent radiodiagnostic imaging of both techniques. Thirteen patients (76%) had one or more sacral meningeal cysts (MC) on MRI scan, whereas CT scan with myelography of the lumbar and sacral region revealed 7 patients (41%) with sacral MC. Sacral MC may be the etiology of chronic perineal pain in many instances, and MRI scan appears to be superior to CT scan with myelography in demonstrating sacral MC. Ten patients with sacral MC were operated on with moderate to excellent results 6 months after operation. Early postoperative results are encouraging, but further follow-up and larger series are required. 
Epidural sufentanil for postoperative analgesia: dose-response in patients recovering from major gynecologic surgery. To determine the lowest effective dose of epidural sufentanil given for analgesia, 41 patients undergoing elective abdominal gynecologic surgery during continuous epidural anesthesia (lidocaine 2%) were randomly assigned to one of four postoperative treatment groups. Patients received an epidural bolus of either 25 (group A), 40 (group B), 55 (group C), or 70 micrograms (group D) sufentanil in 10 mL of saline. They were evaluated for the next 8 h using a 10-cm visual analogue scale. Except for two individuals in group A, all patients achieved a visual analogue scale score of 1 cm or less during the study interval. The onset of analgesia was most rapid in the two higher dose groups (A vs C and D; P less than 0.05). Pairwise comparison between groups showed a significant difference in the time needed to achieve maximum pain relief between the lowest and highest treatment groups (A vs D; P less than 0.05). Duration of analgesia was also significantly longer in groups C and D than in group A (208.0 +/- 21.1 and 224.0 +/- 14.7 vs 140.0 +/- 10.7 min; P less than 0.05). There were no differences among groups with regard to mean respiratory rate, level of sedation, 24-h narcotic requirements, or incidence of nausea, vomiting, and pruritus (P = NS). A single patient in group D suffered profound respiratory depression within seconds of administration. We conclude that, in patients recovering from lower abdominal surgery, a single 40-55-micrograms epidural bolus of sufentanil provides 3-3.5 h of effective analgesia, and that larger doses are not warranted. 
Venous thromboembolism after brain tumor surgery: a retrospective review. We retrospectively reviewed the incidence rate of clinical postoperative deep vein thrombosis and/or pulmonary embolism in 1703 patients undergoing initial craniotomy for meningioma, glioma, or cerebral metastasis. The incidence rate of clinical thromboembolic complications was 1.59% for all tumor groups within the first 4 weeks of surgery. Patients undergoing surgery for meningiomas had a statistically significant increased risk of thromboembolism despite fewer overall perioperative risk factors, when compared with the other tumor groups. The tumor-specific incidence rates of deep vein thrombosis and/or pulmonary embolism for meningioma, glioma, and metastasis were 3.09%, 0.97%, and 1.03%, respectively. Whether this difference was a result of increased surgical time or an inherent property of meningiomas could not be ascertained. 
Tethered cord syndrome complicating spina bifida occulta. A case report. The insidious onset of back and/or leg pain, weakness and spasticity of the lower limb, sensory deficits and neurogenic bladder and bowel in a child with spina bifida might represent a tethered cord syndrome. A case report of a child with sudden neurologic deterioration describes this condition. The successful management in children and adults with tethered cord syndrome is improved with early recognition and careful monitoring. 
Diagnosis and cure of the Wolff-Parkinson-White syndrome or paroxysmal supraventricular tachycardias during a single electrophysiologic test BACKGROUND. We conducted this study to determine the feasibility of an abbreviated therapeutic approach to the Wolff-Parkinson-White syndrome or paroxysmal supraventricular tachycardia, in which the diagnosis is established and radiofrequency ablation carried out during a single electrophysiologic test. METHODS. One hundred six consecutive patients were referred for the management of documented, symptomatic paroxysmal supraventricular tachycardias (66 patients) or the Wolff-Parkinson-White syndrome (40 patients). All agreed to undergo a diagnostic electrophysiologic test and catheter ablation with radiofrequency current. No patient had had such a test previously. RESULTS. Among the 66 patients with paroxysmal supraventricular tachycardias, the mechanism was found to be atrioventricular nodal reentry in 46 (70 percent) (typical in 44 and atypical in 2), atrioventricular reciprocating tachycardia involving a concealed accessory pathway in 16 (24 percent), atrial tachycardia in 2 (3 percent), and noninducible paroxysmal supraventricular tachycardia in 2 (3 percent). A successful long-term outcome was achieved in 57 of 62 patients (92 percent) with paroxysmal supraventricular tachycardia in whom ablation was attempted and in 37 of 40 patients (93 percent) with the Wolff-Parkinson-White syndrome. The only complications were one instance of occlusion of the left circumflex coronary artery, leading to acute myocardial infarction, and one instance of complete atrioventricular block. The mean (+/- SD) duration of the electrophysiologic procedures was 114 +/- 55 minutes. CONCLUSIONS. The diagnosis and cure of paroxysmal supraventricular tachycardia or the Wolff-Parkinson-White syndrome during a single electrophysiologic test are feasible and practical and have a favorable risk-benefit ratio. This abbreviated therapeutic approach may eliminate the need for serial electropharmacologic testing, long-term drug therapy, antitachycardia pacemakers, and surgical ablation. 
Initial 5-fluorouracil trabeculectomy in uncomplicated glaucoma. The effectiveness of trabeculectomy with adjunctive low-dose 5-fluorouracil (5-FU) as the initial surgical procedure in uncomplicated glaucoma was evaluated retrospectively in a consecutive series of 52 patients (mean follow-up, 18.6 +/- 11.7 mos) and 74 control subjects. The cumulative 2-year success (intraocular pressure [IOP] less than 21 mmHg) was 100% in the 5-FU group and 78.9% in the control group (P = 0.01, Wilcoxon test). The 5-FU group had a mean postoperative IOP of 12.5 +/- 4.6 mmHg versus 17.4 +/- 5.7 mmHg in the control group at 2-year follow-up (P = 0.015, t test). Antiglaucoma medications were required in 5.8% of patients in the 5-FU group and in 41.9% of controls within 2 years (P less than 0.0001, Fisher's exact test). These results suggest that low-dose 5-FU at the time of initial trabeculectomy leads to a higher success rate, lower IOP, and less need for antiglaucoma medications postoperatively. 
Importance of the immune response to the Ro/La particle in the development of congenital heart block and neonatal lupus erythematosus. Previous studies have suggested a role for anti-Ro antibodies in the pathogenesis of neonatal lupus erythematosus (NLE). We reexamined the role of the immune response to the Ro/La particle in the development of NLE using newer and more definitive assay techniques. All 15 infants with congenital heart block and NLE had both anti-Ro and anti-La antibodies. Of 8 patients with cutaneous NLE alone, 2 had anti-Ro antibodies alone while the remaining 6 had both anti-Ro and anti-La antibodies. One woman gave birth to 2 children; one had both Ro and La antibodies and developed congenital heart block, the other had only anti-Ro and anti-U1RNP antibodies and was clinically normal. Our study demonstrates that the presence of anti-Ro and anti-La antibodies define the immune response that is associated with the development of congenital heart block of NLE. 
Effects of nonionic versus ionic contrast media on complications of percutaneous transluminal coronary angioplasty. To evaluate the effect of contrast agents on percutaneous transluminal coronary angioplasty (PTCA) complications, 913 patients undergoing 1,058 separate PTCA procedures were prospectively randomized to receive either nonionic iopamidol (Isovue-370) [n = 507 PTCA procedures] or ionic contrast media, meglumine sodium diatrizoate (Renografin-76) [n = 551 PTCA procedures]. Angioplasty operators, technicians, nurses and patients were blinded to the agent used. All patients were pretreated with 0.6 mg of atropine sulfate intravenously before any contrast injections. Hypotension (mean arterial pressure less than 65 mm Hg associated with contrast injections) occurred during 8.5% of PTCA procedures in which the patients were receiving iopamidol and during 9.5% of the procedures in which the patients were given diatrizoate (difference not significant). Bradycardia (heart rate of less than 40 beats/min associated with contrast injections) developed during 5.7% of procedures when patients were given iopamidol and during 5.1% of procedures when patients were given diatrizoate (difference not significant). The need for additional atropine or temporary pacing during the procedure was similar for patients given iopamidol and diatrizoate. The overall incidence of ventricular tachycardia or fibrillation, or both, during the procedure occurred less frequently when iopamidol was used compared with diatrizoate (1 vs 2.5%, p = 0.045). These serious ventricular arrhythmias were attributable to contrast injections in 0.6% of the PTCA procedures when iopamidol was given and in 2.0% of the cases in which diatrizoate was the contrast agent (p = 0.09). Only 1 patient had an allergic reaction to the contrast agent, and this was in a patient who received iopamidol. 
Efficacy and safety of intravenous and oral propafenone in pediatric cardiac dysrhythmias. Propafenone was administered to 58 patients with a mean age of 3.2 years (range 0.1 to 16). Mean intravenous dose was 1.2 mg/kg body weight (range 0.3 to 1.5 mg). The final mean oral maintenance dose was 308 mg/m2 body surface area (range 200 to 600 mg/m2, 16.8 mg/kg body weight). After intravenous application, propafenone was effective in 21 of 36 patients; atrial flutter was converted in 1 of 5 patients, and reentry supraventricular tachycardia was controlled in 15 of 25 patients. Propafenone was partially or completely effective in 3 of 4 patients with chaotic atrial tachycardia. Junctional ectopic tachycardia was suppressed in 2 infants. Thirty-seven patients had oral treatment with a mean follow-up of 2.2 years. Propafenone was effective in 33 of 37 patients (89%); atrial flutter was controlled in 2 patients, ventricular ectopy was suppressed in 1 of 2 patients. In reentry supraventricular tachycardia, propafenone was effective in 25 of 28 patients. Chaotic atrial tachycardia (n = 3) and junctional ectopic tachycardia (n = 2) were controlled after successful intravenous therapy. Systemic side effects were rare. Two patients developed a proarrhythmic effect, and 1 patient with ventricular ectopy after repair of tetralogy of Fallot died suddenly during propafenone maintenance therapy. 
Serum ferritin: a tumor marker for renal cell carcinoma. Serum ferritin levels in 32 patients with renal cell carcinoma were evaluated preoperatively and postoperatively. Serum ferritin concentration was significantly higher in renal cell carcinoma patients compared to controls (259.10 versus 61.30 ng./ml., p less than 0.001). Furthermore, there was a steady and statistically significant increase in serum ferritin levels with advancing disease stage, as well as a significant decrease in serum ferritin levels after nephrectomy for stages 1 and 2 disease. The intracellular content of ferritin as estimated by polyclonal antibody was dramatically increased in renal cancer tissue compared to normal parenchyma. Although serum ferritin regulation is complex and only partly understood, the present study suggests that serum ferritin may be a useful tumor marker for renal cell carcinoma. 
Post-traumatic syringomyelia following uncomplicated spinal fracture. Two cases of post-traumatic syringomyelia presenting 10 and 41 years after spinal injuries that had caused lumbar vertebral fractures but no lasting neurological deficits are reported. In both patients the caudal end of the syrinx cavities, as shown by MRI, corresponded to the level of the previous vertebral fractures. Patients presenting with post-traumatic syringomyelia after uncomplicated spinal fracture are very rare, and the significance of the past history of spinal trauma may be overlooked. 
Clonorchis-associated cholangiocarcinoma: a report of two cases with unusual manifestations. Two cases of Clonorchis-associated cholangiocarcinoma are described along with their cholangiographic features to illustrate the spectrum of pathology ascribed to the injurious effects of the flukes on the bile duct epithelium. This includes adenomatous hyperplasia, extensive fibrosis, and carcinoma. The first case was also complicated by hepatic abscesses, left hepatic lobar atrophy, gastrobiliary and biliarocutaneous fistulae. The second case features an unusually dilated pancreatic duct containing pancreaticoliths that was found later to consist of hyperplastic bile duct epithelium, presumably carried by worm migration in the biliary tree. Liver sections from both patients showed typical features of hepatic clonorchiasis with the cancer. A knowledge of the wide spectrum of clinical presentation of clonorchiasis, particularly cholangiocarcinoma, might aid Western physicians in averting this serious sequela through prompt eradication of the helminthic infection and early recognition and treatment of its complications. 
Comparison of human pain sensation and flexion withdrawal evoked by noxious radiant heat. The purpose of this study was to determine the reliability of flexion withdrawal magnitude as an indicator of pain sensation. In 10 healthy human volunteers, we compared the magnitude and latency of integrated biceps EMG with the subjects' rating of pain, using a visual analog scale, elicited by noxious radiant heat stimuli applied to the dorsal forearm. The magnitude and inverse latency of withdrawal, although variable, increased exponentially as a functions of stimulus temperature. The stimulus response functions for mean withdrawal magnitude and mean pain intensity were similar for lower stimulus temperatures, but at higher temperatures the withdrawal continued to increase exponentially whereas pain intensity reached a plateau. The pain intensity and withdrawal magnitude for each stimulus were poorly correlated. Under the conditions of this experiment, mean pain intensity and mean withdrawal magnitude were both well correlated with stimulus temperature, but the magnitude of withdrawal did not reliably reflect the intensity of pain sensation. 
Neuronal activity up-regulates astroglial gene expression. Neuronal gene expression is known to be modulated by functional activity. This modulation is thought to play a key role in determining the differentiation of developing neurons and regulating the operation of mature neurons. Here we describe a regulation of astroglial gene expression by neuronal activity. We report that intense neuronal activity (electrically induced seizures) in rat hippocampus leads to rapid and dramatic increases in mRNA for glial fibrillary acidic protein (GFAP), an astroglia-specific intermediate filament protein. GFAP mRNA levels increased at sites of stimulation as well as in areas that were synaptically activated by the resultant seizures. When seizures were induced repetitively for many days, levels of GFAP mRNA remained chronically elevated. However, GFAP mRNA returned to control levels within a few days after the cessation of stimulation. The coupling between astroglial gene expression and neuronal activity may be a mechanism through which neuronal activity modulates the function of supporting cells that are responsible for regulating the extracellular microenvironment of the brain. 
Hazards of mattresses, beds and bedding in deaths of infants. Of 52 infants who had died suddenly and were referred to autopsy, nine had lain on adult water beds for the first time; five had died as a result of accidents; two had died on water beds; two were in beds with widely spaced slats; and one had died as a result of strangulation. Three deaths were due to overlying. Three other infants had been placed on sheepskin rugs for the first time and were found dead shortly thereafter. These infants ranged in age from 2 to 9 months, except for a severely mentally retarded nine-year-old with spastic paraplegia. We believe that a general warning should be issued concerning water beds and that soft bedding should not be used for infants. Infants should not be placed unattended or left to sleep on water beds; only beds recommended for infants should be used. Overlying of a young infant is most likely to occur on a water bed, or if the parent is obese or has consumed alcohol. 
Intraperitoneal thrombolytic agents in relapsing or persistent peritonitis of patients on continuous ambulatory peritoneal dialysis. Urokinase or streptokinase was instilled intraperitoneally as an adjunct to the antibiotic therapy in 16 episodes of relapsing or persistent peritonitis in CAPD patients. In eight patients the combination of antibiotics and intraperitoneal thrombolytic agents resulted in clearing of the infection with no recurrences. The treatment failed in eight other patients, who had their peritoneal catheters removed. Six of the last eight patients had either abdominal wall abscesses or persistence of the bacteria on the wall of the peritoneal catheter. Elevated post-intraperitoneal instillation peritoneal fluid neutrophil counts and positive post-instillation peritoneal fluid cultures predicted failure of the intraperitoneal instillation of thrombolytic agents in most instances. Intraperitoneal instillation of urokinase or streptokinase may help cure approximately 50% of the episodes of relapsing for persistent peritonitis. Post-instillation peritoneal fluid cell counts and cultures should be monitored. Radiologic investigation for abdominal wall or intraabdominal abscesses is indicated if intraperitoneal instillation of urokinase or streptokinase fails to eradicate peritonitis. 
Hyperbaric treatment of cerebral air embolism sustained during an open-heart surgical procedure A case of cerebral air embolism sustained during replacement of the mitral valve resulted in postoperative coma and seizures. Hyperbaric treatment, begun 30 hours after the occurrence of the air embolism, resulted in good immediate and long-term recovery. Mild deficits of the left hemisphere were present at follow-up 53 days after the embolus was sustained, and lesser, minimal residua were present at 14-month follow-up. Hyperbaric treatment is the definitive therapy for cerebral air embolism. Although it is most effective when administered early, the outcome may be excellent even with late treatment. 
Hepatocellular carcinoma in Richardson's ground squirrels (Spermophilus richardsonii): evidence for association with hepatitis B-like virus infection. During studies of seasonal obesity, a high frequency of hepatic neoplasms was observed in Richardson's ground squirrels. Of 12 Richardson's ground squirrels examined thoroughly, 7 had mild or moderate degrees of chronic portal hepatitis and 6 (50%) had hepatocellular carcinoma. Serological tests for hepadnavirus surface antigen, anti-core antibody and virion DNA that recognize the ground squirrel hepatitis virus of California ground squirrels (Spermophilus beecheyi) were uniformly negative. Southern blot analyses of EcoRI digests of liver cell DNA demonstrated 3.2 kb fragments that hybridized with a ground squirrel hepatitis virus-specific probe in nontumorous liver tissue from 6 of 10 ground squirrels and in hepatocellular carcinoma specimens from 2 of 5 squirrels indicating infection with a hepadnavirus related to ground squirrel hepatitis virus. Failure, however, to detect serum antibody to ground squirrel hepatitis core antigen suggested probable antigenic differences between the ground squirrel hepatitis virus of California ground squirrels and the putative Richardson's ground squirrel agent. Further studies are required to fully characterize the hepadnavirus of Richardson's ground squirrels and to determine its relationship to hepatocarcinogenesis in this species. 
Adenovirus E1a prevents the retinoblastoma gene product from complexing with a cellular transcription factor. The transforming proteins of several DNA tumour viruses, including adenovirus E1a and simian virus 40 large T antigen, complex with the retinoblastoma (Rb) tumour-suppressor gene product. This requires regions in these viral proteins necessary for transformation and is thought to inactivate the growth-suppressing properties of the Rb protein by disrupting its interaction with cellular targets. Indeed, regions of Rb required to form a complex with E1a and large T antigen are often mutated in transformed cells. The level at which the Rb protein regulates proliferation is unknown, although one possibility is transcription. We have previously characterized a sequence-specific transcription factor, DRTF1, the activity of which is downregulated as embryonal carcinoma stem cells differentiate. DRTF1 is found in several discrete protein complexes (a, b and c) which are of different sizes but have the same DNA specificity. We now show that one of these also contains the Rb protein and, further, that the adenovirus E1a protein causes the dissociation of the Rb protein from this complex. This requires conserved regions 1 and 2 of E1a that are known to be required for efficient transformation. These results demonstrate that the Rb protein forms a complex with a DNA-bound transcription factor, and suggests that the Rb protein might act by regulating transcription. 
Enhanced immunoglobulin levels correlate with infectious complications after surgery in esophageal cancer. Severe septic complications account for the high mortality of patients with esophageal cancer. We examined the levels of immunoglobulins and complements together with infection-related complications in a large number of patients. Enhancements of IgG, IgA, C3, C4, and CH50 were evident in patients with esophageal cancer and were more predominant compared to findings in cases of gastric cancer. Average levels of IgG and IgA immediately before surgery were significantly higher in esophageal cancer patients with postoperative septic complications than in those without such problems. Preoperative radiation therapy and total parenteral nutrition did not significantly alter the levels of immunoglobulins and complements. It would thus appear that the enhancement of IgG and IgA is associated with the occurrence of infectious complications following surgery for patients with esophageal cancer. 
Evaluating painful osteopenia in the elderly. Osteopenia is a frequent finding on radiographs of elderly patients. When the exam is performed for skeletal pain, this finding may be significant. The differential diagnosis for osteopenia is extensive, but individualizing the patient work-up begins with a careful clinical history and laboratory studies. Appropriate radiographic exams can then be requested. A plain radiograph is always the starting point, followed by--as indicated--a nuclear bone scan, computed tomography, and magnetic resonance imaging. 
Cerebrovascular malformation causing sudden death. Analysis of three cases and review of the literature. Three unusual cases of sudden death resulting from cerebrovascular malformation (CVM) are presented. CVMs are highly variable in location and morphology, and may be difficult to detect. Two of the patients discussed here had CVMs that involved the circle of Willis directly, and produced rapidly fatal subarachnoid hemorrhage at the base of the brain; both of these subjects were in their late 30s. One had a history of epilepsy; the other had been completely asymptomatic prior to the catastrophic event. The third was an asymptomatic 6 year old with a cerebellar CVM, who survived long enough for inconclusive neurosurgical intervention. In all three cases, the diagnosis was not made prior to autopsy; in one case, the circumstances of death were initially misleading. The relevant literature is reviewed and discussed, with emphasis on differential diagnosis, anatomic examination, and background investigation. 
Exercise testing in patients with microvascular angina. The widespread use of exercise testing for the detection of myocardial ischemia in patients suspected of having coronary artery disease led to the detection of ischemic changes in many subjects who subsequently were found to have angiographically normal epicardial vessels--the false positive response. Such a result is usually interpreted as indicating that the subject's chest pain is of noncardiac origin. For the past several years, we have studied the mechanism of pain resembling angina that occurs in patients with normal epicardial coronary arteries demonstrated by angiography; we believe these studies have shed some light on this problem. Patients with angiographically normal coronary arteries who present because of a history of angina-like pain and/or ischemic changes detected during exercise electrocardiogram testing were evaluated by measuring great cardiac vein flow (under baseline conditions and after cardiac pacing, with and without intravenous administration of ergonovine) and by radionuclide angiography before and during exercise. We found that a substantial number of these subjects showed inadequate coronary vasodilator reserve and had exercise-induced left ventricular dysfunction suggestive of myocardial ischemia. We concluded from our results that there is a distinct clinical syndrome of myocardial ischemia caused by abnormal resistance responses of the prearteriolar coronary microvasculature. We now refer to this syndrome as microvascular angina. In a series of 115 patients with documented microvascular angina, we also found that only 10% had ischemic ST changes with exercise testing (2% of the men and 17% of the women developed ischemic ST segment changes). 
Breast cancer with bone-only metastases. Visceral metastases-free rate in relation to anatomic distribution of bone metastases. The medical records of 82 patients with breast cancer with bone-only metastases were reviewed. According to the distribution of the metastases by bone scan at the time they were first documented, the patients were divided into three groups: Group A (patients who had bone metastases exclusively cranial to the lumbosacral junction), Group B (patients who had bone metastases exclusively caudal to the junction), and Group C (patients who had bone metastases both cranial and caudal to the junction). Group A had a significantly higher visceral metastases-free rate than Groups B or C. Serial bone scans and radiographs of Group A patients revealed that bone lesions cranial to the junction rarely developed into visceral metastases and that bone lesions extending caudal to the junction frequently developed into visceral metastases. These results indicate that the presence of bone metastases caudal to the lumbosacral junction is predictive of visceral metastases. 
Effects of volatile anesthetics on response to norepinephrine and acetylcholine in guinea pig atria. The in vitro chronotropic and inotropic effects of norepinephrine and acetylcholine in isolated right and left guinea pig atria were examined in the absence and presence of halothane, isoflurane, and enflurane (0.6 and 1.2 MAC). All three anesthetics elicited dose-dependent reductions in contractile force and spontaneous pacemaker activity. The maximal developed tension observed in the presence of norepinephrine was not altered by the anesthetics and corresponding ED50 values increased only in the presence of 1.2 MAC halothane and 1.2 MAC isoflurane. The anesthetics did not affect (a) the maximal positive chronotropic effect of norepinephrine, (b) the ED50 values for its positive chronotropic effect, and (c) acetylcholine-induced negative inotropic and chronotropic actions and did not induce arrhythmic activity even in the presence of the maximally effective neurotransmitter concentrations. These findings indicate that in isolated guinea pig atria volatile anesthetics, in concentrations up to 1.2 MAC, do not alter the inotropic and chronotropic effects of norepinephrine or acetylcholine and do not induce arrhythmogenic action in the presence of the neurotransmitters. These data suggest that altered atrial responsiveness to adrenergic or muscarinic stimulation does not contribute to the development of anesthetic-induced cardiac arrhythmias. 
Stress-induced gastroduodenal lesions and total parenteral nutrition in critically ill patients: frequency, complications, and the value of prophylactic treatment. A prospective, randomized study. OBJECTIVE: To assess the frequency, complications, and value of prophylactic treatment of stress-induced gastroduodenal lesions. DESIGNS: Patients were prospectively randomized to treatment with total parenteral nutrition, either alone, with sucralfate, or with ranitidine. SETTING: A multidisciplinary ICU from a tertiary care referral center. PATIENTS: Ninety-seven patients submitted to prolonged mechanical ventilation, with normal hepatic and renal function, in metabolic stress, and receiving total parenteral nutrition. INTERVENTIONS: On admission, we determined the Acute Physiology and Chronic Health Evaluation II score and the catabolic index score. We also performed an endoscopic examination on day 3, every 7 days subsequently, and whenever needed. Thirty patients received total parenteral nutrition alone. Twenty-four patients received total parenteral nutrition and sucralfate (1 g by nasogastric tube every 4 hrs). Nineteen patients received total parenteral nutrition and ranitidine (50 mg iv every 6 hrs). MAIN RESULTS: The overall occurrence rate of gastroduodenal mucosal damage was 29.6%. The overall frequency rate for stress ulcerations was 15.6% and was 6.2% for stress hemorrhage. There were no deaths secondary to stress hemorrhage. The difference in the frequency of stress-induced mucosal lesions and stress hemorrhage between the studied groups was not statistically significant. CONCLUSIONS: Additional prophylaxis to total parenteral nutrition in the form of sucralfate and ranitidine to prevent acute upper gastrointestinal bleeding is not required in this group of ICU patients. 
Polyethylene wear from retrieved acetabular cups. Laboratory wear testing of ultra high molecular weight polyethylene from 12 Charnley acetabular cups, removed after periods of up to 17.5 years showed that the large patient-to-patient variations in clinical penetration rate cannot be explained by batch-to-batch variation in the wear resistance of the material. Nor was there any evidence of a time-dependent degradation in wear resistance of the material. 
The effects on plasma lipoproteins of a prudent weight-reducing diet, with or without exercise, in overweight men and women. BACKGROUND. The National Cholesterol Education Program (NCEP) recommends a low-saturated-fat, low-cholesterol diet, with weight loss if indicated, to correct elevated plasma cholesterol levels. Weight loss accomplished by simple caloric restriction or increased exercise typically increases the level of high-density lipoprotein (HDL) cholesterol. Little is known about the effects on plasma lipoproteins of a hypocaloric NCEP diet with or without exercise in overweight people. METHODS. We tested the hypothesis that exercise (walking or jogging) will increase HDL cholesterol levels in moderately overweight, sedentary people who adopt a hypocaloric NCEP diet. We randomly assigned 132 men and 132 women 25 to 49 years old to one of three groups: control, hypocaloric NCEP diet, or hypocaloric NCEP diet with exercise. One hundred nineteen of the men and 112 of the women returned for testing after one year. RESULTS. After one year, the subjects in both intervention groups had reached or closely approached NCEP Step 1 dietary goals and reduced their mean body fat significantly (range of reduction in mean fat weight, 4.0 to 7.8 kg). Weight loss on the NCEP diet alone did not significantly change HDL cholesterol levels in either the men or the women as compared with the subjects in the control group. Plasma levels of HDL cholesterol increased significantly more in the men who exercised and dieted (mean [+/- SE] change, +13 +/- 3 percent) than in the men who only dieted (+2 +/- 3 percent, P less than 0.01) or the men who acted as controls (-4 +/- 2 percent, P less than 0.001). HDL cholesterol levels remained about the same in the women who exercised and dieted (+1 +/- 2 percent); they were higher than in the women who only dieted (-10 +/- 3 percent, P less than 0.01), but not higher than in the controls (-3 +/- 3 percent). CONCLUSIONS. Regular exercise in overweight men and women enhances the improvement in plasma lipoprotein levels that results from the adoption of a low-saturated-fat, low-cholesterol diet. 
Subperiosteal abscess in children: scintigraphic appearance. A subperiosteal abscess is an uncommon complication of osteomyelitis in childhood. Bone scanning is very sensitive for the detection of early skeletal infection; however, a subperiosteal abscess has a different and distinctive scintigraphic appearance. The usual increased tracer uptake of osteomyelitis is overshadowed by the presence of a "cold" lesion on the delayed views, probably due to interruption of the vascular supply of the bone. Early recognition of the condition is important, as surgery is indicated to prevent extensive bone necrosis and chronic osteomyelitis. In suspected osteomyelitis, a central photopenic area is highly suggestive of subperiosteal abscess; when such an area is seen, a computed tomographic (CT) scan can be helpful in planning the surgical approach for drainage. Plain radiographs may be unremarkable even when the bone scan and CT findings are dramatic. Five such cases are presented, and a recommended diagnostic approach is discussed that views the two procedures as complementary. 
The management of IIB osteosarcoma. Experience from 1976 to 1985. From 1976 to 1985, 75 IIB osteosarcomas have been treated out of a total of 98 osteosarcomas at the authors' institution. Because of the effective chemotherapy including high-dose methotrexate administered during this time period, the surgical management changed, and only ten patients out of the 75 IIB osteosarcomas required an amputation. The overall result of 76.7% of disease-free, three-year survival was equally distributed regardless of the surgical procedure. Endoprosthesis, resection with or without grafts, and rotationplasties, as well as amputations, revealed similar results. No negative influence from the limb-sparing surgery could be observed. 
Salivary secretion rate, yeast cells, and oral candidiasis in patients with acute leukemia. Stimulated salivary secretion rate was repeatedly determined in 29 patients with acute leukemia during two periods of cytotoxic treatment in myelosuppressive doses. For comparison, the salivary secretion rate was studied in 83 healthy persons and in three other groups of hospitalized patients without malignant disorders. At the start of cytotoxic treatment the secretion rate in the patients with leukemia was lower than in healthy persons. The rate fell significantly after 1 to 3 days and later rose to the level seen in the healthy persons. Several interacting factors may have contributed to the decrease in salivary secretion rate, but the most important factor was probably the use of antiemetic drugs during the first 3 days of the study periods. No relationship was found between salivary secretion rate and the number of gram-negative rods found in the mouth. Patients with low salivary secretion rates had high numbers of yeast cells and more often oral candidiasis. 
CSF monoamine metabolites, cholinesterases and lactate in the adult hydrocephalus syndrome (normal pressure hydrocephalus) related to CSF hydrodynamic parameters. Monoamine metabolites, cholinesterases and lactic acid in lumbar cerebrospinal fluid (CSF) were investigated on patients with the adult hydrocephalus syndrome (idiopathic normal pressure syndrome; AHS, n = 15), Alzheimer's disease (AD, n = 14), multi-infarct dementia (MID, n = 13) and controls (n = 21). Patients had clinical and CSF hydrodynamic investigations. Monoamine concentrations were determined by reversed-phase liquid chromatography, cholinesterases and lactate were determined photometrically. In the AHS patients, CSF monoamine concentrations were not significantly different compared with controls, AD or MID patients. AHS and AD patients showed a similar reduction of CSF acetylcholinesterase activity compared with controls. Positive correlations were found in concentrations of CSF homovanillic acid, CSF 5-hydroxyindoleacetic acid and CSF lactic acid versus CSF outflow conductance (that is, resistance against CSF outflow) in the AHS patients. A similar pattern was observed in a subgroup of MID patients characterised by dilated ventricles and disturbed CSF hydrodynamics. These data suggest that a low CSF outflow conductance may facilitate the clearance of acidic substances from the arachnoid space at the probenecid sensitive active transport site. Alternative explanations would be that a pathologically low CSF outflow conductance is accompanied by an inverse caudorostral flow of CSF or a compromised trans-ependymal diffusion. 
A prospective comparison of laser therapy and intubation in endoscopic palliation for malignant dysphagia. There is little objective long-term follow-up comparing laser therapy with intubation for palliation of malignant dysphagia. In a prospective, nonrandomized two-center trial 43 patients treated with the neodymium:yttrium-aluminum-garnet laser were compared with 30 patients treated by endoscopic intubation; the two groups were comparable for mean age and tumor position, length, and histology. Dysphagia was graded from 0 to 4 (0, normal swallowing; 4, dysphagia for liquids). Pretreatment mean dysphagia grades were similar: laser-treated group, 2.9 (SD, 0.6); intubated group, 3.2 (SD, 0.55). For thoracic esophageal tumors, the percentage of patients achieving an improvement in dysphagia grade by greater than or equal to 1 grade initially and over the long term was similar (laser, 95% and 77%; intubation, 100% and 86%). For tumors crossing the cardia, intubation was significantly better (laser, 59% and 50%; intubation, 100% and 92%, respectively; P less than 0.001). In patients palliated over a long period, however, the mean dysphagia grade over the remainder of their mean dysphagia grade over the remainder of their lives (mean survival: laser, 6.1 months; intubation, 5.1 months) was better in the laser group (1.6 vs. 2.0; P less than 0.01); 33% of laser-treated and 11% of intubated patients could eat most or all solids (P less than 0.05). For long-term palliation, laser-treated patients required on average more procedures (4.6 vs. 1.4; P less than 0.05) and days in the hospital (14 vs. 9; P less than 0.05). The perforation rate was lower in the laser-treated group (2% vs. 13%; P less than 0.02); no treatment-related deaths occurred in either group. For individual patients, the best results are likely to be achieved when the two techniques are used in a complementary fashion in specialist centers. 
Acinetobacter peritonitis in patients receiving continuous ambulatory peritoneal dialysis. Little is written on peritonitis caused by Acinetobacter species in patients receiving continuous ambulatory peritoneal dialysis (CAPD). A retrospective review of medical records, dialysis unit charts, and microbiology culture logbooks identified 18 such patients treated at our hospital. All cases were community-acquired, and no common epidemiologic link between cases was detected. The most common manifestations were abdominal pain or tenderness (13 patients) and cloudy dialysate (six patients); only two patients had fever. Peritonitis without localized intra-abdominal abscess formation occurred in all instances. Intraperitoneal aminoglycoside therapy for 3 to 14 days (mean 10.7 days) eradicated infection in 14 cases. Two patients were successfully treated with 4 days of intraperitoneal gentamicin followed by 8 days of oral ciprofloxacin; another was cured with 10 days of IV ceftriaxone. Tenckhoff catheter removal was necessary in only one patient. Unlike pseudomonal or fungal peritonitis associated with CAPD, infection due to Acinetobacter species is generally responsive to antimicrobials alone. 
The IPR inventory: development and psychometric characteristics. The purpose of this study was to develop, validate, and norm a measure of dimensions of interpersonal relationships that are salient to nursing: social support, reciprocity, and conflict. The selection of these concepts was guided by social exchange and equity theories. In the first phase of the study, 44 respondents were interviewed to provide narrative data from which to develop items so that items would be grounded in lived experience. Content validity of items was judged by a panel of 11 experts. The revised 39-item instrument was tested in successive steps with a total of 340 students, patients, and community residents for reliability and validity, including internal consistency reliability, test-retest reliability, factor analysis, and three forms of validity assessment (theory testing, contrasted groups, and multitrait-multimethod comparison). The three subscales of social support, reciprocity, and conflict demonstrated repeated internal consistency and test-retest reliability. Strong evidence of construct validity was demonstrated for the social support and the conflict subscales; validity of the reciprocity subscale was equivocal. 
Ventilatory responses to hypoxia and hypercapnia in awake rats pretreated with capsaicin. Ventilatory responses to hypoxia and hypercapnia were measured by indirect plethysmography in unanesthetized unrestrained adult rats injected neonatally with capsaicin (50 mg/kg) or vehicle. Such capsaicin treatment ablates a subpopulation of primary afferent fibers containing substance P and various other neuropeptides. Ventilation was measured while the rats breathed air, 12% O2 in N2, 8% O2 in N2, 5% CO2 in O2, or 8% CO2 in O2. Neonatal treatment with capsaicin caused marked alterations in both the magnitude and composition of the hypoxic but not hypercapnic ventilatory response. The increase in minute ventilation evoked by hypoxia in the vehicle-treated rats resulted entirely from an increase in respiratory frequency. In the capsaicin-treated rats the hypoxic ventilatory response was significantly reduced owing to an attenuation of the frequency response. Although both groups responded to hypoxia with a shortening in inspiratory and expiratory times, rats treated with capsaicin displayed less shortening of both respiratory phases. By contrast, hypercapnia induced a brisk ventilatory response in the capsaicin-treated group that was similar in magnitude and pattern to that observed in the vehicle-treated group. Analysis of the components of the hypercapnic ventilatory responses revealed no significant differences between the two groups. We, therefore, conclude that neuropeptide-containing C-fibers are essential for the tachypnic component of the ventilatory response to hypoxia but not hypercapnia. 
Late variation in ventricular function after myocardial infarction. To assess the possible role of variables not related to early infarct artery reperfusion in predicting late changes in ventricular function after infarction, paired early (mean 6.6 +/- 3.5 days after admission) and late (12.7 +/- 7.0 months later) cross-sectional echocardiograms from 54 infarction survivors were retrospectively reviewed. Ejection fraction was calculated from digitized biapical echocardiographic views on a graphics tablet. Changes of 0.10 or more in LVEF were correlated with 23 clinical variables. By stepwise regression analysis, Q-wave infarction and low early LVEF independently predicted late improvement in function. Early high LVEF and interval infarction were the only independent predictors of late declines in function. Overall, when patients were indexed by early left ventricular systolic function, a pronounced late "regression to the mean" was noted with initially high values tending to fall and low values to rise (r = -0.44, p less than 0.001). This effect must be accounted for in any acute intervention trial in myocardial infarction. The occurrence of Q-wave infarction does not exclude late improvement in ventricular function. 
Proliferation and cytolytic function of anti-CD3 + interleukin-2 stimulated peripheral blood mononuclear cells following bone marrow transplantation. We evaluated the proliferation, cytolytic function, and phenotypic characteristics of anti-CD3 plus interleukin-2 (IL-2) stimulated peripheral blood mononuclear cells (PBMCs) from 44 patients with leukemia or non-Hodgkin's lymphoma (NHL) treated with multiagent chemotherapy or following bone marrow transplantation (BMT). BMT patients had decreased cell growth with only a 1.35 +/- 0.25 (autologous BMT for acute lymphoblastic leukemia [ALL]), 1.24 +/- 0.25 (autologous BMT for NHL), and 0.8 +/- 0.1 (allogeneic BMT for leukemia) mean fold increase by day 5 of culture compared with controls (4.0 +/- 0.4), P less than .001. Anti-CD3 + IL-2 activated cells from patients with ALL and NHL who had received autologous BMT and cells from patients with leukemia who underwent allogeneic BMT were more effective in lysing the natural killer (NK) sensitive target, K562, and the NK-resistant target, Daudi, compared with controls. In contrast, cytolysis of K562 and Daudi by cultured PBMCs from patients with ALL and NHL receiving multi-agent chemotherapy was similar to that of controls. Cultures from BMT recipients had a significant increase in CD16+ (autologous ALL 5.7 +/- 1.5%, P less than .01; autologous NHL 12.4 +/- 3.5%, P less than .001; allogeneic 14.3 +/- 2.9%, P less than .001) and CD56+ cells (autologous ALL 27.6 +/- 12.0%, P less than .01; autologous NHL 39.3 +/- 9.5%, P less than .001; allogeneic 42.7 +/- 7.4%, P less than .001) compared with controls (CD16+ 2.5 +/- 0.4%; CD56+ 6.9 +/- 0.9%). Stimulation of PBMCs with anti-CD3 + IL-2 is effective in generating cells with high cytolytic function post-BMT. 
Mesenteric infarction secondary to tumor emboli from primary aortic sarcoma. Guidelines for diagnosis and management. Primary aortic tumors are rare, difficult to diagnose, and often fatal. This case and a review of the literature identified aortic tumors as a potential source of emboli leading to acute mesenteric insufficiency. The case showed the efficacy of magnetic resonance imaging in diagnosing and determining the extent and location of an aortic tumor. 
Tumor cell invasion inhibited by TIMP-2 The 72-kd type IV collagenase is a member of the collagenase enzyme family that has been closely linked with the invasive phenotype of cancer cells. Previous studies have shown that both normal cells and highly invasive tumor cells produce the 72-kd type IV procollagenase enzyme in a complexed form consisting of the proenzyme and a novel tissue inhibitor of metalloproteinases, TIMP-2. The balance between activated enzyme and available inhibitor is thought to be a critical determinant of the matrix proteolysis associated with a variety of pathologic processes, including tumor cell invasion. In the present study, we demonstrate that alteration of the metalloproteinase-metalloproteinase-inhibitor balance in favor of excess inhibitor blocks human fibrosarcoma HT-1080 tumor cell invasion of a reconstituted basement membrane. The HT-1080 cell line produces both the 72-kd and the 92-kd type IV collagenases. Alteration of the type IV collagenase-inhibitor balance was achieved by addition of free TIMP-2 or antibodies to 72-kd type IV collagenase. Native, purified TIMP-2 was inhibitory in the range of 1-25 micrograms/mL. Addition of specific antiserum against the 72-kd type IV collagenase, which did not cross-react with the 92-kd type IV collagenase, inhibited HT-1080 cell invasion to the same extent. These results suggest that metalloproteinases, in particular the 72-kd type IV collagenase, are critical for tumor cell invasion of the reconstituted basement membrane. Our findings demonstrate that addition of the endogenous inhibitor TIMP-2 is able to block invasion. Thus, we recommend initiation of in vivo studies of the therapeutic potential of TIMP-2 to block tumor cell invasion and intravasation into the circulation. 
Load dependence of the effective regurgitant orifice area in a sheep model of aortic regurgitation. Treatment of patients with aortic regurgitation with vasodilators reduces regurgitant volume, ventricular dilation and left ventricular mass. Although these effects are presumably due to afterload reduction, it is also possible that the aortic regurgitant orifice area is not constant. To test the latter hypothesis, aortic regurgitation was created in 10 open chest sheep by partial resection of the noncoronary leaflet under direct visualization. Regurgitant flow was measured with an aortic supravalvular electromagnetic probe; aortic and left ventricular pressures were measured with catheter-tipped micromanometer pressure transducers. The effective regurgitant orifice area was calculated by a modification of the continuity equation in a manner similar to the Gorlin equation. The regurgitant orifice area was measured three times: after aortic regurgitation was created, after mean arterial pressure was increased by 15 to 25 mm Hg with intravenous dopamine and after mean arterial pressure was reduced by 15 to 25 mm Hg with intravenous sodium nitroprusside. Comparison of regurgitant volumes and areas obtained after creation of aortic regurgitation and at the conclusion of the experiment in the absence of dopamine or sodium nitroprusside demonstrated no significant change over time. Dopamine administration was associated with an 86 +/- 81% increase in regurgitant volume (p less than 0.01) and a 38 +/- 44% increase in regurgitant orifice area (p less than 0.01). Sodium nitroprusside administration resulted in a 51 +/- 14% decrease in regurgitant volume (p less than 0.001) and a 28 +/- 21% reduction in regurgitant orifice area (p = 0.007). In this model of acute aortic regurgitation, the effective regurgitant orifice area was altered by increasing or decreasing the aortic transvalvular pressure gradient. 
Primary angiosarcoma of the central nervous system. Study of eight cases and review of the literature. Angiosarcoma arising in the central or peripheral nervous system has rarely been reported. Eight patients with primary angiosarcoma of the central nervous system are described here; these included five males and three females ranging in age from 2 weeks to 72 years (mean 38 years). Of the eight neoplasms, six were located in the cerebral hemispheres and one was in the meninges; the site was unknown in the other. All patients underwent surgical resection. Five of the eight patients died, four within 4 months after surgery and one after 30 months. Two of the remaining three patients were 17 and 27 years old at the time of diagnosis and were alive at follow-up review 39 and 102 months after surgery, respectively. One patient was lost to follow-up monitoring. Microscopically, all eight tumors demonstrated a well-differentiated pattern with irregular vascular channels and intraluminal papillae; in addition, four showed poorly differentiated solid areas. Immunohistochemical staining of neoplastic cells to factor VIII-related antigen and Ulex europaeus agglutinin I was performed in five tumors and was focally positive in four. No correlation could be shown between the histological features and the growth and biological behavior of the tumors. 
Verapamil in the treatment of maternal paroxysmal supraventricular tachycardia. Paroxysmal supraventricular tachycardia (PSVT) is seen somewhat frequently in the emergency department but less frequently during pregnancy. Although verapamil is widely used as the drug of choice for PSVT with a narrow QRS complex in a hemodynamically stable patient, the acute IV use of verapamil during pregnancy has not been well studied. Only a limited number of case reports document its safety and efficacy in the treatment of maternal or fetal PSVT. In general, the use of medication during pregnancy requires careful assessment of both the maternal and fetal risks versus benefits and documentation of patient consent. Because it crosses the placenta, one of the major concerns with the acute use of IV verapamil centers around the drug's potential effect on fetal heart rate. The case we present describes the occurrence of PSVT on two separate occasions in a woman in the third trimester of pregnancy. In both episodes, as much as 10 mg IV verapamil was given with resulting successful conversion to normal sinus rhythm. Fetal heart monitoring during drug administration failed to show significant change in fetal heart rate. 
Meningitis from canine Pasteurella multocida following mastoidectomy. A case of Pasteurella multocida meningitis, following a mastoidectomy is presented. The association of close contact with pets, many of which harbour Pasteurella multocida as part of their normal buccal flora. This case confirms the potential benefit of taking an ear swab prior to mastoid surgery and in seeking an appropriate 'pet' history. 
Dislodgement of a vein graft thrombus by angiographic injection of native coronary artery. A case of retrograde dislodgement of thrombus in a saphenous vein graft during injection of the native right coronary artery is presented. Attention to this previously undescribed complication may allow for timely treatment with emergency surgery or thrombolysis. 
Multifactorial analysis of fertility after conservative laparoscopic treatment of ectopic pregnancy in a series of 223 patients. OBJECTIVES: To lay down the criteria to clearly define whether conservative or radical laparoscopic treatment should be adopted in cases of ectopic pregnancies (EP). DESIGN: Retrospective, noncomparative. SETTING: At the University Hospital of Clermont Ferrand and the La Pergola Clinic at Vichy from July 1974 to December 1987. PATIENTS: This study was carried out in 223 patients who had been treated laparoscopically for EP and who desired future childbearing and who were not lost to follow-up. MAIN OUTCOME MEASURES: The measures chosen to achieve the objective included age, parity, size of hematosalpinx, volume of hemoperitoneum, tubal rupture, location, intrauterine device, ipsilateral and contralateral adhesions, and patient's previous history of salpingitis, EP, solitary tube, and tubal infertility. RESULTS: The general intrauterine pregnancy rate was 67% (149 patients) and the recurrence rate 12% (27 patients). The results according to the studied factors demonstrated that age, parity, and the type of the EP have no influence on the postectopic fertility. The history of the patient, ipsilateral adhesions, or contralateral tubal status significantly reduce the future fertility prognosis and risk of recurrence. CONCLUSIONS: From a multivariable analysis, the authors propose a scoring system to choose the most suitable treatment to preserve fertility and to reduce the risk of recurrence ranging from laparoscopic conservative treatment to laparoscopic salpingectomy with contralateral sterilization. 
Epidemiology and evaluation: steps toward hypertension treatment in the 1990s. The percentage of persons in the United States over age 65--especially over 85--is increasing more rapidly than other age groups. Two thirds of people over age 65 have blood pressure higher than 140 mm Hg systolic or 90 mm Hg diastolic. Isolated systolic hypertension (systolic blood pressure greater than 160 mm Hg with diastolic blood pressure less than 90 mm Hg) is also highly prevalent. In a number of clinical trials, treatment of diastolic hypertension in the elderly has been shown to be beneficial, although the value of treatment of isolated systolic hypertension is not yet established. The benefit of antihypertensive therapy on the incidence of stroke and heart failure has been clearly established, but prevention of the atherosclerotic complications of high blood pressure (sudden death or myocardial infarction, for example) has not been convincingly demonstrated. Since clinical trials designed to investigate this atherosclerotic complication of hypertension have relied on stepped-care regimens (diuretics and beta blockers), the question arises whether the use of different drugs might have a better effect on prevention of myocardial infarction. The basis for this supposition includes the known adverse effects of diuretics and beta blockers on electrolytes, lipid metabolism, glucose metabolism, insulin resistance, and quality of life. Hypertension treatment in the 1990s will focus on the mechanisms by which blood pressure is lowered by various antihypertensive agents, as well as individualization of drug therapy based on coexisting diseases and conditions. Emphasis will be placed on use of monotherapy whenever possible; diuretics in low doses will probably be used more frequently for second-line therapy. In recognition of their lack of adverse lipid effects and their tolerability, first-line therapy with alpha blockers, angiotensin-converting enzyme inhibitors, and calcium antagonists will become increasingly common. The goal of antihypertensive therapy will be to extend the life expectancy of hypertensive patients to that of subjects without high blood pressure; hopefully, these new treatment approaches will bring us closer to that goal. 
Successful repair of a submitral left ventricular infected pseudoaneurysm. Aneurysms of the left ventricle may be congenital or may occur after a myocardial infarction, trauma, or endocarditis. Infective endocarditis can cause destructive injury to the heart in various ways. This report describes the formation of an aneurysm of the left ventricle from trauma of a bacterial vegetation of the mitral valve. Early recognition by echocardiography and magnetic resonance imaging led to successful repair and prevented a catastrophic result. 
Lateral parabrachial nucleus and angiotensin II-induced hypertension. The objective of this study was to determine if ablation of the lateral parabrachial nucleus (LPBN) would prevent angiotensin II-induced hypertension in rats. Thirteen male Sprague-Dawley rats were studied. Bilateral electrolytic lesions in the LPBN were produced in six rats; the remaining seven rats were subjected to sham lesion surgery only. All rats were instrumented with vascular catheters and housed in metabolism cages. Daily measurements during the 16-day protocol included arterial pressure, heart rate, water intake, urine output, and urinary sodium excretion. Periodically throughout the protocol depressor responses to ganglion blockade and to blockade of V1-type vasopressin receptors also were measured. The protocol was divided into three control-period days, 10 days of continuous (24 hr/day) angiotensin II infusion (10 ng/min i.v.), and three recovery-period days. There were no significant differences between the two groups of rats for any variable during the control period. During angiotensin II infusion, sham-lesion rats exhibited a progressive increase in arterial pressure and the depressor response to ganglion blockade and a decrease in urinary sodium excretion. No other variable was significantly changed. In rats with LPBN lesions, arterial pressure was significantly increased only on days 1 and 3 of angiotensin II infusion. No other variable was affected. It was concluded that ablation of the LPBN in rats prevented sustained hypertension during intravenous infusion of angiotensin II by interfering with neurogenic pressor mechanisms normally activated by the peptide. 
Bladder and sphincter behavior in patients with spinal cord lesions. To ascertain the relationship between the clinical neurological level, and bladder and sphincter behavior, the video-urodynamic studies of 489 patients with spinal cord lesions due to a variety of causes were retrospectively analyzed. Patients were classified based on the clinical neurological level, etiology of the lesion and presence or absence of signs of sacral cord involvement. Urodynamic findings were classified as either detrusor hyperreflexia, detrusor-external sphincter dyssynergia, detrusor areflexia or normal. The results indicate that although there was a general correlation between the neurological level of injury and the expected vesicourethral function, it was neither absolute nor specific. For example, 20 of 117 cervical cord lesions had detrusor areflexia, 42 of 156 lumbar cord lesions had detrusor-external sphincter dyssynergia and 26 of 84 sacral cord had either detrusor hyperreflexia or detrusor-external sphincter dyssynergia. However, if one considers the presence of neurological abnormalities, 84% of the suprasacral cord lesions with detrusor areflexia have sacral cord signs. In contrast, all suprasacral cord lesions with no evidence of sacral cord involvement have either detrusor hyperreflexia or detrusor-external sphincter dyssynergia. The positive predictive value for positive sacral cord signs and detrusor areflexia was 87%. The positive predictive value for negative sacral cord signs and detrusor hyperreflexia/detrusor-external sphincter dyssynergia was 81%. These data suggest that the clinical neurological examination alone is not an adequate barometer to predict neurourological dysfunction and that video-urodynamic evaluation provides a more precise diagnosis for each patient. 
The submandibular triangle in squamous cell carcinoma of the larynx and hypopharynx. A 15-year retrospective analysis was carried out at the University of Illinois College of Medicine, Chicago, reviewing the tumor staging and pathology data of 239 patients treated for carcinoma of the larynx and hypopharynx requiring laryngectomy alone, laryngectomy with neck dissection, or laryngopharyngectomy and neck dissection. Surgery was the primary treatment modality in 205 of the 239 cases, with the remaining 34 having surgery to treat radiation therapy failure. Primary tumors were located within the supraglottic region, the glottic region and, less commonly, the pyriform sinus. Ninety-five of the 239 patients either presented with or developed nodal metastases following initial treatment. Of these, only two had tumors within the lymph nodes of the submandibular triangle. This data corroborates impressions that tumors of the larynx and hypopharynx rarely metastasize to the submandibular triangle and that sparing this area during neck dissection for lesions of the larynx would seem justified. 
Cardiac disturbances during the administration of taxol. The clinical development of taxol, a new antimicrotubule agent with a unique mechanism of cytotoxic action, has proceeded slowly due to serious hypersensitivity reactions (HSRs) and shortages in its supply. Nevertheless, large-scale phase II trials have been initiated as taxol has recently demonstrated impressive activity in advanced and cisplatin-refractory ovarian carcinoma. Furthermore, the incidence of HSRs has been reduced substantially with premedications and modifications in the administration schedule. However, various manifestations of potential cardiotoxicity have been observed in several patients who participated in four phase I and II studies of taxol. Asymptomatic bradycardia has occurred in a high proportion of patients, including 29% of ovarian cancer patients who were treated with maximally tolerated doses of taxol in a phase II study. More profound cardiac disturbances, including a range of atrioventricular conduction blocks, left bundle branch block, ventricular tachycardia (VT), and manifestations of cardiac ischemia, have been observed in seven of 140 patients (5%) who received taxol. Descriptions of these events are presented in this report to alert investigators to the potential for these adverse effects. Although these disturbances did not result in serious sequelae in most patients, investigators should continue to maintain a high degree of caution until precise risk factors, frequency, and clinical significance of these adverse cardiac effects are determined. 
Factors affecting the rearrangement efficiency of an Ig test gene. A rearrangement test gene, pHRD, containing the mouse IgH enhancer and the metallothionein promoter, has previously been shown to rearrange efficiently after transfection into a pre-B cell line. Experiments are now reported that assess the requirements of the DNA substrate as well as of the transfected cells for efficient rearrangement. It was found that deletion of the metallothionein promoter or substitution of the IgH enhancer by the kappa enhancer did not affect rearrangement. However, deletion of the Ig enhancer reduced the efficiency. Transfection of pHRD into stable hybrids of pre-B cells and myeloma cells resulted in a high frequency of rearrangement only if certain myeloma chromosomes were lost. Furthermore, pHRD introduced into rearrangement incompetent myeloma cells upon subsequent cell fusion with pre-B cells was rearranged only very rarely and then apparently only immediately after cell fusion. Stable pre-B cell x myeloma hybrids that retained the critical myeloma chromosomes were found to have lost VDJ recombinase activity and transcripts of the RAG-1, RAG-2 and TdT genes. It is concluded that transcription, i.e., the copying of the DNA by polymerase, is probably not required for rearrangement, but that the rearrangement substrate must be in an "open" chromatin state, such as may be provided by transcriptional factors. Furthermore, the absence of rearrangement in myeloma cells is apparently due to the continued action of an inhibitor of rearrangement. 
Effects of subsequent pregnancy on left ventricular function in peripartum cardiomyopathy. Pregnancy has been discouraged in patients with peripartum cardiomyopathy (PPCM) to avoid the risk of precipitating recurrent or progressive left ventricular dysfunction. We assessed left ventricular size and contractile function using echocardiography in four PPCM patients prior to pregnancy, during the third trimester, and a mean of 6 weeks postpartum. Left ventricular mean diameters at end diastole and at end systole prior to pregnancy (5.2 +/- 0.3 and 3.0 +/- 0.2 cm, respectively) did not change during pregnancy (5.2 +/- 0.3 and 3.1 +/- 0.2 cm). Similarly, left ventricular fractional shortening did not alter significantly during pregnancy or postpartum. Furthermore, no patient developed any symptoms or signs of left ventricular failure. All patients had normal babies, including one who had twins. We conclude that PPCM patients whose left ventricular function returns to normal may undertake further pregnancy with a normal fetal outcome and a low risk of recurrent left ventricular dysfunction. 
Smoking and mortality among older men and women in three communities. BACKGROUND. Although cigarette smoking is the leading avoidable cause of premature death in middle age, some have claimed that no association is present among older persons. METHODS. We prospectively examined the relation of cigarette-smoking habits with mortality from all causes, cardiovascular causes, and cancer among 7178 persons 65 years of age or older without a history of myocardial infarction, stroke, or cancer who lived in one of three communities: East Boston, Massachusetts; Iowa and Washington counties, Iowa; and New Haven, Connecticut. At the time of the initial interview, prevalence rates of smoking in the three communities ranged from 5.2 to 17.8 percent among women and from 14.2 to 25.8 percent among men. During five years of follow-up there were 1442 deaths, 729 due to cardiovascular disease and 316 due to cancer. RESULTS. In both sexes, rates of total mortality among current smokers were twice what they were among participants who had never smoked. Relative risks, as adjusted for age and community, were 2.1 among the men (95 percent confidence interval, 1.7 to 2.7) and 1.8 among the women (95 percent confidence interval, 1.4 to 2.4). Current smokers had higher rates of cardiovascular mortality than those who had never smoked (as adjusted for age and community, the relative risk was 2.0 [95 percent confidence interval, 1.4 to 2.9] among the men and 1.6 [95 percent confidence interval, 1.1 to 2.3] among the women), as well as increased rates of cancer mortality (relative risk, 2.4 [95 percent confidence interval, 1.4 to 4.1] among the men and 2.4 [95 percent confidence interval, 1.4 to 3.9] among the women). In both sexes, former smokers had rates of cardiovascular mortality similar to those of the participants who had never smoked, regardless of age at cessation, whereas the rates for all cancers, as well as smoking-related cancers, remained elevated among men who had once smoked. CONCLUSIONS. Our prospective findings indicate that the mortality hazards of smoking extend well into later life, and suggest that cessation will continue to improve life expectancy in older people. 
Pulmonary vascular reactivity in Fischer rats. We previously reported that Fischer (F) rat lungs developed more extensive injury when challenged with oxidants than age-matched Sprague-Dawley (SD) rat lungs. We now describe a reduced pulmonary vascular response to alveolar hypoxia and angiotensin II (ANG II) in F compared with SD rats. The comparative studies were performed with isolated lungs perfused with salt solution or blood, catheter-implanted awake rats, and isolated main pulmonary arterial rings. Isolated lungs from F rats perfused with either blood or salt solution had reduced vasoconstriction in comparison with lungs from SD rats when exposed to alveolar hypoxia or challenged with ANG II. Instrumented awake F rats had a smaller mean increase in total pulmonary vascular resistance (PVR) than SD rats (35 vs. 94 mmHg.min.l-1, P less than 0.05) when challenged with 8% oxygen. The contractile response of isolated pulmonary artery but not thoracic aortic rings to KCl and ANG II was reduced in F compared with SD rats. In addition, F rats exposed to 4 wk of hypobaric hypoxia developed less pulmonary hypertension and right ventricular hypertrophy (when corrected for the hematocrit) than SD rats. We conclude that the oxidant stress-sensitive inbred F rat strain is characterized by a lung vascular bed that is relatively unresponsive to vasoconstricting stimuli. The mechanism underlying this genetic difference in lung vascular control remains to be defined. 
Herniated cervical disk presenting as ischemic chest pain. Myocardial ischemia must be the first concern of every emergency physician in evaluating chest pain in the adult patient. Any suspicion of myocardial ischemia must be promptly evaluated and admitted. The American College of Emergency Physicians has recently published a standards document on the care of chest pain in the adult patient. The emergency physician must be familiar with this document. Once myocardial ischemia and other life-threatening causes are ruled out, one can consider that cervical disk disease may be the cause of chest pain. We present two cases of patients who presented to the emergency department with signs and symptoms consistent with cardiac ischemia. Both patients were found to have herniated cervical disks. Subsequent surgical repair completely relieved their symptoms. Evaluation of the literature shows that this entity was well described from 1950 to the 1960s. Most recent discussions do not mention disk herniation as even an infrequent cause of chest pain. If there is no life-threatening disease present, one should consider cervical disk disease. 
Obstructed central venous catheters. Restoring function with a 12-hour infusion of low-dose urokinase. Thrombotic obstruction frequently prohibits infusion through or withdrawal of blood from central venous catheters and can occur in conjunction with symptomatic thrombosis of the subclavian vein. Thirty catheters were radiographically proved to be obstructed by thrombus and had not responded to at least one instillation of 5000 units of urokinase. All catheters were treated with a 12-hour infusion of urokinase at the rate of 40,000 units/hour. The obstructing thrombus was either eliminated or reduced in size in all instances and full function was restored in all but one catheter. No bleeding complications were seen. Six patients with obstructed catheters also had symptoms of subclavian vein thrombosis. All patients with symptoms of subclavian vein obstruction became asymptomatic on anticoagulant therapy even though no attempt at dissolving the thrombus obstructing the subclavian vein was made. A 12-hour infusion of low doses of urokinase can safely salvage function of obstructed catheters that otherwise may require replacement. Patients with concomitant subclavian vein thrombosis become asymptomatic on anticoagulant therapy without need to dissolve the obstructing thrombus. 
Diabetes mellitus and localizations of obliterating arterial disease of the lower limbs. Thirty patients with intermittent claudication (IC) and treated diabetes mellitus and 30 age- and gender-matched nondiabetic claudicants underwent a vascular examination by noninvasive ultrasound methods (continuous-wave Doppler, duplex scanner). The ankle/arm systolic pressure index did not differ in the two groups. Diabetic patients with IC had more (p less than .001) non-flow-reducing stenoses (lumen reduction less than 50%) and fewer (p less than .002) flow-reducing obstructions (lumen reduction greater than 50%) of the iliac arteries than nondiabetics had. These data are consistent with a preferentially distal (below the inguinal ligament) localization of arterial stenoses in diabetic patients, whereas iliac artery diseases are relatively more severe in nondiabetics. 
A prospective evaluation of arterial intimal injuries in an experimental model. The management of arterial intimal defects remains controversial because of uncertainty concerning their natural history. We developed an experimental canine model to prospectively evaluate posterior wall intimal flaps in the superficial femoral artery. Arterial intimal flaps were constructed in 20 anesthetized dogs (40 arteries) and evaluated by arteriography, and angioscopy, and intravascular ultrasound. Postoperative patency rates at 1 (n = 20) and 3 weeks (n = 20) were compared with a control group of ten animals (n = 20, arteriotomy without intimal flap). Acute thromboses occurred in five experimental arteries with thromboses of eight additional experimental arteries at followup. Control patency was 100%, while experimental group patencies were 75% (p less than 0.05) at 1 week and 60% (p less than 0.009) at 3 weeks. All thrombosed arteries had intimal flaps with greater than 75% luminal stenosis. We conclude that intimal injuries cause arterial thromboses acutely and during subsequent followup. Intimal flaps with stenosis greater than 75% as determined arteriographically are at greatest risk for thrombosis. Angioscopy and intravascular ultrasound characterize arterial intimal defects and may delineate injuries requiring surgical or endovascular repair. 
Internal biliary drainage, parenteral nutrition, and variation in the total parenteral nutrition feeding solutions: influence on the healing of colon anastomosis in jaundiced rats. The influence of preoperative internal biliary drainage and various types of total parenteral nutrition (TPN) on the healing of a colon anastomosis in 50 jaundiced rats was investigated. Jaundice was induced by division and ligation of the common bile duct. After 5 days a colon anastomosis was made. Ten days thereafter the bursting pressure of the anastomosis was measured as an assessment of wound healing. Bursting pressures were significantly lower in jaundiced rats compared with a sham-operated nonjaundiced group. Preoperative internal biliary drainage significantly improved bursting pressure (p less than 0.001) as did preoperative TPN (p less than 0.001). In the second part of the study the influence of four different feeding solutions on the healing of a colon anastomosis was tested. Solutions with and without 20% fat emulsion and a solution with branched-chain amino acids were tested as well as glucose only. No significant differences were observed among these four groups on the parameters tested. 
Angelchik prosthesis complicates treatment of adenocarcinoma in Barrett's esophagus. Indications for use of the Angelchik prosthesis remain controversial, and many surgeons actively involved in the treatment of reflux disease have not used the device. We describe a case that illustrates difficulties associated with resection of a tumor in the presence of this prothesis. Such experience suggests that patients known to have Barrett's esophagus might be better treated with standard antireflux procedures. 
Six-year experience with a comprehensive approach to the treatment of recurrent childhood acute lymphoblastic leukemia (ALL-REZ BFM 85). A relapse study of the BFM group. Between April 1985 and March 1987 130 children and adolescents up to 18 years of age with first relapse of acute lymphoblastic leukemia (ALL) were registered on the stratified and randomized multicentric trial ALL-REZ BFM 85 designed for patients pretreated with intensive front-line therapies. Stratification criteria were time and site of relapse: bone marrow (BM) relapse on or up to 6 months after stopping front-line therapy (group A), BM relapse beyond 6 months after therapy (group B), and isolated extramedullary relapse at any time (group C). Treatment consisted of alternating courses of polychemotherapy including randomly administered high- or intermediate-dose methotrexate (HDMTX:12 g/m2 as 4-hour infusion; IDMTX: 1 g/m2 as 36-hour infusion). During maintenance therapy the patients received daily oral thioguanine and biweekly intravenous (IV) MTX. The overall second complete remission (CR) rate was 92% (groups A, B, and C: 88%, 92%, and 100%), and the probability of event-free survival (EFS) at 6 years is 0.31 +/- 0.04 (groups A, B, and C: 0.18 +/- 0.05, 0.30 +/- 0.07, and 0.72 +/- 0.11). HDMTX did not prove to be superior to IDMTX, which led to premature stopping of randomization. Risk factor analyses showed early relapse, particularly BM relapse within 18 months, and T-cell phenotype to be independent predictors of poor outcome. The incidence of central nervous system (CNS) relapses following BM relapse was 19%, indicating that reprophylaxis to the CNS with IV/intrathecal (IT) MTX was insufficient. For 17 children who received bone marrow transplantation in second CR from HLA-compatible siblings the EFS was 0.53 +/- 0.12 at 5 years. Their outcome was not influenced by the above-mentioned risk factors. With the proposed treatment regimen long-lasting second remissions can be achieved in about one third of patients even after intensive front-line treatment. 
Validity of cerebrovascular mortality rates. Cerebrovascular disease (CVD) mortality rates are being increasingly used to establish a relationship with coronary heart disease risk factors. Cerebrovascular mortality rates suffer from the same general defects as coronary heart disease mortality rates but with greater diagnostic error in regard to subdivisions of CVD or stroke. These vital statistics, whether national or regional, are too inaccurate for scientific use and cannot be regarded as representing true mortality rates for any country. Moreover, clinical CVD is an inappropriate surrogate for severity of atherosclerosis, providing inexact data and allowing indeterminate overlap in epidemiologic studies. 
Tumor regulation of hepatic glutamine metabolism. Fast-growing tumors are major glutamine consumers and may alter host glutamine metabolism to benefit the tumor. Previous studies from our laboratory have demonstrated that the liver switches from an organ of glutamine balance to one of glutamine release with progressive malignant growth. However, the regulation of this change is unclear. This study examined tumor modulation of hepatic glutamine metabolism by determining the activities of glutaminase, the principle enzyme of glutamine degradation, and glutamine synthetase, the principal enzyme of glutamine synthesis. Hepatic glutamine content was also determined. Rats with a fast-growing subcutaneous fibrosarcoma (TBR) and pair-fed controls were studied at 2 and 3 weeks after tumor or sham implantation, when the tumors comprised approximately 5% and 20% of total body weight. Arterial glutamine fell with progressive tumor growth (608 +/- 26 mumol/L in controls vs 494 +/- 15 in TBR, p less than 0.005) and was not attributable to a diminished food intake. Hepatic glutamine content was increased 45% (p less than 0.01) in tumor rats at 2 weeks due in part to a 35% fall in liver glutaminase activity. At 3 weeks, glutamine synthetase activity increased by 43% (0.58 +/- 0.07 mumol/mg of protein/hr in controls vs 0.83 +/- 0.04 in TBR, p less than 0.01) whereas glutaminase remained depressed (2.68 +/- 0.12 mumol/mg of protein/hr in controls vs 2.22 +/- 0.15 in TBR, p less than 0.05) and glutamine content fell compared to 2 week tumor-bearing rats, consistent with accelerated hepatic glutamine release. Tumors may alter liver glutamine metabolism by modulating hepatic enzyme activity in order to provide circulating glutamine for the growing malignancy. 
Phase I trial of fluorouracil modulation by N-phosphonacetyl-L-aspartate and 6-methylmercaptopurine riboside: optimization of 6-methylmercaptopurine riboside dose and schedule through biochemical analysis of sequential tumor biopsy specimens. Preclinical and clinical studies demonstrate that the selective antitumor activity of fluorouracil (5-FU) is enhanced by agents which perturb certain intracellular nucleotide pools. We previously demonstrated that the combination of N-phosphonacetyl-L-aspartate (PALA), which depletes pyrimidine nucleotide pools, and 5-FU yielded a 43% response rate among 37 assessable patients with colorectal carcinoma. In preclinical tumor models, 6-methylmercaptopurine riboside (MMPR), an inhibitor of purine synthesis, elevates phosphoribosylpyrophosphate (PRPP) pools and promotes the anabolism of 5-FU to fluorinated nucleotides. In vivo, the addition of MMPR enhances the therapeutic efficacy of PALA-5-FU. In a phase I trial, we sought to determine the optimal dose and schedule of MMPR in combination with PALA (250 mg/m2 on day 1) and 5-FU (1300 mg/m2 by 24-hour infusion on day 2). MMPR (75-225 mg/m2) was given intravenously on day 1 to 27 patients with solid tumors (15 colorectal, seven breast, five other). Toxic effects were mild to moderate and included leukopenia, mucositis, nausea, or rash. Two of seven patients given MMPR at 225 mg/m2 had grade 3 diarrhea. PRPP was measured using a [14C]orotic acid 14CO2 release assay in tumor biopsy specimens obtained before and 12 hours and 24 hours after MMPR doses were given to 20 patients. The addition of MMPR elevated PRPP pools in human solid tumors. At 12 hours after treatment, two (50%) of four patients showed a twofold or greater elevation of PRPP at the MMPR dose level of 75 mg/m2; a similar elevation was observed in five (71%) of seven patients given 150 mg/m2 MMPR and in three (43%) of seven patients given 225 mg/m2 MMPR. At 24 hours after treatment, results for the respective dose levels of MMPR were two (33%) of six patients, one (20%) of five patients, and four (57%) of seven patients. Administration of the two highest MMPR dose levels appeared to result in a greater increase in tumor PRPP levels. However, toxicity was greater at the 225 mg/m2 dose level; therefore, the 150 mg/m2 dose level was favored. Tumor levels of PRPP decreased between 12 hours and 24 hours in nine (56%) of 16 patients. This time course indicates that MMPR should be administered at the beginning of the 24-hour infusion of 5-FU. 
Age-dependent increase in deleted mitochondrial DNA in the human heart: possible contributory factor to presbycardia. Cardiac function deteriorates with age, and endogenous damage to mitochondrial DNA (mt DNA) is believed to be a major contributory factor to aging. Mitochondria occupy a pivotal position in energy metabolism, and mitochondria have their own DNA, which encodes 13 subunits of the mitochondrial energy transducing system. Other subunits are encoded by nuclear DNA. DNA has been shown to have a high mutation rate, and genetic mutation might primarily be ascribed to mtDNA mutation in the energy transducing system. Recent advances in gene technology, especially in polymerase chain reactions (PCR), permit us to analyze mtDNA mutations in a small quantity of tissue. We devised rapid and accurate methods to detect mitochondrial mutations--the primer shift PCR method, PCR-Southern method, the modified primer shift PCR method, and the asymmetric PCR method. With these methods, we analyzed myocardia mtDNA in human cadavers of various ages (from 3 years old to 97 years old, mean 57 years old). The 7.4 kb deletion of mtDNA was commonly detected in elderly subjects, and the proportion of deleted mtDNA to normal mtDNA increased with age. Deleted mtDNA was observed in all subjects that were over 70 years old. The mutation was based on the directly repeated sequence: 5'-CATCAA-CAACCG-3', which exists in both the adenosine triphosphatase 6 gene and the displacement loop (D-loop) region. Replication impairment occurred at that directly repeated sequence, which caused the elimination of genomes between the adenosine triphosphatase 6 gene and the D-loop region and resulted in a 7.4 kb deletion. 
T-gamma-lymphoproliferative disorder arising in a background of autoimmune disease and terminating in plasma cell dyscrasia with primary amyloidosis. T-gamma-lymphoproliferative disorder, a syndrome of T-cell lymphocytosis with neutropenia has been described in patients with various autoimmune disorders, especially rheumatoid arthritis. We report a case of T-gamma-lymphoproliferative disorder occurring in a 42-year-old white woman with a long history of dermatitis herpetiformis and subsequent development of Coomb's positive autoimmune hemolytic anemia and polymyositis. The peripheral blood lymphocytes showed the T-suppressor cell phenotype (CD2-, CD3-, CD8-, and CD4-). DNA analysis of the peripheral blood lymphocytes revealed a T-cell receptor beta-chain gene rearrangement and an immunoglobulin heavy-chain gene rearrangement. The patient's course was marked by numerous bouts of infection. The unique factor in this patient was the development of a plasma cell dyscrasia and amyloidosis prior to death. 
Is a single quinsy an indication for tonsillectomy? There has recently been some discussion on whether a single quinsy is an indication for tonsillectomy. This paper presents a retrospective study of 36 patients who presented with a quinsy over the past 37 years but did not have interval tonsillectomy. Prolonged follow-up shows that the rate of recurrence of a quinsy can double compared to the recurrence rate under 5 years. Despite this it remains relatively low and an uncomplicated quinsy does not warrant tonsillectomy. 
Total coronary occlusion: a different animal? Provided collateralization is adequate, a chronic total coronary occlusion clinically imitates a 90% stenosis but is exempt from the risk of myocardial infarction. For angioplasty of vessels with chronic total coronary occlusion, technical difficulties and clinical risks are balanced against projected subjective benefit and amount of viable myocardium concerned. The primary success rate is approximately 65% and complications are rare because abrupt vessel reclosure may be common but is harmless. New Q wave infarction in that context has not been reported. The duration of occlusion is the most important predictor of success. The length of the occluded segment is also important. Recurrence averages 68% (21% reocclusion and 47% restenosis) and happens typically within 6 months. The high recurrence rate is due to competitive pressure exerted by collateral vessels and an often suboptimal local result. Even if the primary success rate of angioplasty in vessels with chronic total coronary occlusion can be improved by advanced technology and skill, the clinical yield will remain low compared with that of angioplasty of stenoses. Because low yield procedures must be low risk and low cost, there are definite limits to how sophisticated, risky and expensive new techniques can become. Derivatives of conventional balloon systems are likely to remain the equipment of first choice, perhaps complemented by mechanical drills. Although chronic total coronary occlusions are no clinical menace in contrast to stenoses, they frequently deserve revascularization and are the reason to select bypass surgery over angioplasty. These factors justify endeavors to improve recanalization techniques that help to refine coronary angioplasty of nontotal lesions, because total occlusion, albeit a different animal, is of the same species. 
Effects of long-term amiodarone therapy on the defibrillation threshold and the rate of shocks of the implantable cardioverter-defibrillator. The effects of long-term amiodarone therapy on the defibrillation thresholds and the rate of shocks were evaluated in 62 patients who had implantation of an automatic cardioverter-defibrillator (n = 53) or prophylactic implantation of patch electrodes (n = 9) who were survivors of sudden cardiac death (n = 34) or had refractory rapid ventricular tachycardia (n = 28). There were 53 men and 9 women, with ages ranging from 18 to 76 years (mean +/- SD, 60 +/- 12). Coronary artery disease occurred in 50 patients (80.6%), cardiomyopathy occurred in six (9.7%), valvular heart disease developed in two (3.2%), primary electrical disease developed in two (3.2%), hypertensive heart disease materialized in one (1.6%), and Ebstein's anomaly occurred in one (1.6%). The left ventricular ejection fraction varied from 10% to 75% (mean, 37 +/- 17%). All patients had failed a mean of 3.9 +/- 1.6 antiarrhythmic drugs prior to implantation of the device. Twenty-eight patients (45%) were taking amiodarone up to the time of surgery, with a mean daily dose of 406 +/- 147 mg (range 200 to 800) and for a mean duration of 6.0 +/- 6.7 months (range 1 to 36 months). The mean defibrillation threshold (DFT) was 12.0 +/- 4.4 joules (range 5 to 20) in the group taking amiodarone and was not significantly different from that of the group not taking amiodarone (n = 32) (mean DFT 12.3 +/- 5.5 joules, range 5 to 30; p = 0.77). 
Increased occurrence of arrhythmias in men with ischaemic type ST-segment depression during long-term ECG recording. Prognostic impact on ischaemic heart disease: results from the prospective population study 'Men born in 1914', Malmo, Sweden. The objective of this long-term ECG (LTER) study in 394 68-year-old men, selected at random from the general population of Malmo, Sweden, was to determine the prevalence and occurrence of cardiac arrhythmias and their impact on morbidity and mortality from IHD. According to Lown classification, 29.4% (116 men) had ventricular arrhythmia (VA) group 4-5. Serious ventricular arrhythmia (Lown group 4-5) was more common in men with asymptomatic ischaemic type ST-segment depression (STD) than in those without it (37.8% vs. 26.7%: P less than 0.05). During the mean follow-up period of 53.1 months there were seven IHD deaths (6%) among the 116 patients with VA, Lown 4-5, and nine IHD deaths (3.2%) among the 278 patients without serious VA, Lown 0-3, (P = 0.26). Six and three of these deaths, respectively, were considered to be sudden (P = 0.022). The increased cardiac event rate (fatal or non-fatal MI or deaths due to chronic IHD) associated with a serious ventricular arrhythmia disappeared when history of IHD at baseline and occurrence of STD during LTER were taken into account. The study did not provide any evidence to suggest that ventricular arrhythmia was triggered by myocardial ischaemia. Five of 9 (56%) deaths due to IHD in men with STD occurred among the 38% (37/98) of patients who belonged to Lown class 4-5. It is concluded that the prognostic information derived from LTER can be improved by combined monitoring of STD and ventricular arrhythmias. 
Restenosis 1 to 24 months after clinically successful coronary balloon angioplasty: a necropsy study of 20 patients. This report describes clinical, morphologic and histologic findings at necropsy late (range 1.6 to 24.1 months [average 8.2 months]) after clinically successful coronary balloon angioplasty in 20 patients with coronary angioplasty restenosis. Clinical evidence of restenosis occurred in 14 patients (70%), including 6 patients with sudden coronary death. Of the 20 patients, 14 (70%) had a cardiac cause of death and 6 (30%) had a noncardiac cause of death. Two major subgroups of histologic findings were observed: 1) intimal proliferation (60%), and 2) atherosclerotic plaque only (40%). Of the eight sites with atherosclerotic plaque only, six were eccentric lesions and two were concentric lesions. No morphologic evidence of previous angioplasty injury (cracks, breaks, tears) was observed in the eight patients with atherosclerotic plaque only. Proposed mechanisms for the development of intimal proliferation involve the reaction of smooth muscle cells and platelets, whereas elastic recoil of overstretched eccentric or concentric atherosclerotic lesions represents the most likely explanation for the findings in the latter subgroup. On the basis of these morphologic findings at angioplasty restenosis sites, specific treatment strategies for restenosis after coronary artery balloon angioplasty are proposed. 
Chemotherapy and radiation therapy for anal carcinoma. Survival and late morbidity. This study was performed to evaluate the survival and late morbidity rates of a widely used combined chemotherapy and radiation therapy regimen given to patients with carcinoma of the anal canal. One hundred six patients received radiation therapy (5000 cGy given by two anteroposterior-posteroanterior [AP-PA] opposed fields) and chemotherapy (mitomycin C plus 5-fluorouracil [5-FU]) from 1983 to 1989. Patients with primary tumors (n = 86) had a complete response rate of 84% and a 5-year survival rate of 72%. There was no significant difference in survival rate according to tumor stage. Patients with local recurrence (n = 20) after primary surgery had a complete response rate of 50% and a 5-year survival rate of 40%. Fifteen percent of the patients experienced late treatment-related symptoms including anal incontinence, intestinal obstruction, and chronic pelvic pain. The current treatment regimen is effective but carries a considerable risk of complications. As survival rate was independent of tumor stage, the locoregional treatment should probably be less extensive for small tumors than for advanced tumors. This strategy may reduce the late side effects for patients with small tumors without reducing the survival rate. 
Sonography of the gallbladder: significance of striated (layered) thickening of the gallbladder wall. Sonographic identification of thickening of the gallbladder wall that consists of multiple striations (alternate hypoechoic and hyperechoic layers) has been considered strong evidence of the presence of acute cholecystitis. We studied 27 patients in whom sonograms showed striated thickening of the gallbladder wall to determine the diagnostic significance of this finding. Striations were classified as focal or diffuse. Sonograms were correlated with pathologic findings in 16 patients and with clinical diagnoses and laboratory findings in 11. Patients were categorized as having cholecystitis with or without gangrene or edema of the gallbladder wall unrelated to gallbladder disease. Striated thickening of the gallbladder wall was due to cholecystitis in 10 patients, and all 10 had gangrenous changes at surgery or at pathologic examination. Striations were focal in eight of these patients and diffuse in two. Striated thickening of the gallbladder wall was due to edema of the wall unrelated to gallbladder disease in 17 patients. Causes included congestive heart failure (n = 4), renal failure (n = 5), liver disease (hepatic failure [n = 1], hepatitis [n = 6]), ascites (n = 2), hypoalbuminemia (n = 3), pancreatitis (n = 1), blockage of the lymphatic/venous drainage of the gallbladder (n = 2), and prominent Rokitansky-Aschoff sinuses (n = 1). More than one abnormality was present in five patients. Striations were focal in 11 of these patients and diffuse in six. The sonographic finding of striated gallbladder wall thickening is no more specific for cholecystitis than the observation of gallbladder wall thickening by itself, and it may occur in a variety of diseases. However, in the clinical setting of acute cholecystitis, the presence of striations suggests gangrenous changes in the gallbladder. The extent of the striations (focal or diffuse) is not useful in predicting the cause of the striated gallbladder wall thickening. 
Anastomotic recurrence of carcinoma of the colon and rectum. The value of endoscopy and serum CEA levels. The early diagnosis of anastomotic recurrence after surgery for carcinoma of the colon and rectum is difficult. Whether repeat colonoscopy and serial serum CEA measurements were useful in diagnosing early anastomotic recurrence was examined. A total of 112 patients with carcinoma of the colon and rectum who had undergone resection and anastomosis were followed with frequent colonoscopy and serum CEA measurements. Seventeen patients developed anastomotic recurrence. Fourteen patients had elevated serum CEA levels, and 15 patients had endoscopic evidence suggesting recurrence at the anastomotic site. CT scans of the abdomen and pelvis demonstrated metastatic disease in seven patients, localized anastomotic disease in six patients, and no evidence of disease in four patients. Laparotomy was then carried out in 10 patients. In eight of 10 patients, it was possible to resect localized disease. In a 3-year follow-up study, eight patients were alive, four without any evidence of recurrent disease. Repeat colonoscopy and serum CEA measurements are recommended as postoperative surveillance for carcinoma of the colon and rectum. In select cases laparotomy and resection may prolong survival. 
Significance of atherosclerotic changes of the ascending aorta during coronary bypass surgery with intraoperative detection by echography. Intraoperative echographic studies of the ascending aorta were carried out on 100 of 222 patients having primary coronary bypass surgeries between May 1987 and December 1988. The purpose of this study was to investigate the feasibility of echographic study in evaluating the nature of atherosclerotic disease of the ascending aorta and its incidence and relationship to perioperative cerebrovascular complications in coronary bypass surgery. It was possible to obtain clear echographic images of the aortic wall in these 100 patients which were divided into two groups according to the degree of the degenerative process. Three of 13 patients (23%) (Group II) with severe atherosclerotic changes, suffered perioperative cerebrovascular complications, and early surgical mortality in 2 patients (15%) was caused by cerebrovascular complications. These complications were not seen in 87 patients with less than moderate atherosclerotic changes (Group I). 
Immediate effect of vagotomy on pancreatic insulin secretion. The effect of vagotomy and gastric resection on insulin secretion was examined by the glucagon stimulated C-peptide test in gastrectomy patients (n = 11) without truncal vagotomy and in total gastrectomy patients (n = 10) with truncal vagotomy. The test was performed twice in each patient: 10 minutes after the midline incision was made and then 60 to 90 minutes later when gastric resection or total gastrectomy was completed, during the reconstructive phase of the operation. Gastric resection without truncal vagotomy was followed by a higher increase (48%) in serum C-peptide concentration caused by glucagon stimulation than total gastrectomy with truncal vagotomy (13%). There was a significant (p less than 0.05) increase in the glucagon stimulated glucose-related C-peptide concentration in patients without truncal vagotomy, whereas truncal vagotomy inhibited this increase. These results suggest that truncal vagotomy will produce a reduction in stimulated insulin secretion in humans. 
Tranexamic acid treatment of hemothorax in two patients with malignant mesothelioma. Patients with malignant mesothelioma may present with hemothorax. We used a combination of oral and intrapleural tranexamic acid to treat two patients with this severe complication. Initiation of treatment with this potent anti-fibrinolytic drug resulted in rapid reduction of bleeding and of transfusion requirements. 
Emergency management of the adult female rape victim. Estimates are that one in every six women is raped during her lifetime. The family physician must be able to evaluate and treat the rape victim in the emergency setting. A detailed history, careful physical examination, collection of medical specimens for legal purposes, assessment of the patient's psychologic state, prophylaxis of venereal disease and pregnancy counseling are required. 
Increased cell membrane arachidonic acid in experimental colorectal tumours. Tumour cell membrane fatty acid composition was investigated using an animal model of colorectal carcinogenesis. Eighty six male Wistar rats were fed experimental diets containing either 5% saturated fat or 20% saturated fat. Colorectal tumours were induced by intraperitoneal injection of azoxymethane, and control rats received saline. Animals were killed at intervals up to 26 weeks after the last injection of carcinogen for histology and lipid analysis. Cell membrane fatty acids in colonic mucosa and colorectal tumours were determined by gas liquid chromatography. Animals fed the 20% fat diet developed more carcinomas (28 cancers in 14 rats) than those fed the 5% fat diet (14 cancers in 15 rats; chi 2 = 8.03, p = 0.0046) but they did not develop significantly more adenomas (28 and 24 respectively). Cell membrane fatty acid analysis showed a considerable increase in the content of arachidonic acid (20:4, n-6) in the tumours (mean (SEM) 11.7 (1.5)%) compared with colonic mucosa (4.2 (0.4)%; p less than 0.05). Dietary fatty acid composition was also found to influence the profile of fatty acids in the colonic mucosa. This study suggests that a high saturated fat diet promotes the malignant transformation of colorectal adenomas. The colorectal tumours were characterised by an increased cell membrane arachidonic acid, the precursor of putative cancer promoting prostaglandins. 
Orifice variability of the stenotic aortic valve: evaluation before and after balloon aortic valvuloplasty. The effects of balloon aortic valvuloplasty on orifice variability of the stenotic sclerocalcific aortic valve were evaluated by hemodynamic measurements of aortic valve function in 14 patients before balloon aortic valvuloplasty, during nitroprusside infusion before valvuloplasty, 48 h after valvuloplasty and during nitroprusside infusion 48 h after valvuloplasty. Aortic valve function was assessed by aortic valve area calculations with use of the Gorlin and Cannon formulas. Nitroprusside infusion before balloon aortic valvuloplasty caused no change in mean aortic valve gradient but a significant increase in mean aortic transvalvular flow from 186 +/- 46 to 202 +/- 61 ml/s (p less than 0.05), in Gorlin aortic valve area from 0.49 +/- 0.17 to 0.53 +/- 0.21 cm2 (p less than 0.05) and in Cannon aortic valve area from 0.45 +/- 0.18 to 0.49 +/- 0.22 cm2 (p less than 0.05). Nitroprusside infusion 48 h after valvuloplasty induced no change in mean aortic valve gradient but a significant increase in mean aortic transvalvular flow from 214 +/- 61 to 254 +/- 78 ml/s (p less than 0.005), in Gorlin aortic valve area from 0.71 +/- 0.25 to 0.83 +/- 0.32 cm2 (p less than 0.01) and in Cannon aortic valve area from 0.78 +/- 0.33 to 0.88 +/- 0.40 cm2 (p less than 0.05). Forty-eight hours after valvuloplasty, nitroprusside infusion induced a larger increase (40 +/- 40 ml/s) in mean transvalvular flow than before valvuloplasty (16 +/- 27 ml/s; p less than 0.05) and a larger increase (0.12 +/- 0.14 cm2) in Gorlin aortic valve area than before valvuloplasty (0.05 +/- 0.07 cm2; p less than 0.05). 
Tissue plasminogen activator reduces brain injury in a rabbit model of thromboembolic stroke. Tissue plasminogen activator is an endogenous fibrin-specific serine protease with potent thrombolytic activity. We investigated the efficacy of tissue plasminogen activator in reducing cerebral infarct size after thromboembolic stroke in a rabbit model. Seventeen rabbits were randomized to receive either tissue plasminogen activator (2.5 mg/kg, n = 6) or vehicle control (n = 11). We controlled mean arterial pressure, hematocrit, and arterial blood gases before and after the intracarotid embolization of an autologous clot. Cerebral blood flow (cm3/100 g/min) (mean +/- SEM) was immediately reduced from 55.2 +/- 7.7 to 8.5 +/- 2.5 in the control group and from 61.8 +/- 14.8 to 10.0 +/- 3.5 in the treated group after embolization. Cerebral blood flow recovered significantly within 60 minutes of thrombolytic therapy and attained a value of 59.6 +/- 10.0 cm3/100 g/min 4 hours after embolization, whereas cerebral blood flow in control animals demonstrated only a minimal recovery to 15.3 +/- 8.9 cm3/100 g/min. Cerebral infarct size (percent of hemisphere) was reduced from 34.4 +/- 5.6% in control animals to 8.8 +/- 5.6% in treated animals (mean +/- SEM, p less than 0.01). These results suggest that tissue plasminogen activator may be efficacious in restoring cerebral blood flow and thus limiting infarct size in acute thromboembolic stroke. 
Stage T1 bladder cancer: grade is the primary determinant for risk of muscle invasion. Tumor characteristics believed to predict for deep muscle invasion after transurethral resection of superficial bladder cancer alone were analyzed in 51 patients with stage T1 (stage A) transitional cell carcinoma of the bladder. All patients were treated at Stanford University Medical Center and none had intravesical chemotherapy at any time during the median followup of 78 months. No patient had carcinoma in situ. A total of 14 patients (27%) had deep muscle invasion. None of the patients with grade 1, 5 (22%) with grade 2 and 9 (50%) with grade 3 to 4 tumors had deep muscle invasion. Comparison of the risk of muscle invasion using pathological tumor grade at diagnosis, highest grade at any cystoscopic biopsy before the diagnosis of muscle invasion or highest grade at cystoscopic biopsy immediately antecedent to the cystoscopy at which muscle invasion was diagnosed all showed similar probability of muscle invasion. Mean interval to development of muscle invasion was 6 and 12 months in the grades 2 and 3 to 4 groups, respectively. At 36 months the cumulative probability of invasion-free survival was 62% for grade 2, compared to 50% for grades 3 to 4 cancer patients (p less than 0.005, Gehan). Univariate regression analysis demonstrated grade to be the only significant factor in predicting for invasive disease (p = 0.005), with tumors in the bladder neck to be of borderline significance (p = 0.159). On multivariate logistic regression analysis, grade remained the single tumor variable predicting for invasive bladder cancer (p = 0.004). These data suggest that of routinely available data at diagnosis and during subsequent followup cystoscopic examinations, tumor grade is the most important biological predictor of progression to muscle invasive cancer. 
Efficacy of quinine for falciparum malaria according to previous chloroquine exposure. Chloroquine has been reported to antagonise the anti-parasitic action of quinine against Plasmodium falciparum in vitro. We looked for evidence of any such antagonism in vivo. In 123 Malawian children with cerebral malaria treated with parenteral quinine, the likelihood of survival and the rate of recovery were much the same in patients who had taken chloroquine and those who had not. In these circumstances we found no evidence of chloroquine/quinine antagonism. 
Influence of the ultrasonic surgical aspirator on the dura and spinal cord. An electrohistologic study. The influence of the ultrasonic surgical aspirator on the dura and underlying spinal cord was examined. Spinal-cord-evoked potential was simultaneously recorded. In a test of identical time, the degree of influence on the dura, the pia mater, and the spinal cord increased according to the increase of energy of the ultrasonic surgical aspirator. With 60% energy at 20 seconds and 80% energy at both 10 and 20 seconds, spinal-cord-evoked potential showed wave changes. In light of these results, it is suggested that in using the ultrasonic surgical aspirator on the dura, the electrohistologic safety limit be set at 60% energy and the maximum time duration at one point less than 10 seconds. 
Idiopathic trigeminal pain associated with gustatory stimuli. We present a unique case of a patient with facial pain evoked by gustatory stimuli. Pain was typically evoked by application of sucrose to the ipsilateral anterior 2/3 of the tongue, but not to the contralateral aspect. Pain was referred to the maxillary tuberosity area and, when stronger, to the infraorbital and supraorbital regions. Sucrose was most effective in eliciting pain, whilst saline, citric acid and water had a minimal effect. Spatial or temporal summation of gustatory stimuli was associated with stronger pain of longer duration and shorter latency. Some of the pain characteristics were similar to those of idiopathic trigeminal neuralgia. Thus, pain was elicited by innocuous ipsilateral stimuli, referred out of the stimulus zone, persisted beyond the period of stimulation and could be controlled with carbamazepine. We proposed a central neural mechanism for pain induction with convergence between gustatory stimuli afferents and pain pathways in the trigeminal system. 
Heart rate response to an i.v. test dose of adrenaline and lignocaine with and without atropine pretreatment. In order to evaluate the sensitivity of an adrenaline test dose for detecting intravascular injection and the effect of atropine pretreatment, 90 ASA physical status I and II patients were allocated randomly to two groups, to receive i.v. saline 1 ml (n = 46) or i.v. atropine 0.5 mg (n = 44). Five minutes later, all patients received an i.v. test dose of 2% lignocaine 3 ml with adrenaline 15 micrograms at a rate of 1 ml s-1. The groups were similar with respect to basal heart rate (HR). HR remained unchanged after saline injection, but increased slightly 5 min after atropine injection (mean 78 (SD 15) beat min-1 vs 87 (20) beat min-1 (P less than 0.05). After the test dose of lignocaine with adrenaline, HR increased significantly in both groups at 30 s, 1 and 2 min, and remained increased at 3 min in the atropine group. The maximum increase in HR was greater in the atropine group than in the saline group (31 (4) beat min-1 vs 26 (11) beat min-1 (P less than 0.05). However, when individual maximum HR changes are considered, five patients in the saline group and four in the atropine group had an increase less than or equal to 10 beat min-1, and three patients in the saline group had no change or a decrease in HR. Defining a positive result to a test dose as an increase in HR of greater than 10 beat min-1, the sensitivity of the adrenaline test dose was 83 (5.5)% in the saline group and 91 (3.5)% in the atropine group (ns). 
Radiation therapy for primary carcinoma of the extrahepatic biliary system. An analysis of 63 cases. From 1976 to 1988, 63 patients received radiation therapy for primary cancers of the extrahepatic biliary system (eight gallbladder and 55 extrahepatic biliary duct). Twelve patients underwent orthotopic liver transplantation. Chemotherapy was administered to 13 patients. Three patients underwent intraluminal brachytherapy alone (range, 28 to 55 Gy). Sixty patients received megavoltage external-beam radiation therapy (range, 5.4 to 61.6 Gy; median, 45 Gy), of whom nine received additional intraluminal brachytherapy (range, 14 to 45 Gy; median, 30 Gy). The median survival of all patients was 7 months. Sixty patients died, all within 39 months of radiation therapy. One patient is alive 11 months after irradiation without surgical resection, and two are alive 50 months after liver transplantation and irradiation. Symptomatic duodenal ulcers developed after radiation therapy in seven patients but were not significantly related to any clinical variable tested. Extrahepatic biliary duct cancers, the absence of metastases, increasing calendar year of treatment, and liver transplantation with postoperative radiation therapy were factors significantly associated with improved survival. 
Spinal cord schistosomiasis. A clinical, laboratory and radiological study, with a note on therapeutic aspects. Fourteen patients with schistosomiasis of the spinal cord are described. They fall into two groups: 7 patients had clinical and computer-assisted myelographic evidence of lesions in the conus medullaris or cauda equina, or both. The clinical picture in the remaining 7 patients was usually that of acute or subacute transverse myelitis with normal or equivocal CT myelographic appearances. Granulomas containing bilharzial ova were found in 2 female patients with conus swelling subjected to laminectomy and biopsy. In 1 of these the ova were identified as S. haematobium while in the second, unidentified bilharzial ova were found. A presumptive diagnosis of spinal cord schistosomiasis was made in the remaining 12 patients based on characteristic clinical and investigative profiles. All 13 patients tested showed evidence of bilharzial infection based on positive blood serology or the detection of bilharzial ova, or both. All but 1 patient showed at least one of the following abnormalities on CSF examination: pleocytosis, an elevated protein content and as indicated by the presence of oligoclonal IgG bands, an elevated IgG index and an increased CSF IgG synthesis rate. A CSF bilharzia enzyme-linked immunosorbent assay (ELISA) test, developed to indicate the presence of schistosomal infection within the theca, was found to be sensitive although not entirely specific for the diagnosis of spinal cord schistosomiasis. Eleven of the 14 patients showed rapid clinical improvement, 8 after praziquantel and corticosteroid treatment, 2 after operation and 1 spontaneously. Significant reductions in the CSF cell count, protein concentration and bilharzia ELISA titre, and in intrathecal antibody production, occurred following praziquantel and corticosteroid therapy. The CSF sugar level showed a significant rise. A reduction in conus size was observed in 3 patients when CT myelography was repeated after medical therapy. The normalization of most of the laboratory parameters after combined medical treatment with praziquantel and corticosteroids, together with clinical and radiological improvement, strengthened the presumptive diagnosis of cord schistosomiasis and supports the policy of early intensive medical treatment (as opposed to surgical therapy) for this condition when diagnosed on indirect evidence. 
Malignant melanoma in the 1990s: the continued importance of early detection and the role of physician examination and self-examination of the skin. Despite the exciting new techniques being developed to help diagnose early malignant melanoma, the current standard of care remains periodic examination of the skin. The combination of routine physician examination coupled with self-examination of the skin provides an opportunity for the identification of early malignant melanoma. Removal of such thin lesions can significantly reduce the ever-increasing mortality rate from this potentially serious form of cutaneous cancer. 
The adverse impact of cyclosporine on serum lipids in renal transplant recipients. The extent to which cyclosporine (CsA) directly, or indirectly, influences serum lipid levels in renal transplant patients treated with multiple-drug immunosuppression protocols is unclear. Indeed, patients treated with CsA have reduced corticosteroid requirements, fewer acute rejection episodes, and other differences from patients receiving conventional immunosuppression that may reduce serum lipid levels. We studied patients treated with low-dose CsA, corticosteroids, azathioprine, and Minnesota antilymphocyte globulin ([ALG] n = 205) versus conventional (three-drug) immunosuppression (n = 368) and evaluated the impact of CsA, acute rejection episodes, and other clinical parameters on serum lipids. Fasting serum lipid levels from stable patients transplanted between 1976 to 1989 were studied at 3 (n = 573), 12 (n = 565), 26 (n = 55), and 52 (n = 521) weeks posttransplant using multivariate, linear regression analysis. The incidence of acute rejection episodes was reduced by CsA, but patients with fewer acute rejection episodes in the early posttransplant period had higher serum total cholesterol (increased by .33 +/- .12 mmol/L [13 +/- 5 mg/dL] and .27 +/- .12 mmol/L [10 +/- 5 mg/dL], P less than 0.05, at 3 and 12 weeks, respectively) and low-density lipoprotein (LDL) (increased by .23 +/- .11 mmol/L [9 +/- 4 mg/dL] and .23 +/- .11 mmol/L [9 +/- 4 mg/dL], P less than 0.05). 
Squamous metaplasia in hormonally treated prostatic cancer. Significance during follow-up. A prospective study of 59 hormonally treated prostatic cancer cases was undertaken during follow-up with sequential transrectal palpation and fine-needle aspiration. At initiation of therapy patients' ages ranged from forty-eight to eighty-two years (median, 68 years). The usual follow-up interval was 6 +/- 3 months, and follow-up periods ranged from six months to one hundred twenty months (median 48 months). The cytologic findings were categorized under four cytologic response types and palpation findings under five response grades. Four different degrees of squamous metaplasia (1+, 2+, 3+, 4+) were observed in smears, depending on semiquantitative determination of squamous metaplastic cells in relation to the total amount of benign and malignant epithelial cells in the smear. There were 341 follow-up observations in which both transrectal fine-needle aspiration cytology and palpation were done. In 306 of these, cytologic findings were found to be adequate. Comparison of squamous metaplasia with cytologic response types revealed a highly significant difference between the benign state and recurrence/frank malignancy. This was also true when frequency of squamous metaplasia was compared with palpatory response grades. It was found that squamous metaplasia can be a valuable adjunct to other cytomorphologic changes such as shrinkage of tumor cell size and decrease in size of nucleoli or its disappearance, in determining response to hormonal therapy. 
Effects of lipoprotein (a) on success rate of thrombolytic therapy in acute myocardial infarction. Lipoprotein (a) [Lp(a)] and plasminogen share a high degree of homology as recently evidenced by amino acid and deoxyribonucleic acid analysis. As Lp(a) is enzymatically inactive, it has been suggested that high levels of Lp(a) may suppress the profibrinolytic activity at the cell surface and increase the risk for arteriosclerosis and thrombosis by competitive inhibition of plasminogen. The present study evaluated whether high levels of Lp(a) influence thrombolytic therapy in patients with acute myocardial infarction. Forty-one patients with acute myocardial infarction received a combination low-dose thrombolytic therapy with recombinant tissue-type plasminogen activator (rt-PA) and human single-chain urokinase-type plasminogen activator (scu-PA). This regimen did not induce plasminemia or a lytic state as indicated by well-maintained levels of fibrinogen. Coronary patency was assessed angiographically 90 minutes after initiation of treatment. Thrombolysis was successful in 30 and unsuccessful in 11 patients. Patients with high Lp(a) levels (greater than or equal to 25 mg/dl) (n = 9) responded equally well to thrombolytic therapy (8 of 9, patency 89%) as did patients with normal or low levels of Lp(a) (22 of 32, patency 70%, difference greater than 0.1). Lp(a) levels did not differ significantly between patients with successful and unsuccessful thrombolysis. Our results demonstrate that high levels of Lp(a) do not affect thrombolysis in patients with acute myocardial infarction when low-dose pharmacologic concentrations of rt-PA and scu-PA are applied in combination. 
Mechanism of cyclosporine-induced hypertension. Cyclosporine is a common immunosuppressive agent used in solid organ and bone marrow transplants and the treatment of some immunological diseases. It has been established that treatment with cyclosporine can cause a patient to develop hypertension within a few weeks of treatment. This review will examine this effect and effective ways to treat it. 
A five-year appraisal and hemodynamic evaluation of the Bjork-Shiley Monostrut valve. Two hundred forty-four Bjork-Shiley Monostrut valves were implanted in 225 consecutive patients from October 1983 to December 1988. Aortic valve replacement was performed in 90 patients, mitral valve replacement in 118, and double valve replacement in 16 patients. One patient had tricuspid valve replacement. There were 100 female patients and 125 male patients with a mean age of 54 years (range 2 to 71 years). Present data were completely available for all patients. The cumulative follow-up was 541 patient-years with a mean of 2 years, 5 months. The closing date for follow-up was July 1989, and the closing interval was 2 months. The early mortality rate was 3.1%, and the late mortality rate, 3.1%. The 5-year survival rate was 88% +/- 2.0%: 87% +/- 3.0% for aortic valve replacement, 91% +/- 3.3% for mitral valve replacement, and 75% +/- 9.6% for double valve replacement. The actuarial rates of freedom from thromboembolism at 5 years were 93% +/- 3.2% for aortic, 96% +/- 1.4% for mitral, and 94% +/- 6.1% for double valve replacement. There were no instances of structural valve deterioration. Actuarial rate of freedom from valve-related morbidity and mortality was 86% +/- 2.0% at 5 years: 86% +/- 9.5% for aortic, 87% +/- 3.3% for mitral, and 75% +/- 7.3% for double valve replacement. Effective valve areas (average) of 12 mitral and 12 aortic valve prostheses were calculated at rest and during bicycle exercise: 2.4 cm2 at rest and 2.8 cm2 during exercise in 27 mm aortic valves, 2.4 cm2 at rest and 3.0 cm2 during exercise in 25 mm aortic valves, 2.0 cm2 at rest and 2.4 cm2 during exercise in 27 mm mitral valves, and 2.6 cm2 at rest and 2.5 cm2 during exercise in 29 mm mitral valve. On the basis of our follow-up period of 5 years, we have judged the Bjork-Shiley Monostrut valve reliable, with a low incidence of valve-related morbidity and with acceptably satisfactory hemodynamic characteristics at rest and during exercise. 
Reduction in susceptibility to natural killer cell-mediated lysis of human FO-1 melanoma cells after induction of HLA class I antigen expression by transfection with B2m gene. Induction of HLA class I antigens on cultured melanoma cells FO-1 after transfection with a human or a mouse B2m gene was associated with a statistically significant reduction in their susceptibility to natural killer (NK) cell-mediated lysis. These results indicate that the structural differences between human and mouse beta 2-mu do not abolish the ability of the HLA class I molecular complex to modulate NK cell-mediated lysis of melanoma cells FO-1. The role of HLA class I antigens in the phenomenon is corroborated by the ability of anti-HLA class I MAb to enhance, although to a different extent, the susceptibility of transfected FO-1 cells to NK cell-mediated lysis. Gamma interferon (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) significantly reduced the susceptibility to NK cell-mediated lysis of transfected FO-1 cells. Surprisingly, TNF-alpha reduced the extent of lysis more than IFN-gamma, although the latter cytokine enhanced HLA class I antigen expression more than the former one. This finding, in conjunction with a reduction in the susceptibility to NK cell-mediated lysis of untransfected FO-1 cells incubated with IFN-gamma or TNF-alpha, suggests that the two cytokines reduce NK cell-mediated lysis of transfected cells by modulating not only the expression of HLA class I antigens, but also that of other structures. Induction of HLA class I antigens and their modulation with IFN-gamma did not affect the susceptibility to lymphokine-activated killer (LAK) cell-mediated lysis of transfected FO-1 cells. Characterization of the molecular mechanism(s) underlying abnormalities in HLA class I antigen expression by melanoma cells and of the role of these molecules in the interactions of melanoma cells with various types of effector cells may suggest novel immunotherapeutic approaches to melanoma. 
Evaluation and management of stridor in the newborn. Stridor in a newborn should necessitate an immediate work-up to rule out a life-threatening airway obstruction. Three cases of newborns with stridor are presented. These cases emphasize the need for an immediate and thorough physical examination of any stridorous newborn, followed by radiologic studies and direct laryngoscopy. While other invasive procedures are frequently required for a precise diagnosis, a careful examination with special attention to the quality of the stridor often permits a more effective diagnostic approach in an atmosphere of appropriate urgency. 
Comparative evaluation of loracarbef and amoxicillin-clavulanate for acute otitis media. One hundred five infants and children with acute otitis media were randomized to therapy with loracarbef, an experimental carbacephem antibiotic, or amoxicillin-clavulanate (Augmentin), an approved drug for this disease. Ninety-two were evaluable (46 in each group). Middle ear fluid samples obtained for culture before therapy grew Haemophilus spp. in 30% of cases, pneumococci in 29% of cases, and Moraxella catarrhalis in 15% of cases. beta-Lactamase-producing bacteria were found in 37% of patients. Clinical failure occurred in four loracarbef-treated patients and one amoxicillin-clavulanate-treated patient (P = 0.361). Recurrence of acute otitis media was more common in the 2 to 3 weeks after loracarbef treatment (eight patients) than it was after amoxicillin-clavulanate therapy (three patients), but not significantly so (P = 0.197). Thus, combined failure and recurrence occurred in 12 loracarbef-treated patients and four amoxicillin-clavulanate-treated patients (P = 0.052). Gastrointestinal side effects occurred in 13 loracarbef-treated and 21 amoxicillin-clavulanate-treated patients (P = 0.13). Diaper rash was more common with amoxicillin-clavulanate (22 patients) than with loracarbef (10 patients; P = 0.016). Satisfactory results were achieved with both antibiotics, and adverse effects, although common, were minor. 
Psychosocial aspects of chronic, clinically unconfirmed vulvovaginitis Women with chronic symptoms of vulvovaginitis referred to a university vulvovaginitis clinic were assessed on psychological and social (including sexual) variables to determine whether differences existed among women with unconfirmed vulvovaginitis, women with confirmed vulvovaginitis, and healthy controls. Eighty-three consecutive women with chronic symptoms of vulvovaginitis and 32 asymptomatic control women completed clinical examinations, cultures, and the following psychological tests or questionnaires: the Brief Symptom Inventory, the Center for Epidemiologic Studies--Depression Scale, the Dyadic Adjustment Scale, a sexual behavior and response questionnaire (Campion), and a study questionnaire. Statistical analyses (chi 2 and analysis of variance) were performed on the confirmed and unconfirmed vulvovaginitis and control groups of women. Women with confirmed and unconfirmed vulvovaginitis scored higher than control women on several psychological variables, but women with unconfirmed vulvovaginitis were found to be significantly more emotionally distressed on psychological tests and to report more discomfort during sexual intercourse than both women with confirmed vulvovaginitis and healthy controls. Psychosocial inquiry is important in the clinical assessment and management of such women. 
The role of radical surgery in the management of radiation recurrent and large volume prostate cancer. Twenty-two patients seen between 1975 and 1988 were analyzed who had surgical attempts to cure locally advanced prostate cancer by exenterative procedures or salvage surgery for radiation recurrent disease. Twelve patients (Group I) underwent either a salvage cystoprostatectomy or perineal prostatectomy for radiorecurrent disease, including three patients with a Kock continent urinary diversion done in combination with the salvage operation. Five of the 12 (41.7%) recurrent disease confined to the surgical specimen and 11 of 12 (91.7%) are alive at a mean follow-up of 49 months, including four patients (25%) with a completely negative serum prostate-specific antigen (PSA) value (less than 0.2 ng/dl). All perineal prostatectomy patients are continent, and two of the three Kock pouch patients are continent. Ten of the 22 patients (Group II) had a cystoprostatectomy or exenteration for locally advanced disease that the surgeon did not think was amenable to standard radical prostatectomy. Only one of these ten patients had negative surgical margins, capsule, and seminal vesicles. Nine are alive (although only one patient has no evidence of disease) at a mean follow-up of 59 months. Morbidity was substantial with a 50% major complication rate including four patients requiring reoperation because of bleeding, abscess, bowel obstruction, or colostomy closure. Salvage procedures for radiorecurrent disease can be done safely, even with the inclusion of a continent diversion, and may be curative or provide survival benefit to carefully selected patients. Cystoprostatectomy or exenteration for locally advanced disease does not appear to be a curative endeavor for most patients and may be accompanied by significant morbidity. 
Drug-induced modification of vascular structure: effects of antihypertensive drugs. It has long been realized that hypertension causes alterations in the peripheral vasculature, with the arterial wall becoming thicker and the lumen relatively smaller. This is particularly true in small resistance arteries, but larger vessels are also affected. The precise mechanisms remain to be determined, although it is highly likely that growth-promoting autacoids are involved as well as mechanical forces. Numerous studies of hypertension in animal models and a few in hypertensive humans have tried to establish the reversibility of these changes after successful lowering of blood pressure. Too few data are available to form firm conclusions, but thiazides and hydralazine-like vasodilators appear to have only a minimal effect on the vasculature. On the other hand, angiotensin-converting enzyme inhibitors are clearly effective, and alpha-blockers may be active. However, it is difficult to derive even tentative conclusions from the available information on calcium antagonists and beta-blockers. These results are discussed in the context of future therapeutic and investigative approaches. 
Correlation between sexual abuse and somatization in women with somatic and nonsomatic chronic pelvic pain. After a comprehensive clinical and psychological evaluation, 99 women with pelvic pain of at least 6 months' duration and normal findings at laparoscopy were divided into two groups, including 47 women with probable somatic causes of pain (group 1) and 52 women without identifiable somatic abnormality (group 2). Women without identifiable somatic abnormality (group 2) were younger, had higher mean somatization scores, and reported an earlier mean age at first intercourse, a higher number of total sexual partners, and a higher prevalence of sexual abuse before the age of 20. Within group 2 (nonsomatic pain) but not within group 1, mean somatization scores were significantly higher among women with a history of sexual abuse than among women with a negative history. When analyzed as risks for nonsomatic pelvic pain, the positive predictive value of both a history of sexual abuse and a high somatization score was 78% (relative risk compared with that of women with zero or one risk factor, 2.1; p less than 0.0001). These data suggest that the psychosocial profile of women with nonsomatic pelvic pain differs from that of women with somatic pelvic pain and that previous sexual abuse is a significant predisposing risk for somatization and non-somatic chronic pelvic pain. 
Restenosis 1 to 24 months after clinically successful coronary balloon angioplasty: a necropsy study of 20 patients. This report describes clinical, morphologic and histologic findings at necropsy late (range 1.6 to 24.1 months [average 8.2 months]) after clinically successful coronary balloon angioplasty in 20 patients with coronary angioplasty restenosis. Clinical evidence of restenosis occurred in 14 patients (70%), including 6 patients with sudden coronary death. Of the 20 patients, 14 (70%) had a cardiac cause of death and 6 (30%) had a noncardiac cause of death. Two major subgroups of histologic findings were observed: 1) intimal proliferation (60%), and 2) atherosclerotic plaque only (40%). Of the eight sites with atherosclerotic plaque only, six were eccentric lesions and two were concentric lesions. No morphologic evidence of previous angioplasty injury (cracks, breaks, tears) was observed in the eight patients with atherosclerotic plaque only. Proposed mechanisms for the development of intimal proliferation involve the reaction of smooth muscle cells and platelets, whereas elastic recoil of overstretched eccentric or concentric atherosclerotic lesions represents the most likely explanation for the findings in the latter subgroup. On the basis of these morphologic findings at angioplasty restenosis sites, specific treatment strategies for restenosis after coronary artery balloon angioplasty are proposed. 
Acute postinfarction septal rupture: long-term results. From 1973 to 1989, 66 patients received early surgical repair for acute postinfarction ventricular septal rupture. Mean age was 64 +/- 7 years (range, 45 to 80 years). Ventricular septal rupture occurred soon after acute myocardial infarction (3.4 +/- 4 days), and the first medical treatment occurred 6.7 +/- 7 days after onset of acute myocardial infarction. Three patients had a previous myocardial infarction. The site of the rupture was anterior in 38 patients (57%) and posterior in 28 (43%). Forty-four patients (67%) were in shock at the time of admission. Intraaortic balloon pumping was used preoperatively in 28. Operation was performed at the time of maximal efficacy of medical treatment. The same technique was used in all cases. Associated procedures included coronary bypass grafting in 5 patients and valvar operation in 5. The patients have been carefully followed up for up to 16 years. Hospital mortality was 45% (30 patients) and was cardiac related or due to acute renal failure in 25 patients (83%). No correlation could be revealed between early death and age, sex, preoperative intraaortic balloon pumping, or year of operation. Location of the ventricular septal rupture (early mortality of 57% for posterior versus 37% for anterior ventricular septal rupture) and shock at the time of admission (52% versus 32%) showed a trend toward significance (0.08 less than or equal to p less than 0.10). Response to initial active therapy has a strong predictive value (mortality of 70% in unresponsive patients versus 14% in responders; p less than 0.001). 
Acute traumatic cervical epidural hematoma from a stab wound. Cervical spinal epidural hematoma is an infrequent entity that usually requires emergency decompressive therapy because of rapid neurologic dysfunction. We present the case of a 34-year-old man who presented to the emergency department with minimal symptomatology after a stab wound to the neck. A computed tomography myelogram of the cervical spine revealed a cervical spinal epidural hematoma. This case illustrates an unusual presentation as well as etiology of cervical spinal epidural hematoma. 
Gastric duplication cyst. Endoscopic presentation as an ulcerated antral mass. A case of a 53-year-old man who presented with epigastric pain and weight loss is described. Endoscopy showed a smooth antral mass with what appeared to be a central overlying ulcer. Computerized tomography and upper gastrointestinal series confirmed the presence of a gastric mass. Laparotomy and local resection showed a gastric duplication comprised of two cysts, one with communication to the stomach lumen. Gastric duplication is a rare entity, especially in the adult. Though generally benign, local ulceration or fistula formation can cause symptoms and may suggest a more malignant process that warrants investigation. 
Biomechanics of fixation systems to the cervical spine. The biomechanical evaluation of a cervical spine implant must include flexural and torsional testing if it is used for stabilizing a traumatic unstable motion segment. A cadaveric model is presented that allows flexural and torsional testing of a cervical spine motion segment, measuring the tilting angle, the translation, and the torsional angle. After measuring the intact segments, in the first series, a so-called posterior instability was created and stabilized posteriorly with the hook-plate and sublaminar wiring; anteriorly with the H-plate; and with combinations of these implants. In a second series, their stabilizing effect after complete discoligamentous instability was tested. With isolated posterior instability, it was found that the flexural stability is preserved, whereas torsional stability is markedly reduced. In cases of isolated posterior instability, only hook plating alone or its combination with anterior H-plating seemed to bring about a higher torsional stability than the intact specimen. In cases of complete discoligamentous instability, only anterior H-plate and posterior hook plate procedures combined or the hook plate alone was able to guarantee both torsional and flexural stability higher than the intact spine. Exclusive posterior wiring without postoperative external immobilization in complete discoligamentous instability may result in permanent subluxation of the functional unit. Exclusive anterior H-plate fixation in complete discoligamentous instability requires additional external immobilization in the postoperative phase to prevent flexion and torsion. 
Postoperative vasospasm after antegrade mesenteric revascularization: a report of three cases. Vascular reconstruction for chronic intestinal ischemia can be accomplished by endarterectomy or aortomesenteric bypass. In our practice, antegrade bypasses from the supraceliac aorta to the celiac axis and superior mesenteric artery are currently the most frequently used techniques. Such reconstructions often use multiple or bifurcated large diameter vascular prostheses and have demonstrated excellent long-term patency. Despite these salutory results, we have noted an unusual perioperative response in three of these patients, which is the subject of this report. All three patients underwent uncomplicated elective mesenteric revascularization with grafts (diameter greater than or equal to 6 mm) originating in the supraceliac aorta. Indications for operation included (1) history of postprandial pain, (2) documentation of weight loss, and (3) angiographic evidence of advanced atherosclerotic disease with appropriate collateral development. Episodes of abdominal pain occurred 5 to 20 days after operation when normal food intake was reinstituted. In two patients immediate angiograms revealed patent grafts with diffuse mesenteric vasospasm. Treatment with intravenous hyperalimentation and nifedipine for 10 days resulted in complete resolution of symptoms. In the third patient, symptoms were totally relieved by temporary reduction in oral intake and administration of nifedipine. A later angiogram revealed a patent graft. All patients have remained asymptomatic and regained normal weight. This pattern of postrevascularization pain has not been seen in our patients undergoing revascularization with small (i.e., venous) conduits originating in the infrarenal aorta. The cause appears to be a heightened myogenic response of a "protected" vascular bed when suddenly exposed to the high perfusion pressure and blood flow of large caliber antegrade conduits. Prophylaxis with calcium channel blockers and use of smaller diameter grafts (5 mm) may avoid this disturbing syndrome. 
Immunohistological diagnosis of "plasmacytoid T cell lymphoma" in paraffin wax sections. An immunohistological study of paraffin wax embedded tissue from three cases of plasmacytoid monocyte neoplasms, using a panel of antibodies which react with fixation resistant leucocyte markers, is reported. This neoplasm was found to have a distinctive antigenic profile, being negative for CD3 and elastase, but positive for CD43 and CD68. This immunological phenotype, coupled with its characteristic morphological features, should facilitate the recognition of this rare neoplasm in routinely processed tissue. Furthermore, the term "plasmacytoid monocyte sarcoma" is proposed to designate it because it is inappropriate to refer to it as a lymphoma. As all cases have been associated with a myeloproliferative disorder (usually an acute or chronic myeloid leukaemia), these tumours probably represent the accumulation in lymphoid tissue of neoplastic cells which have differentiated along the plasmacytoid monocyte pathway. 
Migraine--why and how a cortical excitatory wave may initiate the aura and headache. A large number of clinical and neurophysiological observations are reviewed that clearly indicate that the symptoms of migraine aura result from a spread of an excitatory wave along the cortex from a primary focus. This excitation may start as a consequence of information overload to a low threshold cortical area. The transient neuronal excitation is followed by a long-lasting period of reduced cortical flow, which involves a substantial component of active constriction of resistance vessels, even persisting for several hours during the headache phase. When the excitatory wave has reached and activated free pain fiber endings in sufficiently many cortical vessels, off-branching peripheral motor endings of these fibers may become activated via axon reflexes. These motor endings may be located in cortical microvessels or in small vessels around large dural vessels. This leads to a neurogenic inflammation in the vessel walls, experienced as headache by the sufferer. The wall of dural sinuses offers a rational explanation for the beneficial effect of most medications used in migraine. 
Pelvic denervation for chronic pain associated with endometriosis: fact or fancy? The efficacy of presacral neurectomy and amputation of the uterosacral ligaments in the treatment of chronic pelvic pain has been debated for decades. These procedures used to be done mainly in women with normal pelves, but more recently they have been performed during conservative surgery for treatment of endometriosis. In the 1980s the rapid spread of laparoscopic surgery has led to an increasing number of endoscopic denervations in patients with chronic pelvic pain associated with endometriosis. However, an analysis of literature data has failed to prove that presacral neurectomy and amputation of the uterosacral ligaments are effective and did not demonstrate better results with the use of lasers rather than electrocoagulation. Moreover, no valid comparison has yet been made between laparotomy and laparoscopic methods. 
A phase II study of days 1 and 8 cisplatin and recombinant alpha-2B interferon in advanced non-small cell lung cancer. Preclinical data from studies of human lung cancer xenografts suggest that the cytotoxic effects of cisplatin are enhanced by alpha-interferon. To verify the above observations, the authors initiated a Phase II trial in advanced non-small cell lung cancer (NSCLC). Cisplatin was given at 100 mg/m2 during a 28-day cycle in a divided day 1 and day 8 schedule. Starting on day 1, alpha-2B interferon was administered intramuscularly at a dose of 5 million units three times a week continuously for a minimum of 2 months. Between January 1989 and September 1989, 30 patients were evaluated for response and toxicity. According to the staging system proposed by Mountain, 20 patients had Stage IV disease, 7 had Stage IIIB disease, and 3 had Stage IIIA disease. Expression of neuron-specific enolase (NSE) and Leu-7 was immunohistochemically investigated to evaluate possible relationship to treatment response. The response rate was 13.3% (95% confidence interval [CI]: 1.2% to 25%). The four responders showed positivity for NSE, and two of them were positive for Leu-7. An average of three cycles was given. The mean dose intensity administered was 83% of the projected dose for cisplatin and 92% of the projected dose for alpha-2B interferon. A standard scale was used to assess interferon toxicity. Hematologic, renal, and systemic side effects were not significant. In advanced NSCLC the addition of alpha-2B interferon did not increase the cisplatin-induced response rate. Further studies should be performed to determine the real value of chemotherapy response in tumors showing positive immunoreactivity for neural markers such as NSE and Leu-7. 
Gastrointestinal carcinoid tumors. Fifty-five patients were evaluated and treated for gastrointestinal (GI) carcinoid tumors at our institution from 1968 through 1988. Thirty patients had primary tumors smaller than 1 cm and were treated surgically or endoscopically by local excision, whereas 25 underwent resection with regional lymphadenectomy for larger primaries. At the time of initial treatment 17 patients demonstrated metastasis. Although 13 of these patients had primary tumors larger than 2 cm, in four patients with ileal carcinoids, the primary measured 0.8 to 1.5 cm. Serosal involvement was present in nine of 17 patients with metastasis. With a follow-up range of 3 months to 20 years, six patients have died with metastatic carcinoid tumor, two patients died without evidence of disease, 12 patients are alive with metastasis, and 35 patients are alive, free of disease. In this series three determinants for risk of metastasis in GI carcinoid tumors were evident: primary size, serosal penetration, and primary site in the small intestine. In patients with any of these risk factors, resection with regional lymphadenectomy is recommended. 
Adrenocorticotropic hormone-independent bilateral adrenocortical macronodular hyperplasia as a distinct subtype of Cushing's syndrome. Enzyme histochemical and ultrastructural study of four cases with a review of the literature. Four patients with adrenocorticotropic hormone (ACTH)-independent bilateral adrenocortical macronodular hyperplasia (AIMAH) were examined. All of them were men whose ages ranged from 37 to 52 years. Plasma cortisol levels were high, with a loss of diurnal rhythmicity, and plasma ACTH was undetectable. Adrenal cortisol secretion was not suppressed by dexamethasone, but it was ACTH responsive. Test results for corticotropin-releasing hormone (CRH) also were negative. Image analyses revealed a normal sella turcica and significantly enlarged adrenal glands, which showed enhanced uptake of isotope. Both adrenal glands in all cases were between 72 and 176 g in combined weight and were composed of, and distorted by, yellow nodules. Histologically, small cortical cells with or without lipid, occasional clear cells, and rare compact cells of the usual size were increased in number in the glandular cords. Enzyme histochemically, cortical cells showed weaker activity for 3 beta hydroxysteroid dehydrogenase and other enzymes than did usual cortisol-producing adenomas. Ultrastructurally, they had moderately to poorly developed smooth endoplasmic reticulum. Nonnodular areas of the cortex consisting of nonproliferating cells were atrophic and contained no compact cell zone. This is similar to the adrenal cortices attached to cortisol-producing adenomas. These features are unique to AIMAH and suggest the presence of a distinct subtype of Cushing's syndrome. 
Diagnosis and monitoring of subarachnoid hemorrhage by transcranial color-coded real-time sonography. Thirty-six patients with acute spontaneous subarachnoid hemorrhage (26 caused by rupture of an aneurysm) were examined by transcranial color-coded real-time sonography by using a 2.25-MHz ultrasound transducer. In 20 of these 26 patients (76%), the aneurysm could be identified by a characteristic abnormal blood flow pattern within the aneurysm in coronal and axial scanning planes by transcranial color-coded real-time sonography. Blood within the basal cisterns, on top of the tentorium, and within the ventricles and parenchyma was sonographically detected by increased echodensity in 75%. In addition, cerebrospinal fluid circulation disturbances and cerebral vasospasm were detected in two-dimensional B-mode images in 85% and 100%, respectively. In Doppler mode, intravascular blood flow velocity could be quantified. We conclude that transcranial color-coded real-time sonography, a new, noninvasive method for diagnosis and follow-up of patients with subarachnoid hemorrhage, allows detection of the primary vascular lesion and monitoring of complications. 
Correlates of postural hypotension in a community sample of elderly blacks and whites. Postural hypotension is thought to be prevalent among the elderly, but few community-based studies of this condition have been conducted. In addition, little is known about postural hypotension in blacks despite well documented racial differences in hypertension and stroke. Data on 659 elderly (greater than or equal to 60 years of age) participants in a survey of two rural, biracial townships were analyzed to describe the frequency and correlates of postural hypotension. Twelve percent of the 659 adults experienced a drop of 10 mmHg or greater in systolic blood pressure on going from sitting to standing (supine measures were not available). This degree of postural hypotension was twice as common for whites as for blacks (14.5% vs 7.5%, P = 0.01). Postural hypotension was associated with elevated sitting blood pressure and showed positive but statistically non-significant relationships with anti-hypertensive medications and leanness. The association between race and postural hypotension persisted after adjusting for these and other risk factors (OR = 2.2, 95% CI:1.2,4.0). 
Gall stone disease in African patients with sickle cell anaemia: a preliminary report from Yaounde, Cameroon. Cholecystosonography was undertaken in 90 patients with sickle cell disease aged 15 years and over. Gall stones were found in 26 (28.9%) patients. There was no sex difference, but the incidence increased with age from 13.2% at under 20 years to 75% at 30 years and over. The mean serum cholesterol and total and unconjugated bilirubin concentrations were not significantly different between patients with and without gall stones. As most (80.8%) stones were radiolucent they were probably of pigment type, containing little or no calcium, and further investigation into how they are produced is needed. Sickle cell patients with acute abdominal crisis should have gall bladder disease excluded before a diagnosis of vascular crisis is made. 
Coronary heart disease risk factor profiles in black patients with non-insulin-dependent diabetes mellitus: paradoxic patterns. PURPOSE: Non-insulin-dependent diabetes mellitus (NIDDM) in black Americans consists of two variants: one with insulin resistance and one with normal insulin sensitivity. This study examined whether cardiovascular disease risk factors are significantly different between the two variants. PATIENTS AND METHODS: Twenty-two black patients with NIDDM in near-normoglycemic remission who were receiving no pharmacologic therapy for NIDDM were evaluated for insulin sensitivity by the euglycemic insulin clamp, plasma insulin levels, degree of obesity, glucose metabolism, serum total, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) cholesterol levels, and fasting plasma triglyceride levels. RESULTS: Fifty-nine percent of these patients had normal insulin sensitivity (glucose disposal rate in response to a 1 mU.kg-1.minute-1 insulin infusion greater than 6.0 mg.kg-1.minute-1). The insulin-sensitive patients were less obese (body mass index [BMI] 26.5 +/- 0.6 versus 30.8 +/- 0.9 kg/m2) and had lower fasting plasma insulin levels (56.9 +/- 7.8 versus 88.0 +/- 6.0 pmol/L), lower serum cholesterol (4.47 +/- 0.30 versus 6.39 +/- 0.26 mmol/L), lower serum LDL cholesterol (2.77 +/- 0.31 versus 4.51 +/- 0.27 mmol/L), and lower fasting plasma triglyceride levels (0.83 +/- 0.08 versus 1.45 +/- 0.16 mmol/L) than the insulin-resistant patients. Serum HDL cholesterol was not different between the two groups and was in the high-normal range (1.31 +/- 0.08 and 1.19 +/- 0.07 mmol/L). Univariate analysis demonstrated that serum total cholesterol, LDL cholesterol, and fasting plasma triglycerides were highly correlated with insulin-mediated glucose disposal and fasting plasma insulin. The differences in insulin sensitivity and lipid profiles were independent of obesity, as they were present in six insulin-resistant and six insulin-sensitive patients matched for BMI. CONCLUSIONS: Black patients with the insulin-sensitive variant of NIDDM have a low risk factor profile for cardiovascular disease as compared with those with the insulin-resistant variant, who have a high risk factor profile. A high prevalence of the insulin-sensitive variant of NIDDM in the black population might explain the lower prevalence of angina and myocardial infarction in black patients with NIDDM as compared with white patients with NIDDM. 
Decreased adherence of interleukin 6-treated breast carcinoma cells can lead to separation from neighbors after mitosis. Interleukin 6 (IL-6) has been shown to inhibit the proliferation, but increase the motility, of wild-type ZR-75-1 human ductal breast carcinoma cells, a line of cells that resemble closely the malignant cells cultured from the ascitic effusion. IL-6-treated cells lose their epithelial character, become stellate or fusiform in shape, and migrate away from neighbors. In the wild-type ZR-75-1 cells, IL-6 causes cell-cell separation in preformed colonies as well as postmitotically. We have now investigated the action of IL-6 in clone B ZR-75-1 cells, which are morphologically distinct from wild-type ZR-75-1 cells. In the more polygonal rather than cuboidal clone B cells, IL-6 did not cause early inhibition of DNA synthesis and it caused little cell-cell separation in preformed colonies. However, IL-6 treatment markedly prolonged the interval between mitosis and readherence of daughter cells to their neighbors and the substratum. Supernatants from IL-6-treated cultures contained detached viable cells in increased numbers. Intermitotic intervals were prolonged in IL-6-treated cultures. IL-6-treated dividing breast carcinoma cells are characterized by an increased probability of separation from neighbors and the substratum. 
Visual function in patients undergoing long-term total parenteral nutrition. To evaluate the effects of long-term total parenteral nutrition (TPN) on eye function, 27 adults and 12 children in the UCLA Home TPN Clinic underwent ophthalmoscopic examination and visual-function testing. Direct inspection of the fundus showed a marked granularity of the retinal pigmented epithelium in some patients. About one-half of the children and one-third of the adults tested had at least one and usually two abnormalities in their electroretinogram. Determination of blood nutrients thought to affect vision revealed that zinc and vitamin E were within normal range. Vitamin A concentrations were above normal in 10 of 19 adults and selenium concentrations were below normal in 10 of 10 children and 17 of 21 adults tested. Linoleic and linolenic acid concentrations were low; plasma, platelet, and urine taurine concentrations were significantly lower than normal. Despite these diffuse nutrient abnormalities, only zinc and vitamin E concentrations correlated significantly with any index of visual function. 
Lymphomas in University College Hospital, Ibadan, Nigeria. The authors reviewed 508 cases of lymphoma seen during a 16-year period in University College Hospital, Ibadan, Nigeria. Hodgkin's disease was diagnosed in 95 (18.6%) patients, of which 45% had mixed cellularity type; 19%, lymphocyte predominance; 18%, nodular sclerosis; and 18%, lymphocyte depletion. The age distribution showed a single mode in the 11 to 25-year-old group. Male preponderance was more marked in children who made up 32% of the Hodgkin's disease patients. Non-Hodgkin's lymphoma occurred in 413 cases, of which 296 (71.7%) were high-grade malignancies. Burkitt's tumor occurred in 211 (41.5%) patients, 95% of whom were children, and showed a male to female ratio of 1.7:1. Compared with previous findings in this hospital, Hodgkin's disease showed increased proportions of the lymphocyte predominant and nodular sclerosing types. However, the characteristics of Burkitt's lymphoma did not change appreciably in the last three decades. 
Influence of environmental temperature on the blood pressure of hypertensive patients in Montreal. To assess the influence of environmental temperature on blood pressure, we analyzed 42,813 readings of systolic and diastolic blood pressures in recumbent and upright positions in 2,000 hypertensive patients in our clinic in correlation to noon temperature and mean daily temperature in Montreal. The sample comprised 860 men and 1140 women with an average age of 55 years. Analysis of variance showed highly statistically significant negative correlations for all blood pressure values between different noon temperature, as well as mean daily temperature, groups. The greatest difference for systolic blood pressure was 7 mm Hg, and for diastolic blood pressure it was 3 mm Hg, within the -24 degrees C to 27 degrees C temperature range. The same relationship between blood pressure and different environmental temperatures was also seen when the blood pressure recordings were divided between temperature below 0 degree C and above 0 degree C, ie, within the winter or summer months. This environmental effect may have a clinically significant impact because thermosensitivity appears to be related to hypertension. 
Increased tryptase levels in suction-blister fluid from patients with urticaria. The levels of tryptase in the suction-blister fluid from patients with chronic urticaria, urticaria pigmentosa, cholinergic urticaria, urticarial dermographism, prurigo of unknown origin, eczema, psoriasis, atopic dermatitis, and from healthy controls were studied. The blister fluid from controls contained up to 15 micrograms/l of tryptase, whereas that from patients with active urticaria contained greater than 50 micrograms/l. This study demonstrates that patients with urticaria have mast cells that readily release tryptase in both the lesional and non-lesional areas of skin. 
Nephrogenic rests in Wilms tumor patients with the Drash syndrome. The histological specimens from 12 patients with the Drash syndrome were identified from the National Wilms Tumor Study Group and reviewed for the presence of nephrogenic rests. Of 7 patients with the complete Drash syndrome 6 were evaluable for nephrogenic rests, including 5 (83%) who demonstrated intralobar nephrogenic rests. Of 5 (80%) partial Drash syndrome cases 4 (80%) were also intralobar nephrogenic rest positive. Neither group had perilobar nephrogenic rests identified. In a control population of Wilms tumor patients without the Drash syndrome only 39 of 274 (14%) with unilateral tumor had intralobar nephrogenic rests identified, whereas 26 of 92 (28%) bilateral cases had intralobar nephrogenic rests. There was a significantly higher rate of intralobar nephrogenic rests in complete and partial Drash syndrome cases than in the general Wilms tumor population (p less than 0.001). Wilms tumor patients with intralobar nephrogenic rests and the Drash syndrome present at a younger age and have a higher rate of bilaterality than rest negative Wilms tumor patients. The strong association of intralobar nephrogenic rests in the Drash syndrome approaches that found in the aniridia complex. However, in other syndromes associated with Wilms tumor, such as the Beckwith-Wiedemann syndrome and hemihypertrophy, there is a high prevalence of perilobar nephrogenic rests. In view of the high incidence of intralobar nephrogenic rests in complete and partial Drash syndrome patients, it is probable that events leading to Wilms tumor in patients with the Drash syndrome occur at an early stage in nephrogenesis. 
Nonfunctioning parathyroid carcinoma. Parathyroid carcinoma is a rare clinical entity accounting for only 4 per cent of all cases of parathyroid neoplasia. Nonfunctioning parathyroid carcinoma is even rarer. Previously, virtually all patients with these lesions were treated for a nonspecific neck mass. However, in the present case, a preoperative diagnosis of nonfunctioning parathyroid carcinoma was made based on the technetium pertechnetate/thallium 201 subtraction scan. The authors report on the 14th case of nonfunctioning parathyroid carcinoma, a review of the literature, and guidelines for the preoperative and operative evaluation of neck masses suspected to be parathyroid carcinoma. 
Children with epilepsy: the effect of seizures, syndromes, and etiological factors on cognitive functioning. Overall, children with epilepsy have poorer concentration and mental processing and are less alert than age-matched controls. The relationship between cognitive functioning and epilepsy is complex, however, with widely differing degrees of intellectual impairment--ranging from minimal to severe and progressive--related to diverse types of epileptic seizures, syndromes, and etiological factors. Prolonged and frequently repeated seizures are typically associated with more severe effects on cognitive functioning, particularly if epilepsy is symptomatic, i.e., secondary to a demonstrable brain lesion. A combination of such factors may contribute to the mental deterioration seen in many children suffering from severe epilepsy. 
Phase I study of liposomal MTP-PE-activated autologous monocytes administered intraperitoneally to patients with peritoneal carcinomatosis. We have conducted a phase I study with autologous monocytes activated ex vivo and administered intraperitoneally in nine patients with peritoneal carcinomatosis. Blood monocytes were collected by leukapheresis and then purified by counterflow elutriation (up to 10(9) cells, with a purity of greater than 90%). Ex vivo activation was obtained by incubating these cells with 1 micrograms liposomal MTP-PE/10(6) monocytes for 18 hours in hydrophobic culture bags at 37 degrees C in 5% carbon dioxide humidified air. The activated monocytes were then infused in the peritoneal cavity once a week for 5 consecutive weeks through an implanted peritoneal infusion system, Port-A-Cath (Pharmacia Deltec, St Paul, MN), on an intrapatient dose-escalating schedule (10(7) to 10(9) monocytes). No severe adverse reactions occurred. Toxicity was mild, the chief acute reactions being fever (27%), chills (13%), and abdominal pain (25%). None of the side effects led to dose reduction. No consistent change in hemostatic function, liver function, or renal function was observed. Significant increases in granulocyte counts, neopterine, and acute phase reactants (fibrinogen, C-reactive protein) occurred in the peripheral blood. In vitro monocyte activation was demonstrated by the relapse of procoagulant activity and monokines (interleukin-1 [IL-1], IL-6, and tumor necrosis factor-alpha [TNF alpha]) in the supernatants of cultured monocytes. Evidence for in vivo monocyte activation was provided by the increase of these monokines in the peritoneal fluids. Kinetic studies with indium-111 (111In)-labeled activated autologous monocytes in five patients suggest that these infused monocytes may remain in the peritoneal cavity for up to 7 days. This locoregional immunotherapeutic approach seems to be encouraging in view of adjuvant therapeutic modality in ovarian cancer patients with minimal residual intraabdominal disease following second-look laparotomy. 
Cancer screening by primary care physicians. Can we explain the differences? BACKGROUND. Physicians perform cancer screening tests less often than recommended. METHODS. Forty primary care physicians were surveyed to assess their knowledge, attitudes, and experiences regarding cancer and cancer screening, and patients' medical records were reviewed to measure physicians' screening rates. RESULTS. Over 80% of physicians believed doctors should urge screening. On average, 23% of their patient visits were scheduled primarily for preventive care interventions. Screening performance scores expressed the percentage of compliance with the American Cancer Society's recommendations and demonstrated the low levels of compliance for six out of seven tests; however, there was substantial variance in performance among physicians. The best predictors of screening performance were (1) the percentage of visits scheduled primarily for prevention (mammography, and pelvic and breast examinations [P less than .05]); and (2) the number of medical journals read regularly (stool occult blood test [P less than .01], sigmoidoscopy [P less than .01], and Papanicolaou smear [P less than .02]). Also, female physicians performed more Papanicolaou smears (P less than .05) and scheduled more visits for preventive care (P less than .001). CONCLUSIONS. A small group of predictors explain large portions of the variance in cancer screening performance. 
Rehabilitation in rheumatic diseases. What's new. In the past decade, considerable change has occurred in concepts of rehabilitation in patients with rheumatic diseases. This includes approaches to functional assessment and outcome, new concepts in exercise, and new orthotics. 
Intermediate septal accessory pathways: electrocardiographic characteristics, electrophysiologic observations and their surgical implications Intermediate septal accessory pathways are located in close proximity to the atrioventricular (AV) node and His bundle, have unique features that distinguish them from typical anterior and posterior accessory pathways and have been associated with a high risk for unsuccessful pathway division and the production of complete AV block after surgery. Between July 1986 and May 1990, 4 of 70 patients (3 men and 1 woman; mean age 33 +/- 13 years) undergoing surgery for accessory pathway division were found to have an intermediate septal accessory pathway. The presenting arrhythmia was atrial fibrillation with rapid anterograde conduction over the accessory pathway in two patients and recurrent orthodromic reciprocating tachycardia in two patients. In all patients, the delta wave on the electrocardiogram (ECG) was inverted in lead V1, but two patterns of delta wave configuration were observed. In three patients (type 1 intermediate septal accessory pathway), the delta wave was upright in lead II, inverted in lead III and isoelectric in lead a VF; the transition from a negative to an upright delta wave occurred in lead V2. The fourth patient exhibited a different delta wave pattern (type 2 intermediate septal accessory pathway). The delta wave was upright in each of leads II, III and aVF; the transition from a negative to an upright delta wave occurred at lead V3. Intraoperative electrophysiologic study localized the atrial insertion of type 1 pathways to the midpoint of Koch's triangle close to the AV node. 
Septicaemia after colonoscopy in patients with cirrhosis. Two patients with ulcerative colitis and chronic active hepatitis with cirrhosis, who developed Gram negative septicaemia after colonoscopy are described. These and two similar reported cases indicate that giving prophylactic antibiotics to patients with cirrhosis undergoing colonoscopy should be considered, particularly when the cirrhosis is advanced. 
The chemoreflex control of breathing and its measurement. The chemoreflex control of breathing is described in terms of a graphical model. The central chemoreflex, the ventilatory response to carbon dioxide mediated by the central chemoreceptors, is modelled as a straight-line relation between the ventilatory response and the arterial level of carbon dioxide. The peripheral chemoreflex, the ventilatory response to carbon dioxide and hypoxia mediated by the peripheral chemoreceptors, is broken into two relations. First, a straight-line relation between the ventilatory response and the arterial level of carbon dioxide whose slope (sensitivity) increases as the oxygen level varies from hyperoxic to hypoxic. Second, a rectangular hyperbolic relation between the ventilatory response and the arterial level of oxygen with ventilation increasing with increasing hypoxia. The three ventilatory response relations (one central and two peripheral) add to produce the total chemoreflex ventilatory response which forms the feedback part of the respiratory regulator. The forward part consists of the relation between the arterial level of carbon dioxide and ventilation when ventilation is controlled (the metabolic hyperbola). The forward and feedback parts of the respiratory regulator can be combined so as to predict resting ventilation and carbon dioxide levels under a number of circumstances. Methods of measurement of these chemoreflex ventilatory responses are also described so as to illustrate the physiological principles involved in the model. 
Are demented patients with Parkinson's disease accurately reflected in prevalence surveys? A survival analysis. We re-reviewed 257 patient records previously reviewed for an incidence study of dementia in Parkinson's disease (PD) to determine the frequency, date of death, and cause of death. We posited that if disease duration is shortened when dementia occurs, then dementia may be far more common than reflected in prevalence studies. There were 17 deaths among 65 demented patients and 28 deaths among 168 nondemented patients. When we matched a subset of the nondemented patients to the demented patients by age and disease duration distributions, the demented subjects had significantly more deaths (p less than 0.02), and survival among demented subjects was decreased (p less than 0.05). Dementia was a significant predictor of death in this sample. We conclude that dementia reduces survival in patients with PD. Incidence is a much better measure of dementia in PD than prevalence because shortened duration makes it less likely to detect dementia in prevalence surveys. 
Management of nasal fractures. Fracture of the nasal skeleton is a relatively common injury. Satisfactory treatment requires appropriate skills, diagnosis, and management. Some injuries require immediate attention; others are better treated in delayed fashion. Closed reduction provides satisfactory treatment in the majority of nasal fractures; however, open reduction often is a more appropriate choice. Injuries to the nasal septum should be recognized and given proper treatment. 
Monthly pulses of vincristine and prednisone prevent bone marrow and testicular relapse in low-risk childhood acute lymphoblastic leukemia: a report of the CCG-161 study by the Childrens Cancer Study Group. On study CCG-161 of the Childrens Cancer Study Group (CCSG), 631 children with acute lymphoblastic leukemia (ALL) at low risk for relapse were randomized to receive monthly pulses of vincristine-prednisone (VCR-PDN ) during maintenance therapy in addition to standard therapy with mercaptopurine (6MP) and methotrexate (MTX), and either cranial irradiation during consolidation or intrathecal (IT) MTX every 3 months during maintenance. All patients received six doses of IT MTX during induction and consolidation. With a minimum follow-up time of 4.25 years, 76.7% receiving VCR-PDN were in continuous complete remission at 5 years, in contrast to 63.9% receiving GMP-MTX alone (P = .002). The difference in relapse-free survival was due primarily to bone marrow relapse (P = .0008), and in boys also to testicular relapse (P = .003). Among the nonirradiated patients, the 5-year disease-free survival (DFS) was 79.4% for patients randomized to the VCR-PDN pulses, in contrast to 61.2% for the patients randomized to receive 6MP-MTX alone (P = .0002). Among the irradiated patients, the DFS was not significantly different. Of the four combinations of maintenance and CNS therapy studied, the highest DFS was achieved with VCR-PDN pulses and maintenance IT MTX. 
Quality of life before and after orthotopic hepatic transplantation. Fifty-three nonalcoholic patients were evaluated prior to liver transplantation and again approximately 3 years after surgery using the Sickness Impact Profile and Social Behavior Adjustment Schedule. Test-retest scores reflected significant improvement across all health and psychosocial scales of the Sickness Impact Profile. On the Social Behavior Adjustment Schedule, significant improvement was observed on scales measuring disturbed behavior, social role performance, and burden. Comparisons between groups indicated that the liver transplant patients were still impaired on eight of the Sickness Impact Profile scales after transplant; however, the severity of disturbance was not considered to be clinically significant. No between-group differences were noted on the Social Behavior Adjustment Schedule. These results indicate that liver transplantation is associated with substantial improvement in life quality, although as a group, the patients undergoing this surgery do not recover to the level of functioning demonstrated by normal individuals. 
Chylothorax complicating right upper lobectomy. Chylothorax after pleuropulmonary surgery is unusual. We have described the case of a patient in whom this complication followed a right upper lobectomy. Early recognition is important to avoid potential morbidity and mortality. 
Safety and efficacy of repeat thrombolytic treatment after acute myocardial infarction. Thrombolytic treatment for acute myocardial infarction increases the risk of subsequent reocclusion of the infarct related artery. The efficacy and safety of repeat thrombolytic treatment was assessed in 31 patients treated with streptokinase (n = 13) or tissue plasminogen activator (n = 18) a median of five days (1-716) after the first infusion. The indication for readministration was prolonged chest pain with new ST segment elevation. Efficacy was assessed by infarct artery patency at angiography at a median of eight days after readministration in 22 patients and by non-invasive criteria in 23 patients (reperfusion was deemed to be likely if serum creatine kinase was not increased or reached a peak less than 12 hours after infarction). Angiography showed patency of 70% of the infarct arteries after readministration of streptokinase and of 75% after tissue plasminogen activator. The corresponding patency rates assessed noninvasively were 73% and 75%. Reinfarction was prevented in nine (29%) patients. Allergic reactions occurred in four of eight patients who received streptokinase twice (plasmacytosis and acute reversible renal failure developed in one patient). Two patients had major bleeding and two minor bleeding, all after tissue plasminogen activator, and one of them died of cerebral haemorrhage. Repeat thrombolytic treatment results in late patency rates similar to the rates after the initial administration. Allergic reactions were common in those treated twice with streptokinase. 
A prospective evaluation of hepatic resection for colorectal carcinoma metastases to the liver: Gastrointestinal Tumor Study Group Protocol 6584. We report here the results of the first multiinstitutional prospective evaluation of patients considered to have potentially resectable hepatic metastases from colorectal carcinoma. One hundred fifty-six patients were enrolled from 15 institutions. Six patients were subsequently excluded. One hundred fifty patients underwent surgery and are evaluable for analysis (median follow-up time, 3.1 years; range, 4 months to 5.1 years). Curative resection could be performed on 46% of patients (69 of 150), noncurative resection on 12% (18 of 150), while 42% were found to be unresectable (63 of 150). Thirty-day surgical mortality and morbidity rates in patients with attempted resection were 2.7% and 13%, respectively. The curative resection group was observed to have an improved median survival (37.1 months) compared with the noncurative resection group (21.2 months) and the unresectable group (16.5 months) (P less than .01). Computed tomographic (CT) scan was a poor predictor for resectability, and age was not a contraindication to curative resection. Preoperative carcinoembryonic antigen (CEA) values were also a poor predictor for resectability. However, the median CEA value 61 to 180 days postsurgery was significantly higher in unresectable patients compared with median CEA levels in noncuratively and curatively resected groups (P less than .01). Our results imply that curative resection leads to an increase in median survival. Noncurative resection provides no benefit to asymptomatic patients, since unresectable and noncurative resection groups have similar life expectancies. Longer follow-up will be needed to demonstrate the ultimate impact of curative resection on survival. 
Mitotane enhances cytotoxicity of chemotherapy in cell lines expressing a multidrug resistance gene (mdr-1/P-glycoprotein) which is also expressed by adrenocortical carcinomas. P-Glycoprotein (Pgp), product of the mdr-1 gene, is a 130- to 180-kDa plasma membrane phosphoglycoprotein which mediates multidrug resistance in cell culture by increasing efflux of the natural product chemotherapeutic agents. High levels of expression of mdr-1/Pgp are found in both the normal adrenal and adrenocortical cancers. By RNA in situ hybridization the expression in adrenocortical cancer is shown to be widely distributed. The present study demonstrates that decreased drug accumulation mediated by mdr-1/Pgp can be overcome by clinically achievable concentrations of mitotane (o,p'-DDD). The increase in drug accumulation with the addition of mitotane is due at least in part to a decrease in drug efflux and results in an increase in cytotoxicity when agents of the natural product class are used. This effect is observed in cells with a broad range of mdr-1/Pgp expression, including levels comparable to those found in most adrenocortical cancers. Similar increases in drug accumulation can be demonstrated in an unselected adrenocortical cancer cell line that expresses mdr-1/Pgp. The finding that multidrug resistance mediated by mdr-1/Pgp can be reversed by mitotane provides a rational basis for exploring the use of mitotane in combination with natural product chemotherapeutic agents in adrenocortical cancer. 
Establishment and characterization of a human carcinoid in nude mice and effect of various agents on tumor growth. The authors have established a long-term tissue culture cell line (BON) derived from a metastatic human carcinoid tumor of the pancreas. The cells have been in continuous passage for 46 months. Tissue culture cells produce tumors in a dose-dependent fashion after SC inoculation of cell suspensions in athymic nude mice. BON tumors, grown in nude mice, are histologically identical to the original tumor; they possess gastrin and somatostatin receptors, synthesize serotonin and chromogranin A, and have a doubling time of approximately 13 days. The antiproliferative effects of the long-acting somatostatin analogue, SMS 201-995 (300 micrograms/kg, t.i.d.), and 2% alpha-difluoromethylornithine on BON xenografts in nude mice were examined. Tumor size was significantly decreased by day 14 of treatment with either agent and at all points of analysis thereafter until the animals were killed (day 33). In addition, tumor weight, DNA, RNA, and protein contents were significantly decreased in treated mice compared with controls. Establishment of this human carcinoid xenograft line, BON, provides an excellent model to study further the biological behavior of carcinoid tumors and the in vivo effect of chemotherapeutic agents on tumor growth. 
Xenobiotic enzyme profiles and Parkinson's disease. Xenobiotic enzymic systems have been studied in Parkinson's disease. Platelet monoamine oxidase-B activity is increased by the use of phenylethylamine but decreased by the use of dopamine as substrate. Enzymes involved with sulfur oxidation and methylation are underactive. 
Emergency medical services and the pediatric patient. III: Resources of ambulatory care centers. Ambulatory care centers have emerged as a new health care resource in many communities. Little information is available about the services that these centers offer to pediatric patients. A national survey of 254 ambulatory care centers was undertaken to determine their characteristics, including the number of pediatric patients seen, staffing patterns, and pediatric equipment and supplies available. Most clinics were located in urban areas and were within 5 miles of a hospital. They were staffed primarily by physicians who were board certified in emergency medicine, internal medicine, or family medicine. Not all centers had registered nurses on duty and few used extended-role nurses or physicians's assistants. The centers saw an average of 18 patients younger than 18 years of age per day. Some ambulatory care centers received emergency medical service and private ambulance calls and encountered serious illness such as chest pain, seizures, and anaphylaxis; the majority, however, handled mainly minor injuries and illnesses. Although most had pediatric equipment and supplies, some did not have a complete set of pediatric resuscitation equipment even though they were part of the emergency system offering care to the pediatric population. 
Associated neurologic and ophthalmologic findings in congenital oculomotor nerve palsy. Unlike acquired oculomotor nerve palsy in childhood, the congenital form is usually considered to be an isolated disorder, not associated with other neurologic or systemic disease. In a series of 14 patients with this diagnosis, 10 had associated neurologic disorders. Clinical-neuroradiologic correlation identified the brainstem as the site of the lesion in some patients. The ipsilateral pupil was involved in 12 patients and was miotic with a trace or no reaction to light on the side of the palsy in 8 of the 12 patients. In two of these eight patients, the pupil was documented to be dilated and fixed in early infancy and subsequently became miotic at several months of age, concurrent with emergence of other signs of aberrant reinnervation. Pupillary miosis as a result of aberrant reinnervation appears to be much more frequent after congenital than acquired pupillary-involving oculomotor palsy. Four patients showed better visual acuity in the paretic eye, an unexpected finding. The paretic eye appeared to have a fixational advantage if the patient had nystagmus, presumably due to asymmetric dampening of the nystagmus. Significant anisometropia and astigmatic errors in the paretic eye were present in essentially all patients. 
Combined treatment of symptomatic gallbladder stones by extracorporeal shock-wave lithotripsy (ESWL) and instillation of methyl tert-butyl ether (MTBE). Twenty-four patients with symptomatic gallbladder stones (12 radiolucent and 12 calcified) were treated by a combined approach of extracorporeal shock-wave lithotripsy (ESWL) and subsequent instillation of methyl tert-butyl ether (MTBE). The patients received a mean of 1500 +/- 185 shock-wave discharges. The mean instillation time of MTBE was 13 +/- 4.2 hr. Treatment was tolerated without major adverse effects. Within a time period of three to five days eight of 12 patients with pure radiolucent stones and four of 12 with calcified stones became stone-free. After a median follow-up of five months (range: one week to 26 months), a total of 11 patients (92%) with radiolucent stones and of eight patients (66%) of those with calcified stones were free of stones, fragments, or debris. These clearance rates appear high when compared with reports on monotherapy with ESWL or MTBE, suggesting a positive effect of a combined approach in selected patients. Two patients exhibited recurrent stones after six and seven months, respectively. 
Transpalpebral extrusion of a silicone sponge exoplant. We report an unusual case of scleral buckle extrusion in a 63-year-old woman. A 5 mm silicone sponge exoplant eroded through Tenon's capsule, conjunctiva, and full-thickness upper eyelid, traversing the tarsal plate. 
The role of endoscopic papillotomy in ascending cholangitis. The role of endoscopic papillotomy in calculous cholangitis is unclear. A retrospective review of 41 patients admitted to hospital with calculous cholangitis was carried out. There were 30 women and 11 men and their ages ranged between 49 and 98 years (mean age 77). All patients presented with abdominal pain, tenderness, chills, and fever. Clinical jaundice was present in 95 per cent of the patients. Initial endoscopic papillotomy was successful in 17 of the 41 patients. In 24 patients cholangitis persisted or recurred and further therapy was carried out. Surgery was successful in controlling sepsis in ten of the 24 patients. Repeat endoscopic papillotomy was successful in four of 13 patients. Surgery was successful in one of nine patients who had failed repeat endoscopic papillotomy. Nasobiliary drainage and percutaneous transhepatic drainage of the common bile duct after failed repeat endoscopic papillotomy was successful in only two of nine patients. Six patients died after failed repeat endoscopic papillotomy. We conclude that initial endoscopic papillotomy should be attempted in patients with calculous cholangitis. Surgical exploration of the common bile duct should then be carried out if initial endoscopic papillotomy fails to control cholangitis. 
Outcome of infants and children with dilated cardiomyopathy. A review of 81 infants and children with dilated, poorly contracting left ventricles without associated structural abnormalities was undertaken to identify risk factors for poor outcome, which could be used in selecting candidates for cardiac transplantation. Significant atrial or ventricular dysrhythmias, or both, were detected on presentation or during follow-up in 24 patients. Arrhythmias were present in only 8 of 51 survivors (16%) but were detected in 16 of 30 patients (53%) who died (p less than 0.05). Patients dying suddenly were even more likely to have had documented dysrhythmias (8 of 11, p less than 0.05). Left ventricular shortening fraction was similar in survivors and nonsurvivors (14.9 +/- 1.0% vs 15.3 +/- 1.7%). Left ventricular end-diastolic pressure in 44 patients who had cardiac catheterization averaged 20.8 +/- 1.6 mm Hg. Left ventricular end-diastolic pressure was significantly higher in patients who died than in those who survived (29.5 +/- 2.2 vs 15.0 +/- 1.6 mm Hg, p less than 0.001). Analysis of actuarial survival revealed that mortality was highest during the first 6 months after presentation (19% mortality). Survival declined more gradually thereafter and was 70% at 2 years, 64% at 5 years and 52% after 11.5 years. Age at initial presentation did not have any significant impact on survival. However, left ventricular end-diastolic pressure greater than 25 torr was associated with a significantly increased mortality rate (p less than 0.05). Early cardiac transplantation should be considered in patients with markedly elevated left ventricular end-diastolic pressure or complex atrial or ventricular arrhythmias. 
Upper abdominal cancer surgery in the very elderly. From January 1981 to December 1987, 59 major upper abdominal operations were performed on 57 patients aged 80 to 90 years at Memorial Sloan-Kettering Cancer Center. Procedures for primary adenocarcinoma of the stomach, distal esophagus, pancreas, or hepatobiliary system were performed with curative intent or for palliation in 34 of 59 patients (58%) and bypass with limited or no resection in 13 of 59 patients (22%) patients. Emergency operations were performed in six (10%) patients for gastric bleeding, perforation, or outlet obstruction. Six (10%) patients underwent laparotomy for benign biliary obstruction (1), splenectomy for secondary thrombocytopenia (2), or gastrectomy for sarcoma (2) or lymphoma (1). Hospital mortality was 15% overall and 9% for major resections, 15% for bypass, and 67% for emergency procedures. Major complications occurred in 10 (20%) elective procedures. Mortality was associated with respiratory or cardiac failure while complications most commonly included arrhythmias and wound infection. Mean postoperative hospitalization was 18 days overall and 45 patients (76%) were discharged home. Median survival following major resection was 17.5 months but less than 2 months after bypass procedures. A protocol of pre-operative evaluation, intra-operative hemodynamic monitoring and postoperative intensive care has been formalized for use in elderly or poor-risk patients. 
Insulin-dependent diabetes mellitus and hypertension. Contrasting results have been reported regarding the prevalence of hypertension in insulin-dependent diabetes mellitus (IDDM), showing a slightly higher or normal percentage of IDDM patients with elevated blood pressure levels than in the general population. Most of the cross-sectional and prospective studies on the prevalence of hypertension in IDDM show an association between microalbuminuria and elevated blood pressure levels. However, it is not clear whether hypertension is simply secondary to kidney damage or whether hypertension occurs with or even before the development of impaired kidney function. Patients with IDDM have a higher exchangeable body Na+ pool. Na+ retention in IDDM is accounted for by several metabolic and hormonal abnormalities such as hyperglycemia, hyperketonemia, hyperinsulinemia, altered secretion, and resistance to atrial natriuretic peptide. High blood pressure appears to be dependent, at least at some phase, on expansion of extracellular fluid volume as a consequence of defects in the renal secretion of Na+ and water. On the other hand, a tendency toward Na+ retention characterizes all patients with IDDM, whereas hypertension develops only in a subgroup of diabetic patients. One possible explanation for these findings is that a genetic predisposition plays a role in creating susceptibility to hypertension and perhaps to diabetic nephropathy independent of diabetes, even if Na+ retention can further deteriorate this susceptibility to hypertension. With regard to this issue, it has recently been suggested that the risk of kidney disease in patients with IDDM is associated with a genetic predisposition to hypertension. Furthermore, diabetic nephropathy occurs in familial clusters, because diabetic siblings of nephropathic diabetic patients show a higher frequency of diabetic nephropathy than the diabetic siblings of nonnephropathic diabetic patients. One of the possible genetic markers that could be useful to identify the diabetic patients with susceptibility to hypertension and diabetic nephropathy is the Na+(-)Li+ countertransport activity in erythrocytes. 
Sonography in the diagnosis of acute appendicitis. Acute appendicitis can be a diagnostic dilemma. The classic triad of leukocytosis, pain at McBurney's point and a history compatible with appendicitis has a diagnostic accuracy rate of only 80 percent. Ultrasonography, combined with this triad, can improve the diagnostic accuracy, decreasing the negative laparotomy rate from 20 percent to less than 10 percent. 
Source of tubercle bacilli in cervical lymph nodes: a prospective study. A prospective study searching for associated mycobacterial infection of the upper aerodigestive tract in patients with cervical tuberculous lymphadenitis (TBLN) was carried out. One hundred and thirteen patients with a clinical suspicion of cervical TBLN were included. All patients had a physical examination of the upper aerodigestive tract. Routine endoscopy and biopsy of the nasopharynx were performed. All of them had surgery to the cervical lymph node. Seventy-five patients had histologically confirmed cervical TBLN. Culture of the lymph node specimen showed Mycobacterium tuberculosis in 68 (90 per cent). In 45 (60 per cent) patients with cervical TBLN the primary foci of infection could not be found. Twenty-nine (39 per cent) had radiographic evidence of active or healed pulmonary tuberculosis. Sputum culture from two patients showed Mycobacterium tuberculosis. Five patients (six per cent) had tuberculous nasopharyngitis. In one of them (one per cent) the tuberculous nasopharyngitis was primary as no other evidence of mycobacterial infection was found. In the present study, mycobacterial infection of other parts of the upper aerodigestive tract was not found. 
Down-regulation of messenger ribonucleic acid and protein levels for estrogen receptors by phorbol ester and calcium in MCF-7 cells. Treatment of MCF-7 cells, a human mammary carcinoma cell line, with phorbol ester [12-O-tetradecanoylphorbol-13-acetate (TPA)] or calcium ionophore (A23187) was associated with striking effects on levels of estrogen receptor (ER) mRNA, specific binding of 17 beta-[3H]estradiol [( 3H]E2), and immunoreactive ER. TPA (10(-7) M) caused a time-dependent reduction of ER mRNA which was below the level of detection after 9 h. Similar effects of TPA appeared at levels of specific binding of [3H]E2 as well as immunoreactive ER. In contrast, TPA induced an increase in mRNA for beta-actin. Incubation of MCF-7 cells with increasing concentrations of TPA (10(-11)-10(-7) M) was associated with biphasic effects on ER mRNA and proteins. Levels of immunoreactive progesterone receptors (PR) were induced by E2 (10(-9) M) in a time-dependent manner. In the presence of TPA (10(-7) M), where ER levels were suppressed, no induction of PR was observed. Removal of TPA (10(-7) M) after 10 h (ER mRNA) or 22 h (ER proteins) of treatment was associated with a continued suppression of both mRNA and protein levels during the entire incubation period (48 h). Treatment with A23187 (2 x 10(-7) M) also caused a time-dependent down-regulation of levels of ER mRNA and proteins. These effects occurred somewhat more slowly than those of TPA. Levels of beta-actin mRNA were not changed by this treatment. These results indicate that changes in estrogen sensitivity are mediated by calcium-dependent protein kinases in human mammary carcinoma MCF-7 cells. 
Examination of cardiorespiratory changes during upper gastrointestinal endoscopy. Comparison of monitoring of arterial oxygen saturation, arterial pressure and the electrocardiogram. Critical events including hypoxaemia, arrhythmias and myocardial ischaemia may occur more frequently during endoscopic procedures than during anaesthesia. A study was undertaken to assess the cardiovascular changes and to evaluate suitable monitoring techniques to detect critical events during sedation and endoscopy. Twenty patients scheduled to undergo a prolonged endoscopic procedure which required deep sedation were studied. Continuous recordings of electrocardiogram, heart rate and arterial oxygen saturation were made and arterial pressure was recorded at one-minute intervals. The study commenced immediately before administration of sedatives, continued for the duration of the examination and for one hour following the examination. Oxygen saturation decreased in all patients during the examination to a mean of 82.9% (SD 11.9), and remained below baseline for the duration of the examination and into the recovery period. Statistically significant increases and reductions of systolic arterial pressure and rate-pressure product were found during the procedures compared with baseline values recorded before administration of sedatives. Sixteen of the 20 patients developed tachycardia during the examination. Ten patients developed ectopic foci which were supraventricular, ventricular or both in origin. Electrocardiogram changes resolved during the recovery period. Myocardial ischaemia was assessed by S-T segment depression and a significant correlation was found between S-T segment depression and hypoxaemia, although the magnitude of the S-T depression was small and may not have been detected clinically. No correlation was found between S-T segment depression and arterial pressure, heart rate or rate-pressure product. 
Pathogenesis of pulmonary edema during interleukin-2 therapy: correlation of chest radiographic and clinical findings in 54 patients. The pathogenesis of pulmonary edema that occurs during interleukin-2 therapy has often been attributed to an increase in pulmonary capillary permeability. However, renal insufficiency, fluid overload, and hypotension also develop in many patients. These manifestations of systemic toxicity may contribute to the development of pulmonary edema during therapy. Understanding the cause of pulmonary edema during interleukin-2 therapy could directly affect patients' care. Therefore, we reviewed the chest radiographs and clinical course of 54 patients who received high-dose interleukin-2 therapy and lymphokine-activated killer cells for advanced carcinoma. The type, frequency, and course over time of pulmonary abnormalities were recorded and correlated with clinical measures of renal function, fluid status, and blood pressure. Focal or diffuse parenchymal lung opacities were found on radiographs in 43 (80%) of 54 patients. Findings of interstitial pulmonary edema were most common, occurring in 76% of patients. Weight gain, hypotension, and elevation of the serum creatinine level were not associated statistically with interstitial edema. Diffuse air-space disease developed in 20% of patients. Focal consolidation, which was associated with positive central venous catheter cultures (p less than .03), developed in 28% of patients. Pleural effusion occurred in 48% of patients and was associated with all types of parenchymal disease. These data suggest that the frequent development of pulmonary edema during interleukin-2 therapy is not due to renal insufficiency, fluid overload, or hypotension, but is more likely the result of an interleukin-2-related increase in pulmonary capillary permeability. 
Identification of the viral genes responsible for growth of strains of reovirus in cultured mouse heart cells. Viral growth in specific tissue is usually required in order to lead to pathology. Two reovirus isolates (type 1 Lang and type 3 Dearing) differ in their capacity to grow in cultured mouse heart cells. The mammalian reoviruses contain a genome of 10 double-stranded RNA gene segments. By the use of 37 reassortant viruses (consisting of viruses with different combinations of genes derived from the two parents), difference in capacity of different strains to grow in heart cells was mapped to three different genes, all of which encode viral core proteins: the M1 gene (P less than 0.000044); the L1 gene (P = 0.00094); and the L3 gene (P = 0.019). Using the same set of reassortant viruses, the L1 (P = 0.00015) and L3 (P = 0.0065) genes were involved in differences of the ability of viral strains to grow in mouse L cells (fibroblasts), but the M1 gene (P = 0.12) was not. These findings suggest that the M1 gene plays an important and specific role in determining the relative capacity of certain viral strains to grow in the heart. Thus, we have identified viral genes responsible for differing growth capacity in heart muscle cells in culture. These findings provide a novel system for studies of viral myocarditis at a molecular genetic level. 
Iliopectineal bursitis: an unusual cause of iliofemoral vein compression. The iliopectineal bursa is the largest bursa in the region of the hip joint. Enlargement of the bursa occurs in several conditions and may be manifested by groin pain, a pelvic or inguinal mass, or lower extremity edema due to compression of the external iliac or common femoral vein. A case of lower extremity edema secondary to external iliac/common femoral vein compression caused by an enlarged iliopectineal bursa is presented. The pathophysiology, methods of diagnosis, and forms of therapy are discussed. 
Insulin and cardiovascular disease. Paris Prospective Study. The Paris Prospective Study is a long-term investigation of coronary heart disease (CHD) risk factors in a large population of working men. The baseline cohort included 7028 men, 6093 who had a 75-g oral glucose tolerance test with measurement of plasma insulin and glucose levels (0 and 2 h) and 125 who were known non-insulin-treated diabetic patients. After a mean follow-up of 11 yr, 126 deaths ascribed to CHD were reported. Major independent predictors of CHD death were blood pressure, smoking, plasma cholesterol level, and fasting and 2-h postload plasma insulin level. Impairment of glucose tolerance, including overt diabetes, did not rank as an independent predictor when other baseline variables were accounted for. In the subset of the baseline cohort who presented with impaired glucose tolerance or diabetes (n = 943), 26 died from CHD during the follow-up. The strongest independent predictor of subsequent CHD death in this subsample with abnormal glucose tolerance was plasma triglyceride level. In view of the accumulating evidence that hyperinsulinemia and hypertriglyceridemia generally occur in the same type of subjects, in relation to insulin resistance and central obesity, the epidemiological findings of the Paris Prospective Study and of other investigations support the hypothesis that a constellation of mild metabolic abnormalities may play a deleterious role with regard to cardiovascular disease risk. 
Resectoscopic myomectomy. OBJECTIVE: To evaluate safety and efficacy of resectoscopic myomectomy for control of menorrhagia, dysmenorrhea, and/or reproductive wastage. DESIGN: Retrospective consecutive patient follow-up. SETTING: Private practice, outpatient, hospital. PATIENTS: All patients (92) having resectoscopic myomectomy between September 1, 1986 and December 31, 1989. INTERVENTIONS: Resectoscopic myomectomy with or without concomitant procedures such as endometrial ablation. MAIN OUTCOME MEASURES: Assessment of dysmenorrhea, menorrhagia, and reproductive outcome after surgery. RESULTS: Elimination of dysmenorrhea in 24 of 28, absence of menorrhagia in 65 of 80, and pregnancy in 10 of 13 with two abortions in a total of 11 gestations. One patient was admitted and treated with one unit of autologous blood and mechanical tamponade with an intrauterine balloon. Three cases of uterine perforation had no sequelae. One patient had mild endometritis responding to outpatient antibiotics. Two cases of leiomyosarcoma were diagnosed histologically and accounted for two of the three hysterectomies noted during follow-up. CONCLUSIONS: Resectoscopic myomectomy is a safe, effective, and relatively simple outpatient surgical procedure. 
Abundant expression of EBER1 small nuclear RNA in nasopharyngeal carcinoma. A morphologically distinctive target for detection of Epstein-Barr virus in formalin-fixed paraffin-embedded carcinoma specimens. The highly restricted expression of the Epstein-Barr virus (EBV) genome in malignancy has limited the use of EBV detection methods applicable to formalin-fixed paraffin-embedded carcinoma specimens. In EBV-transformed lymphocytes very short nonprotein coding EBV transcripts (EBERs) are expressed in much higher abundance (10(7) copies per cell) than other EBV latency transcripts. Using a 3H riboprobe, the authors demonstrated EBER1 expression in NASOPHARYNGEAL CARCINOMAS (NPCs) as well as in parotid salivary gland. Recognition of EBER1 expression was facilitated by the intensity of hybridization and its characteristic morphology (nuclear with nucleolar sparing). EBER1 expression was not demonstrated in other epithelial malignancies arising from mucosal surfaces (oropharynx, uterine cervix) from which EBV shedding has been detected. Repeat study of the NPC specimens with digoxigenin-labeled probe yielded hybridization signal with subcellular morphologic detail and without background in a 12-hour procedure. Thus the EBER1 transcript is an appropriate target for in situ hybridization detection of EBV in formalin-fixed paraffin-embedded carcinoma specimens. 
Disorders of hypopigmentation in children. The most common disorders of hypopigmentation in children are pityriasis alba, vitiligo, nevus depigmentosus, and tinea versicolor. Pityriasis alba usually presents as ill defined, scaly patches of hypomelanosis on the cheeks of children with an atopic diathesis. The face is also a favored site for vitiligo, but the distribution is periorificial, and the pigment loss is complete because of a destruction of melanocytes. Vitiligo is an acquired, progressive disorder in contrast to nevus depigmentosus, which is a stable, congenital leukoderma. The localized form of nevus depigmentosus must be distinguished from an ash leaf spot, the earliest cutaneous manifestation of tuberous sclerosis, whereas the systematized form may be confused with hypomelanosis of Ito, another neurocutaneous disorder. The lesions of tinea versicolor favor the upper trunk of adolescents, and potassium hydroxide examination of the associated scale reveals hyphal and yeast forms of P. orbiculare. Any inflammatory process in the skin such as dermatitis or psoriasis can resolve with areas of hypopigmentation. 
Effect of hemostatic agents in canine gastric serosal blood vessels. The efficacy of various sclerotherapeutic agents in the control of acute bleeding, via subserosal injection, was assessed in 10 dogs. Blood flow rate (BFR) from severed gastric serosal vessels (diameter, 1.6 to 2.2 mm) was measured for 3 min (ml/min) for a control group and the agent used. The agents tested were 5 ml of normal saline (NS), 5 ml of 3% hypertonic saline (HS), 5 ml of 1:10,000 epinephrine in NS, 5 ml of 1:10,000 epinephrine/HS, 5 ml of 1:20,000 epinephrine/HS, 2 ml of old thrombin "cocktail" (thrombin, cephapirin + 1% tetradecyl), and 2 ml of fresh thrombin cocktail (total seven). One agent was tested per dog; there were one to two dogs in each subgroup. All of the agents showed significant reduction in BFR (except old thrombin) when compared with BFR of control vessels. The reduction ranged from 30% to more than 75% after 1:10 epinephrine/HS. Complete hemostasis was achieved in up to 47% of vessels using 1:20 epinephrine/HS. Overall, the epinephrine solutions achieved the best results. No systemic effects were observed with the use of any of the agents. Histological studies showed that epinephrine caused mild tissue damage, whereas the cocktail caused significant tissue necrosis. This serosal vessel model permits comparison of the effectiveness of each agent; however, clinical extrapolation to mucosal vessels in a patient and the long-term histological changes are not known. 
Myasthenia gravis in childhood and infancy. Usefulness of electrophysiologic studies. The diagnostic yield of electrodiagnostic tests was evaluated in 21 children with myasthenia gravis (MG). Twelve children had juvenile autoimmune MG, four had neonatal MG, four had congenital MG, and one had MG with arthrogryposis. Repetitive stimulation (RS) of the ulnar nerve was performed in every patient, sometimes with sensitization by ischemia. When the RS test was negative, the spinal or facial nerve was tested. In the group with neonatal MG, the RS test disclosed a significant decrement in 75% of the patients. Among the 17 other children, the overall percentage of positive RS tests was 88%. An ulnar nerve RS test was positive in 41% of them. Sensitization of ulnar nerve RS by ischemia improved the diagnostic yield to 66%. A spinal or facial nerve RS test was positive in seven of 10 patients. These results confirmed the diagnostic value of RS, with sensitization by ischemia, when necessary, in childhood MG whenever a careful technique is provided. 
A low dose bacillus Calmette-Guerin regimen in superficial bladder cancer therapy: is it effective? Bacillus Calmette-Guerin (BCG) intravesical therapy represents a major advance in the treatment of superficial transitional cell carcinoma of the bladder. To date, however, the optimal treatment schedule must be defined and the toxicity related to the treatment is significant. The preliminary results of a randomized ongoing study performed to evaluate the effectiveness and relative toxicity of a low dose (75 mg.) BCG regimen in the treatment of superficial bladder cancer therapy are reported. A total of 126 patients (70 for prophylaxis of recurrent stages Ta and T1 papillary tumors and 56 for treatment of carcinoma in situ or with microinfiltration of the subepithelial connective tissue) underwent a 6-week course of 75 mg. BCG (Pasteur vaccine). An additional course was given in patients who failed to respond to the induction course. Maintenance therapy was administered in complete responders monthly for 1 year and then quarterly for 1 year. The prophylaxis group (transurethral resection plus BCG) was randomized versus transurethral resection alone (63 patients, control group). A complete response in the prophylaxis, control and therapy groups was observed in 74, 17 and 57% of the patients, respectively, while 4, 17 and 12.5%, respectively, experienced tumor progression. The additional course of therapy increased the response rate. On the contrary, previous unsuccessful intravesical chemotherapy did not affect the response rate. In regard to toxicity, irritative disturbances (27%) and fever (17%) appeared to be significantly decreased compared with the rates reported in the literature. No major complications were experienced. In conclusion, a low dose (75 mg.) Pasteur strain BCG regimen was effective as prophylaxis against recurrent superficial papillary tumors and as treatment of carcinoma in situ or with microinfiltration of the subepithelial connective tissue. Toxicity related to the treatment appeared to be low. 
Issues, goals, and guidelines in selecting first-line drug therapy for hypertension. Modern antihypertensive therapy is enriched by an explosion in drug development that makes available increasingly specific agents whose effects have advanced our understanding of pressor mechanisms. This and other research into hypertensive mechanisms has defined the clinical, pharmacological, and endocrinologic heterogeneity of human hypertension. The sum of these developments is a greatly enhanced ability to identify curable and definable causes of hypertension and to pathophysiologically stratify the remaining cases of essential hypertension. Modern treatment can be much more specific than before. When long-term drug therapy is indicated, the regimen is more likely to achieve a primary goal for each patient, that is, the fewest possible drugs in the smallest amount and in lowest frequency. Two clinically quantifiable mechanisms for long-term arteriolar vasoconstriction can be identified within the spectrum of human hypertension. The first, renin-mediated vasoconstriction, is directly related to the plasma renin level. The second, sodium-volume-related vasoconstriction, is marked by a reciprocally subnormal renin level and involves abnormal sodium retention and calcium transport. A baseline renin-sodium profile can identify the pressure of one of these two forms of vasoconstriction and therefore is the key for the diagnosis of the two curable disorders that fully express one of the two pressor mechanisms--renovascular hypertension and primary aldosteronism. Renovascular hypertension, more common than once thought, is often cured by angioplasty. It is important to diagnose these curable forms before beginning long-term drug therapy. The renin-sodium profile, used in conjunction with serum potassium and creatinine measurements, is valuable not only in screening patients for curable forms, but also for stratifying the remainder according to the pathophysiological vasoconstrictor mechanism that underlies the hypertension. Converting enzyme inhibitors or beta-blockers are, by themselves, often effective in correcting the hypertension of high- or medium-renin patients, whereas calcium antagonists, diuretic agents, or alpha-blockers alone are most effective against the low-renin form of vasoconstriction. In the large midzone of renin values, if monotherapy fails, a rational basis for combined antirenin-antisodium volume therapies can be developed. 
Animal models of fulminant hepatic failure. The six requirements for a satisfactory animal model of fulminant hepatic failure are reversibility, reproducibility, death from liver failure, a therapeutic window, a large animal model, and minimal hazard to personnel. Different models may be required to evaluate the various types of liver failure seen in man. The available models include surgical anheptic and devascularization procedures, as well as hepatotoxic drug administration using agents such as carbon tetrachloride, acetaminophen, or galactosamine. Currently combined surgical and drug models appear to provide the best model but the search for the ideal models continues. 
Epipalatus: a rare intraoral teratoma. A wide range of discrete head and neck tumors are developmental, including those termed choristoma, hamartoma, dermoid cysts, teratoid tumors, and true teratomas. In classifying various teratomas, consideration is given to the embryonal layers represented within the substance of the tumor and to their level of organizational complexity. By definition, a hamartoma is a tissue mass, present at or near the time of birth, that is benign and native to the site of origin. Growth capacity of a hamartomatous process parallels that of the host organism. A choristoma, on the other hand, is a mass of tissue that is foreign to the site of discovery and is thought to result from growth to displaced primordial tissue that is histologically normal for that tissue. 
Magnetic resonance imaging for detecting and treatment monitoring of orthotopic murine bladder tumor implants. We assessed the feasibility of magnetic resonance imaging (MRI) for detection and treatment monitoring of early stage orthotopic murine bladder (MBT-2) tumor implants. Thirty mice were scheduled for imaging at six, 14, 18 and 21 days after tumor implantation. Using a volume imaging coil, MRI demonstrated very early orthotopic tumors, the detection of which would otherwise have been impossible by clinical signs only. Sequential accurate assessment of tumor size was achieved by inflation of the bladders with a fixed volume of Gadolinium-DTPA contrast. The presence of established MBT-2 intravesical tumors was confirmed by gross pathology and light microscopy of the corresponding whole mount bladder sections. Histological examination of the corresponding tumor specimens revealed the presence of transitional cell bladder carcinoma which correlated very well with the topography and depth of tumor involvement as indicated on MRI. The The mice tolerated repeated MR imaging well. Early tumors at day 14 were detectable on MRI (with serial tumor growth to day 21), with no clinical signs of disease. In a subsequent study, response to intravesical tumor necrosis factor alpha (TNF-alpha) immunotherapy was monitored with serial MRI. The serial MR images from six tumor-bearing mice (three controls and three TNF-alpha treated) have been selected to illustrate the consistent findings of this study. Sequential MRI scans of TNF-alpha treated mice revealed retardation of tumor growth that correlated well with the corresponding histologic examination. The orthotopic tumor and MRI model described is ideal for preclinical evaluation of new potential intravesical chemotherapy and immunotherapy agents. 
Studies on the cellular origin of neurothekeoma: clinical, light microscopic, immunohistochemical, and ultrastructural observations. The clinical, histopathologic, and immunohistochemical features of 11 cases of neurothekeoma are reported. One case was examined by electron microscopy. The mean age of the patients was 27.1 years; the study comprised eight female and three male patients. Most lesions were nondescript papules and located on the upper part of the body, seven cases of neurothekeoma on the head. Eight cases were classified as cellular neurothekeoma on the basis of a striking fascicular pattern and three cases as myxomatous neurothekeoma because of prominent myxoid stromal change. All cellular neurothekeomas failed to express S-100 protein, whereas the three myxomatous types were strongly positive for this marker. Other than vimentin, there was no significant immunoreactivity with other immunohistochemical markers. Ultrastructural study of one case of cellular neurothekeoma was inconclusive for cell type although a perineurial origin could not be excluded. On the basis of these results, we conclude that cellular neurothekeoma differs from myxomatous neurothekeoma not only by clinical and histologic findings but also by immunoreactivity with S-100 protein. These findings also suggest the existence of two distinct subtypes of neurothekeoma and possible origin of the two variants of neurothekeoma from different cell types or at least variation in phenotypic expression of a common cell type. On the other hand, it cannot be excluded that these two variants are different stages in the natural history of neurothekeoma. 
Differences in prostaglandin metabolism in cultured aortic and pulmonary arterial endothelial cells exposed to acute and chronic hypoxia. In vivo, a marked difference in blood oxygen tension exists between the pulmonary artery and the aorta. Responses of vascular endothelial cells from these vessels to changes in ambient oxygen might be influenced by the oxygen tension to which they are continuously exposed in vivo or by their anatomic site. To explore this hypothesis, we initially studied the production of the cyclooxygenase metabolites prostacyclin and thromboxane in bovine aortic and main pulmonary arterial endothelial cells grown in 21% O2 and exposed to different degrees of acute hypoxia over a wide range of times. We found that short-term hypoxia (3% or 0% O2) rapidly and transiently activates the cyclooxygenase pathway in both cell types, with a more rapid response in bovine aortic endothelial cells. To determine whether culture in an oxygen tension similar to that to which main pulmonary arterial endothelial cells are exposed in vivo alters this response, we evaluated these cyclooxygenase metabolites in bovine aortic and main pulmonary arterial endothelial cells cultured long-term in 3% O2, both at baseline and after exposure to acute anoxia (0% O2). In both cell types, we found a decrease in prostacyclin and thromboxane synthesis at baseline and evidence of an increase in the Vmax of thromboxane synthetase following stimulation with exogenous arachidonic acid. In chronically hypoxic cells exposed to acute anoxia, there were marked differences in enzyme activity compared with that in endothelial cells maintained in 21% O2 with differences depending on the origin of the endothelial cells. In bovine aortic endothelial cells, production of neither cyclooxygenase metabolite increased; in bovine main pulmonary arterial endothelial cells, only thromboxane production increased, suggesting isolated activation of the cyclooxygenase-thromboxane synthetase pathway. These studies demonstrate that acute and chronic hypoxia have profound effects on endothelial cell cyclooxygenase metabolism and that these effects depend on the duration and degree of the hypoxic exposure and the vascular bed from which the endothelial cells are derived. 
Lupron retards proliferation of ovarian epithelial tumor cells cultured in serum-free medium. Some patients with recurrent ovarian epithelial cancer respond favorably to treatment with GnRH agonists. This effect was proposed to be mediated by suppression of pituitary gonadotropin release. The present in vitro study investigated effects of human gonadotropin (Pergonal LH/FSH, 1:1) and Lupron, a GnRH agonist, on proliferation of an ovarian cancer cell line, 2774, which is estrogen receptor negative and grows well in serum-free, defined medium. Pergonal, 10 IU/mL or 30 IU/mL, did not enhance cell proliferation, which argues against stabilization of ovarian tumors in vivo due to decreased serum gonadotropin. Lupron, 1.4 micrograms/mL and 140 micrograms/mL, retarded cell division by day 6-8 of culture, in a dose-dependent manner. Flow cytometric cell cycle phase DNA analysis demonstrated Lupron caused a reversible 5-6% increase in the portion of cells in rest phase, G0/G1, compared to controls during log growth, and a corresponding decrease in the portion of cells in DNA synthesis, S phase. However, long-term culture, 3 weeks, with Lupron failed to arrest cells in G0/G1, and experimental cultures plateaued at cell number similar to control cultures. We conclude Lupron's effect on ovarian cancer cell proliferation is independent of gonadotropin and steroid, involves a cell cycle regulatory event, and duration of benefit observed in vivo for some patients may be related to total tumor volume at the time of treatment. 
Mechanism of analgesia induced by hypnosis and acupuncture: is there a difference? Hypnosis and acupuncture can alleviate experimentally induced pain but the mechanism of analgesia remains unclear for both techniques. Experimental pain was induced by cold pressor test (CPT) in 8 male volunteers. Analgesic effect of hypnosis (HA) and acupuncture (AA) was assessed before and after double-blind administration of placebo or naloxone, in a prospective, cross-over study. We found that pain intensity was significantly lower with HA as compared with AA, both with naloxone (P less than 0.001) and placebo (P less than 0.001). Within HA or AA groups, pain scores did not differ significantly when naloxone or placebo was administered. During AA, however, pain scores were similar to control values when naloxone was given (P = 0.05) but decreased significantly with placebo (P less than 0.002). Analog scales for pain intensity and pain relief showed a good correlation (r = 0.94). Plasma levels of beta-endorphins did not change significantly in any combination. Heart rate, peripheral arterial blood pressure and skin conductance were very insensitive indices to assess pain intensity or relief, as well as intensity of acupuncture stimulation or depth of hypnotic trance. We conclude: (1) HA and AA can significantly reduce pain from CPT, and HA is more effective than AA: (2) HA and AA are not primarily mediated by the opiate endorphin system; and (3) plasmatic levels of beta-endorphins are not significantly affected by either HA or AA nor by naloxone or placebo administration. 
Mechanisms of asphyxial brain damage, and possible pharmacologic interventions, in the fetus. An examination of the cellular and molecular mechanisms of neuronal cell damage may lead to the design of pharmacologic interventions during presumed or actual fetal asphyxia. Hypoxia-ischemia in its severest form results in insufficient adenosine 5'-triphosphate production. The most important effect of this is failure of adenosine 5'-triphosphate-dependent membrane functions, which maintain ionic homeostasis, that is, ionic pumping. There is K+ efflux and Na+ influx across the cell membrane, depolarization of the cell membrane, opening of the voltage-dependent calcium channels, and entrance of Ca++ into the cell. Cytosolic Ca++ is also increased by Ca++ efflux from the mitochondria and the sarcoplasmic reticulum. Ca++ is a toxin in high cytosolic concentrations; it activates phospholipases A and C, which cause membrane breakdown and release of free fatty acids, including arachidonic acid. The membrane is damaged, lysis occurs, and the neuron dies. High cytosolic Ca++ also causes release of excitatory amino acids (especially glutamate), which overwhelm the suppressant neurotransmitters, causing seizures, increased metabolism, and aggravation of the insufficient adenosine 5'-triphosphate availability. Thromboxane A2 is generated from arachidonic acid, increasing smooth muscle tone and thereby worsening the ischemia. Cyclooxygenase activity also results in formation of oxygen-free radicals that contribute to cell membrane damage, lysis, and death. Possibilities for pharmacologic interventions include (1) calcium channel blockers and antagonists, (2) excitatory neurotransmitter blockers, (3) oxygen-free radical scavengers (e.g., superoxide dismutase), (4) cyclooxygenase or prostaglandin synthesis inhibitors, and (5) seizure suppressants (e.g., phenobarbital). Some of these treatments have been shown experimentally to limit neuronal death in the adult and fetus, and after more investigative work they may be applicable to clinical practice. 
The expression of CD22 (Leu 14) and CD11c (LeuM5) in chronic lymphoproliferative disorders using two-color flow cytometric analysis. The monoclonal antibodies (MoAbs) CD22 and CD11c recognize B-lymphocyte- and monocyte-associated antigens, respectively. Reports indicate that when these two MoAbs co-express, they represent a unique marker for hairy cell leukemia (HCL) although neither is specific for that disease. The authors evaluated the expression and diagnostic utility of CD22 and CD11C in specimens from 26 normal subjects, 29 patients, with various nonlymphoproliferative disorders (NLPDs), and 75 patients with different types of chronic lymphoproliferative disorders (CLDs) using two-color flow cytometric analysis of peripheral blood lymphocytes. Lymphocytes co-expressed CD22 and CD11c in less than or equal to 3% of the normal subjects and in less than or equal to 6% of the patients with NLPDs. These markers were expressed in greater than 10% of the lymphocytes of 46% (32/69) of the patients with B-cell CLDs: B-cell chronic-lymphocytic leukemia, 9/41; B-cell non-Hodgkin's lymphoma, 8/14; HCL, 11/11; B-cell lymphoproliferative disorder (NOS), 1/2; and B-cell prolymphocytic leukemia, 1/1. None (0/6) of the lymphocytes of patients with T-cell CLDs expressed greater than 10% CD22-positive (CD22+) or CD11c-positive (CD11c+) cells. The HCL cases demonstrated a unique CD22+CD11c+ fluorescence histogram pattern, distinct from other lymphoproliferative disorders, that was characterized by uniformly intense CD11c and CD22 fluorescence. Differences in the expression of the CD22+CD11C- and CD22+CD11C+ phenotypes between diagnostic groups were found, most notable was a paucity of CD22+CD11c+ cells in lymphocytes of patients with HCL. CD22 also had more variable expression than CD19 and HLA-DR in the cases of B-cell CLD. This study demonstrates that the CD22+CD11c+ phenotype is not unique to HCL but is a consistent feature of that disorder and that the immunofluorescence pattern of co-expression in HCL is diagnostically useful. 
Benign recurrence of a pilocytic cerebellar astrocytoma 36 years after radical removal: case report. A benign recurrence of a cerebellar juvenile astrocytoma was found in a 52-year-old woman 36 years after the initial radical removal, which was performed when she was 16 years of age. To our knowledge, this is the third detailed case report of the late benign recurrence of cerebellar astrocytoma after total removal. The problem of recurrence of cerebellar astrocytoma is reviewed. 
Recurrent mild abruptio placentae occurring immediately after repeated electroconvulsive therapy in pregnancy. We present a case in which electroconvulsive therapy was performed repeatedly in pregnancy because of severe depression with psychotic features and failure of chemical treatment. Each electroconvulsive treatment was immediately followed by uterine contractions and active uterine bleeding, possibly representing recurrent abruptio placentae occurring in association with the treatment. Transient acute episodes of maternal hypertension between 180/90 and 190/100 mm Hg, documented within minutes after application of each electroconvulsive treatment, might explain the abruptio placentae manifested by active uterine bleeding and uterine hyperstimulation. 
Long-latency neurodegenerative disease in the western Pacific. The western Pacific parkinsonism-dementia and amyotrophic lateral sclerosis complex is a prototypical neurodegenerative disorder found among inhabitants of Guam, New Guinea (Irian Jaya, Indonesia) and Japan (Kii Peninsula, Honshu). Nonviral environmental factors peculiar to the affected populations seem to play a prominent etiologic role. Although cause-effect relationships cannot be established by epidemiologic studies alone, we have shown in all three affected population groups that individuals develop the amyotrophic lateral sclerosis variant of this disorder after heavy exposure to the raw or incompletely detoxified seed of neurotoxic cycad plants. Since long periods may elapse between cycad exposure and the appearance of neurological disease in humans, cycads may harbor a "slow toxin" that causes the postmitotic neuron to undergo slow irreversible degeneration. Two cycad neurotoxins are recognized, one of which (cycasin) is known to have long-latency effects (tumorigenesis) on mitotic neurons and replicating cells in other tissues. This paper explores the possible relationship between tumorigenesis and long-latency neurotoxicity, and discusses possible biologic markers of cycad exposure and subclinical neurodegenerative disease. 
Interleukin 4 suppresses the spontaneous growth of chronic myelomonocytic leukemia cells. We studied the effects of IL-4 on the spontaneous proliferation of chronic myelomonocytic leukemia (CMMoL) cells in vitro. IL-4 (100 U/ml) suppressed the spontaneous DNA synthesis by approximately 50% in 5 of 8 cases examined. IL-4 (100 U/ml) also inhibited the spontaneous colony formation by CMMoL cells in a methylcellulose culture by 50-97% in all of the 10 cases in which spontaneous colonies were formed. This IL-4-mediated suppression of the growth of CMMoL cells was completely abolished by the addition of anti-IL-4 neutralizing antibodies. The spontaneous CMMoL colonies were substantially suppressed by the addition of either anti-IL-6 or anti-granulocyte/macrophage colony-stimulating factor (GM-CSF) antibodies to the colony assay system: the addition of both anti-IL-6 and anti-GM-CSF antibodies resulted in greater than 80% inhibition of the colony formation by CMMoL cells. On the other hand, none of anti-IL-1-beta, anti-granulocyte-CSF, anti-macrophage-CSF, or anti-tumor necrosis factor-alpha antibodies affected the CMMoL colony formation. In the supernatants from 24-h cultures of CMMoL cells, high levels of IL-6 and GM-CSF were demonstrated in 9 of 9 and 2 of 9 cases examined, respectively. IL-4 (100 U/ml) almost completely inhibited the secretion of IL-6 and GM-CSF by CMMoL cells. These observations suggest that IL-4 suppresses the spontaneous proliferation of CMMoL cells by inhibiting their production of IL-6 and/or GM-CSF, both of which could act in vitro as an autocrine growth factor for CMMoL cells. 
A cell cycle-responsive transcriptional control element and a negative control element in the gene encoding DNA polymerase alpha in Saccharomyces cerevisiae. Transcription of the POL1 gene of Saccharomyces cerevisiae, which encodes DNA polymerase alpha, the DNA polymerase required for the initiation of DNA replication, has previously been shown to be cell cycle regulated. To understand how the POL1 gene senses cell cycle position, we have investigated the cis-acting elements that respond to the factors that govern cell cycle progression. In this report we demonstrate that a region of 54 nucleotides containing the repeated element ACGCGT, which conforms to an Mlu I restriction endonuclease recognition site, contains all information necessary for transcriptional activation and cell cycle responsiveness. Although oligonucleotides lacking either one or both of the repeated Mlu I sites can function as an upstream activating sequence, the presence of at least one Mlu I site stimulates expression and, moreover, is absolutely essential for cell cycle regulation. A synthetic oligonucleotide corresponding to a 19-base-pair sequence in the POL1 promoter containing one Mlu I site can function as an autonomous cell cycle-responsive upstream element (upstream activation sequence) with temporal regulation indistinguishable from that previously described for the POL1 gene. Thus, the Mlu I site is an essential part of a cis-acting element responsible for the observed periodic activation. This sequence differs from previously defined cell cycle-responsive transcriptional control elements in the yeast HO endonuclease and histone genes. We also present evidence for a negative regulatory element in the 5' flanking region of the Mlu I upstream activation sequence. 
Resolution of chronic pelvic pain after laparoscopic lysis of adhesions. Thirty women undergoing laparoscopic lysis of adhesions for the treatment of chronic pelvic pain were prospectively evaluated for the presence of a chronic pain syndrome. At follow-up, of those with chronic pain syndrome (10), four (40%) reported continued improvement or resolution of pain during daily activities of dyspareunia, whereas of those without chronic pain syndrome (20), 15 (75%) were better (p = 0.06). When these two complaints are evaluated individually, both pain during daily activities (p less than 0.05) and dyspareunia (p less than 0.05) are more likely to improve after lysis of adhesions in women without chronic pain syndrome. Prognosis was not related to the number of previous operations, adhesion score, or other physical parameters. Laparoscopic lysis of adhesions is generally worthwhile in the treatment of chronic pelvic pain, although the presence of psychosocial compromise warrants preoperative evaluation and concomitant treatment. 
Colectomy, mucosal proctectomy, and ileal pouch-anal anastomosis. A prospective trial of optimal antibiotic management. The ideal prophylactic antibiotic regimen has not been established for patients undergoing colectomy, mucosal proctectomy, and endorectal ileoanal anastomosis, a prolonged operation frequently accompanied by abdominal and pelvic contamination and associated with an infection rate up to 20%. The aim of this study was to evaluate, in a prospective, randomized, double-blind fashion, the efficacy of a short perioperative course compared to an extended postoperative course of intravenous antibiotics (cefoxitin) in patients undergoing colectomy with ileoanal anastomosis. Forty patients with ulcerative colitis or familial polyposis coli received a mechanical and oral antibiotic bowel preparation and a standard three-dose perioperative course of intravenous cefoxitin. Patients then were randomized to receive intravenous cefoxitin, 1 g every 6 hours, or placebo for 5 days. No differences in overall postoperative morbidity were observed and neither group developed intra-abdominal, pelvic, or wound infections. It is concluded that a standard three-dose perioperative course of intravenous antibiotics provides adequate prophylaxis in the prevention of infectious complications in patients undergoing colectomy, mucosal proctectomy, and ileoanal anastomosis. 
Patient activity, sports participation, and impact loading on the durability of cemented total hip replacements. Patients with either cemented surface replacements or cemented stemmed hip prostheses and who regularly participate in sporting activities or heavy labor after total joint arthroplasty are at twice the long-term risk of requiring revision surgery for loosening as patients who are less active. For patients with surface replacement total hip arthroplasty (THA), the adverse effects of activity are greatest in patients with preoperative diagnoses other than osteoarthritis, and were seen by the sixth year postsurgery. For patients with conventional stemmed prostheses, the effects of patient activity are not seen until about ten years postsurgery. For resurfacing THA for osteoarthritis, the long-term of loosening is primarily in patients who participate in high impact activities. 
Presenting features and prognosis of chronic lymphocytic leukemia in younger adults. We have analyzed 117 younger patients with chronic lymphocytic leukemia (CLL) (mean age, 44.5 years; SD, 4.8; range, 19 to 49; male/female ratio, 2.08) with three main objectives: (1) to see whether these patients have distinctive presenting clinical features; (2) to investigate the impact of the disease on survival; and (3) to analyze whether already well-known prognostic factors are also useful when applied to these patients. As compared with an older age population (greater than or equal to 50 years), there were no major differences in presenting features except for an increased proportion of males (2.08 v 1.21; P less than .025) and a higher hemoglobin level (13.47 +/- 2.70 g/dL v 12.84 +/- 2.77 g/dL; P less than .05) in the younger group. Median survival is 12.3 years (expected median from a control group, 31.2 years). Clinical stages, bone marrow patterns, blood lymphocyte counts, and its doubling time are all useful to separate different risk groups of patients. Whereas patients with favorable prognostic factors have a survival probability of about 80% 14 years after diagnosis, those with poor prognostic features have a median survival of less than 3 years. It is concluded that CLL in younger adults has no major distinctive presenting features and that known prognostic factors are useful to separate different risk groups of patients. These results should be of help in planning therapy for younger persons with CLL. 
Long-term efficacy and safety of terazosin alone and in combination with other antihypertensive agents. This open, multicenter phase III study was designed to assess the efficacy and long-term safety of terazosin (1 to 40 mg/day), alone or in combination with other antihypertensive drugs, in 364 patients with mild to moderate essential hypertension. Compared with baseline values, long-term terazosin monotherapy or combination therapy resulted in consistent decreases in both systolic and diastolic blood pressures, with a mean reduction in supine diastolic pressure of 12 to 14 mm Hg. The numbers of patients with controlled blood pressure at the last evaluable visit of each therapy period were as follows: terazosin alone, 106 of 245 (43%); terazosin with added diuretic, 70 of 112 (63%); diuretic with added terazosin, 47 of 88 (53%); and terazosin plus diuretic with added beta-blocker, 22 of 32 (69%). Most adverse events were mild or moderate in severity. Only pain in extremities had a higher incidence during long-term treatment (6%, 181 to 360-day period) than during initial short-term treatment (5%, 1 to 90-day period). Three of six syncopal events occurred during the initial 180 days of treatment; this 0.8% (3/364) incidence was comparable with that reported previously for short-term studies. Only one case of syncope occurred during terazosin monotherapy. Terazosin was judged to be a safe and effective long-term medication for the treatment of hypertension. 
The "make/break test" as a diagnostic tool in functional weakness. Strength was measured in four major muscle groups with a hand-held dynamometer. The "make" and "break" technique was used with and without encouragement, and fatiguability was tested in patients with organic weakness and patients with functional weakness. Patients with functional weakness could be distinguished from the other two groups by an increase in strength greater than 20% with the break compared with the make technique. Additionally they tend to show larger increases in strength with encouragement and their "fatiguability" was less. 
Enhanced detection of the t(14;18) translocation in malignant lymphoma using pulsed-field gel electrophoresis. The t(14;18) chromosomal translocation that results in the juxtaposition of the bcl-2 proto-oncogene with the heavy chain JH locus is a common cytogenetic abnormality in human lymphoma. In particular, it is seen in about 85% of follicular lymphoma (FL) and up to one-third of diffuse lymphomas (DL). The chromosome 18 breakpoints have been shown to cluster into two regions. The major breakpoint region (mbr) within the 3' untranslated region of the bcl-2 proto-oncogene accounts for approximately 60% of the cases and the minor cluster region (mcr) 30 kb 3' of bcl-2 accounts for approximately 25% of the breakpoints. Because of variability in the position of the breakpoint, detection of the t(14;18) by Southern blot analysis provides an important clonal marker for the tumor. However, conventional electrophoresis (CE) fails to detect the translocation in 15% to 25% of cases. We have applied pulsed-field gel electrophoresis (PFGE) to the detection of the t(14;18) in a series of lymphoma prospectively analyzed by CE, polymerase chain reaction (PCR), and cytogenetic analysis. PFGE readily detected t(14;18) rearrangements as indicated by comigration of bands detected with probes for the mbr region (chromosome 18) and the JH locus (chromosome 14). In a series of 40 patients with FL, this method proved to be the most comprehensive for detection of the translocation compared with standard methods; in fact, in one case only PFGE was able to detect the chromosomal rearrangement. Ten percent of the FL cases were negative by all methods tested. In a separate analysis of matched tissue specimens from cases of tumor progression of FL to diffuse lymphoma, PFGE detected a common t(14;18) rearrangement confirming a clonal origin in seven of seven cases, whereas CE detected a rearrangement in only three of seven cases. Overall, PFGE was able to detect a translocation in 8 of 12 cases that were negative by CE and four of eight negative by cytogenetic analysis. In conclusion, PFGE analysis is more comprehensive than CE, PCR, and cytogenetic analysis for the detection of the t(14;18) breakpoint in tissue biopsies of malignant lymphoma. 
Small bowel tumours: yield of enteroscopy. A total of 258 patients with obscure gastrointestinal bleeding were referred for small bowel enteroscopy, a procedure which allows endoscopic evaluation of most of the small intestine. A small bowel tumour was found in 5% of patients. In 50% of patients no diagnosis could be made, but when the cause of obscure bleeding was discovered small bowel tumours were the single most common lesion in patients younger than 50 years. Small bowel tumours causing gastrointestinal bleeding may remain undetected despite extensive diagnostic evaluation. We conclude that small bowel tumours are the most common cause of obscure gastrointestinal bleeding in patients less than 50 years of age. Small bowel enteroscopy is diagnostic of small bowel tumours even when all previous diagnostic studies, including enteroclysis and angiography, are negative. 
Effect of DN-1417 on photosensitivity and cortically kindled seizure in Senegalese baboons, Papio papio. The effect of DN-1417, a thyrotropin-releasing hormone (TRH) analogue, on photosensitivity and cortically kindled seizures was examined in seven Senegalese baboons (Papio papio). Intravenous (i.v.) administration of 2 mg/kg had no effect on either photosensitivity or cortically kindled seizures. When this agent was administered intracisternally, both the photomyoclonic response and cortically kindled seizures were suppressed for 4-5 days. A study of the transcallosal response also showed a long-lasting attenuation of the early positive wave (P1) amplitude (peak latency, 5-10 ms) elicited by a single stimulus after cisternal injection of DN-1417. These findings are consistent with the assumption that endogenous TRH is involved in suppression of epileptic seizures. 
Comparison of extradural and intravenous diamorphine as a supplement to extradural bupivacaine. The influence of route of administration (extradural as compared with intravenous) of diamorphine 0.5 mg/hour as a supplement to extradural bupivacaine (0.125% at 15 ml/hour) was investigated in two groups of 20 patients who underwent major abdominal gynaecological surgery. Significantly more patients in the intravenous group withdrew because of inadequate analgesia (p less than 0.05). Those in the extradural group were significantly more drowsy throughout the study (p less than 0.01), but no major side effects were encountered. 
Extracranial-intracranial bypass to reduce the risk of ischemic stroke. Extracranial-intracranial (EC-IC) bypass surgery is an operative procedure in which the superficial temporal artery is anastomosed to the middle cerebral artery. The operation, first described in 1969, was employed to circumvent otherwise surgically inaccessible atherosclerotic lesions high in the internal carotid system or in the middle cerebral artery. This assessment compares the findings from 13 surgical series of EC-IC bypass (1464 patients) with those reported in the only prospective, randomized, cooperative trial of this procedure (1377 patients). Analysis of the outcomes in the 1464 patients included in the surgical series produced insufficient evidence to support a conclusion that post-EC-IC bypass stroke rates were lower than the rates of either the medically or surgically treated groups in the controlled clinical trial. In the absence of reliable, objective evidence of the existence of a group of patients in whom surgical intervention is superior to medical treatment in reducing the frequency of stroke, the results of the single controlled clinical trial, which demonstrated no benefit of bypass, must be accepted as the best evidence currently available. 
Importance of experimental models for the development of clinical trials on thromboatherosclerosis. Experimental models of vascular injury have enhanced our understanding of the pathophysiological process leading to vascular obstruction in both spontaneous and accelerated atherosclerosis. Based on experimental findings, we present and discuss a pathological classification of vascular injury or damage and its role in the pathogenesis of various vascular diseases. In addition, these animal models have provided insights into the roles of platelets and lipid metabolism in the evolution and progression of atherosclerosis and have suggested potential therapeutic applications. Thus, based on studies in the pig models, antiplatelet agents have been shown for the first time to have a beneficial effect in preventing the formation and progression of coronary atherosclerotic lesions in humans. Similarly, our findings in high density lipoprotein plasma fractions regarding inhibition and even reversal of the process of atherosclerosis in a hypercholesterolemic rabbit model have added new insights to an explosive field of lipoprotein research and provided new avenues of therapeutic strategies. our in vivo and ex vivo pig models of an extracorporeal perfusion chamber mimicking the various coronary conditions have aided in the understanding of the pathophysiology of the acute coronary syndromes and intensified our search for the ideal antithrombotic regimen in these high-risk patients. Finally, a carotid pig model of balloon angioplasty, a dog model of saphenous vein grafting, and a pig model of heart transplantation not only have provided insights into the pathophysiological process of accelerated atherosclerosis but also are allowing development of new antithrombotic and antiproliferative approaches for the prevention of these accelerated vascular diseases. In summary, we are entering an exciting era in vascular research. Significant advances in our understanding of vascular injury or damage as well as the interactions of blood cells and lipids with the vascular wall have allowed us to formulate new experimental strategies with subsequent clinical application in the prevention and progression of these vascular diseases. 
Differentiation-inducing cytokine P48 exists in a membrane-associated form. P48 is a recently described 48-kDa differentiation-inducing cytokine isolated from the culture medium of the human leukemia line Reh. P48 induces differentiation and cytolytic activity in the promyelocytic cell line HL-60, and stimulates the release of TNF-alpha and IL-1 from peripheral blood monocytes. In further studies designed to examine the biosynthesis and function of P48, surface immunofluorescence flow cytometry analysis as well as 125I surface labeling and immunoprecipitation, revealed the presence of P48 on the surface of Reh cells. Triton X-114-treated Reh cells were partitioned into detergent and aqueous phases and separated by SDS-PAGE. Western blot analysis revealed that P48 partitioned exclusively into the detergent phase, suggesting an integral membrane association. Reh cells fixed with paraformaldehyde, but not K562 or P815, were able to stimulate the release of TNF-alpha from peripheral blood monocytes in a manner similar to that of secreted P48. Isolated plasma membranes from Reh cells could also stimulate TNF-alpha release. This TNF-alpha-releasing activity could be removed from detergent solubilized Reh membranes by immunoaffinity chromatography on an anti-P48 column. This study suggests that, in addition to being secreted into the culture medium, P48 is expressed on the surface of Reh cells in a biologically active form. The membrane form of P48 may be 1) a final maturation step before secretion or 2) a cell membrane-associated form that may be analogous to the membrane forms of TNF-alpha and IL-1. 
A meta-analysis of low-dose aspirin for the prevention of pregnancy-induced hypertensive disease. BACKGROUND.--Pregnancy-induced hypertension (PIH), defined as either isolated hypertension after the 20th week of gestation or hypertension with proteinuria (preeclampsia), occurs in 5% to 15% of pregnancies and is associated with maternal and neonatal morbidity. Previous clinical trials with small numbers of patients have suggested that aspirin in doses of 60 to 150 mg/d during the second and third trimesters reduces the risk of PIH and improves maternal and neonatal outcomes. OBJECTIVE.--We performed a meta-analysis of the six published controlled trials to estimate more precisely (1) the magnitude of protection of aspirin from PIH; (2) the effect of aspirin on severe low-birth-weight infants, cesarean section, and perinatal mortality; and (3) the risk of adverse effects. METHODS.--We critically and independently evaluated study methods, assigned a quality score to each trial, and abstracted quantitative outcomes data. For each outcome, both relative risk (RR) and the number needed to be treated were calculated. RESULTS.--Among 394 subjects from six trials, the RR of PIH among women who took aspirin was 0.35 (95% confidence interval [CI], 0.22 to 0.55) and the number needed to be treated was 4.4, meaning that between four and five high-risk women would need to be treated with aspirin to prevent one case of PIH. Aspirin reduced the risk of severe low birth weight among newborns by 44% (RR = 0.56; 95% CI, 0.36 to 0.88) and reduced the risk of cesarean section by 66% overall (RR = 0.34; 95% CI, 0.25 to 0.48), although the specific indications for cesarean section were generally not described. There was no effect on fetal and neonatal death (RR = 0.88; 95% CI, 0.32 to 2.46), and there were no maternal or neonatal adverse effects associated with taking aspirin. CONCLUSION.--This meta-analysis suggests that low-dose aspirin reduces the risks of PIH and severe low birth weight, with no observed risk of maternal or neonatal adverse effects. 
Relief of right ventricular angina and increased exercise capacity with long-term oxygen therapy. Long-term low-flow oxygen therapy can lead to improved exercise capacity and improved hemodynamics in selected patients with pulmonary hypertension. We report a patient who presented with severe exercise limitation and anginal chest pain that appeared to result from pulmonary hypertension and predominantly right ventricular ischemia. Acute oxygen therapy led to relief of pain but no change in exercise capacity or of pulmonary hypertension. After eight months of oxygen therapy, the patient's pulmonary hypertension was unchanged, but right ventricular hypertrophy and marked increases in exercise cardiac output and exercise capacity developed. Thus, oxygen can relieve right ventricular angina and facilitate the development of compensatory hypertrophy. 
Localization of gene for familial hypertrophic cardiomyopathy to chromosome 14q1 in a diverse US population. BACKGROUND. Familial hypertrophic cardiomyopathy, an inherited primary cardiac abnormality characterized by ventricular hypertrophy, is the leading cause of sudden death in the young. Recent application of restriction fragment length polymorphism markers has provided provocative results, with localization to chromosome 18 (Japanese studies), 16 (Italian studies), 14 (US and French-Canadian studies), and two (National Institutes of Health studies) indicating genetic heterogeneity. Interpretation remains speculative until at least one of these loci is confirmed in unrelated pedigrees by independent investigators. METHODS AND RESULTS. We studied eight unrelated families of varied ethnic origins across the United States. DNA from each individual was digested with restriction enzymes TaqI or BamHI and analyzed by Southern blots followed by hybridization with probes T cell receptor alpha (TCRA), myosin heavy chain beta, D14S25, and D14S26. Multipoint linkage analysis showed a maximum lod score of 4.3, placing the locus 10 cM from D14S26 between D14S26 and TCRA, with an odds ratio of 20,000:1 and 90% confidence limits of 12 cM proximal to D14S25 to 4 cM distal to TCRA. The probability of linkage to 14q1 was more than 99%. CONCLUSIONS. These results indicate that the loci for familial hypertrophic cardiomyopathy in our families is primarily 14q1 but does not exclude other loci in a small proportion of the families. Thus, 14q1 appears to be the locus for familial hypertrophic cardiomyopathy in a significant proportion of the US population. 
Caffeine self-administration, withdrawal, and adverse effects among coffee drinkers. Twenty-two coffee drinkers (three to seven cups per day) underwent repeated double-blind trials to test for caffeine self-administration, withdrawal, and adverse effects. Each trial consisted first of a randomized crossover period of 1 day of decaffeinated coffee and 1 day of caffeinated coffee (100 mg) to assess withdrawal and adverse effects of caffeine. Next, subjects were given 2 days of concurrent access to the two coffees. The relative use of the two coffees was used to assess caffeine self-administration. Reliable caffeine self-administration occurred in three of 10 subjects in study 1 and seven of 12 subjects in study 2. Withdrawal symptoms were headaches, drowsiness, and fatigue. The major adverse effect from self-administration was tremulousness. The occurrence of headaches on substitution of decaffeinated coffee prospectively predicted subsequent self-administration of caffeine. These results indicate that some coffee drinkers exhibit signs of a caffeine dependence, ie, they self-administer coffee for the effects of caffeine, have withdrawal symptoms on cessation, and experience adverse effects. 
Four years of North American registry home parenteral nutrition outcome data and their implications for patient management. The OASIS Registry started annual collection of longitudinal data on patients on home parenteral nutrition (HPN) in 1984. This report describes outcome profiles on 1594 HPN patients in seven disease categories. Analysis showed clinical outcome was principally a reflection of the underlying diagnosis. Patients with Crohn's disease, ischemic bowel disease, motility disorders, radiation enteritis, and congenital bowel dysfunction all had a fairly long-term clinical outcome, whereas those with active cancer and acquired immunodeficiency syndrome (AIDS) had a short-term outcome. The long-term group had a 3-year survival rate of 65 to 80%, they averaged 2.6 complications requiring hospitalization per year, and 49% experienced complete rehabilitation. The short-term group had a mean survival of 6 months; they averaged 4.6 complications per year and about 15% experienced complete rehabilitation. The registry data also indicated HPN was used for 19,700 patients in 1987 with therapy growth averaging about 8% per year. This growth was chiefly from new cancer patients. The number of new patients with long-term disorders in whom HPN was initiated appeared rather constant. We conclude that these clinical outcome assessments justify HPN for long-term patients, but the utility and appropriateness of HPN for the cancer and AIDS patients remains uncertain and requires further study. Medical, social, and fiscal aspects of HPN management in long-term and short-term patients appear to involve quite separate considerations. 
Post-endarterectomy headache and the role of the oculosympathetic system. A study was carried out on headache after carotid endarterectomy. A specific type of headache, similar in its characteristics to "cluster headache", occurred on the operative side in 30% of 54 patients, whereas no such headache occurred after extra-intracranial bypass or peripheral vascular surgery. This postoperative headache was not spontaneously reported by 56% of patients unless they were specifically asked about it. Pharmacological pupillary testing performed in 37 patients revealed that a decreased oculosympathetic activity (with or without adrenoceptor supersensitivity) was constantly associated with post-endarterectomy headache. Although this same abnormality was also observed in 54% of the patients without headache, a statistically significant (p less than 0.01) higher prevalence of decreased oculosympathetic responses was found in the patients with headache. The results suggest that damage to the sympathetic plexus due to the surgical procedure is involved in the development of postoperative "cluster-like" headache. 
Improvement of psoriatic arthritis in a patient treated with bromocriptine for hyperprolactinemia. We describe a woman with psoriatic arthritis who experienced a remarkable improvement of her skin and joint disease while only taking bromocriptine therapy. She was treated with bromocriptine for primary infertility due to hyperprolactinemia. The improvement in joint symptoms appeared to parallel that of the skin. More studies are required to determine the reproducibility of this observation. 
Recovery of costal and crural diaphragmatic contractility from partial paralysis. Since the two muscles (costal and crural) that constitute the diaphragm are separate and histologically different, their individual recovery pattern from neuromuscular blockade also may be different. Therefore, we studied the recovery of force and shortening in the in vivo diaphragm from atracurium-induced neuromuscular blockade in seven pentobarbital anesthetized dogs to assess segmental differences. Transdiaphragmatic pressure (Pdi), shortening of costal and crural segments, integrated electromyogram (EMG), and tidal volume (VT) were measured during spontaneous breathing. After atracurium had reduced VT to 30% of control, breathing parameters were followed until recovered to 90% of control values. In addition, force-frequency curves generated by supramaximal tetanic stimuli of the phrenic nerve were measured. Recovery times for tidal Pdi, tidal EMG, tidal shortening, low-frequency shortening, and twitch Pdi were twice as fast as for VT (40 +/- 4 min), reflecting a slower rate of recovery of accessory inspiratory muscles. High-frequency recovery was typically slower than that of VT. During tidal breathing and tetanic stimulation, costal and crural shortening recovered simultaneously. On the other hand, comparison between costal and crural by analysis of pressure-shortening relationships showed a segmental difference (crural shortened 30% more than costal at the same Pdi), which implied reduced afterload on the crural segment. However, since shortening and pressure were linearly related during paralysis and recovery, measurements of Pdi alone can accurately reflect changes in contractile mass when heterogeneity and afterload are controlled. 
Trends in the pathophysiology and pharmacotherapy of spasticity [editorial] Spasticity develops after supraspinal or spinal lesions of descending motor systems, with obligate involvement of the corticospinal tract. Spasticity is characterized by an increase in muscle tone, which, in contrast to many other types of enhanced muscle tone, shows a marked velocity-dependent increase when the muscle is passively stretched. The pathophysiological mechanisms underlying this spastic muscle tone remain obscure. Three major causes are currently considered possible: (1) changes in the excitability of spinal interneurones; (2) receptor hypersensitivity; (3) formation of new synapses by sprouting. The latter mechanism could account for the long time course over which spastic muscle tone develops in hemiplegic or paraplegic patients, but there is no experimental evidence for this hypothesis. The electromyographic (EMG) gait analysis of patients with spasticity has thrown doubt on the common belief that the velocity-dependent increase in spastic muscle tone is evoked by stretch reflex activity and has led to the idea that spastic muscle tone resides in the muscle fibres themselves. While such a mechanism may contribute to the slowness of active movements in spastic patients, recent experiments on patients with spastic arm paresis have confirmed the classical view that the spastic muscle tone is related to the EMG activity evoked in the passively stretched muscle. This pathological EMG activity is seen during the entire range of the dynamic phase of the stretch, during which a normal muscle exhibits only an early, phasic burst at the highest stretch velocities employed. For the pharmacological treatment of spasticity, substances with different central or peripheral actions are available. Their assumed receptor actions are described, together with their main indications and side-effects. 
Fatal brainstem stroke following internal jugular vein catheterization. Neurologic complications of central venous catheterization are uncommon, and there are no reports of cerebrovascular events. We report a case of massive postoperative vertebrobasilar territory stroke following internal jugular vein cannulation due to inadvertent vertebral artery injury. Autopsy revealed thrombosis at the site of puncture wound in the right vertebral artery, with emboli present in the distal basilar artery. 
Efficient diagnosis of common complaints: a comparative study in the United States and England. BACKGROUND. The purpose of this investigation was to compare the diagnostic efficiency of American and British family and general practitioners, as measured by their utilization of health care resources and the average length of the diagnostic interval, in diagnosing common complaints. METHODS. Several hundred charts from teaching practices in the United States and England were identified by computer search and reviewed. The charts were those of patients who had presented between 1978 and 1988 with a complaint of chest pain and were subsequently diagnosed as having angina pectoris or reflux esophagitis, or who presented with a complaint of shortness of breath and were subsequently diagnosed as having heart failure or asthma. RESULTS. The results of this study, which compared teaching family medicine practices in the United States and England, suggest that American family physicians diagnose common complaints such as chest pain and dyspnea in a shorter time with fewer visits and fewer consultations than their English counterparts, but order approximately the same number of diagnostic tests. CONCLUSIONS. This study demonstrates the difficulties in interpreting international (cross-cultural) comparisons. Differences may be due to varying health care systems, economic factors, physician training, and physician practice styles, as well as patient expectations. 
Complications associated with brachytherapy alone or with laser in lung cancer. Relatively little has been reported about destruction through brachytherapy of mucosa-perforating and extraluminary tumors with probable large vessel involvement causing major hemorrhagic or fistular complications. We report 12 patients subjected to laser and brachytherapy for centrally occluding lung cancer, whom we have periodically followed up from June 1986 until they died. Although all laser procedures were free from complications, necrotic cavitation in five cases, two of which were accompanied by large bronchoesophageal fistulas, and massive fatal hemoptysis occurred in six. Minor complications included radiation mucositis (two), noncritical mucosal scarring (two), and cough (four). Characteristics that will identify patients at risk of developing fatal hemoptysis and fistulas should be better defined by imaging and endoscopic techniques. In such cases, modifying the protocol or using alternative procedures should be considered. Minor complications, such as cough, can be avoided by using topical steroid therapy (eg, beclomethasone dipropionate). 
Genetic control of immunopathology induced by Mycobacterium leprae. The pathogenesis of leprosy is almost totally attributable to the immune response of the host towards Mycobacterium leprae, a virtually non-toxic intra-cellular parasite. At one end of the leprosy spectrum are tuberculoid leprosy patients, who develop immunity but also delayed-type hypersensitivity towards M. leprae; at the other end are lepromatous leprosy patients, who lack helper T cell activity and therefore do not develop immunity, but who can nevertheless produce antibodies that may cause immunopathology due to immune complexes. A range of immunopathology is seen between these poles. 
Genital human papillomavirus infection in men. Diagnosis and treatment with a laser and 5-fluorouracil. One hundred twenty-eight consecutive men, sexual partners (for more than six months) of women treated for genital condylomata acuminata, were evaluated with colposcopy to assess the percentage of infected men among the couples. Ninety-three (73%) of the men were found to have a genital human papillomavirus infection on colposcopically directed biopsies. All but one patient were treated with outpatient colposcopically guided laser vaporization under local anesthesia (one patient with extensive condylomata required general anesthesia). Two weeks after laser surgery, 5% 5-fluorouracil cream, used in the genital area, was initiated on a weekly basis for two months and every other week for two more months. Patients were followed in the clinic with colposcopy performed every eight weeks for six months to evaluate the regimen's results. Thirty-seven (40%) of the 93 men had "clinically" apparent genital HPV infection, and 56 (60%) of the 93 had "subclinical" disease (as determined with colposcopy). The majority of the patients (87 of 93, or 94%) responded to one laser treatment followed by 5-fluorouracil cream and had no visible lesions at six months. Colposcopic evaluation of the male partners of infected women and laser surgery followed by topical 5-fluorouracil therapy appear to be safe and effective in controlling genital HPV infection. 
Sensorineural hearing loss and the Marinesco-Sjogren syndrome. Sensorineural hearing loss has not been previously reported in patients with the Marinesco-Sjogren Syndrome. Two siblings are described where hearing was initially normal but subsequently deteriorated. 
Coughing and central venous catheter dislodgement. Silastic central venous catheters are subject to dislodgement from a variety of causes. Only one occurrence of catheter dislodgement has been previously reported in connection with coughing. We report four additional cases of silastic central venous catheter dislodgement associated with forceful coughing paroxysms, alone or in combination with emesis or rectal tenesmus. Three episodes of catheter dislodgement occurred in adolescents or young adults with cystic fibrosis, who may constitute a particularly high-risk group. Dislodgement in two patients was asymptomatic. These case suggest that patients with frequent or severe paroxysms of increased intrathoracic pressure may be at higher risk of catheter dislodgement. Since dislodgement may be initially asymptomatic and can cause serious complications, a high index of suspicion for dislodgement in patients with silastic central venous catheters and coughing paroxysms is advised. 
Influence of human immunodeficiency virus infection on cell-mediated immunity in chronic D hepatitis. To determine whether the abnormalities of cell-mediated immunity described in chronic D hepatitis are associated with hepatitis D virus (HDV) infection or concomitant human immunodeficiency virus (HIV) infection, serologic and tissue hepatitis B virus (HBV) and HDV markers and T lymphocyte subsets were studied in serum samples from 38 patients with chronic D hepatitis, 26 of whom had HIV infection. Patients with chronic D hepatitis and HIV infection had significantly lower peripheral blood T4:T8 ratios resulting from a significant increase in T8+ (suppressor/cytotoxic) cells, while numbers of T lymphocyte subsets were normal in cases with chronic D hepatitis only. HIV+ patients showed an increase in HBV replication (identified by hepatitis B core antigen in liver and hepatitis B e antigen and HBV DNA in serum) and in HDV replication (tissue D antigen and HDV RNA) without evidence of more active liver disease. Probably the immunologic disturbances detected in chronic D hepatitis are secondary to HIV infection, do not contribute to the pathogenesis of liver injury, and are associated with increased viral B and D replication. 
DuP 753 increases survival in spontaneously hypertensive stroke-prone rats fed a high sodium diet. We studied the effects of the nonpeptide angiotensin II receptor antagonist, DuP 753, on blood pressure, body weight, plasma renin activity, sodium excretion, and mortality in male stroke-prone spontaneously hypertensive rats (SHRsp) fed a 4% NaCl diet for 12 weeks. The rise in blood pressure, due to high sodium intake, was blunted in the first 8 weeks of the study in the DuP 753-treated group; however, it started slowly to rise in the following weeks. In the untreated group, blood pressure rose steadily and it was significantly higher than that of the treated group during the whole experimental period. DuP 753-treated rats gained weight continuously during the study in contrast to the untreated group, where weight gain was arrested after 4 weeks. Plasma renin activity rose significantly after 4 weeks of treatment with DuP 753; by week 6 its values returned to baseline values and remained at these lower values until week 12. In the untreated group, plasma renin activity was not suppressed by high sodium intake after 4 weeks; it continued to rise and it was significantly elevated by 8 and 12 weeks. Survival at 12 weeks was 84% in DuP 753-treated group and 26% in the untreated group. The data demonstrate that DuP 753 decreased mortality and dramatically blunted the blood pressure rise in SHRsp fed a high sodium diet. 
Endometriosis of the terminal ileum simulating the clinical, roentgenographic, and surgical findings in Crohn's disease. A 38-yr-old nulliparous female presented with endometriosis of the terminal ileum which mimicked the clinical, roentgenographic, and surgical findings of Crohn's disease. The patient presented with diarrhea, right lower quadrant pain, fever, and significant weight loss. At surgery, the terminal ileum was inflamed, indurated, thickened, and angulated. Ileal endometriosis may be expected to simulate Crohn's disease, because intestinal endometriosis frequently produces local bowel inflammation, adhesions, stricture, and angulation. Ileal endometriosis should be carefully considered in the differential diagnosis of Crohn's disease in menstruating females who are nulliparous and have dysmenorrhea, dyspareunia, dyschezia, menometrorrhagia, or other perimenstrual symptoms. It is important not to mistake endometriosis for Crohn's disease because endometriosis has a different therapy. 
Clinical and flow cytometry characteristics of malignant pleural effusions in patients after intracavitary administration of methylprednisolone acetate. Ten patients with recurrent pleural effusions due to advanced cancer were treated by intracavitary methylprednisolone acetate (Depo-Medrol [DM], Upjohn, Kalamazoo, MI). They received one to six courses of DM (median, three courses per patient) with doses ranging from 80 to 160 mg per course. Effusion cells were cryopreserved before and during DM installation for subsequent determination of ploidy by flow cytometry. Pleural effusion in all three patients with advanced breast cancer resolved and did not reaccumulate throughout follow-up for 11+, 10+, and 8+ months. Pleural effusion in a patient with metastatic gastric cancer and in two of four patients with adenocarcinoma of unknown origin partially resolved. Altogether six of ten patients (60%) subjectively and objectively benefited from this therapy. All patients tolerated the treatment well with no local or systemic side effects. Flow cytometry showed a reduction in ploidy of effusion cells in all three patients with breast cancer, from a peak mean channel of 6C to nearly 2C after therapy. Transient reduction of ploidy was seen also in the effusion of a patient with unknown primary tumor associated with clinical improvement. The clinical and laboratory data reported offers initial evidence that DM when instilled into the pleural cavity after incomplete thoracentesis may act as effective palliative therapy either alone or in combination with other anticancer agents. 
Total hip arthroplasty following failed internal fixation of hip fractures. A retrospective review was performed on 27 consecutive patients with total hip arthroplasty (THA) following failure of internal fixation of fractures of the proximal femur. The results were comparable to primary THA in femoral neck fractures. Considerably less satisfactory results were obtained in THA in intertrochanteric fractures. Bone loss and medial displacement of the femoral shaft led to high incidence of intraoperative complications and postoperative dislocations. Extreme care must be taken to avoid fracture and penetration of the femoral shaft. Autograft, allograft, or head and neck replacement components should be available for reconstruction of the difficult cases. 
A randomized trial of amsacrine and rubidazone in 39 patients with acute promyelocytic leukemia. Thirty-nine patients with untreated acute promyelocytic leukemia (APL) were randomly allocated to receive rubidazone (zorubicin) 200 mg/m2/d, days 1 to 4 plus cytarabine (Ara C) 200 mg/m2/d, days 1 to 7 (arm A, 21 patients), or amsacrine (Amsa) 150 mg/m2/d, days 1 to 4 plus Ara C 200 mg/m2/d, days 1 to 7 (arm B, 18 patients). Prophylaxis of disseminated intravascular coagulation was made by platelet transfusions and heparin. In case of leukemic resistance, patients received a second course with 2 days of rubidazone (arm A) or Amsa (arm B) and 3 days of Ara C. Patients who achieved complete remission (CR) received three consolidation courses with the two drugs used for induction and maintenance therapy for 3 years. Two patients in arm A and one in arm B were allografted in first CR. Initial characteristics were similar in both arms. In arm A, 18 patients (86%) reached CR, two had hypoplastic death, and one had leukemic resistance after two courses. In arm B, 12 patients (66%) achieved CR, two had early death (CNS bleeding, one case; ventricular fibrillation, one case), and four had resistant leukemia after two courses. The difference in CR rate between the two arms was not significant. In arm A, disease-free survival (DFS) showed a plateau at 54.3% after 34 months (95% confidence interval [CI], 32.1% to 74.9%), with eight CRs longer than 34 months. In arm B, DFS was significantly shorter (P less than .03), showing a plateau at 16.7% after 38 months (95% confidence interval, 4.7% to 44.6%), and only two prolonged CRs were seen. The difference in DFS remained significant after censoring allografted patients and patients who died in CR (one in arm A, two in arm B). Our results suggest that Amsa-Ara C combinations may be inferior to anthracycline-Ara C combinations in the treatment of APL, because they seem to provide shorter DFS and, possibly, a higher incidence of initial leukemic resistance. However, studies with larger numbers of patients are required. 
Clinical findings associated with pulmonary embolism in a rehabilitation setting. In a rehabilitation setting, pulmonary embolism is a relatively frequent and life-threatening complication. Deciding when a patient may be experiencing this condition is difficult, however, because of frequent deficits in patient communication skills (eg, aphasia and cognitive deficits) and the multisystem illnesses affecting many rehabilitation patients. We reviewed the charts of 30 rehabilitation patients transferred emergently during the years 1986 to 1988 with a diagnosis of pulmonary embolism, which was subsequently documented by ventilation-perfusion scanning. The average age of the 30 patients was 65; 63% were women and 20 (67%) had an admitting diagnosis of stroke. The most common new-onset clinical findings in the 24 hours before discharge were unusual facial skin color changes (pale, flushed, or cyanotic) (57%), chest or upper back pain (47%), tachycardia (heart rate more than 100 bpm) (40%), hypoxemia (arterial oxygen saturation less than or equal to 90%) (40%), and fever less than 101F (37%). In 63% of the patients, either anxiety, restlessness, diaphoresis, or dyspnea was also noted in the 24 hours before discharge. The data suggest that careful physician and nursing scrutiny may identify clinical signs characteristic of pulmonary embolism, and that the de novo appearance of these constellations of findings may help to select candidates for ventilation-perfusion scanning. 
Long-term survival in patients operated on for benign peptic ulcer disease. Survival rate was analysed in a cohort of 6459 patients who had undergone partial gastrectomy for benign ulcer disease and who had survived the first year after operation. The cohort was followed for 27-35 years. There was a slight but significant decrease in relative survival rate to 92 per cent (95 per cent confidence interval 87-97 per cent) 35 years after operation. No decrease in relative survival rate was observed during the first 20 years after operation. There was no difference by gender or surgical procedure, but patients operated on for gastric ulcer, compared with duodenal ulcer, and patients operated on at younger ages had a poorer relative survival rate. The effects of partial gastrectomy on survival, both overall and by diagnosis or age at operation, are probably attributable to confounding factors linked with the peptic ulcer disease rather than to the surgical procedure itself. We conclude that partial gastrectomy seems to have very little impact on survival once the patient has survived the first year after operation. 
Mineral spirits inhalation associated with hemolysis, pulmonary edema, and ventricular fibrillation. A previously healthy 42-year-old woman developed severe dyspnea, chest discomfort, and malaise several hours after prolonged exposure to concentrated vapors from mineral spirits. On the way to the hospital, she sustained a cardiopulmonary arrest; on arrival several minutes later, she was found to be in ventricular fibrillation and was resuscitated. Her hospital course included slowly resolving cardiac abnormalities, amnesia, noncardiogenic pulmonary edema, abrupt hemolytic anemia, sustained rhabdomyolysis, and other metabolic abnormalities. It is highly probable that this syndrome represented acute and near-lethal toxicity caused by the inhalational exposure to the petroleum distillate known as mineral spirits. It is important that physicians be aware of this syndrome in order to recognize it on presentation and to warn patients of the risk of such toxic exposure. 
Pituitary adenoma: correlation of half-dose gadolinium-enhanced MR imaging with surgical findings in 26 patients. Sellar magnetic resonance imaging studies obtained with half doses of gadopentetate dimeglumine (0.05 mmol/kg) were prospectively interpreted and retrospectively rated in 26 patients who subsequently underwent transsphenoidal sellar surgery for suspected pituitary adenoma. Studies included a sagittal scout view followed by a non-contrast-material-enhanced, an immediate postcontrast, and a delayed postcontrast T1-weighted image (obtained at 1.0 or 1.5 T). Ten of 11 confirmed microadenomas were identified prospectively; all were identifiable in retrospect. Macroadenomas (12 cases) were well demonstrated. The high signal intensity of the posterior pituitary and of intrasellar hemorrhage was obscured on postcontrast studies. Delayed images proved unnecessary. This prospective evaluation suggests that a half-dose study is comparable to retrospective studies in which full-dose techniques were used for detection of micro- and macroadenomas. Imaging times are reasonably short, and cost of contrast material is potentially reduced. Confirmation with larger studies is required, and careful endocrinologic and clinical follow-up of nonsurgical patients is necessary. 
Metastatic basal cell carcinoma: report of a case presenting with respiratory failure. Metastasis from basal cell carcinoma (BCC) of skin is rare. A case of a 58-year-old male presenting with increasing shortness of breath and right pleural effusion is described. Open right pleural biopsy demonstrated metastatic carcinoma consistent with BCC. Review of medical records from another hospital revealed that four years previously a recurrent BCC had been excised from the left back. One and three years prior to this excision, a skin lesion at this same site had been treated with electrocautery. Review of the skin excision slides demonstrated infiltrating BCC histologically very similar to the metastatic pleural neoplasm. The patient died two months after the pleural biopsy. At autopsy, the cutaneous BCC had not recurred and metastatic BCC extensively infiltrated the pleura bilaterally, with focal involvement of underlying lung parenchyma, subcarinal lymph nodes, diaphragm, and pericardium. 
Effect of temporary occlusion of hypogastric arteries on blood loss during radical retropubic prostatectomy. We report on a prospective, partially randomized study of 130 patients, examining the effect of temporary occlusion of the hypogastric arteries on intraoperative blood loss, perioperative blood replacement and change in preoperative to postoperative hematocrit. We observed no significant difference in any of these parameters when comparing patients who did and did not undergo intraoperative occlusion of the hypogastric arteries. These findings suggest that temporary occlusion of the hypogastric arteries during radical prostatectomy does not have a major effect on the blood loss associated with this operation. Extensive collateral circulation to the prostate and a substantial venous component of blood loss may explain these findings. Banking of 3 units of autologous blood preoperatively would have decreased the need for homologous transfusions in the majority of patients. 
A new manifestation and treatment alternative for heparin-induced thrombosis. We treated a coronary artery bypass patient whose postoperative course was complicated by heparin-induced thrombocytopenia and resultant pulmonary artery and saphenous vein graft thromboses. The pulmonary thromboemboli were found first, and pulmonary blood flow was restored with intravenously administered tissue plasminogen activator (tPA). A short time later, the vein grafts were found to be occluded, and we subsequently performed multivessel percutaneous transluminal coronary angioplasty (PTCA) using tPA as an adjuvant to oral warfarin sodium therapy with excellent results. We conclude that heparin-induced thromboses in the pulmonary arteries are amenable to thrombolytic therapy, including tPA, whereas this regimen appears to have little effect on saphenous vein grafts. We also found that a combination of warfarin and thrombolytic therapy is an alternative regimen for heparin-intolerant patients who require PTCA. 
Seminal polyamines as agents of cervical carcinoma: production of aneuploidy in squamous epithelium. The effects of several polyamines found in seminal fluid on the cell cycle and ploidy of three cervical cell lines and of primary epithelial cells cultured from cervical biopsy specimens were monitored by fluorescent flow cytometry. The rate of cell growth did not change but there were indications of either hypodiploidy or hyperdiploidy in some cultures at certain concentrations of spermine and spermidine. An interaction of exogenous polyamines with the DNA of cervical cells was shown to occur, leading to changes in ploidy with, perhaps, the potential to induce or promote dysplasia. 
The value of class IC antiarrhythmic drugs for acute conversion of paroxysmal atrial fibrillation or flutter to sinus rhythm. In a single-blind randomized study, the efficacy and safety of intravenous propafenone (2 mg/kg body weight per 10 min) versus flecainide (2 mg/kg per 10 min) were assessed in 50 patients with atrial fibrillation or flutter. Treatment was considered successful if sinus rhythm occurred within 1 h. Conversion to sinus was achieved in 11 (55%) of 20 patients with atrial fibrillation treated with propafenone and in 18 (90%) of 20 with atrial fibrillation treated with flecainide (p less than 0.02). If atrial fibrillation was present less than or equal to 24 h, conversion to sinus rhythm was achieved in 8 (57%) of 14 patients in the propafenone group and 13 (93%) of 14 in the flecainide group (p less than 0.05). Atrial flutter was converted in two (40%) of five patients treated with propafenone and in one (20%) of five with flecainide (p = NS). Mean time to conversion was 16 +/- 10 min in the propafenone group versus 18 +/- 13 min in the flecainide group (p = NS). QRS lengthening (83 +/- 15 to 99 +/- 20 ms) was observed only in the patients treated with flecainide (p less than 0.001). Patients successfully treated with propafenone showed significantly higher plasma levels than those whose arrhythmia did not convert to sinus rhythm. Transient adverse effects were more frequent in the flecainide group (40%) than in the propafenone group (8%) (p less than 0.01). In conclusion, at a dose of 2 mg/kg in 10 min, flecainide is more effective than propafenone for conversion of paroxysmal atrial fibrillation to sinus rhythm. However, considering the propafenone plasma levels and very few adverse effects, the dose or infusion rate, or both, used in the propafenone group may not have been sufficient to achieve an optimal effect. Neither drug seems very effective in patients with atrial flutter. 
Longitudinal study of cerebral spinal fluid drainage in polyethylene glycol-conjugated superoxide dismutase in paraplegia associated with thoracic aortic cross-clamping. It has been hoped that pharmacologic prophylaxis in thoracic aortic cross-clamping may avert the unpredictable complication of spinal cord paraplegia, may avoid the mechanical difficulties associated with shunts, partial bypass, or monitoring devices, and may serve as a substitute for or as an adjunct to cerebral spinal fluid drainage. Toward this end 21 mongrel dogs were studied in four groups and underwent 60 minutes of thoracic aortic cross-clamping: group I, five with thoracic aortic cross-clamping; group II, five with thoracic aortic cross-clamping and cerebral spinal fluid drainage; group III, five with thoracic aortic cross-clamping, cerebrospinal fluid drainage and intravenous administration of a single dose (5000 units/kg) of polyethylene glycol-conjugated superoxide dismutase (PEG-SOD) given 15 to 20 minutes before thoracic aortic cross-clamping; and group IV, six with thoracic aortic cross-clamping and PEG-SOD. Paraplegia was graded by the Tarlov method at 24 hours and up to 5 days after thoracic aortic cross-clamping. The carotid and femoral artery pressures, the central venous pressure, and core temperature, taken during the experiment and at the time the dogs were killed, were found to be similar between groups. At 24 hours all dogs in group I were paraplegic; groups II and III had no paraplegic dogs (p less than 0.01), and group IV had fewer paraplegic dogs (two of six) than group I (p less than 0.05). Paraplegia was averted in all dogs treated with cerebral spinal fluid drainage, even 5 days after thoracic aortic cross-clamping. 
QTc prolongation measured by standard 12-lead electrocardiography is an independent risk factor for sudden death due to cardiac arrest. BACKGROUND. QTc prolongation has been implicated as a risk factor for sudden death; however, a controversy exists over its significance. METHODS AND RESULTS. In the Rotterdam QT Project, 6,693 consecutive patients who underwent 24-hour ambulatory electrocardiography were followed up for 2 years; of these, 245 patients died suddenly. A standard 12-lead electrocardiogram and clinical data at the time of 24-hour ambulatory electrocardiography were collected for all patients who died suddenly and for a random sample of 467 patients from the study cohort. In all patients without an intraventricular conduction defect (176 patients who died suddenly and 390 patients from the sample), QT interval duration was measured in leads I, II, and III and corrected for heart rate with Bazett's formula (QTc). In patients without evidence of cardiac dysfunction (history of symptoms of pump failure or an ejection fraction less than 40%), QTc of more than 440 msec was associated with a 2.3 times higher risk for sudden death compared with a QTc of 440 msec or less (95% confidence interval: 1.4, 3.9). In contrast, in patients with evidence of cardiac dysfunction, the relative risk of QTc prolongation was 1.0 (0.5, 1.9). Adjustment for age, gender, history of myocardial infarction, heart rate, and the use of drugs did not alter these relative risks. CONCLUSIONS. These data indicate that in patients without intraventricular conduction defects and cardiac dysfunction, QTc prolongation measured from the standard electrocardiogram is a risk factor for sudden death independent of age, history of myocardial infarction, heart rate, and drug use. In patients with cardiac dysfunction, QTc duration is not related to the risk for sudden death. 
Gadopentetate dimeglumine-enhanced chemical-shift MR imaging of the breast. Standard T1-weighted MR images enhanced with gadopentetate dimeglumine show relatively minimal enhancement of breast lesions due to the high background signal from fat in the breast. Strongly enhancing lesions may become isointense relative to the fat signal and become invisible or indistinct after contrast administration. Fat-suppressed chemical-shift imaging (CSI) combined with administration of gadopentetate dimeglumine improves lesion detection and characterization in other areas of the body where a strong lipid signal is present. We evaluated this technique in the breast. Twenty patients with mammographic lesions were studied with standard unenhanced T1- and T2-weighted images and enhanced T1-weighted images, as well as with CSI before and after administration of gadopentetate dimeglumine. The series were ranked independently for border and matrix characteristics. The border was assessed for a smooth, irregular, or spiculated margin. The matrix or internal substance was evaluated for visibility and type of enhancement, homogeneous or inhomogeneous. The enhanced CSI images were superior to all other images in the depiction of border and matrix characteristics. Of 20 patients, a corresponding mass was detected on MR in 14. In two of the 14 patients, the lesion was seen only in the enhanced CSI images. Chemical-shift artifacts on enhanced T1-weighted images obscured border detail in several cases. Enhanced CSI improves visualization of breast lesions as compared with conventional MR imaging with or without enhancement. The enhanced CSI technique produces differential enhancement between glandular tissue and lesions while suppressing the signal from fat. This improves the visualization of border and matrix characteristics and depicts lesions that otherwise might be obscured. 
Safety-belt injuries in children with lap-belt ecchymosis: CT findings in 61 patients. We have noted a complex of common injuries in children wearing lap-styled safety belts during vehicular accidents. Sixty-one children who were restrained passengers in motor vehicle crashes had linear ecchymosis across the abdomen and had CT for abdominal trauma. Thirteen children (21%) had a lumbar spine injury, and 14 children (23%) injured a hollow viscus (bowel, 12; bladder, two); five children (8%) had both spine and hollow viscus injuries. Abnormal findings on abdominal CT were recognized retrospectively in three of 13 children with lumbar spinal injury. Lateral radiographs of the spine showed lumbar spinal injury in all cases. Free intraperitoneal air was noted in on three (25%) of 12 children with bowel injury. In eight of those children, CT showed large, unexplained collections of peritoneal fluid. The presence of lap-belt ecchymosis should prompt a careful search for spine, bowel, and bladder injury. Recognition of the limitations of CT diagnosis of these injuries is important to reduce errors in interpretation. 
Achromobacter xylosoxidans. An unusual neonatal pathogen. Perinatal acquisition of a rare pediatric pathogen, Achromobacter xylosoxidans, with evidence for in utero transmission, is described. Cultures from the mother and neonate demonstrated A. xylosoxidans. An ascending bacterial infection in the mother with clinical chorioamnionitis is presented as the probable mode of transmission. Postmortem examination of the infant confirmed Achromobacter meningitis. In contrast to the current case with transmission from mother to neonate, previously published neonatal cases of Achromobacter infections indicate that nosocomial transmission of the organism is most common (79%). In addition, the literature review revealed a high mortality associated with meningitis (77%), frequent hydrocephalus, and subsequent neurologic sequelae (36%). To the authors' knowledge, this is the first documented case of maternal-fetal transfer of A. xylosoxidans. 
Complexes of activated protein C with alpha 1-antitrypsin in normal pregnancy and in severe preeclampsia. Protein C is a vitamin K-dependent regulator of blood coagulation. Activated protein C is regulated in plasma in large part by two inhibitors, protein C inhibitor and alpha 1-antitrypsin. Complexes of activated protein C with both inhibitors in plasma samples from subjects with normal or pathologic pregnancy were measured. In normal pregnancy we observed a progressive and significant increase in activated protein C/alpha 1-antitrypsin complex levels, from 9 +/- 3 ng/ml in the first trimester to 16 +/- 3 ng/ml in the third trimester, as well as an increase in alpha 1-antitrypsin plasma levels. In severe preeclampsia, but not in chronic hypertension with superimposed severe preeclampsia, there was a greater increase in activated protein C/alpha 1-antitrypsin levels (25 +/- 10 ng/ml) (p less than 0.001) and a decrease in protein C and protein C inhibitor levels as compared with normal pregnant women at similar gestational ages. These data show an increase in the activation of the protein C pathway in both normal and pathologic pregnancy and provide evidence for an enhancement of thrombin generation in severe preeclampsia compared with chronic hypertension with superimposed severe preeclampsia. 
Broncholithiasis: CT features in 15 patients. Broncholithiasis is a disorder characterized by peribronchial calcific nodal disease that either erodes into an adjacent bronchus or distorts the bronchi. The key radiologic finding is a calcified endobronchial or peribronchial lymph node. To determine the CT findings of broncholithiasis, we retrospectively reviewed the chest radiographs and CT scans of 15 patients with proved broncholithiasis. Ten patients had endobronchial nodes as proved by bronchoscopy, surgery, or lithoptysis. Broncholiths were identified on bronchoscopy in only five cases. Five patients had peribronchial nodes with associated bronchial distortion. Collimation of the CT scans varied; 1.0-cm-, 0.6-cm-, and 0.5-cm-thick sections were obtained. Three patients had both 1.0-cm- and 0.5-cm-thick sections. The calcified lymph node was identified on CT in all 15 patients. CT correctly localized six of 10 endobronchial nodes and four of five peribronchial nodes. Findings due to bronchial obstruction also were seen on CT; atelectasis (n = 11), infiltration (n = 4), bronchiectasis (n = 4), and air trapping (n = 1). An associated soft-tissue mass was not seen in any case. Difficulty in determining the relationship between lymph node and bronchus is due to volume averaging, which can be decreased by scanning thinner sections. CT can suggest the diagnosis of broncholithiasis and is useful when bronchoscopy does not show a broncholith. 
Tocainide therapy in muscle cramps and spasms due to neuromuscular disease. Significant improvement in symptoms of disabling cramps and muscle spasms was obtained in 9 patients with motor neuron diseases, tetany, and myotonic disorders who were treated with tocainide, a lidocaine analog. No significant side effects were observed except for light-headedness and fatigue in 1 patient, who also showed slight prolongation of intraventricular conduction time. Tocainide is useful in treating disabling muscle spasms and cramps associated with conditions characterized by neuromuscular irritability. This effect is probably based on stabilization of the membrane potential at various levels (motor neurons, peripheral nerve, or muscle fiber membrane). 
Headache in transient or permanent cerebral ischemia. Dutch TIA Study Group. We studied headache features in 3,126 patients with acute cerebral or retinal ischemia. Headache occurred in 18% of these patients (in 16% of all patients with transient ischemic attacks, in 18% of patients with reversible ischemic neurologic deficits, and in 19% of patients with minor strokes) and was mostly continuous in all types of attacks. Headache was present in 16% of patients with monocular visual symptoms. The occurrence of headache was not related to the mode of onset, mode of disappearance, or duration of the attack. Patients with headache more often were known to have heart disease. Headache was less frequent in patients with small deep infarcts, who were more often hypertensive, and in patients with infarcts in the anterior circulation; headache was more frequent in patients with cortical infarcts and in patients with infarcts in the posterior circulation. Patients with a relevant small deep infarct on computed tomographic scan and accompanying headache relatively often reported symptoms compatible with cortical ischemia, such as language disorders or a visual field defect. We conclude that headache is a frequent accompanying symptom in patients with acute cerebral and retinal ischemia and that the occurrence of headache is partly related to the underlying cause of the ischemic lesion. 
Arteriovenous malformation in meningothelial meningioma: case report. An unusual association of a meningioma and an arteriovenous malformation is reported. A 68-year-old man developed left homonymous hemianopsia, left hemiparesis, and gaze palsy. Magnetic resonance imaging showed a right occipital mass lesion containing multiple signal-void areas with tubular and honeycomb appearance, suggesting a marked vascular component. An angiogram showed abnormal vasculature in the mass supplied by the posterior cerebral artery and a dural arteriovenous malformation on the tentorium. Neuropathological examination after total removal of the mass revealed a meningothelial meningioma including major portions of an arteriovenous malformation that extended from the dura and leptomeninges, through the meningioma, and into the occipital lobe, where the tumor was located. 
Prognostic significance of the Karnofsky Performance Status score in patients with acute myocardial infarction: comparison with the left ventricular ejection fraction and the exercise treadmill test performance. The MILIS Study Group. The prognostic significance of functional status has not been previously studied in the setting of acute myocardial infarction. We assessed the Karnofsky Performance Status (KPS) score, a simple functional status scale that is commonly used to categorize physical ability, in 849 patients with acute myocardial infarction who were enrolled in the Multicenter Investigation of the Limitation of Infarct Size (MILIS) study. We then compared the KPS score with other predictors of prognosis in these patients. In patients who presented with acute myocardial infarction, a lower KPS score (less than 8 on a scale of 1 to 10) 3 weeks before the index infarction was associated with a higher incidence of congestive heart failure, in-hospital cardiac arrest, and mortality during hospitalization, as compared with patients with KPS scores greater than or equal to 8 (each p less than 0.001). Cumulative 1-year and 4-year mortality rates were significantly higher in patients with KPS scores less than 8, as compared with patients with KPS scores greater than or equal to 8 (42.5% vs. 12.6% at 1 year and 61.6% vs 25.1% at 4 years, respectively; both p less than 0.001). The left ventricular ejection fraction on admission was significantly lower in patients with KPS scores less than 8, as compared with those with KPS scores greater than or equal to 8 (p less than 0.019). The cumulative mortality rate was equally well predicted by low KPS score and by left ventricular ejection fraction (both p less than 0.0001). 
Cerebrovascular disease in hypertensive blacks. There is convincing evidence that all grades of persistent diastolic hypertension, especially in blacks, should be treated in order to prevent stroke and other cardiovascular complications. Studies are now in progress to gather additional information concerning isolated systolic hypertension, especially in the aged. Inasmuch as at least one half or more of stroke deaths in blacks develop as the result of hypertension, lowering blood pressure offers the perfect opportunity to reduce considerably the frequency of this devastating illness. The recent dramatic fall in U.S. stroke mortality, greatest in the black female, is a commendable achievement, but the flattening of the declining mortality curve over the past several years should be a cause for alarm and intensive investigation. 
Choroidal detachment associated with malignant choroidal tumors. The association of choroidal detachment with malignant choroidal tumors is not well recognized. The authors' experience with six cases suggests that choroidal detachment may be associated with both metastatic tumors and choroidal melanoma. In two of these cases, the choroidal or retinal detachment was so massive that echography was necessary to detect the underlying tumor. Three patients presented with painful visual loss, and three patients presented with painless visual loss or a visual field defect. In one patient, the correct diagnosis and appropriate treatment of the choroidal metastasis with external radiation relieved the patient's pain and improved visual acuity from 1/200 to 20/35. Metastatic and primary uveal malignant tumors should be added to the list of causes of choroidal detachment and can be excluded only after thorough clinical, and often echographic, examination. 
Coronary risk factors and the postbypass patient. Atherosclerosis frequently develops in SVGs during the first 10 years. This process appears related to coronary risk factors. Several studies have found an association between hyperlipidemia and atherosclerosis documented at pathology. Late changes attributed to atherosclerosis that were observed at angiography were also significantly related to elevated serum levels of total cholesterol and triglycerides. They also were found in association with diabetes, systemic hypertension, and smoking in some studies. Several clinical studies have documented an association of one or several coronary risk factors with postoperative clinical events, including recurrence of angina, myocardial infarction, heart failure, reoperation because of clinical deterioration, and survival. These factors have been shown to act alone or in combination. The most important is an abnormal lipid profile and diabetes. Smoking and hypertension were seldom found to be significant predictors when considered separately, but appear to play an important role in association with the others. Control of coronary risk factors, particularly hyperlipidemia and smoking, seems mandatory in order to prevent SVG atherosclerosis and progression of the disease in the native coronary arteries. 
Short-term effect of dynamic exercise on arterial blood pressure BACKGROUND. To quantify the duration of postexercise hypotension at different exercise intensities, we studied six unmedicated, mildly hypertensive men matched with six normotensive controls. METHODS AND RESULTS. Each subject wore a 24-hour ambulatory blood pressure monitor at the same time of day for 13 consecutive hours on 3 different days. On each of the 3 days, subjects either cycled for 30 minutes at 40% or 70% maximum VO2 or performed activities of daily living. There was no intensity effect on the postexercise reduction in blood pressure, so blood pressure data were combined for the different exercise intensities. Postexercise diastolic blood pressure and mean arterial pressure were lower by 8 +/- 1 (p less than 0.001) and 7 +/- 1 mm Hg (p less than 0.05), respectively, than the preexercise values for 12.7 hours in the hypertensive group. These variables were not different before and after exercise in the normotensive group. Systolic blood pressure was reduced by 5 +/- 1 mm Hg (p less than 0.05) for 8.7 hours after exercise in the hypertensive group. In contrast, systolic blood pressure was 5 +/- 1 mm Hg (p less than 0.001) higher for 12.7 hours after exercise in the normotensive group. When the blood pressure response on the exercise days was compared with that on the nonexercise day, systolic blood pressure (135 +/- 1 versus 145 +/- 1 mm Hg) and mean arterial pressure (100 +/- 1 versus 106 +/- 1 mm Hg) were lower (p less than 0.05) on the exercise days in the hypertensive but not in the normotensive group. We found a postexercise reduction in mean arterial pressure for 12.7 hours independent of the exercise intensity in the hypertensive group. Furthermore, mean arterial pressure was lower on exercise than on nonexercise days in the hypertensive but not in the normotensive group. CONCLUSION. These findings indicate that dynamic exercise may be an important adjunct in the treatment of mild hypertension. 
The management of geriatric hypertension in health maintenance organizations. OBJECTIVE: To evaluate the quality of medical care received by Medicare enrollees with hypertension in health maintenance organizations (HMOs) compared to that received by a similar group of elderly hypertensives in a fee-for-service (FFS) setting. DESIGN: A quasi-experimental design was used to study an historical cohort of newly evaluated hypertensive patients over a 2-year period. SETTING: Medicare HMO and FFS practice settings. PARTICIPANTS: Eight Medicare HMOs and 87 FFS primary care physicians in the same communities were selected. A sample of 685 elderly hypertensive patients was studied, 336 in FFS settings and 349 in HMOs. MEASUREMENTS AND MAIN RESULTS: An expert panel of physicians selected standards of care for the management of geriatric hypertension, and medical records were reviewed. The results showed significant differences (P less than 0.01) in recording medications (94.5% HMO versus 88% FFS) and smoking histories (75.8% HMO versus 64.7% FFS), checking orthostatic blood pressures (9.5% HMO versus 3.3% FFS), performing funduscopy (44.4% HMO versus 27% FFS), completing cardiac examinations (90.8% HMO versus 79.8% FFS), and obtaining chest x-rays (72.8% HMO versus 64.3% FFS, P less than 0.05). Treatment and follow-up were similar between the two groups, except that FFS hypertensives were more likely to have medications adjusted and electrolytes ordered. CONCLUSIONS: The results suggest that elderly hypertensives in HMOs received equal or better quality of care for most criteria compared to elderly hypertensives in FFS settings. 
Proarrhythmic response to sodium channel blockade. Theoretical model and numerical experiments. BACKGROUND. The use of flecainide and encainide was terminated in the Cardiac Arrhythmia Suppression Trial because of an excess of sudden cardiac deaths in the active treatment group. Such events might arise from reentrant rhythms initiated by premature stimulation in the presence of anisotropic sodium channel availability. Drugs that bind to sodium channels increase the functional dispersion of refractoriness by slowing (a result of the drug-unbinding process) the transition from an inexcitable state to an excitable state. It is interesting that encainide and flecainide unbind slowly (15-20 seconds), whereas lidocaine and moricizine unbind rapidly (0.2-1.3 seconds). METHODS AND RESULTS. With a computer representation of a cable with Beeler-Reuter membrane properties, we found a small (6 msec) vulnerable window that occurred 338 msec after the last drive stimulus. Premature stimuli falling within the vulnerable window resulted in unidirectional block and reentrant activation. In the presence of a slowly unbinding drug, the window was delayed an additional 341 msec, and its duration was extended to 38 msec. The delay (antiarrhythmic effect) before the onset of the vulnerable window and its duration (proarrhythmic effect) were both dependent on the sodium channel availability and the recovery process. Both effects were also prolonged when sodium channel availability was reduced by membrane depolarization. Defining the proarrhythmic potential as the duration of the vulnerable window, we found that hypothetical use-dependent class I drugs have a greater proarrhythmic potential than non-use-dependent drugs. CONCLUSIONS. The antiarrhythmic and proarrhythmic properties of pure sodium channel antagonists are both dependent on sodium channel availability. Consequently, the price for increased antiarrhythmic efficacy (suppressed premature ventricular contractions) is an increased proarrhythmic vulnerability to unsuppressed premature ventricular contractions. 
Comparison of chlorambucil and prednisone versus cyclophosphamide, vincristine, and prednisone as initial treatment for chronic lymphocytic leukemia: long-term follow-up of an Eastern Cooperative Oncology Group randomized clinical trial. The Eastern Cooperative Oncology Group (ECOG) conducted a study in which patients with advanced chronic lymphocytic leukemia (CLL) were randomized between a regimen consisting of chlorambucil (30 mg/m2 orally day 1) and prednisone (80 mg orally days 1 to 5) (C + P) administered every 2 weeks and a more intensive regimen of cyclosphosphamide (300 mg/m2 orally days 1 to 5), vincristine (1.4 mg/m2 intravenously [IV] day 1), and prednisone (100 mg/m2 orally days 1 to 5) (CVP) given every 3 weeks. Treatment was continued for up to 18 months to maximal response. Of the 122 eligible patients, 60 received C + P, while 62 received CVP. With a median follow-up of 7 years, there were no significant differences in survival (4.8 v 3.9 years, P = .12), complete remission (CR) rate (25% v 23%; P = .83), or duration of response (2.0 v 1.9 years; P = .78) between C + P and CVP. Toxicity was modest despite the prolonged treatment. The long median survival of 4.1 years for stage III and IV patients is superior to that usually reported. This could stem from continuing treatment to maximal response rather than an increase in intensity of therapy. These results are comparable to those reported with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) therapy by other investigators. The data suggest that intermittent C + P administered to maximal response continues to be the standard treatment approach for advanced CLL. 
Impact of changing attitudes in carotid surgery on community hospital practice. In 1985, institutional guidelines for the evaluation and performance of carotid surgery were established in our community hospital. During the 5-year period from 1985 through 1989, 159 carotid reconstructions were done. There were four major strokes (3%), one eventually resulting in death, with the second death in this series from a myocardial infarction (mortality 1%). The combined mortality/major stroke morbidity incidence was 3%. Three transient ischemic attacks (2%) postoperatively cleared promptly without residua. During the latter 1980s, an increasing number of vascular surgeons were doing less carotid surgery. Monitoring institutional quality assurance and individual surgeon performance within the community hospital is becoming a reality. Our experience with institutional guidelines for the evaluation and conduct of carotid surgery, together with an assessment of results and ongoing individual surgeon performance, is presented. Maintaining acceptable morbidity and mortality statistics can be enhanced by having a plan for assessment, management, and concurrent review. 
Clonal analysis of T-cell deficiencies in autotransplant recipients. We have used limiting dilution culture methods to determine the frequency of mitogen-responsive T cells in peripheral blood of patients after bone marrow autotransplantation, and have compared their responsiveness to that of allotransplant recipients and normal controls. Autotransplant patients were found to have low responder cell frequencies in tests for lymphokine-secreting helper function, and for IL-2 dependent proliferator and cytotoxic function. Multiple regression analysis showed that function was lower in autotransplant patients than in allorecipients, and lower in male patients for all three functional assays. Patients with clinically significant infection tended to have lower proliferative function in both transplant groups and lower cytotoxic function in the allotransplant population. Graft-versus-host disease was associated with lower T-cell function, but was present only in the allotransplant group; therefore, it cannot account for the even lower levels of function observed in the autotransplant population. Because we observe deficits in T-cell regeneration in autotransplant recipients that are even more severe than in allorecipients, we postulate that cellular immunodeficiency after bone marrow transplantation may reflect limitations in thymic-dependent repopulation rather than an effect of genetic disparity between host and donor (eg, clinical or subclinical graft-versus-host). 
Necrotizing bronchial aspergillosis in a patient receiving neoadjuvant chemotherapy for non-small cell lung carcinoma. We describe a case of necrotizing bronchial aspergillosis which developed after lobectomy following neoadjuvant chemotherapy in a 73-year-old woman with non-small cell lung cancer. The lesion was visualized and biopsied through FBS, which played a useful role for early diagnosis of this disease. Itraconazole therapy was effective and safe. 
Choriocarcinoma of the testis metastatic to the skin. A case of choriocarcinoma of the testis metastatic to the skin is reported. In this case report the primary tumor was first diagnosed by the histopathologic findings in the cutaneous biopsy of a single nodule that appeared on the chest, with both syncytiotrophoblastic and cytotrophoblastic cells in the metastatic solid tumor islands. Using peroxidase-antiperoxidase techniques, beta-human chorionic gonadotropin (beta-HCG) was positive within the cytoplasm of syncytiotrophoblastic cells. The patient was treated with orchiectomy, chemotherapy, and radiotherapy. With these measures there was a decrease of chorionic gonadotropin serum levels to normal limits and 2 years after this treatment there is no evidence of recurrence. 
Cor triatriatum dexter: recognition and percutaneous transluminal correction. Cor triatriatum dexter is a rare congenital anomaly in which an obstructive membrane is located in the right atrium. The detection usually occurs after the sequelae of systemic congestion, coagulopathy, and hepatic dysfunction have set in, leading up to a high surgical risk. A percutaneous balloon correction of cor triatriatum dexter in a patient with advanced right-sided congestive symptoms and hepatic dysfunction is presented. This efficacious method is an alternative to surgical correction and could be extended to the more common cor triatriatum sinistra. 
Renal cell carcinoma involving penis and testis: unusual initial presentations of metastatic disease. Solitary parenchymal metastases of renal cell carcinoma to the penis or testis are rare. We report 1 case of each: in one instance the patient presented with priapism and an asymptomatic primary tumor; in the other, the metastasis presented as an acute change in a long-standing hydrocele more than one year after nephrectomy. Both patients had either positive margins at resection or recurrence after resection of the metastasis. While long-term, disease-free survival has been reported after orchiectomy for isolated metastatic disease, penile involvement appears to carry a very poor prognosis. 
Intratumoral cytogenetic heterogeneity in a benign neoplasm. Cytogenetic findings are reported in a 64-year-old man who had a history of rapid growth of a mass in the left groin area. The histopathologic diagnosis of the tumor was consistent with that of a lipoma with atypia. Cytogenetic analysis was done on an incisional biopsy specimen. The initial biopsy specimen revealed, in addition to normal cells, three different clones: 46,XY,t(12;21)(q13;q21), 46,XY, t(2;12)(q11.2'1.2), t(19;20)(q13.1'3), and 47.XY,+ r. The subsequently excised specimen showed a normal male karyotype (46,XY) and a predominant clone with the karyotype, 47,XY,t(2;12)(q11.2'1.2),t(3;11)(p24'5), + r. One cell with 47,XY, + r was present. In addition, polyploid cells with large markers, rings, and a high frequency of telomeric associations were also observed. 
Possible involvement of inositol-lipid metabolism in malignant hyperthermia. Alpha-adrenoceptor stimulation may induce malignant hyperthermia (MH) in vivo. Consequently, we have investigated the effects of the alpha-adrenoceptor agonist phenylephrine and, for comparison, the effects of the beta-adrenoceptor agonist isoproterenol on inositol-lipid metabolism of malignant hyperthermia susceptible (MHS) and healthy control (MHN) swine. The experiments were performed on electrically stimulated (frequency 0.2 Hz) trabeculae isolated from the right ventricles of the hearts of MHS and MHN animals. After labelling with [3H]inositol for 6 h, different inositol phosphates were measured by high pressure liquid chromatography, including inositol 1-phosphate, inositol 1,4-bisphosphate, inositol 1,3,4-trisphosphate, inositol 1,4,5-trisphosphate (1,4,5-IP3) and inositol 1,3,4,5-tetrakisphosphate. After stimulation with isoproterenol, the inositol phosphate content did not increase or vary between muscle from MHS and MHN animals. In contrast, all inositol phosphates increased after stimulation with phenylephrine in both muscle types, the effects being greater in MHS than in MHN, especially as regards 1,4,5-IP3 content. As 1,4,5-IP3, a presumed second messenger, has been shown to mobilize intracellular calcium, it is concluded that an enhanced alpha-adrenergic response is involved in the development of MH. 
Usefulness of high-frequency analysis of signal-averaged surface electrocardiograms in acute myocardial infarction before and after coronary thrombolysis for assessing coronary reperfusion. The incidence of late potentials on the signal-averaged electrocardiogram before and after coronary thrombolysis was studied in 54 patients with an acute myocardial infarction of less than or equal to 5 hours' duration and with an angiographically documented total occlusion of the infarct-related coronary artery on admission. A significant (p = 0.038) 50% relative reduction in the incidence of late potentials was observed in the group of 35 patients who underwent reperfusion: from 16 of 35 (46%) before to 8 of 35 (23%) at 120 minutes after the start of thrombolytic treatment. No significant reduction was seen in the 19 patients in whom thrombolysis was unsuccessful: from 8 of 19 (42%) before to 7 of 19 (37%) afterward. Despite successful recanalization, late potentials persisted or newly developed after thrombolytic therapy in 8 of 54 patients (15%). It is concluded that successful thrombolysis reduces the incidence of late potentials on the signal-averaged electrocardiogram but that the sensitivity and specificity of this finding are not high enough to allow reliable monitoring of coronary reperfusion at the bedside. 
The use of soap and water in two Bangladeshi communities: implications for the transmission of diarrhea. Efforts to reduce the incidence of diarrheal infections in which enteropathogens are endemic have focused on education about the importance of hand washing to interrupt transmission of such organisms. Since the effectiveness of health education depends on an understanding of the recipients' ideas and customs, we studied perceptions of cleanliness and the role of soap and hand washing in two poor Bangladeshi communities, one rural and one urban. We found that ideas about cleanliness generally are not based on germ theory; cleanliness is viewed in a larger, socioreligious context of purity vs. impurity. Washing serves both physical and spiritual needs and is performed according to defined patterns that may not effectively interrupt transmission of microorganisms. Soap is regarded as a cosmetic rather than an agent for removal of microorganisms. 
Transcatheter occlusion of pulmonary arterial circulation and collateral supply: failures, incidents, and complications. Failures and complications were analyzed retrospectively in 45 patients treated with embolotherapy or occlusion of pulmonary arterial circulation. Pulmonary arterial branches were occluded with steel coils in 19 patients with pulmonary arteriovenous malformations, 17 with hemoptysis of pulmonary artery (PA) origin, and one with massive parenchymal shunt. Bronchial arterial supply to the lung was embolized with small particles in eight cases of hemoptysis and systemic to pulmonary arterial antegrade shunt secondary to chronic thromboembolism. Asymptomatic incidents included catheterization failures, vascular damage, partial occlusion, partial recanalization of the thrombus, ectopic deposition of a coil, and delayed bacterial contamination of the thrombus. A few cases of transient clinical and radiologic signs of pulmonary infarction were observed after complete occlusion of the PA and bronchial artery embolization. This complication was never observed after complete occlusion of main right or left PA, inferior right or left PA, or segmental branches. The management and prevention of these complications, the role of bronchial arterial collateral pathways, and the importance of the site of PA occlusion in the development of pulmonary infarction are discussed. 
Effect of aspirin on heterotopic ossification after total hip arthroplasty in men who have osteoarthrosis. The severity of heterotopic ossification was determined from the radiographs of eighty-three men in whom osteoarthrosis had been treated with a primary total hip arthroplasty with cement. The medical records of these patients were then reviewed, with the reviewer having no knowledge of the radiographic findings. A similar operative approach and technique had been used in all patients. There was no association between the amount of intraoperative loss of blood or the duration of the operation and the severity of formation of heterotopic bone. The over-all rate of occurrence of heterotopic ossification was 72 per cent. Of the fifty-eight patients who had received aspirin throughout their course in the hospital, two (3 per cent) had severe ectopic ossification (grade III or IV8). In contrast, twelve (48 per cent) of the twenty-five patients who had received no aspirin or in whom aspirin had been discontinued so that anticoagulation could be begun had severe heterotopic ossification. The difference in the severity of the ossification between the two groups is significant (p less than 0.0001). 
Inhibition of the metabolism of atrial natriuretic factor causes diuresis and natriuresis in chronic heart failure. Atrial natriuretic factor (ANF) is a peptide hormone secreted by the heart that is degraded in vivo by endopeptidase 24:11 (atriopeptidase). UK 69,578 is a novel atriopeptidase inhibitor that raises plasma levels of ANF in animals and normal volunteers, with associated diuresis and natriuresis. This study examines the effects of UK 69,578 in patients with mild heart failure. UK 69,578 was administered as an intravenous infusion over 20 min in a placebo-controlled, cross-over study to six patients with stable (NYHA Class 2) chronic heart failure. The atriopeptidase inhibitor was well tolerated and no side effects were encountered. Mean baseline plasma ANF was elevated at 88 pg/mL (normal less than 50), and increased 2- to 5-fold after UK 69,578 administration. Plasma ANF did not change significantly following placebo. There was a marked diuresis after UK 69,578 compared to placebo. Urinary sodium excretion doubled for 4 to 6 h, but there was no significant rise in potassium excretion. There was no increase in plasma active renin concentration during the study period. Noninvasive hemodynamic monitoring revealed no significant changes in heart rate, systemic arterial blood pressure, or echocardiographic left ventricular dimensions. However, invasive measurements using a Swan-Ganz catheter demonstrated falls in mean right atrial and pulmonary artery wedge pressures after UK 69,578. There was no change in cardiac output. Thus, inhibition of endopeptidase 24:11 by UK 69,578 results in significant elevation of plasma ANF, with associated diuresis, natriuresis and venodilatation. The compound was well tolerated in these patients with mild chronic heart failure. 
Primary central nervous system lymphoma in acquired immune deficiency syndrome. A clinical and pathologic study with results of treatment with radiation. Primary central nervous system (CNS) lymphoma occurs frequently in patients with the acquired immune deficiency syndrome (AIDS). Seventeen patients with AIDS and biopsy-proven CNS lymphoma were treated with whole-brain radiation. At presentation, most patients were severely debilitated from previous AIDS-related illnesses. Patients generally had focal neurologic symptoms such as seizures and paralysis. Headaches and mental status changes, often noticed after hospital admission, seldom brought our patients to seek medical attention. Computed tomography (CT) scan showed low-density, contrast-enhancing, mass lesions with variable amounts of peritumor edema. Size, location, and pattern of contrast enhancement of the lesions varied. No specific pattern was seen that could be used to distinguish between CNS lymphoma, toxoplasmosis, or other CNS diseases that occur in patients with AIDS. Biopsy results showed angiocentric, high-grade, large cell tumors with frequent necrosis. Immunohistochemical analysis showed B-cell phenotype with small amounts of T-cells, presumably reactive. All patients received irradiation to the whole brain with parallel opposed fields. A variety of doses and treatment regimens were used. Mean survival was only 72 days. Survival was longer in patients with higher pretreatment Karnofsky scores. The correlation between dose and survival was not significant. At completion of therapy, most patients showed improvement in Karnofsky score and had partial improvement in neurologic symptoms. CNS lymphomas in patients with AIDS are responsive to radiation. Posttreatment CT scans showed regression of tumors. Autopsy examinations showed regression of tumors, but also showed concurrent CNS infections, AIDS encephalopathy, and radiation-induced changes within the normal CNS tissue. Opportunistic infections rather than cerebral herniation or uncontrolled lymphoma was the most common cause of death. 
Gradation of unstable angina based on a sensitive immunoassay for serum creatine kinase MB. A newly developed, highly sensitive immunoassay for creatine kinase MB isoenzyme was evaluated in 68 patients with or without different types of ischaemic heart disease. Patients were classified on the basis of clinical criteria in four groups: no ischaemic heart disease, stable angina, unstable angina, and acute myocardial infarction. Enzyme concentration in patients with stable angina was the same (even during exercise) as seen in the patients without ischaemic heart disease. Patients with unstable angina, however, could be divided into two groups. One group showed clear evidence of severe myocardial ischaemia by serial changes and higher mean values of creatine kinase MB up to 40 hours after the onset of symptoms, whereas in the remainder values were stable and resembled those seen in the patients without ischaemic heart disease. The changes in concentration correlated with signs of repetitive ischaemic episodes deduced from continuous ST segment monitoring during the first 24 hours after admission. These findings indicate that patients with unstable angina are a heterogenous group. In some, severe and prolonged ischaemia can be detected by a serological assay with high sensitivity. 
Is it time to use evoked potentials to predict outcome in comatose children and adults? OBJECTIVE: To determine the value of multimodality-evoked potential recordings in predicting outcome in comatose children. DESIGN: Prospective series and literature review. SETTING: Pediatric ICU in a university hospital. PATIENTS: Forty-one children with a Glasgow Coma Scale score of less than 8, who were admitted to the pediatric ICU between 1984 and 1989. INTERVENTIONS: Forty-one patients underwent brainstem auditory-evoked potential testing within 72 hrs of admission. Of these patients, 37 also had somatosensory-evoked potential testing at the same time. Four patients did not receive somatosensory-evoked potential testing for various nonmedical reasons. MEASUREMENTS AND MAIN RESULTS: Multimodality-evoked potential recordings were used to predict outcome in these comatose children. Outcomes were categorized as bad (death or chronic vegetative state) or good (all other outcomes). Survivor outcomes were determined at discharge and on subsequent follow-up visits from 1 to 3 yrs later. There were no false pessimistic predictions, and two false optimistic predictions in this series. A comprehensive literature review of coma outcome prediction, using multimodality-evoked potential recordings, revealed 20 series with 982 additional patients in whom the predictive errors of false optimism and false pessimism could be determined. Five cases of false pessimism and 99 cases of false optimism were identified in the 982 additional patients. If neonates are excluded, the false pessimism number is reduced to three. CONCLUSIONS: A bad outcome can be reliably predicted using multimodality-evoked potential recordings with little chance of a false pessimistic prediction. The acceptable error of false optimism occurs frequently, since patients often die of progressive neurologic and nonneurologic problems that may or may not be present at the time of the evoked potential recordings. Thus, in comatose children, multimodality-evoked potential recordings are a useful adjunct to clinical examination and other diagnostic aids in predicting outcome and in making decisions regarding the degree of intervention to offer. 
Prevention of chronic erosive streptococcal cell wall-induced arthritis in rats by treatment with a monoclonal antibody against the T cell antigen receptor alpha beta. Rats treated with an mAb (R73) against the TCR-alpha beta failed to develop chronic persistent arthritis after injection of streptococcal cell walls. Histologically, R73 mAb-treated rats had mild hyperplasia of synovial lining cells and minimal destruction of cartilage. In contrast, control-treated animals developed marked pannus formation, with pronounced infiltration of mononuclear cells and severe destruction of cartilage and subchondral bone. The preventive effect of R73 mAb on streptococcal cell wall-induced arthritis was associated with the marked depletion of alpha beta + T cells by R73 mAb. These results indicate that T cells play a crucial role in chronic erosive streptococcal cell wall-induced arthritis. 
Hypertrophy of nodules of Arantius and aortic insufficiency: pathophysiology and repair. Aortic insufficiency (AI) due to fibrosis and thickening of the nodules of Arantius in the otherwise normal aortic valve was found in 11 adults (age range, 41 to 65 years) between 1976 and 1988. Nine had concomitant mitral stenosis; 2 had coronary artery disease. In 6 patients AI was graded 3+ or greater; in 5 it was less than 3+. Correction of AI and restoration of cuspid flexibility and apposition by shaving the hypertrophied nodules was accomplished in all, with postrepair AI graded as 1+ or less. There was one hospital death, a patient who had prior mitral operation. Mean follow-up was 68 +/- 56 months. Only 1 patient had late (6 years) recurrent serious (3+) AI. Nine continued to have 1+ or less AI, based on echocardiography or catheterization (n = 6) or on physical examination performed at a mean of 74 months. We conclude that thickening of the nodules of Arantius may cause AI. Long-term correction can be accomplished by sculpturing of the involved cusps. 
The consistency of pulse frequencies and pulse patterns of transcutaneous electrical nerve stimulation (TENS) used by chronic pain patients. This study records the consistency of transcutaneous electrical nerve stimulation (TENS) pulse frequency and pulse pattern used by 13 chronic patients over a 1 year period. The results show that patients prefer specific pulse frequencies and pulse patterns unique to the individual and that they turn to such frequencies and patterns on subsequent treatment sessions. Pulse frequencies and pulse patterns were not related to the cause and site of pain, a finding consistent with previous study in this laboratory. This observation, coupled with the large variability in pulse frequencies and pulse patterns used between individuals, implies that patients prefer such frequencies and patterns for reasons of comfort which may not be related to mechanisms specific to the pain system. 
Tuberculosis of the pancreas: report of three cases. Three cases of pancreatic tuberculosis are described. The first patient presented with abdominal pain, weight loss, anorexia, vomiting, hepatomegaly, and mass in the head of the pancreas, on computerized tomographic (CT) scan. The second patient presented with low grade fever, anorexia, and weight loss, and was investigated for gallbladder disease. The third patient presented with obstructive jaundice and mass lesion in the head of the pancreas. Two patients underwent laparotomy for suspected pancreatic tumors. The findings of pancreatic disease was incidental during laparotomy in the second patient. The histopathology revealed caseating granuloma in all of them. The first patient responded well to treatment, and the second patient stopped treatment after 2 months and is well. The third patient is being followed. If malignancy can be ruled out, tuberculosis should be considered in relevant geographic areas, and a tissue diagnosis should be made. 
Myocardial infarction: assessment with an intravascular MR contrast medium. Work in progress. The effect of a new intravascular magnetic resonance (MR) contrast medium (gadolinium diethylenetriaminepentaacetic acid [DTPA] polylysine) was evaluated in acute, subacute, and chronic myocardial infarctions in rats. Signal intensity (SI) was measured before and after intravenous administration of Gd-DTPA polylysine. Before administration of contrast material, chronic infarctions had lower SI than normal myocardium. With Gd-DTPA polylysine, three zones were identified in acute and subacute stages of myocardial infarction, but in the chronic stage, images demonstrated two zones. In acute and subacute infarctions, Gd-DTPA polylysine produced greater enhancement (over 60 minutes) in the peri-infarction zone than in the normal or infarcted myocardium. In chronic infarctions, Gd-DTPA polylysine had no discernible effect on the SI of the central infarction zone. Overall, it caused no significant hemodynamic effects. MR imaging with Gd-DTPA polylysine produced differential tissue enhancement in myocardial infarctions, which varied according to the age of the infarction. 
Aluminium sulphate in water in north Cornwall and outcome of pregnancy. OBJECTIVE--To determine whether the excess aluminum sulphate accidentally added to the local water supply in north Cornwall in July 1988 had an adverse effect on the outcome of pregnancies. DESIGN--Outcomes of all singleton pregnancies in the affected area at the time of the incident (n = 92) were compared with those in two control groups: pregnancies in this area completed before the incident (n = 68) and pregnancies in a neighbouring area (n = 193). SUBJECTS--Mothers in the three groups, among whom there were 13 miscarriages, five terminations of pregnancy, and 336 live births. MAIN OUTCOME MEASURES--Fetal and perinatal loss, birth weight, gestation, obstetric complications, neonatal condition, and congenital defects. RESULTS--Among 88 pregnancies in women exposed to excess aluminum sulphate there was no excess of perinatal deaths (n = 0), low birthweight (n = 3), preterm delivery (n = 4), or severe congenital malformations (n = 0). There was, however, an increased rate of talipes in exposed fetuses (four cases, one control; p = 0.01). CONCLUSIONS--Because of small numbers it is not possible to say that high doses of aluminum sulphate are safe in pregnancy, but there is no evidence from this study of major problems apparent at birth. 
Acute cardiogenic pulmonary edema treated with mechanical ventilation. Factors determining in-hospital mortality. We reviewed 88 episodes of cardiogenic pulmonary edema (CPE) treated with mechanical ventilation to define the clinical features that predict in-hospital mortality. Fifty-six patients survived to hospital discharge. APACHE II scores were not helpful in prediction. Multiple logistic regression models to predict outcome were developed using variables present at the time of intubation and 24 hours later. The model at the time of intubation indicated mortality was related to systolic blood pressure less than 130 mm Hg, the presence of anterior myocardial infarction, use of calcium channel blockers, age, and absence of prior hospitalization for CPE. A model using additional variables available 24 hours later showed that mortality was related only to the need for vasopressor medication at 24 hours, and systolic blood pressure at intubation less than 130 mm Hg. The predictive power of these models was confirmed by applying them to 46 additional patients. The variables contained in these models suggest that the prognosis of patients with CPE treated with mechanical ventilation depends primarily on the severity of acute left ventricular injury. Variables relating the degree of respiratory failure, however, were not predictive of mortality. These multiple logistic regression models provide a means to compare patients with CPE for quality assessment purposes and for studies of treatment regimens, and may also provide information useful to patient and family counseling regarding the value of continued aggressive intensive care. 
Intra- and interindividual variability of glucose tolerance in an elderly population. The intra- and interindividual variability of the oral glucose tolerance test (OGTT) and other risk factors was investigated in 237 subjects, aged 64-87, examined annually in the period 1971-1975. Coefficients of intraindividual variation (CVa) were calculated from individual regressions on time. The lowest CVa was found for the summary index including fasting glucose (area under the curve, AUC): 10.0 +/- 4.9%. For fasting and 30, 60, and 120 min glucose the values ranged from 12 to 18%. The CVa's were not associated with age, gender, drug use, and disease prevalence, and may also be applied to other populations. The reliability coefficient depended on the prevalence of diabetes in the population and was higher than observed in younger populations. The highest reliability coefficient was observed for AUC: 0.81. For the combined information of OGTT, reflected by AUC or by classification according to WHO criteria, the variability was comparable to that of other cardiovascular risk factors such as serum total cholesterol. 
Tolerance to intravenous nitroglycerin in patients with congestive heart failure: role of increased intravascular volume, neurohumoral activation and lack of prevention with N-acetylcysteine To better understand the mechanism of nitrate tolerance in patients with congestive heart failure, 13 patients received a 24 h infusion of nitroglycerin (1.5 micrograms/kg body weight per min) with or without N-acetylcysteine (225 mg/kg per 24 h). The infusions were separated by a 24 h nitrate-free interval. By the end of the nitroglycerin infusion, mean arterial pressure had returned to baseline values and there was a significant increase in ventricular filling pressures and systemic vascular resistance compared with values after 1 h of treatment. The simultaneous infusion of N-acetylcysteine had no effect on these changes. Although a strict fluid restriction of 1.5 liters/day was maintained for 1 week before and throughout the study, after 24 h of nitroglycerin infusion there was a significant and similar degree of hemodilution whether nitroglycerin was infused alone (9.1 +/- 4.3%) or with N-acetylcysteine (8.7 +/- 4.1%). This hemodilution corresponded to an increase in intravascular volume of 745 +/- 382 ml, most of which occurred during the 1st h. Plasma renin activity increased and plasma atrial natriuretic peptide decreased during the infusion. The results of this study suggest that nitrate tolerance is multifactorial. In addition to the previously described pharmacologic tolerance to the effect of nitroglycerin on vascular smooth muscle, a capillary fluid shift from the extravascular to intravascular space appears to be involved, especially during the 1st h of the infusion. A third mechanism, reflex neurohumoral activation, also seems to contribute to the genesis of nitroglycerin tolerance. 
A new provocative test for chronic mesenteric ischemia. A new provocative test for chronic mesenteric ischemia is described, based upon the demonstration of a fall in the intramural pH of the small bowel after introduction of a test meal into the stomach. Intramural pH (pHI) is determined indirectly by tonometry, utilizing a tonometer passed per os. Postoperative assessment of revascularization procedures is also possible by the same technique. Application of the test in an 84-yr-old woman showed good correlation between a preoperative fall in jejunal intramural pH and abdominal pain, and the absence of a fall postoperatively after successful revascularization. 
High dietary linoleic acid affects the fatty acid compositions of individual phospholipids from tissues of Atlantic salmon (Salmo salar): association with stress susceptibility and cardiac lesion. For 16 wk Atlantic salmon (Salmo salar) post-smolts were fed practical-type diets that contained either fish oil (FO) or sunflower oil (SO) as the lipid component. Both diets contained adequate (n-3) polyunsaturated fatty acids (PUFA). All the phospholipids of heart and liver from SO-fed fish had increased levels of 18:2(n-6), 20:2(n-6) and 20:3(n-6); phosphatidyl choline (PC) and phosphatidyl ethanolamine (PE) also had increased 20:4(n-6). There was a general decrease in 20:5(n-3) in the phospholipids, reflected in an increase in the 20:4(n-6)/20:5(n-3) ratio, especially in PC and PE. The fatty acid compositions of phospholipids from brain and retina were much less affected by dietary linoleate than those of heart and liver. Fish fed SO developed severe heart lesions that caused thinning of the ventricular wall and muscle necrosis. The fish fed SO also were susceptible to a transportation-induced shock syndrome that caused 30% mortality. These results establish that a diet with a low (n-3)/(n-6) ratio can cause changes in fatty acid metabolism that are deleterious to the health of salmonid fish, especially when subjected to stress. 
Molecular heterogeneity and cellular localization of carboxypeptidase H in the islets of Langerhans. The intracellular distribution and molecular heterogeneity of carboxypeptidase H was studied in rat insulinoma tissue and isolated islets of Langerhans by a combination of immunohistochemical, ultrastructural, subcellular fractionation, and immunoblotting analyses. Immunofluorescence microscopy of islets demonstrated the presence of carboxypeptidase H in both insulin-containing B cells and glucagon-containing A cells. Quantitative ultrastructural analyses of islet B cells indicated that the enzyme was concentrated in mature insulin secretory granules, clathrin-coated condensing granules, and to a lesser extent the Golgi apparatus. Carboxypeptidase H activity was localized principally to secretory granule subfractions of insulinoma tissue, where it was present for the major part (70%) as a form which is readily solubilizable at pH values prevailing in the granule interior (5.5). This species migrated as a diffuse band of 53-57 kilodaltons (kDa) on immunoblot analysis using antisera raised against the purified native enzyme. In contrast, the insoluble form which was associated with the granule membrane at pH 5.5, migrated as a relatively compact band of 55-57 kDa. Carboxypeptidase H activity was also present in subcellular fractions which contained Golgi membranes together with elements of the endoplasmic reticulum, and in a low density secretory granule fraction which may represent immature granules. The enzyme in these compartments, like the granule membrane species, migrated as a compact 55-57 kDa band on immunoblots. Two-dimensional electrophoretic immunoblot analysis of secretory granules suggested that both membrane and soluble forms of the enzyme were glycoproteins and that the terminal glycosylation was similar in both instances. Antiserum raised against the deduced C-terminal 11 amino acids of the cloned carboxypeptidase H sequence recognized the 55-57 kDa membrane component in granules but did not react with the 53-57 kDa soluble species. A major difference between the soluble and membrane forms therefore appears to be a structural modification or proteolytic removal of the C-terminal domain in the trans-Golgi or early secretory granule compartment. The concept that proteolysis is involved is further supported by the observation that the relative proportion of the high and low mol wt forms of the enzyme in different subcellular fractions correlated with that of proinsulin and insulin, respectively. The membrane association of the 55-57 kDa form of carboxypeptidase H is disrupted at pH values of 9 and is dependent on ionic strength. This further suggests that the C-terminus of the protein may have an important role in the sorting or concentration of the enzyme in vesicular elements of the regulated pathway of secretion. 
Relation of stenosis morphology and clinical presentation to the procedural results of directional coronary atherectomy BACKGROUND. Directional coronary atherectomy has recently become available to treat coronary stenoses. This study was performed to determine the relation of patient characteristics and stenosis morphology to procedural outcome with directional coronary atherectomy to gain insight into which patients might be best treated with this device. METHODS AND RESULTS. Four hundred stenoses from 378 patients consecutively treated at six major referral institutions were analyzed. Angiographic data were assessed at a central angiographic laboratory using standardized morphological criteria and computer-assisted quantitative dimensional analyses. Procedural success was achieved in 87.8% of stenoses, and major ischemic complications (death, myocardial infarction, and emergency bypass surgery) occurred in 6.3% of patients. Lesion success and complications were closely correlated with recognized modified American College of Cardiology/American Heart Association Task Force lesion morphological criteria. Observed for type A stenoses were 93% success and 3% complication rates; for type B1 stenoses, 88% success and 6% complication rates; and for type B2 stenoses, 75% success and 13% complication rates, respectively. There were too few type C stenoses treated to analyze. Furthermore, multivariate testing demonstrated stenosis angulation (multivariate p less than 0.001), proximal tortuosity (p less than 0.001), decreased preatherectomy minimum lumen dimension (p = 0.032), and calcification (p = 0.041) to correlate independently with adverse outcome and complex, probably thrombus-associated stenoses to have a favorable outcome (p = 0.055). Operator experience (p = 0.020) and a history of restenosis (p = 0.022) also favorably influenced outcome. CONCLUSIONS. The procedural outcome of directional coronary atherectomy is highly associated with coronary stenosis morphology. Furthermore, after appropriate stratification for morphology and clinical presentation, overall atherectomy procedural outcome may be similar to that achieved with coronary angioplasty. However, specific subsets of patients may have relatively better outcome with either atherectomy or balloon angioplasty. 
Through a looking glass. A new technique to demonstrate directional hypokinesia in unilateral neglect. A line cancellation task was performed by right brain-damaged patients with neglect in two response conditions. The task was presented either in normal view or through a 90 degree angle mirror with direct view prevented. The latter decouples the direction of visual attention and of arm movement. In the mirror condition, 4 of 18 patients cancelled lines only in right hemispace which means that they directed their visual attention to the left but failed to execute movements towards contralateral hemispace--what has been termed directional hypokinesia. In contrast, 10 patients cancelled lines only in left hemispace in the mirror condition, which accords better with attention-representation deficit hypotheses. Our results support a division of the neglect syndrome according to whether perceptual or premotor deficits are predominant. 
Malignant peritoneal mesothelioma in childhood with long-term survival. A diffuse, well-differentiated, malignant peritoneal mesothelioma (MPM) developed in a nine-year-old girl. She received limited chemotherapy and radiation therapy and is alive and well without clinical evidence of disease 109 months after diagnosis. The neoplastic cells stained immunohistochemically for cytokeratin and epithelial membrane antigen but were unreactive with B72.3, anti-carcinoembryonic antigen, and anti-Leu-M1. Ultrastructurally, the tumor cells had abundant desmosomes, numerous tonofilament bundles, and variable-length microvilli. These findings confirm the mesothelial nature of the cells. Features consistent with malignancy included DNA aneuploidy by flow cytometric analysis and diffuse peritoneal involvement. The three previously described survivors with MPM were also premenarchal girls. Some MPMs in premenarchal girls have an indolent biologic behavior similar to that of low-grade peritoneal serous neoplasia or well-differentiated papillary mesothelioma in adult women. 
Valve-related complications with the Hancock I porcine bioprosthesis. A twelve- to fourteen-year follow-up study. Valve-related morbidity and mortality after heart valve replacement with the Hancock I porcine bioprosthesis has been retrospectively analyzed. From June 1974 through December 1976, 253 Hancock I bioprostheses (150 mitral and 103 aortic) were inserted in 220 selected patients who survived the operation and had follow-up until June 1989 (mean follow-up 13.5 years, with an accumulative follow-up of 2956.4 patient-years). One hundred seventeen patients had mitral valve replacement, 70 had aortic valve replacement, and 33 had combined mitral and aortic valve replacement. There were 27 thromboembolic events. The probability of being free from thromboembolism at 14 years was 81.0% +/- 7.4% for the mitral valve replacement group, 85.4% +/- 6.7% for the aortic group, and 67.1% +/- 18.4% for the mitral-aortic group. Fifteen episodes of prosthetic valve endocarditis occurred. There were 10 instances of nonstructural dysfunction (paravalvular leaks) in seven mitral valves (4.6%) and in three aortic valves (2.9%). One hundred twenty-two bioprostheses in 106 patients resulted in structural deterioration. The probability of freedom from structural deterioration at 14 years was 37.2% +/- 3.9% for the mitral group, 43.9% +/- 7.1% for the aortic group, and 30.1% +/- 8.9% for the mitral-aortic group. The logistic regression analysis between age at the time of operation and bioprosthetic life (structural deterioration-free period) demonstrates a linear regression curve (r = 0.53). There were 56 late deaths (27 patients died at reoperation). The actuarial survival rate (including hospital mortality) at 14 years was 57.2% +/- 5.4% for the entire series, with no statistically significant difference between groups. The probability of remaining free from valve-related morbidity and mortality at 14 years was 16.7% +/- 4.8% for the mitral group, 20.8% +/- 6.2% for the aortic group, and 14.0% +/- 7.0% for the mitral-aortic group. The long-term results of this series show that the clinical performance of the Hancock I porcine valve appears satisfactory during the first 6 years. The behavior of this bioprosthesis at 14 years' follow-up changes drastically, because only a minor group of patients is free from valve-related complications, justifying the restriction of its use for selected patients. 
Endothelial cell seeding. Endothelial cell seeding is the transplantation of vascular endothelial cells to denuded vascular surfaces. Seeding theoretically reduces the probability of graft or vessel thrombosis and of neointimal fibrous hyperplasia. Thus far, clinical seeding trials disclosed modest improvements in patency and the development of hyperplastic anastomotic lesions in failed grafts. Seeding inefficiency theoretically contributes to anastomotic hyperplasia. The inefficiency is linked to two steps in the seeding process, namely harvesting and cell retention. Of these, cell retention on the seeded surface is the more critical. Priorities for future research should be set first on the retention of seeded endothelium in vitro and second on improved and standardized methods of cell harvesting. 
Production and characterization of tumor infiltrating lymphocyte clones derived from B16-F10 murine melanoma. The adoptive transfer of tumor infiltrating lymphocytes (TIL) in conjunction with recombinant interleukin-2 (rIL-2) for the treatment of advanced cancer has recently been under intense investigation. Despite extensive research, the precise surface phenotype of TIL remains to be fully defined. To elucidate this unsolved problem, we established 11 TIL clones derived from rIL-2 expanded TIL obtained from B16-F10 murine melanoma tumors. These clones could be divided phenotypically into four groups: CD8 (+) T-cell clones, natural killer (NK)-cell clones, NK-like CD8 (+) T-cell clones, and double negative T-cell clones. Functionally, CD8 (+) T-cell clones demonstrated specific cytotoxic activity against B16-F10 melanoma cells, whereas NK-cell clones and double negative T-cell clones demonstrated only non-specific cytotoxic activity against NK-sensitive YAC-1 cells. NK-like CD8 (+) T-cell clones showed dual cytotoxic activity. Clones T1 [a CD8 (+) T-cell clone] and T2 [an NK-like CD8 (+) T-cell clone] which had cytotoxic activity against B16-F10 melanoma cells, demonstrated a proliferative response against immunoblotted B16-F10 melanoma antigens, whereas clones T7 (an NK-cell clone) and T10 (a double negative T-cell clone), which had no cytotoxic activity against B16-F10 cells, demonstrated no proliferative response against them. Winn assays revealed that only the CD8 (+) T-cell clone (T1) had an antitumor effect in vivo, whereas the double negative T-cell clone (T10) and NK-like CD8 (+) T-cell clone (T2) stimulated tumor growth in vivo. Adoptive immunotherapy using tumor-specific, highly cytotoxic TIL clones may represent a useful future immunotherapeutic option for the treatment of human tumors. 
Symptomatic cerebral vasospasm following tumor resection: report of two cases. The authors report two cases of symptomatic cerebral vasospasm following resection of an acoustic neuroma and a left sphenoid wing meningioma. Vascular spasm was documented by transcranial Doppler and angiography studies. Both patients responded to hypervolemic therapy. Possible mechanisms contributing to this rare complication are discussed. 
Colonic epithelial dysplasia or carcinoma in a regional group of patients with ulcerative colitis of more than 15 years duration. Colonoscopic screening for neoplasia was performed in a regional group of ulcerative colitis patients with a disease duration of greater than or equal to 15 years. A total of 121 patients, aged less than 80 years, were invited to participate, of whom 100 (83%) accepted colonoscopy, including biopsies in 15 standard locations of the entire colon, plus additional biopsies from all visible lesions. Unequivocal dysplasia was found in one patient with extensive colitis and a disease duration of 31 years. A polyp with highly differentiated adenocarcinoma was found in the sigmoid colon of a patient with intermittent rectum involvement, 37 years after the ulcerative colitis diagnosis had been made. Biopsy specimens from the remaining 98 patients showed no signs of dysplasia or cancer. Thus the frequency of pre-malignant or malignant changes is very low compared with the results of similar studies, and the rationale for general colonoscopic surveillance programmes for such patients is open to question. 
The role of alkaline phosphatase isoenzymes as tumor markers for testicular germ cell tumors. The role of serum alkaline phosphatase as a tumor marker for testicular germ cell disease was investigated in 26 patients with testicular seminoma and 13 with nonseminomatous germ cell testis tumors. Placental alkaline phosphatase-like enzyme was elevated in 50% of the stage I seminoma patients and in all patients with stages II to III disease. In addition, liver (tissue unspecific) alkaline phosphatase was elevated in 10 and 83% of the patients, respectively. Lactic dehydrogenase and beta-human chorionic gonadotropin (beta-HCG) were detected in 50 to 60% of the patients with stage I seminoma. By combining placental alkaline phosphatase-like enzyme, lactic dehydrogenase and beta-HCG, 75% of the stage I and 100% of the stages II and III seminoma patients could be identified correctly. Placental alkaline phosphatase-like enzyme in serum also occurred with nonseminomatous germ cell tumor but less frequently, while liver alkaline phosphatase was not detected at all. Thus, placental alkaline phosphatase-like enzyme and liver alkaline phosphatase were predominantly determined in the serum of patients with seminoma. In studies of tumor tissues from 31 of these patients, those with normal serum placental alkaline phosphatase-like enzyme levels had significantly lower tissue placental alkaline phosphatase-like enzyme levels than patients with elevated serum levels (p less than 0.01). Seminoma tissues showed significantly higher levels of placental alkaline phosphatase-like enzyme and liver alkaline phosphatase than nonseminomatous germ cell tumors (p less than 0.01), explaining the infrequent elevation of serum placental alkaline phosphatase-like enzyme and liver alkaline phosphatase found in patients with nonseminomatous germ cell tumors. 
Hepatitis B virus DNA in cervicovaginal cells. Hepatitis B virus DNA sequences were detected in seven (12.1%) of 58 cervicovaginal cell specimens that were obtained from pregnant women by polymerase DNA amplification assay. The presence of hepatitis B virus DNA in these cells raises the possibility that infected cervicovaginal cells may be a source through which hepatitis B virus can be transmitted from infected mothers to their newborns and between heterosexual partners. 
Noninvasive determination of left ventricular output and wall stress in volume overload and in myocardial disease by cine magnetic resonance imaging. The current study used cine magnetic resonance imaging to determine the effect of increasing severity of valvular regurgitation on systolic wall stress and to demonstrate that wall stress was disproportionately increased in relation to the severity of regurgitation in patients with myocardial disease. A total of 39 patients with predominantly mitral (n = 22) or aortic (n = 17) regurgitation with (n = 13) and without (n = 26) myocardial disease and 10 normal volunteers were examined with cine magnetic resonance imaging (MRI) at 1.5 T. Left ventricular (LV) cardiac output (CO) and peak systolic (PS) wall stress (WS) and end-systolic (ES) WS were calculated from blood pressure recordings, carotid pulse tracings, and wall thickness (h) and diameter (D) measurements obtained from cine MRI. Patients were classified into three degrees of severity according to their LV regurgitant volume (RV). Myocardial disease was defined by an ejection fraction (EF) of less than 40%. Mean LV EF was 61 +/- 3% in normal volunteers, 64 +/- 3% in patients with regurgitation, and 25 +/- 2% in patients with myocardial disease. LV CO was directly related to RV in patients without myocardial disease, whereas it was disproportionately low in relation to RV in patients with myocardial disease. PS WS was significantly higher in severe mitral and/or aortic regurgitation compared with moderate, mild, and no mitral and/or aortic regurgitation. Compared with the degree of regurgitation, PS WS was disproportionately higher in patients with myocardial disease. Thus LV CO and WS rise progressively with increasing severity of regurgitation. Disproportionately high systolic WS relative to RV indicates the presence of myocardial disease. 
QRS interval fails to predict coronary disease incidence. The Framingham Study. The Framingham Study cohort of 5209 white men and women was examined to determine the long-term incidence of manifestations of new coronary heart disease as a function of QRS interval on subjects' baseline electrocardiograms (recorded at the 9th biennial examination). Over 18 years of follow-up, age-adjusted incidence of myocardial infarction, angina pectoris, and coronary death appeared unrelated to baseline QRS prolongation in both sexes, by Cox regression. Subjects with left bundle-branch block fared no worse than those with right pattern. These relations held whether or not subjects with baseline electrocardiographic abnormalities other than intraventricular block were excluded from consideration. In sum, QRS duration is an unimportant predictor of coronary disease in this Framingham population. 
Membranous nephropathy related to hepatitis B virus in adults. BACKGROUND. The natural course of adult hepatitis B virus (HBV)-related membranous nephropathy in areas where HBV infection is endemic (characterized by vertical and horizontal transmission of HBV in early childhood) has not been fully defined. METHODS. We evaluated the clinical features, pathological findings, serologic profiles, therapeutic responses, and prognoses of 21 patients with adult-onset HBV-related membranous nephropathy. The patients were followed for a mean of 60 months (range, 12 to 108). Only patients with evidence of glomerular capillary deposition of hepatitis B e antigen (HBeAg) in a renal-biopsy specimen were included. RESULTS. The clinical features and serologic studies suggested that the patients had acquired chronic HBV infection in early childhood; moreover, other causes of membranous nephropathy had been excluded. All were seropositive for hepatitis B surface antigen and had high titers of antibody to hepatitis B core antigen at first clinical presentation. HBeAg was detected in the serum of 17 patients (81 percent), yet only 3 had even slightly increased plasma alanine aminotransferase levels. The clinical response to therapy with interferon alfa was disappointing; only one of the five patients treated had a complete remission with seroconversion to antibody to HBeAg. Contrary to reports of studies in children, spontaneous remission of the nephrotic syndrome or proteinuria was uncommon in the adults with HBV-related membranous nephropathy whom we studied. Proteinuria and HBV antigenemia persisted in untreated patients. During the follow-up period, 29 percent of the patients had progressive renal failure and 10 percent required maintenance dialysis therapy. CONCLUSIONS. The course of HBV-related membranous nephropathy in adults in areas where HBV is endemic is not benign. Regardless of treatment, the disease has a slowly but relentlessly progressive clinical course in approximately one third of patients. 
Once-daily fosinopril in the treatment of hypertension. This multicenter, dose-ranging study evaluated the antihypertensive effectiveness of once-daily administration of fosinopril sodium in 220 patients with supine diastolic blood pressure of 95-115 mm Hg. After a 4-week placebo period, patients were randomly assigned to double-blind therapy with either placebo or 10, 40, or 80 mg fosinopril once daily for 4 weeks. If treatment goals were not met, chlorthalidone 25 mg/day was added for weeks 5 to 8. Thereafter, patients could enter the long-term, open-label phase and receive 10-80 mg/day fosinopril plus chlorthalidone, if needed. After 4 weeks of monotherapy, the average decreases in supine diastolic blood pressure were 9% (10 mg), 11.5% (40 mg), and 12.5% (80 mg) compared with 6% in the placebo group. After 8 weeks, the average decreases, with or without diuretic therapy, were 12.5-18.2%, compared with 10.8% with placebo. Blood pressure continued to be well controlled, and the patients showed no evidence of tachyphylaxis or tolerance through 12-15 months of treatment. Fosinopril was well tolerated. During the short-term phase, no patient withdrew because of adverse events possibly related to fosinopril; during the long-term phase, nine of 148 patients (6.1%) withdrew for that reason. In patients with mild-to-moderate hypertension, once-daily fosinopril (40 and 80 mg) provided significant antihypertensive effects with or without diuretic therapy. The 10 mg dose was effective in some patients and may be considered a starting dose. 
The management of IIB osteosarcoma. Experience from 1976 to 1985. From 1976 to 1985, 75 IIB osteosarcomas have been treated out of a total of 98 osteosarcomas at the authors' institution. Because of the effective chemotherapy including high-dose methotrexate administered during this time period, the surgical management changed, and only ten patients out of the 75 IIB osteosarcomas required an amputation. The overall result of 76.7% of disease-free, three-year survival was equally distributed regardless of the surgical procedure. Endoprosthesis, resection with or without grafts, and rotationplasties, as well as amputations, revealed similar results. No negative influence from the limb-sparing surgery could be observed. 
Appendicitis in cystic fibrosis. Appendicitis is said to be uncommon and difficult to diagnose in cystic fibrosis. The clinical and radiological features in nine patients with cystic fibrosis who had appendicitis were studied. All but one of the patients had an appendiceal abscess at surgery. Four patients had a delay in diagnosis of greater than three days before the correct diagnosis was made. This delay may have been due to a more indolent presentation or because these patients were initially considered to have distal intestinal obstruction syndrome. Appendicitis should be considered in the differential diagnosis if a contrast enema demonstrates extrinsic compression of the caecum. Ultrasound, computed tomography, and gallium scans were found to be of limited help in our series. 
Dietary omega-3 fatty acids decrease mortality and Kupffer cell prostaglandin E2 production in a rat model of chronic sepsis. We tested the hypothesis that substitution of omega-3 fat for dietary omega-6 fat would reduce mortality and decrease Kupffer cell prostaglandin E2 (PGE2) production in a rat model of chronic sepsis. Rats were fed via gastrostomy for 12 days with isonitrogenous, isocaloric diets containing 15% of calories as either safflower oil (omega-6) or a 10:1 mixture of menhaden oil (omega-3) and safflower oil. After five days of feeding, animals received an intra-abdominal abscess of defined bacterial content. Survivors were killed on post-laparotomy day 6 in conjunction with liver perfusion and protease liver digestion for Kupffer cell isolation. Kupffer cell PGE2 production was measured by radioimmunoassay after 18 hours of cell culture and again after stimulation with 0 LPS, 10 ng/ml LPS, and 10 micrograms/LPS. Mortality was decreased in menhaden oil-fed animals compared with safflower oil-fed animals (16% vs. 35%). Kupffer cell PGE2 production was decreased in menhaden oil-fed animals at 18 hours (354 +/- 54 vs. 570 +/- 95 pg/0.1 ml; p = 0.09) and after stimulation with 10 micrograms/ml LPS (140 +/- 41 vs. 288 +/- 45 pg/0.1 ml; p = 0.03) compared with safflower oil-fed animals. 
Abdominal desmoids: CT findings in 25 patients. Desmoids are histologically benign but locally aggressive fibrous tumors. Although overall they are rare lesions, they are a common manifestation of Gardner syndrome. We retrospectively reviewed clinical records and CT scans of 25 patients with abdominal desmoids. The number, location, and CT characteristics of the lesions were recorded for each patient. Tumors were solitary in 72% of patients and multiple in 28%. Fifty percent were located in the abdominal wall, 41% in the mesentery, and 9% in the retroperitoneum. More than two thirds of the lesions had well-defined borders, with the remainder displaying an infiltrative outer margin. The majority of tumors had attenuation values equal to (47%) or greater than (41%) the attenuation of muscle on contrast-enhanced CT scans. Complications attributable to the desmoid were commonly detectable on CT (hydronephrosis occurred in 36% and small-bowel obstruction in 20%). Our results detail the spectrum of CT findings and complications caused by abdominal desmoids. 
Adrenaline injection for endoscopic haemostasis in non-variceal upper gastrointestinal haemorrhage. Over a 30-month period, 53 patients with actively bleeding non-variceal lesions of the oesophagus, stomach or duodenum were treated by endoscopic injection of 1/10,000 adrenaline. Initial haemostasis was obtained in 50 cases, and permanent haemostasis in 44. Emergency surgery for bleeding was required in nine patients overall, and there were four deaths. All lesions requiring surgery were located on the posterior wall of the duodenum or the lesser curve of the stomach, and all but one had evidence of an exposed arterial vessel. Adrenaline injection is an effective, safe and simple method of endoscopic haemostasis. 
Professional mammographic quality assessment program for a community hospital. The evaluation of mammographic interpretations is a difficult challenge for a professional quality assessment program. As most images are read by a single observer and pathologic proof is obtained only if prompted by the report or if clinical symptoms warrant surgical intervention, it is difficult to construct a meaningful quality assessment program. The authors designed a program on the basis of a mammographic coding system that allows both individual physicians and practice groups to be evaluated. The program examines mammographic reports to determine the consistency of reporting by each physician and by the entire group. In addition, the program facilitated periodic evaluation of physicians with use of test cases. The coding system provided an easy method of correlating the mammographic reports with pathology reports from biopsy specimens, allowing a more thorough examination of possible systematic errors in the evaluation of the examinations, as well as enabling calculation of the positive predictive value for the diagnosis of cancer. The professional quality assessment program can be easily implemented in a busy clinical setting to evaluate whether mammograms were read consistently and "correctly" and to provide a method of continuing education for the physicians. 
Malignant fibrous histiocytoma of the gastrointestinal tract in a patient with neurofibromatosis. Malignant fibrous histiocytoma (MFH) of the gastrointestinal tract is extremely rare. A case of MFH of the colon associated with neurofibromatosis is presented. MFH is a high-grade soft-tissue sarcoma of fibroblast cell origin with a strong propensity for metastasis and recurrence. Immunochemical markers help to differentiate MFH from other sarcomas. The most successful treatment of MFH is surgical extirpation. Adjuvant chemotherapy and radiotherapy have not been definitively shown to be of value. 
Clinical follow-up and progression of carotid atherosclerosis determined by duplex scanning in patients suffering from TIA. We investigated the clinical outcomes and the progression of the internal carotid arterial lesions of a group of patients presenting with hemispheric TIAs. The cumulative frequency of TIAs during a mean follow-up period of 40 +/- 14 months was 14%, and no relationship was found between new TIAs and the presence of known cardiovascular risk factors or plaque characteristics as determined by duplex scanning. With the exception of one patient who died of stroke, none of the patients developed a permanent neurologic deficit. The cumulative death rate was 6.5%; myocardial infarction was the most common cause (3 out of 7). Anatomic progression of plaques was determined by duplex scanning in 22% of the internal carotid arteries. No relationship between progression of these plaques and the development of new TIAs was evident. We conclude that, in this group of patients, TIAs do not inevitably lead to stroke and that TIAs are not predictable based on risk factors or plaques characteristics. 
Limb salvage surgery for bone and soft tissue sarcoma. A phase II pathologic study of preoperative intraarterial cisplatin. Preoperative therapy has been tested as part of limb salvage therapy for localized bone and soft tissue sarcoma of the extremities. The activity of cisplatin (CDDP) by intraarterial (IA) infusion was evaluated in 40 cases of which 36 were evaluable for response. All patients had high-grade sarcomas. All but 3 patients received 3 or 4 courses (24 patients received 4 courses) of CDDP at a dosage of 120 to 150 mg/m2 given over 6 hours every 2 weeks by IA infusion. Patients younger than 18 years of age received the higher dose of CDDP. Treatment was well tolerated with combination antiemetics. One patient experienced severe hearing loss with the first cycle of the higher CDDP dose. Pathologic evaluation of resected osteosarcoma showed a favorable response (90% or greater necrosis) in 8 of 20 evaluable cases and in 3 of 4 patients with malignant fibrous histiocytoma (MFH) of bone (without osteoid). In soft tissue sarcomas, minimal (50% to 89%) necrosis was seen in two of nine cases and none had 90% or greater necrosis. Patients received postoperative chemotherapy based on pathologic response, but the value of this postoperative adjuvant therapy requires further follow-up and is uncertain in this small study. IA CDDP can often cause significant tumor necrosis in patients with bone sarcomas, whereas soft tissue sarcomas are less sensitive to this therapy. 
Importance of experimental models for the development of clinical trials on thromboatherosclerosis. Experimental models of vascular injury have enhanced our understanding of the pathophysiological process leading to vascular obstruction in both spontaneous and accelerated atherosclerosis. Based on experimental findings, we present and discuss a pathological classification of vascular injury or damage and its role in the pathogenesis of various vascular diseases. In addition, these animal models have provided insights into the roles of platelets and lipid metabolism in the evolution and progression of atherosclerosis and have suggested potential therapeutic applications. Thus, based on studies in the pig models, antiplatelet agents have been shown for the first time to have a beneficial effect in preventing the formation and progression of coronary atherosclerotic lesions in humans. Similarly, our findings in high density lipoprotein plasma fractions regarding inhibition and even reversal of the process of atherosclerosis in a hypercholesterolemic rabbit model have added new insights to an explosive field of lipoprotein research and provided new avenues of therapeutic strategies. our in vivo and ex vivo pig models of an extracorporeal perfusion chamber mimicking the various coronary conditions have aided in the understanding of the pathophysiology of the acute coronary syndromes and intensified our search for the ideal antithrombotic regimen in these high-risk patients. Finally, a carotid pig model of balloon angioplasty, a dog model of saphenous vein grafting, and a pig model of heart transplantation not only have provided insights into the pathophysiological process of accelerated atherosclerosis but also are allowing development of new antithrombotic and antiproliferative approaches for the prevention of these accelerated vascular diseases. In summary, we are entering an exciting era in vascular research. Significant advances in our understanding of vascular injury or damage as well as the interactions of blood cells and lipids with the vascular wall have allowed us to formulate new experimental strategies with subsequent clinical application in the prevention and progression of these vascular diseases. 
Endogenous opiates modulate the postapnea ventilatory response in the obstructive sleep apnea syndrome. Defense of ventilatory homeostasis against recurrent hypercapnia, hypoxia, and acidosis resulting from apnea in obstructive sleep apnea syndrome (OSAS) is dependent on compensatory mechanisms operative between episodes of airway obstruction. This investigation was designed to examine whether endogenous opiate activity modulates the compensatory ventilatory response to apnea in OSAS. Polysomnography and quantitative measurement of tidal volume was performed in 12 patients with moderate to severe OSAS during a morning nap study before and after intravenous administration of 10 mg of naloxone. Apnea index was not significantly altered. There was a small but significant shortening of apneas (postnaloxone apnea duration, 91.2% of prenaloxone; p = 0.002 by ANOVA). Tidal volume of the first postapnea breath and minute ventilation extrapolated from the first two postapnea breaths, but not frequency, increased significantly after naloxone (postnaloxone first breath volume, 112.7% of prenaloxone value [p = 0.03], with a similar increase for minute ventilation, 115.1% [p = 0.007]). The volume of the first postapnea breath was correlated with the duration of the previous apnea, both before (r = 0.59, p = 0.0001) and after naloxone. Despite this, analysis of covariance with apnea duration as the covariate confirmed a significant independent increase in postapnea breath volume after naloxone (p = 0.001). Naloxone also altered sleep architecture, increasing percent time awake during the study period (prenaloxone, 36.3 +/- 15.6%; postnaloxone, 56.7 +/- 22.4%; p = 0.0003) and decreasing total sleep time and percent time in Stage 1. Furthermore, naloxone increased continuity of awake periods (mean length of awake periods increased from 27.0 +/- 8.4 to 66.0 +/- 66.6 s after naloxone, p = 0.05). 
Radiographic fallopian tube recanalization: absorbed ovarian radiation dose. Absorbed radiation dose to the ovaries during radiographic fallopian tube recanalization was estimated in 29 patients with use of thermoluminescent dosimeters placed in the vaginal fornix. With an average fluoroscopic time of 8.5 minutes +/- 5.5 and an average of 14 +/- 5 105-mm spot radiographs obtained, the average absorbed dose to the ovaries was 8.5 mGy +/- 5.6 (0.85 rad +/- 0.56). Technical guidelines for keeping patient radiation exposure to a minimum during this new interventional procedure are suggested. 
Patterns of failure in Hancock pericardial bioprostheses. A series of Hancock pericardial valve bioprostheses was reviewed for cases of primary valve failure. Thirteen mitral and 10 aortic valve explants were recovered from 21 adult patients. Mitral valves had been in place for a mean of 56.4 months, and aortic valves for 53.8 months. All valves failed with cusp tears from stents (with a mean of 1.7 for mitral valves and 2.6 for aortic valves) in a predictable pattern, suggesting that wear and stress at cusp stitch sites are important in their pathogenesis. The topography of these tears is illustrated as are the less common associates of primary failure, such as calcification, fibrosis, and thrombosis. Similarities and differences of this valve's failure compared with that of the Ionescu-Shiley pericardial valve are discussed. 
Left bronchial isomerism associated with bronchomalacia, presenting with intractable wheeze. The cause of the Williams Campbell syndrome (bronchomalacia with bronchiectasis) is controversial. A boy with bronchomalacia, bifid ribs, and left bronchial isomerism presented with intractable wheeze mimicking asthma. The combination of the abdominal, bronchial, and atrial anatomy seen in this child has been described only once previously. The coexistence of these congenital abnormalities in this boy supports a congenital cause for the Williams Campbell syndrome. The need to assess wheezy children critically is emphasised. 
Rapid thrombus dissolution by continuous infusion of urokinase through an intracoronary perfusion wire prior to and following PTCA: results in native coronaries and patent saphenous vein grafts. Even with aspirin and heparin therapy, thrombus present prior to or forming after percutaneous transluminal coronary angioplasty (PTCA) results in significant complications. We report on 33 patients who were treated with continuous infusion of Urokinase through an intracoronary perfusion wire for 24 hr because of visible intracoronary thrombus. Seventeen native vessels (9 pre-PTCA and 8 post-PTCA) and sixteen saphenous vein grafts (12 pre-PTCA and 4 post-PTCA) were treated. All vessels were patent at the time of perfusion wire placement. Complete thrombus resolution, successful PTCA and sustained patency was seen in 31 of 33 patients. One native vessel treated post PTCA (originally occluded) re-occluded. One saphenous vein graft treated prior to PTCA showed improvement in thrombus but distal embolization with balloon inflation occurred. No significant complications related to the intracoronary infusion technique were observed. In conclusion, rapid lysis of intra-coronary thrombus can be accomplish safely using this technique and can result in improved PTCA outcome. 
Surgical treatment of the Wolff-Parkinson-White syndrome by epicardial electrical ablation A new operation to eliminate accessory pathways--epicardial electrical ablation--is described. In a group of 201 patients without concomitant disease, the mortality rate was 0.5% and the overall efficacy of the operation for free wall accessory pathways, 98%. A retrospective clinical study of 44 unselected patients was performed to examine how safe epicardial electrical ablation is. The criteria for intraoperative effectiveness were disappearance of both the delta wave and retrograde conduction and inability to induce tachycardia. In the postoperative and follow-up periods, the following were reviewed: electrocardiograms; Holter monitor recordings (24 to 26 hours); release of the myocardial-specific isoenzyme of creatine kinase; intracardiac hemodynamics and myocardial contractility (radionuclide methods); selective coronary arteriograms and ventriculograms; mean work capacity (bicycle ergometer); diagnostic transesophageal electrical stimulation; and histology of the area of ablation. The main conclusion of this study is that epicardial electrical ablation is a highly efficient and safe operation for surgical elimination of parietal accessory pathways in patients with Wolff-Parkinson-White syndrome. Its advantages are its technical simplicity and the opportunity to review results immediately during the operation. 
Relationship between insulin sensitivity, insulin secretion and glucose tolerance in cirrhosis. Hepatic insulin extraction is difficult to measure in humans; as a result, the interrelationship between defective insulin secretion and insulin insensitivity in the pathogenesis of glucose intolerance in cirrhosis remains unclear. To reassess this we used recombinant human C-peptide to measure C-peptide clearance in cirrhotic patients and controls and thus derive C-peptide and insulin secretion rates after a 75-gm oral glucose load and during a 10 mmol/L hyperglycemic clamp. Cirrhotic patients were confirmed as insulin-insensitive during a euglycemic clamp (glucose requirement: 4.1 +/- 0.1 mg/kg/min vs. 8.1 +/- 0.5 mg/kg/min; p less than 0.001), which also demonstrated a low insulin metabolic clearance rate (p less than 0.001). Although intolerant after oral glucose, the cirrhotic patients had glucose requirements identical to those of controls during the hyperglycemic clamp (cirrhotic patients: 6.1 +/- 1.0 mg/kg/min; controls: 6.3 +/- 0.7 mg/kg/min), suggesting normal intravenous glucose tolerance. C-peptide MCR was identical in cirrhotic patients (2.93 +/- 0.16 ml/min/kg) and controls (2.96 +/- 0.24 ml/min/kg). Insulin secretion was higher in cirrhotic patients, both fasting (2.13 +/- 0.26 U/hr vs. 1.09 +/- 0.10 U/hr; p less than 0.001) and from min 30 to 90 of the hyperglycemic clamp (5.22 +/- 0.70 U/hr vs. 2.85 +/- 0.22 U/hr; p less than 0.001). However, with oral glucose the rise in serum C-peptide concentration was relatively delayed, and the insulin secretion index (secretion/area under 3-hr glucose curve) was not elevated. Hepatic insulin extraction was reduced both in fasting and during the hyperglycemic clamp (p less than 0.001). 
Platelet-activating factor in stroke and brain injury. Platelet-activating factor, an endogenous phospholipid of proinflammatory, hemostatic, and vasoactive properties, is synthesized by neurons and in injured brain. Platelet-activating factor is released together with eicosanoids such as thromboxane A2, prostacyclin, and leukotrienes. Its effects in neurons are mediated through a specific receptor coupled to phospholipase C and phosphoinositol metabolism. The cerebrovascular effects of platelet-activating factor include disruption of the blood-brain barrier, edema formation, and vasospasm. It has also been described to possess direct toxicity to neuronal cells in culture. Discovery and development of several highly potent and selective antagonists to platelet-activating factor receptors facilitated experimental studies underscoring the role of this factor as an endogenous mediator in cerebral disorders, particularly cerebral ischemia and trauma. Significant biochemical, microvascular, functional, and behavioral recovery has been demonstrated using these antagonists in an array of experimental models of focal and global ischemia in the central nervous system (CNS). Clearly, studies of platelet-activating factor in experimental models of CNS ischemia and reperfusion injury open a new perspective on phospholipid metabolism in stroke and offer an exceptionally promising therapeutic prospect. Data supporting this factor as a mediator of specific pathological sequelae in stroke and neuroinjury are surveyed in this review. We discuss the mechanisms and significance of platelet-activating factor-mediated effects and propose directions for future studies. 
Hypertension as a causative diagnosis of patients entering end-stage renal disease programs in the United States from 1980 to 1986. Treatment of hypertension has decreased the incidence of stroke and congestive heart failure consequential to hypertension. To determine whether the incidence of hypertension as a causative diagnosis of end-stage renal disease (ESRD) is also decreasing, we examined the records of the Health Care Financing Administration (HCFA) from 1980 to 1986 regarding the causative diagnoses of patients entering ESRD programs. We found that the incidence of patients entering ESRD programs increased during the study period. Hypertension as a causative diagnosis was a constant proportion of the increase. The greatest increase occurred in patients age 55 or more years. This was strikingly true of black patients. We conclude that there has not been a decrease in the incidence of hypertension as a causative diagnosis for patients entering ESRD programs and that this may be a reflection that treatment of hypertension does not prevent the development of ESRD in some patients. We propose that prospective studies be undertaken to determine whether this is the case. 
Hyperthyroidism due to a pituitary adenoma composed of two different cell types, one secreting alpha-subunit alone and another cosecreting alpha-subunit and thyrotropin. A 37-yr-old female presented with clinical signs and symptoms of mild hyperthyroidism, high serum levels of free T4 (24.2 pmol/L), free T3 (11.7 pmol/L), and sex hormone-binding globulin (157 nmol/L) as well as measurable (by immunofluorometric assay) serum TSH concentrations (1.9 mU/L) in the absence of any known methodological interference. The above finding indicated the presence of hyperthyroidism due to inappropriate secretion of TSH, whose neoplastic origin was documented by computed tomographic scan showing a 1-cm pituitary adenoma. The diagnosis was confirmed by elevated alpha-subunit levels (9.2 micrograms/L) and alpha-subunit/TSH molar ratio (25.2) as well as absent TSH suppression after T3 administration. TRH injection (200 microgram, iv) caused impaired TSH (from 3.0 to 4.8 mU/L) and unexpectedly exaggerated alpha-subunit (from 8.8 to 18.2 micrograms/L) responses. Such a discrepancy was also observed after other dynamic tests. Double gold particle immunostaining of the adenomatous tissue removed at surgery showed that all of the cells contained secretory granules positive for alpha-subunit, while very few cells were positive for TSH beta and alpha-subunit. In conclusion, the present study demonstrates the existence of TSH-induced hyperthyroidism due to a pituitary adenoma composed of two different cell types: one secreting alpha-subunit alone and another cosecreting alpha-subunit and TSH. 
Evaluation of valvular heart disease with cine gradient echo magnetic resonance imaging. Electrocardiographic referenced repetitive gradient echo magnetic resonance imaging (cine GRE) has been used to detect and quantify valvular regurgitation. Regurgitation is recognized as a signal void in the high intensity blood pool on these images. Mitral regurgitation causes a signal void in the left atrium in systole, and aortic regurgitation produces one in the left ventricle in diastole. The specificity, sensitivity, and diagnostic accuracy of cine GRE for the detection of mitral and aortic regurgitation was greater than 0.93, 0.89, and 0.92, respectively. The severity of regurgitation has been quantified as the difference in the stroke volume between the two ventricles by measuring the volume of the blood pool, as shown in the stack of magnetic resonance tomograms. Severity has also been assessed by measuring the volume of the signal void. Finally, measurements of the volume of aortic regurgitation have recently been achieved by using velocity-encoded cine GRE. This technique provides a direct measurement of retrograde flow in the aorta during diastole. New cine GRE imaging techniques provide a noninvasive means for quantification of valvular as well as ventricular function. 
Cerebral haemorrhage in a French prospective population study. The incidence of cerebral haemorrhage was studied from a population-based stroke registry. The incidence was 12.3 per 100,000 per year in women and 13.9 per 100,000 per year in men, with a peak in the eighth decade and a male preponderance. Haemorrhages were deep seated and mostly due to hypertension. Recognised clinical characteristics of haemorrhage are acute onset, convulsion, vomiting, and disturbed consciousness. This study showed that cerebral haemorrhage may present with pure motor deficit or transient deficit preceding the stroke. The mortality was 51% in the first month, and 61% by two years. 
Cellular intermediate filament networks and their derangement in alcoholic hepatitis. Intermediate filaments are major components of most eukaryotic cells that form from the polymerization of protein subunits that are expressed in tissue and development specific fashions. The interactions of intermediate filaments with a myriad of other cellular proteins and structures give rise to a complex overall cellular architecture that is likely responsible for cellular well-being. The mature 10-nm filaments are relatively stable cellular structures, but the intermediate filaments undergo major morphological and biochemical changes, especially during mitosis, differentiation, and in response to certain drugs. Evidence exists that hepatocyte intermediate filaments (keratin filaments) are deranged in alcoholic hepatitis, an inflammatory liver disease of alcoholics and heavy spree drinkers. The classical and characteristic pathological hepatocyte inclusion bodies of alcoholic hepatitis, Mallory bodies, are composed in part of normal keratins that likely derive from the pre-existing hepatocyte intermediate filament network. It is unclear if intermediate filament network derangement in alcoholic hepatitis is directly caused by the actions of ethanol or its metabolites on intermediate filaments or their associated structures, or whether alcohol causes a cellular insult or injury elsewhere and a subsequent response (e.g., immune) causes intermediate filament network derangement. The precise mechanisms responsible for intermediate filament derangement remain to be elucidated; however, experimental data exist that support and refute several hypotheses. Hopefully, further studies will help determine a better overall understanding of the abnormalities of intermediate filaments and their relationship to the pathophysiology of alcoholic hepatitis and other diseases. 
Pleuropulmonary complications of endoscopic variceal sclerotherapy. The most common pulmonary complication of EVS is pleural effusion. The most clinically significant pulmonary complication of EVS is delayed perforation with formation of esophagopleural or esophagobronchial fistula. Pneumonia, empyema, pulmonary infarction, and atelectasis can also occur. Endoscopic variceal sclerotherapy probably does not cause ARDS, but that issue remains unsettled. Transient relative pulmonary hypertension during EVS is probably of no clinical significance, but caution is urged when sclerosing varices in a patient with borderline right heart function. 
An unusual problem during surgical removal of a broken guidewire. At operation, it proved impossible using traction alone to remove an angioplasty guidewire that was lodged in an intermediate artery. The problem was solved by passing a Teflon catheter over the wire, thus protecting the left main coronary artery while freeing the entrapped distal end of the guidewire. 
Delayed sternal closure for life-threatening complications in cardiac operations: an update. Over a 7-year-period, 25 patients had delayed sternal closure after open heart operations out of 34 patients whose sternum was not closed. The indications were extreme cardiac dilatation and uncontrollable mediastinal hemorrhage. This represented a 1.79% incidence in the overall open heart surgical experience at our unit. Sternal closure was performed at a mean of 2.64 days after the initial operation. Eighteen patients (52.9%) left the hospital alive and well, representing a 72% survival rate among patients undergoing delayed sternal closure. No mediastinal or fatal infection developed and only 1 patient had late superficial wound infection after delayed sternal closure. We conclude that delayed sternal closure is an effective method to treat severe complications after cardiac operations. 
Brain tumors occurring before 1 year of age: a retrospective reviews of 22 cases in an 11-year period (1977-1987). Congenital brain tumors have been reported infrequently and their management remains ill defined. An 11-year review (1977-1987) of all children with brain tumors with the onset of symptoms before 1 year of age was completed. Twenty-two children with the following histological diagnoses were treated: astrocytoma (7 patients), primitive neuroectodermal tumor (6 patients), papilloma or carcinoma of the choroid plexus (3 patients), malignant teratoma (2 patients), dermoid tumor (2 patients), embryonal rhabdomyosarcoma (1 patient), and chloroma (1 patient). Fifteen tumors were supratentorial in location, and 7 were infratentorial. Initial symptoms were hydrocephalus (32%), focal neurological deficit (23%), asymptomatic increase in head circumference (18%), failure to thrive (14%), and seizures (4.5%). The goal of treatment was a radical excision when possible, with primary chemotherapy in the last 6 years of the review period. Radiation therapy was the adjunct to surgery in the initial 5-year period. All patients with papillomas of the choroid plexus and dermoid lesions underwent a total resection with no recurrence. All 7 astrocytomas were supratentorial, with 6 occurring in the diencephalon. Five of the seven patients with astrocytomas survived more than 5 years. The 6 primitive neuroectodermal tumors were located equally between the supra- and infratentorial spaces. Four of the 6 infants with these tumors received chemotherapy (2 received chemotherapy alone; 2 received chemotherapy and radiation therapy) and are tumor free 2 to 9 years later. A fifth child received radiation therapy alone early in the series and survived only 4 months. The family of the other child refused adjunctive treatment. 
Bleeding esophagogastric varices. Ways to treat active episodes and prevent recurrence. Bleeding from esophagogastric varices carries a high mortality rate. Active variceal bleeding can usually be temporarily controlled medically with a combination of intravenous vasopressin and nitroglycerin, with balloon tamponade, or with endoscopic sclerotherapy. Because of the high likelihood of recurrence, long-term treatment, such as repeated sclerotherapy, propranolol therapy, or shunt surgery, is necessary. The proper selection of such measures requires consideration of the site of variceal bleeding, local availability of specialized techniques, and patient factors. Only liver transplantation reverses the liver damage and offers hope of improved long-term survival. As success at identifying high-risk patients by endoscopic features improves, propranolol or other pharmacologic prophylaxis may become an acceptable treatment. 
Nutritional management of inflammatory bowel disease. The etiology and specific treatment of Crohn's disease and ulcerative colitis are unknown, and the treatment strategy for patients with inflammatory bowel disease is essentially symptomatic and supportive. The malnutrition that frequently accompanies inflammatory bowel disease is a manifestation of intestinal failure and should be vigorously corrected with total parenteral nutrition, elemental diets, or both. Evidence exists for the value of total parenteral nutrition and elemental diets as primary therapy for inflammatory bowel disease in selected patients. Judicious nutritional therapy remains a cornerstone in the adjunctive management of these patients. 
Aortic distensibility in patients with isolated hypercholesterolaemia, coronary artery disease, or cardiac transplant. The stiffness of the thoracic aorta can be assessed non-invasively. If aortic stiffness can be shown to be related to coronary heart disease, perhaps it can be used to identify which patients with hypercholesterolaemia are most likely to have atheromatous changes and thus to be selected for intensive cholesterol-lowering treatment. Hence the distensibility of the transverse aortic arch was measured by echocardiography of the aortic arch in four groups of patients--symptom-free patients with normal serum cholesterol; symptom-free patients with raised serum cholesterol; patients with coronary heart disease (all with raised serum cholesterol), and post-heart-transplant patients. In all groups distensibility fell with age. The regression slope was steeper (p less than 0.05) for patients with known coronary disease than for either of the disease-free groups, and among cardiac transplant recipients there was also a segregation of distensibility values between those with and without atheroma in their native hearts. The results indicate that aortic distensibility might be an indicator of coronary heart disease and that it might be useful in identifying which symptom-free subjects with modest hypercholesterolaemia should be treated aggressively. 
Interactions between calcium channel blockers and the anticonvulsants carbamazepine and phenytoin. We describe a retrospective analysis of the frequency of adverse interactions between calcium channel blockers and anticonvulsant drugs (phenytoin and carbamazepine) in a series of 43 patients. Ten patients receiving carbamazepine and three patients receiving phenytoin exhibited symptoms or signs of toxicity. Toxicity occurred with both diltiazem and verapamil, but not with nifedipine. These results emphasize the need for careful clinical and laboratory monitoring of patients receiving both classes of medication. 
Unique odontogenic tumor with dentinogenesis and features of unicystic plexiform ameloblastoma. A case of an atypical odontogenic tumor with features of unicystic plexiform ameloblastoma and odontoblastic differentiation with deposition of tubular dentin matrix is reported. The significance of dentinogenesis, amelogenesis, and calcification in odontogenic tumors is discussed. 
Basement-membrane thickening of the vocal cords in sudden infant death syndrome. Sudden infant death syndrome remains the leading cause of death in infants between the ages of 1 month and 1 year. Diagnosis at autopsy is usually reached by process of elimination, as no obvious cause of death is recognized. The larynges of 23 sudden infant death syndrome victims, as well as 6 infants and 3 fetuses who died of other known causes, were examined in this study. While thickening of the basement membrane of the vocal cords was apparent in all sudden infant death syndrome victims, no such finding was present in the larynges of infants and fetuses dying of other causes. Thus, it is suggested that basement-membrane thickening may serve as a diagnostic tool for identification of sudden infant death syndrome at autopsy. 
Case report of laparoscopic cholecystectomy in the third trimester of pregnancy. Laparoscopic cholecystectomy has not been reported during pregnancy. This is the first reported case of a cholecystectomy by laparoscopic technique in the third trimester of pregnancy. The patient (and her baby) had a rapid, uneventful recovery identical to that of a nonpregnant patient. 
Angiography in unstable angina. Within the last decade, it has been appreciated that the acute coronary syndromes of unstable angina, non-Q-wave, and Q-wave myocardial infarction often share a common pathogenesis based on plaque disruption and thrombosis. Such "acute" lesions frequently have a characteristic angiographic appearance with sharp overhanging edges, irregular borders, and intraluminal lucency. This review focuses on the benefits and limitations of qualitative assessment of coronary lesion morphology, with respect to the sensitivity, specificity, and prognostic significance of complex lesions and intracoronary thrombi. Angiographic findings following thrombolysis for unstable angina are discussed, as well as the possible role for thrombolytic therapy as an adjunct to angioplasty in unstable angina. 
High-molecular-weight alkaline phosphatase in serum has properties similar to the enzyme in plasma membranes of the liver. Partially purified high-molecular-weight alkaline phosphatase from serum was compared with two other forms of the enzyme from the human liver, enzyme in native plasma membranes and purified alkaline phosphatase as a hydrophilic dimer. In a high-molecular-weight form from serum and plasma membranes, and when treated with 1% (v/v) Triton X-100, alkaline phosphatase showed a major band on gradient gel electrophoresis with a mobility equivalent to 400 kD. Nondetergent-treated material from both sources did not enter the gel and was in the voided volume of a gel permeation column. Stimulation of catalytic activity by four different phospholipids and by albumin yielded similar results for high-molecular-weight alkaline phosphatase and for the enzyme in plasma membranes, but these were different from the hydrophilic form. Inhibitors of alkaline phosphatase had similar effects on all forms. Of the three forms of the enzyme, only the hydrophilic dimer did not become incorporated into liposomes or adsorb to octyl-Sepharose after solubilization with Triton X-100 and removal of the detergent. Km (substrate concentration to give half maximal velocity) values with p-nitrophenylphosphate and heat and sodium dodecyl sulfate stabilities were similar for all forms. In the high-molecular-weight form from serum and in plasma membranes, alkaline phosphatase and 5'-nucleotidase showed similar rates of release by phosphatidylinositol phospholipase C. Three preparations of phospholipase D failed to release alkaline phosphatase from either the high-molecular-weight form or from plasma membranes. Based on these similarities, it is probable that the complex of high-molecular-weight alkaline phosphatase in serum most often originates from fragments of hepatic plasma membranes. 
Stimulation of a Ca(2+)-dependent protein kinase by GM1 ganglioside in nerve growth factor-treated PC12 cells. We have investigated the ability of exogenous gangliosides to modulate nerve growth factor (NGF) signal transduction in PC12 cells. The effects of exogenous ganglioside GM1 on multiple protein kinase activities were assayed by analyzing site-specific serine phosphorylation of tyrosine hydroxylase (TyrOHase) by two-dimensional phosphopeptide mapping. In the presence of NGF, exogenous GM1 (1-10 microM) increased 32P incorporation into TyrOHase phosphopeptide T2, a Ca2+/calmodulin-dependent protein kinase substrate whose phosphorylation is not normally affected by NGF treatment. In the absence of NGF, GM1 treatment had no significant effects on TyrOHase phosphorylation. The removal of extracellular Ca2+ or blockade of dihydropyridine-sensitive Ca2+ channels prevented the GM1-induced increases in 32P incorporation into phosphopeptide T2. Exogenous GM1 also potentiated K+ depolarization-induced increases in the phosphorylation of TryOHase. These results suggest that the stimulatory effects of exogenous GM1 ganglioside on NGF actions may be due to its ability to potentiate a Ca(2+)-dependent signaling pathway. 
Colonic hyperproliferation induced in rats and mice by nutritional-stress diets containing four components of a human Western-style diet (series 2). In a previous study colonic hyperplasia and hyperproliferation were induced in mice and rats by a nutritional-stress diet, based on the AIN-76A semisynthetic diet modified to contain four suggested high-risk components of the human Western-style diet: increased fat and phosphate and decreased calcium and vitamin D contents. In this study the effect of raising calcium alone to near the median level (0.22 mg/kcal) and to a high level (1.3 mg/kcal), comparable to adult human dietary intake, was tested in mice and rats while retaining the three other high-risk components. With median calcium intake the nutritional-stress diet induced hyperproliferation of epithelial cells in colonic crypts, with increased numbers of proliferating cells in crypt columns in sigmoid colon of mice (P less than 0.001) and rats (P = 0.02) and in the ascending colon of mice (P = 0.01). With high calcium intake, hyperproliferation was reduced almost to control amounts in the presence of unchanged fat, phosphate, and vitamin D. 
DNA analysis of atrial myxomas. The atrial myxoma is a primary tumor of the heart which may have an uncertain clinical course. In this study, we performed flow cytometric DNA analysis of 15 paraffin-embedded atrial myxomas and correlated DNA ploidy status and proliferative fraction with clinical findings. Twelve of 15 cases (80 percent) were diploid and the remaining three cases (20 percent) were aneuploid. Two patients with aneuploid histograms were free of tumor at the time follow-up; the third patient experienced local tumor recurrence and metastases. Five patients with diploid myxomas demonstrated an elevated (greater than or equal to 17 percent) proliferative cell cycle fraction; four of these patients experienced embolic phenomenon or tumor recurrence. This pilot study suggests that an atrial myxoma with either aneuploid DNA content or elevated proliferative fraction may be associated with aggressive biologic behavior. 
Induction of cytosolic free calcium elevation in rat vascular smooth-muscle cells by cerebrospinal fluid from patients after subarachnoid hemorrhage. The purpose of this study was to determine the effects of cerebrospinal fluid (CSF) from patients with subarachnoid hemorrhage (SAH) on cytosolic free calcium in cultured rat vascular smooth-muscle cells using the fluorescent intracellular calcium indicator fura-2/AM. Samples of CSF were collected from 12 patients (seven with and five without vasospasm) on Days 2, 6, 11, and 16 after SAH. Control CSF samples were obtained from five patients 6 to 9 months after they had undergone successful aneurysm surgery following an SAH. All CSF samples in both the non-vasospasm and vasospasm groups, regardless of the day of sampling after the SAH, induced significantly higher transient intracellular calcium elevations when compared to levels induced by control CSF. Furthermore, the addition of 2 mM ethyleneglycol-bis (beta-aminoethylether)-N,N'-tetra-acetic acid (EGTA) caused a slight reduction in the peak height in the CSF-induced intracellular calcium rise which declined more rapidly to basal levels than those studied without EGTA. In the non-vasospasm group, the intracellular calcium concentration remained stable after SAH throughout the study period. In contrast, in the vasospasm group, this concentration was highest on Day 2 post-SAH, but sharply decreased on Day 6 and rose again on Day 11. This result correlated with the clinical signs of vasospasm in these patients. These findings indicated that the intracellular calcium elevations induced by CSF obtained after SAH were due to the combination of the influx of extracellular calcium and the mobilization of intracellular calcium from storage sites. The changes in intracellular calcium concentrations in vascular smooth-muscle cells induced by CSF obtained from patients on successive days following SAH suggest that the substances that induce this repeat calcium elevation on Day 11 post-SAH may be the key spasmogens for vasospasm after SAH. 
Role of sympathetic activity in blood pressure reduction with low calorie regimen. To investigate the effects of a low calorie regimen on sympathetic function and its relation to blood pressure response, 22 untreated obese essential hypertensive patients (50 +/- 2 years, body mass index 29 +/- 1 kg/m2) were hospitalized and a diet was prescribed of 2,000 kcal/day for 5 days (control period) followed by 800 kcal/day for 21 days without changing salt intake (8-10 g/day). The dose of intravenous phenylephrine infusion needed to elevate systolic blood pressure 20 mm Hg (CD20) and the 24-hour urinary excretion of norepinephrine (UNE) were measured. During the low calorie period, blood pressure normalized in 14 patients (responder group, 124 +/- 3/79 +/- 4 mm Hg) and eight remained hypertensive (poor responder group, 158 +/- 6/103 +/- 3 mm Hg). At the control period, blood pressure and body mass index were similar, but the responder group had higher UNE (134 +/- 15 micrograms/day) and CD20 (127 +/- 11 micrograms) than the poor responder group (89 +/- 6 micrograms/day and 79 +/- 13 micrograms, respectively). During the low calorie period, both UNE (87 +/- 15 micrograms/day) and CD20 (74 +/- 10 micrograms) decreased in the responder group; no change was seen in the poor responder group. Changes in UNE and systolic blood pressure were correlated (r = 0.6, p less than 0.05). In conclusion, suppression of sympathetic activity plays a role in blood pressure reduction during moderate caloric restriction. 
Detection of preclinical Parkinson's disease with PET. Putamen 18F-dopa uptake of patients with Parkinson's disease (PD) is reduced by at least 35% at onset of symptoms; therefore, positron-emission tomography (PET) can be used to detect preclinical disease in clinically unaffected twins and relatives of patients with PD. Three out of 6 monozygotic and 2 out of 3 dizygotic unaffected PD co-twins have shown reduced putamen 18F-dopa uptake to date. In addition, an intact sibling and a daughter of 1 of 4 siblings with PD both had low putamen 18F-dopa uptake. These preliminary findings suggest there may be a familial component to the etiology of PD. PET can also be used to detect underlying nigral pathology in patients with isolated tremor and patients who become rigid taking dopamine-receptor blocking agents (DRBAs). Patients with familial essential tremor have normal, and those with isolated rest tremor have consistently low, putamen 18F-dopa uptake. Drug-induced parkinsonism is infrequently associated with underlying nigral pathology. 
Sudden hearing loss due to AIDS-related cryptococcal meningitis--a temporal bone study. We have presented the clinical history and temporal bone findings in a patient who manifested sudden hearing loss, and who subsequently was found to have cryptococcal meningitis associated with AIDS. The histopathologic findings are similar to earlier reports in patients without AIDS. Because cryptococcal infection is so much more common in AIDS patients than in the general population, it must be considered a causative factor when presented with an AIDS patient with progressive or sudden hearing loss. This offers the patient a chance for timely and effective treatment. 
Pulmonary hypertension and polymorphonuclear leukocyte elastase after esophageal cancer operations. To evaluate the role of polymorphonuclear leukocyte (PMN) elastase in pulmonary impairment occurring after operation for esophageal cancer, 10 patients were randomized preoperatively into two equal groups. One group received a placebo infusion and the other, an infusion of the PMN elastase inhibitor ulinastatin. In the placebo group, the mean plasma PMN elastase level increased from 154 +/- 23 micrograms/L preoperatively to 449 +/- 56 micrograms/L at 6 hours postoperatively (p less than 0.01), whereas the mean plasma fibronectin concentration decreased from 490 +/- 70 micrograms/mL preoperatively to 265 +/- 81 micrograms/L on postoperative day 2 (p less than 0.01). The mean pulmonary vascular resistance increased markedly from 151 +/- 24 dynes.s.cm-5.m-2 preoperatively to 284 +/- 76 dynes.s.cm-5.m-2 at 6 hours postoperatively (p less than 0.01). In the group given ulinastatin, 150,000 units every 12 hours from the start of the operation, the mean PMN elastase value at 6 hours postoperatively was lower (275 +/- 66 micrograms/L; p less than 0.01) and the fibronectin level on postoperative days 1 and 2, higher (p less than 0.05). A lower pulmonary vascular resistance was noted into day 2 (p less than 0.05). Our results suggest that PMN elastase may participate in the development of postoperative pulmonary impairment. 
Nucleolar organizer regions in various human brain tumors. Nucleolar organizer regions (NOR's) are loops of deoxyribonucleic acid (DNA) which transcribe to ribosomal ribonucleic acid (RNA) by RNA polymerase I. They possess vital significance in the ultimate synthesis of cellular proteins. A silver colloid staining technique for demonstration of NOR-associated proteins (Ag-NOR's) was applied to paraffin-embedded sections from 128 varied brain tumors and to chromosomal preparations from cultured brain-tumor cells. There was a statistically significant difference in the mean number of Ag-NOR's per nucleus between low-grade tumors (1.98/nucleus) and high-grade tumors (2.95/nucleus). It is suggested that the mean number of Ag-NOR's may represent the proliferative potential of brain tumors. Furthermore, high-grade tumors usually showed relatively large Ag-NOR's in a scattered distribution. In chromosomal preparations, the cultured cells displayed five to 12 Ag-NOR's on acrocentric chromosomes. Five of eight cell lines examined demonstrated ectopic Ag-NOR's. This simple staining technique can be easily applied to routinely processed paraffin-embedded sections and will become a useful tool for quick estimation of the proliferative potential of human brain tumors. 
Childhood haemangiomas of the head and neck. Haemangiomas of the head and neck in children may be of several histological types, the clinical course depending on the group to which the haemangioma belongs. Treatment may be required if the haemangioma interferes with the airway, as in the subglottic group, or if the lesion becomes ulcerated with subsequent haemorrhage, as in capillary cavernous haemangiomas. Most haemangiomas require no immediate treatment as they involute spontaneously, though parental reassurance will be of paramount importance. Those lesions which persist may be amenable to treatment at a later date, the laser probably offering the best long-term results in terms of cosmesis as in the case of port-wine stains. Superselective embolization is becoming the treatment of choice for arterial haemangiomas. This paper is designed to clarify the histological and clinical features of these tumours and their management in view of considerable confusion in the literature encountered in our study. 
Patterns of morbidity and mortality in typhoid fever dependent on age and gender: review of 552 hospitalized patients with diarrhea. Features of typhoid fever were correlated with age and gender through a review of the charts of 552 hospitalized culture-positive patients with diarrhea in Bangladesh. Seizures occurred more frequently in children from birth through 10 years of age (5%-11%) and pneumonia more frequently in children from birth through 5 years of age (8%-15%) than in older age groups (P less than .05), whereas intestinal perforation occurred more frequently in patients greater than or equal to 11 years of age (5%-25%) than in younger age groups (P less than .005). Compared with older age groups, children from birth through 10 years of age were more anemic, those from birth through 5 years of age had a higher mean white blood cell count, and those from birth through 1 year of age had a lower mean blood carbon dioxide content (all P less than .05). Female patients were more severely anemic than male patients (P less than .05). The case-fatality rate was 4.3% overall, with the highest rates for children from birth through 1 year of age (11%) and adults greater than or equal to 31 years of age (10%). Female patients had a higher case-fatality rate (6%) than male patients (3%), although the difference was not significant (P greater than .05). Death was independently associated with seizures, intestinal perforation, pneumonia, and delirium or coma. These results indicated that the patients with typhoid fever who were at highest risk of complications and death were children from birth through 1 year of age and adults greater than or equal to 31 years of age. 
An improved method for computerized tomography-planned transperineal 125iodine prostate implants. Transperineal 125iodine implants of the prostate can be performed with ultrasound guidance, a simple technique that has met with widespread acceptance. However, ultrasound does not allow good visualization of the pubic bones in relation to the pelvic outlet, and the pubic bones may interfere with needle placement in the anterior peripheral aspect of the prostate. Adequate irradiation of the entire periphery of the prostate is important to assure tumor control, since most tumors are multicentric and may involve the anterior aspect of the prostate. A computerized tomography-based treatment planning procedure that allows for angulation of transperineal needles to avoid the pubic bones and still reaches the most peripheral aspects of the gland is described. The technique also allows for the use of transrectal ultrasound and fluoroscopy to verify correct needle placement in the prostate at the procedure. Early treatment results, based on prostate specific antigen and regression of palpable tumors, are encouraging. 
Spatial and temporal registration of cardiac SPECT and MR images: methods and evaluation. Image registration may assist in the integration of information from multiple sources by allowing direct point-for-point comparisons of studies. To determine the usefulness of such a technique, a method for the spatial and temporal registration of four-dimensional single photon emission computed tomographic (SPECT) and magnetic resonance (MR) cardiac images was developed. Automatically detected left ventricular endocardial surfaces were used to determine the best transform between the two sets of surface points, and that transform was applied to the original SPECT image. A fused image created from the MR and the transformed SPECT images combined the information in both. The authors tested the method with seven patient studies. Registration reduced the distance between the MR and SPECT left ventricular endocardial surfaces by 30%, to an average of 2.7 mm. The authors found that, by using the fused images, perfusion abnormalities could be easily localized and correlated to high-resolution endocardial wall motion and systolic wall thickening. 
Intractable partial epilepsy: evaluation and treatment. Partial (focal or localization--related) epilepsy is the most common seizure disorder encountered in patients with epilepsy. These seizures are focal at onset-that is, emanating from a localized region of the brain. Patients with partial epilepsy may have seizures that are refractory to antiepileptic drug medication. The financial burden for these patients includes the cost of medical care and often the loss of employment. Psychosocial deterioration may be progressive as long as the seizures are intractable. Management includes confirmation of the type (or types) of seizures, exclusion of an intracranial epileptogenic lesion, and use of appropriate antiepileptic drug therapy. Referral of affected patients to a comprehensive epilepsy center for possible surgical treatment and investigational drug studies should be considered. In the care of the patient with intractable partial epilepsy, the goals should be to render the patient free of seizures and to allow the patient to become a participating and productive member of society. 
The role of echocardiography/Doppler in catheter balloon treatment of adults with aortic and mitral stenosis. Doppler and two-dimensional echocardiography (2DE) have played a major role in the evaluation of patients undergoing catheter balloon treatment of aortic and mitral stenosis. Doppler/2DE has made possible an understanding of the mechanism of increase in valve area. Before the procedure, Doppler/2DE provides a reasonable estimate of the severity of the valvular stenosis and associated cardiac abnormalities. The evaluation of mitral valve morphology by 2DE before catheter balloon treatment has shown that patients with excellent leaflet motion and minimal increase in valve thickness have the greatest increase in mitral valve area. During the procedure, Doppler/2DE can aid in the transseptal puncture, in positioning the balloons across the stenotic orifice, and in the immediate assessment of changes in valve function and complications. The estimate of the aortic and mitral valve gradients and areas by Doppler/2DE before catheter balloon treatment shows a reasonable correlation with hemodynamic measurements. Immediately after the procedure, the Doppler/2DE estimates of aortic valve gradient and area show a fair correlation with data from cardiac catheterization, provided care is taken to avoid technical problems. Doppler/2DE assessment of mitral valve area immediately after catheter balloon commissurotomy (CBC) shows a poor correlation with catheterization data, which has been attributed to rapid changes in left atrial compliance and gradient. However, the correlation of Doppler estimates of mitral valve area with catheterization data improves at 3 months after CBC. Serial evaluations of patients after aortic or mitral catheter balloon dilatation should permit detection of restenosis and valve regurgitation and assessment of ventricular function and may provide valuable insights into the mechanisms of restenosis and changing clinical status. 
Liver tumor promotion: effect of phenobarbital on EGF and protein kinase C signal transduction and transforming growth factor-beta 1 expression. Phenobarbital (PB) added to the medium of cultured rat hepatocytes alters epidermal growth factor (EGF) dependent mitogenesis in a biphasic manner; PB concentrations less than 1.5 mM are growth stimulatory but higher concentrations significantly inhibit normal hepatocyte proliferation. In contrast, the growth of putative preneoplastic cells is inhibited less by high concentrations of PB. Mechanistic studies designed to test the ability of PB to alter the early events of EGF signal transduction demonstrate that PB neither competes with EGF for binding to the EGF receptor nor alters EGF-induced receptor down-regulation. However, pretreatment with PB (greater than 1 mM) results in a transient inhibition of EGF binding to hepatocytes. The kinetics of this effect are similar to those obtained when hepatocytes are exposed to the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), a skin tumor promoter and activator of Ca2+/phospholipid-dependent protein kinase C. However, several observations suggest that distinct mechanisms mediate the responses to these two tumor promoters. First, the inhibitory effects of PB and TPA on EGF binding are additive. Also down-regulation of EGF receptors in response to TPA occurs with hepatocytes, A431 epidermal carcinoma cells, HepG2 hepatoma cells, and rat liver epithelial cells, but only hepatocytes are sensitive to PB. Furthermore, translocation of protein kinase C to the membrane occurs in hepatocytes treated with TPA but not in those treated with PB. The chronic treatment of rats with PB further sensitizes hepatocytes to EGF receptor down-regulation by in vitro PB while desensitizing them to EGF receptor down-regulation by TPA. This latter effect is correlated with a decreased ability of TPA to induce translocation of protein kinase C to the membrane. PB significantly increases the intracellular concentration of TGF-beta 1 in periportal hepatocytes but not in putative preneoplastic cells. TGF-beta 1 may therefore have an important function in regulating early stages of cell cycle progression in proliferating hepatocytes. 
Analysis of reconstruction for anterior mandibular defects using AO plates. The functional and cosmetic outcome of 11 patients who had anterior arch mandibulectomy for stage II-IV oral cavity carcinoma and were reconstructed with AO stainless-steel or titanium plates was retrospectively analyzed. Although the complication rate was high, plate removal was uncommon. Patients were afforded good function and cosmesis. Severity of postoperative infection corresponded to a low preoperative absolute lymphocyte count, which suggests that increased preoperative diet supplementation may decrease the incidence of early infections. Improved mandibular function and esthetics may allow future patients to be offered early reconstruction routinely. 
Persistent extrapyramidal syndrome with dystonia and rigidity caused by combined metoclopramide and prochlorperazine therapy. We have reported the case of a 58-year-old woman with cerebral palsy who experienced a persistent, generalized syndrome of dystonia and rigidity (tardive dystonia-parkinsonism) while being treated for vomiting with metoclopramide in combination with prochlorperazine. This syndrome was more severe than is typically seen in drug-induced extrapyramidal syndromes and may have contributed to her death. The extreme severity of this disorder was probably related to the use of a combination of dopamine antagonists in a patient who had premorbid cerebral dysfunction. Although dopamine antagonists should always be used with caution in individuals with cerebral dysfunction, this particular combination of antiemetics should probably be avoided in such patients. 
Cardiac anaesthesia in a patient with myotonic dystrophy. We describe a patient with myotonic dystrophy who required open-heart surgery for an atrial septal defect. He also had a sick sinus syndrome and an abnormal myocardium on histological examination. Anaesthesia using fentanyl, droperidol, nitrous oxide and a low concentration of enflurane was uneventful. Atelectasis of the left lung developed on the first postoperative day after removal of the tracheal tube. This was successfully treated by fibreoptic bronchoscopy. 
Respiratory compliance during sedation, anesthesia, and paralysis in infants and young children. Although total respiratory compliance (Crs) has been shown to fall in adults on induction of halothane anesthesia, no successful paired studies have been reported in children. The multiple occlusion technique was used to measure Crs in 17 infants and young children during sedated sleep (CrsS) and shortly after, following induction of halothane anesthesia (CrsA). Crs fell in all but one infant after induction of anesthesia, with a mean fall of 34.7% (range 0-58%). This was accompanied by a reduction in tidal volume and increase in frequency in every case. In 7 of the 17 children, who were to be paralyzed for surgical purposes, Crs was also measured in this anesthetized-paralyzed state. When tidal volume administered during manual ventilation was similar to that observed during measurement of CrsA, Crs during this low-volume ventilation was similar to CrsA. When tidal volume was increased and Crs remeasured, there was a significant increase in every case, with the high-volume Crs within 10% of CrsS in all but one child, in whom there was a 31.4% increase with respect to CrsS. Changes in tidal volume accounted for approximately 50% of the variability in each state. These results demonstrate a highly significant fall in Crs in infants and young children after induction of halothane anesthesia. In addition it appears that this reduction in Crs can be reversed by paralyzing the child and manually ventilating with tidal volumes approximating those seen during sedation. 
Thrombolytic and pharmacokinetic properties of chimeric tissue-type and urokinase-type plasminogen activators. BACKGROUND. Chimeric molecules comprising the A-chain of tissue-type plasminogen activator (t-PA) and the catalytic domain of urokinase-type plasminogen activator (u-PA) have intact enzymatic characteristics of u-PA, partial fibrin-binding properties of t-PA, and thrombolytic properties in animal models comparable with but not superior to those of single-chain u-PA (scu-PA). Deletion of the finger and growth factor domains (t-PA-delta FE/scu-PA-e) in such chimeras further reduces their affinity for fibrin. METHODS AND RESULTS. A detailed investigation of the thrombolytic potency and the pharmacokinetics of t-PA and u-PA chimeras was performed in quantitative animal models for thrombolysis. In hamsters with pulmonary embolism, in rabbits with jugular vein thrombosis, and in baboons with femoral vein thrombosis, the thrombolytic potency (percent lysis per milligram of compound administered per kilogram of body weight) of t-PA-delta FE/scu-PA-e was significantly higher than that of recombinant scu-PA (rscu-PA, Saruplase) as shown by a maximal rate of 720 +/- 170% versus 45 +/- 5% lysis per milligram of compound per kilogram of body weight (mean +/- SEM, p less than 0.01) in hamsters, 210 +/- 18% versus 49 +/- 3% lysis per milligram of compound per kilogram of body weight (mean +/- SEM, p less than 0.01) in rabbits, and 310 +/- 73% versus 90 +/- 0.3% lysis per milligram of compound per kilogram of body weight (p less than 0.01) in baboons. However, the specific thrombolytic activity (percent lysis per microgram per milliliter steady-state plasma antigen level) of t-PA-delta FE/scu-PA-e was not significantly different from that of rscu-PA in hamsters (210 +/- 57% versus 160 +/- 27% lysis per microgram per milliliter antigen level) and was lower than that of rscu-PA in rabbits (37 +/- 4% versus 130 +/- 5% lysis per microgram per milliliter antigen level; p less than 0.01). In dogs with a combined femoral vein blood clot and a platelet-rich femoral arterial eversion graft thrombosis, 0.25 mg/kg body wt bolus injections of t-PA-delta FE/scu-PA-e produced significantly more venous clot lysis (90 +/- 5%, n = 10) than 0.25 mg/kg rscu-PA (26 +/- 3%, n = 10) (p less than 0.001) and, at the arterial side, more frequent (10 of 10 dogs versus three of 10 dogs) and more persistent (six of 10 dogs versus none of 10 dogs) recanalization (p = 0.002). After bolus injection in hamsters, rabbits, or baboons, t-PA-delta FE/scu-PA-e had a fourfold to sixfold longer initial half-life than rscu-PA and a slower plasma clearance of sixfold in hamsters, 10-fold in rabbits, and more than 10-fold in baboons. CONCLUSIONS. These results indicate that t-PA-delta FE/scu-PA-e has a markedly enhanced thrombolytic potency toward venous and arterial thrombi caused by a delayed in vivo clearance with relatively maintained specific thrombolytic activity. These properties suggest that the chimera may be clinically useful for thrombolytic therapy by bolus administration in patients with thromboembolic disease. 
The effect of steroid therapy on recovery from tonsillectomy in children. A prospective, randomized, double-blind study to determine the postoperative effects of steroids in tonsillectomy was performed on 25 children from 4 to 12 years of age. A single intravenous dose of dexamethasone or a placebo was administered at onset of surgery. Other preoperative and postoperative medications, including antibiotics, anesthesia, and surgical techniques were standardized as noted in this article. The ability to return to a full or semifull diet occurred on the third and fourth postoperative days, significantly sooner in the steroid-treated patients than in the control patients. By the fifth and sixth days, the control group were eating as well as those children who received steroids. No significant differences were observed in postoperative pain, nausea, emesis, fever, or in the need for postoperative pain medications. This preliminary article concludes that a single preoperative dose of steroid results in an earlier return to a normal (full) diet in children who had undergone tonsillectomy. 
Heterogeneity of epithelial marker expression in routinely processed, poorly differentiated carcinomas. The application of immunohistochemical markers against epithelial antigens has proved useful for studying tumor differentiation and in aiding tumor diagnosis. However, the reactivity of various epithelial markers with poorly differentiated carcinomas (the situation in which they are most often used) has not been well established. As a result, it is unclear how negative results should be interpreted and how often more than one antibody may be needed to document the epithelial nature of poorly differentiated neoplasms. We studied 98 poorly differentiated epithelial tumors with AE1, CAM 5.2, and EMA to assess the use of these markers in their diagnosis. Both CAM 5.2 and EMA provided support for epithelial differentiation in 71% (70/98) of the cases, while AE1 stained 50% (49/98) of the tumors; CAM 5.2 was the single most useful marker in the subset of poorly differentiated neuroendocrine carcinomas, staining 20 (77%) of 26 tumors. Use of these markers in pairs increased the recognition of epithelial differentiation (at least one marker showing positive staining) as follows: AE1/CAM 5.2, 80% (78/98); AE1/EMA, 87% (85/98); and CAM 5.2/EMA, 99% (97/98). Thirty carcinomas stained with all three markers, 34 with two markers, and in 34 cases only one antibody supported epithelial differentiation. Twelve (21%) of 58 tumors showed evidence of S100 reactivity. None of the 71 cases to which PD7 was applied showed staining This study indicates that poorly differentiated carcinomas are heterogeneous in their expression of antigens recognized by AE1, CAM 5.2, and EMA. Moreover, these results quantitate the probability of reactivity with poorly differentiated carcinomas for each marker and support the use of one or more antibodies in a "backup" panel when a negative result is obtained with a single antibody and the diagnosis of carcinoma is still suspected. 
Hyperbaric treatment of cerebral air embolism sustained during an open-heart surgical procedure A case of cerebral air embolism sustained during replacement of the mitral valve resulted in postoperative coma and seizures. Hyperbaric treatment, begun 30 hours after the occurrence of the air embolism, resulted in good immediate and long-term recovery. Mild deficits of the left hemisphere were present at follow-up 53 days after the embolus was sustained, and lesser, minimal residua were present at 14-month follow-up. Hyperbaric treatment is the definitive therapy for cerebral air embolism. Although it is most effective when administered early, the outcome may be excellent even with late treatment. 
Echocardiographic detection of coronary artery disease during dobutamine infusion. BACKGROUND. Two-dimensional echocardiography performed during dobutamine infusion has been proposed as a potentially useful method for detecting coronary artery disease. However, the safety and diagnostic value of dobutamine stress echocardiography has not been established. METHODS AND RESULTS. In this study, echocardiograms were recorded during step-wise infusion of dobutamine to a maximum dose of 30 micrograms/kg/min in 103 patients who also underwent quantitative coronary angiography. The echocardiograms were digitally stored and displayed in a format that allowed simultaneous analysis of rest and stress images. Development of a new abnormality in regional function was used as an early end point for the dobutamine infusion. No patient had a symptomatic arrhythmia or complications from stress-induced ischemia. Significant coronary artery disease (greater than or equal to 50% diameter stenosis) was present in 35 of 55 patients who had normal echocardiograms at rest. The sensitivity and specificity of dobutamine-induced wall motion abnormalities for coronary artery disease was 89% (31 of 35) and 85% (17 of 20), respectively. The sensitivity was 81% (17 of 21) in those with one-vessel disease and 100% (14 of 14) in those with multivessel or left main disease. Forty-one of 48 patients with abnormal echocardiograms at baseline had localized rest wall motion abnormalities. Fifteen had coronary artery disease confined to regions that had abnormal rest wall motion, and 26 had disease remote from these regions. Thirteen of 15 patients (87%) without remote disease did not develop remote stress-induced abnormalities, and 21 of 26 (81%) who had remote disease developed corresponding abnormalities. CONCLUSIONS. Echocardiography combined with dobutamine infusion is a safe and accurate method for detecting coronary artery disease and for predicting the extent of disease in those who have localized rest wall motion abnormalities. 
Systemic lupus erythematosus presenting as an intracranial bleed. A previously healthy 12-year-old girl presented with fever and mental status changes without focal neurologic deficit. A CBC and computed tomography scan revealed thrombocytopenia and an intracranial bleed. Further laboratory studies were consistent with systemic lupus erythematosus. This case emphasizes the need to maintain a high index of suspicion for atypical presentations of an uncommon childhood illness. 
Late cardiac tamponade after open-heart surgery. Late cardiac tamponade occurred in 74 patients 5-287 (median 16) days after open-heart surgery and was treated with pericardiocentesis or surgery. The overall incidence of late cardiac tamponade was 1.3%. After valve operations it was 2.6% and after isolated coronary surgery 0.7% (53/2,028 vs. 18/2,661, p less than 0.002). The diagnosis was assessed by echocardiography in 93% of cases. Pericardiocentesis, attempted in 65 cases (88%), was curative in 80% but failed in 20%. Eight of the latter 13 underwent emergency surgery and five were medically treated. Failure of pericardiocentesis was associated with posterior location of fluid, clots, echo-free space less than 20 mm or myocardial insufficiency. The subxiphoid part of the wound was surgically re-entered in ten cases and the entire sternotomy in seven. Four patients (5%) died within 30 days of the primary intervention. All hospital survivors were observed for a median of 44 (range 11-115) months. Three (4%) had recurrent pericardial effusion requiring repeat pericardiocentesis, but none had pericardial constriction. The 5-year survival rate was 73%. 
A community-based study of incidence, risk factors and outcome of transient ischaemic attacks in Umbria, Italy: the SEPIVAC study. The SEPIVAC study is a community-based epidemiological survey of incidence and outcome of transient ischaemic attacks (TIAs) and strokes in the territory of the 6th Local Health Unit, Umbria, Italy, where 49,218 people live, from 1 September 1986 to 31 August 1989. All cases were registered with the study either by notification from general practitioners (GPs) or by a check of hospital admission within the study area and in the two hospitals of Perugia. There were 94 incident cases of TIAs (45 males, 49 females), thus giving a crude rate of 0.64 per 1000 per year [95% conficence intervals (CI) 0.52/0.78]. The rate adjusted to the European population is 0.42 (CI 0.33/0.54). Mean age was 69.4 years, and females were significantly older than males. The weighted relative risk for males was 1.19 (CI 0.79/1.79). Thirty-one patients were treated at home by their GPs. Females had hypertension more frequently than males, whereas males smoked more frequently; we did not find any other statistically significant difference in the distribution of risk factors. Twelve patients out of 58 who had CT had an infarct, and 29 out of 54 submitted to Doppler ultrasonography had carotid stenosis. At 1 month, 4 patients had suffered an ischaemic stroke, 1 of whom died. At 6 months, 3 further strokes and 2 further deaths (1 due to myocardial infarction) had occurred. 
A dose-response study of nalbuphine for post-thoracotomy epidural analgesia. The analgesic efficacy and side-effects of epidural nalbuphine (0.075-0.3 mg.kg-1) were compared with epidural morphine 0.1 mg.kg-1 in a randomised double-blind study in post-thoracotomy patients. The drugs were administered via a lumbar epidural catheter one hour before the end of surgery. Efficacy was assessed using visual analogue pain scores and supplementary iv fentanyl requirements; respiratory function was studied with an inductive plethysmograph and arterial blood gas analysis; and plasma nalbuphine levels were measured. Pain scores and fentanyl supplementation were lowest in the morphine group (P less than 0.01). No dose-response effect was apparent in the nalbuphine dose-range studied. Respiratory depression was more common in patients receiving morphine (higher mean PaCO2P less than 0.01, more frequent apnoeas greater than 15 sec P less than 0.05, and incidence of PaCO2 greater than 50 mmHg requiring naloxone P less than 0.01). There were no differences in haemodynamic variables, sedation, or other side-effects among the groups. The pharmacokinetic profile of epidural nalbuphine was similar to that seen with rapid iv injection. The results indicate that, relative to morphine, lumbar epidural nalbuphine is an ineffective analgesic after thoracotomy. Despite the lower incidence of respiratory depression its administration by this route cannot be recommended. 
The human hematopoietic progenitor cell antigen (CD34) in vascular neoplasia. The human hematopoietic progenitor cell antigen CD34 is synthesized and expressed by early normal hematopoietic progenitor cells and by many acute leukemias. Anti-CD34 antibodies also have been reported to stain blood vessels in tissue sections, and, more recently, CD34 mRNA has been detected in vascular endothelial cells. Therefore, the authors studied the diagnostic utility of immunohistochemical CD34 antigen detection in tumors of endothelial cell derivation and compared the results with stains for von Willebrand (vW) factor. A wide variety of epithelial and mesenchymal neoplasms also were examined to assess the specificity of CD34 for vascular neoplasia. Seven cases of angiosarcoma (seven of seven), five cases of Kaposi's sarcoma (five of five), and eight cases of epithelioid hemangioendothelioma (eight of eight) were moderately to strongly positive for CD34. This reactivity was equally intense in frozen sections, alcohol-fixed tissue, and formalin-fixed specimens. In many cases, the malignant endothelial cells stained more strongly than adjacent benign endothelium. Moreover, in most cases CD34 positivity was quantitatively and qualitatively stronger than staining for vW factor. Two cases of hemangiopericytoma (two of two) were CD34 positive but stained less intensely than the angiosarcomas, Kaposi's sarcomas, or hemangioendotheliomas. Five of six cases of hemangioma also stained positively for CD34; the nonreactive tumor in this group was the only one among 28 vascular neoplasms studied that was not reactive for CD34. In comparison, 9 of the 28 vascular tumors did not stain for vW factor. Three hundred fifty-seven tumors of nonvascular derivation also were examined for CD34 antigen expression. Focal light staining was seen in one pulmonary squamous cell carcinoma; moderate to intense staining was observed in half of the epithelioid sarcomas studied (8 of 16) and in a minority of leiomyosarcomas (3 of 22). These findings indicate that CD34 is a sensitive and relatively specific marker for neoplasms of vascular origin. 
Prevalence of HIV, hepatitis B and associated risk behaviours in clients of a needle-exchange in central London. In order to determine the prevalence of risk behaviour for, and antibodies to HIV and hepatitis B in clients of a needle-exchange scheme in central London we employed an anonymous, self-administered questionnaire along with salivary antibody testing by immunoglobulin (Ig) G antibody capture immunoassay. Two hundred and thirty-two subjects (193 men, 39 women; median age 32) participated; a response rate of 89%. Clients were long-term, frequent injectors. Lending used equipment at any time was reported by 55%, and borrowing by 52%. Of those who had shared needles and syringes during the last year, the majority had lent to, or borrowed from, one person only (53 and 55%, respectively). Younger clients (less than 29 years of age) reported more recent sharing than older clients (greater than 30 years of age). Five out of 211 (2.4%) samples tested for anti-HIV were positive. One hundred and eleven out of 199 (56%) samples were positive for anti-hepatitis B core (HBc). In this population of needle-exchange attenders there is no evidence of further spread of HIV, and a low prevalence of HIV infection appears to have been sustained. However, the high prevalence of anti-HBc provides evidence of previous risk behaviour and so constant vigilance is necessary if further viral spread is to be avoided. This study has established an acceptable method for the anonymous surveillance of current risk behaviour and salivary antibodies to HIV and hepatitis B virus (HBV) in a drug-using population. 
Conventional screen/film vs reduced exposure photostimulable phosphor plate imaging in lower extremity venography: an ROC analysis. Half-exposure phosphor plates used in venography substantially reduce the total X-ray exposure to a patient while increasing the chance that all images will be of excellent diagnostic quality. Simultaneous half-exposure phosphor plate and full-exposure conventional screen/film venograms were obtained of 35 patients and compared by using receiver operating characteristic (ROC) analysis. The area under the ROC curve ranged from 0.67 to 0.78 for conventional films and 0.68 to 0.91 for phosphor plates. Group performances on conventional films vs phosphor plates were not statistically different. No statistically significant difference in individual performance with the two techniques was seen in seven of the eight interpreters at the 95% confidence level. The eighth interpreter performed significantly better with phosphor plates than with conventional films. Interpreters with and without specific experience in phosphor plate venography were grouped separately, and performance of the two groups was compared in each technique. No difference in performance was found between the groups when interpreting conventional venograms, but, when interpreting phosphor plate venograms, the group with specific experience performed significantly better than they had with conventional venograms, and significantly better than the other group did at interpreting either conventional or phosphor plate venograms. We conclude that phosphor plate venograms made at a 50% reduction in X-ray exposure are equal to, and may surpass, conventional screen/film venograms for diagnosing acute venous thrombosis of the calf and thigh. We recommend expanding the indications for phosphor plate radiography to include contrast venography of the lower extremities. 
Sulphadiazine desensitization in patients with AIDS and cerebral toxoplasmosis. The objectives of this study were to evaluate the efficacy of a sulphadiazine desensitization protocol to treat patients with AIDS and cerebral toxoplasmosis (CT) and known sulphonamide allergy, to ensure that an adequate dose of sulphadiazine (2-4 g/day) was achieved rapidly (within 4-5 days), and to assess the effect of concurrent corticosteroid (CS) administration on the success rate of the regimen. Sixteen patients with CT and a past history or current manifestations of sulphonamide allergy were desensitized to sulphadiazine from October 1988 to December 1989. The protocol employed the oral administration of gradually increasing increments of sulphadiazine 3-hourly over 5 days. Success was defined as tolerance of 2-4 g oral sulphadiazine per day for at least 7 days until death or the present time without any allergic reactions. Our success rated overall was 10 out of 16 patients (62%). Seven patients achieved a final dose of 4 g/day and three a dose of 2 g/day. Concurrent CS administration did not appear to affect the outcome in the small number of patients studied. Our sulphadiazine regimen rapidly, successfully and safely desensitized patients with CT and sulphonamide allergy, allowing the optimal first-line treatment to continue. The aetiology of allergy in HIV-infected patients and the mechanisms by which desensitization works are unknown. 
Transureteroureterostomy and terminal loop cutaneous ureterostomy in advanced pelvic malignancies. Transureteroureterostomy was combined with terminal loop cutaneous ureterostomy, without complications, in 8 patients with advanced pelvic malignancy and a poor prognosis. Urinary diversion was palliative in all patients and followed pelvic exenteration in 4, debulking of pelvic tumor in 2 and radical cystectomy in 1, while 1 had inoperable bladder cancer. All patients had at least unilateral hydroureteronephrosis preoperatively. In each case a postoperative excretory urogram revealed significant improvement of the hydroureteronephrosis and the serum creatinine improved or stabilized. No patient had ureteral stomal stenosis or retraction. Mean survival was 5 months, with the longest survival being 1 year. Transureteroureterostomy in conjunction with terminal loop cutaneous ureterostomy is an effective technique of urinary diversion in selected patients with a poor prognosis and advanced pelvic malignancy, decreasing operative time while avoiding the morbidity associated with a ureterointestinal operation or nephrostomy. 
Effect of a new synthetic ascorbic acid derivative as a free radical scavenger on the development of acute pancreatitis in mice. The therapeutic effects of CV 3611, a new synthetic free radical scavenger prepared from an ascorbic acid derivative, on choline deficient, ethionine enriched (CDE) diet induced acute pancreatitis in mice were evaluated and compared with those of superoxide dismutase. Time/course studies after subcutaneous injection of CV 3611 in normal mice showed a peak plasma concentration of mean (SEM) 0.54 (0.09) micrograms/ml at one hour, with a gradual decrease over the next 10 hours, while a peak concentration in pancreatic tissue of mean (SEM) 425 (33) ng/g tissue was achieved at three hours and the drug was undetectable at 12 hours. Survival rates and activities of pancreatic enzymes (amylase, lipase, elastase I) were compared in control mice and animals that received CV 3611 before or at the time of feeding the CDE diet. The survival rate was observed in a no treatment group and mice given pretreatment or treatment with CV 3611 or superoxide dismutase. The survival rate was significantly better in the treatment group given CV 3611 (p less than 0.02), but superoxide dismutase had no significant effect on survival. The increases in the three serum enzyme activities were significantly less at 48 hours in the groups given pretreatment or treatment with CV 3611 than in the no treatment group. These results indicate that CV 3611, which has been proved to pass through the cell membrane and to have a long half life in plasma and tissue, had an important therapeutic effect on the development of acute pancreatitis. They also suggest that oxygen derived free radicals may play an important role in the development of acute pancreatitis. 
Postheparin plasma diamine oxidase values in the follow up of patients with small bowel Crohn's disease. Measurement of postheparin plasma diamine oxidase (PHD) activity has been proposed to assess mucosal integrity in several diseases of the small intestine. In Crohn's disease, PHD values identify a group of patients with predominantly small bowel mucosal damage. To determine the role of mucosal involvement in the progression of small bowel Crohn's disease and whether different PHD values can predict different outcomes the changes in PHD values in 41 patients with small bowel Crohn's disease admitted consecutively to our department were investigated. The test was performed during periods of active disease and after either medical or surgical treatment had resulted in improvement. PHD values were significantly lower than in normal subjects (normal range 3.7-7.7 U/ml). In 35 patients with active disease (Crohn's disease activity index (CDAI) greater than 150) two groups were identified by choosing a cut off value of 2 U/ml: 93% of the 15 patients with PHD values lower than 2 U/ml (mean (SD) 1.36 (0.46) U/ml) relapsed at least once in the following year, while only the 20% of the 20 whose values were higher than 2 U/ml (mean (SD) 3.69 (1.50)) relapsed in the same period. The data were statistically significant (Yates's corrected chi 2 = 15.63; p less than 0.0001). The positive and negative predictive values of the test were 93% and 80%, respectively. During relapses, PHD values were consistently lower than previous values, and increased significantly after effective medical or surgical treatment. In the six patients in whom there were no changes in disease activity (CDAI persistently less than 150), there was no change in PHD values. 
Factors influencing outcome of prednisone dose reduction in myasthenia gravis. We reviewed retrospectively 114 prednisone dose reduction attempts in 63 myasthenic patients. Dose reduction was considered successful if a patient remained asymptomatic for more than 1 year on no prednisone or a stable low dose of prednisone. Successful dose reduction attempts were more common in patients taking azathioprine, but thymectomy did not influence taper outcome. Slower rate of dose reduction and higher ending dose of prednisone improved the chance of success. 
Revision osteoarticular allograft transplantation in weight-bearing joints. A clinical review. The early results of revision osteoarticular allografts in weight-bearing joints are reported. Sixteen consecutive patients underwent surgery over a six-year period between 1982 and 1988. At the time of review eight patients (50%) had surviving second allografts with an average follow-up time of 48 months (range 12 to 87). Five patients were graded excellent according to the Mankin scale, one good and two fair. Eight patients (50%) required further surgery, but only two patients came to amputation. 
Controlled clinical trials of drug treatment for hypertension. A review. We reviewed the designs and major results of 17 large-scale, controlled, clinical trials that reported the effects of drug treatment for hypertension on morbidity or mortality. Seven trials conducted in study populations with more-severe hypertension (diastolic blood pressures 100-120 mm Hg or higher), including the more-severe stratum of the Veterans Administration Trial, showed large reductions in stroke, other "hypertensive" events, and, in one trial, total mortality. Of 11 trials in populations with less-severe hypertension (diastolic blood pressures predominantly below 105 mm Hg), including the less-severe stratum of the Veterans Administration Trial, nine met the criteria for pooling of results. Among the aggregate 43,000 patients in the nine trials who were followed up for an average of 5.6 years, mean diastolic blood pressure reduction was 5.8 mm Hg, and a significant 11% reduction in total mortality was observed. This benefit was largely attributable to a 38% reduction in fatal strokes; nonfatal strokes were similarly reduced. Coronary heart disease mortality was 8% lower in drug treatment than in control groups, but this difference was not significant. A similar result was observed for combined coronary mortality and nonfatal myocardial infarction. A possible explanation for the inconclusive result regarding coronary end points was an adverse trend, observed in several trials, in a subgroup with baseline resting electrocardiographic abnormalities. Because all the trials except the propranolol arm of the Medical Research Council trial used drug regimens based on thiazide-like diuretic agents, and because there are now several new drug classes proposed as initial therapy, additional large-scale clinical trials may need to be considered. 
Resting energy expenditure in patients with non-small cell lung cancer. Resting energy expenditure (REE) was determined in 30 patients with newly detected non-small cell lung cancer. Measured values were compared with the values predicted by the Harris-Benedict (HB) formula. Mean REE was 20% higher than predicted. Sixty percent of the patients (18 patients) had an elevated REE (greater than or equal to 115%) compared with this formula. The prevalence of hypermetabolism in a group of patients with gastric and colorectal cancer was only 13% (13 of 104 patients). When corrected for fat-free mass (FFM), REE was still significantly higher (P less than 0.001) in the lung cancer group compared with the gastric and colorectal cancer group. Whereas weight loss in healthy men leads to an adaptational decrease in energy expenditure (EE), weight loss in the patients with lung cancer was accompanied by an increase in REE. Tumor stage, tumor localization, pulmonary function, or smoking behavior could not explain the observed increase in REE in patients with lung cancer. Therefore, these metabolic alterations appear to be tumor mediated. 
Gastric leiomyosarcoma. Prognostic factors and surgical management. Information on gastric leiomyosarcoma, such as important prognostic factors, patterns of disease recurrence, and optimal methods of treatment, are derived from limited patient experience. We address these questions, with specific focus on whether an advantage could be demonstrated for radical resection compared with wide local excision, by retrospectively investigating 53 patients who underwent surgical treatment at Mayo Clinic, Rochester, Minn. Abdominal pain and/or gastrointestinal bleeding associated with an intramural or exogastric mass were typical features of this disease. Only tumor size and histologic grade were statistically significant prognostic factors. With analysis of survival curves and patterns of recurrence, neither the addition of lymphadenectomy nor the wider tumor-free margins of a radical gastrectomy seemed superior to the more conservative local excision. Therefore, wide local excision remains the preferred treatment when technically feasible. 
Alveolitis correlates with clinical pulmonary involvement in primary Sjogren's syndrome. Bronchoalveolar lavage (BAL) was performed in 23 patients with primary Sjogren's syndrome (1Ss) and ten healthy controls to evaluate alveolitis and correlate it with pulmonary and systemic manifestations. Patients with 1Ss had higher BAL total cell count (9.2 +/- 6.7 millions/ml vs 6.1 +/- 2.9 millions/ml) and higher percentage of lymphocytes 23.3 +/- 15.6 percent vs 6.5 +/- 2.9 percent, p less than 0.001) than controls. Twelve patients (group A) constituted the "high alveolitis" group (lymphocytes greater than 15.2 percent) and ten (group B) constituted the "low alveolitis" group (lymphocytes less than 15.2 percent). Group A had more frequent cough (6/12 vs 2/10, p = 0.07), dyspnea (4/12 vs 1/10), and roentgenologic evidence of interstitial lung disease (5/12 vs 0/10, p less than 0.05). They also had lower total lung capacity (85.6 +/- 14.2 percent pred vs 105.8 +/- 23.3 percent pred, p less than 0.05) and Dco (87.7 +/- 20.6 percent pred vs 103.6 +/- 21.0 percent pred). All patients with +3 or +4 grading or lymphocytic infiltrates in lip biopsy specimen belonged in group A (5/12). Finally, T-helper/T-suppressor ratio was lower in group A than in group B. The intensity of alveolitis was not correlated with clinical or serologic manifestations of systemic disease. 
Comparison of exercise radionuclide angiography with thallium SPECT imaging for detection of significant narrowing of the left circumflex coronary artery. Although quantitation of exercise thallium tomograms has enhanced the noninvasive diagnosis and localization of coronary artery disease, the detection of stenosis of the left circumflex coronary artery remains suboptimal. Because posterolateral regional wall motion during exercise is well assessed by radionuclide angiography, this study determined whether regional dysfunction of the posterolateral wall during exercise radionuclide angiography is more sensitive in identifying left circumflex disease than thallium perfusion abnormalities assessed by single-photon emission computed tomography (SPECT). One hundred ten consecutive patients with CAD were studied, of whom 70 had a significant stenosis of the left circumflex coronary artery or a major obtuse marginal branch. Both regional function and segmental thallium activity of the posterolateral wall were assessed using visual and quantitative analysis. Left ventricular regional function was assessed objectively by dividing the left ventricular region of interest into 20 sectors; the 8 sectors corresponding to the posterolateral free wall were used to assess function in the left circumflex artery distribution. Similarly, using circumferential profile analysis of short-axis thallium tomograms, left ventricular myocardial activity was subdivided into 64 sectors; the 16 sectors corresponding to the posterolateral region were used to assess thallium perfusion abnormalities in the left circumflex artery territory. Qualitative posterolateral wall motion analysis detected 76% of patients with left circumflex coronary artery stenosis, with a specificity of 83%, compared with only 44% by qualitative thallium tomography (p less than 0.001) and a specificity of 92%. Whereas quantitation of thallium activity increased the sensitivity for detecting left circumflex coronary artery stenosis to 80% with a specificity of 55%, it did not achieve statistical significance when compared with qualitative wall motion analysis. 
Cerebrovascular hemodynamic changes associated with carotid endarterectomy. To evaluate the effect of carotid surgery on the cerebral circulation, transcranial Doppler sonography and ocular pneumoplethysmography were performed on 36 patients who underwent unilateral carotid endarterectomy. Ocular pneumoplethysmography and transcranial Doppler sonography tests were performed within a week before and after operation, and transcranial Doppler sonography was repeated greater than or equal to 30 days after operation. Middle and anterior cerebral arteries were insonated bilaterally, and flow velocities ipsilateral (iMCAFV or iACAFV) and contralateral (cMCAFV or cACAFV) to the side of surgery were recorded. The iMCAFV and iACAFV increased significantly in the immediate postoperative period, and the iMCAFV remained elevated on the second follow-up study. Patients with greater than or equal to 75% ipsilateral carotid stenosis (N = 23) had increased iMCAFV, iACAFV, and decreased cACAFV after operation, whereas those with less than 75% stenosis (N = 13) had no significant transcranial Doppler sonography changes. Those with greater than or equal to 75% contralateral carotid stenosis (N = 17) had significant increases in iMCAFV, cMCAFV, and iACAFV after operation, whereas those with less than 75% contralateral carotid stenosis had no significant transcranial Doppler sonography changes. A subset of patients (N = 13) did not increase iMCAFV after surgery. The ocular pneumoplethysmography changes were significantly different in both groups when preoperative and postoperative values were compared. We conclude that carotid endarterectomy can cause lasting cerebral hemodynamic changes, but that its effects are not uniform among all patients. 
Ischaemic myelopathy secondary to disseminated intravascular coagulation in AIDS. A 39-year-old patient with AIDS presented with a rapidly progressive myelopathy with a partial Brown-Sequard syndrome. He died, 9 weeks after onset of the first neurological signs, from diffuse encephalopathy. Neuropathological examination revealed multiple, usually small, frequently haemorrhagic, infarcts or various ages and numerous fibrin thrombi in medium and small penetrating vessels and capillaries of the brain and spinal cord, characteristic of disseminated intravascular coagulation. There were no inflammatory changes. Immunohistochemical studies for human immunodeficiency virus, cytomegalovirus, varicella zoster virus, herpes simplex virus type 1 and type 2 were negative. Ischaemic spinal cord lesions due to disseminated intravascular coagulation may represent an unusual cause of focal, non-inflammatory, non-tumoral, myelopathic syndrome in AIDS. 
Papaveretum infusions in infants under 6 months of age. The effectiveness of a continuous low dose papaveretum infusion for the relief of postoperative pain was assessed in 29 infants aged 1-6 months nursed on the infant surgical ward following major abdominal surgery. Trained nursing staff were able to adjust the dosage within prescribed guidelines and satisfactory analgesia was obtained with a regimen which delivered up to 0.0375 mg/kg/hour, approximately half the dose recommended in children older than 12 months. There was one case of clinically significant respiratory depression. 
Nonparallel effects of renin inhibitor treatment on plasma renin activity and angiotensins I and II in hypertensive subjects. An assay-related artifact. Nonparallel effects of renin inhibitor treatment on plasma renin activity (PRA) and the plasma levels of angiotensins (ANG), as well as on blood pressure, have been observed in subjects with hypertension. This study addresses the possibility that renin inhibitors may show a high degree of plasma protein binding in vivo and that displacement of protein-bound inhibitor during the assay of PRA in vitro may lead to overestimation of renin inhibition. Indeed, with the ultrafiltration technique it was found that 96% of the novel renin inhibitor Ro 42-5892, when added to EDTA plasma, was bound to protein. The angiotensinase inhibitors phenylmethylsulfonyl fluoride (PMSF) and 8-hydroxy-quinoline sulfate (8-OHQ), which are currently used in PRA assays, caused a displacement of protein-bound inhibitor, thereby increasing its free concentration. This displacement was sufficient to explain the reduction in IC 50 of Ro 42-5892, which was seen in the PRA assay when PMSF and 8-OHQ were added to plasma. Such reductions in IC 50 were also seen with the renin inhibitors CGP 29-287, CGP 38-560A, and SR 43-845. When Ro 42-5892 was given, 1 mg/kg intravenously in 10 min, to subjects with hypertension, it appeared that plasma ANG I and II returned to baseline after 6-8 h, whereas PRA measured in the presence of PMSF and 8-OHQ was still suppressed. However, when PRA was measured without these angiotensinase inhibitors, the inhibition of PRA was parallel to the suppression of ANG I and II. 
Internal mammary artery to lung parenchyma fistula after aortocoronary bypass grafting. Two unusual cases of internal mammary artery fistulization to lung parenchyma after coronary revascularization are reported. They were incidentally discovered during coronary angiography, and one of them was successfully closed with a percutaneous transvenous coil-spring occluder. The cause is thought to be the direct contact between the dissected mammary artery pedicle and the lung parenchyma. 
Quickscan: Doppler ultrasound emulation of angiography--its value prior to arteriography in peripheral vascular disease. The prevalence of peripheral vascular disease demands a quick, reliable, non-invasive technique for initial assessment. We have devised a new method which combines the two physical principles that (1) Doppler shift is proportional to blood velocity and (2) blood velocity is inversely proportional to arterial cross-section with the ability to track probe position using a non-contacting method. An image of the probe track and any arterial narrowing is shown superimposed on an outline of the patient. Pressure measurement, scan and graphics with final report take about 20 minutes. The accuracy of this system in peripheral vascular disease was evaluated. Thirty-one patients underwent quickscan (QS) and arteriography within an average time of 7 days. Abdominal aorta, common iliac-common femoral, superficial femoral and popliteal artery segments were graded independently as normal, significant stenosis (greater than 50% of diameter) or occluded by both techniques. Of 197 segments, QS correctly assessed 106 normal, 22 stenosed and 28 occluded segments. Four equivocal angiographic stenoses were normal on QS and three severe stenoses were graded occlusion. Fifteen segments on angiography and five on QS were not assessed. For the iliac and superficial femoral artery segments, sensitivity and specificity averaged 77% and 86%, respectively, for all grades. Aortic statistics were invalid (only one significant lesion). Six out of eight popliteal occlusions were correctly diagnosed by QS, but no popliteal stenoses were detected out of six shown on arteriography. Low numbers may contribute to this discrepancy but an improved popliteal scanning method may be necessary. We find initial QS an invaluable aid to direct percutaneous angiography and to indicate potential sites for angioplasty. 
Resection and reconstruction of the carotid bifurcation with polytetrafluoroethylene grafts; operative technique. Preliminary results in 25 procedures and indications. Although carotid endarterectomy is the standard procedure, the purpose of this paper is to describe a new surgical technique and indicate its role in the surgery of cervical cerebrovascular disease. The technique consists of resection of the pathologic carotid artery bifurcation followed by its total replacement with a bifurcated thin-wall polytetrafluoroethylene (PTFE) graft constructed by the surgeon. Prosthetic graft reconstruction of the carotid bifurcation (PGRCB) was performed in 21 patients (25 procedures) from November 1984 to May 1987. Many patients were over 70 years old. The indications for surgery were transient ischemic attacks (TIA)'s in 10 patients (high-grade stenosis), established stroke with mild deficit in 3 patients (high-grade stenosis). Eight patients (high-grade stenosis) were asymptomatic and 4 had vertebro-basilar symptoms. In 11 procedures the indications were the same as for standard carotid endarterectomy (significant stenosis and/or ulcerated plaque). In 14 cases, the procedure was justified by extensive lesions involving a long segment of the internal carotid artery (2 restenoses, 12 calcified lesions). In the perioperative period, there were no deaths and no TIA's. The 25 procedures were assessed one month postoperatively by ultrasonic imaging and venous substraction angiography. All the grafts were patent with perfect restoration of the carotid bifurcation anatomy. Systematic follow-up study was carried out in 1987. Three patients had died of non-neurologic causes and one was lost to study. The remaining 19 procedures were evaluated with an average follow-up of 19 months (range 7 to 32 months). The patients were asymptomatic and all the grafts remained patent including one stenosis (greater than 50%) at the common carotid artery anastomosis. Because recent studies have documented a much higher rate of technical defects or recurrent stenosis after carotid endarterectomy, we believe that PGRCB merits consideration, particularly in difficult endarterectomies, and in recurrent carotid stenosis. Furthermore it seems acceptable to advocate PGRCB in aneurysms of the internal carotid artery and in post-irradiation arteritis. 
Structural abnormalities of the craniofacial complex and congenital malformations. This article was meant to be a very cursory survey of the multiple defects that abnormal development can produce in all areas of the craniofacial complex. Careful examination for these abnormalities should lead the clinician to earlier referral of patients for additional examination by a genetics team. This often enables more focused care for the individual and better counseling concerning future pregnancies. Aase points out that "funny looking face" or "syndromic facies" is no longer helpful. Accurate assessment of the face with measurement leads to better diagnosis and ultimately better patient care. All children with facial defects deserve early intervention by a multidisciplined craniofacial team including geneticists, surgeons, dentists, speech pathologists, and other specialists. Part of the process of early referral to this team involves early detection and recognition in the neonatal period. It is hoped that this article stimulates the pediatrician to be aware of these abnormalities, recognize their importance, and seek additional help for patients, no matter what their age. 
Immaturity and aneuploidy in human oocytes after different stimulation protocols. OBJECTIVE: To study immaturity and aneuploidy in human oocytes after two different stimulation protocols. DESIGN: Retrospective. SETTING: Outpatient IVF clinic/laboratory. PATIENTS: One hundred forty-three patients of whom 65 were stimulated with clomiphene citrate (CC)/human menopausal gonadotropin (hMG) and 78 were stimulated with gonadotropin-releasing hormone agonist (GnRH-a)/hMG. Only patients with at least one oocyte unfertilized were included in this study. RESULTS: Stimulation with GnRH-a/hMG, as compared with CC/hMG stimulation, resulted in larger numbers of oocytes (P less than 0.00001), a higher fertilization rate (P less than 0.02), and oocyte retrieval at a later average cycle day (P less than 0.000005). Cytogenetic findings of immaturity were observed in 33.9% of unfertilized oocytes after CC/hMG stimulation, compared with only 17.8% after GnRH-a/hMG stimulation (P less than 0.0005). Aneuploidy findings were the same for both groups. CONCLUSION: In GnRH-a/hMG stimulation, oocytes approach the normal day of ovulation more closely. This may allow for better oocyte maturation and higher fertilization and pregnancy rates. 
Comparison of intravenous bolus injection or continuous infusion of recombinant single chain urokinase-type plasminogen activator (saruplase) for thrombolysis. A canine model of combined coronary arterial and femoral venous thrombosis. The thrombolytic efficacy of recombinant unglycosylated full length single chain urokinase-type plasminogen activator (rscu-PA, saruplase), applied either as single intravenous bolus or as a continuous infusion over 60 minutes, was studied in 5 randomized blinded groups of 5 dogs with combined copper coil induced coronary artery thrombosis and 125I-fibrin labeled femoral vein clots. Infusion of 1 mg/kg recu-PA (group I) induced coronary recanalization in 4 of 5 dogs and 98 +/- 1% (mean +/- SEM) venous clot lysis. Bolus injection of 1 mg/kg recu-PA (group II) caused reflow in 3 of 5 dogs and 88 +/- 5 percent venous clot lysis. Infusion of 0.5 mg/kg rescu-PA (group III) achieved reflow in 3 of 5 dogs and 52 +/- 6% venous clot lysis. Bolus injection of 0.5 mg/kg rscu-PA (group IV) induced reflow in 4 of 5 dogs and 48 +/- 12% venous clot lysis. Placebo infusion (group V) was associated with late recanalization in 1 of 5 dogs and 18 +/- 8% venous clot lysis. Coronary artery reocclusion after reflow was not observed in groups I and II, but occurred in 2 of 3 animals in group III and in 3 of 4 animals in group IV (P = .02). The time to reflow in responsive animals was 22 +/- 5 minutes with infusion of 0.5 or 1 mg/kg rscu-PA and 14 +/- 1 minute with bolus injection of 0.5 or 1 mg/kg (P = .14). Depletion of fibrinogen and alpha 2-antiplasmin to less than 25% of baseline levels was observed in the 5 dogs given 1 mg/kg rscu-PA by bolus and in 3 of the 5 dogs given 1 mg/kg rscu-PA via infusion, but in none of the dogs that received 0.5 mg/kg rscu-PA (P less than .001). Plasma clearance rates were 170 +/- 44 and 230 +/- 30 mL/minute after bolus injection and 190 +/- 47 and 310 +/- 56 mL/minute during infusion of rscu-PA for the 1 mg/kg and 0.5 mg/kg doses respectively. Thus, intravenous bolus injection of rscu-PA (saruplase) appears to be equipotent to an infusion over 60 minutes for both coronary and venous thrombolysis. This animal model of combined arterial and venous thrombolysis may be useful for the evaluation of new thrombolytic strategies. 
Adrenal carcinoma presenting with postmenopausal vaginal bleeding. A 63-year-old woman presented with a 3-day history of vaginal bleeding. Pelvic examination and ultrasound revealed bilateral atrophy of the ovaries and a uterus of 8.8 x 3.3 x 4.0 cm. Serum estradiol (E2) was 300 pg/mL. Cushing syndrome was diagnosed biochemically, and computed tomography of the abdomen revealed a 5-cm left adrenal mass and tumors in the liver and lung. A pathologic diagnosis of metastatic adrenal carcinoma was made after surgery. This case demonstrates that adrenal carcinoma can produce high E2 levels in a postmenopausal woman, leading to uterine enlargement and vaginal bleeding. Adrenal carcinoma should therefore be included in the differential diagnosis of postmenopausal vaginal bleeding. 
Plasma endothelin in human essential hypertension. Plasma endothelin immunoreactivity was measured in normal controls, in mild essential hypertensive patients with no antihypertensive treatment, in moderate to severe hypertensives whose blood pressure was controlled by treatment, and in moderate to severe hypertensives whose blood pressure was not controlled by treatment. Endothelin immunoreactivity levels in plasma in the four groups were similar, but had a positive correlation with blood pressure in hypertensives although not in normotensives. The concentration in plasma of both C-terminal and N-terminal atrial natriuretic peptide also had a positive correlation with blood pressure in these hypertensive patients. We conclude that if plasma immunoreactive endothelin levels represent the result of endothelial production of endothelin, in absence of changes in catabolism of the peptide, essential hypertensive patients do not appear to have increased production of endothelin. 
Effects of ultrasound and trolamine salicylate phonophoresis on delayed-onset muscle soreness. The purpose of this study was to determine the effects of ultrasound and phonophoresis using an anti-inflammatory-analgesic cream (trolamine salicylate) on delayed-onset muscle soreness (DOMS). Repeated eccentric contractions were used to induce DOMS in the elbow flexors of 40 college-aged women. Subjects were then assigned randomly to one of four groups: (1) group 1 (n = 10) received sham ultrasound using placebo cream, (2) group 2 (n = 10) received sham ultrasound using trolamine salicylate cream, (3) group 3 (n = 10) received ultrasound using placebo cream, and (4) group 4 (n = 10) received ultrasound using trolamine salicylate cream. Subjects were treated on 3 consecutive days. Muscle soreness and active elbow range of motion were assessed daily prior to each treatment. The subjects in group 3 experienced an increase in DOMS, whereas no increase in soreness was observed in the subjects in group 4. The authors concluded that ultrasound enhanced the development of DOMS but that this enhancement was offset by the anti-inflammatory-analgesic action of salicylate phonophoresis. These findings suggest that salicylate phonophoresis may be useful in clinical situations in which it is desirable to administer ultrasound without increasing inflammation. 
Insulin and glucagon levels in fulminant hepatic failure in man. The behavior of insulin and glucagon and related metabolic substrates was assayed in plasma of patients with fulminant hepatic failure. All 12 subjects were provided the same nutritional support. High levels of insulin and glucagon were present at all times and no difference was observed between surviving patients (four) and those who died (8). Elevated values for branched-chain and aromatic amino acids as well as alanine were present. Statistically significant lower levels of aromatic amino acids and consequently a greater branched chain-aromatic amino acid ratio was found in surviving vs nonsurviving patients. A significantly greater level of alpha-fetoprotein was found in patients who survived as compared to those who died. 
Flecainide in the treatment of fetal tachycardias. Fourteen mothers were treated with flecainide for fetal atrial tachycardias associated with intrauterine cardiac failure. Twelve of the 14 fetuses responded by conversion to sinus rhythm. One of the 12 fetuses subsequently died in utero. The remaining fetuses suffered no morbidity and were alive and well 3 months to 2 years after delivery. The two fetuses in whom atrial tachycardia did not convert with flecainide were successfully treated with digoxin. These results compare favourably with previous forms of antiarrhythmic treatment. After recent reports of the side effects of flecainide treatment, however, it has been advised that this drug should be confined to high risk patients and those with life threatening arrhythmias. The use of flecainide for fetal arrhythmias should be limited to patients with severe fetal hydrops and supraventricular tachycardias. It should not be the first drug of choice in atrial flutter. 
The study of serum apoprotein levels as indicators for the severity of angiographically assessed coronary artery disease. Serum apoprotein A-I (Apo A-I) and B (Apo-B) concentrations were determined in 40 subjects undergoing coronary angiography for past myocardial infarction and angina pectoris, and the authors studied the relationship between the apoprotein concentrations and the severity of coronary artery disease (CAD). During this study, serum total cholesterol, triglyceride, and high-density lipoprotein, low-density lipoprotein, and very low density lipoprotein cholesterol concentrations were determined to control analysis. The results showed that the decrease in serum Apo A-I levels was the best indicator distinguishing CAD from non-coronary artery disease; the Apo B/Apo A-I ratio had the most consistent association with the severity of CAD as assessed by angiography; Apo B/Apo A-I values ranging from 0.98 to 1.00 might be considered critical values for early CAD. 
Cost effectiveness of incremental programmes for lowering serum cholesterol concentration: is individual intervention worth while? OBJECTIVE--To evaluate the relative cost effectiveness of various cholesterol lowering programmes. DESIGN--Retrospective analysis. SETTING--Norwegian cholesterol lowering programme in Norwegian male population aged 40-49 (n = 200,000), whose interventions comprise a population based promotion of healthier eating habits, dietary treatment (subjects with serum cholesterol concentration 6.0-7.9 mmol/l), and dietary and drug treatment combined (serum cholesterol concentration greater than or equal to 8.0 mmol/l). MAIN OUTCOME MEASURE--Marginal cost effectiveness ratios--that is, the ratio of net treatment costs (cost of treatment minus savings in treatment costs for coronary heart disease) to life years gained and to quality of life years (QALYs) saved. RESULTS--The cost per life year gained over 20 years of a population based strategy was projected to be 12 pounds. For an individual strategy based on dietary treatment the cost was about 12,400 pounds per life year gained and 111,600 pounds if drugs were added for 50% of the subjects with serum cholesterol concentrations greater than or equal to 8.0 mmol/l. CONCLUSIONS--The results underline the importance of marginal cost effectiveness analyses for incremental programmes of health care. The calculations of QALYs, though speculative, indicate that individual intervention should be implemented cautiously and within more selected groups than currently recommended. Drugs should be reserved for subjects with genetic hypercholesterolaemia or who are otherwise at very high risk of arteriosclerotic disease. 
Congestive gastropathy and Helicobacter pylori: an endoscopic and morphometric study. Congestive gastropathy is a frequent cause of upper gastrointestinal haemorrhage in patients with portal hypertension. The pathogenesis is thought to involve venous congestion with gastric mucosal capillary dilatation. We studied the relation between gastric mucosal capillary dilatation, measured morphometrically, and endoscopic appearances in 74 patients with portal hypertension and 20 control subjects. We also investigated the frequency of gastric colonisation with Helicobacter pylori. Mucosal capillaries in patients were significantly dilated compared with control subjects (p less than 0.001) but the degree of dilatation was not related to the severity of the endoscopic appearances. H pylori was identified in 19 of 74 (26%) patients but was not related to the severity of the endoscopic appearances. These results suggest that other factors in addition to mucosal venous and capillary congestion are important in the pathogenesis of endoscopic congestive gastropathy and that gastric colonisation with H pylori is unlikely to be one of these factors. 
Carotid and coronary atherosclerosis. What are the connections? In recent years research has revealed an association between carotid atherosclerosis and coronary atherosclerosis that parallels the long-recognized association between clinically manifest cerebrovascular disease and clinically manifest coronary artery disease (CAD). Validation of B-mode ultrasonography as a method for quantitative imaging of the extracranial carotid arteries has made it possible to identify risk factors for extracranial carotid atherosclerosis and its progression and to test pharmacologic agents for their ability to retard that progression. Extent of atherosclerosis in the extracranial carotid arteries has been shown to be a risk factor or "marker" for symptomatic CAD. In addition, CAD has been identified as an important predictor of progression of extracranial carotid atherosclerosis. 
Neurologic complications of infective endocarditis. Neurologic syndromes often complicate the management of infective endocarditis (IE). We retrospectively reviewed 166 episodes of native valve endocarditis to assess the occurrence and implications of nonfocal encephalopathy, meningitis, salient headache, back pain, and brain abscess. Neurologic complications occurred in 35% (58/166) of patients: 41% (54/133) of mitral or aortic valve IE and 12% (4/33) of tricuspid valve IE. Of 133 cases of mitral or aortic valve IE, encephalopathy occurred in 14%, meningitis in 5%, and salient headache in 3%. All neurologic complications occurred more often with Staphylococcus aureus infection (67%) than with viridans streptococci (22%), including encephalopathy (22% versus 7%), meningitis (17% versus 0%), stroke (39% versus 16%), and death (39% versus 9%). Encephalopathy was associated with virulent organisms, increased patient age, and uncontrolled infection. Clinical, radiologic, and neuropathologic data all suggest that infective microemboli are often etiologic in IE-related encephalopathy. There were no macroscopic brain abscesses clinically identified. Meningitis occurred only with virulent organisms. While many clinical aspects of IE have changed in recent years, the frequency and gravity of neurologic complications have not. 
Cytogenetic abnormalities in uterine leiomyomata. Uterine leiomyomata are thought to be monoclonal tumors; however, the factors involved in the neoplastic proliferation of uterine leiomyomata are unknown. The purpose of the present study was to characterize uterine leiomyomata using cytogenetic techniques. Thirteen leiomyoma specimens were obtained by hysterectomy or myomectomy. Short-term cultures were successfully established for all specimens, and metaphase spreads were prepared by conventional techniques. Clonal chromosome rearrangements were detected in seven leiomyoma specimens (54%). These rearrangements involved chromosome bands 12q14-15 in five specimens, including three tumors with a specific translocation, t(12;14)(q14-15;q23-24). Chromosome rearrangements involving chromosome band 7q22 were identified in two specimens. A normal 46,XX karyotype was observed in six specimens. Myometrial specimens from two patients with abnormal leiomyoma karyotypes were normal cytogenetically. These results suggest that spontaneous chromosome rearrangements may be responsible for the initiation and proliferation of leiomyoma growth. 
Composite tissue transfer in limb-salvage surgery. After extensive resection due to extremity sarcoma, the inability to cover the defect for satisfactory healing and limb function has been an indication for amputation rather than limb salvage. We report herein our experience with seven limb-salvage cases in which we closed difficult and complex defects with composite tissue transfers utilizing microvascular techniques. Free-flap transfers were used to cover soft-tissue defects after extensive resection of primary and locally recurrent tumor and to manage radiation-induced complications. The grafts healed well when infected irradiated tissue was covered, and the grafts tolerated postoperative irradiation. Composite tissue transfer also provided soft-tissue coverage around distal joints that would not have been adequately protected with a skin graft. Complications were minimal, and all patients maintained good extremity function. No patient who underwent composite tissue transfer has had a local recurrence. A free-flap composite tissue transfer can extend the indications for limb-salvage surgery and offers an alternative to amputation in selected patients. 
Nitroprusside in preeclampsia. Circulatory distress and paradoxical bradycardia. In severe preeclampsia, short-term peripartum management of hypertension with hydralazine is complicated by relatively prolonged hypotensive episodes, resulting in fetal distress. We hypothesized that nitroprusside's rapid onset and brief antihypertensive action would permit more controlled blood pressure reduction. Nitroprusside was infused into 10 invasively monitored subjects until mean arterial pressure either 1) was gradually reduced 10-20% or 2) fell abruptly. Subjects fell into two groups, defined by whether the hypotensive effect of nitroprusside was accompanied by a fall in heart rate (group A, n = 8) or a rise (group B, n = 2). Group B showed the expected sinoaortic baroreceptor reflex elevations in heart rate (+17 +/- 6 beats/min) in response to moderate falls in mean arterial pressure (-32 +/- 9 mm Hg) elicited by moderate doses (1.03 +/- 0.23 micrograms/kg/min). However in group A, steep reductions in mean arterial pressure (-75 +/- 22 mm Hg, p less than 0.0001), significantly greater than in group B (p less than 0.05), occurred at much lower doses (0.35 +/- 0.23 micrograms/kg/min; p less than 0.05) and were accompanied by falls in heart rate (-21 +/- 7 beats/min). The apparently paradoxical falls in heart rate and extreme hypotensive responses in group A indicate severe circulatory compromise, corresponding to the cardiac and vasomotor depression that characterizes severe hemorrhage and other forms of acute/severe hypovolemic hypotension. This hemodynamic pattern represents a cardiopulmonary baroreceptor reflex presumably related to the Bezold-Jarisch reflex. The appearance of this pattern in the present study probably reflects the imposition of nitroprusside's prominent venous dilator action on the relatively reduced blood volume that generally characterizes severe preeclampsia. 
Captopril protects against myocardial injury induced by magnesium deficiency. We have previously reported that antioxidant drug intervention protects against magnesium deficiency-induced myocardial lesions. In the present study, Golden Syrian male hamsters were fed either a magnesium-deficient diet or a magnesium-supplemented diet. Animals from each group received sulfhydryl-containing angiotensin converting enzyme inhibitors: captopril, epi-captopril (a stereoisomer of captopril), and zofenopril* (arginine blend of zofenopril containing a free SH group); another group of animals received the non-sulfhydryl-containing angiotensin converting enzyme inhibitor enalaprilat. The animals were killed after 14 days, and their hearts were isolated for morphological and morphometric analyses. Hematoxylin and eosin-stained sections were examined by a computer image analysis system for a morphometric determination of the severity of myocardial injury. Captopril reduced both the density of lesions, from 0.32 to 0.08 lesions/(mm2) (p less than 0.01), and the area fraction of lesions, from 7.42 x 10(-4) to 2.03 x 10(-4) lesion area/(mm2) (p less than 0.01), as well as the degree of inflammatory infiltration around the blood vessels. Epi-captopril and zofenopril* were virtually equipotent to captopril, but enalaprilat afforded only slight (nonsignificant) protection. These results indicate that a significant component of the protective effect of captopril in this model was attributable to its sulfhydryl moiety, rather than solely due to the inhibition of the angiotensin converting enzyme. These data further support our previous findings of possible free radical participation in cardiomyopathy due to magnesium deficiency. 
A prospective randomized trial of adjuvant chemotherapy with bolus versus continuous infusion of doxorubicin in patients with high-grade extremity soft tissue sarcoma and an analysis of prognostic factors. A prospective randomized trial was conducted to compare the cardiotoxic and therapeutic effects of doxorubicin (60 mg/m2 every 3 to 4 weeks) administered by bolus or 72-hour continuous infusion as adjuvant chemotherapy in 82 eligible patients after resection of high-grade soft tissue sarcoma of the extremity or superficial trunk. Cardiac toxicity, defined as a 10% or greater decrease in left ventricular ejection fraction as assessed by radionuclide cineangiography, was evaluated in 69 patients. Cardiotoxicity was seen in 61% of patients in the bolus treatment arm with the median doxorubicin dose of 420 mg/m2. Among patients who received continuous infusion, 42% had cardiotoxicity with a median dose of 540 mg/m2. The rate of cardiotoxicity as a function of the cumulative dose of doxorubicin was significantly higher in the bolus treatment arm (P = 0.0017). Two patients in each group had clinical congestive heart failure, with one cardiac death occurring in each. There was a trend toward a lower rate of metastasis (P = 0.19) and a significantly lower rate of death of disease (P = 0.036) for patients treated with the bolus dose. Cox model analysis identified three unfavorable characteristics for the rate of developing a distant metastasis: blood transfusion within 24 hours of operation (P less than 0.00001), tumor deep to the fascia and 5 cm or more in size (P = 0.0043), and a histologic subtype other than liposarcoma (P = 0.0002). The unfavorable effect of continuous infusion was not selected in the model (P = 0.16). Adjuvant chemotherapy for patients with soft tissue sarcoma is investigational. Furthermore, the impact of perioperative blood transfusion merits further study. 
Influence of angiotensin converting enzyme inhibition on pump function and cardiac contractility in patients with chronic congestive heart failure. Eleven patients with coronary artery disease and chronic heart failure were studied before and three months after the angiotensin converting enzyme inhibitor enalapril was added to their frusemide medication. The following were measured: left ventricular pressure and volume with transient occlusion of the inferior vena cava, radionuclide angiography, and hormone concentrations in plasma. As in other reported studies, the clinical condition of the patients improved and their exercise tolerance increased moderately. Addition of enalapril reduced end diastolic and systolic pressure, reduced ventricular volume, and concomitantly increased the ejection fraction. The end systolic pressure-volume relation shifted to the left as it did in a similar animal study. In the animal study unloading by a vasodilator did not induce a leftward shift, so it can be inferred that in the present study unloading combined with a decrease in the angiotensin concentration was instrumental in remodelling the heart. Though unloading was expected to have a beneficial effect on the oxygen supply/demand ratio of the heart, the patients still showed the same drop in the ejection fraction during exercise as they did before treatment with enalapril, and early diastolic filling did not improve. Normally, regression of cardiac dilatation is only found if pump function improves; the present study showed that unloading in combination with angiotensin converting enzyme inhibition reshapes the ventricle without improving intrinsic pump function. 
Feeding regimens after pyloromyotomy. In a prospective randomized study three different feeding regimens after operation were compared in 74 babies with infantile hypertrophic pyloric stenosis: gradual regarding of feeds over 48 h (regimen 1), rapid regarding of feeds over 16 h (regimen 2), and initial starvation followed by full normal feeds at 24 h (regimen 3). No significant difference between the treatment groups was found either in episodes of vomiting after operation (regimen 1, 2.9 episodes in 21 patients; regimen 2, 3.6 episodes in 28 patients; regimen 3, 3.6 episodes in 25 patients) or in the mean duration of postoperative hospital stay (regimen 1, 59.3 h; regimen 2, 47.8 h; regimen 3, 56.7 h). We conclude that vomiting following pyloromyotomy is self-limiting and independent of the timetable or composition of the postoperative dietary regimen. 
Emergency treatment of headache. Headache is a frequent presenting complaint in the emergency department. Once a diagnosis is established, and significant organic disease can be ruled out, relief of pain must be addressed. Referral for follow-up care and narcotic habituation is a recurrent problem for the emergency physician. This article discusses the differential diagnosis of headache, evaluation of the emergency room patient, and treatment of the patient with headache. 
Neutrophils express the high affinity receptor for IgG (Fc gamma RI, CD64) after in vivo application of recombinant human granulocyte colony-stimulating factor. Fc receptors are important effector molecules of neutrophilic granulocytes (polymorphonuclear neutrophils [PMN]), connecting phagocytic cells and the specific immune response. Neutrophils from healthy donors express the low-affinity receptors for IgG Fc gamma RII (CD32) and Fc gamma RIII (CD16), but not the high-affinity receptor Fc gamma RI (CD64). The latter has been found on neutrophils from patients with certain bacterial infections and can be induced in vitro after incubation with interferon-gamma. We show here that neutrophils strongly express Fc gamma RI after in vivo application of recombinant human granulocyte colony-stimulating factor (rhG-CSF). PMN from patients receiving rhG-CSF displayed higher cytotoxicity against Daudi lymphoma cells in vitro compared with control patients and with healthy donors. Fab fragments against Fc gamma RII (monoclonal antibody [MoAb] IV.3) inhibited neutrophil-mediated cytotoxicity of healthy donors but not of patients during rhG-CSF therapy. Therefore, expression of Fc receptors by PMN was investigated by flow cytometry and the mean fluorescence intensity (MFI) was compared. After staining with MoAb 32.2 against Fc gamma RL, the median MFI of neutrophils from G-CSF patients (median, 4.78; range, 2.40 to 8.50; n = 5) was significantly higher (P = .002 and P = .001, respectively) than the median MFI of patients not receiving G-CSF (median, 1.23; range, 1.01 to 1.58; n = 6) and the median MFI of healthy donors (median, 1.04; range, 0.67 to 1.12; n = 6). Fc gamma RI disappeared after the discontinuing of the G-CSF injections, but was reinduced during the next treatment cycle with rhG-CSF. The high expression of Fc gamma RI during rhG-CSF therapy correlated with enhanced cytotoxicity. In vitro incubation with rhG-CSF also enhances cytotoxicity, but only minor increments in Fc gamma RI expression were observed. Thus, during in vivo application of rhG-CSF neutrophils acquire an additional potent receptor for mediating tumor cell killing in vitro by induction of the high-affinity receptor for IgG (Fc gamma RI, CD64). 
Management of intraoperative rupture of aneurysm without hypotension. A retrospective analysis was performed on all aneurysms operated on by one of us (SLG) from July 1980 to October 1988 to determine the factors that govern outcome from the intraoperative rupture of aneurysms. A total of 276 consecutive surgical procedures for 317 intracranial aneurysms produced 41 perioperative or intraoperative ruptures for analysis. Five cases were pre-exposure ruptures, 3 of which occurred during anesthetic induction. Four of these patients died, and 1 made a good recovery. Of the remaining 36 cases, outcome was analyzed in terms of the adjuncts used to deal with the intraoperative rupture. There was no statistically significant difference in outcome between those cases in which tamponade was used to control hemorrhage versus temporary clipping; however, those cases in which hypotension was used did less well than those in which it was not used. From October 1986 to October 1988, 108 operations for 132 aneurysms were performed without the use of induced hypotension. There were 16 intraoperative ruptures (14.8%). All 16 of these patients made a good recovery. In the group before 1986, of which there were 20 intraoperative ruptures (of 168 operations, 11.9%), 11 of those 20 patients suffered a permanent deficit or died. We conclude that hypotension may not be a necessary adjunct to the management of intraoperative rupture of aneurysms. 
Vaccination for prevention of CAPD associated staphylococcal infection: results of a prospective multicentre clinical trial. 124 stable CAPD patients from 8 Australian and 3 New Zealand centers were randomly assigned in a blinded fashion to one of two groups to study the effect of vaccination using commercial preparations consisting of a combined staphylococcus toxoid and whole killed staphylococci (SB) or normal saline solution (SS) on the incidence of peritonitis and exit site infection and S. aureus nasal carriage over a 12-month prospective period. In addition, levels of IgG, IgA, IgM, C3 and C4 were monitored during the trial period in serum and dialysate; serum levels of anti-alpha hemolysin and dialysate levels of fibronectin and specific antistaphylococcal antibodies were also measured. Over the period, treatment with SB or SS did not affect the incidence of peritonitis, catheter-related infection or S. aureus nasal carriage. However, vaccination with SB elicited a significant increase in the level of serum anti-alpha hemolysin throughout the 12 month duration of the study, although the level of increase was unrelated to the subsequent rate of peritonitis. Vaccination with SB but not SS elicited a significant increase in the dialysate level of specific antibodies against S. aureus. Serum levels of IgG, IgA, IgM, complement C3 and C4 were within the normal range in the CAPD patients studied and remained unaffected by vaccination with SB. In addition, dialysate levels of IgG, IgA, IgM, complement C3 and C4 were 50-100 times lower than corresponding serum levels and remained unaffected by vaccination. In summary, immunisation with an anti-staphylococcal agent was not successful in reducing peritonitis or exit site infection in CAPD patients. 
Transfusion-related chronic liver disease in sickle cell anemia. The medical records and liver biopsies of nine sickle cell patients with chronically elevated liver function tests were retrospectively reviewed to determine the etiology of chronic liver disease. There were eight women and one man with a mean age of 30 yr. All patients had hemoglobin SS. Eight patients were referred for elevated aminotransferases and one for an elevated alkaline phosphatase. Hemosiderosis was present in all of the biopsies. Two patients had cirrhosis. Chronic hepatitis was noted in two patients, and five patients had cholestasis. Two patients had serologic markers demonstrating HBV exposure but no patients were HBsAg positive. Erythrophagocytosis, sinusoidal dilatation, and Kupffer cell hyperplasia were present in all of the liver biopsies. Transfusion-related causes were the most common significant pathologic findings in our patients, and appeared to be the etiologies of chronic liver disease in sickle cell patients. 
The effects of L-dopa on excessive daytime sleepiness in narcolepsy. We examined the effects of L-dopa on the excessive daytime sleepiness of six narcoleptic patients while using a double-blind design and objective measurements of vigilance. The two treatment periods, L-dopa or placebo, lasted for 2 weeks each, separated by a 1-week washout period. In addition to the standard Multiple Sleep Latency Test (MSLT), two different tests assessed the daytime vigilance: the Analogue Vigilance Scale (AVS) and the Four Choice Reaction Time Test (FCRTT). L-dopa improved vigilance and performance as evaluated by the AVS and the FCRTT, while the capacity to fall asleep rapidly remained unchanged as evaluated by the MSLT. Results of the present study suggest that L-dopa is effective in improving the vigilance level of narcoleptic patients and raises the hypothesis that dopamine may play a role in the physiopathology of excessive daytime sleepiness of this condition. 
Extremely high maternal serum alpha-fetoprotein levels at second-trimester screening. Maternal serum alpha-fetoprotein (MSAFP) screening is widely used for the detection of open neural tube defects (NTDs) and a variety of other anomalies and complications. We examined the outcomes of 44 pregnancies with MSAFP elevations of 8 or more multiples of the median (MoM) from among 40,676 screened pregnancies. At the initial evaluation by ultrasound, 82% of the patients had at least one finding that may have accounted for the elevation. Approximately 45% of the fetuses had a major fetal anomaly, 25% died, 16% had an identifiable placental abnormality, and 5% had an underestimation of gestational age; 18% of the elevations remained unexplained after ultrasound. In follow-up of the pregnancies, all of those with an unexplained elevation after initial ultrasound had at least one obstetric complication or placental abnormality. The overall positive predictive value of an MSAFP value of 8 or more MoM for NTDs was 22.7%. The proportion of infants born alive in the overall group was low, with only 16 live births among 46 fetuses. The majority of the nonviable outcomes were associated with a fetus with a major anomaly that was terminated or died before 20 weeks. Of the live-born infants, 31% had a major anomaly, 19% had intrauterine growth retardation (IUGR) and an anomaly, 12.5% had IUGR without an anomaly, and 25% were preterm. Eighty-eight percent of those pregnancies with a live-born infant had at least one obstetric complication. Among pregnancies with MSAFP of 8 or more MoM, the majority are associated with large structural fetal anomalies or fetal death before 20 weeks. 
Bone marrow dosimetry in rats using direct tissue counting after injection of radio-iodinated intact monoclonal antibodies or F(ab')2 fragments. Normal rats were injected intravenously with 131I- and 125I-labeled intact murine and chimeric mouse-human monoclonal antibodies directed against carcinoembryonic antigen or with the corresponding F(ab')2 fragments. At different times after injection, individual animals were killed and radioactivity of blood and major organs, including bones and bone marrow, was determined. Ratios comparing radioactivity concentration in different tissues with that of bone marrow were calculated and found to remain stable during several effective half-lives of the antibodies. Mean bone marrow radioactivity was 35% (range, 29%-40%) of that of blood and 126% (range, 108%-147%) of that of liver after injection of intact Mabs or F(ab')2 fragments. In nude rats bearing human colon carcinoma xenografts producing carcinoembryonic antigen, relative bone marrow radioactivity was slightly lower than that in normal rats. 
A comparative trial of the reactogenicity and immunogenicity of Takeda acellular pertussis vaccine combined with tetanus and diphtheria toxoids. Outcome in 3- to 8-month-old infants, 9- to 23-month-old infants and children, and 24- to 30-month-old children. The reactogenicity and immunogenicity of the Takeda acellular pertussis vaccine combined with tetanus and diphtheria toxoids were compared in 139 infants aged 3 to 8 months, 60 infants and children aged 9 to 23 months, and 99 children aged 24 to 30 months. Good antibody responses to pertussis toxin (PT), filamentous hemagglutinin (FHA), and agglutinogens occurred in all age groups after both the third and fourth doses. After the fourth (booster) dose, the mean antibody values in initially seronegative infants vaccinated at 3 to 8 months of age were as follows: anti-PT, 67.8 enzyme-linked immunosorbent assay units (EU) per milliliter; anti-FHA, 149.5 EU/mL; the agglutinin titer was 125.6. The values in initially seronegative children vaccinated at 24 to 30 months of age were as follows: anti-PT, 92.9 EU/mL; anti-FHA, 251.7 EU/mL; the agglutinin titer was 275.8. Reactions following immunization were minimal. Except for drowsiness after the first dose in infants, there were no clinically significant differences in reactions between infants and older children. The findings in this study coupled with the recent demonstration of efficacy of this vaccine in 2-year-old children supports the recent Japanese recommendation to lower the age of immunization with acellular pertussis vaccine combined with tetanus and diphtheria toxoids to 3 months. 
Interleukin-2 induces early multisystem organ edema mediated by neutrophils. Interleukin-2 (IL-2), an agent known to activate neutrophils (PMN) with thromboxane (Tx)B2 release, produces pulmonary edema within 6 hours of intravenous infusion. This study tests the role of PMN in mediating the edema. Anesthetized rats received 10(6)U recombinant human IL-2 (n = 15) or vehicle (n = 14) as a constant intravenous infusion during a period of 1 hour. At this time there was leukopenia 3.63 +/- 0.43 (x10(3)/mm3) relative to vehicle-infused control rats 6.12 +/- 0.86 and a decline in PMN, 2.19 +/- 0.14 relative to control value of 3.33 +/- 0.05 (both p less than 0.05). After 6 hours edema, as measured by increase in the wet to dry weight (W/d) ratio, was present in the lungs (4.93 +/- 0.20 relative to control 4.06 +/- 0.10), heart (4.09 +/- 0.11 versus 3.76 +/- 0.08), liver (3.50 +/- 0.10 versus 3.18 +/- 0.10), and kidney (4.25 +/- 0.07 versus 4.00 +/- 0.07) (all p less than 0.05). There was increased lung permeability demonstrated by bronchoalveolar lavage fluid protein concentration of 1970 +/- 210 micrograms/mL relative to control 460 +/- 90 micrograms/mL (p less than 0.05). Interleukin-2 resulted in lung PMN sequestration of 53 +/- 7 PMN/10 high-power fields (HPF) relative to 23 +/- 2 PMN/10 HPF in controls (p less than 0.05) and increased plasma TxB2 levels to 1290 +/- 245 pg/mL relative to control 481 +/- 93 pg/mL (p less than 0.05). Pretreatment of other rats (n = 8) with selective anti-rat neutrophil antiserum 18 hours before the experiment led to a peripheral PMN count 10% of baseline and prevented edema in the lungs (W/d ratio 4.20 +/- 0.16) and heart (3.67 +/- 0.07) (both p less than 0.05) but not liver or kidney. Protein in lung lavage was reduced to 760 +/- 220 micrograms/mL (p less than 0.05). The protection afforded by leukopenia was associated with lack of PMN sequestration and prevention of the increase in plasma Tx levels (484 +/- 120 pg/mL, p less than 0.05). These data indicate that the rapid induction of lung and heart edema with a 1-hour infusion of IL-2 in the rat is mediated, in large part, by activated PMNs. 
Prevalences of diabetes and cardiovascular disease risk factors in Hindu Indian subcommunities in Tanzania. OBJECTIVES--To seek differences in the prevalence of diabetes mellitus and other coronary heart disease risk factors, and to identify factors associated with these differences within a Hindu Indian community. DESIGN--Population based cross sectional survey. SETTING--Dar-es-Salaam, Tanzania. SUBJECTS--Of 20 Hindu subcommunities categorised by caste in Dar-es-Salaam, seven were randomly selected. 1147 (76.7%) of 1495 subjects aged 15 or over participated. MAIN OUTCOME MEASURES--Blood glucose concentrations (fasting and two hours after oral glucose loading), serum total cholesterol and serum triglyceride concentrations, blood pressure, and height and weight. RESULTS--The subcommunities differed substantially in socioeconomic characteristics and lifestyle. Overall, 9.8% of subjects (109/1113) had diabetes, 17.0% (189/1113) impaired glucose tolerance, 14.5% (166/1143) hypertension, and 13.3% (151/1138) were obese. The mean fasting blood glucose concentration was 4.9 mmol/l, the blood glucose concentration two hours after oral loading (75 g) 6.0 mmol/l, the total cholesterol concentration 4.9 mmol/l, the serum triglyceride concentration 1.4 mmol/l, and body mass index (weight/height: kg/m2) 24.3. Systolic and diastolic blood pressures were 121 and 77 mm Hg respectively. There were important intercommunity differences even after standardisation for age, sex, and body mass index--for example, in mean fasting blood glucose concentration (range 4.5 (Jains) to 5.9 mmol/l (Patels)), serum total cholesterol concentration (range 4.5 (Jains) to 6.2 mmol/l (Suthars)), systolic blood pressure (range 110 (Limbachias) to 127 mm Hg (Bhatias)), and prevalences of diabetes (range 3.4% (3/87 Limbachias) to 18% (20/111 Navnats)) and hypertension (range 5.7% (5/87 Limbachias) to 19.4% (43/222 Bhatias). Variables which showed significant linear correlation with subcommunity variations were entered into a multiple regression model. Intercommunity variations persisted. The Limbachia and Jain communities had the lowest prevalence of and mean values for coronary heart disease risk factors and the Bhatia and Patel communities had the highest. CONCLUSIONS--In this series intercommunity variations in disease and risk factors might have been related to genetic, dietary, socioeconomic, and lifestyle differences but could not be explained by the characteristics studied. Studies of Indian subcommunities are warranted to confirm and extend these descriptive findings and explore the genetic basis of diabetes. Communities of Indian origin should not be perceived as homogeneous. 
Differing patterns of striatal 18F-dopa uptake in Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy. Using positron emission tomography (PET), we studied regional striatal 18F-dopa uptake in 16 patients with L-dopa-responsive Parkinson's disease (PD), 18 patients with multiple system atrophy, and 10 patients with progressive supranuclear palsy. Results were compared with those of 30 age-matched normal volunteers. The patients with PD showed significantly reduced mean uptake of 18F-dopa in the caudate and putamen compared to controls, but while function in the posterior part of the putamen was severely impaired (45% of normal), function in the anterior part of the putamen and in the caudate was relatively spared (62% and 84% of normal). Mean 18F-dopa uptake in the posterior putamen was depressed to similar levels in all patients. Unlike patients with PD, the patients with progressive supranuclear palsy showed equally severe impairment of mean 18F-dopa uptake in the anterior and posterior putamen. Caudate 18F-dopa uptake was also significantly lower in patients with progressive supranuclear palsy than in patients with PD, being depressed to the same level as that in the putamen. Mean 18F-dopa uptake values in the anterior putamen and caudate in patients with multiple system atrophy lay between PD and progressive supranuclear palsy levels. Locomotor disability of individual patients with PD or multiple system atrophy correlated with decline in striatal 18F-dopa uptake, but this was not the case for the patients with progressive supranuclear palsy. We conclude that patients with PD have selective nigral pathological features with relative preservation of the dopaminergic function in the anterior putamen and caudate, whereas there is progressively more extensive nigral involvement in multiple system atrophy and progressive supranuclear palsy. 
Common complaints with cardiac implications in children. Chest pain, palpitations, and dizziness are not infrequent complaints in the office of a primary care physician. Historical events and physical findings can lead to a more accurate determination of cardiac causes of these symptoms. Electrocardiogram and chest radiographs are two additional tests most often helpful in determining cardiac causes of symptoms. 
Telangiectatic osteogenic sarcoma of the extremities. Results in 17 patients treated with neoadjuvant chemotherapy. Seventeen patients with telangiectatic osteogenic sarcoma (TOS) of the extremities were treated with neoadjuvant chemotherapy, according to two different protocols. Preoperatively, the patients received high-dose methotrexate (HD-MTX) and cisplatinum (CPD) (HD-MTX/CPD) and doxorubicin. CPD was delivered intraarterially, the other drugs intravenously. Limb-salvage surgery was performed in 12 instances, and five patients were treated with amputation. Postoperative chemotherapy was tailored according to the grade of chemotherapy-induced necrosis. In 13 cases (86%), the resultant grade of necrosis was greater than 90% (good responders). The mean follow-up interval was 3.5 years with a range of 18 to 78 months. Fourteen patients (82%) remained continuously disease-free, while three patients developed lung metastases. Two of these died because of uncontrolled disease, whereas the third patient is alive and disease-free after metastasectomy. No local recurrences were observed. These results are better than those observed in 215 contemporary cases of conventional osteosarcoma treated with the same protocols. This study confirms that TOS is not a uniformly lethal tumor as suggested by prior reports. By employing neoadjuvant chemotherapy, a high percentage of patients with TOS can be cured, and in most of them, a limb-sparing surgery is possible and safe. 
Significance of prostatic intraepithelial neoplasia on prostate needle biopsy. Prostatic intraepithelial neoplasia (PIN) is a putative premalignant change in the human prostate. Previously, the spatial association of PIN with invasive carcinoma has been described in the study of total prostatectomies. PIN is frequently recognized in prostate needle biopsy specimens in which no carcinoma is apparent. To further define the potential significance of PIN, we performed repeat ultrasound-guided prostate needle biopsy in 21 men who had PIN identified on prostate biopsy performed because of an abnormal finding on digital rectal examination. Twelve patients (57%) had carcinoma identified on their second procedure including all who had intermediate- and high-grade PIN on the initial procedure. Prostate-specific antigen correlated with PIN grade and carcinoma on the secondary procedure, although this did not achieve statistical significance. Men with PIN on prostate needle biopsy should undergo repeat sampling to exclude missed carcinoma. 
Smoking and hypertension: risk factors for carotid stenosis. The prevalence of smoking, hypertension and diabetes mellitus was assessed in 221 patients suffering from internal carotid stenosis and compared with the prevalences in two sex- and age-matched control groups composed of subjects having normal Doppler findings and from non-neurological outpatients. Of the subjects with carotid stenosis 27.6% were hypertensive smokers in comparison with 9.5% and 17.2% in the two control groups. The difference of the stenosis cohort from the two control groups was significant (P less than 0.01 and P = 0.016 respectively). There was no statistically significant differences between the occurrence of diabetes and hypertension in non-smokers and patients who smoked. In 394 investigated patients suffering from carotid stenosis or occlusion an obstruction index, based on the Doppler shift frequency, was calculated. This index was lowest in the normotentive non-smokers. It was only insignificantly higher in the hypertensive non-smokers but significantly so in the normotensive smokers. The index was highest in the hypertensive non-smokers. It was concluded that cigarette smoking, especially if associated with hypertension, is a determinant risk factor for carotid stenosis and occlusion. 
Complications of endoscopic sphincterotomy. A prospective series with emphasis on the increased risk associated with sphincter of Oddi dysfunction and nondilated bile ducts. Mostly retrospective series with limited use of sphincter of Oddi manometry have indicated that early complications are more common when endoscopic sphincterotomy is performed for sphincter of Oddi dysfunction than for common duct stones. The current study was undertaken to prospectively evaluate the frequency and type of complications of endoscopic sphincterotomy performed for sphincter of Oddi dysfunction compared with endoscopic sphincterotomy performed for other conditions. Four hundred twenty-three patients underwent sphincterotomy for sphincter of Oddi dysfunction (166), common duct stone(s) (163), tumor (60), and miscellaneous reasons (34). Patients were observed in the hospital for at least 24 hours after the procedure, and 30-day follow-up data were obtained. The overall complication rate was 6.9%, but complications were more frequent when sphincterotomy was performed for sphincter of Oddi dysfunction than for all other indications (10.8% vs. 4.3%; P = 0.009). Precut sphincterotomy was more frequently required in the sphincter of Oddi dysfunction group (21.1% vs. 11.7%, P = 0.009) but was no more likely to result in a complication (6.2%) than standard sphincterotomy. The risk of a complication was considerable for a small-diameter common bile duct (less than or equal to 5 mm), particularly when sphincterotomy was performed for sphincter of Oddi dysfunction (37.5%). The overall 30-day mortality rate was 1.7%, but the procedure-related mortality rate was believed to be 0.2%. It is concluded that endoscopic sphincterotomy for sphincter of Oddi dysfunction is more hazardous than for other conditions, particularly when a small common bile duct is present. 
Intrahepatic cholangiocarcinoma in hepatolithiasis: A frequently overlooked disease. Five cases of intrahepatic cholangiocarcinoma were found among 101 cases of hepatolithiasis. There was no definite sign of cholangiocarcinoma in ERCP and image studies of four cases. The possibility of the existence of occult cholangiocarcinoma should be kept in mind, especially when unusual presentations, such as body weight loss, anemia, palpable abdominal mass, and intractable pain, appear. An intraoperative frozen-section examination should be considered under the following circumstances: (1) whitish nodular mass over liver, (2) mucinous substance within bile duct, and (3) enlarged, firm lymph nodes clustered along the hepatic arteries and/or celiac arteries. 
Injury to the pre-pubertal vas deferens. I. Histological analysis of pre-pubertal human vas. There is very little information in the literature on the development of the human vas deferens. Therefore, the age at which the pre- or para-pubertal vas deferens becomes large enough for a vasovasostomy to be technically feasible is unknown. To determine the age or degree of sexual maturity at which a microscopic vasovasostomy is technically feasible, we collected surgical or autopsy vasa from 34 young males over a three year period, and correlated vasal size to age and Tanner stage (degree of sexual maturity ranging from 1-childhood to 5-adult). The specimens were embedded and sectioned transversely in glycol methacrylate. Using image analysis, the total transverse area and diameter, and luminal area and diameter was determined for each specimen. Surprisingly, there was no change in vasal size from birth up through 11 years. From age 15 years and on, the vas was adult in size. The vas develops to adult size between Tanner stages 2 and 3. The average external and luminal diameters of pre-midpuberty specimens (Tanner stages 1 and 2) were 1.0 and 0.19 (mm.) and the diameters of post-midpuberty specimens were 2.1 and 0.43 (mm.), respectively. These results suggest that, in the event of a recognized iatrogenic injury to the vas deferens after midpuberty, a repair by a traditional microsurgical vasovasostomy is possible. If the vas is injured before midpuberty it may be technically difficult to repair by traditional microsurgical methods. 
Functional, biochemical, and histopathologic consequences of high-dose interleukin-2 administration in rats. A variety of side effects have been reported with the use of interleukin-2 alone or in combination with lymphokine-activated killer cells in patients with disseminated neoplasms. The present study was undertaken to determine the effects of high-dose interleukin-2 administration in normal rats. Sprague-Dawley rats were treated with intravenous recombinant interleukin-2 (900,000 IU/kg/day) for 9 consecutive days. Animals were placed in individual metabolic cages, and arterial blood pressure, food intake, body weight, and urine output were monitored. On day 10, animals were killed by exsanguination, various tissues were harvested, and a variety of hematologic and chemical assays were performed. The results were compared with those of placebo-injected normal control and pair-fed groups. The interleukin-2-treated group exhibited anorexia, weight loss, hypotension, anemia, leukocytosis, lymphocytosis, eosinophilia, hypercalcemia, azotemia, and a marked urinary concentration defect. Histologic examination of various tissues revealed widespread infiltration with mono-nuclear cells and eosinophils in most organs, especially in the lungs and liver of interleukin-2-treated animals. Other abnormalities included severe panlobular hepatitis, hepatocellular necrosis, and thymic involution. Renal involvement was mild and consisted of focal interstitial infiltration by mononuclear cells. According to these observations, administration of high-dose interleukin-2 in normal rats results in a score of significant functional, biochemical, and histologic abnormalities. 
Frequency of the hypercalcemia-leukocytosis syndrome in oral malignancies. There have been a number of reports over the last 15 years of patients with cancer who develop both leukocytosis and hypercalcemia, particularly in patients with cancers of the oral cavity. In this study, the authors report the frequency of hypercalcemia and leukocytosis in 225 patients with oral malignancies. Ten patients (4.4%) had hypercalcemia, 11 patients (4.9%) had leukocytosis, and five (2.2%) had both hypercalcemia and leukocytosis. The occurrence of these two distinct paraneoplastic syndromes in the same patients was greater than could have been expected from chance alone (chi-square = 45.8, P less than 0.0001). This study demonstrates that although hypercalcemia and leukocytosis are relatively uncommon in oral cancers, when they do occur they are frequently associated. To the knowledge of the authors, this is the first report in which the frequency of the association hypercalcemia and leukocytosis is studied in detail in large numbers of patients with oral cancer. 
Lack of correlation between P pulmonale and right atrial overload in chronic obstructive airways disease. The correlation between P pulmonale and right atrial overload in chronic lung disease was studied. Right atrial pressure, pulmonary artery pressure, and cardiac output were measured with a Swan-Ganz catheter in nine patients with chronic lung disease and P pulmonale on the electrocardiogram (P wave amplitude of greater than or equal to 2.5 mm (0.25 mV) in leads II, III, and a VF. The results were compared with those in six patients with an atrial septal defect (left to right shunt greater than or equal to 50%) and six patients with pulmonary hypertension (mean pressure greater than or equal to 30 mm Hg without left sided heart disease). Right atrial volume and wall thickness were measured in 10 cases of P pulmonale among 1000 necropsy cases and compared with 141 normal hearts from the same series. The patients with P pulmonale did not show a significant increase in right atrial or pulmonary artery pressures. None of the patients with an atrial septal defect or pulmonary hypertension had P pulmonale on the electrocardiogram. In the necropsy cases of P pulmonale mean (1 SD) in right atrial volume (32 (12) ml) and wall thickness (1.5 (0.7) mm) were not significantly increased (40 (14) ml and 1.4 (0.5) mm in the normal hearts). There was a significant inverse relation between the presence of P pulmonale and the cardiothoracic ratio. In all the patients with P pulmonale chest x ray showed a low cardiothoracic ratio, a considerably depressed diaphragm, and a pendulous heart. This study showed no correlation between P pulmonale and right atrial overload in chronic lung disease. 
Alteration of whole-body protein kinetics according to severity of surgical trauma in patients receiving total parenteral nutrition. This study was conducted to clarify the mechanisms of body nitrogen losses according to the severity of surgical trauma. Thirteen male patients who underwent operation for esophageal cancer (group E), and 11 men (who underwent gastric or colorectal surgeries (group GC) were studied. The measurement of whole-body protein turnover, synthesis, and breakdown were made preoperatively on the 3rd and 10th postoperative day with constant infusion of [15N]glycine during isocaloric and isonitrogenous total parenteral nutrition. Significant increases in the rates of whole-body protein turnover (flux) and breakdown were seen in group E on the 3rd postoperative day (p less than 0.01, p less than 0.01, respectively), whereas the increases were not significant in group GC. The rates of whole-body protein flux and breakdown were significantly greater in group E than group GC (p less than 0.01, p less than 0.01, respectively). The rate of protein synthesis significantly increased in group E (p less than 0.05), but did not alter or slightly decreased in group GC. The rates of whole-body protein flux and breakdown in group E were still significantly greater on the 10th postoperative day than preoperatively. It was concluded that unchanged or slightly decreased rates of whole-body protein synthesis with slightly increased breakdown were seen in the group of patients who underwent gastric or colorectal surgery, whereas synthesis increased significantly with a greater increase of breakdown in patients receiving severe surgical procedures, esophagectomy for esophageal cancer. 
Benefits of implantable defibrillators are overestimated by sudden death rates and better represented by the total arrhythmic death rate Benefits of the implantable defibrillator on survival were studied in 56 consecutive patients (concomitant coronary bypass or arrythmia surgery in 15) during an 8 year period between 1982 and 1990. During a follow-up period of 29 +/- 25 months, six patients had a sudden death and eight patients had a nonsudden cardiac death. Nonsudden cardiac deaths included three surgical deaths (death within 30 days after the surgery; two in patients without and one in a patient with concomitant cardiac surgery), one arrhythmia-related nonsudden death (death within 24 h after an arrhythmic event despite initial termination of the arrhythmia by the implantable defibrillators) and four nonarrhythmic cardiac deaths. The actuarial survival rate free of events at 1, 2 and 3 years was 96%, 96% and 92%, respectively, for sudden death, 91%, 91% and 87% for sudden death and surgical mortality and 89%, 89% and 85% for total arrhythmic death (sudden death, surgical mortality and arrhythmia-related nonsudden death). Thus, in patients treated with an implantable defibrillator, 1) the rate of sudden death is low (8% at 3 years); 2) 50% of nonsudden cardiac deaths are causally related to arrhythmia (surgical mortality or arrhythmia-related nonsudden death); 3) the total arrhythmic death rate is substantially higher than the sudden death rate; and 4) benefits of an implantable defibrillator are overestimated by reported sudden death and nonsudden cardiac death rates. The benefits may be better represented by the total arrhythmic death and nonarrhythmic cardiac death rates. 
Stroke from other etiologies masquerading as migraine-stroke. There has been a recent increase in the number of studies dealing with migraine-stroke. I describe five patients in whom migraine-stroke was the clinical diagnosis but in whom the subsequent clinical events or autopsy showed a different mechanism for the cerebral infarction. Three patients had arterial dissection (one proven at autopsy), one had marantic endocarditis that had been missed on two echocardiograms (proven at autopsy), and one had generalized atherosclerosis and diabetes. These patients demonstrate that important and different etiologies may produce what seems to be the migraine-stroke syndrome. The result may be failure to recognize specific therapeutic measures that could have vitally important benefit to the patient. 
Low peptic ulcer and high gastric cancer prevalence in a developing country with a high prevalence of infection by Helicobacter pylori. We compared the prevalence rates of peptic ulcer (duodenal and gastric) and gastric cancer in 1,796 dyspeptic Peruvian patients with those reported in 2,883 similar patients from developed countries. The prevalence of total peptic ulcer was significantly lower, and that of gastric cancer significantly higher, in the Peruvian patients. The prevalence of gastric ulcer was lower but not significantly so. We deduced that the significantly lower prevalence of total peptic ulcer was directly related to the low prevalence rate of duodenal ulcer. We hypothesize that the reason for these differences was probably a higher prevalence of Helicobacter pylori-associated chronic atrophic gastritis with hypochlorhydria in the Peruvian patients. Hypochlorhydria decreases the predisposition to peptic ulcer (especially duodenal ulcer), and chronic atrophic gastritis may predispose an individual to gastric cancer. 
Clinical implications of late proven patency after successful coronary angioplasty. BACKGROUND. The introduction of percutaneous transluminal coronary angioplasty (PTCA) has changed the pattern of intervention in coronary artery disease. However, the long-term results in patients undergoing successful, elective, native-vessel PTCA are not yet fully characterized. Because the healing and subsequent proliferative response after angioplasty are time related, it was the purpose of the present study to determine the long-term outcome in patients whose dilated arteries have been demonstrated to be patent 4-12 months after successful, uncomplicated PTCA. METHODS AND RESULTS. The patients were grouped on the basis of the 4-12 month catheterization into those whose vessels were angiographically "normal" or had luminal irregularities only at the PTCA sites (396 patients), those whose vessels also had luminal irregularities elsewhere with or without PTCA site luminal irregularities (680 patients), and those with significant obstructive disease (more than 50% diameter narrowing) at sites other than the PTCA sites (426 patients). Of 1,502 such patients, long-term follow-up was available in 1,491. At the time of the original angioplasty, the normal patients had a 1.8% incidence of multivessel disease; luminal irregularity patients, 9.4%; and obstructive disease patients, 58.7%. At angiographic restudy, 16.4% of the obstructive disease patients continued to have multivessel disease. The patients were followed for the events of death, myocardial infarction, coronary surgery, and repeat PTCA. The 6-year survival rate was 95%; cardiac survival, 96%; and freedom from all events, 65%. The strongest correlate of events during follow-up was the angiographic status of the undilated segments. At 6 years, freedom from cardiac events was noted in 77% of the normal group, 61% of the luminal irregularity group, and 55% of the obstructive disease group. Diabetes and hypertension were also independent correlates of events. CONCLUSIONS. Results from the present study show that associated disease in undilated segments is a strong predictor of late events in patients after successful, uncomplicated, reatenosis-free PTCA. However, the need for further revascularization was frequent even in patients without obstructive disease. Completeness of revascularization is appropriate when possible, and limiting progression of coronary disease at sites remote from those dilated should improve on these late results. 
Pressure therapy for the control of hypertrophic scar formation after burn injury. A history and review. Devastating functional problems can result from the formation of hypertrophic scar tissue after burn injury. Although a patient with burns may have several medical problems to contend with because of the injury, most ongoing rehabilitation difficulties are a consequence of the continual wound contraction that occurs in immature burn scars. Treatment of hypertrophic burn scar consists of several surgical options and of pressure therapy, which traditionally involves wearing garments made from elasticized fabric. This article reviews the treatment of hypertrophic scar tissue, with emphasis on its history and on nonsurgical methods of managing the burn scar. 
Repolarization inhomogeneities in ventricular myocardium change dynamically with abrupt cycle length shortening. BACKGROUND. In single heart cells, abrupt changes in stimulation rate elicit complex alterations in repolarization. The effects of rate change on dispersion of repolarization, however, have not been well characterized. METHODS AND RESULTS. To determine the effects of abrupt cycle length (CL) shortening on spatial inhomogeneity of repolarization in a syncytium of ventricular cells, 124 action potentials were simultaneously recorded from Langendorff-perfused guinea pig hearts using high-resolution optical mapping with voltage-sensitive dye. The distribution of ventricular action potential durations (APDs) mapped during each cardiac cycle was used to calculate mean APD and repolarization dispersion index (DI), defined as the variance of the distribution. After abruptly shortening CL from 500 to 300 msec, mean APD declined exponentially in normoxic controls (by 23 +/- 3 msec, p less than 0.0001). This response was characterized by beat-to-beat oscillations of APD that were synchronized at all ventricular sites. After 30 minutes of hypoxia, mean APD decreased from 175.0 +/- 13.3 to 76 +/- 25.7 msec. However, during hypoxia, abrupt CL shortening lowered mean APD by only an additional 6 +/- 6 msec, and APD oscillations were no longer synchronized throughout the ventricle. In controls, beat-to-beat DI decreased significantly (-51.0 +/- 6.8%, p less than 0.01) by the sixth post-CL shortening beat and then recovered (by 15-20 beats). In contrast, DI failed to decrease during hypoxia (+7.1 +/- 23%). Two mechanisms for the transient decline of DI in controls were identified: synchronous APD oscillations and transient diminution of the apical-to-basal ventricular APD gradient. CONCLUSIONS. These data demonstrate that inhomogeneity of ventricular repolarization, as measured by DI, changes dynamically with CL shortening. Furthermore, the hypoxic ventricle does not attenuate DI after abrupt CL shortening and thereby lacks a physiological response expected to diminish vulnerability to arrhythmias. 
Physical activity on the job and cancer in Missouri. We conducted a series of case-control studies to investigate the risks of 16 cancer types in relation to occupational physical activity. These studies were based on Missouri Cancer Registry data for 17,147 White male cancer patients registered between 1984 and 1989. Colon cancer risk was increased for both the moderate (odds ratio (OR) = 1.1; 95% confidence interval (CI) = 1.0, 1.3) and low (OR = 1.2; 95% CI = 1.0, 1.5) activity levels. Similar elevations were observed for prostate cancer at the moderate (OR = 1.1; 95% CI = 1.0, 1.3) and low (OR = 1.5; 95% CI = 1.2, 1.8) levels of activity, and for cancer of the testis at the low activity level (OR = 2.2; 95% CI = 1.3, 3.7). An opposite trend (p less than 0.01) was noted for lung cancer, which showed decreased risk at the moderate (OR = 0.9; 95% CI = 0.8, 1.0) and low (OR = 0.8; 95% CI = 0.6, 0.9) activity levels. These associations suggest that further study of the relationship between physical activity and site-specific cancer risk is warranted. 
Interaction between free radicals and excitatory amino acids in the formation of ischemic brain edema in rats. Both oxygen free radicals and excitatory amino acids have been implicated as important cellular toxins in ischemic brain. Recent in vitro studies suggest that there may be a mutual interaction between these two mediators. We explored the relation between oxygen free radicals and excitatory amino acids in the development of ischemic brain edema in vivo. Male Sprague-Dawley rats were treated with the free radical scavenger dimethylthiourea 1 hour before ischemia or with the excitotoxin antagonist MK-801 30 minutes before ischemia produced by occlusion of the middle cerebral artery. Groups of seven or eight animals were treated with vehicle, low-dose (375 mg/kg) dimethylthiourea, high-dose (750 mg/kg) dimethylthiourea, low-dose (0.5 mg/kg) MK-801, high-dose (2.0 mg/kg) MK-801, or both high-dose dimethylthiourea and low-dose MK-801. After 4 hours of ischemia, brain water content was determined. In eight vehicle-treated controls, mean +/- SEM water content of tissue in the center of the ischemic zone was 83.29 +/- 0.18%. A significant reduction of brain edema was observed in all drug-treated groups: for example, 50.2% (p less than 0.001) in the high-dose dimethylthiourea group, 53.7% (p less than 0.001) in the low-dose MK-801 group, and 66.4% (p less than 0.001) in the combined dimethylthiourea and MK-801 group. Combined treatment with dimethylthiourea and MK-801 provided no significant additive effect over that resulting from treatment with MK-801 alone. 
Heart transplantation in children: an international survey. A survey of cardiac transplantation in children provided data from 381 transplantations in 362 patients from 32 centers in the United States and ten international centers. The number of transplantations continues to increase, in part because of transplantations in infants with hypoplastic left heart syndrome and patients with congenital defects. The immunosuppression regimens were more uniform than in the 1985 survey, and triple therapy was most common. Actuarial survival rates were 85% at 1 month, 72% at 1 year, 64% at 3 years, and 60% at 5 years. However, these improved rates are still not equal to the survival of the overall cardiac transplant population, in part because of lower survival rates in neonates. Ventricular dysfunction and rejection, rather than infection, were the leading causes of death. Rejection and infection were the most frequent complications. Also common were hypertension (39%) and seizures (25%), whereas coronary artery disease (8%) was unusual. Functional results were excellent in 85%, and only 7% were disabled. Questions concerning growth rates and many other aspects cannot yet be answered. However, it is apparent that cardiac transplantation in the pediatric population is a very worthwhile endeavor. 
A mathematical computer stimulation model for the development of colonic polyps and colon cancer. Currently known information about the development and progression of colon polyps and cancer is summarized and organized into a mathematical computer simulation model that successfully predicts the natural history of colon polyp and cancer development for an average patient with (1) familial polyposis coli (2) genetic susceptibility as measured by a positive family history, and (3) negative family history with a high fat diet. The mathematical model uses four distinct types of cells (normal, transformed, polypoid, and cancerous) and two kinetic processes (mutation and promotion). Arachidonic acid metabolites play a role in the model in the promotion of cancer from polyps, and account for that promotion through: (1) their effect on encouraging more polypoid cells in mitosis to move toward cancer; and (2) their immunosuppressive effect over time. The model also shows that one defect in allowing more cells to mutate to the transformed state is sufficient to account for the chain of events leading to the clinical sequelae of familial polyposis coli. A second genetic effect at another point in the process is unnecessary. The mechanism of action of Sulindac on colon polyps is explained by the model through inhibition of production of arachidonic acid metabolites, most notably prostaglandin E. 
Antibodies against acetaldehyde-modified epitopes: presence in alcoholic, non-alcoholic liver disease and control subjects. Several studies have recently shown the presence of antibodies against acetaldehyde-modifications in the sera of alcoholic patients. To assess the specificity of this immune response, plasma immunoreactivity with proteins modified in vitro by acetaldehyde was measured using an enzyme-linked immunosorbent assay in 97 alcoholic patients with varying degrees of alcoholic liver disease, in 35 patients with non-alcoholic liver diseases and in 33 control subjects who were social drinkers. All three groups showed some response against acetaldehyde-modified epitopes. The highest plasma reactivities were found in alcoholics, especially those with steatosis and alcoholic hepatitis. Plasma from patients with non-alcoholic liver disease and control subjects also reacted with the acetaldehyde conjugates, but to a lesser extent than plasma from alcoholics. The reliability of these antibodies as markers of either alcohol abuse or alcoholic liver disease therefore appears to be low. However, further studies using more precisely modified proteins or elucidation of the classes of immunoglobulin involved in the immune response against the modified proteins may give clearer differences between the three groups. 
Activation of cardiac sympathetic afferents during coronary occlusion. Evidence for reflex activation of sympathetic nervous system during transmural myocardial ischemia in the dog. BACKGROUND. Left ventricular sympathetic afferent nerves are located mainly in superficial epicardial layers. Reflex excitatory responses mediated by sympathetic afferent nerves have been observed during myocardial ischemia in cats and humans but not in dogs. Previous canine studies have induced ischemia by occlusion of a coronary artery. Extensive collateral circulation in the canine heart may limit ischemia of epicardial layers during simple coronary occlusion, resulting in little stimulation of sympathetic afferent nerves and minimal reflex excitatory responses. METHODS AND RESULTS. In anesthetized dogs with sinoaortic and vagal deafferentation, we determined whether reflex sympathoexcitatory responses mediated by sympathetic afferents occurred during transmural myocardial ischemia. Reflex sympathoexcitation was quantitated by direct recording from either efferent renal (n = 20) or cardiac (n = 5) sympathetic nerves. Responses of arterial pressure and efferent sympathetic nerve activity were measured during simple occlusion of the anterior descending artery (LAD alone) and during LAD occlusion with a circumflex stenosis (LAD + CIRC). This circumflex stenosis was adjusted to abolish coronary vasodilator reserve without reducing basal flow. We observed significantly greater reflex increases in renal (32 +/- 5%) and cardiac (58 +/- 15%) nerve activity during LAD + CIRC than during LAD alone (14 +/- 6% and 8 +/- 7%, respectively). Reflex changes in renal nerve activity during LAD + CIRC were abolished by interruption of cardiac sympathetic afferent pathways (n = 5). In eight experiments, myocardial blood flow was measured during the two coronary occlusions. These experiments confirmed that LAD + CIRC elicited more transmural ischemia in the LAD distribution than did LAD alone. However, these experiments also revealed that LAD + CIRC elicited endocardial ischemia in the circumflex distribution. In five additional experiments, regional sympathetic deafferentation of the posterior left ventricle by epicardial application of 88% phenol along the atrioventricular groove had no significant effect on renal nerve responses to LAD + CIRC (36 +/- 5% increase before phenol versus 31 +/- 3% increase after phenol). These results indicate that endocardial ischemia in the circumflex distribution did not contribute to the reflex increases in nerve activity that were noted during LAD + CIRC. CONCLUSIONS. Reflex sympathoexcitation mediated by cardiac sympathetic afferents can be elicited in dogs. However, these responses are significant only during ischemia that is transmural and involves the superficial epicardial layers of the left ventricle. 
DNA sequence analysis and restriction fragment length polymorphism (RFLP) typing of the HLA-DQw2 alleles associated with dermatitis herpetiformis. Dermatitis herpetiformis (DH) is a blistering autoimmune skin disease associated with a 95-100% incidence of the HLA class II antigen HLA-DQw2. Although the precise role of this antigen in the pathogenesis of DH is unclear, one theory proposes that patients with DH possess a molecularly unique subtype of the HLA-DQw2 antigen that causes immune abnormalities eventuating in the clinical manifestations of DH. To test this hypothesis, we performed DNA sequence analysis on the highly polymorphic HLA-DQB1 and HLA-DQA1 loci of eight patients with dermatitis herpetiformis. All DQB1 alleles sequenced were identical to the previously described HLA-DQB*0201 allele from HLA-DQw2 normal subjects. In addition, DQA1 alleles sequenced were identical to those alleles previously associated with HLA-DQw2 (DQA*0201, DQA*0501). These data document that although HLA-DQw2 appears to be a necessary element in the pathogenesis of DH, the development of DH is not dependent on the presence of a unique HLA-DQw2 antigen. HLA-DQ allelic typing by restriction fragment length polymorphism analysis of PCR-amplified HLA-DQA1 and HLA-DQB1 fragments was also performed in ten patients with DH to determine the allelic distribution among both HLA-DR3 (eight patients) and non-DR3 (two patients) DH patients. At the HLA-DQ beta chain locus, all patients possessed the DQB1*0201 allele. At the HLA-DQ alpha chain locus, all HLA-DR3 patients and one non-DR3 patient displayed a pattern consistent with the DQA1*0501 allele, whereas one non-DR3 patient displayed a pattern consistent with the DQA1*0201 allele. These data document that patients with DH do not express a unique HLA-DQw2 heterodimer, that the HLA-DQw2 molecules present in patients with DH have no DNA sequence differences from those found in normal HLA-DQw2 subjects and therefore that susceptibility to DH is not due to a unique HLA-DQw2 molecule. 
Gallium-SPECT in the detection of prosthetic valve endocarditis and aortic ring abscess. A 52-yr-old man who had a bioprosthetic aortic valve developed Staphylococcus aureus bacteremia. Despite antibiotic therapy he had persistent pyrexia and developed new conduction system disturbances. Echocardiography did not demonstrate vegetations on the valve or an abscess, but gallium scintigraphy using SPECT clearly identified a focus of intense activity in the region of the aortic valve. The presence of valvular vegetations and a septal abscess was confirmed at autopsy. Gallium scintigraphy, using SPECT, provided a useful noninvasive method for the demonstration of endocarditis and the associated valve ring abscess. 
The pathophysiology of chronic relapsing experimental allergic encephalomyelitis in the Lewis rat. Electrophysiological studies were performed in Lewis rats with chronic relapsing experimental allergic encephalomyelitis (EAE) induced by inoculation with guinea-pig spinal cord and adjuvants and treatment with low dose cyclosporin A. During clinical episodes there was conduction failure in the central nervous system (CNS), namely the spinal cord dorsal columns, and in the afferent fibres in the peripheral nervous system (PNS). The following observations indicated that the conduction failure was mainly due to demyelination-induced conduction block: (1) rate-dependent conduction block in the CNS and PNS; (2) temporal dispersion due to slowing of PNS conduction; (3) restoration of PNS conduction by cooling; (4) restoration of CNS conduction by ouabain; (5) previously demonstrated histological evidence of primary demyelination in the dorsal columns, dorsal root ganglia and dorsal roots; and (6) the temporal association of restoration of conduction with remyelination. However, it is likely that CNS and PNS axonal degeneration, which occurs in this disease, also contributed to the conduction failure. In clinical remissions there was restoration of conduction in the CNS and PNS which can be explained by ensheathment/remyelination by oligodendrocytes and Schwann cells, respectively. In most rats during clinical episodes the cerebral somatosensory evoked potential was reduced in amplitude and prolonged in latency, which can be accounted for by demyelination and axonal degeneration in the CNS and PNS components of the afferent pathway. In 2 rats with episodes of EAE, however, this potential was markedly increased in amplitude, which might have been due to demyelination-induced conduction block of descending pathways that normally inhibit synaptic transmission in the afferent pathway. In well-established remission there was residual conduction failure in the CNS and PNS which can be mainly accounted for by axonal degeneration. 
Low-dose co-trimoxazole for prevention of Pneumocystis carinii pneumonia in human immunodeficiency virus disease The efficacy and tolerability of low, intermittent doses of co-trimoxazole (160 mg trimethoprim and 800 mg sulfamethoxazole given Monday, Wednesday, Friday) for prophylaxis against Pneumocystis carinii pneumonia (PCP) was assessed retrospectively in 116 patients with the acquired immunodeficiency syndrome (AIDS) and AIDS-related complex at high risk of PCP. 92% were receiving concomitant zidovudine. 71 with previous episode(s) of PCP were followed a mean of 18.5 months (range 3-42). 45 without past PCP but with depletion of CD4 cells to less than 200/microliters were observed for a mean of 24.2 months (range 9-40). PCP did not develop in any patient on co-trimoxazole. 33 (28%) had side-effects, mainly rash, pruritus, and nausea. 15 discontinued co-trimoxazole, but only 11 (9%), who withdrew in the first month, were clearly drug-intolerant. Thus, low-dose, thrice weekly co-trimoxazole completely prevents AIDS-associated PCP, is cost-effective, and well tolerated by more than 85% of patients. Controlled comparisons of this regimen with other prophylactic agents are warranted. 
Automated pupil perimetry. Pupil field mapping in patients and normal subjects. The authors developed an automated method of pupil perimetry by linking an infrared video pupillometer to a Humphrey Field Analyzer. Software was developed to automatically analyze the pupil responses to focal light stimuli and display the results graphically. All 76 locations of Humphrey program 30-2 could be tested twice within 5.5 minutes and the relative sensitivity of the field was determined by comparing the amplitude of pupil constriction or latency time at each stimulus location. The mean pupil responses within annular areas at 3 degrees, 9 degrees, 15 degrees, 21 degrees, and 27 degrees were shown to be linearly related to log stimulus intensity over a 15 dB range under low level mesopic conditions (3.15 asb bowl background). In normal subjects, the superior temporal quadrant usually had the greatest mean pupillomotor response and the inferior nasal quadrant had the least. Pupil responses in the temporal field were larger than corresponding locations in the nasal field. Patients with visual field defects who underwent testing by pupil perimetry showed pupillary deficits in the same location within the field, providing evidence that pupil perimetry may be a useful, objective means of assessing visual field function. 
Diltiazem-induced psychosis and a possible diltiazem-lithium interaction. Calcium channel blockers are being used increasingly for a variety of cardiovascular problems. Diltiazem hydrochloride, a benzothiazepine derivative, has been reported to have a low incidence of adverse side effects. We report a case of acute psychosis associated with the use of diltiazem in a patient receiving lithium carbonate therapy. Both diltiazem hydrochloride and lithium carbonate have calcium antagonist effects in the central nervous system, and we review their mechanisms of action. A possible synergistic drug interaction between diltiazem and lithium is reported. 
Effects of 30-h sleep loss on cardiorespiratory functions at rest and in exercise. The effects of 30-h sleep deprivation on cardiorespiratory function either at rest or in exercise were studied in 15 young healthy male volunteers. All subjects performed 1-min incremental exercise tests on a bicycle ergometer until exhaustion and endurance exercise tests at 3/4 of their maximal work rates. Arterialized venous blood samples were withdrawn at rest and during exercise tests to investigate the influence of sleep loss on blood gases. In addition, resting plasma catecholamine levels were also measured in ten subjects. The results showed that 1) resting heart rate, plasma catecholamine levels, and blood pH were decreased while minute ventilation (VI) and CO2 production (VCO2) were increased after 30 h of sleep loss (P less than 0.05), and 2) the maximal exercise performance was reduced by sleeplessness, as indicated by the decreases in the maximal heart rate, peak VI, peak VCO2, peak O2 consumption, and time to exhaustion (P less than 0.05). However, no significant changes in exercise endurance, arterialized venous pH, and PCO2 were found in exercise after sleep deprivation either. We therefore conclude that 30-h sleep loss alters cardiorespiratory function at rest and the ability to perform maximal exercise but not exercise endurance. 
Autoantigen recognition by thyroid-infiltrating T cells in Graves disease. Graves disease is a common form of human autoimmune thyroiditis. It shares many pathological features and HLA associations with other, less easily studied, organ-specific autoimmune conditions such as insulin-dependent diabetes mellitus, and hence it is also a useful model for understanding these other diseases. We have previously shown that thyroid-infiltrating T cells in Graves disease that have been recently activated in vivo specifically recognize autologous thyroid epithelial cells. However, the autoantigens involved were not defined. In this study, we have made use of antigen-independent T-cell cloning techniques to show that at least three different thyroid antigens, three different epitopes on a single antigen, and two HLA class II elements are involved in this recognition process in a single individual. This demonstrates that T cells that are present and activated at the site of a human autoimmune disease may show considerable heterogeneity in their recognition of autoantigen on the target tissue. This contrasts with the limited heterogeneity recently reported in some animal models and has potentially important implications for both our understanding of the autoimmune process in humans and the design of immunotherapies to reverse it. 
Solitary expression of CD7 among T-cell antigens in acute myeloid leukemia: identification of a group of patients with similar T-cell receptor beta and delta rearrangements and course of disease suggestive of poor prognosis. In a series of 100 acute myeloid leukemia (AML) patients defined by cytochemistry and immunophenotyping, 20 expressed T-lymphocyte associated antigens on the surface of their blasts. While 15 expressed two or more T-cell antigens, five were found to express only CD7. All patients belonged to the French-American-British type M4, and four were under the age of 40. Despite intensive chemotherapy, four never obtained a complete remission and the fifth died of relapse after an allogenic bone marrow transplantation. While 12 randomly selected T-cell antigen negative AML patients showed only few rearrangements in Ig- or T-cell receptor (TCR) genes, such genetic alterations were demonstrated in four of five patients for the TCR delta gene and in all patients for the TCR beta gene. Interestingly, DNA fragments of similar size were demonstrated in three of five patients for both the beta and delta genes. These data suggest that the solitary presence of CD7 among T-cell antigens in otherwise clearcut AML cases identifies a group of patients with similarities in antigen receptor gene configuration as well as outcome. 
Smoking-attributable mortality and years of potential life lost--United States, 1988. Smoking is a leading cause of diseases associated with premature mortality in the United States; in 1985, these diseases accounted for an estimated 390,000 premature deaths. In this report, mortality data and estimates of smoking prevalence for 1988 are used to calculate smoking-attributable mortality (SAM), years of potential life lost (YPLL), and age-adjusted SAM and YPLL rates for the United States. Calculations were performed using Smoking-Attributable Mortality, Morbidity, and Economic Cost (SAMMEC II) software, which includes relative risk estimates for 22 adult (i.e., greater than or equal to 35 years of age) smoking-related diseases and relative risk estimates for four perinatal (i.e., less than 1 year of age) conditions. Age-, sex-, and race-specific mortality data for 1988 were obtained from CDC's National Center for Health Statistics. Data on burn deaths caused by cigarettes were obtained from the Federal Emergency Management Agency. The estimated number of deaths among nonsmokers from lung cancer attributable to passive smoking was obtained from a report of the National Academy of Sciences. Age-, sex-, and race-specific current and former smoking prevalence rates in 1988 for adults aged greater than or equal to 35 years and for women aged 18-44 years were estimated by linear extrapolation using National Health Interview Survey data for 1974-1987. 
Tumor necrosis factor receptors in lymphoid tissues and lymphomas. Source and site of action of tumor necrosis factor alpha. Tumor necrosis factor alpha (TNF alpha), which is produced by germinal center dendritic reticulum cells (DRC) in lymphoid tissue, plays a regulatory role in a local immune response. However no information is available on the nature and location of cells responding to this cytokine. Thus TNF receptor distribution was investigated in situ by immunohistochemistry using monoclonal antibodies directed against the p75 and p55 receptor proteins. Receptor expression was unique and restricted to the lymphoreticular tissue. The p75 receptor was found on activated lymphocytes and interdigitating reticulum cells of the T-cell area, whereas the p55 receptor was confined to the germinal center DRCs, which are the main site of TNF alpha production. The two receptor proteins were expressed on distinct cell populations of the lymphoid system and no coexpression was observed. Preliminary results indicate that TNF receptor (TNFR) expression is regulated; Upregulation of TNFR proteins was found in reactive hyperplasia together with increased TNF alpha expression. In lymphoproliferative disorders, expression of the p75 receptor and TNF alpha was found mainly in high-grade malignant non-Hodgkin lymphomas. In summary, TNF alpha produced by germinal center DRCs might regulate an in vivo immune response through autocrine and paracrine pathways. Thus TNF alpha might signal, through the distinct TNFR proteins, the p55 and p75 receptor, which are expressed on different cell types in lymphoid tissue. 
Diagnosis and localization of laceration of the thoracic duct: usefulness of lymphangiography and CT. The usefulness of lymphangiography and CT in the diagnosis and localization of laceration of the thoracic duct was evaluated in 12 patients with chylothorax or chylous ascites after surgery. Bipedal lymphangiography was performed in all 12 patients. The last four patients studied also had CT after lymphangiography. Seven patients had abnormal findings on lymphangiograms; five with leaks from the thoracic duct, one with a lymphocele in a nephrectomy bed, and one with obstructed intestinal lymphatic vessels after thoracotomy. Five patients had no evidence of lymphatic leakage. CT in one patient with evidence of a leak on lymphangiography showed extravasation of contrast medium into the mediastinum and pleural space. CT in three patients with no abnormalities on lymphangiography also showed no abnormalities. Four of the five thoracic duct lacerations and the lymphocele were confirmed surgically. The diagnosis of obstructed intestinal lymphatic vessels was supported clinically. Four of the five patients with normal findings on lymphangiograms had resolution of their pleural effusions and no evidence of recurrence during a follow-up period of 1-27 months. One patient with normal findings on lymphangiography had an alternative diagnosis established at surgery. Laceration of the thoracic duct was accurately diagnosed and localized with lymphangiography, which allowed definitive surgical repair. CT was of little additional value in diagnosing these injuries. 
Bilateral diaphragm paralysis after cardiac surgery with topical hypothermia. Bilateral diaphragm paralysis is a rare but important complication of open heart surgery. Two cases were found among 360 prospectively studied patients undergoing open heart surgery during one year. Both patients had insulin dependent diabetes with peripheral neuropathy and this may have contributed to their diaphragm paralysis. The patients were studied postoperatively for one year with measurements of lung function, nocturnal oximetry, diaphragmatic function, and phrenic nerve conduction. Treatment with intermittent positive airway pressure ventilation by nasal mask was effective in both patients. After nine months one patient had recovered completely with normal phrenic nerve conduction and diaphragmatic function; the other continues most of his normal daytime activities, but still requires nasal positive airway pressure ventilation for six hours at night. 
Physiological and anatomical evidence for a magnocellular defect in developmental dyslexia. Several behavioral studies have shown that developmental dyslexics do poorly in tests requiring rapid visual processing. In primates fast, low-contrast visual information is carried by the magnocellular subdivision of the visual pathway, and slow, high-contrast information is carried by the parvocellular division. In this study, we found that dyslexic subjects showed diminished visually evoked potentials to rapid, low-contrast stimuli but normal responses to slow or high-contrast stimuli. The abnormalities in the dyslexic subjects' evoked potentials were consistent with a defect in the magnocellular pathway at the level of visual area 1 or earlier. We then compared the lateral geniculate nuclei from five dyslexic brains to five control brains and found abnormalities in the magnocellular, but not the parvocellular, layers. Studies using auditory and somatosensory tests have shown that dyslexics do poorly in these modalities only when the tests require rapid discriminations. We therefore hypothesize that many cortical systems are similarly divided into a fast and a slow subdivision and that dyslexia specifically affects the fast subdivisions. 
High expression of the DNA methyltransferase gene characterizes human neoplastic cells and progression stages of colon cancer. DNA methylation abnormalities occur consistently in human neoplasia including widespread hypomethylation and more recently recognized local increases in DNA methylation that hold potential for gene inactivation events. To study this imbalance further, we have cloned and localized to chromosome 19 a portion of the human DNA methyltransferase gene that codes for the enzyme catalyzing DNA methylation. Expression of this gene is low in normal human cells, significantly increased (30- to 50-fold by PCR analysis) in virally transformed cells, and strikingly elevated in human cancer cells (several hundredfold). In comparison to colon mucosa from patients without neoplasia, median levels of DNA methyltransferase transcripts are 15-fold increased in histologically normal mucosa from patients with cancers or the benign polyps that can precede cancers, 60-fold increased in the premalignant polyps, and greater than 200-fold increased in the cancers. Thus, increases in DNA methyltransferase gene expression precede development of colonic neoplasia and continue during progression of colonic neoplasms. These increases may play a role in the genetic instability of cancer and mark early events in cell transformation. 
Arachidonic acid and docosahexaenoic acid are increased in human colorectal cancer. Increased arachidonic acid concentrations in experimental rodent colonic cancer have been described recently. In humans, a reduced erythrocyte stearic acid to oleic acid ratio has been reported in patients with colorectal cancer and it has been proposed that similar changes exist in the cancer tissue. The long chain fatty acids in the cancers of 15 patients with colorectal cancer were measured and compared with values in the unaffected mucosa. The values were expressed as mean (SD) mg fatty acid/g tissue and compared by analysis of variance. In the cancer tissue arachidonic acid was increased (0.703 (0.109) mg/g v 0.603 (0.127) mg/g, p less than 0.05) as was docosahexaenoic acid (0.211 (0.066) mg/g v 0.148 (0.039) mg/g, p less than 0.001). In contrast, the stearic acid to oleic acid ratio in the cancer tissue was increased rather than decreased, as previously suggested (0.36 (0.05) v 0.29 (0.7), p less than 0.01). Increased arachidonic acid and docosahexaenoic acid concentrations may be related to reduced lipid peroxidation, which is a feature of rapidly growing cells. Alternatively, the increased arachidonic acid values could be due to enhanced desaturase activity upon linoleic and linolenic acid, leading perhaps to increased formation of prostaglandins and other lipoxygenase products. 
bcl-1 rearrangement. Frequency and clinical significance among B-cell chronic lymphocytic leukemias and non-Hodgkin's lymphomas. The authors investigated the structural organization of the bcl-1 locus, a putative oncogene associated with reciprocal chromosomal translocation t(11;14), by Southern blot hybridization analysis and its frequency, distribution, and prognostic significance in a panel of 156 clinically and pathologically well-defined B-cell chronic lymphocytic leukemias (CLLs) and non-Hodgkin's lymphomas (NHLs). The authors detected bcl-1 rearrangements in only 2 of 42 CLLs and 4 of 114 NHLs, specifically 3 of 29 diffuse small lymphocytic and 1 of 10 diffuse small cleaved cell and none of 5 diffuse intermediate lymphocytic, 13 follicular predominantly small cleaved, 17 follicular mixed small cleaved and large cell, 4 diffuse mixed small and large cell, 26 diffuse large cell, and 10 diffuse small noncleaved cell lymphomas. None of seven cases of Rai stage III or IV CLL or seven diffuse large cell lymphomas occurring as Richter's syndrome exhibited bcl-1 rearrangements. In conclusion, the bcl-1 locus rearranges in only about 4% of B-cell CLLs and NHLs, is predominantly rearranged in low-grade B-cell neoplasms, and does not appear to be preferentially associated with those occasional CLLs and low-grade NHLs displaying clinical aggressiveness, advanced clinical stage, or large cell transformation (Richter's syndrome). Therefore the demonstration of bcl-1 rearrangement does not appear to have clinically useful prognostic significance. 
Long-term spinal administration of morphine in cancer and non-cancer pain: a retrospective study. Records of 313 patients who had been treated with spinal morphine via an implanted Port-A-Cath were reviewed. In 284 cases the Port-A-Cath was implanted for epidural delivery of morphine in patients with cancer-related pain. These patients were treated for a mean of 96 (range 1-1215) days. There was a wide variation in dose requirements, minimum daily dose ranging from 0.5 to 200 mg and maximum daily dose from 1 to 3072 mg. However, there was no clear trend to increasing dose as period of epidural morphine administration increased. The most frequent complications were pain on injection (12.0% incidence), occlusion of the portal system (10.9%), infection (8.1%) and leakage of administered morphine such that it did not all reach the epidural space (2.1%). In all but 1 case infections were limited to the area around the portal or along the catheter track. All infections resolved without sequelae following removal of the portal and/or administration of antibiotics. In 17 patients Port-A-Caths were implanted for the intrathecal delivery of morphine to control cancer-related pain. These patients also exhibited wide variations in morphine dose requirements. Port-A-Caths were also implanted for delivery of spinal morphine in 12 patients with chronic pain which was not related to cancer and which failed to respond to other therapies. These patients were treated for a mean of 155 (range 2-575) days. Port-A-Caths were removed from 7 of these patients, primarily due to infection (2 cases) and inadequate pain relief and pain on injection (2 cases). 
Naloxone reverses pattern of obstruction of the distal common bile duct induced by analgesic narcotics in hepatobiliary imaging. It is widely known that narcotics, such as morphine, cause spasm of the sphincter of Oddi, increasing pressure in the common bile duct. This pharmacologic effect has been applied to hepatobiliary scintigraphy in patients with chronic cholecystitis or cholestasis to reducing the time required for a diagnostic study. However, this feature of narcotics could result in delayed or nonvisualization of the small bowel, simulating a distal common bile duct obstruction, in patients requiring parenteral narcotic analgesics who must undergo hepatobiliary scintigraphy. We report on three patients where administration of intravenous naloxone hydrochloride (Narcan), a narcotic antagonist, was helpful in distinguishing narcotic-induced spasm of the sphincter of Oddi from true obstruction of the common bile duct. 
Intrarectal sonography. A new technique for the assessment of rectal tumors. Preoperative staging of rectal tumors provides a selective therapeutic approach. Twenty-three patients were evaluated with prospective intrarectal sonography. Endosonography identified all 21 rectal lesions. Two patients with previous rectal carcinoma had no evidence of recurrence. Thirteen of 17 patients (76%) with rectal carcinoma were correctly staged by endosonography. A submucosal leiomyosarcoma and pararectal arachnoid cyst were correctly identified. Preoperative assessment of lymph node status was accurate in five of ten patients (50%). Results of preoperative digital rectal examination predicting rectal wall involvement correlated with pathologic findings in 11 of 15 patients (73%). Intrarectal sonography is an important staging technique for preoperative evaluation of rectal wall invasion and guides appropriate surgical intervention. 
Anatomic consideration for sacral screw placement. Instrumentation of the lumbosacral spine increasingly involves screw fixation to the sacrum. Recommended locations and techniques for screw placement vary, particularly when bicortical purchase of the sacrum is performed. The purpose of this study was to describe the critical anatomy and potential injuries to neurovascular and visceral structures anterior to the sacrum. Lack of awareness can lead to life-threatening complications. The study included 22 fresh human cadavers with no prior spinal surgery. Specimens were placed in a prone position, and the lumbosacral spine was exposed. Two 6.5-mm screws were inserted using one of two techniques, respectively: Starting just inferior to the S1 facet one screw was angled 25 degrees caudally and 30 degrees laterally; in the second technique, lateral inclination was increased to 45 degrees. In addition, all specimens had screws placed in the S2 pedicles. An anterior dissection was performed to allow evaluation of the neurovascular and visceral structures at risk for injury by, or adjacent to, the screw tips. All significant neurovascular structures in the area of concern were constant in position. The internal iliac vein and the lumbosacral nerve trunk were most at risk for injury by the 30 and 45 degrees laterally directed screws. The sigmoid colon, though close to the S2 screw, was protected by its mesentery. Screws placed in the S1 pedicle were least likely to injure the neurovascular bundle. A lateral and a midline safe zone were identified. 
Plasma sodium-potassium ATPase inhibition activity in low- and normal-renin hypertension. Thirty-seven subjects with low- and normal-renin hypertension (plasma renin activity less than 0.45 ng/L/sec on a 100 mmol Na diet) were studied on a 10 and 100 mmol sodium diet (100 mmol K and 25 mmol Ca) to examine the effect of varied sodium intake on plasma Na,K-ATPase inhibitory activity (NKAIA) (% inhibition). On the 10 mmol Na diet, plasma NKAIA correlated with mean arterial pressure (MAP) (r = 0.384, P = .019). On the 100 mmol Na diet, plasma NKAIA correlated with daily urinary sodium excretion (r = 0.384, P = .019). With the increase in sodium intake, the mean change in MAP was 0.5 +/- 7.8 mm Hg (range -12.7 to 16.3) and the mean change in plasma NKAIA was -4.2 +/- 11.2% inhibition (range -37.5 to 16). The change in MAP was correlated to the change in plasma NKAIA (r = 0.384, P = .019). Plasma NKAIA is related to mean arterial pressure or urinary sodium excretion depending on the dietary sodium intake, and is related to sodium-induced changes in MAP in low and normal renin hypertensive patients. 
Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). SHEP Cooperative Research Group OBJECTIVE.--To assess the ability of antihypertensive drug treatment to reduce the risk of nonfatal and fatal (total) stroke in isolated systolic hypertension. DESIGN.--Multicenter, randomized, double-blind, placebo-controlled. SETTING.--Community-based ambulatory population in tertiary care centers. PARTICIPANTS.--4736 persons (1.06%) from 447,921 screenees aged 60 years and above were randomized (2365 to active treatment, 2371 to placebo). Systolic blood pressure ranged from 160 to 219 mm Hg and diastolic blood pressure was less than 90 mm Hg. Of the participants, 3161 were not receiving antihypertensive medication at initial contact, and 1575 were. The average systolic blood pressure was 170 mm Hg; average diastolic blood pressure, 77 mm Hg. The mean age was 72 years, 57% were women, and 14% were black. INTERVENTIONS.--Participants were stratified by clinical center and by antihypertensive medication status at initial contact. For step 1 of the trial, dose 1 was chlorthalidone, 12.5 mg/d, or matching placebo; dose 2 was 25 mg/d. For step 2, dose 1 was atenolol, 25 mg/d, or matching placebo; dose 2 was 50 mg/d. MAIN OUTCOME MEASURES.--Primary.--Nonfatal and fatal (total) stroke. Secondary.--Cardiovascular and coronary morbidity and mortality, all-cause mortality, and quality of life measures. RESULTS.--Average follow-up was 4.5 years. The 5-year average systolic blood pressure was 155 mm Hg for the placebo group and 143 mm Hg for the active treatment group, and the 5-year average diastolic blood pressure was 72 and 68 mm Hg, respectively. The 5-year incidence of total stroke was 5.2 per 100 participants for active treatment and 8.2 per 100 for placebo. The relative risk by proportional hazards regression analysis was 0.64 (P = .0003). For the secondary end point of clinical nonfatal myocardial infarction plus coronary death, the relative risk was 0.73. Major cardiovascular events were reduced (relative risk, 0.68). For deaths from all causes, the relative risk was 0.87. CONCLUSION.--In persons aged 60 years and over with isolated systolic hypertension, antihypertensive stepped-care drug treatment with low-dose chlorthalidone as step 1 medication reduced the incidence of total stroke by 36%, with 5-year absolute benefit of 30 events per 1000 participants. Major cardiovascular events were reduced, with 5-year absolute benefit of 55 events per 1000. 
Ataxic hemiparesis associated with ipsilateral cerebellar syndrome caused by a paracentral gyrus lesion. The authors report a case of ataxic hemiparesis and an ipsilateral cerebellar syndrome in relation to a glioblastoma of the paracentral gyrus region. The physiopathology of this clinical presentation caused by compression of the corticopontine tract is discussed. 
Early angioplasty in patients with acute myocardial infarction complicated by hypotension. Emergency percutaneous transluminal coronary angioplasty was performed in 62 patients with acute myocardial infarction complicated by hypotension. All patients were treated within 12 hours of the onset of chest pain. Angioplasty was completely successful (residual lesion less than or equal to 50%) in 48 patients, partially successful (patent vessel greater than 50% residual lesion) in four patients, and unsuccessful in 10 patients. Patients in whom angioplasty was successful had a hospital mortality rate of 19%; those in whom angioplasty was unsuccessful or only partially successful had hospital mortality rates of 60% and 50%, respectively, (p = 0.012). Patients with occlusion of the proximal left anterior descending vessel had the highest failure rate (42%) and the highest mortality rate (67%). Other univariate predictors of hospital mortality were older age and elevated end-diastolic pressure. Successful emergency angioplasty improves mortality in patients with acute infarction complicated by hypotension. 
Protection by 16,16-dimethyl prostaglandin E2 and dibutyryl cyclic AMP against complement-mediated hepatic necrosis in rats. 16,16-Dimethyl prostaglandin E2, a known cytoprotective agent, was examined for its ability to protect the liver against complement-mediated necrosis induced by an intravenous injection of a monoclonal antibody against a rat liver-specific antigen in rats. The hepatic injury induced by the antibody was characterized by (a) rapid development of numerous massive hemorrhagic foci of necrotic liver cells, (b) marked increases in serum liver enzyme activities and (c) pronounced reduction in the CH50 level, presumably as a result of complement consumption in the liver. Pretreatment with 16,16-dimethyl prostaglandin E2 at intraperitoneal doses of 20 and 100 micrograms/kg suppressed the hepatic injury, as evidenced by markedly mitigated liver-cell necrosis and much smaller increases in the serum-enzyme activities compared with the values in diseased control animals. The prostaglandin analogue failed to prevent serum complement consumption in response to the antibody injection or affect the CH50 level at the preinjury stage, indicating that neither complement inactivation nor interference with the antigen-antibody reaction was involved in the hepatic protection. The hepatoprotective doses of 16,16-dimethyl prostaglandin E2 produced a significant increase in liver cyclic AMP content in a dose-related manner. In addition, intravenous dibutyryl cyclic AMP at 3 and 10 mg/kg dose-dependently prevented histological and biochemical changes in the hepatic damage without altering the rate of reduction in serum complement activity. Like 16,16-dimethyl prostaglandin E2, dibutyryl cyclic AMP did not affect the preinjury CH50 level. 
Iron chelation therapy and lung transplantation. Effects of deferoxamine on lung preservation in canine single lung transplantation. Reperfusion injury is a limiting factor in lung transplantation. Deferoxamine is an iron chelator that inhibits the formation of oxygen-derived free radicals. We investigated the effects of deferoxamine on posttransplantation lung function in a canine model of single lung transplantation. Twelve dogs underwent left lung transplantation after 20- to 24-hour hypothermic storage in a modified Euro-Collins solution. In six experiments donor and recipient received a 10 mg/kg dose of deferoxamine before harvest and transplantation, and 10 mg/kg was added to the preservation solution. Arterial oxygen tension, alveolar-arterial oxygen difference, pulmonary vascular resistance, and dynamic lung compliance were measured. Data were recorded for 6 hours after ligation of the native pulmonary artery. At the end of the study the mean arterial oxygen tension was 175.1 mm Hg for the deferoxamine treated group versus 71.1 mm Hg for the control group (p less than 0.001), and the alveolar-arterial oxygen difference was less in the deferoxamine-treated group: 502.3 versus 606.0 mm Hg (p less than 0.001). The mean pulmonary vascular resistance was lower throughout the study, and after 6 hours it was 455.1 dynes/sec/cm(-5) in the deferoxamine-treated group versus 663.7 dynes/sec/cm(-5) in the control group (p less than 0.035). Compliance was similar in both groups. We conclude that deferoxamine improves lung preservation and early posttransplantation function in canine single lung transplantation. 
Comparative efficacy and safety of bepridil and diltiazem in chronic stable angina pectoris refractory to diltiazem. The Bepridil Collaborative Study Group. The efficacy and safety of bepridil hydrochloride (200 to 400 mg/day) were evaluated in patients with chronic stable angina refractory to maximal tolerated doses of diltiazem (median 360 mg/day) in a randomized, multicenter, double-blind, parallel study. Baseline diltiazem data were obtained during a 2-week period, after which 86 patients were randomized to bepridil (n = 46) or diltiazem (n = 40). Angina frequency, nitroglycerin consumption and ischemic manifestations induced by exercise treadmill testing were evaluated over 8 weeks. Bepridil significantly (p less than 0.05) increased time to angina onset, time to 1 and 2 mm of ST-segment depression, total exercise time and total work over baseline values. Changes in time to angina onset and time to 1 mm of ST-segment depression were significantly (p less than 0.05) greater for bepridil than for diltiazem. Angina frequency and nitroglycerin consumption did not differ significantly between groups. Compared with baseline, bepridil significantly (p less than 0.001) decreased heart rate (mean 4 beats/min) and prolonged QTc (mean 35 ms). The most frequent adverse effects in both groups were nausea, asthenia, dizziness, headache and diarrhea. Four patients taking bepridil and 1 taking diltiazem withdrew from the study because of adverse reactions. No sudden deaths, myocardial infarctions or instances of sustained ventricular tachycardia or torsades de pointes occurred in either group. The data indicate that bepridil provided safe and effective antianginal and antiischemic therapy in patients with chronic stable angina who exhibited less than optimal response to maximal tolerated doses of diltiazem. 
Combined vitrectomy, cataract extraction, and posterior chamber intraocular lens implantation in diabetic patients. Combined extracapsular cataract extraction, pars plana vitrectomy, and posterior chamber intraocular lens implantation was performed in six eyes with proliferative diabetic retinopathy. These eyes all had minimal iris vascular changes and were at reasonably low risk for developing intraoperative and postoperative complications. The surgery must be relatively brief and the endophotocoagulation accurate. Initial visual acuities ranged from light perception to 4/200. With an average follow-up of 9.7 months, final acuities ranged from 4/200 to 20/40. 
Inefficacy and proarrhythmic effects of flecainide and encainide for sustained ventricular tachycardia and ventricular fibrillation. OBJECTIVE: To assess the efficacy of encainide and flecainide in treating patients with sustained ventricular arrhythmias. DESIGN: Patients were treated with encainide or flecainide. Efficacy was assessed by comparing the results of programmed ventricular stimulation while patients received therapy with the results while they were drug free. SETTING: The electrophysiology laboratory of the University of California at San Francisco. PATIENTS: Forty-nine patients with spontaneous or inducible sustained ventricular tachycardia or ventricular fibrillation for whom treatment with at least one class IA antiarrhythmic agent had failed. INTERVENTIONS: Patients were treated with encainide, 35 to 50 mg three or four times daily, or flecainide, 100 to 200 mg twice daily. RESULTS: Arrhythmia worsened early in 5 of 16 patients receiving encainide and 3 of 33 patients receiving flecainide. Patients with poor left ventricular function were more likely to exhibit proarrhythmia (P = 0.02). Nine of eleven patients receiving encainide and 23 of 28 patients receiving flecainide who had repeat programmed ventricular stimulation while receiving drug therapy still had inducible, poorly tolerated ventricular tachycardia. CONCLUSION: Encainide and flecainide have a low efficacy rate and a high incidence of worsening of arrhythmia in patients with sustained ventricular arrhythmias, particularly when this condition is associated with poor left ventricular function. 
Serial angiography in a spontaneous dissecting anterior cerebral artery aneurysm. Intracranial dissecting aneurysms are uncommon, and little is known concerning the natural history of these lesions. In this paper we present a rare case of dissecting aneurysm of the anterior cerebral artery in which a true diagnostic sign of "double lumen" was demonstrated. Sequential changes in angiographic features shown on serial angiographic studies are described, and diagnosis is briefly discussed. 
Pathogenesis of severe acute respiratory infections in the developing world: respiratory syncytial virus and parainfluenza viruses. Respiratory syncytial virus (RSV) and parainfluenza viruses (PIVs) are the most frequently isolated pathogens in infants and children with acute lower respiratory infection (LRI) in the developed world. Less information is available about their importance in LRI in the developing world, but they are probably important there also. The pathogenesis of viral bronchiolitis and pneumonia involves inoculation and early replication in the upper respiratory tract, followed by aspiration into the lower respiratory tract when both the mucosal and systemic immune systems are involved in a specific response. Both disease and recovery reflect processes of viral replication (with attendant cellular destruction) and of immune response (with attendant direct cellular destruction and release of pathogenic, along with beneficial, mediators). Factors predisposing to bacterial superinfection are poorly understood except in animal models. Conditions leading to heightened susceptibility to severe disease in the developed world are particularly common in the developing world. Increasing information on RSV and PIV infections in the developing world will likely point to their importance. Strategies for prevention of severe illnesses due to these viruses will follow from concepts elucidated through animal models and studies of infants in the developed world. 
Magnetic resonance imaging in the staging of renal cell carcinoma. A prospective study has been carried out to examine the role of magnetic resonance imaging (MRI) in the investigation of renal cell carcinoma in 24 patients. In all cases the inferior vena cava (IVC) was well demonstrated with MRI. In 14 out of 15 patients where surgical correlation was available, the MRI and operative staging were in agreement. Magnetic resonance imaging and computed tomographic (CT) staging were in agreement in 16 out of the 17 patients where both were performed. In one case, CT suggested hepatic invasion but this was found not to be present on MRI and at operation. Magnetic resonance imaging also provided substantial additional information in three patients, including two cases where MRI demonstrated a patent IVC that appeared occluded on CT (one of which also had vertebral metastases seen on MRI but missed on CT) and one case where CT failed to demonstrate minimal involvement of the IVC. Magnetic resonance imaging is an accurate means of staging renal cell carcinoma with clear advantages over CT. In no case in this series was inferior vena cavography found to be necessary. 
Monitoring of irrigating fluid absorption during transurethral prostatectomy. A study in anaesthetised patients using a 1% ethanol tag solution. A simple, reliable method to detect absorption of irrigating fluid during transurethral prostatectomy is to tag irrigating fluids with 1% ethanol and monitor expired breath ethanol concentrations. This method correlated well (n = 0.79) with other existing methods of absorption monitoring in 20 anaesthetised patients. Ethanol (1%) tagging does not alter the optical quality of the irrigating fluid and is harmless to the patient. The technique is non-invasive, repeatable, cheap and gives instant results. It can be used in anaesthetised or awake patients and can detect absorption of as little as 100-150 ml in any 10-minute period. 
Cholelithiasis after treatment for childhood cancer. The authors evaluated the risk of development of cholelithiasis in 6050 patients treated at a single hospital for various childhood cancers with different therapeutic modalities, including chemotherapy, surgery, radiation therapy, and bone marrow transplantation, from 1963 to 1989. Patients with underlying chronic hemolytic anemia or preexisting gallstones were excluded. Nine female and seven male patients with a median age of 12.4 years (range, 1.2 to 22.8 years) at diagnosis of primary cancer had gallstones develop 3 months to 17.3 years (median, 3.1 years) after therapy was initiated. Cumulative risks of 0.42% at 10 years and 1.03% at 18 years after diagnosis substantially exceed those reported for the general population of this age group. Treatment-related factors significantly associated with an increased risk of cholelithiasis were ileal conduit, parenteral nutrition, abdominal surgery, and abdominal radiation therapy (relative risks and 95% confidence intervals = 61.6 [27.9-135.9], 23.0 [9.8-54.1], 15.1 [7.1-32.2], and 7.4 [3.2-17.0], respectively). There was no correlation with the type of cancer, nor was the frequency of conventional predisposing features (e.g., family history, obesity, use of oral contraceptives, and pregnancy) any higher among the affected patients in this study than in the general population. Patients with cancer who have risk factors identified here should be monitored for the development of gallstones. 
Long-term effect of thrombolytic therapy on left ventricular ejection fraction after acute myocardial infarction. To assess the long-term effect of thrombolytic therapy on left ventricular (LV) systolic function, 222 patients with acute myocardial infarction treated with intravenous tissue plasminogen activator within 4 hours of symptom onset underwent assessment of LV ejection fraction (EF) by radionuclide equilibrium angiography at hospital discharge and 1 year later. Mean EF at hospital discharge (46 +/- 12) was similar to that at 1 year (45 +/- 13). Stepwise multivariate linear regression analysis identified EF at discharge and patency of the infarct-related artery before discharge as independent predictors of EF change at 1 year (p = 0.0002 and 0.003, respectively). Random assignments to invasive versus conservative treatment strategies or to early versus delayed beta-blocker therapy did not affect EF change during follow-up. No significant deterioration of EF was observed in patients with larger infarcts. However, EF decreased from 45 +/- 10 at hospital discharge to 39 +/- 12 (p = 0.005) at 1-year follow-up in a subgroup of patients with history of prior infarction. Thus, patients with acute myocardial infarction, treated with intravenous tissue plasminogen activator early after onset of symptoms, appear to have stable LV function between hospital discharge and 1 year follow-up. The change in EF between hospital discharge and 1 year can be predicted from the EF value at discharge, patency of the infarct-related artery before discharge and history of previous myocardial infarction. 
Effect of insulin and plasma amino acid concentration on leucine metabolism in cirrhosis. Clinically stable patients with cirrhosis demonstrate insulin resistance with regard to glucose metabolism. However, much less is known about the two major factors, insulin and plasma amino acid concentration, that regulate protein metabolism in cirrhotic patients. To examine this question, we performed paired euglycemic insulin clamp studies in combination with 14C-leucine and indirect calorimetry. In the first study insulin alone was infused, and the plasma amino acid concentration was allowed to decline. During the second study a balanced amino acid solution was infused with insulin to increase the total plasma amino acid concentration approximately twofold. Insulin-mediated glucose disposal (4.68 vs. 6.45 mg/kg-min, p less than 0.01) was significantly impaired by 30% in cirrhotic patients during both insulin clamp studies. In the postabsorptive state, cirrhotic patients manifested low plasma leucine (76 vs. 102 mumol/L) and alpha-ketoisocaproate (19 vs. 30 mumol/L) concentrations, but all parameters of leucine turnover were normal. When insulin alone was infused, the endogenous leucine flux (an index of protein degradation) declined similarly in cirrhotic patients (30.8 mumol/m2-min) and control (26.9) subjects, and this was accompanied by a similar decrease in plasma leucine concentration (31% vs. 33%). The decline in circulating leucine concentration was accompanied by a parallel decline in leucine oxidation (5.1 vs. 4.6 mumol/m2-min) and nonoxidative (28.9 vs. 26.0 mumol/m2-min) leucine disposal, which were of similar magnitude in cirrhotic patients and control subjects, respectively. In both cirrhotic patients and control subjects, combined hyperinsulinemia/hyperaminoacidemia elicited a similar stimulation of nonoxidative leucine disposal (an index of protein synthesis) and leucine oxidation while causing a greater suppression of endogenous leucine flux than observed with insulin alone. Thus the suppressive effect of insulin on protein degradation and the stimulatory effect of insulin/amino acid infusion on protein synthesis are not impaired in cirrhotic patients, demonstrating a clear-cut dissociation between the effects of insulin on protein and glucose metabolism. 
Novel approach to iatrogenic bile peritonitis. Bile peritonitis after injury to the biliary tree is a serious complication that requires exploratory laparotomy. Our patient had an obstructing ampullary carcinoma, and generalized bile peritonitis developed from attempted percutaneous transhepatic cholangiography. The patient's condition was managed by peritoneal lavage and endoscopic transampullary stenting, with immediate relief of pain and toxicity. Exploratory laparotomy was avoided, and an eventual pylorus-sparing Whipple resection was the definitive treatment. We believe this to be the first report of successful nonoperative treatment of a patient with bile peritonitis with obstructive jaundice. 
Comparative efficacy of cimetidine, famotidine, ranitidine, and mylanta in postoperative stress ulcers. Gastric pH control and ulcer prevention in patients undergoing coronary artery bypass graft surgery. To determine the comparative efficacy of several histamine (H2)-receptor antagonists (cimetidine, famotidine, and ranitidine) and the antacid Mylanta-II (Stuart Pharmaceuticals, Wilmington, DE) in gastric pH control and the prevention of postoperative stress ulceration, a prospective, randomized study was performed in a homogeneous population of patients with elective coronary artery bypass. None of the 57 patients in the study population had a documented history of ulcer disease. There were four treatment groups, each with similar demographics (age and sex). Cimetidine-treated group consisted of 15, famotidine-treated group of 18, ranitidine-treated group of 19, and antacid-treated group of 5 patients. There was no hemodynamically significant postoperative gastrointestinal bleeding in any of the patients. When the agents were compared for efficacy of gastric pH control, statistically better pH control was found in the famotidine- and ranitidine-treated groups (P less than 0.003) than in the cimetidine-treated group (pH less than or equal to 4.0) during the 20-hour observation period. Side effects (hematologic and neurological) were noted only in the cimetidine-treated group. The results of this study indicate that in patients in postoperative intensive care, better gastric pH control, and thus prevention of gastric stress ulcers, is achieved with either famotidine or ranitidine rather than cimetidine or antacid. 
Abnormal permeability precedes the development of a gluten sensitive enteropathy in Irish setter dogs. Intestinal permeability to 51Cr-EDTA was examined during the development of gluten sensitive enteropathy in dogs bred from affected Irish setters and reared on a normal wheat containing diet. Comparisons were made with litter mates reared on a gluten free diet and with a control group of age matched, clinically healthy Irish setters reared on the normal diet. Studies at 4, 6, 8, and 12 months of age were correlated with morphometric and biochemical examinations of peroral jejunal biopsy specimens. Permeability was increased at all ages in the group fed gluten free diet compared with control dogs, although there were no differences in villus height, intraepithelial lymphocyte density, and alkaline phosphatase activity. At four months, permeability in the normal diet group was greater than in controls, although comparable with that in the gluten free diet group. Permeability in the normal diet group increased further in conjunction with the development of partial villus atrophy and reduced alkaline phosphatase activity, and by 12 months permeability was significantly greater than in their gluten free diet litter mates and the control dogs. The findings suggest that an underlying permeability abnormality may be involved in the pathogenesis of gluten sensitive enteropathy in Irish setter dogs. 
Acute inflammation: the underlying mechanism in delayed onset muscle soreness? It is well documented in animal and human research that unaccustomed eccentric muscle action of sufficient intensity and/or duration causes disruption of connective and/or contractile tissue. In humans, this appears to be associated with the sensation of delayed onset muscle soreness (DOMS). During the late 1970's, it was proposed that this sensation of soreness might be associated with the acute inflammatory response. However, subsequent research failed to substantiate this theory. The present article suggests that the results of much of the research concerning DOMS reflect events typically seen in acute inflammation. Similarities between the two events include: the cardinal symptoms of pain, swelling, and loss of function; evidence of cellular infiltrates, especially the macrophage; biochemical markers such as increased lysosomal activity and increased circulating levels of some of the acute phase proteins; and histological changes during the initial 72 h. In the final section of this paper, a theoretical sequence of events is proposed, based on research involving acute inflammation and DOMS. 
alpha Fetoprotein producing early gastric cancer with liver metastasis: report of three cases. Three cases of alpha fetoprotein producing early gastric cancer are presented. Liver metastases occurred in all patients shortly after curative gastrectomy and all died within two years. The incidence of liver metastasis was significantly higher than that in alpha fetoprotein negative early gastric carcinoma (p less than 0.001). The incidences of lymph node metastasis and invasion in lymph vessels and veins were also substantially higher in this group of patients. Two radical hepatic resections, including extended right lobectomy, were performed on one patient but the tumour recurred immediately. 
Abnormal left ventricular diastolic filling in eccentric left ventricular hypertrophy of obesity. Left ventricular (LV) diastolic filling pattern of obese subjects with eccentric LV hypertrophy was studied. Findings were compared with those of normal control subjects and hypertensive patients with concentric LV hypertrophy. M-mode, 2-dimensional and Doppler echocardiograms were recorded in 11 obese (body mass index greater than 30 kg/m2) normotensive patients with eccentric LV hypertrophy, 10 normal control subjects, and 18 nonobese, hypertensive patients with concentric LV hypertrophy whose antihypertensive medications were discontinued 2 weeks before study. LV hypertrophy was defined as LV mass/height greater than 143 g/m. Hypertrophy in the obese patients was eccentric: Their LV internal dimension (61 +/- 3 mm) was greater than that of hypertensive patients (55 +/- 5 mm, p less than 0.001) and normal control subjects (55 +/- 2 mm, p less than 0.01); their septal (10.7 +/- 0.7 mm) and posterior (10.9 +/- 0.6 mm) wall thicknesses were smaller than those of the hypertensive patients (12.2 +/- 1.7 mm, p less than 0.05 and 11.7 +/- 1.2 mm, respectively, difference not significant). Pulsed-wave Doppler echocardiographic filling indexes were used to evaluate LV diastolic filling. Obese patients had a higher peak velocity of atrial filling (69 +/- 14 vs 54 +/- 15 cm/s, p less than 0.05), lower early/atrial filling velocity ratio (1.0 +/- 0.26 vs 1.32 +/- 0.21, p less than 0.05), prolonged deceleration half-time (108 +/- 9 vs 86 +/- 15 ms, p less than 0.01) and lower peak filling rate corrected to stroke volume (4.08 +/- 0.68 vs 4.96 +/- 0.88 stroke volume/s, p less than 0.05) than normal control subjects. 
Coexistent hemangioblastoma and arteriovenous malformation of the cerebellum. Case report. A case of cerebellar hemangioblastoma and coexistent arteriovenous malformation (AVM) is presented. Angiography displayed the AVM, but histological examination revealed a coexisting hemangioblastoma. Various theories concerning the etiology of this condition are discussed. 
Branched-chain-enriched amino acid solutions in patients with liver failure: an early example of nutritional pharmacology. The use of BCAA in the treatment of hepatic failure has been controversial. Even in retrospect, it is difficult to know why this controversy existed and why it has been so emotional, except for the fact that such a treatment modality has flown in the face of conventional therapy of hepatic encephalopathy, and also, probably more importantly, directly attacked some of the cherished notions of the nature of hepatic encephalopathy. Time and distance have allowed some of the controversy to die down, and as time has elapsed it has become clear that at least in the area of nutritional support of patients with hepatic failure, BCAA are the preferred alternative to treat patients who are otherwise protein intolerant. A recent unbiased review using the techniques of meta-analysis has concluded that the BCAA are efficacious for the treatment of patients with hepatic encephalopathy. Since this manuscript was completed another study has been reported. In this study, it was notable that those patients treated with oral BCAA became neurologically normal, a finding which the authors found very striking. 
Effect of epidural clonidine on analgesia and pharmacokinetics of epidural fentanyl in postoperative patients. Epidural clonidine produces postoperative analgesia in patients and potentiates opioid analgesia in animals. The aim of the current study was to assess the effect of epidural clonidine on the plasma concentrations and analgesic effect of fentanyl after epidural administration. Twenty ASA physical status 2 or 3 patients recovering from abdominal surgery were allocated randomly to receive either epidural fentanyl (100 micrograms in 10 ml isotonic saline; EF group) or epidural fentanyl (same dose) plus epidural clonidine (150 micrograms; EF + C group) in isotonic saline solution. Analgesia was assessed over a period of 12 h after epidural injection. Venous samples were obtained until 360 min after epidural injection for radioimmunoassay determination of plasma fentanyl concentration. Onset of analgesia was similar in the two groups of patients (13 +/- 6 and 13 +/- 3 min, respectively, after injection), but duration was more than doubled in the patients receiving clonidine (543 +/- 183 vs. 250 +/- 64 min). Peak plasma fentanyl concentrations (Fmax) and the time to reach Cmax (Tmax) were comparable in the two groups (0.29 +/- 0.15 ng.ml-1 at 16.2 +/- 14.8 min in the EF group and 0.27 +/- 0.11 ng.ml-1 at 8.3 +/- 5.5 min in the EF + C group), as were plasma concentrations at each definite time of measurement. Drowsiness and hypotension were noticed in the EF + C group. Thus, epidural clonidine appears to prolong epidural fentanyl analgesia without affecting its plasma concentration. 
Tissue-specific activation of cardiac angiotensin converting enzyme in experimental heart failure. In addition to the circulating renin-angiotensin system, recent data demonstrate the existence of tissue renin-angiotensin systems that may be important in cardiovascular homeostasis. However, the relative activities of the circulating and tissue renin-angiotensin systems have not been examined previously in pathophysiological states, such as congestive heart failure. The present study was performed to examine the status of plasma and tissue angiotensin converting enzyme (ACE) activities in compensated experimental heart failure induced by coronary artery ligation in the rat. Three groups of male Sprague-Dawley rats were examined: 1) nonoperated rats (NO, n = 5), 2) sham-operated rats (SO, n = 5), and 3) heart failure rats (HF, n = 11). Rats were studied an averaged of 85 days postoperatively. In HF animals, plasma renin concentration and serum ACE activities were not different compared with NO and SO control animals. Cardiac ACE activity was 50% greater in the right ventricle than the interventricular septum in NO and SO rats. Both right ventricular and interventricular septal ACE activity increased approximately twofold in HF animals as compared with NO and SO groups (p less than 0.05). In contrast, pulmonary, aortic, and renal ACE activities were not altered in HF rats compared with control animals. A positive correlation existed between the histopathological size of myocardial infarction and the level of right ventricular ACE activity (r = 0.75, p less than or equal to 0.05). Such a relation between infarct size and either serum or noncardiac tissue ACE activities was not observed. 
Safety and possible efficacy of fiberoptic bronchoscopy with lavage in the management of refractory asthma with mucous impaction. Mucous impaction may be suspected in asthmatic exacerbation when, despite aggressive medical management, patients continue to produce sputum containing mucous plugs and exhibit prominent rhonchi and/or wheezes on chest auscultation. Spirometric measurements in this setting corroborate lack of improvement and reveal significant impairment in indices that may reflect small airways function (FEF25-75). We hypothesized that clearance of inspissated secretions by fiberoptic bronchoscopy with lavage (FOBwL) may promote or hasten the clinical improvement of such patients. Fifty-one therapeutic FOBwL were accomplished in 19 patients during 20 episodes of stabilized yet refractory asthma with mucous impaction. No significant complications were encountered. After FOBwL, spirometric measurements of FEV1, FEF25-75, and FVC increased significantly (P less than .01, paired t test), and correlated with relief of dyspnea and mobilization of secretions with cough. FOBwL can be safely performed in stabilized, refractory asthma, and with apparent efficacy. Further investigation is needed to document the therapeutic utility of FOBwL in refractory asthma. 
Ultrasonic evaluation of gallbladder function prior to non-surgical treatment of gallstones. A comparative analysis of ultrasonic and oral cholecystographic assessment of gallbladder function in symptomatic patients with cholelithiasis is presented. Ultrasonic evaluation demonstrated non-contractile gallbladders in all but one patient with non-opacification during oral cholecystography, whereas all those opacifying on oral cholecystography contracted on ultrasonography. Both techniques showed similar abilities to quantify the size and number of biliary calculi within the limits necessary to determine suitability for treatment. Although computed tomography remains necessary to quantify gallstone density prior to non-surgical treatment, ultrasonography is a safe, acceptable, cheap and preferable alternative to oral cholecystography in assessing gallbladder function. 
Emergence of a B-cell lymphoblastic lymphoma in a patient with B-cell chronic lymphocytic leukemia: evidence for the single-cell origin of the two tumors. A patient is described who presented with a chronic lymphocytic leukemia (CLL) and later developed a lymphoblastic lymphoma. The cells from the CLL were typical mature B lymphocytes as could be assessed by morphologic, cytochemical, and surface marker analyses. The cells from the lymphoblastic lymphoma were immature B cells that expressed CD10, CD20, and HLA-DR markers, but not surface Ig or cytoplasmic mu chains, and were negative for terminal deoxynucleotidyl transferase (TdT). The cells of two continuous cell lines, obtained from the bone marrow and the peripheral blood of the patient, had the same phenotype as the lymphoblastic lymphoma cells, did not contain the Epstein-Barr virus genome, and displayed malignant features in vitro, including the capacity to form colonies in agar. The two cell lines also shared identical chromosomal abnormalities, a finding which suggests that they derived from the same malignant cell already present in vivo. Such chromosomal abnormalities were not seen in the karyotype of the peripheral blood cells at the onset of the disease. Analysis of the Ig heavy chain genes using a DJ-specific probe showed the very same monoclonal rearrangement in the cells from the B-CLL, the lymphoblastic lymphoma and the two cell lines, thus demonstrating their common clonal origin. By contrast, a monoclonal rearrangement of the lambda chain gene locus was found in the B-CLL cells only, a finding consistent with their exclusive capacity to express surface IgM lambda. This patient represents a rare case in whom a chronic lymphoproliferative disorder with mature malignant cells transforms into a lymphoblastic lymphoma characterized by cells frozen at a very early maturational stage. The possible mechanisms leading to such transformation within the same cell clone are discussed. 
Wildervanck or cervico-oculo-acoustic syndrome and MRI findings. In 1952, Wildervanck described the first case of what he styled the cervico-oculo-acoustic (COA) syndrome. This comprises Klippel Feil's (KF) anomaly (congenitally fused cervical vertebrae), congenital sensorineural deafness and Duane's retraction syndrome (deficient abduction with retraction on adduction). Since that original paper, there have been further reports describing this triad, either completely or incompletely. A further case of this syndrome is reported and the first report of MRI head scan findings in this condition is presented. In addition, the origin of mirror movements observed as part of the KF syndrome are discussed. 
Hepatobiliary cryptosporidiosis and cytomegalovirus infection mimicking metastatic cancer to the liver. A cholestatic syndrome caused by sclerosing cholangitis and papillary stenosis has been described in patients with the acquired immunodeficiency syndrome and hepatobiliary cryptosporidiosis and cytomegalovirus infection. The case of a 41-year-old homosexual man with the acquired immunodeficiency syndrome who presented with abdominal pain, diarrhea, fever, and cholestasis is reported. A percutaneous transhepatic cholangiogram showed that the extrahepatic and right-sided intrahepatic ducts were normal. Computerized tomography of the abdomen showed multiple hypodense lesions in the liver. Guided needle biopsies of several of these lesions showed severe confluent necrotizing pericholangitis with cytomegalovirus-infected cells. Numerous cryptosporidia were seen attached to biliary epithelium. The unique histopathologic and radiographic features of this case should be added to the spectrum of hepatobiliary manifestations of the acquired immunodeficiency syndrome. 
Multiple miliary osteoma cutis. We describe the clinical, radiographic, histologic, and metabolic features of an unusual case of multiple miliary osteoma cutis in an otherwise healthy 57-year-old woman. Although the pathogenesis of this rarely reported entity is not fully understood, the novel application of a dynamic bone study revealed a high rate of internal bone remodeling within the lesion. This finding prompted a brief therapeutic trial of a diphosphonate, not previously reported in the treatment of this condition. 
A prospective study of respiratory failure after high-risk surgery on the thoracoabdominal aorta. From June 1960 to September 1990, 1414 patients underwent repair of thoracoabdominal aortic aneurysms, of whom 112 (8%) had pulmonary complications requiring respiratory support with tracheostomy; subsequently 45 (40%) died in the hospital. We determined by stepwise logistic regression analysis, in a prospective study of high-risk type I and II thoracoabdominal aortic aneurysms repairs, the independent predictors of respiratory failure, defined as respiratory ventilation exceeding 48 hours after operation. In 98 patients studied, 38 (39%) were women, 60 (61%) were men, 54 (55%) had type II thoracoabdominal aortic aneurysms, 34 (35%) had aortic dissection, 19 (19%) were nonsmokers, 40 (41%) exsmokers, and 39 (40%) active smokers. Before operation, 55 (56%) had chronic pulmonary disease with respiratory failure developing in 58% (p = 0.0005 versus no chronic pulmonary disease, 10/43, 23%), and of the 26 patients in the lower quarter of forced expiratory volume (1 sec) (FEV1 less than or equal to 1.45 L) respiratory failure developed in 61% (p = 0.035). In-hospital survival was 98% and 83% (p = 0.008), respectively, and cumulative survival at 6 months by Kaplan-Meier analysis was 96% and 80% (p = 0.004, log-rank test), respectively, for patients without respiratory failure (N = 56/98, 57%) and with respiratory failure (N = 42/98, 43%). On univariate analysis, the following were associated with respiratory failure (p less than 0.05): FEV1, FEV1% predicted, FVC, FEF25, FEF25% predicted, FEF25-75, FEF25-75% predicted, PaCO2 Pao2, symptoms, smoking history, chronic pulmonary disease, cryoprecipitate volume, postoperative neuromuscular deficit, cardiac complications, reoperation for bleeding, renal complication, stress ulceration, postoperative creatinine level, postoperative dialysis, and postoperative encephalopathy. The independent predictors of respiratory failure were (p less than 0.05): chronic pulmonary disease, smoking history, cardiac and renal complications. In patients with chronic pulmonary disease, the only independent predictor was FEF25 (p = 0.030). These observations may be of value in selecting patients for elective operation. 
Preventive therapy for malaria. The incidence of malaria in travelers returning to the United States has been increasing. Persons visiting areas where malaria is endemic should use insect repellent, wear clothing that covers the arms and legs, and remain in screened areas between dusk and dawn. Chemoprophylaxis for travelers consists of weekly doses of chloroquine; a new drug, mefloquine, should be used in the increasing number of countries where chloroquine-resistant malaria is found. Travelers to these areas should carry three tablets of pyrimethamine-sulfadoxine, which should be taken for presumptive treatment of malaria at the onset of chills and fever. It is essential that chemoprophylaxis be continued for four to five weeks after departure from endemic areas. In travelers who develop symptoms of malaria after returning from an endemic area, it is imperative that treatment be started even if blood smears are negative. 
Wohlfart-Kugelberg-Welander syndrome: serum creatine kinase and functional outcome. The medical records of 31 patients (19 male and 12 female) with clinical and electrophysiologic features of Wohlfart-Kugelberg-Welander syndrome were reviewed. The reported age at onset ranged from less than one year to 46 years, and the age at diagnosis ranged from three to 66 years. Proximal muscle weakness, especially of the lower extremities, and muscular atrophy were the predominant clinical features. Elevated serum creatine kinase levels were noted in four female and 12 male patients, and the degree of elevation was higher in the male patients (up to 32 times the upper limit of normal) than in the female patients. On initial evaluation, two patients were wheelchair-bound, whereas the others were ambulatory. On follow-up evaluation three to 32 years later (mean, 15.5 years), 11 patients used wheelchairs, although only three were wheelchair-bound. The disease followed a steady, slowly progressive course. The outcome of ambulatory status did not correlate with the initial creatine kinase determination. 
Characterization of fibronectin attachment by a human transitional cell carcinoma line, T24. The ability of transitional cell carcinoma cells to adhere to and invade the extracellular matrix is important in invasion and metastasis. The glycoprotein fibronectin is associated with laminin and Type IV collagen in the bladder basement membrane. We characterized the interaction between T-24 cells, a cell line derived from an invasive transitional cell tumor, and fibronectin. The cells use the alpha 5 beta 1 heterodimeric integrin receptor complex to mediate adherence via the classical (RGDS) fibronectin binding site. The importance of the alpha 5 beta 1 receptor to T-24 function is unknown and under investigation. 
Human papillomavirus types 16 and 18 in adenocarcinoma of the uterine cervix. Many reports have shown a link between human papillomavirus (HPV) and cervical squamous neoplasia. However, the association of HPV with cervical adenocarcinoma has been studied less extensively. The authors evaluated the presence of HPV-DNA in 106 patients with adenocarcinoma of the uterine cervix by in situ hybridization, using 35S-labeled probes for HPV 16 DNA and HPV 18 DNA. The overall prevalence of HPV-DNA was 18% (19 of 106). HPV 16 was present in 2 (2%) cases, HPV 18 was observed in 15 (14%) cases, and both HPV 16 and HPV 18 were found in 2 (2%) cases. There was a correlation between HPV-DNA positivity and tumor stage (P less than 0.01) and tumor size (P less than 0.05), but there was no relationship between HPV-DNA positivity and tumor differentiation, proliferation (S-phase fraction), ploidy, lymph node metastases, or five-year survival rate. These results suggest that HPV 18 DNA is associated with cervical adenocarcinoma but the presence of HPV 18 has no influence on overall survival. 
Acute health effects in a community after a release of hydrofluoric acid. Approximately 3,000 persons were evacuated from a Texas community after 24,036 kg (53,000 lb) of caustic hydrofluoric acid (HF) were released from a nearby petrochemical plant. Emergency room and hospital records of 939 persons who were seen at two area hospitals were reviewed. Most persons who presented at the emergency rooms were female (56%) or black (60%), and their mean age was 33.9 y. The most frequently reported symptoms were eye irritation (41.5%), burning throat (21%), headache (20.6%), and shortness of breath (19.4%). Physical examination results were normal for 49% of the cases; however, irritation of the eyes, nose, throat, skin, and lungs were noted on other exams. Decreased pulmonary function was demonstrated by pulmonary function tests (forced expiratory volume in the first second, less than 80% of predicted value, 42.3%); hypoxemia (pO2 less than 80 mm Hg, 17.4%) and hypocalcemia (less than 8.5 mg/dl, 16.3%) were also noted. Ninety-four (10%) of the cases were hospitalized, and more than 83% of all cases were discharged with a primary diagnosis of "HF exposure." There are several reports of individuals who are acutely and chronically exposed to HF; however, we are unaware of other published reports that describe exposure of a community to HF. This incident represented a unique opportunity to study the immediate health impact on a community of residents who were exposed to a hazardous materials release. Results of this analysis suggest that (a) initial health problems should be followed up, (b) any long-term health effects of HF exposure must be assessed, and (c) the health impact on the population at risk should be determined. 
Nocturnal sleep in Huntington's disease. Nocturnal sleep was studied in 16 inpatients with Huntington's disease. In comparison with healthy controls, patients exhibited a disturbed sleep pattern with increased sleep onset latency, reduced sleep efficiency, frequent nocturnal awakenings, more time spent awake and less slow wave sleep. These abnormalities correlated in part with duration of illness, severity of clinical symptoms, and degree of atrophy of the caudate nucleus. Patients showed an increased density of sleep spindles. 
Persistent diarrhea and fecal shedding of retroviral nucleic acids in children infected with human immunodeficiency virus. Gastrointestinal dysfunction is a serious problem in many children infected with human immunodeficiency virus (HIV), the etiology of which has not been clearly defined. Quantitative nucleic acid amplification was used to study the correlation between shedding of HIV nucleic acids and gastrointestinal symptoms in HIV-infected infants and children. Many with HIV infection and persistent diarrheal disease shed HIV nucleic acids in their feces, as did an HIV-infected patient without apparent diarrheal disease. HIV nucleic acids were not found in feces of non-HIV-infected individuals. Intestinal infection with HIV appears to be important in the pathophysiology of gastrointestinal dysfunction in infants and children with HIV infection. Furthermore, the fecal shedding of HIV may play a role in HIV transmission in environments prone to high levels of fecal-oral contamination. 
Early orthopedic intervention in burn patients with major fractures. Surgical treatment of concurrent orthopedic trauma in burn patients is controversial. During a 10-year period, 101 patients were treated for major fractures and burn injuries. Twenty-eight patients with 34 fractures were treated with early operative fixation. The mean TBSA burned was 20%. Ten fractures were open (4 grade I, 5 grade II, and 1 grade III) and 24 were closed. Seventy-five percent of patients had a definitive orthopedic procedure within 24 hours of burn. Intramedullary nails were used in 13, ORIF in 15, external fixation in 3, and percutaneous fixation in 4. Ten patients had burns overlying the fracture site and the surgical incision was made through burned tissue. Four were associated with open fractures. Two orthopedic complications occurred: nonunion of a femoral neck fracture and angulation of a tibial plateau fracture. The goal of orthopedic management in the polytrauma burn patient is to achieve early reduction to allow optimal wound care and early patient mobility. A team approach to patient selection and management is mandatory. 
Deletion of mitochondrial DNA in patients with combined features of Kearns-Sayre and MELAS syndromes. A 9-year-old girl and an 11-year-old boy had ptosis, progressive external ophthalmoplegia, pigmentary retinopathy, and sensorineural hearing loss. The girl had diabetes mellitus and the boy had hypoparathyroidism. Both children also developed recurrent vomiting and cerebral infarcts with lactic acidosis. Muscle biopsy specimens showed ragged-red fibers and Southern analysis demonstrated a distinct heteroplasmic deletion of muscle mitochondrial DNA in each patient but no evidence of the point mutation in the transfer RNALeu(UUR) gene recently identified in mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). These 2 children had combined features of Kearns-Sayre syndrome and MELAS, suggesting that mitochondrial DNA deletions occasionally can have pleomorphic clinical expression. 
Verbal dyspraxia in treated galactosemia. Galactosemia is an inborn error of metabolism that causes life-threatening illness a few days after galactose-containing milk is fed to a newborn. Early treatment with a strict lactose-free diet results in rapid improvement, and, until recently, it was thought that the long-term prognosis in such infants was usually good. The speech characteristics of 24 patients treated for galactosemia were examined. Fifty-four percent had the specific speech disorder, verbal dyspraxia. This finding was not related to age at diagnosis, severity of symptoms in the newborn period, or to biochemical control. There may be, however, a relation between dyspraxia and diminished IQ scores observed in the group of patients with dyspraxia judged as "severe." The findings indicate the association of a specific and unusual speech defect with a specific and rare metabolic disorder. 
Endoscopic fine needle aspiration cytology in the diagnosis of gastro-oesophageal and colorectal malignancies. In a prospective study we compared the diagnostic accuracy of endoscopic fine needle aspiration cytology with that of brush cytology and forceps biopsy in relation to gross tumour pattern and site in 265 confirmed consecutive cases of malignancy of the oesophagus, stomach, colon, and rectum. Aspiration cytology gave the highest diagnostic accuracy (94%), which was significantly better than that of brush cytology (84.9%) and biopsy (87.2%) (p less than 0.005). The difference was mainly related to tumour pattern. When compared to brush cytology and biopsy aspiration cytology was significantly better in submucosal tumours (92.9% v 7.1% and 14.3%, p less than 0.001); in infiltrative malignancies (95.8% v 90.1% and 78.9%, p less than 0.01), and in ulceronecrotic malignancies (90.9% v 36.4% and 45.4%, p less than 0.05). In polypoid malignancies there was a significant trend (p less than 0.05) in favour of forceps biopsy, with a diagnostic yield of 100% compared with 95% for aspiration cytology and 93.3% for brush cytology. The accuracy of the different techniques was not significantly related to the site of the tumour. The cumulative accuracy of aspiration cytology and biopsy was significantly better than that of biopsy and brush cytology (98.5% v 90.9%, p less than 0.005). Aspiration cytology was diagnostic in 21 of 24 lesions that were negative with both brush cytology and biopsy. There were no false positive cytology or histology results. We conclude that aspiration cytology is a simple, safe, and reliable technique with a high diagnostic yield and is of particular value in submucosal, infiltrative, and ulceronecrotic tumours. 
Variation in intravaginal pressure measurements. The wide variation in intravaginal pressure measurements of the circumvaginal muscles (CVM) was studied in five subjects under well-controlled conditions. Previous research and clinical observations have indicated that fluctuations in the measurement of intravaginal pressure may be associated with time of day, day of testing, and existing stress factors. Subjects were assessed four times per day, on four consecutive days, for a total of 16 assessments. At each of the 16 conditions for a given subject, 10 CVM contractions lasting 12 seconds each were recorded and the variables, maximum pressure (MP10), peak maximum pressure (PMP), and abdominal pressure were analyzed. The within-subject variance was 15.5 (SD = 3.9); the between-subject variance was 132.4 (SD = 11.5). The effects of day, time, and stressor were analyzed by ANOVA specifically designed for variance estimates; no significant differences were found. The clinical observations that led to the study were not supported when systematically investigated. However, consistent data collection procedures appeared to reduce within-subject variance. 
Partial lamellar sclerouvectomy for ciliary body and choroidal tumors. The authors reviewed the postoperative course, visual results, histopathologic findings, and mortality data on 95 consecutive patients with tumors of the ciliary body and/or choroid who were managed by a partial lamellar sclerouvectomy. This surgical procedure is designed to remove the uveal tumor and leave intact the outer sclera and sensory retina. In this group of 95 patients, vitreous hemorrhage occurred in 79 (83%) cases, intraretinal or subretinal hemorrhage in 33 (35%), retinal detachment in 26 (28%), and cataract in 32 (34%). Most of the vitreous and retinal hemorrhages resolved spontaneously, sometimes leaving subretinal or preretinal fibrosis. A number of the postoperative retinal detachments resolved spontaneously, but retinal detachment surgery was necessary in 16 patients (17%), mostly in the earlier years of the survey. Most of the cataracts were mild and did not require surgery. The eventual postoperative visual acuity was equal to or better than the preoperative visual acuity in 23 cases (24%) over a mean follow-up period of 5 years. Enucleation was eventually necessary in 15 cases (16%), usually because of residual or recurrent tumor. Histopathologic diagnosis was uveal melanoma in 81 cases (85%) and other tumors in 14 cases (15%). There were no orbital recurrences, but distant metastases developed in five patients (5%), all of whom had undergone enucleation for recurrence of the intraocular melanoma. Although the surgical technique is difficult, partial lamellar sclerouvectomy appears to be a reasonable therapeutic option in selected cases of posterior uveal tumors. 
Telecanthal approach for meningiomas in the ethmoid and sphenoid sinuses. In three cases involving meningiomas in the ethmoid and sphenoid sinuses, transbasal spreading of the interocular distance (telecanthal approach) was used for tumor removal and reconstruction of the skull base. This telecanthal approach involves 1) bilateral en bloc removal of the superior lateral rim of the orbit, the nasal bone, and the posterior lateral wall of the orbit; 2) detachment of the medial canthal ligaments; and 3) spreading of the interocular distance. This approach provides a wide working space beneath the anterior half of the midline skull base, and needs neither a facial incision nor significant retraction of the brain. The surgical technique and its modification are described. The discussion focuses not only on comparisons with other techniques, but on the indications for this approach. Meningiomas originating in the paranasal sinuses are rare; a brief review of the literature concerning the clinicopathological features and pathogenesis is also given. 
National outcomes of cataract extraction. Endophthalmitis following inpatient surgery. We analyzed the likelihood of rehospitalization for endophthalmitis in 338,141 Medicare beneficiaries over age 65 years who were admitted to US hospitals for cataract extraction in 1984. This cohort represents approximately one half of all persons who underwent cataract extraction under the Medicare program in 1984. Extracapsular extraction was performed in 195,587 (58%) of cases, intracapsular cataract extraction in 99,971 (30%), and phacoemulsification in 28,474 (8%). The risk of rehospitalization for endophthalmitis in the year following surgery was 0.17% for intracapsular cataract extraction compared with 0.12% for extracapsular extraction or phacoemulsification (P less than .002). The risk of endophthalmitis at 1 month was higher for intracapsular cataract extraction than for extracapsular extraction or phacoemulsification (0.11% vs 0.085%), although the difference did not reach statistical significance. Cataract surgery accompanied by anterior vitrectomy increased the 1-month risk of rehospitalization for endophthalmitis to 0.41%, more than a four-fold increase over that for cataract surgery alone (0.09%; P less than .05). The rates of endophthalmitis at 1 year were 0.58% and 0.13%, respectively, for cataract surgery with anterior vitrectomy and cataract surgery alone (P less than .0001). No significant differences in the rate of rehospitalization for endophthalmitis were observed based on the use of an intraocular lens, age, or race. Endophthalmitis within 1 year of surgery was 1.2 times more frequent in men than in women (0.16% vs 0.13%; P = .03). Overall, the likelihood of postoperative endophthalmitis from a national sample is consistent with case series previously reported. 
Plasma immunoreactive endothelin-1 in experimental malignant hypertension. We measured plasma concentrations of immunoreactive endothelin-1 (irET-1) in the prehypertensive and hypertensive phases in spontaneously hypertensive rats (SHR) and in malignant hypertension caused by deoxycorticosterone acetate (DOCA)-salt administration in SHR. We also measured concentrations of this peptide in another model of malignant hypertension, the two-kidney, one clip (2K1C) renovascular hypertensive rats chronically given caffeine. Plasma irET-1 concentrations in young (6-week-old) and mature (18-week-old) SHR did not differ from those of age-matched Wistar-Kyoto (WKY) rats. Four weeks of treatment with DOCA-salt increased blood pressure, blood urea nitrogen, serum creatinine, and plasma irET-1 in SHR but not in WKY rats. Eight weeks of DOCA-salt treatment further increased these values in SHR. Plasma irET-1 concentrations were not increased in the 2K1C rats. Six weeks of caffeine administration increased blood pressure, blood urea nitrogen, serum creatinine, plasma renin activity, and plasma irET-1 in the 2K1C rats but not in the sham-operated rats. High-performance liquid chromatographic profiles of plasma extracts pooled from these rats with malignant hypertension showed that a major component of irET-1 eluted in the position of synthetic ET-1 (1-21). Furthermore, acute hypertension induced by angiotensin II or phenylephrine did not affect the plasma irET-1 concentration in rats. The results suggested that the plasma ET-1 concentration is increased in rat models of malignant hypertension and that the high blood pressure itself is not the main factor involved in the increase of plasma ET-1. 
Stage B adenocarcinoma of the prostate: transrectal US and pathologic correlation of nonmalignant hypoechoic peripheral zone lesions. Various benign conditions have been found to cause hypoechoic lesions in the prostate gland, thus mimicking the sonographic appearance of early prostatic cancer. Transrectal sonograms in a large series of patients with biopsy-proved clinical stage B prostatic cancer were retrospectively reviewed to determine the pathologic correlate to benign hypoechoic peripheral zone lesions. Transrectal sonograms demonstrated hypoechoic lesions that did not represent cancer in 25 of 160 patients examined. All lesions were contralateral to the carcinoma. Pathologic correlation was found in 24 of the 25 lesions. The results of this study show that contralateral hypoechoic lesions in patients with pathologically proved prostatic cancer do not necessarily imply bilateral tumor involvement; they accounted for benign lesions that mimicked the sonographic appearance of malignant tumors and thus produced a false-positive rate for cancer in the contralateral lobe of 16% of patients (25 of 160) with clinical stage B cancer. 
Comparison of efficacy of automatic implantable cardioverter defibrillator in patients older and younger than 65 years of age. PURPOSE: The efficacy of the automatic implantable cardioverter defibrillator (AICD) was compared in elderly patients and younger patients with life-threatening ventricular tachyarrhythmias. Clinical characteristics, surgical complications, and long-term survival rates were compared between the two age groups. PATIENTS AND METHODS: A retrospective study was conducted of 54 elderly patients (greater than 65 years) and 79 younger patients (less than 65 years) who had had AICDs implanted for recurrent symptomatic ventricular tachycardia and/or ventricular fibrillation. RESULTS: In 85% of elderly patients and 78% of younger patients, coronary artery disease was the underlying disease (NS). The mean left ventricular ejection fraction was 31.4 +/- 14.3% in the elderly patients and 35.7 +/- 17.6% in the younger patients (NS). Concomitant myocardial revascularization was performed in 37% of elderly patients and 29% of younger patients (NS); however, only 4% of elderly patients had concomitant left ventricular resection or cryoablation, compared with 15% of younger patients (p less than 0.001). Two patients in each age group died perioperatively (4% versus 3%, NS), and no significant difference in surgical morbidity or length of hospital stay following AICD implantation was noted between the age groups. In conjunction with AICD, elderly patients more commonly received antiarrhythmic drugs, with 54% of elderly patients taking amiodarone at the time of hospital discharge compared with 29% of the younger patients (p less than 0.008). In contrast, beta-blockers were more commonly used in younger patients (16% versus 2%, p less than 0.03). At a mean follow-up of 25 months, 11 (20%) elderly patients and 16 (20%) younger patients had died. Six deaths in elderly patients and five deaths in younger patients were classified as arrhythmic deaths (NS); however, only one younger patient and three elderly patients died suddenly (NS). Calculated survival curves demonstrated similar survival rates in the two age groups with approximately 90%, 87%, and 80% of the patients alive at 1, 2, and 3 years, respectively. Theoretic survival curves calculated from appropriate AICD shocks demonstrated significantly lower survival compared with actual survival. CONCLUSION: It is concluded that AICD is a very effective treatment for life-threatening ventricular tachyarrhythmias, and this benefit applies to elderly patients as well as younger patients. 
High incidence of antibodies to hepatitis C virus in alcoholic cirrhosis: fact or fiction? An enzyme immunoassay (Ortho-HCV ELISA) for antibodies against the hepatitis C virus was used to test serum samples from 39 patients with alcoholic cirrhosis and 34 patients with alcoholic hepatitis or fatty liver. The frequency of a positive result in the cirrhotics was significantly higher than in the alcoholics without cirrhosis (38.5% vs 8.8%, P less than 0.01). However, the positive results in the cirrhotics were associated with high gammaglobulin concentrations, and optical density values in the assay correlated closely with serum globulin (r = 0.73, P less than 0.01). The findings suggest that serum from patients with alcoholic cirrhosis may contain a component that give false-positive results in the assay. 
Paraesophageal hernia causing colonic obstruction. In a paraesophageal hernia, the esophagogastric junction remains below the hiatus while portions of the fundus or other parts of the stomach herniate in front and to the left of the esophagogastric junction through the hiatus into the thorax. We describe an unusual presentation of a paraesophageal hernia, in which herniation of the splenic flexure of the colon led to colonic obstruction. 
Psychophysiological parameters of migraine and muscle-contraction headaches. Previous headache studies have been unable to verify the presumed presence of headache. Attempting to correct this design fault, the present study assessed four psychophysiological measures (frontalis EMG, temporal BVP, temporal and finger skin temperature) and salient subjective measures in 13 migraineurs, eight muscle-contraction headache sufferers, and 13 age-matched normals. All subjects submitted to two 30-minute sessions of quiet monitoring, and for the headache subjects, one of the sessions was headache active. A bogus, but convincing preliminary "assessment" revealed insufficient headache activity in the headache active session, forcing subjects to reschedule that session in the future when a strong headache was present. A parallel manipulation was employed with the normal subjects. A MANOVA failed to discriminate within- or between-group differences on the psychophysiological measures. Self-reported pain was uncorrelated with the psychophysiological indices. These results cast further doubt on the validity of the psychophysiological measures employed in this study, the same ones routinely endorsed by headache researchers and therapists. We discuss problems of recruitment, compliance, and attrition in basic headache research. 
Effects of dietary calcium on blood pressure, vascular reactivity and vascular smooth muscle calcium efflux rate in Zucker rats. Previous data from this laboratory indicate that hypertension in insulin resistant Zucker obese rats is accompanied by an impairment in vascular smooth muscle Ca2+ efflux. Since insulin resistant states are also generally salt-sensitive and dietary Ca2+ reduces blood pressure in some salt-sensitive states, we evaluated the effects of dietary Ca2+ on blood pressure and vascular reactivity and examined whether these effects are due to increased vascular smooth muscle Ca2+ efflux. We assigned 16 obese and 16 lean rats to a normal (0.5%) or high (1.5%) Ca2+ diet for 28 days, following which intraarterial blood pressure and in vitro vascular smooth muscle 45Ca efflux and vascular reactivity responses to phenylephrine and serotonin were measured. Blood pressure was elevated in the obese rats on both diets (P less than 0.2), and the high calcium diet lowered both systolic and diastolic pressure in both the lean and obese rats (P less than 0.5). Vascular reactivity was higher in the obese rats (P less than 0.2), but dietary Ca2+ exerted opposite effects on vascular reactivity to the agonists. High Ca2+ reduced sensitivity to serotonin in the obese rats by 54% (P less than .05) without affecting sensitivity in the lean rats. In contrast, the high Ca2+ diet increased sensitivity to phenylephrine by 31% in both groups (P less than .01). 45Ca efflux was lower in the obese rats compared to the lean rats (P less than .05), and the high Ca2+ diet increased this rate by 23% in the lean, but not the obese, rats (P less than .05). 
Using anticoagulants safely. Guidelines for therapeutic and prophylactic regimens [published erratum appears in Postgrad Med 1991 Sep 1;90(3):48] Heparin and warfarin sodium (Coumadin, Panwarfin, Sofarin) are used most often to treat acute and recurrent venous thromboembolic disease, arterial disease, valvular heart disease, and atrial fibrillation. These agents along with dextran, pneumatic compression devices, and gradient stockings are also used to prevent deep venous thrombosis and pulmonary embolism in patients at high risk (eg, those with venous stasis, lower limb or spinal cord trauma, clotting abnormalities). Anticoagulation therapy is monitored by maintaining the activated partial thromboplastin time and the prothrombin time in the therapeutic range. 
Clonal immunoglobulin gene rearrangement in the infarcted lymph node syndrome. The authors report a case of complete lymph node infarction in which a specific etiology could not be determined by morphologic or immunophenotypic studies; however, clonal rearrangement of the immunoglobulin gene was demonstrated by Southern blot hybridization of DNA extracted from the necrotic tissue. A subsequent lymph node biopsy later was diagnosed as malignant lymphoma, using morphologic, immunophenotypic and genotypic criteria. Identical clonally rearranged bands were present in DNA from both the infarcted nodal and the subsequent tissue biopsies. In the setting of lymph node necrosis, gene rearrangement studies may provide diagnostic information concerning clonality, even if morphologic and immunophenotypic studies are indeterminate for a lymphoproliferative process. 
Cerebral structure on magnetic resonance imaging in language- and learning-impaired children. Using magnetic resonance imaging 20 language- and learning-impaired children were compared with 12 normal control subjects. Gross brain structure was remarkably normal in the language- and learning-impaired group. Semiautomated morphometry was used to measure hemispheric volumes and cerebral asymmetries in six cerebral regions. The volume of the left posterior perisylvian region was significantly reduced in language- and learning-impaired children. Asymmetries in inferoanterior and superoposterior cerebral regions were also significantly different in this group. Results of descriptive group comparisons of estimated volumes of other cerebral gray-matter structures raise the possibility that some language- and learning-impaired children may have additional volume reductions in cortical and subcortical structures. The results suggest that hemispheric specialization of function may be anomalous in this population. 
Intraovarian abscess treated with laparoscopic aspiration and povidone-iodine lavage. A case report. Intraovarian abscess is an unusual form of pelvic inflammatory disease usually managed with laparotomy. A patient with prolonged morbidity from an intraovarian abscess following pelvic inflammatory disease associated with an intrauterine contraceptive device was managed with laparoscopically guided needle aspiration of the abscess and povidone-iodine lavage. Laparoscopy should play a greater role in the management of pelvic inflammatory disease. 
Hemifacial spasm. Occurrence in multiple sclerosis. We present six patients with hemifacial spasm and multiple sclerosis. To our knowledge, this association has not been described previously in the North American literature. Magnetic resonance imaging was obtained in all the patients and plaques consistent with multiple sclerosis were identified. In two patients the plaques were seen in the area of the facial nucleus on the involved side. We suggest that hemifacial spasm can be a manifestation of multiple sclerosis. These cases illustrate the utility of magnetic resonance imaging in the investigation of hemifacial spasm. Our findings also support a central (nuclear) origin in multiple sclerosis associated with hemifacial spasm. 
Venous thromboembolism after brain tumor surgery: a retrospective review. We retrospectively reviewed the incidence rate of clinical postoperative deep vein thrombosis and/or pulmonary embolism in 1703 patients undergoing initial craniotomy for meningioma, glioma, or cerebral metastasis. The incidence rate of clinical thromboembolic complications was 1.59% for all tumor groups within the first 4 weeks of surgery. Patients undergoing surgery for meningiomas had a statistically significant increased risk of thromboembolism despite fewer overall perioperative risk factors, when compared with the other tumor groups. The tumor-specific incidence rates of deep vein thrombosis and/or pulmonary embolism for meningioma, glioma, and metastasis were 3.09%, 0.97%, and 1.03%, respectively. Whether this difference was a result of increased surgical time or an inherent property of meningiomas could not be ascertained. 
Elevated cerebrospinal fluid pressures in patients with cryptococcal meningitis and acquired immunodeficiency syndrome. Increased intracranial pressure has been a noteworthy problem in some of our patients with cryptococcal meningitis and acquired immunodeficiency syndrome (AIDS), and this appears to be a feature observed in patients with cryptococcal meningitis reported in the literature. Whereas most attention of clinicians is presently focused on optimizing the antifungal regimen, so as to improve on high failure rates in cryptococcal meningitis in AIDS, little attention has been paid to the problem of intracranial hypertension. We argue that visual loss and some of the cases of death early after the onset of chemotherapy may be related to high cerebrospinal fluid (CSF) pressure, regardless of antifungal therapy. The possible pathophysiologic mechanisms are discussed, and we postulate that the mechanism is reduced CSF outflow possibly due to increased outflow resistance, not necessarily accompanied by prominent cerebral edema. Optimal therapy of this complication is not yet established, but some measures that may be helpful are ventricular shunting, frequent high-volume lumbar punctures, and possibly glucocorticoids. 
Barriers to cholesterol testing in a rural community. BACKGROUND. The purpose of this study was to investigate the factors that determine whether residents in a rural community have their cholesterol tested. METHODS. A population-based survey was conducted in 1987 as part of a community-oriented primary care project that sought to define and address the causes of and burden caused by increased cardiovascular disease in an economically depressed agricultural region of New York. All of the residents living in two towns in the region who were over 16 years of age and who lived in their homes year-round were surveyed. Demographic information was obtained from the participants, as well as information about previous cholesterol testing and their cardiovascular-risk knowledge and behaviors. The serum cholesterol of each participant was measured. RESULTS. Of the 557 households contacted, 508 (91%) households participated. A total of 1063 persons over 16 years of age were surveyed, and 973 (92%) were screened for cholesterol. Overall, 24% reported prior cholesterol testing. Logistic regression analysis identified several independent factors that were associated with a reduced likelihood of ever having had a cholesterol test. These factors included: (1) age under 45 years, (2) having less than 12 years of education, (3) having an income of less than $10,000, (4) not having health insurance, (5) not having visited a physician within the previous year, and (6) practicing three or more high-risk cardiovascular behaviors. The participants' cardiovascular knowledge made no independent contribution to having had their cholesterol levels tested. CONCLUSIONS. Many of the factors that prevent cholesterol testing are socially determined. The results of this study suggest that financial and social barriers are two of the major obstacles to residents of rural communities having their cholesterol levels tested. 
Lymphocytic gastritis in nonulcer dyspepsia. The prevalence of lymphocytic gastritis, a specific form of chronic gastritis characterized by infiltration of gastric superficial epithelium with T lymphocytes, has been established in nonulcer dyspepsia. Among a population sample of 586 patients at risk for gastric carcinoma, 0.83% of patients with nonulcer dyspepsia and 1.63% of patients with chronic active gastritis showed lymphocytic gastritis. Among routine gastric biopsies from 5130 patients, only five cases met histological and immunohistochemical criteria of lymphocytic gastritis. 
Sleep apnea in infants who succumb to the sudden infant death syndrome. Previous studies have shown the frequency of respiratory pauses to be altered in groups of infants at risk for the sudden infant death syndrome (SIDS). In this study, we assess the frequency of apneic pauses during quiet sleep and rapid eye movement sleep in control infants and infants who subsequently died of SIDS. Sleep states were identified in 12-hour physiological recordings of SIDS victims and matched control infants, and the number of respiratory pauses from 4 to 30 seconds in duration was computed for quiet sleep and rapid eye movement sleep. SIDS victims 40 to 65 days of age showed significantly fewer apneic pauses than did age-matched control infants across the two sleep states. Fewer short respiratory pauses accounted for most of the reduction in number of apneic events in the SIDS victims during both sleep states. During the first month of life, SIDS victims did not differ significantly from control neonates on this measure. The finding that this respiratory difference exists during the second month of life, just before the period of maximal risk for SIDS, but not earlier, may have implications for the etiology of SIDS deaths. 
Myeloablative therapy and unpurged autologous bone marrow transplantation for poor-prognosis neuroblastoma: report of 34 cases. From October 1984 to November 1987, 34 patients aged from 1 year 1 month to 7 years 7 months with resistant or relapsed neuroblastoma (NB) (group 1, 10 patients), unselected disseminated NB (group 2, 14 patients), or selected disseminated NB (group 3, 10 patients) received myeloablative therapy (MAT) followed by unpurged autologous bone marrow transplantation (ABMT) at the end of an intensive protocol, which included high-dose chemotherapy and surgery to the primary tumor. Median time from diagnosis to MAT and ABMT was 6 months (5 months from last relapse to MAT and ABMT in the relapsed patients). The MAT regimen included vincristine, fractionated total body irradiation (TBI), and melphalan. Seventeen patients were grafted in complete remission (CR), five in very good partial remission (VGPR), 10 in partial remission (PR), and two in progressive disease (PD). The acute toxic death rate was 2.9%. The overall progression-free survival was 29%. The median progression-free survival was 20 months for the 17 patients grafted in CR, 6 months for the five patients grafted in VGPR, and 12 months for the 10 patients grafted in PR. 
Variation of initial serum bilirubin rise in newborn infants with type of illness. Hyperbilirubinaemia in newborn infants is generally regarded as a problem, and bilirubin itself as toxic metabolic waste, but the high frequency in newborn infants suggests that the excess of neonatal bilirubin may have a positive function. To investigate the hypothesis that bilirubin has a role as a free-radical scavenger, the rate of rise in serum bilirubin in the first few days of life was measured in 44 infants with five illnesses thought to enhance free-radical production and in 58 control infants. The infants were selected from 2700 consecutive births by exclusion of those with factors known to affect bilirubin metabolism, including enteral feeding. The control infants were those who seemed to be ill and received treatment, including restriction of enteral feeds, but in whom no illness, or disorders not related to free-radical production, were found. The mean serum bilirubin rise was significantly lower in the combined illness group than in the control group (36.1 [95% Cl 26.9-45.3] vs 66.7 [55.9-77.5] mumol.l-1.day-1; p less than 0.0001). In subgroup analyses the mean rises in infants with circulatory failure, neonatal depression/asphyxia, aspiration syndromes, and proven sepsis were significantly lower than in controls matched for gestational age and birthweight, but rises in infants with respiratory distress and their matched controls did not differ. These findings are consistent with the hypothesis that bilirubin is consumed in vivo as an antioxidant. Such consumption may operate in vivo in addition to the standard pathways for bilirubin metabolism (production, isomerisation, and excretion). 
Stereopsis after unilateral anterior temporal lobectomy. Dissociation between local and global measures. In man, an impairment in stereopsis may occur following damage outside the occipital lobes. If local and global stereopsis can be dissociated, this may imply that different mechanisms mediate these functions. We tested 44 patients with unilateral anterior temporal lobe excisions and 23 normal control subjects on two tasks. In the local stereopsis task, subjects indicated which of two pins varying in disparity between 4 and 512 s of arc was closer. Results showed no threshold impairment in any group. In the global stereopsis task, random-dot stereograms varying in binocular correlation were presented in random order, and subjects indicated if the squares perceived in depth were in front of or behind the screen. At binocular correlations between 50% and 70%, left and right temporal lobectomy resulted in a deficit, which was more marked following right-sided excisions. These results are concordant with earlier work (Ptito and Zatorre, 1988), and with other evidence of a right hemisphere superiority in treating binocular depth information. Moreover, the fact that global stereopsis is impaired in the presence of intact local stereopsis suggests that closely related but not identical mechanisms are involved, and fits the notion that there is a hierarchical organization of the visual pathways originating in the striate cortex leading into temporal cortex. Global stereopsis would thus be mediated in temporal lobe areas that receive information about local disparities from more posterior regions. 
A randomized controlled trial of a 12-month course of recombinant human interferon-alpha in chronic delta (type D) hepatitis: a multicenter Italian study. To determine whether long-term therapy with recombinant interferon-alpha can improve the course of chronic delta hepatitis, 61 Italian patients with this disease were randomly assigned to receive either interferon-alpha-2b three times a week (5 MU/m2 for 4 mo and then 3 MU/m2 for another 8 mo) or no treatment. At the end of the 12-mo study, all patients were followed-up for 12 additional months. Normalization or decrease of more than 50% from baseline of serum ALT levels occurred in 42% of treated patients the fourth month of therapy, 26% the twelfth month and 3% the twenty-fourth month vs. 7%, 7% and 0%, respectively, in the control group. However, relapses occurred in 7 of 8 (87.5%) responders 1 to 10 mo (mean = 3.5 mo) after cessation of therapy. Liver biopsies were carried out at baseline and during the twelfth month of treatment. Histological improvement, mostly caused by decrease of portal inflammation, was observed in 57% of treated and 36% of untreated patients. Measures of antiviral activity (serum hepatitis delta virus RNA and intrahepatic hepatitis delta antigen) showed similar levels in treated and control patients. In treated patients the percentage of patients who were negative for HDV RNA never exceeded that of baseline. Although interferon-alpha in the dosage given in this study had no antiviral effect on patients with chronic hepatitis D, it reduced hepatic inflammation as measured by ALT levels. Whether a longer duration or reinstitution of interferon-alpha therapy would achieve long-term control of ALT levels and prevent chronic liver damage is not known. 
Beriberi heart disease in a schizophrenic with an unusual diet. A 37-year-old male presented with peripheral edema of sudden onset. Other signs of heart failure were absent. Subsequent evaluation revealed that the patient was a schizophrenic whose diet consisted almost entirely of carbohydrates. A clinical diagnosis of beriberi heart disease was made and the patient improved dramatically within several days of thiamine supplementation. The presentation of beriberi heart disease in developed countries is discussed. Emphasis is placed on food faddists and psychiatric patients in whom clinical findings may be subtle or absent. 
Microscopic activity in ulcerative colitis: what does it mean? To determine the prognostic importance of microscopic rectal inflammation we followed up 82 patients (aged 21 to 78 years, 44 men) with chronic quiescent ulcerative colitis over 12 months. At trial entry each patient underwent a rectal biopsy and sections were graded independently by two histopathologists. A chronic inflammatory cell infiltrate of varying severity was present in all biopsy specimens, and 58% had crypt architectural irregularities. In addition, 32% had evidence of acute inflammatory activity: 28% acute inflammatory cell infiltrate, 11% crypt abscesses, and 22% mucin depletion. Agreement between the two histopathologists for the presence of each of these features was 94% (90-98%). During the 12 month follow up 27 patients (33%) relapsed after a mean interval of 18 weeks (range 3-44 weeks). Relapse rates were unrelated to duration or extent of disease or to the type of maintenance drug treatment. In patients with an acute inflammatory cell infiltrate 52% relapsed, whereas in the absence of such an infiltrate only 25% relapsed (p = 0.02). Similarly, relapse rates were higher in the presence of crypt abscesses (78% v 27%, p less than 0.005), mucin depletion (56% v p less than 0.02), and breaches in the surface epithelium (75% v 31%, p = 0.1). The presence of a chronic inflammatory cell infiltrate or crypt architectural irregularities, however, bore no relation to the frequency of colitis relapse. 
The incidence and relationship of cervical spine anomalies in patients with cleft lip and/or palate. The relationship, incidence, and distribution of cervical spine anomalies were assessed in 468 patients with cleft lip and/or palate. The patients were placed into four groups: lip and/or alveolar; complete unilateral or bilateral; isolated palatal; and soft palate or submucous clefts. Cervical anomalies were observed in 22% of the cleft patients and in 7% of the noncleft group. Patients with soft palate and submucous clefts had the highest incidence of vertebral anomalies (45%), whereas patients with cleft lip and/or alveolus had an incidence similar to the noncleft group. Patients with complete unilateral and bilateral clefts also had a higher incidence (15.6% to 19.0%) of anomalies than the noncleft group. Cervical anomalies occurred primarily in the occipital-C1-C2 region. The possible implications of these findings are discussed. 
The use of direct mail to increase clinician knowledge: an intervention study. A probability sample of American general practitioner dentists, 40 years of age or older, in solo private practice, was the target of two direct mail interventions offered at two different times, to test whether knowledge regarding prophylaxis of patients at risk for infective endocarditis could be improved. Tests of knowledge were responses in a mail questionnaire to clinical vignettes, designed to elicit the content of antibiotic regimens used for patients at risk. The research design enabled detection of (1) the effect of the interventions; (2) the differences in their effect; (3) the attenuation of their effect; and (4) the effect of time. Where baseline knowledge was low, it was improved and did not rapidly disappear. Both mail interventions were equally effective, in most instances, and there was no attenuation of the interventions' effect and no effect of time on the control groups' knowledge over a 4 1/2 month period. The results suggest that it is possible to improve clinicians' knowledge of expert recommendations through direct mail intervention. 
Budd-Chiari syndrome in association with Behcet's disease. Budd-Chiari syndrome developed in 3 patients with preexisting Behcet's disease. Benign intracranial hypertension was the chief presenting complaint in one patient, who later suffered extensive inferior vena caval and hepatic vein thrombosis, with manifestations of Budd-Chiari syndrome. She did not respond to treatment and subsequently died of hepatic coma. In the other 2 patients, Budd-Chiari syndrome was confirmed by liver biopsy. Both patients made a good recovery and remain well at the time of this report. 
Biplane transesophageal echocardiography: clinical applications of the long-axis plane. Tomography of the heart and great vessels is limited during conventional transesophageal echocardiography by the inability to rotate the transducer at the end of the transesophageal echocardiographic endoscope. A biplane transesophageal echocardiographic probe has been developed recently with a second transducer capable of long-axis imaging that yields long-axis views in addition to the familiar short-axis views. We describe our experience with 37 patients with a variety of cardiovascular diseases. In 17 patients new diagnostic information was obtained, although management was not changed. Long-axis scanning was particularly useful in the assessment of diseases of the thoracic aorta, valvular morphology and regurgitation, and congenital heart disease. Important limitations of the biplane imaging system include reduced image quality and a continued inability to rotate the transducer to obtain any desired plane of imaging. Nonetheless, biplane imaging enhances the versatility of transesophageal echocardiography and improves three-dimensional conceptualization of cardiac disease. 
Arachnoid cyst of the cerebellopontine angle manifesting as contralateral trigeminal neuralgia: case report. A case of an arachnoid cyst in the cerebellopontine angle manifesting as contralateral trigeminal neuralgia is presented. Decompression and excision of the lesion resulted in total relief of symptoms. The possible causes of contralateral trigeminal neuralgia are briefly reviewed, and the surgical treatment of this entity is discussed. 
Alpha 2-macroglobulin-kallikrein complexes detect contact system activation in hereditary angioedema and human sepsis. Activation of the contact system has been documented in severe sepsis and hereditary angioedema, but a sensitive, specific, and quantitative assay for assessing the degree of involvement of this proteolytic enzyme cascade is not yet available. We have developed a quantitative sandwich enzyme-linked immunosorbent assay (ELISA) for the alpha 2-macroglobulin-kallikrein (alpha 2M-Kal) complex using an F(ab')2 derivative of a monospecific polyclonal antibody against alpha 2 M as the capture antibody and a unique murine monoclonal antibody, 13G11, against the heavy chain of kallikrein as the detector antibody. The assay does not detect complexes in normal plasma but reacts with complexes generated by activating normal plasma with dextran sulfate at 4 degrees C in a range of 5 to 375 nmol/L. A close correlation of the ELISA with an amidolytic assay for alpha 2M-Kal was documented. Patients with sepsis syndrome but negative bacterial blood cultures did not show elevated plasma complexes, whereas a majority of those with positive blood cultures did show modest elevation and a single patient with septic shock showed a very high level of alpha 2M-Kal complex. Similarly, a patient with classic hereditary angioedema (HAE) showed increased concentration of complexes on three separate occasions during attacks but normal levels between attacks. Two other HAE patients did not show elevated levels at quiescent periods. The ELISA for alpha 2M-Kal appears to be sensitive, specific, and quantitative, and it can be used to reflect the degree of contact system activation in human sepsis and in HAE attacks. 
Progressive loss of speech output and orofacial dyspraxia associated with frontal lobe hypometabolism. Three patients are described with slowly progressive loss of speech and dysarthria associated with orofacial dyspraxia, initially with intact written language, who subsequently developed more widespread cognitive abnormalities. Positron emission tomography (PET) revealed bifrontal hypometabolism in all of the patients, most marked in the inferior and lateral portions of both frontal lobes, with some extension into the parietal and temporal cortices in one case. These patients may represent a further example of focal progressive cortical degeneration. 
Mucocutaneous disease in pediatric human immunodeficiency virus infection. Children with HIV infection may develop a wide variety of infectious and inflammatory diseases of the skin. These disorders are often more severe and more difficult to treat than in the healthy child. In some cases, disorders of the skin or mucous membranes may provide an early clue to the presence of pediatric HIV infection. 
Overwhelming necrotizing tracheobronchitis due to inadequate humidification during high-frequency jet ventilation. Necrotizing tracheobronchitis (NT) associated with conventional mechanical ventilation or high-frequency jet ventilation (HFJV) is a lesion reported most often in neonates. In most cases, a specific cause is not identified. We describe a case of NT in an adult that occurred during HFJV and was attributable to inadequate humidification. 
Helicobacter pylori-negative duodenal ulcer. PURPOSE PATIENTS AND METHODS: Helicobacter pylori (HP) is present in more than 90% of duodenal ulcers (DUs). To investigate the pathophysiology in those patients with DU who are HP-negative compared with those who are HP-positive, we interviewed consecutive patients prior to endoscopy regarding factors often associated with ulcer disease. At esophagogastroduodenoscopy, antral biopsy specimens were obtained for urease test, culture, and Warthin Starry staining for HP in all patients with DU who did not have active bleeding. RESULTS: Compared with HP-positive patients who had DU, HP-negative patients with DU were more likely to be aspirin users and less likely to have had prior ulcers. HP-positive patients with DU had more severe antral inflammation than HP-negative patients. Whites were more likely to be HP-negative than blacks. HP-negative patients with DU most commonly presented with bleeding, whereas HP-positive patients with DU presented with pain. CONCLUSIONS: Our findings suggest a different mechanism for DUs in patients who are HP-positive versus those who are HP-negative, and this difference might have a bearing on treatment. The absence of HP should lead to a more thorough search for nonsteroidal anti-inflammatory drug/aspirin use, Zollinger-Ellison syndrome, and other potential causes of DUs. 
Increased MR signal intensity due to cervical myelopathy. Analysis of 29 surgical cases. The cases of 29 patients with cervical myelopathy, who had been treated by anterior spine fusion, were reviewed. The relationship between pre- and postoperative magnetic resonance (MR) images was investigated with special reference to increased signal intensity in the spinal cord on the T2-weighted images and the relevance of this finding to clinical conditions. Preoperatively, there were areas of increased signal intensity in 12 patients whereas there were no areas of increased signal intensity in the other 17. The lesions were not clearly demonstrated on T1-weighted images. The pre- and postoperative clinical condition of the patients whose preoperative MR images showed areas of increased signal intensity in the spinal cord on T2-weighted images was worse than that of the patients who did not have areas of increased signal intensity. Of the 12 patients with regions of increased signal intensity preoperatively, five showed decreased signal intensity postoperatively compared to the preoperative levels and seven had no change. The postoperative recovery of the five patients who showed decreased signal intensity postoperatively was better than that of the seven patients who exhibited no change. The areas of increased MR signal in the spinal cord might be due to edema, cord gliosis, demyelination, or microcavities. 
Intraosseous vascular malformations of the orbit. Intraosseous vascular malformations are rare benign tumors involving the bones of the orbit. The diagnosis should be considered when a patient presents with an enlarging mass fixed to bone in the upper face, and the characteristic x-ray appearance should be looked for on plain films. Treatment is local excision of the bone containing the tumor and immediate reconstruction with autogenous bone. 
Impedance plethysmography: a new method for continuous muscle perfusion monitoring. Vigilant postoperative monitoring of the buried muscle flap is critical after free transfer because early diagnosis of vascular insufficiency is essential to allow prompt correction. We have identified a monitoring method utilizing needle electrodes and impedance plethysmography that gives a beat-to-beat representation of muscular perfusion. In 25 New Zealand White rabbits the gastrocnemius muscle was isolated on its vascular pedicle, and two intramuscular needle electrodes were placed. The instantaneous impedance changes of the muscle (corresponding to the pulsatile volume changes of perfusion) were measured and recorded. Using this representation of perfusion, an independent judge was able to correctly diagnose muscular ischemia 100 percent of the time (n = 25). Further, the judge was able to correctly distinguish the ischemia as arterial (n = 10) or venous (n = 10) in origin 100 percent of the time. Additionally, we monitored muscle perfusion transcutaneously in five free muscle flaps and demonstrated a reliable impedance signal that correlated with perfusion. 
Importance of antithrombin therapy during coronary angioplasty. Angioplasty procedures with balloons, cutters or lasers all may greatly enlarge the arterial lumen, but luminal diameter may decrease because of mural thrombus in 70% to 80%, smooth muscle proliferation, vasoconstriction or recoil. Thrombin binds to arterial wall matrix and fibrin within a thrombus. Heparin dose-dependently decreases platelet and thrombus deposition but does not eliminate these even at high doses. Specific thrombin inhibition started before angioplasty experimentally prevents mural thrombus and limits platelet deposition to a single layer or less. Experimentally, anticoagulant and antifibrin effects occur at lower antithrombin blood levels and lower activated partial thromboplastin times (1.7 times control). Because platelets are so sensitive to thrombin, the higher level of thrombin inhibition required may occur at a specific level (activated partial thromboplastin time greater than or equal to 2 times control); this is not defined in humans. The duration of therapy is not defined in animals or humans. Thrombus and thrombin may be related to cellular proliferation. 
A pathophysiological interpretation of unresponsiveness to spironolactone in a stepped-care approach to the diuretic treatment of ascites in nonazotemic cirrhotic patients. It has been hypothesized that the magnitude of proximal sodium reabsorption affects the response to aldosterone antagonists in nonazotemic cirrhotic patients with ascites. To verify this hypothesis, we evaluated intrarenal sodium handling by lithium clearance in 51 nonazotemic ascitic cirrhotic patients and in 23 controls who were maintained on the same low-sodium diet (80 mmol/day). Seven of 51 cirrhotic patients underwent spontaneous diuresis, whereas 44 required diuretic treatment. Treatment was started with spironolactone at a dose of 150 mg once daily. The dose was increased to 300 mg and then to 500 mg once daily if no response ensued. Cirrhotic patients who did not experience ascites mobilization with 500 mg spironolactone were then treated with a combined diuretic regimen that included spironolactone at a fixed dose (500 mg once daily) and furosemide at an initial dose of 50 mg once daily. The dose was increased to 100, 150 and 200 mg once daily if no response was noticed. Response to diuretic treatment was defined as body weight loss greater than 700 gm every 3 days until ascites became clinically undetectable. Nonresponders (43%) to spironolactone showed lower sodium fractional excretion (0.34% +/- 0.28% vs. 0.80% +/- 0.50%; p less than 0.001) because of a lower fractional sodium delivery to the distal tubule (18.2% +/- 5.8% vs. 23.4% +/- 7.2%; p less than 0.025) than responders. 
Correction of non-24-hour sleep/wake cycle by melatonin in a blind retarded boy. A 9-year-old, blind boy with severe mental retardation with a chronic sleep/wake disturbance had a circadian rhythm of 24.75 hours and an internal desynchronization of the endogenous rhythms. Treatment with oral melatonin given at 6 PM induced a regular sleep/wake pattern. Melatonin, in this patient, convincingly entrained the endogenous rhythm to the appropriate chronological 24-hour day. 
Symptomatic hyponatraemia due to inappropriate antidiuretic hormone secretion following minor surgery. A rare case of the syndrome of inappropriate antidiuretic hormone secretion occurring after minor surgery is presented. A ten-year-old, previously healthy boy underwent general anaesthesia for detorsion and right orchiopexy. Throughout the operations, which lasted for one hour, he received 120 ml Ringer's lactate solution. The immediate postoperative period was uneventful. Twenty-two hours postoperatively he was found unconscious with generalized tonic-clonic seizures. Simultaneously obtained serum sodium concentration (121 mEq.L-1) serum osmolarity (265 mEq.L-1), urine sodium concentration (87 mEq.L-1) and urine osmolarity (525 mEq.L-1) suggested inappropriate antidiuretic hormone secretion which was confirmed by an elevated serum arginine-vasopressin (AVP) level of 14.5 pcg.ml-1 (normal 1-5 pcg.ml-1) measured by radioimmune assay. He was treated with a single iv dose of 30 mg furosemide and fluid restriction, which produced a gradual increase of his serum sodium concentration to normal within two days. He was well during the remainder of his hospitalization. 
Epidemiology of colonic symptoms and the irritable bowel syndrome. Functional gastrointestinal disease is believed to be very common, but reports of its prevalence have not usually evaluated random community samples, and validated questionnaires have not been used to elicit symptoms. The prevalence of specific colonic symptoms and the irritable bowel syndrome among representative middle-aged whites was determined from a defined population, and the impact of these symptoms on presentation for medical care was measured. An age- and sex-stratified random sample of 1021 residents of Olmsted County, Minnesota, aged 30-64 years, was obtained. All subjects were mailed a valid self-report questionnaire that identified gastrointestinal symptoms and functional gastrointestinal disorders. The response rate was 82% (n = 835). The age- and sex-adjusted prevalence of abdominal pain (more than six times in the prior year) was 26.2 per 100 (95% confidence interval, 23.1-29.2). The prevalence of chronic constipation (hard stools and straining and/or less than 3 stools per week greater than 25% of the time) was 17.4 (95% confidence interval, 14.8-20.0), whereas the prevalence of chronic diarrhea (loose watery stools, and/or greater than 3 stools per day greater than 25% of the time) was 17.9 (95% confidence interval, 15.3-20.5). The prevalence of abdominal pain and disturbed defecation was similar in women and men, except that infrequent defecation and straining at stool were more common in women. Using the Manning symptom criteria to identify irritable bowel syndrome (greater than or equal to 2 of 6 symptoms in those with abdominal pain more than six times in the prior year), the prevalence of irritable bowel syndrome was 17.0 per 100 (95% confidence interval, 14.4-19.6). Overall, 71 persons (9%) reported visiting a physician for abdominal pain or disturbed defecation in the prior year; a subset of variables related to pain severity were the best predictors of health care seeking after adjustment for age and gender. However, these accounted for only 22% of the log likelihood. In conclusion, more than one third of an unselected middle-aged population reported chronic abdominal pain or disturbed defecation, and more than one in six had symptoms compatible with the irritable bowel syndrome. Only a minority had presented for medical evaluation; moreover, the characteristics of the abdominal complaints did not explain the seeking of health care in most cases. 
Hypoprothrombinemia and hemorrhage in a surgical patient treated with cefotetan. For 4 days before surgical repair of a diverticulitic colovesical fistula and for 6 days after, a 63-year-old man was treated with 2 g of intravenous cefotetan disodium every 12 hours for associated urosepsis with bacteremia. Postoperatively, the patient followed a diet of intravenous nutrition only. Uneventful convalescence was interrupted by signs of sudden major blood loss, accompanied by prolonged prothrombin time. After stabilization with packed red blood cells, fresh plasma, crystalloids, and parenteral vitamin K, laparotomy revealed a huge intra-abdominal clot, which was evacuated. This case illustrates the risk of unexpected hypoprothrombinemia and hemorrhage in a cefotetan-treated surgical patient who demonstrated none of the usual comorbid conditions generally described in patients with antibiotic-induced hypoprothrombinemia. Like cefamandole nafate, cefoperazone sodium, moxalactam disodium, and other cephalosporins containing the methylthiotetrazole side chain, cefotetan appears to pose an unusual risk of major bleeding. 
Sticks and stones may break my bones ... reasoning about illness causality and body functioning in children who have a chronic illness. Children's concepts about illness causality and bodily functioning change in a predictable way with advancing age. Differences in the understanding of these concepts in healthy children vs children with a chronic illness have not been clearly delineated. This study included 49 children with a seizure disorder, 47 children with an orthopaedic condition, and 96 healthy children, all with normal intelligence and ranging in age from 5 to 16 years. It demonstrates systematic differences in children's general reasoning skills and in their understanding of concepts about illness causality and bodily functioning, as a function of their age and experience of illness. At all ages, children who had a condition with orthopaedic involvement reported less sophisticated general reasoning and concepts about illness than did healthy children; children with a seizure disorder reported similar general reasoning skills to those of healthy children, but considerably less sophisticated concepts about illness. Children's concepts about body functioning did not differ as a function of the presence of a chronic illness. When their different levels of general cognitive reasoning were statistically controlled, children with a chronic illness had somewhat more sophisticated concepts about bodily functioning than did healthy children. Differences in conceptual development among children with different types of illnesses lead to interesting speculations with regard to the effects of particular illness characteristics on children's cognitive development. 
Wolf blade plate ankle arthrodesis. Fifteen patients, each of whom had a Wolf blade plate ankle arthrodesis, were followed for a mean of 56 months. The mean age at the time of operation was 46.7 years. The preoperative diagnosis was posttraumatic arthritis in 16 cases and one each of degenerative arthritis, rheumatoid arthritis, and avascular necrosis of the talus. Eighteen of the 19 cases fused for a fusion rate of 94.7%. The average fusion position was 2.9 degrees of plantar flexion and 5 degrees of valgus. All patients whose ankle fused were satisfied with their results. The average Mazur postoperative score was 75 (range, 33-91). Five patients had delayed wound healing. The Wolf blade plate is a simple and easy method to fuse the ankle. Minimal dissection is required and a fusion rate of 95% is obtainable. 
Epiglottic laryngoplasty after hemilaryngectomy for glottic cancer. Epiglottic laryngoplasty is technically feasible as a one-stage procedure with excellent functional results. Although the Kambic-Sedlacek-Tucker (K-S-T) technique of glottic reconstruction offers early extubation with an adequate airway, a subsequent wide neoglottis may increase the chance of aspiration and a poor voice. To better restore the laryngeal functions of closure and phonation, we made some modifications on the original K-S-T technique as follows: (1) One of the lateral margins of the epiglottis with the aryepiglottic fold is sutured to the arytenoid region of the cricoid rather than a thyroid cartilage remnant. A neo-arytenoid is formed. (2) The other lateral margin of the epiglottis with the aryepiglottic fold is sutured to the cut edge of the false and true cord instead of a thyroid ala remnant. Therefore both margins of the epiglottis with the aryepiglottic folds are lowered as much as possible to the level of the glottis. A new pseudocord is formed. (3) A cartilage cut is made at the anterior aspect of the epiglottis, leaving its laryngeal surface of mucoperichondrial intact. A new anterior commissure with a sharp angle is shaped by this maneuver. Nineteen hemilaryngectomies with modified epiglottic laryngoplasty have been performed by members of the Department of Otolaryngology of Guangxi Medical College since 1984. Results in this series are fairly good and indicate that the modified epiglottic laryngoplasty is effective in enhancing functional results in terms of respiration, deglutition, and phonation. 
Selective chemical vestibulectomy: preliminary results with human application. The involved membranous labyrinth of patients with medically intractable Meniere's disease is being accessed by means of a fenestration of the bony horizontal semicircular canal in preparation for the application of a 125 or 250 mcg flake of solid streptomycin. Sensory information originating in the affected vestibular end organ is selectively blocked from reaching the central nervous system. This uniformly results in the rapid elimination of vertiginous symptoms, and at these calculated doses yields preservation of (or in some cases improvement in) preoperative cochlear thresholds. The rationale for this procedure, as detailed in earlier investigations of animals, will be briefly reviewed before highlighting our preliminary results in adult clinical trials. 
Acute twin-twin transfusion: a possible mechanism for brain-damaged survivors after intrauterine death of a monochorionic twin. Intrauterine death of one twin in monochorionic pregnancies is associated with increased mortality and morbidity for the survivor. This has been attributed to the consequences of intrauterine disseminated intravascular coagulation (DIC) initiated by the dead twin. We describe a case in which the fetal cerebral and renal lesions typically found in survivors occurred without any derangement in coagulation. Instead, acute twin-twin transfusion was suggested by the presence of severe anemia in the surviving fetus at delivery. We suggest that the lesions frequently found in the survivors are often due to acute hemodynamic and ischemic changes resulting from acute twin-twin transfusion at the time of intrauterine death, rather than to late-onset DIC. This hypothesis has an important implication for future management: Intervention must occur before intrauterine death if neurologic sequelae in the survivor are to be prevented. 
Priming by platelet-activating factor of endotoxin-induced lung injury and cardiovascular shock. Platelet-activating factor (PAF) is a glycerophospholipid known for its unusual potent vasoactive and proinflammatory activities. The present study examined whether PAF might serve as a priming factor in endotoxin-induced tumor necrosis factor-alpha (TNF alpha) synthesis, cardiovascular shock, and lung injury in anesthetized rats. Intravenous infusion of PAF (1 pmol/kg/min for 60 minutes, n = 5) alone or endotoxin (0.1 micrograms/kg i.v. bolus, n = 5) failed to alter blood pressure, serum TNF alpha and thromboxane B2, platelet and leukocyte count, and hematocrit, nor was lung histology, myeloperoxidase activity, and water content changed. In contrast, the combined administration of PAF and endotoxin markedly elevated serum TNF alpha (1,359 +/- 362 pg/ml, n = 5, p less than 0.01) and thromboxane B2 (43 +/- 5 pg/100 microliters, n = 8, p less than 0.01) along with hypotension, hemoconcentration, leukopenia, and thrombocytopenia. Most notably, the combined regimen caused neutrophil aggregation, adhesion, and accumulation into the lung parenchyma along with platelet-fibrin deposits in postcapillary venules, pulmonary edema, and increased lung myeloperoxidase activity. The role of PAF in this process was confirmed by 1) the prevention of the priming effect by pretreatment with the PAF antagonist BN 50739 (n = 5), and 2) the failure of lyso-PAF, the cardinal nonactive PAF-metabolite, to prime for endotoxin-induced production of TNF alpha (n = 4). These data suggest that PAF could serve as a key mediator in priming for endotoxin-induced tissue injury, especially the typical pulmonary pathophysiology of adult respiratory distress syndrome, a severe pathological outcome of septic shock, burns, and multiple organ injury. 
Alterations in proteoglycan synthesis common to healing wounds and tumors. Wound healing and tumor stroma generation share several important properties, including hyperpermeable blood vessels, extravasation of fibrinogen, and extravascular clotting. In both, the deposits of fibrin gel serve initially as provisional stroma and later are replaced by granulation tissue. Proteoglycans (PG) are also important constituents of the extracellular matrix, but their composition and role in healing wounds and tumor stroma generation are poorly understood. The authors used immunohistochemical and biochemical methods to investigate the dermatan sulfate proteoglycan (DSPG) and chondroitin sulfate proteoglycan (CSPG) composition of healing skin wounds and solid tumors. By immunohistochemistry, the great majority of normal guinea pig and human dermis stained weakly for CSPG and strongly for decorin. In contrast, the granulation tissue of healing skin wounds and scars stained intensely for CSPG and weakly or not at all for decorin; however decorin staining was restored to normal intensity after digestion with chondroitin ABC lyase, suggesting that decorin antigenic sites had been masked by glycosaminoglycan (GAG) chains. Like wounds, the stroma of several carcinomas (line 1 guinea pig, human breast, colon, basal cell, and squamous) stained strongly for CSPG and weakly or not at all for decorin, but decorin staining developed after chondroitin ABC lyase digestion. Thus healing wounds and tumor stroma express a common pattern of altered PG staining, adding another to the properties these pathologic entities share. Proteoglycans extracted from healing wounds after in situ labelling with [35S] Na sulfate contained more CSPG than normal dermis with significantly longer GAG chains. Granulation tissue also synthesized more DSPG than normal skin, with greater heterogeneity and longer GAG chains. These alterations in PG synthesis correlate with the cell proliferation, migration, and collagen synthesis that accompany wound healing and may provide clues to the mechanisms responsible for both wound healing and tumor stroma generation. 
Incidence of gallstones in liver cirrhosis. We conducted a longitudinal follow-up of 72 patients with liver cirrhosis (LC) in order to assess gallstone (GS) incidence. The period of survey was 24.5 +/- 12.2 months. Patients were divided into two groups: group I--26 patients with ascites at the start or appearing during follow-up, and Group II--46 patients with compensated LC (no ascites) throughout the survey. During follow-up, 12 of 72 (16.6%) patients developed GS. The global cumulative incidence of GS was 5.5 cases/100 people/year. Age and sex had no influence on the incidence of GS in LC; neither had etiology or cirrhosis. On the contrary, the study revealed a significant increase in the incidence of GS in decompensated cirrhosis. In group I patients, GS appeared more frequently (34.6%) than in group II patients (6.5%) (chi 2 9.479; p less than 0.002). The cumulative incidence of GS was five times higher in decompensated versus compensated LC. 
Mycosis fungoides: cutaneous T-cell lymphoma [published erratum appears in Am Fam Physician 1991 Jun;43(6):1954] Most patients with mycosis fungoides are between 40 and 60 years of age. The disease has three clinical stages: (1) the premycotic, or patch, stage, consisting of macular, scaling, faint pink to red pruritic patches, usually on unexposed surfaces; (2) the mycotic, or plaque, stage, consisting of reddish, purple-brown plaques, often annular in shape and symmetric in distribution, and (3) the tumor stage, consisting of red-brown to violaceous, dome-shaped, firm tumors with a predilection for the face and body folds. The Sezary syndrome is a leukemic variant. Treatment depends on the extent of disease and includes topical or systemic chemotherapy, radiotherapy and psoralen plus long-wave ultraviolet light therapy. 
Fatal rupture of the intracranial carotid artery during transluminal angioplasty for vasospasm induced by subarachnoid hemorrhage. Case report. The authors report the clinical course, radiographic findings, and gross and microscopic pathology of a patient with fatal rupture of the supraclinoid segment of the left internal carotid artery during transluminal angioplasty for subarachnoid hemorrhage-induced vasospasm. The rupture most likely resulted from a small portion of aneurysm neck which remained unclipped, thereby leaving an area of structural weakness in the arterial wall at the site of clipping. The area of structural weakness predisposed the artery to rupture upon the addition of transmural pressure induced by balloon inflation during transluminal angioplasty. Caution is advised when performing transluminal angioplasty in the region of aneurysm clipping since the vessel lumen "recreated" during the clipping procedure may contain some residual and structurally incomplete aneurysm neck in the vessel wall. 
Selective salpingography and fallopian tube recanalization Obstruction of the uterine (proximal) end of the fallopian tube is noted on up to 20% of hysterosalpingograms and has a variety of underlying causes. Definitive diagnosis and treatment in the past have required laparoscopy or laparotomy with tubal resection. Selective salpingography and fallopian tube recanalization with fluoroscopically guided catheters has emerged as an improved method both for diagnosis and treatment in these patients. Technical success rates for overcoming the obstruction and visualizing distal tubal anatomy range from 76% to 95%. Pregnancy rates after the procedure vary depending on the patient populations studied; however, early results indicate a greater than 50% intrauterine pregnancy rate by 1 year. The rate of ectopic pregnancy is approximately 10% and that of early tubal reocclusion is less than 30%. Selective salpingography and fallopian tube recanalization is recommended as the first intervention in patients with obstruction of the proximal fallopian tube. 
Distribution of BCA-225 in adenocarcinomas. An immunohistochemical study of 446 cases. BCA-225 is a glycoprotein identified in human breast carcinoma cells that has been reported to show a restricted distribution in other human tissues. To further define the presence of BCA-225 in human carcinomas, the authors performed an immunohistochemical study, applying a commercially available monoclonal antibody to BCA-225 to formalin-fixed, paraffin-embedded sections of 446 adenocarcinomas from a variety of sites. BCA-225 expression was found to be common in adenocarcinomas of the breast (98%), kidney (94%), ovary (80%), and lung (74%) but was infrequent in adenocarcinomas of the gastrointestinal tract (10-16%). Adenocarcinomas of the prostate, bile ducts, thyroid, endometrium, endocervix, and pancreas showed an intermediate frequency of BCA-225 expression (36-68%). Although rare tumor cells in three hepatocellular carcinomas showed reactivity for BCA-225, staining of more than 10% of the tumor cells was not seen in any of the 23 hepatocellular carcinomas that were studied. The authors conclude that BCA-225 is expressed commonly in human adenocarcinomas and that it is not a breast-specific antigen. Antibodies to BCA-225 may have utility in helping one to exclude hepatocellular carcinoma in certain clinical settings. 
Carotid endarterectomy in a community hospital: a change in physicians' practice patterns. A total of 243 consecutive carotid endarterectomies (CEA) performed at Providence Medical Center in Portland, Oregon, were retrospectively reviewed over a 22-month period. Of these, 137 patients (56%) underwent CEA for asymptomatic disease, 52 (37%) of whom had stenotic lesions of 79% or less. There were 6 deaths (3%) and 12 strokes (5%). Four strokes were in asymptomatic patients. These data prompted development of criteria for CEA: (1) hemisphere-specific transient ischemic attacks, reversible ischemic neurologic deficits, or amaurosis fugax with an appropriate carotid lesion; (2) completed stroke with major recovery and significant carotid stenosis; (3) asymptomatic lesion with greater than 80% stenosis (D+) either by carotid arteriogram or non-invasive lab evaluation; and (4) other indications only with a supporting second opinion from a disinterested vascular surgeon, neurosurgeon or neurologist. A prospective review followed institution of the guidelines. In 21 months, 148 operations were performed, a 36% reduction over the initial study period. Of these, 46 (31%) were for asymptomatic lesions. Two patients (4%) did not fulfill the guideline criteria. There were six strokes (4%) and no deaths. The reduction of CEAs appears to be related to a significant decrease in "inappropriate" operations being performed. Surgeons' familiarity with the data rather than external pressures seems to be the major factor in changing practice patterns. The decrease in stroke/death rate is not statistically significant. 
Transcutaneous oxygen tensions in assessing the treatment of healed venous ulcers Transcutaneous oxygen tension (Ptc,O2) was assessed as an indicator of risk of reulceration in 68 limbs with healed venous ulcers. Ptc,O2 was also used to assess two methods of ulcer prophylaxis. Measurements were made over the gaiter skin, the healed ulcer and the upper arm. The results were expressed as a ratio of the lower limb readings over those taken from the arm. Patients were randomized, after the ulcer had healed, to elastic stockings and stanozolol, or elastic stockings and surgical ligation of incompetent superficial veins. Patients who declined to participate in the study were prescribed elastic stockings only. Those limbs remaining healed at 12 months had Ptc,O2 ratios remeasured. The Ptc,O2 ratios from limbs that reulcerated were not significantly lower than those from limbs remaining healed. The Ptc,O2 ratio was significantly increased in limbs treated by stanozolol and elastic stockings (P less than 0.05) and by surgery and elastic stockings (P less than 0.05). There was no significant increase in Ptc,O2 in limbs treated by elastic stockings alone. In those treated by surgery and elastic stockings, there was a significant improvement in limbs with normal deep veins (P less than 0.01), but not in limbs with post-thrombotic changes on ascending phlebography. Although these two methods of ulcer prophylaxis improve the Ptc,O2 ratio, a high ratio has not been shown to be beneficial in preventing ulcer recurrence. 
Improving compliance in an inner-city hypertensive patient population. Because hypertension is a "silent" disease process, compliance with therapy is always a problem. In the inner city, where socioeconomic factors such as poverty, illiteracy, and substance abuse raise additional barriers to effective health care, poor compliance with antihypertensive regimens can reach epidemic proportions--as it did in our clinic in the early 1970s. After identifying the major causes of poor compliance in our patients, we instituted measures that led directly to greatly improved compliance and control, among them the expansion of clinic hours, the expediting of laboratory services, and the training of nurse-therapists to assume many of the responsibilities of running the clinic. In recent years a number of new antihypertensive agents have been introduced, and these new drugs have afforded patients better blood pressure control through less complex drug regimens with fewer serious side effects. Indeed, we observed a strong correlation between patient compliance and the administration of agents with longer dosing intervals and improved side effects profiles. This observation led us to consider whether transdermal clonidine--which requires weekly, rather than daily, administration--might not be an especially effective means of controlling blood pressure in inner-city patients. To test this hypothesis, we enrolled 20 patients, all of them blacks, in a pilot study of this unique delivery system. Blood pressure was adequately controlled in all 18 patients who completed the study, and patients were uniformly enthusiastic about this alternative to daily dosing. As a result, compliance with this mode of therapy was excellent. 
Cardioreparative effects of lisinopril in rats with genetic hypertension and left ventricular hypertrophy. BACKGROUND. In genetic and acquired hypertension, a structural remodeling of the nonmyocyte compartment of the myocardium, including the accumulation of fibrillar collagen within the interstitium and adventitia of intramyocardial coronary arteries and a medial thickening of these vessels, represents a determinant of pathological hypertrophy that leads to ventricular dysfunction. METHODS AND RESULTS. To evaluate the benefit of angiotensin converting enzyme inhibition in reversing this interstitial and vascular remodeling in the rat with genetic spontaneous hypertension (SHR) and established left ventricular hypertrophy (LVH), we treated 14-week-old male SHR with oral lisinopril (average dose, 15 mg/kg/day) for 12 weeks. Myocardial stiffness and coronary vascular reserve to adenosine (800 micrograms/min) were examined in the isolated heart; myocardial collagen and intramural coronary artery architecture were analyzed morphometrically. In lisinopril-treated SHR compared with 14-week-old baseline or 26-week-old untreated SHR and age- and sex-matched Wistar-Kyoto (WKY) controls, we found 1) a regression in LVH and normalization of blood pressure, 2) a complete regression of interstitial fibrosis, represented by a decrease of interstitial collagen volume fraction from 7.0 +/- 1.3% to 3.2 +/- 0.3% (p less than 0.025; WKY, 2.8 +/- 0.5%), 3) normalization of myocardial stiffness constant from 19.5 +/- 0.9 to 13.7 +/- 1.3 (p less than 0.025; WKY, 13.8 +/- 2.2), 4) a reversal of intramural coronary artery remodeling, including a decrease in the ratio of perivascular fibrosis to vessel lumen size from 1.4 +/- 0.2 to 0.4 +/- 0.1 (p less than 0.025; WKY, 0.6 +/- 0.1) and medial thickening from 12.3 +/- 0.6 to 7.4 +/- 0.5 microns (p less than 0.005; WKY, 7.4 +/- 0.4 microns), and 4) a restoration of coronary vasodilator response to adenosine from 12.3 +/- 0.9 to 26.0 +/- 1.4 ml/min/g (p less than 0.005; WKY, 21.8 +/- 2.2 ml/min/g). Thus, in SHR with LVH and adverse structural remodeling of the cardiac interstitium, lisinopril reversed fibrous tissue accumulation and medial thickening of intramyocardial coronary arteries and restored myocardial stiffness and coronary vascular reserve to normal. CONCLUSIONS. These cardioreparative properties of angiotensin converting enzyme inhibition may be valuable in reversing left ventricular dysfunction in hypertensive heart disease. 
Fetal akinesia deformation sequence (Pena-Shokeir phenotype) associated with acquired intrauterine brain damage. An infant with Pena-Shokeir phenotype was born to a cocaine-using mother. The pathologic findings included polyhydramnios, facial anomalies, arthrogryposis, camptodactyly, pulmonary hypoplasia, and tetralogy of Fallot. The neuropathologic findings were diffuse brainstem and spinal cord neuronal degeneration and focal cerebral infarction, consistent with acquired intrauterine ischemic damage. 
Diagnosis and localization of laceration of the thoracic duct: usefulness of lymphangiography and CT. The usefulness of lymphangiography and CT in the diagnosis and localization of laceration of the thoracic duct was evaluated in 12 patients with chylothorax or chylous ascites after surgery. Bipedal lymphangiography was performed in all 12 patients. The last four patients studied also had CT after lymphangiography. Seven patients had abnormal findings on lymphangiograms; five with leaks from the thoracic duct, one with a lymphocele in a nephrectomy bed, and one with obstructed intestinal lymphatic vessels after thoracotomy. Five patients had no evidence of lymphatic leakage. CT in one patient with evidence of a leak on lymphangiography showed extravasation of contrast medium into the mediastinum and pleural space. CT in three patients with no abnormalities on lymphangiography also showed no abnormalities. Four of the five thoracic duct lacerations and the lymphocele were confirmed surgically. The diagnosis of obstructed intestinal lymphatic vessels was supported clinically. Four of the five patients with normal findings on lymphangiograms had resolution of their pleural effusions and no evidence of recurrence during a follow-up period of 1-27 months. One patient with normal findings on lymphangiography had an alternative diagnosis established at surgery. Laceration of the thoracic duct was accurately diagnosed and localized with lymphangiography, which allowed definitive surgical repair. CT was of little additional value in diagnosing these injuries. 
Bacterial infection and peripheral vascular disease. Whole blood filterability was monitored in 16 nondiabetic peripheral vascular disease (PVD) patients within forty-eight hours of onset of bacterial infection, after ten to seventeen days antibiotic therapy and again, ten days later, after convalescence. The whole blood filterability rate was constantly disturbed before infection in these patients; the impairment worsened significantly (as was expected during infection), but after convalescence the whole blood filterability rate did not return to preinfection levels. This further significant impairment in whole blood filterability was inversely correlated with a reduction in the patients' pain-free walking time as determined by a standard treadmell test performed after convalescence and compared with their average times before infection. 
Intra-ocular pressure variations during extracorporeal circulation and some influencing factors. Intra-ocular pressure (IOP) variations during extracorporeal circulation (ECC) and some influencing factors were studied prospectively in 38 patients undergoing cardiovascular surgery. IOPs were measured pre-operatively, during ECC (after 5 min, 10 min, 25 min and every 15 min thereafter), and on the 1st, 2nd and 3rd postoperative days. IOP, haematocrit, arterial perfusion pressure, partial O2 pressure, partial CO2 pressure, pH and blood bicarbonate levels were measured simultaneously. After the beginning of ECC, arterial perfusion pressure and haematocrit values decreased suddenly, while IOP raised immediately. Sudden increase of blood volume in the beginning of ECC can be the probable cause of IOP elevation. Afterwards, IOP levels decreased to pre-ECC levels. We think that the drop is due to the effect of mannitol in the priming solution and hyposecretion of aqueous humour due to insufficient nutrition-oxygenation of corpus ciliaris after haemodynamic stabilization. 
Cost-effectiveness of prophylaxis in total hip replacement. A theoretical analysis was performed regarding the cost-effectiveness in terms of lives saved (reduction of fatal pulmonary embolism [PE]) and in terms of money (dollars spent for prevention and treatment) of seven strategies in the management of venous thromboembolic disease in patients over 39 years of age undergoing elective total hip replacement (THR). Strikingly, this theoretical analysis suggests that low-dose warfarin combined with clinical surveillance of deep vein thrombosis would reduce the incidence of fatal PE from 20 per 1,000 patients to 4 per 1,000 patients and simultaneously reduce the charges for venous thromboembolic disease from $550,000 to about $400,000 per 1,000 patients. Based on this analysis, we strongly recommend this measure on a routine basis. Adding venography or duplex sonography routinely to this prophylactic regimen would, in this theoretical analysis, reduce the incidence of fatal PE from 4 per 1,000 patients to 0.15 per 1,000, but adds charges of $200,000 per extra life saved in the case of routine venography and $50,000 in the case of routine sonography. Low-dose warfarin prophylaxis combined with routine sonography does not generate more charges than no prophylaxis with no screening while drastically reducing the incidence of fatal PE from 20 to 0.3 per 1,000 patients. Where duplex sonography is not easily available, a 12-week postoperative course of low-dose warfarin for every patient with no routine screening will be efficacious in reducing fatal PE and as cost-effective. 
Treatment of pancreatic pseudocysts with octreotide. Pancreatic pseudocysts are a common and painful complication of chronic pancreatitis. Seven patients (six male, one female; mean age 49.9 years) with chronic pancreatitis complicated by pseudocysts and persistent pain were treated with the pancreatic anti-secretory drug octreotide for 2 weeks. Octreotide caused no notable changes in the size of the pseudocysts of three patients. In the remaining four patients, the pseudocysts decreased in size by a mean of 42% (range 29-52%), and pain disappeared completely. These findings suggest a role for octreotide in the treatment of pancreatic pseudocysts. 
A simple radiologic method to estimate the quantity of bowel gas. Patients with functional bowel disorders frequently complain of bloating and abdominal pain, but no practical method is available to measure intestinal gas objectively. To evaluate a new technique, we evaluated 54 abdominal radiographs from 19 patients. A gastroenterologist and a radiologist independently outlined the intestinal gas bubbles in these films. Areas of gas bubbles were measured with a computer digitizing board. Bowel gas was also measured in 24 healthy controls, and in five emergency room patients, supine and erect radiographs were compared to evaluate the effects of position on bowel gas patterns. The two evaluators agreed well on the measured areas of bowel gas (r = 0.96), showing that this is a reliable method. Bowel gas was significantly greater in patients than in controls but did not correlate with symptoms. Bowel gas was significantly greater in supine than upright films, showing that the position of the patient must be standardized. 
Primary angiosarcoma of adrenal gland presenting as paraneoplastic syndrome: case report. Angiosarcoma is an uncommon neoplasm that rarely involves the adrenal gland. We report on a patient with primary angiosarcoma of the adrenal gland who presented with symptoms best characterized as a paraneoplastic syndrome. 
Reversal of acute exacerbations of chronic obstructive lung disease by inspiratory assistance with a face mask. BACKGROUND. Patients with acute exacerbations of chronic obstructive pulmonary disease may require endotracheal intubation with mechanical ventilation. We designed, and here report on the efficacy of, a noninvasive ventilatory-assistance apparatus to provide inspiratory-pressure support by means of a face mask. METHODS. We assessed the short-term (45-minute) physiologic effects of the apparatus in 11 patients with acute exacerbations of chronic obstructive pulmonary disease and evaluated its therapeutic efficacy in 13 such patients (including 3 of the 11 in the physiologic study) who were treated for several days and compared with 13 matched historical-control patients. RESULTS. In the physiologic study, after 45 minutes of inspiratory positive airway pressure by face mask, the mean (+/- SD) arterial pH rose from 7.31 +/- 0.08 to 7.38 +/- 0.07 (P less than 0.01), the partial pressure of carbon dioxide fell from 68 +/- 17 mm Hg to 55 +/- 15 mm Hg (P less than 0.01), and the partial pressure of oxygen rose from 52 +/- 12 mm Hg to 69 +/- 16 mm Hg (P less than 0.05). These changes were accompanied by marked reductions in respiratory rate (from 31 +/- 7 to 21 +/- 9 breaths per minute, P less than 0.01). Only 1 of the 13 patients treated with inspiratory positive airway pressure needed tracheal intubation and mechanical ventilation, as compared with 11 of the 13 historical controls (P less than 0.001). Two patients in each group died. As compared with the controls, the treated patients had a more transient need for ventilatory assistance (3 +/- 1 vs. 12 +/- 11 days, P less than 0.01) and a shorter stay in the intensive care unit (7 +/- 3 vs. 19 +/- 13 days, P less than 0.01). CONCLUSIONS. Inspiratory positive airway pressure delivered by a face mask can obviate the need for conventional mechanical ventilation in patients with acute exacerbations of chronic obstructive pulmonary disease. 
Occlusive peripheral vascular disease: a multicenter trial of fluorescence-guided, pulsed dye laser-assisted balloon angioplasty. Fluorescence-guided, laser-assisted balloon angioplasty was performed in 129 patients with iliac and femoropopliteal artery chronic occlusions (range, 0.5-50.0 cm; mean length, 9.9 cm) after failure of recanalization with standard guide-wire techniques. Laser recanalization and short-term angiographic success were achieved in 101 (72%) and 95 (68%) of 140 occlusions, respectively. Laser and balloon angioplasty failures were encountered in heavily calcified plaques or after perforations and dissections. Complications included perforations (19%), hematomas (5%), thromboses (4%), and distal embolizations (4%). Real-time fluorescence spectroscopy identified thrombus, white fibrous plaque, and media but could not avoid perforations in many cases because laser wire advancement outdistanced fluorescence sensing. Disruption of tissue by means of pressure transients and/or mechanical advancement occurred in at least 36% of lesions where the laser energy was insufficient (less than 0.4 J/cm) to ablate significant tissue. Integration of fluorescence guidance with pulsed dye laser ablation is feasible, but additional refinements are necessary to increase safety and efficacy. 
Predicting chemically induced duodenal ulcer and adrenal necrosis with classification trees. Binary tree-structured statistical classification algorithms and properties of 56 model alkyl nucleophiles were brought to bear on two problems of experimental pharmacology and toxicology. Each rat of a learning sample of 745 was administered one compound and autopsied to determine the presence of duodenal ulcer or adrenal hemorrhagic necrosis. The cited statistical classification schemes were then applied to these outcomes and 67 features of the compounds to ascertain those characteristics that are associated with biologic activity. For predicting duodenal ulceration, dipole moment, melting point, and solubility in octanol are particularly important, while for predicting adrenal necrosis, important features include the number of sulfhydryl groups and double bonds. These methods may constitute inexpensive but powerful ways to screen untested compounds for possible organ-specific toxicity. Mechanisms for the etiology and pathogenesis of the duodenal and adrenal lesions are suggested, as are additional avenues for drug design. 
Therapeutic defibrination with ancrod does not protect canine myocardium from reperfusion injury. The purpose of this study was to determine whether normal fibrinogen contributes to the development of myocardial reperfusion injury by acting as a substrate in vivo for neutrophil adhesion. This was tested in a dog model of acute myocardial infarction that used pentobarbital anesthetized dogs subjected to 90 min regional myocardial ischemia and 5 h reperfusion. Dogs were treated with 1 unit/kg Ancrod (venom from the Malayan pit viper, Agkistrodon rhodostoma) or vehicle i.v. 60 min after left circumflex coronary artery occlusion. Therapeutic defibrination was verified in Ancrod-treated dogs by measurements of clottable fibrinogen, alpha-2 antiplasmin and plasminogen, by the activated partial thromboplastin time and by immunoelectrophoresis. Fibrinogen was depleted to below detectable limits of the assay (less than 0.05 mg/ml) after treatment with Ancrod. The defibrination effect was accomplished by the expected activation of the fibrinolytic system: alpha-2 antiplasmin was decreased by 10% and plasminogen activity was decreased by 30% with Ancrod treatment. There were no measureable differences between the two treatment groups in heart rate, mean arterial blood pressure, rate pressure product or circumflex coronary blood flow throughout the 90 min of regional ischemia or during the 5 h of reperfusion. The relative severity of ischemia between the two treatment groups was similar when assessed with radiolabeled microsphere measurement of myocardial blood flow. The accumulation of neutrophils (measured by myeloperoxidase activity) within the myocardium after reperfusion was not reduced by prior depletion of fibrinogen. 
Foreign body in the gastrointestinal tract: intraluminal migration of laparotomy sponge. We have reported a case of complete transluminal migration of a retained laparotomy sponge that caused repeated partial small bowel obstruction. Diagnosis was made when roentgenograms showed multiple positions of the laparotomy marker. The sponge was surgically removed. This is the 69th reported case of complete transluminal migration and distal movement of a laparotomy sponge. 
Ceftazidime as monotherapy or combined with teicoplanin for initial empiric treatment of presumed bacteremia in febrile granulocytopenic patients. In a prospective randomized study, 120 febrile, granulocytopenic patients received as initial therapy ceftazidime with or without teicoplanin. At the onset of fever, patients had no obvious infectious focus. For 103 assessable episodes, initial bacteremias were detected in 18 of 51 patients (35%) given ceftazidime and 20 of 52 patients (38%) given the combination; 13 and 17 bacteremias caused by gram-positive bacteria occurred in these groups, respectively. There was no difference in terms of the final response (25 of 51 patients [49%] treated with ceftazidime alone versus 33 of 52 patients [63%] given the combination), and the morbidity was comparable for both treatment groups. The duration of fever and of total antibiotic therapy were similar in both groups. Initial therapy was modified in 26 patients (51%) treated with ceftazidime, with 20 surviving the infection, and in 19 patients (37%) treated with the combination, with 15 surviving. Persistent fever was the main reason for changing treatment, and no patient died of a gram-positive infection. Subsequent infective events occurred in 16 patients (31%) given ceftazidime and in 25 patients (48%) given the combination. Lung infiltrates developed in 12 and 13 patients, respectively, but more new infections occurred in the combination group. Allergic skin reactions were also more frequent in this group. Thus, while teicoplanin provides simple, reliable, and safe treatment of patients with presumed gram-positive infections, it is not useful when given empirically to this patient population, and treatment may result in more infective complications and adverse events. 
Pulmonary mass and air meniscus sign in a 19-year-old man. Sacrococcygeal teratoma is rarely diagnosed in adults. Pulmonary mass as the presenting clinical form of the malignant variety of this germ-cell tumor is exceptional. We report herein such a case with the noticeable peculiarity of showing the air meniscus sign on chest roentgenographic examination. 
Occult papillary microcarcinoma of the thyroid--a potential pitfall of fine needle aspiration cytology? The use of fine needle aspiration cytology detected papillary carcinoma in two patients with multinodular goitre measuring 0.7 cm and 0.9 cm in diameter, respectively. Like most of the cases from previous large series, the tumours progressed slowly as shown by absence of enlarged glands on surgical exploration and no clinical signs of metastasis after two and five years of follow up. This study shows that aspiration cytology can detect a virtually harmless occult papillary carcinoma that will oblige patients to have surgery. This very occasional "pitfall" of fine needle aspiration should not preclude this well known beneficial method from being used in the management of thyroid disease. 
The risk of axillofemoral bypass grafting for acute vascular occlusion. The hypothesis of the present study is that axillofemoral bypass grafting for acute vascular occlusion has results significantly inferior to an elective procedure. We reviewed 53 patients undergoing primary axillofemoral bypass grafting at the University of Virginia from 1984 to 1989. We found that patients who were admitted with acute vascular occlusion had a higher incidence of perioperative complications (63% vs 26%, p = 0.001), perioperative mortality (26% vs 3%, p less than 0.05), lower graft patency at 1 year (60% vs 90%, p less than 0.05), lower rate of freedom from reoperation in first year (50% vs 82%, p less than 0.01), and lower rates of limb salvage (76% vs 94%, p less than 0.05) than patients undergoing axillofemoral bypass grafting for chronic symptoms or conditions. These two groups did not differ in any of the other risk factors or perioperative characteristics examined. We conclude axillofemoral bypass grafting performed for indications other than acute vascular occlusion is associated with acceptable morbidity, mortality, graft patency, and limb salvage rates. 
Thermographic observations on rats with experimental neuropathic pain. Infrared thermographic images were obtained from the plantar hind paws of rats with an experimental nerve injury that produces signs of neuropathic pain. Thermograms confirmed that the experimental neuropathy produces signs resembling those of patients with neuropathic pain. The hind paws on the nerve-damaged side were abnormally hot, abnormally cold, or apparently normal 8-16 days post injury, a variability that is seen clinically in neuropathic pain patients. Abnormally cold hind paws became warm as soon as the injured sciatic nerve was transected, indicating that the underlying vasoconstriction was mediated by neural impulse activity. Xylazine (Rompun), a sympatho-inhibitory alpha 2-adrenoceptor agonist that normally increases cutaneous temperature, caused the hind paw on the control side to warm, as anticipated, while causing paradoxical cooling of abnormally hot hind paws, and even of 'normal temperature' paws on the nerve-injured side. These findings shed light on possible mechanisms underlying abnormal deviations of skin temperature as a symptom of nerve injury. The findings also attest to the usefulness of the experimental animal model of neuropathic pain and of the thermographic method. 
DuP 753 increases survival in spontaneously hypertensive stroke-prone rats fed a high sodium diet. We studied the effects of the nonpeptide angiotensin II receptor antagonist, DuP 753, on blood pressure, body weight, plasma renin activity, sodium excretion, and mortality in male stroke-prone spontaneously hypertensive rats (SHRsp) fed a 4% NaCl diet for 12 weeks. The rise in blood pressure, due to high sodium intake, was blunted in the first 8 weeks of the study in the DuP 753-treated group; however, it started slowly to rise in the following weeks. In the untreated group, blood pressure rose steadily and it was significantly higher than that of the treated group during the whole experimental period. DuP 753-treated rats gained weight continuously during the study in contrast to the untreated group, where weight gain was arrested after 4 weeks. Plasma renin activity rose significantly after 4 weeks of treatment with DuP 753; by week 6 its values returned to baseline values and remained at these lower values until week 12. In the untreated group, plasma renin activity was not suppressed by high sodium intake after 4 weeks; it continued to rise and it was significantly elevated by 8 and 12 weeks. Survival at 12 weeks was 84% in DuP 753-treated group and 26% in the untreated group. The data demonstrate that DuP 753 decreased mortality and dramatically blunted the blood pressure rise in SHRsp fed a high sodium diet. 
Cystic cerebellar schwannoma: case report. We report a case of cerebellar schwannoma in a 64-year-old woman. The tumor was defined on computed tomographic and magnetic resonance imaging scans and confirmed on surgery. The solid part of the tumor appeared to be derived from the inferior vermis of the cerebellum, the cystic part extending toward the medulla oblongata and the foramen magnum. The problem of preoperative diagnosis based on magnetic resonance imaging findings is discussed. 
The value of portable chest roentgenography in adult respiratory distress syndrome. Comparison with computed tomography. In 17 patients with adult respiratory distress syndrome, we used data derived from computed tomographic (CT) scan densitometric analysis to validate the value of portable chest roentgenograms in objectively estimating the amount of pulmonary edema. Chest roentgenograms and CT scans were taken in the same ventilatory conditions (apnea at 10 cm H2O of positive end-expiratory pressure [PEEP]); blood gas samples and hemodynamic parameters were collected at the same time. Roentgenographic analysis was undertaken by independent observers using two standardized scoring systems proposed in the literature. CT scan analysis was performed using the CT number frequency distribution and the gas lung volume (measured by helium dilution technique) to estimate quantitatively the lung density, the lung weight, and the percentage of normally aerated and nonaerated tissue. Knowing the mean CT number of the pulmonary parenchyma in a group of normal subjects, we also inferred the ideal lung weight expected in the study population and computed the excess tissue mass as the difference between actual and ideal lung weight. Both the roentgenographic scoring systems showed direct correlation with the pulmonary impairment as detected by CT scan densitometric analysis (CT number, percentage of nonaerated tissue, lung weight, and excess tissue mass; p less than 0.01) and inverse relation with the percentage of normally aerated tissue (p less than 0.01). We also found a relationship between roentgenographic scores and the impairment in gas exchange as detected by shunt fraction (p less than 0.05). We conclude that standardized reading of portable chest roentgenograms by means of scoring tables is a valuable tool in estimating the amount of pulmonary edema in a patient with adult respiratory distress syndrome. 
Which asymptomatic patients should undergo routine screening carotid duplex scan? The benefits of obtaining a routine screening carotid duplex scan have not been established for patients with peripheral vascular disease but no signs or symptoms of carotid artery disease. We retrospectively reviewed all carotid duplex scans (4,000) performed at our institution between 1985 through 1989 and found for analysis 91 scans in 78 patients who underwent a screening duplex scan because of the presence of peripheral vascular disease. Patients with carotid bruits, abnormal carotid pulses, and focal or nonspecific neurologic symptoms were excluded. Thirty-three percent of these patients had carotid stenosis of 16% to 50%, 14% had carotid stenosis greater than or equal to 50%, and 5% had stenosis greater than or equal to 75%. Individual risk factors for atherosclerosis, including elderly age, coronary artery disease, hypertension, diabetes, smoking, and a recent or past history of cardiac or vascular surgery, did not predict the detection of high-grade carotid stenosis. However, all 11 of the patients with carotid stenosis greater than or equal to 50% were 68 years of age and older, and this age range, in combination with the various risk factors, increased the incidence of significant carotid artery stenosis (greater than or equal to 50%) to as high as 45%. We conclude that routine screening carotid duplex scan is indicated in elderly patients (age greater than or equal to 68 years) with peripheral vascular disease, even in the absence of any signs or symptoms of carotid artery disease, when other atherosclerotic risk factors are present. 
Inhibitory effects of the gastrin receptor antagonist (L-365,260) on gastrointestinal tumor cells. A selective gastrin receptor (GR) antagonist, L-365,260 is bound to the GR on AR42J cells with a potency 7.5-fold less than G17 (50% inhibitory concentration [IC50] G17, 6 x 10(-9) mol/l; IC50 L365-260, 4.5 x 10(-8) mol/l). G17 is mitogenic for AR42J cells, as assessed by 75Se-selenomethionine uptake and L-365,260 at concentrations of 2.5 x 10(-6) mol/l and 2.5 x 10(-7) mol/l, (55X and 5.5 X the dose required to displace 50% 125I G17, respectively), and reduced optimal G17 stimulated mitogenesis in 75% of experiments. The basal growth of two human colon cancer cell lines, LoVo and C146 was reduced by L-365,260 (2.5 x 10(-7) mol/l) after 5 days of treatment to 44% and 64% of the control, respectively. However, inhibition was followed by a rebound of growth to control levels. The growth of AR42J xenografts in nude mice was increased by administration of G17 (10 micrograms/mouse/d, P less than 0.027). This increase was blocked by coadministration of oral L-365,260 (5 mg/kg/d, P less than 0.034). L-365,260 could be an important therapeutic agent in slowing the growth of GR-positive, G17-sensitive gastrointestinal tumors. 
Slipped capital femoral epiphysis. A quantitative analysis of motion, gait, and femoral remodeling after in situ fixation. A prospective clinical study was done for quantitative examination of motion of the hip, gait, and proximal femoral remodeling after in situ fixation of a slipped capital femoral epiphysis. In situ fixation was performed in forty-five consecutively treated patients (fifty-six hips). Thirty-nine (87 per cent) of the patients returned for examination two years after treatment. The greatest percentage of motion of the hip returned within six months after treatment. Despite loss of internal rotation of the hip, the mean foot-progression angle was 10.8 degrees. Radiography and computerized tomographic scanning revealed minimum change in the relationship of the femoral head to the femoral shaft and no change in the neck-shaft angle. Motion returned despite minimum osseous remodeling. The early return of motion (in the first three months) may have been due to relief of pain, spasm, and synovitis, while soft-tissue stretching and resorption of bone in the anterolateral part of the femoral neck may have accounted for the remainder of the increase in internal rotation. 
Dissection of the protein kinase cascade by which nerve growth factor activates MAP kinases. Mitogen activated protein (MAP) kinases (MAPKs) are a family of protein-serine/threonine kinases activated as an early intracellular response to a variety of hormones and growth factors. They are unique in requiring both serine/threonine and tyrosine phosphorylation to become active and are the only examples of protein-serine/threonine kinases activated by tyrosine phosphorylation. Nerve growth factor (NGF) promotes differentiation of phaeochromocytoma (PC12) cells, which respond by conversion within hours from a chromaffin-like to a sympathetic neuron-like phenotype. NGF stimulation of PC12 cells increases the activity of two protein kinases by greater than 20-fold within minutes, both strikingly similar to MAPKs. They are inactivated by either protein-tyrosine phosphatases or the protein-serine/threonine phosphatase termed protein phosphatase 2A (ref. 8), they activate protein S6 kinase-II (refs 9, 10), and they phosphorylate identical threonine residues on myelin basic protein (our unpublished results) to those phosphorylated by other MAPKs. Immunological data indicate that these protein kinases, termed peak-I and peak-II (Fig. 1a) are probably ERK2 and ERK1, respectively, two widely expressed MAPK isoforms. Here we identify the 'MAP kinase kinases' (MAPKKs) in PC12 cells which are activated by NGF and report that MAPKKs are dependent on serine/threonine phosphorylation for activity and promote phosphorylation of serine/threonine and tyrosine residues on MAPKs. 
Assessment of a daily combined preparation of isoniazid, rifampin, and pyrazinamide in a controlled trial of three 6-month regimens for smear-positive pulmonary tuberculosis. Singapore Tuberculosis Service/British Medical Research Council In a study in Singapore 310 patients with sputum smear-positive pulmonary tuberculosis were allocated at random to daily chemotherapy with streptomycin, isoniazid, rifampin, and pyrazinamide (1) for 2 months (2SHRZ), (2) for 1 month (1SHRZ), or (3) for 2 months without streptomycin (2HRZ). This was followed for all patients by three times weekly isoniazid and rifampin to a total duration of 6 months. During the initial period of daily chemotherapy the patients were also allocated at random to be given their HRZ either as a combined formulation (Rifater), each tablet containing 50 mg isoniazid, 120 mg rifampin, and 300 mg pyrazinamide, or as three separate drugs. During the Rifater versus separate drugs comparison the most common spontaneous complaints were of nausea and vomiting, reported by 8% of 155 patients receiving Rifater and 7% of 155 separate drugs. Other adverse effects were also reported in similar proportions in the two series. Among 271 patients with drug-susceptible strains of tubercle bacilli pretreatment there were no bacteriologic failures during chemotherapy. During 18 months of subsequent follow-up bacteriologic relapse occurred in 3 (7%) of 46 2SHRZ, 2 (5%) of 42 1SHRZ, and 3 (8%) of 40 2HRZ patients allocated to Rifater and in 0 of 47 2SHRZ, 1 (2%) of 46 1SHRZ, and 1 (2%) of 44 2HRZ patients allocated to separate drugs. There was no evidence of therapeutic benefit from continuing SHRZ administration beyond 1 month or from adding streptomycin to HRZ. The relapse rates were slightly higher in the Rifater series (p = 0.04). Further follow-up and results from other studies are therefore needed fully to assess the combined preparation. 
Heart rate response during exercise testing and ambulatory ECG monitoring in patients with syndrome X. The response of the heart rate during exercise testing and 24-hour ambulatory electrocardiographic (ECG) monitoring performed with patients not receiving antianginal treatment was assessed in 26 patients (9 men and 17 women; mean age 51 +/- 8 years) with syndrome X (angina pectoris with normal coronary arteries), in 27 patients with coronary artery disease (10 men and 17 women; mean age 55 +/- 9 years), and in 21 healthy subjects (8 men and 13 women; mean age 47 +/- 11 years). In patients with syndrome X the slope of the regression line of heart rate versus time (heart rate/time slope) during exercise testing was similar to that of patients with coronary artery disease (3.3 +/- 0.8 versus 3.1 +/- 1.2 beats/min), but significantly lower than that in healthy subjects (4.2 +/- 1.1 beats/min; p less than 0.003). In patients with syndrome X the intercept of the heart rate/time slope was significantly higher than that in coronary artery disease patients and healthy subjects (102 +/- 15, 86 +/- 18, and 90 +/- 16 beats/min, respectively; p less than 0.015). Resting preexercise heart rate was also significantly higher in syndrome X, compared with coronary artery disease patients and healthy subjects (91 +/- 16, 79 +/- 16, and 80 +/- 14 beats/min, respectively). During ambulatory ECG monitoring, mean diurnal heart rate (from 6 AM to 6 PM) was higher in patients with syndrome X (83 +/- 8 beats/min) than in patients with coronary artery disease (75 +/- 8 beats/min) and healthy subjects (74 +/- 11 beats/min) (p less than 0.02). 
Human immunodeficiency virus infection among homeless men in a New York City shelter. Association with Mycobacterium tuberculosis infection. The human immunodeficiency virus (HIV) seroprevalence among a selected sample of 169 high-risk homeless men residing in a congregate shelter in New York City, NY, was 62%. Seropositivity for HIV correlated significantly with intravenous drug use (odds ratio, 3.3; 95% confidence interval, 1.4 to 4.4) and active tuberculosis (odds ratio, 7.0; 95% confidence interval, 3.4 to 13.5). Most cases of active tuberculosis were among homeless men with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex; and significant CD4 lymphocyte depletion was associated with active tuberculosis. Total time homeless correlated positively with active and latent tuberculosis infection. Compliance rates with return for HIV antibody test results, medications, and follow-up visits were 70%, suggesting a significant degree of knowledge, awareness, and personal concern regarding HIV infection among homeless men; yet 28% of homeless intravenous drug users continue active drug injection, despite HIV infection. Cohabitation in overcrowded congregate dormitories creates a risk of airborne transmission of tuberculosis, which is a common reactivation infection in HIV-seropositive homeless men. Medically appropriate housing should be provided to such homeless persons, and expanded HIV antibody testing, counseling, and medical services on site should be offered to residents of shelters. 
An eyelash nidus for dacryoliths of the lacrimal excretory and secretory systems. We treated two patients with dacryolithiasis secondary to an eyelash. The first patient underwent dacryocystorhinostomy for a stone within the lacrimal sac. In the second patient the dacryolith was removed from a lacrimal gland ductule. Eyelashes found in the tear film or conjunctival fornices during routine examination should be removed to prevent the possible occurrence of dacryolithiasis. 
Catecholamine responses to histamine infusion in man. To evaluate the effects of histamine-induced hypotension on plasma catecholamine levels, eight normal men, aged 20 to 40 years, were infused with incremental doses of histamine starting at 0.2 microgram/kg/min at a 30 degree tilt position with monitoring of blood pressure (BP) and heart rate. Histamine dosage was increased every 5 minutes by 0.1 to 0.2 microgram/kg/min until mean BP fell greater than 15 mm Hg or a dosage of 1.6 micrograms/kg/min was reached. Plasma catecholamine samples were taken between the fourth and fifth minute of each histamine dosage. Identical measurements were made during nitroglycerin-induced hypotension in these subjects. Histamine produced threefold greater increases in heart rate and plasma norepinephrine (NE) levels than did nitroglycerin for comparable decreases in BP. Although NE levels increased twofold to fivefold from baseline with histamine infusion, epinephrine levels increased minimally at the highest doses or not at all. Our data demonstrate that histamine selectively releases NE from adrenergic nerve terminals without significant adrenal catecholamine release. We suggest that neural NE release plays an important role in the cardiac effects of histamine. 
Radiotherapy of advanced laryngeal cancer using three small fractions daily. Since 1983, we have treated advanced (UICC stages III and IV) squamous carcinomas of the larynx by primary radiotherapy, using three small fractions a day, 3-4 h interfraction interval, 5 days per week. The early patients received doses per fraction of 1.5 Gy, and a total dose of approximately 70 Gy, given as a split-course over 6 to 7 weeks. While overall tumor control and laryngeal preservation was good, a number of severe late radiation reactions were seen. The schedule was then modified, with a reduction in the fraction size to 1.1 Gy, the total dose to 60 Gy, and the overall time to 4 weeks, with omission of the mid-treatment "split." Since 1986, we have treated 26 patients in this way. Acute reactions are brisk, but rapidly healing. Loco-regional control was achieved in 22 patients, only one of whom has relapsed to date, in a solitary node, salvaged by radical neck dissection. Four have died of uncontrolled loco-regional malignancy, and three of intercurrent disease while in clinical remission. No serious late morbidity has been observed in surviving patients, and vocal quality is good in the majority. These results suggest that this hyperfractionated and accelerated radiotherapy schedule may offer an acceptable nonsurgical, voice-preserving treatment for advanced laryngeal carcinoma; it can be used in a normally working radiotherapy department. 
Double-blind randomized multicenter study comparing Maalox TC tablets and ranitidine in healing of duodenal ulcers. The efficacy of ranitidine 150 mg twice daily and Maalox TC three tablets four times daily were compared in patients with endoscopically confirmed duodenal ulcer. Seventy-nine patients were randomly allocated to double-blind, double-dummy treatment, stratified for smokers. Endoscopy was repeated after four weeks. Those unhealed continued treatment for a further two weeks before final endoscopy. Per protocol analysis in 53 patients showed ulcer healing rates at week 4 and at weeks 4 and 6 combined of 78 and 89% on Maalox TC, and of 81 and 91% on ranitidine, respectively. The same analysis gave overall healing rates of 81% in smokers and 100% in nonsmokers, irrespective of treatment. Both treatments provided early ulcer pain relief. Diarrhea was a commoner side effect in patients on Maalox TC. The study showed Maalox TC and ranitidine were equally effective in healing duodenal ulceration. 
Multicenter trial of prophylaxis with clindamycin plus aztreonam or cefotaxime in gynecologic surgery. A prospective, randomized, multicenter study was conducted on the efficacy and safety of two prophylactic antibiotic regimens in both abdominal and vaginal hysterectomy. Patients received three intravenous doses of clindamycin (900 mg) plus either aztreonam (1 g) or cefotaxime (1 g); the doses were given at the induction of anesthesia and 8 and 16 hours later. A total of 170 patients undergoing abdominal hysterectomy and 142 patients undergoing vaginal hysterectomy completed the trial and were evaluated. Following abdominal hysterectomy infections occurred at the operative site in 1.2% of patients given a regimen including aztreonam and in 4.7% of those given a regimen including cefotaxime; the difference between the two groups was not significant. Neither were significant differences observed in the incidence of fever, the incidence of bacteriuria, the need for postoperative antibiotics, or the duration of postoperative hospitalization, although results were slightly better for patients receiving clindamycin plus aztreonam. Following vaginal hysterectomy, slightly but not significantly better results for the same parameters were obtained in the group given clindamycin plus cefotaxime. Diarrhea was the only adverse reaction attributable to antibiotic treatment and occurred more frequently in patients given cefotaxime. It was concluded that the two regimens were similarly effective and safe in preventing infections following hysterectomy. 
Post-sclerotherapy bacterial peritonitis. Endoscopic variceal sclerotherapy has been associated with a number of complications. Peritonitis after sclerotherapy has rarely been reported. In this retrospective review of 213 consecutive sclerotherapy procedures among 65 patients over a 3-yr period, we found that six cases of peritonitis occurred, for an incidence of approximately 3%. All patients developing post-sclerotherapy peritonitis had low ascitic fluid protein. However, this did not differ from patients who did not develop peritonitis. No patient on antibiotics at the time of sclerotherapy developed peritonitis. Peritonitis should be considered in the diagnosis of post-sclerotherapy fever. The role of prophylactic antibiotics to prevent this complication is uncertain. 
Renal atrophy or infarction in children with neuroblastoma. Twelve children with adrenal or upper abdominal paraaortic neuroblastoma developed unilateral or bilateral renal atrophy or infarction. At presentation, the children ranged in age from 2 weeks to 9.7 years. Neuroblastomas were stage II (n = 1), III (n = 2), IV-S (n = 2), and IV (n = 7). Treatment varied but included surgery, chemotherapy, localized abdominal irradiation, and/or bone marrow transplantation. Six children developed ipsilateral renal atrophy, five experienced ipsilateral or bilateral acute perioperative renal infarction, and one developed contralateral renal infarction unrelated to surgery. During treatment, two patients required hemodialysis; both subsequently died. Creatinine concentrations in eight patients have been in the normal range. Two patients have had mildly but persistently elevated creatinine levels. Renal damage from primary effects of the tumor can develop in children with adrenal or upper abdominal neuroblastoma. Treatment, especially surgical resection of the primary tumor, chemotherapy, and radiation therapy, can compound such damage. 
Prognostic factors in childhood acute encephalitis. We have studied the prognostic factors in 462 children, from 1 month to 16 years old, with acute encephalitis. Death occurred in 2.8% patients, 6.7% were severely damaged and 90.5% were cured with no or only minor sequelae. The risk of death or severe damage in patients less than 1 year of age was 5.0-fold (95% confidence limits, 2.2 to 11.6; P less than 0.001) greater than that of older children. When compared with those children whose level of consciousness had been normal before admission, children who had been disoriented before admission had a 3.9-fold (1.1 to 14.3, P less than 0.05) risk and those who had been unconscious had a 25.4-fold (7.3 to 88.1, P less than 0.001) greater risk of death or severe damage. The risk of death or severe damage in patients with herpes simplex virus encephalitis was 11.7-fold (3.8 to 35.8, P less than 0.001) and in patients with Mycoplasma pneumoniae encephalitis it was 7.0-fold (2.6 to 18.7, P less than 0.001) that of other children. All patients with none of the above mentioned risk factors were cured without any major sequelae. We conclude that specific attention should be paid to the youngest patients, especially to those with an impaired level of consciousness, and all available measures should be focused on early detection of herpes simplex virus or M. pneumoniae infection. 
Metastases of a gastric adenocarcinoma presenting as colonic polyposis. Report of a case. The authors report a case of multiple colonic metastases of a gastric signet ring cell adenocarcinoma, presenting as colonic polyposis revealed by diarrhea, iron deficiency anemia, and left supraclavicular lymph node. 
The induction and maintenance of central sensitization is dependent on N-methyl-D-aspartic acid receptor activation; implications for the treatment of post-injury pain hypersensitivity states. Repetitive stimulation of small diameter primary afferent fibres produces a progressive increase in action potential discharge (windup) and a prolonged increase in the excitability of neurones in the spinal cord following the stimulus. Previous studies have demonstrated that windup is the consequence of the temporal summation of slow synaptic potentials and that the slow potentials and windup are reduced by pretreatment with N-methyl-D-aspartic acid (NMDA) antagonists. We have now examined whether primary afferent induced hypersensitivity states in flexor motoneurones are also dependent on the activation of NMDA receptors and whether windup is a possible trigger for the production of the central hypersensitivity. Both a non-competitive (MK-801) and a competitive (D-CPP) NMDA antagonist, at doses that did not modify the baseline reflex, reduced the facilitation of the flexor reflex produced by either brief electrical stimulation of the sural nerve (1 Hz for 20 sec at C-fibre strength), or by the cutaneous application of the chemical irritant mustard oil. These antagonists also prevented windup from occurring in the motoneurones. When the the MK-801 and the D-CPP were administered once a state of central facilitation had been induced by prior treatment with mustard oil, they returned the facilitated reflex to its pretreatment level. These results indicate that NMDA receptors are involved in the induction and maintenance of the central sensitization produced by high threshold primary afferent inputs. Because central sensitization is likely to contribute to the post-injury pain hypersensitivity states in man, these data have a bearing both on the potential role of NMDA antagonists for pre-emptive analgesia and for treating established pain states. 
C terminus of the small GTP-binding protein smg p25A contains two geranylgeranylated cysteine residues and a methyl ester. smg p25A, also known as the rab3A protein, is a small GTP-binding protein that has been implicated in intracellular vesicle transport and the secretion of neurotransmitters. It has been shown to bind reversibly to membranes, though its cDNA-predicted sequence contains no obvious membrane-binding domains. However, smg p25A does contain a cDNA-predicted C-terminal Cys-Ala-Cys sequence at positions 218 through 220, which suggests that it may be posttranslationally modified. In the present study we used two different approaches to investigate this possibility. First, we incubated pheochromocytoma cells with [3H]mevalonolactone, examined the proteins that became labeled by two-dimensional gel electrophoresis, and demonstrated that two of these proteins exactly corresponded to smg p25A. Second, we purified smg p25A from bovine brain membranes and analyzed both the full-length protein and a proteolytically derived C-terminal peptide by a combination of high performance liquid chromatography and mass spectrometry. This approach revealed that the protein's C-terminal region is methyl-esterified and contains two geranylgeranyl groups linked via thioether bonds to Cys-218 and Cys-220. Since smg p25A is one of several small GTP-binding proteins that share a C-terminal Cys-Xaa-Cys consensus sequence (where Xaa is an unspecified amino acid), our results suggest that these proteins may be similarly geranylgeranylated and methyl-esterified. 
Pericardial haemorrhage causing right atrial compression after cardiac surgery: role of transoesophageal echocardiography. After cardiac surgery transoesophageal echocardiography showed a large thrombus compressing the right atrium in three hypotensive patients. No satisfactory images were obtained by transthoracic imaging, which is often difficult in ventilated patients after cardiac surgery. Transoesophageal echocardiography, however, provided rapid diagnostic information and permitted prompt surgical intervention. 
Impact of diagnosis-related groups on the quality of postoperative care of patients with neck dissections. Two hundred eighty patients underwent neck dissection over a 10-year period: 138 during the 5-year period before the institution of Diagnosis-Related Group (DRG) reimbursement and 142 during the 5 years after DRG regulations. A comparison of these two groups by site of tumor, stage of disease, histopathology, previous treatment, type of neck dissection, whether neck dissection was carried out alone or in combination with another procedure, presence of preexisting disease, postoperative complications, and mortality revealed no significant differences. A 35% reduction in the length of hospital stay from 16 to 10 days was identified in the post-DRG group with no detrimental effects on patient care. The variables found to have the greatest impact on length of hospital stay were the extent of operation and postoperative complications. 
Monomorphous histiocytoma in a child. Report of a case with ultrastructural features suggestive of dendritic cell differentiation. The authors describe a rapidly growing soft tissue tumor of predominantly histiocytic composition in an 8-year-old child. The tumor cells were identified as elements of the mononuclear phagocyte system by histologic, histochemical, immunologic, and electron microscopic study. Despite the presence of a minor fibroblastic component, the tumor did not conform to established criteria for a diagnosis of malignant fibrous histiocytoma. Formation of frequent desmosome-like intercellular junctions raised the possibility of dendritic reticulum cell differentiation, since the latter cells seem to be the only elements of the mononuclear phagocyte system that display such specialized cell junctions. The results of immunostaining were discrepant with those reported for normal dendritic reticulum cells, but the currently available information makes it doubtful that the entire neoplastic spectrum of dendritic cell differentiation can currently be diagnosed in surgical pathology. 
Effects of a meal on hemodynamic function at rest and during exercise in patients with hypertrophic cardiomyopathy. Many patients with hypertrophic cardiomyopathy experience postprandial exacerbation of their symptoms. The vasodilation associated with eating may be deleterious in hypertrophic cardiomyopathy, especially during exercise. To examine the hemodynamic effects of a meal in hypertrophic cardiomyopathy, 11 patients were studied with invasive hemodynamic monitoring during exercise testing in the fasting state and 45 min after a 740 kcal (3,100 J) meal. The meal induced a decrease in systemic vascular resistance index at rest (mean +/- SD, -17 +/- 14%), increases in mean right atrial (31 +/- 21%), mean pulmonary artery (14 +/- 14%) and mean pulmonary capillary wedge (17 +/- 14%) pressures and an increase in cardiac index (18 +/- 10%) due to an increased heart rate without any significant change in stroke volume. During postprandial exercise, heart rate, rate-pressure product, cardiac index and cardiac filling pressures were higher than during fasting exercise and one patient had a decrease in exercise blood pressure compared with the fasting test. Five patients with postprandial exacerbation of symptoms in everyday life had a lesser increase in systemic arterial pressure and stroke volume during both exercise tests and a smaller increase in cardiac index after the meal than did the six patients without postprandial symptom exacerbation, suggesting more severe cardiac disease. It is concluded that patients with hypertrophic cardiomyopathy have an abnormal hemodynamic response to food, in which stroke volume fails to increase and pulmonary capillary wedge and pulmonary artery pressures increase. These adverse changes persist during postprandial exercise and may predispose to exertional collapse in certain patients. 
Optimum concentration of bupivacaine for combined caudal--general anesthesia in children. Caudal epidural anesthesia has become widely accepted as a means of providing postoperative pain relief and intraoperative supplementation to general anesthesia for children. To determine the best concentration of bupivacaine for combined general-caudal anesthesia in children, 122 children aged 1-8 yr scheduled for outpatient inguinal herniorrhaphy were randomized to receive, in a double-blind fashion, caudal anesthesia with bupivacaine in one of six concentrations (0.125, 0.15, 0.175, 0.2, 0.225, or 0.25%). After incision, a programmed reduction in inspired halothane resulted, if tolerated by the subject, in an inspired halothane concentration of 0.5% 10 min after incision. End-tidal halothane concentration at hernia sac ligation for subjects receiving 0.175% bupivacaine (0.55 +/- 0.03%) was less than that for subjects receiving 0.15% bupivacaine (0.75 +/- 0.05%; P less than 0.05). Subjects receiving 0.175% bupivacaine also were discharged earlier from the postanesthesia care unit (PACU) (27 +/- 1 min) than were subjects receiving 0.15% bupivacaine (38 +/- 5 min; P = 0.05). Children receiving greater than or equal to 0.2% bupivacaine tended to complain more of leg weakness after surgery; however, the difference did not reach statistical significance (39 of 67 vs. 16 of 47; P = 0.057). The incidence of complaints of leg weakness and paresthesia was positively correlated with bupivacaine concentration (r = 0.706; P = 0.05). Subjects receiving 0.125% bupivacaine had higher pain scores on arrival to the PACU than did those receiving 0.2% bupivacaine (P = 0.05); there were no other differences in pain scores. 
Functional and urodynamic characteristics of bladder substitution with detubularised right colonic segment. A total of 19 patients underwent bladder replacement with a detubularised right colonic segment; 14 males underwent complete substitution after cystoprostatectomy and 5 females had augmentation after subtotal cystectomy. The mean follow-up time was 20 months. Urodynamic evaluation showed a low pressure reservoir with a mean capacity of 580 ml and normal closure pressure. Sensitivity of the bladder to cold was normal in the augmentation group but was lacking in all patients in the total substitution group. In all except 1 patient the neobladder emptied effectively upon straining without significant residual urine. Seventeen patients were completely continent by day and 10 by night; 1 patient developed hyperchloraemic acidosis requiring treatment. Bladder substitution is superior to the standard ileal or colonic conduits with regard to quality of life, and the use of a right colonic segment is functionally comparable with neobladders composed of the ileum or a combination of the right colon and ileum. The latter are more difficult to fabricate and so may have more complications. 
Effect of cisapride on delayed gastric emptying in gastro-oesophageal reflux disease. Some patients with gastro-oesophageal reflux disease have delayed gastric emptying. This study investigates the effect of cisapride on gastric emptying in 34 patients with proved reflux and delayed gastric emptying of solids. They were enrolled in a double blind controlled crossover study. Placebo or cisapride (10 mg) tablets were given three times a day for three days followed by further assessment of gastric emptying. The protocol was repeated with the crossover tablet. Gastric emptying was assessed by a dual radionuclide technique. The percentage of a solid meal remaining in the stomach at 100 minutes (% R100 minutes) and the time taken for 50% of the liquid to empty (T50 minutes) were calculated and analysed by the Wilcoxon matched pairs signed ranks test and expressed as medians (ranges). For gastric emptying of solids the initial % R100 minutes (70 (60-100)%) was not significantly different from placebo (71 (35-100)%). After cisapride treatment a significant acceleration (p less than 0.001) in gastric emptying occurred (% R100 minutes, 50.5 (28-93)%). Similarly with gastric emptying of liquids, the initial T50 minute value was 26.5 (12-82) minutes, after placebo the value was 28 (11-81) minutes, but this was significantly accelerated with cisapride (p less than 0.03) to 22.5 (6-61) minutes. The acceleration in gastric emptying occurred in the proximal portion of the stomach for gastric emptying of both solids and liquids suggesting that this is the principal site of action of cisapride. We conclude that cisapride significantly accelerates gastric emptying of both solids and liquids in patients with gastro-oesophageal reflux disease and delayed gastric emptying. 
Myelin splitting in the spongy lesion in Leigh encephalopathy. A spongy lesion consists of numerous vacuoles, mainly in the central gray matter, and is a characteristic finding in subacute necrotizing encephalopathy (Leigh encephalopathy); the cause of this lesion is unknown. An ultrastructural study on the vacuolated lesions in the left putamen of a patient with subacute necrotizing encephalopathy due to a deficiency of mitochondrial enzyme complexes I and IV revealed that the vacuoles were formed through the splitting of myelin. Because myelin splitting is commonly caused by toxic or metabolic diseases in humans and experimental animals, we believe that the vacuolation was due to the splitting of myelin which was caused by abnormal mitochondrial metabolism, even though this lesion is most commonly found in the white matter. We do not know whether the spongy lesion is formed only through myelin splitting in patients with subacute necrotizing encephalopathy; however, myelin splitting must play an important role in the formation of the spongy lesion. 
Depression and fatigue in the primary care physician. Fatigue is a symptom that is found in a variety of psychiatric disorders. The nature of a physician's life may foster such symptoms that can be either a reaction to work or a sign of an emotional disorder. This article summarizes various developmental stages that can lead to such problems. These difficulties may also be found in the physician's family and can be easily overlooked. 
Prolonged QT interval and risk of sudden death in South-East Asian men. Sudden death in sleep occurs in substantial numbers among young men in South-East Asia. The frequencies of electrocardiographic abnormalities were measured in groups with varying risks of such sudden death. The mean heart-rate-corrected QT interval (QTc) was significantly (p less than 0.05) greater among 123 Laotian refugees in Thailand at high risk (405 [95% confidence interval 397-413] ms) than in 77 Laotian refugees in the United States at lower risk (364 [359-369] ms) and 199 non-Asian US residents at negligible risk (358 [354-362] ms). Among refugees in Thailand, prolonged QTc interval was associated with poor thiamine status and a history of seizure-like episodes in sleep. Thiamine deficiency may be a cause of prolonged QT interval and sudden death in this region. 
MR imaging in hydatid disease. Hydatid cysts may develop anywhere in the body as a result of the presence of a viable parasite (Echinococcus granulosus). Depending on the condition of the parasite, the host reaction, and therapy, the hydatid cyst will degenerate and may eventually collapse, leaving an area of calcification in the host tissue. The purpose of this pictorial essay is to demonstrate the use of MR imaging in the diagnosis of the various stages of hydatid disease and in monitoring response to therapy. 
Nucleokinesis: distinct pattern of cell translocation in response to an autocrine motility factor-like substance or fibronectin [published erratum appears in Proc Natl Acad Sci U S A 1991 Aug 15;88(16):7456] Human lung adenocarcinoma cells develop bipolar shape with prominent pseudopodia (greater than or equal to 200 microns) when cultured in the presence of autocrine motility factor (AMF)-like substance or on fibronectin-coated substrata. AMF was partially purified from a human lung adenocarcinoma cell line and has a peak biological activity at a molecular mass of 67 kDa. Using time-lapse photography, we observed that during AMF- or fibronectin-induced cell translocation, the nuclei of some bipolar cells are transported to the opposite end of the cell, while gross cell shape and position remain unchanged. Following this nuclear movement, which we call "nucleokinesis," the posterior pseudopodium is retracted behind the nucleus. Thus, extension of a pseudopodium followed by nucleokinesis in the same direction and retraction of the cell body behind the nucleus is a normal motile sequence in translocating bipolar cells. This suggests that nucleokinesis is a distinct step in whole-cell translocation of bipolar cells on biological substrata and that pseudopodia can be used as nuclear transport organs. In contrast, adenocarcinoma cells cultured on artificial substrata and in the absence of AMF display a fibroblast-like motility pattern with the nucleus centrally located within the migrating cell. 
Clinical and electrodiagnostic features of X-linked recessive bulbospinal neuronopathy. We describe four men from two kinships affected with X-linked recessive bulbospinal neuronopathy, and one sporadic case. All developed postural tremor, weakness, and fasciculations, with onset from age 25 to 39 years. Weakness began in the pelvic girdle or hands, with dysphagia or dysarthria occurring years later in two. Sensory symptoms were present in only one, who also had diabetes mellitus. In contrast, sural nerve action potentials were small or absent in all. Needle EMG showed widespread chronic partial denervation with reinnervation. The characteristic twitching of the chin produced by pursing of the lips consisted of repetitive or grouped motor unit discharges, rather than fasciculations. Broader awareness of the distinctive features of bulbospinal neuronopathy will probably increase the frequency of its recognition. Diagnosis is important for purposes of providing a prognosis for affected men and genetic counseling for affected families. 
Use of albumin as a volume expander. In some hospitals, albumin products account for 10% of the pharmaceutical budget. As much as 60% of these prescriptions are empiric, and from 40 to 70% of albumin that is administered is given for inappropriate reasons. Although the reasons for albumin administration vary, prevention or reversal of hypovolemia is part of the reason in the majority of cases. 
Venous obstruction: an analysis of one hundred thirty-seven cases with hemodynamic, venographic, and clinical correlations. One hundred thirty-seven limbs with venous obstruction were analyzed. The arm/foot venous pressure differential and reactive hyperemia tests were found to be useful techniques to diagnose and grade venous obstruction. Traditional techniques including venography and ambulatory venous pressure are inferior in this regard. The newer techniques have provided newer insights in venous obstruction which are detailed herein. The hand-held Doppler was surprisingly very sensitive in grade I as well as in more severe forms of obstruction. Neither anatomic locale of obstruction nor its extent determined hemodynamic severity. Extensive proximal lesions could be hemodynamically mild, and conversely distal crural obstructions and single segment lesions could be hemodynamically severe. Phlebographic appearance was a poor index of collateralization. The paradoxical venous pressure response to the reactive hyperemia test in grade IV obstruction was found to be due to suppression or delay of the reactive hyperemia response itself in the presence of severe venous obstruction. The pain of venous claudication may be related to this phenomenon. Skin ulceration in the presence of venous obstruction was related to the associated reflux rather than the hemodynamic severity of the obstruction itself. The Linton procedure was found to be useful in treating such skin ulcerations. After perforator disruption, obstruction did not become hemodynamically worse, but reflux as measured by the Valsalva test improved with ulcer healing. The improvement in reflux related to Valsalva offers for the first time a hemodynamic rationale for the Linton procedure. 
Epidemiology of acute respiratory infections in children of developing countries. Acute respiratory infections cause four and a half million deaths among children every year, the overwhelming majority occurring in developing countries. Pneumonia unassociated with measles causes 70% of these deaths; post-measles pneumonia, 15%; pertussis, 10%; and bronchiolitis and croup syndromes, 5%. Both bacterial and viral pathogens are responsible for these deaths. The most important bacterial agents are Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus. The data on bacterial etiology of pneumonia during the first 3 months of life are limited, and almost no information on the role of chlamydia and pertussis in this age period is available. The distribution of viral pathogens in developing countries can be summarized as follows: respiratory syncytial virus, 15%-20%; parainfluenza viruses, 7%-10%; and influenza A and B viruses and adenovirus, 2%-4%. Mixed viral and bacterial infections occur frequently. Risk factors that increase the incidence and severity of lower respiratory infection in developing countries include large family size, lateness in the birth order, crowding, low birth weight, malnutrition, vitamin A deficiency, lack of breast feeding, pollution, and young age. Effective interventions for prevention and medical case management are urgently needed to save the lives of many children predisposed to severe disease. 
Prevention of anastomosis leakage: an artificial connective tissue. Anastomosis leakage still causes considerable morbidity and mortality after digestive tract surgery. We report here our experience of the use of reconstituted connective tissue created from elastin, fibronectin and collagen in preventing anastomosis leakage and closing intestinal fistulas. In animal studies (56 rats), this connective tissue was used as a patch applied with fibrin sealant to the edges of a 1 cm diameter colonic defect. In a clinical evaluation, eight patients had an intestinal fistula closed by a simple sewn suture reinforced by a sealed patch and seven patients had a high risk anastomosis reinforced by a sealed patch, in most cases as an alternative to staged surgery. In animal studies, complete reconstitution of the three colonic layers was obtained without retraction and without inflammatory reaction within 40 days, while the patch was slowly resorbed. In clinical trials all 15 defects and anastomoses healed without complication. Three patients died from other causes and, at autopsy, the patch was found to have remained in place covering the suture line. If these results are confirmed by a prospective clinical trial, such biomaterial offers the possibility of reducing the occurrence of anastomosis leakage, especially in high risk circumstances. 
Elective versus emergency cesarean hysterectomy cases in a residency program setting: a review of 129 cases from 1984 to 1988. A retrospective study was performed to compare elective versus emergency cesarean hysterectomy in a residency program. We noted the following statistically significant differences between emergency and elective cases: (1) Estimated blood loss (mean +/- SD) for emergency and elective cases was significantly different at 1495 +/- 772 and 875 +/- 396 ml (p = 0.001). (2) Operative time in emergency cases was significantly longer than in elective cases (105 +/- 38 vs 83 +/- 27 minutes, p = 0.003). (3) The incidence of transfusion was 68% in our emergency cases and 14.6% in the elective series (p less than 0.05). (4) Febrile morbidity in our series was 40% in emergency cases and 18.3% in elective cases (p less than 0.05). Our series was comparable to previous series reported. Our experience suggests that cesarean hysterectomy can be performed safely in a residency training program when done as an elective procedure in the well-prepared patient. 
Cardiovascular effects of volatile anesthesia in rabbits: influence of chronic heart failure and enalaprilat treatment. Circulatory responses to isoflurane and halothane anesthesia were studied in eight rabbits with biventricular cardiomyopathy induced by doxorubicin (Adriamycin, 14 mg/kg IV over 7 wk) and in eight controls (saline injections). In preliminary operations pulsed-Doppler flow probes were placed on the ascending aorta, left renal artery, and lower abdominal aorta. Each group was studied after 4, 6, and 7 wk of treatment. The development of congestive heart failure (CHF) was associated with decreases in mean arterial pressure and cardiac output (CO) of 14% and 16%, respectively, (P less than 0.05) and an increase in heart rate. In controls, each anesthetic agent produced dose-related decreases in mean arterial pressure and increases in heart rate, but not significant changes in CO. Renal blood flow was reduced to a similar degree by 1.3 MAC halothane (24% decrease) and 1.3 MAC isoflurane (21% decrease); hindlimb blood flow was reduced only by halothane. As CHF developed there was an attenuation of the heart rate response to anesthesia. Halothane, but not isoflurane, significantly reduced CO in more advanced stages of CHF. The changes in renal blood flow and hindlimb blood flow with each anesthetic in the CHF group were similar to those observed in controls and did not vary with week of treatment. Administration of the angiotensin-converting enzyme inhibitor enalaprilat (0.2 mg/kg IV) reversed the CO and renal blood flow effects of halothane except after 7 wk of treatment in the CHF group, when the combination of halothane and enalaprilat resulted in severe circulatory depression. 
Dilatation of ascending aorta in patients with repaired coarctation. The long-term outcome following repair of typical aortic coarctation in adulthood may be complicated by disorders of the ascending aorta. Follow-up averaging 15 years revealed a 3.8% incidence of dilatation of the ascending aorta after such late repair. Hypertension and concomitant aortic valvular disease were common in these patients. Aortic dilatation can appear years after coarctation repair, irrespective of the operative technique and its success, and can lead to death from aortic dissection or rupture of an aortic aneurysm. Careful follow-up after coarctation repair in adulthood is advisable to detect late aortic complications. 
Multicenter study of superficial bladder cancer treated with intravesical bacillus Calmette-Guerin or adriamycin. Results of long-term follow-up. We evaluated 158 cases of patients with superficial bladder cancers (Stages Ta, T1, and Tis). These cases were treated with either intravesical bacillus Calmette-Guerin (BCG) (Tice strain) or Adriamycin (ADR), in a multicenter, nonrandomized study. One hundred thirty-one of these patients were followed up; the results continue to show a higher percentage of initial complete remissions with BCG (68%) than with ADR (57%). With additional therapy, both BCG and ADR achieved complete remission in 83 percent of the patients. When 7 failures with patients taking ADR were switched to BCG and the disease cleared, the rate of complete remission for BCG rose to 85 percent. The recurrence rate per 100 patient-months was only slightly different for BCG (0.9) and ADR (0.8). The percentage of progressions continued to be higher for BCG (8%) than for ADR (5%). Cystectomies were performed in 2.5 percent of the BCG patients. Using the Cox regression model with covariates, we found drug treatment, tumor grade, and sex to be statistically significant in determining failures throughout the protocol. Although both BCG and ADR were effective over the course of the study, BCG is the drug of choice for residual tumor (Stages T1 and Tis). 
Chronic morphine therapy for cancer pain: plasma and cerebrospinal fluid morphine and morphine-6-glucuronide concentrations. Morphine-6-glucuronide (M-6-G) is an active metabolite that may contribute to the clinical effects produced by systemic administration of morphine. To help clarify the extent to which M-6-G may cross the blood-brain barrier and exert effects, we employed high-performance liquid chromatography with electrochemical detection to measure the concentrations of M-6-G and morphine in the plasma and either ventricular (three patients) or lumbar (eight patients) CSF of cancer patients receiving chronic morphine therapy. The mean ratio of morphine in ventricular CSF:morphine in plasma was 0.71; the same ratio for M-6-G was only 0.077. The average molar ratio of M-6-G: morphine in ventricular CSF was 0.207, and the average molar ratio in plasma was 1.89. Although sampling problems render the lumbar CSF results less reliable, they were very similar. Thus, plasma contained approximately twice as much M-6-G as morphine, whereas CSF contained only one-fifth to one-third as much. These data confirm that M-6-G in plasma is distributed into CSF, but to a far lesser extent than morphine. They help explain animal data demonstrating much higher potency of M-6-G on administration into CSF than systemic administration and indicate that the degree to which M-6-G contributes to morphine effects in humans remains an unresolved question. 
Ascitic fluid pH and lactate: insensitive and nonspecific tests in detecting ascitic fluid infection. Ascitic fluid pH and lactate concentration have been proposed as useful tests for the detection of ascitic fluid infection. However, past studies involved small numbers of infected patients, and all did not use optimal culture techniques. This large study was performed using highly sensitive culture methods and sought (a) to compare the sensitivity, specificity and accuracy of pH and lactate to that of the ascitic fluid neutrophil count and (b) to determine whether evaluation of ascitic fluid pH or lactate (or arterial-ascitic fluid pH or lactate gradient) would result in improved decision-making regarding empirical treatment of suspected ascitic fluid infection. Analysis of 206 ascitic fluid specimens obtained in 175 patients, including 101 infected specimens, revealed that ascitic fluid (or arterial-ascitic fluid) pH and lactate were less than 50% sensitive in detecting bacterial peritonitis and that these tests did not improve clinical decision-making about empirical treatment of suspected ascitic fluid infection. Although statistically significant differences in ascitic fluid pH were detected between infected samples and control samples, these differences did not appear to be clinically helpful. The ascitic fluid pH was 0% sensitive in detecting the presence of bacteria in the absence of neutrophils (i.e., no such specimens had a pH lower than 7.35). Ascitic fluid pH correlated well with neutrophil count and appears to be, at least in part, an indirect measure of the presence of neutrophils in ascitic fluid. Measurement of pH or lactate (or arterial-ascitic fluid gradients) is not helpful in the clinical management of infected ascitic fluid. 
Klinefelter's syndrome and liver adenoma. We describe the occurrence of a liver adenoma in a young patient with Klinefelter's syndrome, diagnosed by classic 47,XXY karyotype in all investigated cells and a sex hormone imbalance. To our knowledge, this is the first report of such an association, which might suggest a simple coincidence. However, a pathogenetic link between Klinefelter's syndrome and liver adenoma can be suggested in view of the following facts: Liver adenoma mostly affects women of child-bearing age using oral contraceptives. It is very rare in men, and affected men frequently have been treated with androgens. Both groups are characterized by a sex hormone imbalance. Also, the risk of breast cancer, another hormone-sensitive tumor, is greatly elevated in men with Klinefelter's syndrome, possibly due to sex hormone imbalance. 
Heart rate response during exercise testing and ambulatory ECG monitoring in patients with syndrome X. The response of the heart rate during exercise testing and 24-hour ambulatory electrocardiographic (ECG) monitoring performed with patients not receiving antianginal treatment was assessed in 26 patients (9 men and 17 women; mean age 51 +/- 8 years) with syndrome X (angina pectoris with normal coronary arteries), in 27 patients with coronary artery disease (10 men and 17 women; mean age 55 +/- 9 years), and in 21 healthy subjects (8 men and 13 women; mean age 47 +/- 11 years). In patients with syndrome X the slope of the regression line of heart rate versus time (heart rate/time slope) during exercise testing was similar to that of patients with coronary artery disease (3.3 +/- 0.8 versus 3.1 +/- 1.2 beats/min), but significantly lower than that in healthy subjects (4.2 +/- 1.1 beats/min; p less than 0.003). In patients with syndrome X the intercept of the heart rate/time slope was significantly higher than that in coronary artery disease patients and healthy subjects (102 +/- 15, 86 +/- 18, and 90 +/- 16 beats/min, respectively; p less than 0.015). Resting preexercise heart rate was also significantly higher in syndrome X, compared with coronary artery disease patients and healthy subjects (91 +/- 16, 79 +/- 16, and 80 +/- 14 beats/min, respectively). During ambulatory ECG monitoring, mean diurnal heart rate (from 6 AM to 6 PM) was higher in patients with syndrome X (83 +/- 8 beats/min) than in patients with coronary artery disease (75 +/- 8 beats/min) and healthy subjects (74 +/- 11 beats/min) (p less than 0.02). 
Association of immunoreactive eosinophil major basic protein with placental septa and cysts. A protein that is immunochemically indistinguishable from the major basic protein of the eosinophil granule is present at elevated concentrations in the plasma of pregnant women. Major basic protein has been localized to placental trophoblasts known as X cells. Because X cells are located in placental septa and septal cysts, we tested whether the numbers of these structures are correlated with plasma levels of major basic protein. Data analysis revealed strong positive correlations between maternal plasma major basic protein concentrations and the number of placental septa, septal cysts, and subchorial cysts and the presence of subchorial fibrin deposits. No significant correlation was found between plasma major basic protein levels and other variables examined, such as placental weight. Thus major basic protein is a specific marker for septa and cysts, presumably because it is an X-cell product. The study of major basic protein may aid in delineating the function and ontogeny of X cells, as well as their role in fibrin deposition and in septa and cyst formation. 
Experimental model of left ventricular failure. A model of chronic cardiac failure has undergone extensive hemodynamic investigation. Under anesthesia the homonymous and second diagonal coronary arteries of sheep have been ligated. The resulting myocardial infarction caused significant acute hemodynamic impairment (paired two-tailed t tests), mean pulmonary artery pressure increasing from 7.31 +/- 0.94 to 13.80 +/- 1.19 mm Hg (p less than 0.001), pulmonary artery diastolic pressure increasing from 4.94 +/- 1.03 to 11.13 +/- 1.27 mm Hg (p less than 0.001), and directly measured left ventricular end-diastolic pressure increasing from 9.31 +/- 1.52 to 17.42 +/- 1.82 mm Hg (p less than 0.001) after infarction documented with invasive monitoring. There was a hemodynamically significant left ventricular aneurysm (paired two-tailed t tests) in animals studied 3 months later, with increased mean pulmonary artery pressure from 7.20 +/- 1.15 to 13.80 +/- 2.00 mm Hg (p = 0.009), an increase in pulmonary artery diastolic pressure from 4.60 +/- 1.30 to 12.10 +/- 2.06 mm Hg (p = 0.006), and an increase in left ventricular end-diastolic pressure from 11.00 +/- 1.94 mm Hg before infarction to 17.00 +/- 2.69 mm Hg (p = 0.038). We conclude that this is a useful model of chronic left ventricular failure that is reproducible and applicable to investigations of therapeutic options in chronic heart failure. 
The clinical and endocrine outcome to trans-sphenoidal microsurgery of nonsecreting pituitary adenomas. From 1962 to 1987, 126 patients underwent trans-sphenoidal surgery for primary treatment of pituitary adenomas unassociated with clinical or biochemical evidence of hormonal overproduction. There were 73 male and 53 female patients (mean age, 50 +/- 12 years). Before surgery, 56% of the patients (70 of 124) had headaches, 74% (94 of 126) had deterioration of vision, and 12% (15 of 126) had ophthalmoplegia. Endocrine evaluation revealed the presence of hypogonadism in 75% (87 of 115), adrenal insufficiency in 36% (46 of 126), and hypothyroidism in 18% (21 of 122). Plasma prolactin was increased in 65% (56 of 86) with a mean level of 39 +/- 14 micrograms/l (normal, 3 to 20 micrograms/l). Radiologic enlargement of the sella turcica was documented in all cases: 67% (84 of 126) had enclosed and 33% (42 of 126) had invasive adenomas. After surgery, vision was normalized or improved in 75% (71 of 94) of the patients. Thyroid, adrenal, and gonadal functions were improved in 14% (three of 22), 41% (19 of 46), 11% (ten of 87), were unchanged in 82% (100 of 122), 77% (97 of 126), 89% (102 of 115), and worsened in 15% (19 of 22), 8% (ten of 126), 3% (102 of 115), respectively. Permanent diabetes insipidus occurred in 5% (seven of 126). Two patients died during the immediate postoperative period. The recurrence rate in patients with a mean follow-up of 6.4 +/- 4.2 years was 21% (15 of 71). These data indicate that trans-sphenoidal microsurgery is an effective and safe initial treatment for patients with nonsecreting pituitary adenoma and may reverse hypopituitarism. 
The current approach to the medical diagnosis of low back pain. A small number of patients who present with low back pain will have an underlying medical disorder as the source of their pain. Patients who fail to respond to conservative management with controlled physical activity and nonnarcotic analgesics should have a thorough re-evaluation to detect possible sources of nonmechanical pain. Symptoms of fever, weight loss, recumbency pain, morning stiffness, acute severe pain, or colicky back pain represent specific entry points into the algorithm for diagnosis of back pain from underlying systemic illnesses. These patients will generally require a plain roentgenographic examination with subsequent scintography, MRI, CT, laboratory work, and biopsy as indicated by any positive findings during the diagnostic work-up. Therapy for individuals with nonmechanical low back pain is directed at the specific medical disorder that is the cause of their symptoms. 
Melanocytic differentiation of human neuroblastoma: expression of a human melanosome-associated antigen. Five human neuroblastoma cell lines were examined for expression of a human melanosome-associated antigen (HMSA). Only cell line SK-N-SH reacted with a monoclonal antibody, HMSA-2, shown to recognize melanosomal glycoproteins. To further characterize the melanocytic lineages of SK-N-SH, three morphologically distinct clones designated SK-N-SH-N (neuroblast type), SK-N-SH-F (fibroblast type), and SK-N-SH-EP (epithelial type) were established by colony formation cloning. By fluorescence-activated cell sorter analysis and tyrosinase assay, we found that only SK-N-SH-EP and SK-N-SH-F reacted with HMSA-2 and had tyrosinase activity. These results suggest that epithelial-type and fibroblast-type cells appear to possess the melanocytic potential, but not neuroblast-type cells. Furthermore, SK-N-SH-EP was found to spontaneously convert to neuroblast-type or fibroblast-type cells, whereas SK-N-SH-N and SK-N-SH-F clones have remained morphologically stable. Our results suggest that at least one neuroblastoma cell line, SK-N-SH, may be an excellent model for investigating clonal maturation and the melanocytic differentiation of neuroblastoma. 
Levels of morphine and metabolites in CSF during respiratory depression after intraventricular morphine injection. We report a case of respiratory depression after intracerebroventricular morphine administration of a dose inadvertently 10 times greater than the typical daily dose. At the time of the respiratory dysfunction, the concentrations of morphine and its metabolites in cerebrospinal fluid (CSF) and plasma samples were determined. On comparison of these results with previous clinical studies in which there was no respiratory depression, no relationship was found between the occurrence of respiratory depression and the concentration of morphine or its metabolites in the CSF. The occurrence and characteristics of respiratory depression may be related to the concentrations of morphine and its metabolites in bulbar tissue. 
Influence of progressive and of transient hypoxia on upper airway resistance in normal humans. In order to evaluate the influence of hypoxia on upper airway patency, we measured the response of upper airway resistance (UAR) to progressive (P) normocapnic hypoxia (Rebuck's method) and transient (T) hypoxia (three to five breaths to 100% N2) in 11 normal men. Breath-by-breath inspiratory UAR was calculated at isoflow during exclusive nasal breathing. The UAR response to hypoxia was characterized by the changes in nasal resistance and pharyngeal resistance (PR) as a function of SaO2, mean inspiratory flow (VT/Tl), and changes in the end-expiratory lung volume (EELV) measured with an inductance vest. The ventilatory response to hypoxia was greater during T (-0.31 +/- 0.03 L/min/%SaO2; mean +/- SEM) than during P (-0.27 +/- 0.03 L/min/%SaO2, p = 0.05). UAR decreased as SaO2 decreased; this decrease was steeper during T than during P hypoxia (delta PR/%SaO2: 3.9 +/- 0.5 during P and 2.5 +/- 0.2 during T, p = 0.05). For the whole group, there was no difference in the slope of the decrease in UAR with increasing VT/Tl between the two hypoxic tests (delta PR/delta VT/Tl: -0.85 +/- 0.1 during P and -0.70 +/- 0.1 during T, p greater than 0.05). However, in four subjects, the slope of the relationship PR/VT/Tl during T remained steeper than during P. EELV increased as SaO2 decreased, with a greater increase during progressive than during transient hypoxia. 
High frequency of the Gaucher disease mutation at nucleotide 1226 among Ashkenazi Jews. Reliable estimates of the frequency of Gaucher disease-producing mutations are not available. The high frequency of Gaucher disease in the Ashkenazi Jewish population is due to the occurrence of a mutation at nucleotide (nt) 1226. We have screened 593 DNA samples from normal Ashkenazi Jews, as well as 62 DNA samples from all our Ashkenazi Jewish patients with Gaucher disease, for the presence of the 1226 mutation. In the 593 presumed normal Ashkenazi Jewish individuals the 1226 mutation was identified in the heterozygous state in 37 and in the homozygous state in two, giving a gene frequency of .035 for the mutation. This 1226 mutation represented 73% of the 124 Gaucher disease alleles in Jewish Gaucher disease patients. Accordingly we estimate that the gene frequency for Gaucher disease among the Ashkenazi Jewish population is .047, which is equivalent to a carrier frequency of 8.9% and a birth incidence of 1:450. 
Aortic-carotid artery pressure differences and cephalic perfusion pressure during cardiopulmonary resuscitation in humans. OBJECTIVE: Animal studies have shown an aortic-carotid artery pressure difference during cardiopulmonary resuscitation (CPR), which compromises cerebral perfusion. This pressure difference is most marked with prolonged CPR and can be abolished with administration of high doses of epinephrine. To better understand the mechanism of cerebral blood flow during CPR in humans, we determined the aortic-carotid artery pressure difference, the cephalic perfusion pressure (the carotid artery-jugular vein pressure difference), and thoracic inlet venous "valving" (the central venous-jugular vein pressure difference), while administering standard doses of epinephrine. DESIGN: Prospective study with randomization as to which side the carotid artery was catheterized. SETTING: The resuscitation room of a large urban hospital's emergency department. PATIENTS: Fifteen adults in normothermic, nontraumatic prehospital cardiac arrest treated according to Advanced Cardiac Life Support guidelines, including administration of 1 mg epinephrine iv every 5 mins. INTERVENTIONS: The descending aorta, cervical common carotid artery, internal jugular vein, and central venous system were catheterized. Pressures were recorded during standard CPR for 5 mins after administration of 1 mg epinephrine iv. MEASUREMENTS AND MAIN RESULTS: Most patients received CPR for greater than 20 mins before the first epinephrine dose and for greater than 45 mins before pressure recording as described above. There was no significant difference between aortic and carotid artery compression and relaxation phase pressures. The mean +/- SD compression central venous-jugular vein pressure difference was 22.1 +/- 15.0 mm Hg, and the mean cephalic perfusion pressure was 20.8 +/- 19.5 mm Hg. CONCLUSIONS: There is no clinically important aortic-carotid artery pressure difference during human CPR using the standard dose of epinephrine, even with prolonged CPR. Despite carotid artery patency and thoracic inlet venous valving, the cephalic perfusion pressure is low during CPR in humans. 
Dutch general practice care for patients with epilepsy: results from the Dutch National Survey of Morbidity and Interventions. This study aimed to assess the share which Dutch general practice has in the care of patients with epilepsy. During a 3-month period 400,000 patient contacts in 103 general practices with a total list of 335,000 patients were registered, 1536 of these, concerning 1059 patients, concerned epilepsy. Contacts with patients with known epilepsy in Dutch General Practice were handled mainly by the practice nurse and most involved repeat prescriptions. Patients suspected of having epilepsy had more attention from the General Practitioner. The involvement of General Practitioners in the care of epilepsy was found to be small, but not unimportant. GPs are in a crucial position as regards the detection of epilepsy. They can enlarge their role in respect of patients with known epilepsy and improve continuity of care. 
Hemodynamic study during transdermal application of nitroglycerin tape in patients with cirrhosis. We studied 14 patients with portal hypertension and cirrhosis using portal and hepatic vein catheterizations to determine the effects of transdermal application of nitroglycerin tape (containing 10 mg of nitroglycerin and capable of releasing 6 to 7 mg of nitroglycerin in 12 hr) on splanchnic hemodynamics. Patients randomly received nitroglycerin (n = 7) or a placebo (n = 7). No significant changes were observed after the administration of the placebo. In contrast, transdermal nitroglycerin caused a significant reduction in portal pressure, as evaluated by measurements of the portal venous pressure gradient (-22%, p less than 0.01). The reduction of portal pressure was due to a decrease in the portal venous pressure, with no changes in the free hepatic venous pressure. Despite the fall in portal pressure, the hepatic blood flow was maintained. These findings suggest that transdermal nitroglycerin could be potentially useful in the treatment of portal hypertension associated with cirrhosis. 
Auer rod-like inclusions in circulating lymphoma cells. Circulating malignant lymphocytes from a 55-year-old woman with small cleaved follicular center cell lymphoma contained azurophilic splinter-shaped cytoplasmic inclusions. By light microscopic and ultrastructural criteria, these structures closely resembled Auer rods found in acute myeloid leukemia; however, the authors could not find cytochemical evidence of lysosomal origin (results were negative for myeloperoxidase, Sudan black B, acid phosphatase, and periodic acid-Schiff). Immunostaining and flow cytometric analysis confirmed a monoclonal IgM-kappa immunophenotype of the circulating malignant lymphoid cells. The inclusions did not show specific immunoglobulin staining by light microscopic or electron microscopic immunostaining techniques. The authors conclude that these membrane-bound inclusions probably represent aberrant lysosomes in the malignant cells. 
Cell cycle regulation of histone H1 kinase activity associated with the adenoviral protein E1A. Several cellular proteins form stable complexes with the proteins encoded by the adenovirus early region 1A (E1A) gene in extracts derived from adenovirus infected or transformed cells. Two of the cellular proteins that bind to E1A have been identified; one, a 105-kilodalton protein (pRb), is the product of the retinoblastoma gene, and the other, a 60-kilodalton protein, is a human cyclin A. Two other proteins that bind E1A have now been shown to be related to p34cdc2. This E1A complex displayed histone H1-specific kinase activity; the kinase activity was modulated during the cell division cycle, and association of pRb with E1A apparently was not required for this activity. 
Comparison of standard external CPR, open-chest CPR, and cardiopulmonary bypass in a canine myocardial infarct model. STUDY OBJECTIVES: After cardiac arrest, open-chest CPR (OCCPR) and cardiopulmonary bypass (CPB) have demonstrated higher resuscitation rates when compared individually with standard external CPR (SECPR). We compared all three techniques in a canine myocardial infarct ventricular fibrillation model. TYPE OF PARTICIPANTS: Twenty-six mongrel dogs were block-randomized to receive SECPR and advanced life support (nine), CPB (nine), or OCCPR (eight). DESIGN AND INTERVENTIONS: All dogs received left anterior descending coronary artery occlusion followed by four minutes of ventricular fibrillation without CPR and eight minutes of Thumper CPR. At 12 minutes, dogs received one of three resuscitation techniques. After resuscitation, all animals received four hours of intensive care. Animals that were resuscitated had histochemical determination of ischemic and necrotic myocardial areas. MEASUREMENTS: Intravascular pressures were measured and coronary perfusion pressure was calculated during baseline, cardiac arrest, resuscitation, and postresuscitation periods. Percent necrotic myocardium, percent ischemic myocardium, and necrotic-to-ischemic ratios were determined for resuscitated animals. Epinephrine dosage and number of countershocks were determined for each group. MAIN RESULTS: Nine of nine CPB and six of nine OCCPR, compared with two of eight SECPR animals, were resuscitated (P less than .01). Three of nine CPB and OCCPR and two of eight SECPR dogs survived to four hours (P = NS). Coronary perfusion pressure two minutes after institution of technique was significantly higher with CPB (75 +/- 37 mm Hg) and OCCPR (56 +/- 31 mm Hg) than in SECPR animals (16 +/- 16 mm Hg, P less than .04). Epinephrine required for resuscitation was significantly less with CPB (0.10 +/- 0.02 mg/kg) than for SECPR (0.28 +/- 0.11 mg/kg, P less than .002). The ratio of necrotic to ischemic myocardium at four hours was significantly lower with CPB (0.15 +/- 0.31) and OCCPR (0.39 +/- 0.25) than for SECPR (1.16 +/- 0.31, P less than .02). CONCLUSION: OCCPR and CPB produce higher coronary perfusion pressures and improved resuscitation rates from ventricular fibrillation when compared with SECPR in this canine myocardial infarct cardiac arrest model. CPB and OCCPR yielded similar resuscitation results, although less epinephrine was required with CPB. 
Ultrasound detection of fetal aneuploidy in patients with elevated maternal serum alpha-fetoprotein. Increasing confidence in the ability of high-resolution ultrasound to detect neural tube and ventral wall defects has enabled us to offer a revised risk estimate to the patient with an elevated maternal serum alpha-fetoprotein (MSAFP) level, such that amniocentesis may not be necessary. Recent authors have suggested that a reduced emphasis on follow-up amniocentesis fails to consider an increased risk for chromosomal anomalies in pregnancies with an elevated MSAFP, and that amniocentesis should still be performed. We reviewed our ultrasound findings from patients who underwent amniocentesis for evaluation of an elevated MSAFP and who had a karyotype prepared from the amniotic fluid sample. Four abnormal karyotypes were detected among 313 amniocenteses, and three of these were correctly predicted based on an abnormal ultrasound. The risk of an unexpected fetal aneuploidy after a normal consultative ultrasound in our series was one in 310. This is comparable to the risk of detecting abnormal chromosomes in the fetus of a 32-year-old woman, an age at which amniocentesis is not routinely offered. 
Hepatocellular carcinoma in Italian patients with cirrhosis BACKGROUND AND METHODS. Patients with cirrhosis of the liver are recognized as being at risk for hepatocellular carcinoma. The magnitude of the risk, the natural history of this disease, and the possibilities for detecting potentially curable tumors in patients in the Western world are unknown. To address these questions, we examined 447 Italian patients with well-compensated cirrhosis (which was of viral origin in 62 percent of them) from 1985 through 1990, performing serum alpha-fetoprotein assays and real-time ultrasonography every 3 to 12 months. RESULTS. Hepatocellular carcinoma was found in 30 patients (7 percent) at base line and in another 29 patients (7 percent of 417 patients free of tumor at base line) during follow-up periods averaging 33 months (range, 1 to 48). The cumulative hazard of the development of hepatocellular carcinoma during follow-up was higher among patients with persistently elevated serum alpha-fetoprotein levels (12 with tumors among 42 with such levels) than among those with fluctuating levels (11 among 82) or those with consistently normal levels (6 among 255). Only 17 patients had potentially operable tumors. The proportion of potentially operable tumors among those detected during follow-up was significantly lower than the proportion at enrollment (4 of 29 vs. 13 of 30, P = 0.027). The survival at one year of the 12 patients who underwent surgery was 67 percent, and the tumor-recurrence rate was 60 percent. Outcome was not appreciably different for the five patients who refused surgery. CONCLUSIONS. In the West, as in Asia, patients with cirrhosis of the liver are at substantial risk for hepatocellular carcinoma, with a yearly incidence rate of 3 percent. Our screening program did not appreciably increase the rate of detection of potentially curable tumors. 
Isolated muscle hypertrophy as a sign of radicular or peripheral nerve injury. Two patients with isolated neurogenic hypertrophy of the trapezius muscle due to accessory nerve injury and a patient with neurogenic hypertrophy of the anterior tibial muscle due to chronic radicular lesion L4 are described. Electromyography of the affected muscles showed dense continuing spontaneous discharges of complex potentials. Muscle biopsy performed in two patients showed abundant hypertrophic muscle fibres, identified in one case by ATP-ase reaction as being of predominantly type I. In the majority of previously reported patients with neurogenic muscle hypertrophy confined to the calf muscle, a passive stretch mechanism was suggested as a cause of the hypertrophy. It is assumed that the excessive spontaneous muscle activity gave rise to the hypertrophy in these patients. This may also be true in previously reported patients with neurogenic hypertrophy and similar spontaneous activity in electromyography. 
Management of panfacial fractures. Panfacial injuries are those that involve trauma to the lower, middle, and upper facial bones. They often are accompanied by multisystem- or polytrauma and require a team approach for management. Although stabilization of the overall status of the patient takes precedence, early and total restoration of facial form and function should be the goal of the maxillofacial surgeon. 
Ralitoline: a reevaluation of anticonvulsant profile and determination of "active" plasma concentrations in comparison with prototype antiepileptic drugs in mice. Ralitoline (RLT) is a new thiazolidinone derivative with potent anticonvulsant activity in different seizure models. During Phase I studies, RLT was well tolerated in human volunteers and showed linear pharmacokinetics in the dose range tested (up to 150 mg). Since RLT will soon be entering clinical Phase II studies, we were interested in obtaining predictive data for effective plasma concentrations in patients. For this purpose, the anticonvulsant potency of RLT was determined in four seizure models in mice, and plasma levels were measured at time of peak drug effect. The four models were the threshold for maximal (tonic extension) electroshock seizures (MES), the threshold for clonic seizures determined by i.v. infusion of pentylenetetrazol (PTZ), the traditional MES test with supramaximal (50 mA) stimulation, and generalized clonic seizures induced by s.c. administration of PTZ. Furthermore, median minimal "neurotoxic" doses (TD50s) were determined by the rotorod and chimney test for calculation of protective indices. All data obtained for RLT were compared with data obtained with standard antiepileptic drugs: phenobarbital, phenytoin, valproate, and diazepam. The onset of anticonvulsant action after i.p. injection of RLT was very rapid, and the peak drug effect was already obtained after 2 min. In the MES models, RLT was the most potent compound. "Active" plasma levels ranged from approximately 300 ng/ml in the MES threshold test to approximately 1,300 ng/ml in the MES test. RLT was also capable of increasing the PTZ threshold, whereas, possibly because of its short duration of action in mice, it was not very active in the s.c. PTZ seizure test. 
The prognostic value of endotracheal tube-air leak following tracheal surgery in children. In an effort to determine if the endotracheal tube-leak pressure has prognostic value in relation to a successful outcome after one-stage laryngotracheal reconstruction or cricoid split surgery, a retrospective analysis was performed on 17 children who had undergone such surgery. The daily leak pressures, length of intubation, and ultimate outcome of attempts at extubation were noted. One hundred percent of patients with a leak pressure of less than 20 cm H2O on the day before extubation were successfully extubated. In contrast, the failure rate was 100% in children extubated with a leak of greater than 30 mm H2O. The difference between these two groups was statistically significant (chi 2, 13.03). Sixty percent of patients with leak pressures in the range of 21 to 30 cm H2O were successfully extubated. The endotracheal tube-leak pressure is a parameter that has prognostic value, and should be considered in determining when to extubate children who have undergone tracheal reconstructive surgery. 
Interaction of baroreceptor and chemoreceptor reflex control of sympathetic nerve activity in normal humans. Animal studies have demonstrated that activation of the baroreflex by increases in arterial pressure inhibits cardiovascular and ventilatory responses to activation of peripheral chemoreceptors (PC) with hypoxia. In this study, we examined the influences of baroreflex activation on the sympathetic response to stimulation of PC and central chemoreceptors in humans. PC were stimulated by hypoxia (10% O2/90% N2) (n = 6) and central chemoreceptors by hypercapnia (7% CO2/93% O2) (n = 6). Responses to a cold pressor stimulus were also obtained as an internal reflex control to determine the selectivity of the interactive influence of baroreflex activation. Baroreflex activation was achieved by raising mean blood pressure by greater than 10 mmHg with intravenous infusion of phenylephrine (PE). Sympathetic nerve activity (SNA) to muscle was recorded from a peroneal nerve (microneurography). During hypoxia alone, SNA increased from 255 +/- 92 to 354 +/- 107 U/min (P less than 0.05). During PE alone, mean blood pressure increased and SNA decreased to 87 +/- 45 U/min (P less than 0.05). With hypoxia during baroreflex activation with PE, SNA did not increase (50 +/- 23 U/min). During hypercapnia alone, SNA increased from 116 +/- 39 to 234 +/- 72 U/min (P less than 0.01). Hypercapnia during baroreflex activation with PE increased SNA from 32 +/- 25 U/min during PE alone to 61 +/- 26 U/min during hypercapnia and PE (P less than 0.05). Like hypercapnia (but unlike hypoxia) the cold pressor test also increased SNA during PE. We conclude that baroreflex activation selectively abolishes the SNA response to hypoxia but not to hypercapnia or the cold pressor test. The inhibitory interaction of the baroreflex and the peripheral chemoreflex may be explained by convergence of baroreceptor and peripheral chemoreceptor afferents on neurons in the medulla. 
Osteochondrodysplasia in Fryns syndrome. Various skeletal abnormalities have been identified in roentgenograms of persons with Fryns syndrome, but to our knowledge, no histopathologic description of bone or cartilage has been published. We describe disordered endochondral and intramembranous bone formation in a premature female infant with Fryns syndrome. This infant and a full sibling (ie, had same set of parents) with Fryns syndrome in addition exhibited delayed ossification of the basiocciput and of cervical vertebral bodies, also previously undescribed in Fryns syndrome. These findings expand the spectrum of Fryns syndrome to include osteochondrodysplasia. 
Pylorus and antroseromuscular flap-preserving gastrectomy--a new type of reconstruction after subtotal gastrectomy for treatment of gastroduodenal ulcer: clinical and experimental study. To avoid motility disturbances after Billroth gastrectomy, the authors designed pylorus and antroseromuscular flap-preserving subtotal gastrectomy (PAFPG). Results showed that gastric motility and emptying time of dogs after PAFPG were close to normal. PAFPG was applied to 125 consecutive patients with gastroduodenal ulcers (gastric ulcer, 15 patients; duodenal ulcer, 94 patients; and combined ulcers, 16 patients) confirmed by barium examination and fibro-gastroendoscopy. All patients recovered smoothly, none of them had postoperative complication. Gastric acid output reduction rates were as follows: basal acid output, 85.05% +/- 8.13%; maximal acid output, 81.76% +/- 10.85%; peak acid output, 81.42% +/- 10.15%. The incidence of postoperative enterogastric reflux (endoscopically) and the concentration of cholic acids in gastric juice were significantly lower in patients after PAFPG than after Billroth I or II gastrectomy. Results suggest that PAFPG reduced gastric acid outputs definitely and overcame adverse motility consequences after Billroth I or II gastrectomy desirably. 
Astrocytoma and associated arteriovenous malformation. A case is reported of a cerebral arteriovenous malformation occurring in continuity with an astrocytoma. Possible etiologies of this unusual association are discussed. 
Clinical management of patients receiving thrombolytic therapy. Rapid delivery of thrombolytic therapy to suitable patients with acute myocardial infarction can limit myocardial damage and reduce the risk of death. This requires an emergency department team approach following a written protocol to initiate thrombolytic therapy within 45 minutes of the patient's arrival at the emergency department. Nurses and physicians caring for patients with acute myocardial infarction must be aware of inclusion and exclusion criteria, drug preparation, dosage and administration, recommended adjunctive therapies, and potential complications associated with pharmacologic thrombolysis. All patients with acute myocardial infarction should be carefully screened for their potential for receiving thrombolytic therapy with a favorable benefit/risk ratio. 
Management of patients with facial trauma and associated ocular/orbital injuries. Ocular injury can be associated with facial fractures in a significant percentage of cases. It is mandatory for surgeons treating such fractures to be familiar with the types of orbital injuries, the appropriate physical examination and diagnostic tests, and the management techniques involved in treating traumatic visual loss. This article reviews the diagnostic and therapeutic approaches to this important problem. 
Sustained supraventricular tachyarrhythmias following coronary artery bypass surgery comparing mammary versus saphenous vein grafts. This retrospective study was designed to determine the incidence of sustained supraventricular tachyarrhythmias (SVTs) in patients undergoing coronary artery bypass grafting (CABG) with internal mammary artery (IMA) grafts, Group A, compared with those with saphenous vein grafts (SVG), Group B. Among 569 consecutive patients who underwent CABG surgery in the same institution, a total of 80 cases from Group A and 80 cases from Group B were selected for this study after application of exclusion criteria. Excluded from this study were the following: patients with preexisting or prior history of SVTs, significant left ventricular dysfunction (ejection fraction less than 40%), postoperative myocardial infarction, drug toxicity or electrolyte imbalance, and advanced chronic obstructive lung disease. Group A consisted of 63 men and 17 women and Group B consisted of 52 men and 28 women. All patients were monitored either in ICU or by telemetry for a period of three to six days after surgery and all had a predischarge 12-lead electrocardiogram. Both groups were fairly comparable in most of their clinical profile and number of grafts. The incidence of SVTs in Group A was 31% (25 of 80 patients) and in Group B was 24% (19 of 80 patients). Furthermore, the incidence of postoperative pericarditis was noted in 35% (28 of 80 patients) of Group A and in 19% (15 of 80 patients) in Group B. The authors conclude that male tobacco smokers of Group A tended to have a significantly higher incidence of postoperative pericarditis with a higher trend for postoperative SVTs than patients from Group B. 
Stress and alcohol interaction: an update of human research. The literature on alcohol and stress in human subjects carried out since 1981 is reviewed. The review covers selected aspects of the interaction of alcohol and stress. (1) Most of the review focuses on the role of stress on alcohol ingestion. Retrospective research based on data from the Health and Nutrition Examination Survey indicated an increase in alcohol consumption with anxiety in certain groups of, as yet not well characterized, individuals. For example, although still insufficiently documented, stress does not appear to play a significant role in alcohol ingestion by women and the elderly. By contrast, stress does appear to play a role in the control of alcohol ingestion by adolescents. Prospective studies employing questionnaire-interview formats generally support an effect of stress on alcohol ingestion. However, studies employing male college aged social drinkers did not find a correlation between levels of stress and ingestion of alcohol. Alcoholics also differ in the reasons for drinking alcohol, but generally ingest alcohol to lessen anxiety/stress. It is clear that the Tension Reduction Hypothesis as originally postulated is no longer adequate. Many new models based on an interaction of alcohol and stress have been proposed to explain the control of alcohol consumption. Considering the multidimensionality of factors that appear to contribute to the control of alcohol ingestion, it is unlikely that a single model could possibly be relevant to alcohol ingestion under all conditions. More likely different models may be relevant to alcohol consumption under specific conditions, or for specific populations. (2) Alcohol has been reported to decrease anxiety in agoraphobics. The self-medication by agoraphobics may contribute significantly to their alcohol abuse. (3) Alcohol has also been reported to decrease tremor of the hands in stressed subjects as well as in patients with essential tremor. (4) Although a number of studies have employed electrodermal activity in studies aimed at the interaction of alcohol and stress, the results have been rather inconsistent. (5) The controversy on the purported beneficial effect of alcohol on the cardiovascular system persists. A number of studies have shown a J- or U-shaped relationship between alcohol ingestion and incidence of coronary heart disease. Alcohol may also influence stress-induced changes in blood pressure. Although a number of studies have demonstrated lower blood pressure in individuals ingesting less than two drinks per day compared with abstainers or heavy alcohol imbibers, the evidence is not conclusive. (6) It is not clear whether the interaction of alcohol and stress involves alterations in plasma catecholamines. 
The role of plasminogen activator in adhesion prevention. The reduction in peritoneal plasminogen activator activity (believed to be the pathogenic mechanism of adhesion formation) and its replacement with recombinant tissue plasminogen activator (rt-PA) have been investigated in the prevention of initial (primary) and recurrent adhesion production. Other, potentially harmful, effects of intra-abdominal rt-PA application have also been examined. This included effects on wound and colonic healing and hemostasis. The prevention of adhesion formation was studied in primary and recurrent adhesion formation using a rabbit model. Primary adhesions formed in one of 14 occasions (7 per cent) with rt-PA compared with 12 of 15 occasions (80 per cent) with placebo (chi-square equals 15.542, p less than 0.001). Recurrent adhesions formed on two of 27 occasions (7 per cent) with rt-PA compared with 22 of 28 occasions with placebo (79 per cent) and 12 of 12 occasions with control rabbits (100 per cent, chi-square equals 40.588, p less than 0.0001). The application of rt-PA to abdominal wounds in the rabbit failed to show any reduction in wound strength at four, seven and ten days. Colonic anastomotic healing was unaltered by rt-PA at three, five and seven days. There was no difference seen in hemorrhagic events between control, placebo or rt-PA rabbits at any stage. The use of rt-PA is an exciting development in the field of adhesion prevention; it is an effective inhibitor of adhesion formation and intra-abdominal administration appears safe in a rabbit model. 
Synchronous primary mucosal melanoma and mucoepidermoid carcinoma of the maxillary antrum. We present a case of contiguous primary malignant melanoma of the nose and maxillary antrum and mucoepidermoid carcinoma of the maxillary antrum. We believe that this association has not been previously recorded; whether this represents divergent differentiation in a single tumour or 'collision' of two separate tumours is uncertain. 
Variation in intravaginal pressure measurements. The wide variation in intravaginal pressure measurements of the circumvaginal muscles (CVM) was studied in five subjects under well-controlled conditions. Previous research and clinical observations have indicated that fluctuations in the measurement of intravaginal pressure may be associated with time of day, day of testing, and existing stress factors. Subjects were assessed four times per day, on four consecutive days, for a total of 16 assessments. At each of the 16 conditions for a given subject, 10 CVM contractions lasting 12 seconds each were recorded and the variables, maximum pressure (MP10), peak maximum pressure (PMP), and abdominal pressure were analyzed. The within-subject variance was 15.5 (SD = 3.9); the between-subject variance was 132.4 (SD = 11.5). The effects of day, time, and stressor were analyzed by ANOVA specifically designed for variance estimates; no significant differences were found. The clinical observations that led to the study were not supported when systematically investigated. However, consistent data collection procedures appeared to reduce within-subject variance. 
Extracranial vertebral artery dissection following tonic clonic seizure. A 34 year old woman developed cerebral infarction, following a tonic-clonic seizure. A vertebral artery dissection was demonstrated and may have been caused by arterial trauma during the seizure. This cause of morbidity following convulsive seizures may have been overlooked in the past and needs to be recognised in view of the potential benefits of anticoagulation. 
A prospective study of parental history of myocardial infarction and coronary artery disease in men. The relation between parental history of myocardial infarction (MI) and risk of coronary artery disease (CAD) was prospectively examined among 45,317 U.S. male health professionals who were free of diagnosed CAD, 40 to 75 years of age in 1986 and followed for 2 years. These men provided details of parental history of MI, including their parents' age at the first event, their personal history of hypertension, hypercholesterolemia and diabetes mellitus, and a detailed dietary assessment completed at baseline. During 72,454 person-years of follow-up, 181 non-fatal MIs were documented, 49 men died from MI or sudden death, and 140 underwent coronary artery surgery or angioplasty. Compared with men without any history of parental MI, those whose mothers or fathers had had an MI at less than 70 years of age had a substantially elevated risk of MI (relative risk = 2.2, 95% confidence interval, 1.2 to 3.8 for maternal history; relative risk = 1.7, 95% confidence interval 1.2 to 2.3 for paternal history). Risk of MI increased with decreasing age at parental MI. Paternal but not maternal history of MI was related to increased risk of coronary artery surgery. These associations were not appreciably altered by controlling for diet or established risk factors, either individually or in multivariate models. These prospective data indicate that a history of MI in either parent is associated with an increased risk of CAD among men. 
Comparison of the effects of torasemide and furosemide in nonazotemic cirrhotic patients with ascites: a randomized, double-blind study. In a randomized double-blind trial we compared the effects of torasemide, a new loop diuretic, and furosemide in nonazotemic cirrhotic patients with ascites during a 3-day period in association with potassium canrenoate (200 mg/day) administration. Doses of loop diuretics administered in this trial (10 and 25 mg/day of torasemide and furosemide, respectively) had been shown to be equipotent in healthy subjects. Torasemide induced significantly greater natriuresis than furosemide (p less than 0.02), with a twofold greater percentage increase in basal values (day 1: 130% vs. 50%; day 2: 104% vs. 42%; and day 3: 65% vs. 26%, respectively). Body weight loss was significantly higher during torasemide (p less than 0.02) administration, and the overall decrease at the end of the treatment was twice as high for furosemide (2.5 +/- 0.6 kg vs. 1.3 +/- 0.4 kg, respectively). Diuresis was also higher during torasemide administration, but the difference was not significant (p = 0.08). The extent of kaliuresis observed during the two treatments was almost identical despite the striking differences in the natriuretic response. The effects of the two treatments on plasma electrolytes, creatinine clearance, blood urea nitrogen, mean arterial pressure, heart rate and plasma arginine vasopressin concentration were similar. Both drugs caused increases in plasma renin activity at the end of the treatment, whereas plasma aldosterone concentration slightly increased only after torasemide administration. Despite the presence of a trend toward a more pronounced effect on these parameters after torasemide administration, no significant difference between the two treatments was observed. 
Neurophysiological observations on the effects of botulinum toxin treatment in patients with dystonic blepharospasm. Botulinum toxin treatment improves dystonic blepharospasm by inducing transient paresis of the orbicularis oculi muscle. It is not known if it also reduces the enhanced brainstem neuronal excitability found in this disorder. We have performed conventional electromyography (EMG) and blink reflex excitability studies on fifteen patients with blepharospasm before and after botulinum toxin treatment. Denervation signs were found with needle EMG in all treated muscles. Amplitude of the facial compound muscle action potential (CMAP) and R1 response was reduced after botulinum toxin injections. In blink reflex excitability studies, the recovery of R2 response was enhanced after treatment even when patients were tested at the time of maximal benefit from botulinum toxin injections. The results suggest that there is little influence of botulinum toxin treatment upon the enhanced excitability of brainstem interneurons in patients with blepharospasm. 
Clinical stage I nonseminomatous germ cell tumors of testis. Observation vs retroperitoneal lymph node dissection. Between 1980 and 1989, 186 patients with testicular tumors were seen at Roswell Park Memorial Institute. Of these, 66.6 percent (124/186) were diagnosed to have nonseminomatous germ cell tumors (NSGT) and 22 percent (41/186) were clinically determined to have Stage I disease. Patients with clinical Stage I NSGT either underwent observation or retroperitoneal lymph node dissection (RPLND). Recurrence in the observation group of patients was 23.5 percent (4/17) between four and eighteen months (mean 10 months) with the retroperitoneum being the most common site. All but 1 patient (80%) were salvaged with platinum-based combination chemotherapy. Of the 24 patients who had RPLND, 21 percent (5/24) had a false-negative metastatic evaluation. All the patients who had surgically documented metastatic disease were successfully treated with chemotherapy. The similar recurrence rates in the observation group and the false-negative RPLND group suggest that the failure rate in the observation group is a result of the inability to stage accurately patients with NSGT. RPLND continues to be the standard therapy in patients with clinical Stage I disease. Despite its high recurrence rate, observation should, however, be offered to well-motivated and selected patients since salvage platinum-based combination chemotherapy is very effective and the majority of patients in this group are spared a major operative procedure. 
Cure of early-stage Hodgkin's disease with subtotal nodal irradiation. Ninety-four consecutive patients with Stage I or II Hodgkin's disease who presented supradiaphragmatically were treated with radiation therapy alone at the Mallinckrodt Institute of Radiology from January 1978 through December 1986. Fifty-two patients (55%) were staged pathologically, and 42 (45%) were staged clinically. The latter included lymphangiography and/or abdominal computed tomographic scan. Most patients with B symptoms and/or bulky disease were excluded from this series. Seventy-four patients were treated with subtotal nodal irradiation (mantle and periaortic fields). The spleen was treated if the patient had not undergone splenectomy. Twenty patients received mantle irradiation only. No patient received total nodal irradiation. All patients had an initial complete response. With a minimum follow-up of 7 months (median, 7.7 years; seven patients died before 3 years of follow-up, but all other patients had at least 3 years of follow-up), 81 patients (86%) remained disease-free. Six of 52 (12%) of the pathologically staged group had a relapse, as did seven of 42 (17%) of the clinically staged group (P = 0.68). Eight of 57 Stage I patients versus five of 37 Stage II patients had a relapse (P greater than 0.99). Analysis of disease-free survival by age, histologic findings, sex, and sites of involvement did not predict relapse. The pelvis was the most common site of failure (nine patients, 10%). However, only three patients (3%) failed in the pelvis alone. These results indicate that patients who, after adequate clinical staging with selective use of staging laparotomy, are found to have Stage I and II Hodgkin's disease may be treated with subtotal nodal irradiation with a high rate of cure. 
Concurrent nitroglycerin administration decreases thrombolytic potential of tissue-type plasminogen activator. Dynamic coronary vasoconstriction may play a role in coronary artery reocclusion after successful thrombolysis. The effect of nitroglycerin on the thrombolytic effects of recombinant tissue-type plasminogen activator (rt-PA) was examined in dogs with an electrically induced occlusive coronary artery thrombus. Eleven dogs were randomly given rt-PA alone and seven rt-PA with nitroglycerin. The dose of rt-PA was 0.75 mg/kg body weight given over 20 min and the dose of nitroglycerin was 125 micrograms/min for 40 min. The reperfusion rate in the dogs given rt-PA alone was 73% (8 of 11 dogs) and that in the rt-PA plus nitroglycerin group was 57% (four of seven dogs) (p = NS). The time to thrombolysis (or reperfusion) in dogs receiving rt-PA plus nitroglycerin was 70% greater than in those receiving rt-PA alone (means +/- SD/29.8 +/- 9.9 versus 17.6 +/- 5.9 min, p less than 0.02), and the duration of reperfusion much shorter (11 +/- 17 versus 42 +/- 16 min, p less than 0.02). Peak coronary blood flow after reperfusion in dogs receiving rt-PA plus nitroglycerin was also less than in those receiving rt-PA alone (36 +/- 52 versus 63 +/- 20 ml/min, p less than 0.02). Reocclusion occurred in all dogs given rt-PA with nitroglycerin and in six of eight given rt-PA alone (p = NS). Plasma concentrations of rt-PA were lower when nitroglycerin was given with rt-PA alone (427 +/- 279 versus 1,471 +/- 600 ng/ml, p less than 0.01). 
Destructive lesions in demyelinating disease. Three cases are presented in which clinical and radiological features suggested the diagnosis of glioma but surgical biopsy revealed a demyelinating process, with tissue destruction and cyst formation in two. One patient had clinically definite multiple sclerosis. Two had probable acute disseminated encephalomyelitis. Treatment with high dose steroids is appropriate when there is clinical or investigative evidence to suggest the presence of demyelinating disease, before deciding on biopsy. 
Mortality, cardiovascular risk factors, and diet in China, Finland, and the United States. Mortality, cardiovascular risk factors, and diet were compared in Tianjin province, People's Republic of China; in North Karelia Province, Finland; and in the United States as a whole. People in Tianjin received 7 percent of their energy intake from saturated fats, whereas people in the United States received 13 percent and those in North Karelia received 20. The mean blood cholesterol levels for men were 158 milligrams per deciliter (mg per dl) for Tianjin, 216 mg per dl for the United States, and 241 mg per dl for North Karelia. The smoking prevalence among men was highest in Tianjin (66 percent), followed by the United States (42 percent) and Finland (36 percent). The differences among mortality rates for the three locales were less pronounced among women than among men. Age-standardized total mortality for women was highest for Tianjin and lowest in North Karelia. The reverse was true for men. Age-standardized total mortality for men was lowest in Tianjin and highest in North Karelia. Age-standardized ischemic heart disease mortality for men was lowest in Tianjin (99 per 100,000) and highest in North Karelia (730 per 100,000). For women, the corresponding figures were 83 per 100,000 in Tianjin and 164 per 100,000 in North Karelia. Although salt intake was higher in Tianjin than in North Karelia, the blood pressure was on average lower in persons from Tianjin than in those from North Karelia. The stroke mortality rate in Tianjin, however, was much higher than in either Finland or the United States. 
Intraoperative facial nerve monitoring: prognostic aspects during acoustic tumor removal. Intraoperative facial nerve monitoring with electrical stimulation (IFNMES) has become an integral part of acoustic tumor surgery. We reviewed the records of fifty-six patients who underwent translabyrinthine acoustic tumor removal with IFNMES. There was excellent correlation between intraoperative facial nerve activity and immediate postoperative facial nerve function (24 hours after surgery and at hospital discharge). Our data would suggest that patients who exhibit less than 500 microvolts of ongoing EMG activity during surgery, and who yield at least a 500-microvolt contraction when stimulated with 0.05 milliamps at the brainstem after tumor removal, can expect an excellent immediate facial nerve result (grade I or II). 
An animal model for colon cancer metastatic cell line with enhanced metastasizing ability. Establishment and characterization. We have developed an animal model for colon cancer metastasis and produced a metastasizing tumor after using a microinjection technique to inject SW480 cells into the cecal wall of athymic nude mice during "minilaparotomy." After the metastatic foci formed in murine lung, an in vitro primary culture was performed and a new metastatic cancer cell line, which was designated as CC-ML3, was established. The studies included: 1) the comparison between SW 480 and CC-ML3 in morphology, growth kinetics, seeding and plating efficiency, and karyotype; and 2) carcino-embryonic antigen determination, origination, and metastatic ability of CC-ML3. The results showed that CC-ML3 was significantly different from SW480 in vitro and possessed a high metastatic potential in vivo. This newly developed animal model may thus be useful for studying the biology and pathogenesis of metastasis of human colonic cancer. 
Differential effects of atrial natriuretic peptide and dopamine on urinary protein excretion in chronic glomerulonephritis. 1. To examine whether or not atrial natriuretic peptide-induced proteinuria simply results from increases in urine flow or glomerular filtration rate, we infused dopamine (1 microgram min-1 kg-1) and alpha-human atrial natriuretic peptide (0.025 microgram min-1 kg-1) into nine patients with chronic glomerulonephritis and nine essential hypertensive patients without renal damage, and compared the effects of the two agents on renal function and urinary protein excretion. 2. In patients with chronic glomerulonephritis, dopamine infusion significantly increased urinary sodium excretion (+59%), renal blood flow (+20%) and creatinine clearance (+14%). However, urinary protein excretion was not changed. Addition of atrial natriuretic peptide to the dopamine infusion further increased urinary sodium excretion and maintained creatinine clearance at the same level. In contrast to the infusion of dopamine alone, atrial natriuretic peptide markedly increased urinary protein excretion (77 versus 229 mg min-1 m2, P less than 0.02). Furthermore, the addition of atrial natriuretic peptide elevated the urinary protein/creatinine ratio (1.55 versus 5.35, P less than 0.05), while dopamine alone did not (1.55 versus 1.45, not significant). 3. In essential hypertensive patients, dopamine and dopamine plus ANP showed renal effects similar to those of chronic glomerulonephritis; however, the urinary excretion of protein was not changed significantly. 4. These results suggest that atrial natriuretic peptide may increase urinary protein excretion mainly by increasing the permeability of the damaged glomeruli to protein rather than by simply increasing urine flow or glomerular filtration. Possible mechanisms underlying the proteinuria-increasing effects of atrial natriuretic peptide are discussed. 
Transabdominal and transvaginal sonography of ovarian masses. This chapter outlined the sonographic appearances of most ovarian tumors using both transabdominal and transvaginal sonography. The use of transabdominal and transvaginal sonography for the early detection of ovarian carcinoma seems promising and should be pursued in several institutions as clinical trials. 
Long-term health risks and benefits of oral contraceptive use. The contraceptive effect of oral contraceptive use provides an important health benefit, particularly in developing countries, where the risks of pregnancy and childbearing are increased. Several important noncontraceptive health benefits of oral contraceptive use include the prevention of endometrial and ovarian cancers. Data are generally reassuring concerning the risks of oral contraceptive use, which include cardiovascular disease and breast and cervical cancer. 
Malignant potential of the cryptorchid testis. A follow-up study of 224 male patients from Rochester, Minnesota, diagnosed with cryptorchidism during the period from 1935 through 1974 was conducted to assess the frequency of subsequent testicular neoplasms. Age-specific rates for testicular neoplasm in this community were used to estimate an expected number for comparison with that observed. Two malignant testicular neoplasms have occurred in this cohort; thus, the standardized morbidity ratio was 11.4 (95% confidence interval, 1.4 to 41.1). Of the 158 patients born in the community, 11% were known to have birth weights of less than 2,500 g, approximately twice the expected occurrence. Increased risks were also noted for inguinal hernia, hypospadias, Down's syndrome, cleft lip or palate (or both), clubfoot, and congenital heart disease, for which the standardized morbidity ratios were 3.6, 4.7, 17.8, 11.3, 11.7, and 2.7, respectively. The increased risk for malignant neoplasms observed in this cohort of patients with cryptorchidism is consistent with that found in earlier studies. 
Endoscopic transthoracic electrocautery of the sympathetic chain for palmar and axillary hyperhidrosis Endoscopic transthoracic electrocautery of the sympathetic chain has been the preferred treatment for palmar or axillary hyperhidrosis in this unit since 1980. A retrospective study was carried out of the first 112 patients with case material derived from a postal questionnaire, chart review and outpatient assessment. Eighty-five patients undergoing bilateral transthoracic electrocautery who replied to the questionnaire (76 per cent response rate) form the basis of this study. There were 65 females and 20 males with a mean age of 24.3 years (range 15-40 years). The hands alone were affected in 20 patients (24 per cent), the axillae alone in 17 (20 per cent) and both areas in 48 (56 per cent). Mean hospital stay was 3.1 days (range 1-7 days). Outcome was assessed by 92 per cent of patients immediately after operation as 'very much improved' or 'moderately improved', and this assessment persisted in 85 per cent after a mean follow-up of 43 months (range 3-95 months). Cosmetic results were rated as satisfactory by 95 per cent. Apart from pain after operation, morbidity was limited to transient Horner's syndrome in three patients, surgical emphysema in three, and pneumothorax requiring a chest drain in one. A repeat procedure was needed in one patient because of an inadequate first operation. Some compensatory hyperhidrosis occurred in 54 (64 per cent) patients. As a minimally invasive procedure, endoscopic transthoracic electrocautery should be considered the treatment of choice for palmar and axillary hyperhidrosis. 
Rare presentation of a parapharyngeal schwannoma. Schwannoma, or neurilemmoma, is included in the differential diagnosis of masses in the parapharyngeal space. Schwannomata do not usually cause acute inflammation, and therefore do not tend to present as emergencies as in this case, in which there was acute respiratory embarrassment. 
Primary malignant melanoma of male urethra. A case of primary malignant melanoma of the male urethra is reported. Treatment included partial urethrectomy, bilateral inguinal and iliac lymphadenectomy, and post-surgical systemic chemotherapy. After thirty-six months, the patient is alive with cutaneous, pelvic lymph node, and gastric metastases. 
Parental sex effect in familial amyotrophic lateral sclerosis. Since a parental sex effect has been reported in Huntington's disease, we looked to see whether a similar effect is apparent in adult (autosomal dominant) familial ALS. We analyzed the data for 145 patients, with an onset age range of 20 to 68 years and a known affected parent (AP), from 52 families described in the literature. There was a significant increase in the percentage of patients inheriting the gene from an affected mother as a function of the age at onset. There was also a significant correlation between AP and offspring age at onset only when the AP was the mother. 
Carotid endarterectomy in elderly patients Between 1971 and 1989, 749 carotid endarterectomies were performed at our institution for symptomatic carotid occlusive disease in patients older than 70 years of age. Of these procedures, 693 were done in patients 71 through 80 years of age, and 56 were done in patients between the ages of 81 and 90 years. The neurologic morbidity and perioperative mortality in the former group were 2.9% and 1.4%, respectively, whereas in the latter group the corresponding values were 5.4% and 0%, respectively. For the entire group, the neurologic morbidity was 3.1% and the mortality was 1.3%. Of the 23 new postoperative neurologic deficits, 19 (83%) occurred in high-risk patients with severe preoperative neurologic or medical risks, and 14 (61%) of these deficits were minor. In selected elderly patients with symptomatic hemodynamically significant carotid occlusive disease, endarterectomy seems to be a safe procedure that is associated with acceptably low perioperative morbidity and mortality. 
Resting energy expenditure in patients with newly detected gastric and colorectal cancers. Resting energy expenditure (REE) was measured in 104 patients with newly detected gastric or colorectal (GCR) cancer and was compared with two groups of control subjects without cancer: healthy subjects (H control subjects) and patients with nonmalignant diseases of the gastrointestinal tract (GI patients). REE in GCR-cancer patients was not significantly different from REE in GI patients or H control subjects. Comparison of measured REE with predicted REE obtained from prediction equations may erroneously suggest that increased REE is a contributing factor in the development of cancer cachexia. No significant differences in REE were found when patients with liver metastases were compared with patients without metastases. There were no differences in REE between gastric and colorectal cancer patients. The decrease in energy expenditure, which normally occurs during starvation and weight loss in healthy men and women, could not be demonstrated in weight-losing, GCR-cancer patients. In conclusion, elevation of REE contributes little to the pathogenesis of cancer cachexia in GCR-cancer patients. 
Events in the Cardiac Arrhythmia Suppression Trial (CAST): mortality in the entire population enrolled [published erratum appears in J Am Coll Cardiol 1991 Sep;18(3):888] To test the hypothesis that suppression of ventricular arrhythmias by antiarrhythmic drugs after myocardial infarction improves survival, the Cardiac Arrhythmia Suppression Trial (CAST) was initiated. Suppression was evaluated before randomization during an open label titration period. Patients whose arrhythmias were suppressed were randomized in the main study and those whose arrhythmias were partially suppressed were randomized in a substudy. Overall survival and survival free of arrhythmic death or cardiac arrest were lower [corrected] in patients treated with encainide or flecainide than in patients treated with placebo. However, the death rate in patients randomized to placebo therapy was lower than expected. This report describes the survival experience of all patients enrolled in CAST and compares it with mortality in other studies of patients with ventricular arrhythmias after myocardial infarction. As of April 18, 1989, 2,371 patients had enrolled in CAST and entered prerandomization, open label titration: 1,913 (81%) were randomized to double-blind, placebo-controlled therapy (1,775 patients whose arrhythmias were suppressed and 138 patients whose arrhythmias were partially suppressed during open label titration); and 458 patients (19%) were not randomized because they were still in titration, had died during titration or had withdrawn. Including all patients who enrolled in CAST, the actuarial (Kaplan-Meier) estimate of 1-year mortality was 10.3%. To estimate the "natural" mortality rate of patients enrolled in CAST, an analysis was done that adjusted for deaths that might be attributable to encainide or flecainide treatment either during prerandomization, open label drug titration or after randomization. Because the censoring procedure excluded patients treated with encainide or flecainide after randomization, the mortality estimate will be less than the unadjusted mortality estimate of 10.3%. 
Acute lung injury following reperfusion after ischemia in the hind limbs of rats. In this study, we proposed that oxygen free radicals participate in the acute pulmonary injury that follows limb ischemia/reperfusion. Using an established model of hind limb ischemia, reproducible lung injury occurred after reperfusion. Lung microvascular permeability was measured with 125I-BSA and increased two-fold after 30 minutes of reperfusion. Pulmonary injury was blocked with DMSO, DMTU, allopurinol, indomethacin, and SOD plus catalase. The degree of pulmonary neutrophil sequestration as assessed by tissue myeloperoxidase activity was significantly diminished in animals pretreated with antioxidants. Pretreatment with indomethacin did not attenuate the neutrophil sequestration within the pulmonary parenchyma. These data suggest that increased lung microvascular permeability and neutrophil accumulation occur following hind limb ischemia/reperfusion. Therapeutic interventions with oxygen radical inhibitors blocked this process, while the prostaglandin inhibitor, indomethacin, only reduced lung permeability. 
Antibodies to neutrophil cytoplasmic antigens: serologic marker for Sweet's syndrome. Seven patients with a clinical and histologic diagnosis of Sweet's syndrome were tested for the presence of circulating antibodies to neutrophil cytoplasmic antibodies. Six of the seven patients had detectable antibodies to neutrophil cytoplasmic antibodies at a serum dilution of at least 1:20. Antibodies to neutrophil cytoplasmic antibodies were not found in serum from patients with a range of cutaneous diseases, some known to cause clinical or histologic confusion with Sweet's syndrome. The detection of circulating antibodies to the neutrophil cytoplasm may be of possible diagnostic value in Sweet's syndrome. 
Effects of postural changes versus exercise on the electrophysiologic parameters of the accessory pathway. The electrophysiologic profile of the accessory pathway was studied in 17 patients (mean age +/- standard deviation 32 +/- 14 years) with Wolff-Parkinson-White (WPW) syndrome who were either lying down in a supine position, standing, or undergoing isometric or dynamic treadmill exercise. There were significant decreases in the PP interval after isometric exercise, standing and dynamic exercise (supine 764 +/- 224, standing 638 +/- 146, isometric 605 +/- 170, treadmill 455 +/- 86 ms; p less than 0.05). Both anterograde and retrograde accessory pathway refractory periods were measured after a constant drive of 400 ms during lying down supine, standing and isometric and treadmill exercise (Bruce protocol stage II). There was no significant decrease in the anterograde accessory pathway refractory period during isometric exercise (lying down 265 +/- 22 to isometric exercise 256 +/- 13 ms, p less than 0.05), but there were significant decreases (p less than 0.05) during standing (246 +/- 24 ms) and treadmill exercise (235 +/- 17 ms). The retrograde accessory pathway refractory period also showed a significant decrease (supine 272 +/- 16, isometric 267 +/- 23, standing 249 +/- 15, treadmill 237 +/- 17 ms; p less than 0.05). The relative change in refractory periods was greater when patients changed from lying down to standing than when they changed from standing to treadmill exercise, despite obvious higher adrenergic neuronal activities during exercise. These findings suggest that testing the accessory pathway during free standing can give a reliable indication of the sensitivity of the accessory pathway to sympathetic stimulation. 
Continuous arteriovenous rewarming: report of a new technique for treating hypothermia. Survival is rare after major trauma if core temperature falls below 32 degrees C. Available rewarming methods are often ineffective. We utilized arterial and venous catheters to create a circulatory fistula through the heating mechanism of a modified commercially available counter-current fluid warmer to achieve simple, rapid extracorporeal rewarming. 
Misoprostol compared with sucralfate in the prevention of nonsteroidal anti-inflammatory drug-induced gastric ulcer. A randomized, controlled trial. OBJECTIVES: To compare the efficacy and frequency of adverse experiences of misoprostol and sucralfate in the prevention of gastric ulcers in patients receiving nonsteroidal anti-inflammatory drug (NSAID) therapy. DESIGN: A prospective, randomized, single-blind, multicenter trial. PATIENTS: Patients with osteoarthritis receiving treatment with ibuprofen, piroxicam, or naproxen and experiencing abdominal pain were eligible. INTERVENTIONS: Patients who were expected to receive at least 3 months of NSAID therapy and who did not have a gastric ulcer at the time of the initial screening endoscopy were randomized to receive misoprostol, 200 micrograms four times a day, or sucralfate, 1 g four times a day. A gastric ulcer was defined as a lesion of the gastric mucosa 0.3 cm or greater in diameter. Patients were followed clinically, and repeat endoscopies were performed after 4, 8, and 12 weeks. MAIN MEASUREMENT: The development of a gastric ulcer, which was regarded as a prophylaxis failure. RESULTS: Two hundred fifty-three patients were evaluable for efficacy analysis. A gastric ulcer developed in 2 of the 122 (1.6%, 95% CI, 0.3% to 6.4%) patients on misoprostol, compared with 21 of 131 patients on sucralfate (16%, CI, 10.4% to 23.7%). The difference in ulcer rates was 14.4% (CI, 10.4% to 19.5%; P less than 0.001). CONCLUSION: In patients receiving chronic NSAID therapy for osteoarthritis, treatment with misoprostol for 3 months was associated with a significantly lower frequency of gastric ulcer formation, compared with treatment with sucralfate (P less than 0.001). 
Characterization of the proliferative response of a CD4-8- thymic T lymphoma cell line to stimulation by thymic cellular elements. E710.2 is a cloned T cell line that was isolated from an AKR/J thymic tumor. This clone expresses Thy-1, heat-stable Ag, and the CD3/TCR complex but does not express CD4 or CD8. When the E710.2 cell line is injected into syngeneic mice, it grows as a malignant tumor in lymphoid organs and the thymus. In contrast, this cell line does not grow in vitro under standard culture conditions. This latter property allowed us to analyze the in vitro responsiveness of this CD4-CD8- cell line to stimulation by pharmacologic agents and cellular elements from the spleen and thymus. E710.2 cells proliferate when stimulated with phorbol esters or when cocultured with thymocytes or splenocytes. We could not detect soluble stimulatory factors in cultures of E710.2 and/or lymphoid cells, suggesting that cell contact might be required for this response. The stimulatory activity in thymus and spleen appears to be broadly expressed, because all cell subsets that were examined from these tissues stimulate this cell line. The stimulation of E710.2 cells is not MHC-restricted and is not inhibited by anti-MHC mAb. Furthermore, the responsiveness of these cells is not decreased when the TCR/CD3 complex is modulated from the cell surface. Similarly, TCR/CD3-deficient E710.2 variant clones retain their responsiveness to thymic and splenic cell stimulation. These findings suggest that there is a TCR-independent pathway of activation in E710.2 that is stimulated by a broadly expressed, non-MHC-encoded molecules(s). 
Coexpression of CD4 and CD8 on peripheral blood T cells and lamina propria T cells in inflammatory bowel disease by two colour immunofluorescence and flow cytometric analysis. Using two colour immunofluorescence with fluorescein isothiocyanate and phycoerythrin labelled monoclonal antibodies and multiparameter flow cytometry, we investigated the coexpression of CD4 and CD8 antigens on peripheral blood lymphocytes and lamina propria lymphocytes of patients with ulcerative colitis and Crohn's disease and normal control subjects. Both the absolute number and the proportion of peripheral blood CD4+, CD8+ cells in inflammatory bowel disease were small but significantly increased compared with those in normal control subjects. Peripheral blood lymphocytes activated with phytohaemagglutinin showed appreciably increased coexpression of CD4+, CD8+. These CD4, CD8 positive cells were large and granular. Thus the increased number of peripheral blood CD4+, CD8+ cells in inflammatory bowel disease suggests that chronic immune activation occurs not only in the active state of the disease but also in remission. The proportion of CD4+, CD8+ cells in the lamina propria was greater than in peripheral blood in normal subjects, suggesting chronic immune stimulation of the local immune system. This was also seen in patients with Crohn's disease or inactive ulcerative colitis. The proportion of CD4+, CD8+ cells was, however, significantly less in the lamina propria of patients with active ulcerative colitis. Whether this implies a possible defect in mucosal immunoregulation in active ulcerative colitis cannot be determined from these results. 
The clinical and endocrine outcome to trans-sphenoidal microsurgery of nonsecreting pituitary adenomas. From 1962 to 1987, 126 patients underwent trans-sphenoidal surgery for primary treatment of pituitary adenomas unassociated with clinical or biochemical evidence of hormonal overproduction. There were 73 male and 53 female patients (mean age, 50 +/- 12 years). Before surgery, 56% of the patients (70 of 124) had headaches, 74% (94 of 126) had deterioration of vision, and 12% (15 of 126) had ophthalmoplegia. Endocrine evaluation revealed the presence of hypogonadism in 75% (87 of 115), adrenal insufficiency in 36% (46 of 126), and hypothyroidism in 18% (21 of 122). Plasma prolactin was increased in 65% (56 of 86) with a mean level of 39 +/- 14 micrograms/l (normal, 3 to 20 micrograms/l). Radiologic enlargement of the sella turcica was documented in all cases: 67% (84 of 126) had enclosed and 33% (42 of 126) had invasive adenomas. After surgery, vision was normalized or improved in 75% (71 of 94) of the patients. Thyroid, adrenal, and gonadal functions were improved in 14% (three of 22), 41% (19 of 46), 11% (ten of 87), were unchanged in 82% (100 of 122), 77% (97 of 126), 89% (102 of 115), and worsened in 15% (19 of 22), 8% (ten of 126), 3% (102 of 115), respectively. Permanent diabetes insipidus occurred in 5% (seven of 126). Two patients died during the immediate postoperative period. The recurrence rate in patients with a mean follow-up of 6.4 +/- 4.2 years was 21% (15 of 71). These data indicate that trans-sphenoidal microsurgery is an effective and safe initial treatment for patients with nonsecreting pituitary adenoma and may reverse hypopituitarism. 
Inhibitory effect of non-steroidal anti-inflammatory drugs on mucosal cell proliferation associated with gastric ulcer healing To find out whether non-steroidial anti-inflammatory drugs (NSAIDs) inhibit the proliferation of mucosal cells that normally leads to healing of gastric ulcers a microdissection technique was used to quantify mitosis in gastric glands at the ulcer edge in relation to that in the adjacent mucosa. The regeneration index thus obtained of the ulcer edge was greater in the 9 subjects with gastric ulcers not taking NSAIDs (mean index 3.1 [SEM 0.61]) than that in the 8 patients taking NSAIDs (index 1.49 [0.16]). In rats in which gastric ulcers were produced with a cryoprobe, the ulcers were larger and slower to heal in those receiving indomethacin than in controls; also, immunohistochemical staining indicated significantly fewer mitotic cells in glands adjacent to the ulcer in indomethacin-treated rats (8 mitoses [SEM 3]) than in control animals (25 [5]). The prostaglandin E1 analogue misoprostol reversed the inhibition of healing and substantially restored the proliferative rate in the animals. Inhibition of epithelial cell division normally involved in gastric ulcer healing would contribute to the high prevalence of gastric ulcer during NSAID therapy. 
Relation of arteriographically defined coronary artery disease to serum lipoprotein particles mapped with monoclonal antibodies. BACKGROUND. This study was designed to investigate the relation of a molecular analysis of apolipoprotein B (apoB)-containing atherogenic lipoprotein particles to coronary artery disease (CAD) in middle-aged men. METHODS AND RESULTS. Two groups of men were studied. The first consisted of 97 patients with angiographically documented CAD (greater than 50% stenosis of at least one coronary artery). The second group consisted of 145 subjects without symptomatic CAD, who served as controls. In both groups, measurements were obtained for total cholesterol level, triglyceride level, cholesterol contents in apoB- and nonapoB-containing particles (LpB, LpnonB), total apoB and apolipoprotein AI (apoAI levels), lipoprotein particles recognized by monoclonal antibodies anti-apoB (LpBL3, LpBL5, LpBL7) and anti-apoAI (LpAI-2GII). Taking into account age, body mass index, hypertension, diabetes, smoking habits, and drug consumption, the analysis showed that the mean levels of cholesterol were identical in both groups but differed when cholesterol content in LpB and LpnonB subfractions were assessed, thus reflecting an increase in the low density fraction and a decrease in the high density fraction, respectively. This was confirmed by an increase in total apoB and a decrease in total apoAI. Measurements of LpBL3, LpBL5, LpBL7, and LpAI-2GII particles also discriminated between the two groups. After adjustment for cholesterol content in LpnonB particles, a difference in total apoB was no longer significant between groups, whereas LpBL3, LpBL5, and LpBL7 levels remained significantly higher in CAD patients. CONCLUSIONS. The measurement of separate concentrations of apoB in different particles may permit a more-accurate assessment of CAD risk than measurements of total apoB levels. 
Clinical significance of pericardial rub with regional ventricular dilatation. To elucidate the clinical characteristics associated with regional ventricular dilatation in the early phase of myocardial infarction (MI), 228 patients with acute Q-wave anterior MI were studied. Forty-nine patients (21 percent) had echocardiographically demonstrated regional ventricular dilatation (an abnormal bulge in the left ventricular contour during both systole and diastole) on the third hospital day. Careful auscultation revealed that a pericardial rub was present in 49 patients (21 patients with and 28 patients without regional ventricular dilatation) during the first three days after hospital admission. Multivariate analysis was performed to determine the relative importance of pericardial rub with six other clinical variables related to regional ventricular dilatation. Pericardial rub and cardiac output were the significant factors related to the presence of regional ventricular dilatation. Thus, a pericardial rub, in concert with impaired left ventricular function, is a physical sign associated with regional ventricular dilatation, and anatomically transmural infarction is the possible factor explaining their association. 
Diagnosis and management of systemic Wegener's granulomatosis presenting with anterior ocular inflammatory disease. The ocular and systemic features of 10 patients whose Wegener's granulomatosis presented with corneoscleral inflammatory disease are described. Marginal corneal infiltrates were seen in all patients with anterior scleritis and were a valuable sign of disease activity. Nine out of 10 patients had symptoms of systemic vasculitis on presentation; seven had renal impairment; three had chest x-ray abnormalities. Autoantibodies against neutrophil cytoplasmic determinants (ANCA) were present in all cases. In seven patients the scleritis responded well to pulsed immunosuppressive therapy followed by long term oral steroids and cyclophosphamide. Oral steroid therapy alone failed to control severe disease. Corneoscleral disease was not a cause of visual loss. It is important to realise that inflammatory corneoscleral disease may be the presenting feature of a severe systemic vasculitis. 
Chronic anterior uveitis in leprosy: an insidious cause of blindness. Chronic low grade anterior uveitis is the commonest cause of blindness in leprosy. It is usually asymptomatic until the late stages, and often patients seek help only after irreversible visual impairment has occurred. We present herewith several cases of this entity to emphasise the insidious nature of the disease, the extent of ocular damage it can cause, and the importance of early detection and treatment. 
Retinoid-mediated transcriptional regulation of keratin genes in human epidermal and squamous cell carcinoma cells. Vitamin A and other retinoids profoundly inhibit morphological and biochemical features of epidermal differentiation in vivo and in vitro. To elucidate the molecular mechanisms underlying the differential expression of epidermal keratins and their regulation by retinoids, we examined retinoid-mediated changes in total protein expression, protein synthesis, mRNA expression, and transcription in cultured human keratinocytes and in squamous cell carcinoma (SCC-13) cells of epidermal origin. Our studies revealed that the epidermal keratins, K5, K6, K14, and K16, their mRNAs, and their transcripts were diminished relative to actin as a consequence of retinoic acid (RA) treatment. The effects were most pronounced in SCC-13 and were detected as early as 6 hr post-RA treatment, with enhancement over an additional 24-48 hr. Repression was also observed when 5' upstream sequences of K14 or K5 genes were used to drive expression of a chloramphenicol acetyltransferase reporter gene in SCC-13 keratinocytes. Both cell types were found to express mRNAs for the RA receptors alpha and gamma, which may be involved in the RA-mediated transcriptional changes in these cells. The rapid transcriptional changes in epidermal keratin genes were in striking contrast to the previously reported slow transcriptional changes in simple epithelial keratin genes. 
A clinicopathologic study of node-based, low-grade, peripheral T-cell lymphoma. Angioimmunoblastic lymphoma, T-zone lymphoma, and lymphoepithelioid lymphoma. Postthymic (peripheral) T-cell malignancy shows marked diversity in histopathologic appearances as well as in clinical and prognostic aspects. Histologic findings and clinical behavior of 110 cases of the three specific types of low-grade, peripheral T-cell lymphomas, i.e., lymphoepithelioid (LeL), angioimmunoblastic (AILD), and T-zone (TzL) lymphomas, were studied. There were 74 men and 36 women (age range, 24 to 90 years; median, 58). Histologic study of LeL, AILD, and TzL showed prominent reactive features which are distinct from those of high-grade, T-cell lymphomas (pleomorphic/immunoblastic types). Corresponding to the differences in the histologic pictures of each type, there were differences in the clinical pictures and prognosis. Hypergammablobulinemia (greater than 4 g/dl) was more common in AILD than in the others. However, these three types exhibited a widely variegated, sometimes overlapping spectrum of histologic appearances, and it was extremely difficult to distinguish one from the other on several occasions. The same was true of their clinical and laboratory findings, and they had a relatively favorable prognosis as compared with pleomorphic/immunoblastic lymphomas. Although the conventional phenotypic analysis showed the prominent mixture of helper/inducer and cytotoxic/suppressor T-cells with a varying degree of B-cells and histiocytes, the double immunohistochemical study revealed that the neoplastic cells consisted predominantly of helper/inducer cells. Furthermore, five cases (5%) showed the morphologic transition among the three types or development into pleomorphic/immunoblastic lymphoma. They seemed to constitute a comprehensive and yet distinct group of T-cell lymphomas. Based on morphologic findings and clinical data, the authors demonstrated the distinct character of the node-based, low-grade, T-cell lymphomas and also the relationship among the three types in this group. The results of phenotypic and genotypic analyses also support the concept proposed here. 
A new anticancer drug delivery system for the management of carcinomatous peritonitis. To develop a new drug delivery system for the treatment of carcinomatous peritonitis, we constructed 5-fluorouracil poly L-microcapsules (5Fu-mc) by the organic phase separation technique and examined their drug-releasing capacities and anticancer effects. The microcapsules consisted of in vitro dissolvable polymolecular poly L-lactic acid and 5-fluorouracil (5Fu). The 5Fu-mc was about 200 microns in diameter and had a 5Fu content of about 40% (weight/weight). 5Fu-release time from the microcapsules was about 50 hours in vitro and about 48 hours in vivo. After the release of the 5Fu, the poly L-lactic acid was metabolized very slowly in the peritoneal cavity. The 5Fu-mc caused fewer side effects than the equivalent dose of a 5Fu solution. In addition, macroscopic and microscopic examinations of various abdominal organs revealed no toxic effects from the microcapsules. After administration of 5Fu-mc into the abdominal cavity of rats with AH-130 carcinomatous peritonitis, the 5Fu concentration remained at a high level for an extended period in the ascites but fell rapidly to low levels in the plasma. In conclusion, the present studies indicated that the 5Fu-mc were much more effective in prolonging the life of tumor-bearing hosts while producing less systemic side effects than a 5Fu solution. 
New recurring chromosomal translocations in childhood acute lymphoblastic leukemia. We identified seven new recurring translocations among 483 cases of acute lymphoblastic leukemia (ALL) with adequate chromosome banding studies. Four were apparently balanced [t(1;3)(p34;p21), t(7;9)(p15;p23-p24), t(12;13)(p13;q14), t(17;19)(q22;p13)], while three were unbalanced with the formation of a dicentric chromosome [dic(7;9)(p13;p11), dic(7;12)(p11;p12), and dic(12;17)(p11;p11-p12)]. One translocation was observed in five cases, two in four cases, and the remaining four in two cases each. The modal chromosome numbers in these 21 cases were 45 (n = 11), 46 (n = 8), and 47 (n = 2). Eight of the 11 cases with a dicentric chromosome had a modal number of 45. Only a single translocation was found in 14 cases (67%), representing the sole structural abnormality in six cases. In three of the seven translocation subgroups, the blast cells were consistently of B lineage (pre-B, early pre-B, or both); in all others, they represented both the B and T lineages. The small size of these subgroups prevented definitive clinical correlations, although it may be important that two of the four cases with a t(17;19) and an early pre-B-cell immunophenotype had disseminated intravascular coagulation, an event usually observed in acute promyelocytic leukemia or T-cell ALL. These findings add substantially to the existing list of nonrandom chromosomal translocations in childhood ALL and may help to explain the genetic alterations leading to the loss of normal growth control mechanisms in this disease. 
Surgical treatment of the Wolff-Parkinson-White syndrome by epicardial electrical ablation A new operation to eliminate accessory pathways--epicardial electrical ablation--is described. In a group of 201 patients without concomitant disease, the mortality rate was 0.5% and the overall efficacy of the operation for free wall accessory pathways, 98%. A retrospective clinical study of 44 unselected patients was performed to examine how safe epicardial electrical ablation is. The criteria for intraoperative effectiveness were disappearance of both the delta wave and retrograde conduction and inability to induce tachycardia. In the postoperative and follow-up periods, the following were reviewed: electrocardiograms; Holter monitor recordings (24 to 26 hours); release of the myocardial-specific isoenzyme of creatine kinase; intracardiac hemodynamics and myocardial contractility (radionuclide methods); selective coronary arteriograms and ventriculograms; mean work capacity (bicycle ergometer); diagnostic transesophageal electrical stimulation; and histology of the area of ablation. The main conclusion of this study is that epicardial electrical ablation is a highly efficient and safe operation for surgical elimination of parietal accessory pathways in patients with Wolff-Parkinson-White syndrome. Its advantages are its technical simplicity and the opportunity to review results immediately during the operation. 
Proportionate mortality trends: 1950 through 1986 Mortality trends in the United States from 1950 through 1986 were analyzed for the conditions that are or have recently been among the six leading causes of death. The age-adjusted mortality rate for all causes has decreased from 841.5 to 541.7 per 100,000 population. Cause-specific, age-adjusted mortality rates have declined from 1950 through 1986 for cerebrovascular disease, injuries, perinatal conditions, heart disease, and influenza and pneumonia. Time trends in the proportion of persons dying of each of these diseases, however, have varied; the proportion dying of cerebrovascular disease, injuries, and perinatal conditions has decreased, and the proportion of persons dying of heart disease and influenza and pneumonia has remained fairly stable from 1950 through 1986. During this same time, age-adjusted death rates have increased for chronic obstructive pulmonary disease and have remained fairly stable for malignant neoplasms, while the proportions of persons dying of chronic obstructive pulmonary disease and malignant neoplasms have increased dramatically. For people aged 35 to 64 years, malignant neoplasms have now overtaken heart disease as the leading cause of death. For those aged 65 years and older, heart disease remains the leading cause of death, accounting for almost 50% of all deaths in persons 85 years and older. 
Hyperoxia prevents hypoxia-induced bronchial hyperreactivity via a cyclooxygenase-independent mechanism. We tested the hypothesis that prior exposure to alveolar hyperoxia prevents the hypoxia-induced enhancement of bronchial reactivity, possibly via a cyclooxygenase-dependent mechanism. In 15 sheep, specific lung resistance (sRL) was measured before and after 30 min of exposure to either air or a hypoxic gas mixture (13% O2). The sheep then inhaled 50 breaths of aerosolized 5% histamine solution (n = 9) or 10 breaths of 2.5% carbachol solution (n = 9), and measurements of sRL were repeated. On subsequent days the above protocols were repeated after a 30-min exposure to hyperoxia (O2 greater than or equal to 95%), without or after pretreatment with indomethacin (2 mg/kg). After air-sham exposure, carbachol and histamine increased mean sRL to 370 +/- 40 (SE) and 309 +/- 65% of baseline, respectively. Exposure to the hypoxic gas mixture had no effect on baseline sRL but enhanced the airway responsiveness to carbachol and histamine; mean sRL increased to 740 +/- 104 and 544 +/- 76% of baseline, respectively (P less than 0.05). Prior 30-min exposure to hyperoxia prevented the hypoxia-induced enhancement of bronchial reactivity to carbachol (sRL = 416 +/- 66% of baseline) and histamine (sRL = 292 +/- 41% of baseline) without affecting the airway responsiveness to these agents after air. Pretreatment with indomethacin did not reverse the protective effects of hyperoxia or the hypoxia-induced enhancement of bronchial reactivity. We conclude that 1) prior exposure to alveolar hyperoxia prevents the hypoxia-induced enhancement of bronchial reactivity and 2) neither the protective effects of hyperoxia nor the hypoxia-induced enhancement of bronchial reactivity is mediated via a cyclooxygenase-dependent mechanism. 
Pathophysiology of myocardial perfusion in hypertension. Chronic and acute hypertension have multiple untoward effects on the coronary circulation, several of which may either mimic or markedly worsen the clinical manifestations of coronary artery disease. Early after the onset of left ventricular hypertrophy secondary to hypertension, coronary vasodilator reserve is significantly impaired. During cardiac hypertrophy secondary to hypertension, the coronary arteries fail to enlarge in concert with ventricular enlargement. This failure results in a relative decrease by approximately 50% in the ratio of epicardial vessel diameter to the mass of myocardium perfused. The lower range of coronary subendocardial autoregulation is altered by chronic renovascular hypertension. A variety of vascular smooth muscle homeostatic mechanisms are abnormal in genetic models of hypertension, as is endothelium-dependent vascular relaxation. Acute hypertension may enhance constriction to serotonin, most likely through the release of potent vasoconstrictor substances from leukocytes and platelets that adhere to the endothelium as a result of endothelial damage. Finally, many of the consequences of myocardial infarction are worsened in the setting of hypertension and left ventricular hypertrophy. 
Homing and progression patterns of childhood acute lymphoblastic leukemias in severe combined immunodeficiency mice. The aim of this study was to analyze the homing and progression patterns of childhood acute lymphoblastic leukemias (ALL) in mice with severe combined immunodeficiency (SCID). Upon intraperitoneal (IP) transfer, cells from relapse samples of three children with T-lineage ALL spread hematogenously and infiltrated the non-lymphoid and/or lymphoid organs with a pattern reminiscent of the human clinical disease. These mice either died or were killed in extremis at a mean of 9 weeks. Moreover, cell lines established in vitro from two of these samples manifested identical homing and progression in the SCID mouse as compared with the original patients' cells. Thus, long-term culture of the primary leukemic T cells did not alter their invasive potential and migration pattern. When engrafted IP, three cell lines established from pre-B-ALL cases displayed primarily a lymphatic spread with induction of local tumor masses and kidney/liver nodules. Mice were killed at 11 to 13 weeks, but had not developed imminently fatal leukemia. However, when transferred intravenously, one pre-B ALL cell line was able to spread hematogenously and to infiltrate both lymphoid and non-lymphoid tissues. Overall, these data demonstrate that the SCID mouse provides an efficient and reproducible model to study the pathogenesis of childhood ALL, and may be a suitable system for evaluating therapy. 
Hemilaryngectomy for salvage of radiation therapy failures. Radiation therapy has been the treatment most frequently used for early vocal cord cancer with surgery usually in the form of total laryngectomy held in reserve as a salvage option. We report our experience in selected patients who, having failed radiation therapy for their early vocal cord cancers, underwent frontolateral hemilaryngectomy as attempted salvage surgery. Between 1977 and 1986, fourteen patients at the University of Pittsburgh Eye and Ear Hospital underwent hemilaryngectomy for salvage of their stage I vocal cord squamous cell carcinoma after full-course radiation therapy had been unsuccessful. Over this same time period, 77 patients underwent total laryngectomy for salvage of radiation therapy failure. Three patients failed hemilaryngectomy, two of whom were ultimately salvaged with total laryngectomy. Thus a 79% salvage rate was achieved with hemilaryngectomy with an average followup of 90 months. The overall cure rate was 93% (13 of 14) with voice preservation in 86% (12 of 14). Decannulation, postoperative infection, and initiation of oral intake were not influenced by age. Such problems occurred more often in patients undergoing radiation therapy compared to those undergoing hemilaryngectomy without previous radiation therapy. These results indicate that hemilaryngectomy may be used for the salvage of radiation therapy failures of stage I vocal cord carcinoma with good success and without undue morbidity. 
Orthostatic vital signs in emergency department patients. STUDY OBJECTIVE: To examine the variability and define the normal ranges of orthostatic vital signs in an emergency department population. DESIGN: Descriptive. TYPE OF PARTICIPANTS: Adult ED patients with no history of recent blood or fluid losses. MEASUREMENTS: Lying and standing heart rate and blood pressure measured by an automated instrument. RESULTS: In 132 presumed euvolemic patients, the statistical normal ranges (mean +/- 2 SD) of orthostatic vital signs were wide: on standing, the heart rate range was from decreases 5.0 to increases 39.4 beats per minute; for systolic blood pressure, the range was decreases 20 to increases 25.7 mm Hg; and for diastolic blood pressure, the range was decreases 6.4 to increases 24.9 mm Hg. In this sample, 43% had "positive" orthostatic vital signs according to currently accepted values. CONCLUSION: The data from this study indicate that there is a wider than expected variation in orthostatic vital signs among presumed euvolemic ED patients. 
Depression of factor XII-dependent fibrinolytic activity characterizes patients with early myocardial reinfarction after recombinant tissue-type plasminogen activator therapy. Twenty patients with acute myocardial infarction treated with recombinant tissue-type plasminogen activator (rt-PA) had endogenous factor XII-dependent fibrinolytic activity levels measured throughout the hospital period and those levels were prospectively correlated with the incidence of recurrent myocardial infarction until 8 weeks after hospital discharge. Within the follow-up period, recurrent myocardial infarction was observed in 8 patients, whereas the remaining 12 patients showed no clinical evidence of recurrence. The patients in the reinfarction group were characterized by a more pronounced depletion of and sustained lower levels of factor XII-dependent fibrinolytic activity than were the patients with no reinfarction (p less than 0.05). The decrease in fibrinolytic activity during rt-PA therapy was significantly associated with a depletion of functional alpha 2-antiplasmin, the primary plasmin inhibitor. These results indicate that, paradoxically, coronary thrombolysis with rt-PA involves depletion of endogenous factor XII-dependent fibrinolytic activity levels, which constitutes a risk for early myocardial reinfarction. 
Ig repertoire of human polyspecific antibodies and B cell ontogeny. A total of 463 EBV Ig-secreting clones were derived from embryonic tissues, cord blood, and adult peripheral blood. Subcloning and analysis of the H and K loci (germline vs rearranged DNA status) of 44 primary clones insured clonality in at least 92% of cases. Whatever the cell origin, a somewhat constant proportion of clones (i.e., 11 to 16%) expressed polyspecific antibodies when tested on a panel of nine Ag, including self-Ag. The VH and VK repertoires have been studied using VH1-VH6 and VK1-VK4 family-specific probes. For all EBV clones the VH and VK utilization was similar to that of the normal untransformed population. A correlation was observed between the level of expression and the gene number for VH, whereas a clear distortion appeared for VK. Moreover, the usage pattern of VH and VK families of the polyspecific clones did not significantly differ from that of clones of unknown specificity, suggesting that polyspecificity was not linked to a restricted repertoire. 
Prospective randomized evaluation of two regimens for converting from continuous to intermittent feedings in patients with feeding gastrostomies. Forty enterally fed male patients were randomized to one of two regimens designed to determine the better means of converting them from continuous to intermittent enteral feedings. All patients received a nutritionally complete iso-osmolal 1 kcal/cc formula containing 6 g of nitrogen/L beginning on the second postgastrostomy day. Half of the patients (20) were randomized to a discontinuous regimen abruptly changing from continuous to gradually increasing intermittent feedings until reaching their nutritional goals. Intravenous fluids were given to maintain normal fluid balance. The other 20 patients were randomized to an overlapping regimen, receiving continuous feedings at a decreasing rate while intermittent feedings were progressively increased. Intravenous fluids were used during the first three stages only. There were no significant differences (p less than 0.05) in major diagnosis, type of gastrostomy, age, weight, height, admission or discharge serum albumin concentration, calculated basal energy expenditure (BEE), or nutrient goals (1.5 X BEE, 1.5 g of protein/kg per day). 
First-pass nuclear magnetic resonance imaging studies using gadolinium-DTPA in patients with coronary artery disease. Nuclear magnetic resonance (NMR) imaging has been shown to accurately portray cardiac anatomy and function. To investigate the potential of NMR imaging for the assessment of coronary stenosis in patients with chest pain, ultrafast NMR imaging in conjunction with a T1 (longitudinal relaxation time) contrast agent was performed in 17 patients with chest pain who had undergone cardiac catheterization. These included 12 patients with significant coronary artery stenoses and 4 who underwent repeat NMR study after myocardial revascularization. Cardiac images at rest were obtained during rapid intravenous injection of gadolinium-DTPA (0.04 mM/kg). Electrocardiographic-gated images were acquired over 380 ms, with repetitive images obtained every 3 to 4 s. After contrast injection, there was pronounced signal enhancement in the right ventricular cavity, followed by enhancement in the left ventricular cavity and myocardium. Regional myocardium perfused by a diseased vessel demonstrated a lower peak signal intensity (p = 0.001) and lower rate of signal increase (p = 0.001) than did myocardium perfused by coronary arteries without stenosis. Repeat NMR study after revascularization showed an increase in peak signal intensity (p less than 0.002). These results demonstrate the clinical potential of dynamic gadolinium-DTPA-enhanced NMR imaging for the assessment of coronary artery disease in patients with chest pain. In combination with anatomic and functional NMR imaging, this technique has the potential to provide a comprehensive noninvasive cardiac evaluation of patients with suspected coronary artery disease. 
Severe 5-fluorouracil toxicity secondary to dihydropyrimidine dehydrogenase deficiency. A potentially more common pharmacogenetic syndrome. This study describes the inheritance of a defect in pyrimidine catabolism and its association with drug-induced toxicity in a patient receiving 5-fluorouracil (FUra) as adjuvant chemotherapy for breast carcinoma. The study population included the affected patient (proband), nine of her blood relatives, and seven healthy volunteers. The activity of dihydropyrimidine dehydrogenase (DPD), the initial enzyme of pyrimidine (and FUra) catabolism, in peripheral blood mononuclear cells was measured in each subject by a specific radiometric assay using FUra as the substrate. The proband had no detectable DPD activity. When enzyme levels in the proband and relatives were compared with that in controls, an autosomal recessive pattern of inheritance was demonstrated. This is the third patient with severe FUra toxicity secondary to an alteration in pyrimidine catabolism and the second from our clinic population suggesting that the frequency of this genetic defect may be greater than previously thought. Monitoring DPD activity may be important in the management of patients experiencing severe toxicity secondary to FUra chemotherapy. 
Characterization of liver epithelial cells transfected with myc and/or ras oncogenes. While many liver tumors contain activated myc and ras oncogenes, the mechanisms by which these genes contribute to cellular transformation is poorly understood. Activated versions of the cellular oncogenes, c-myc and/or c-H-ras were transfected into normal rat liver epithelial cells to identify cellular pathways that are altered in the cells containing the oncogenes. The results of these and other investigations indicate that the biological properties associated with the transfection of c-myc include immortalization, reduced contact inhibition of growth, activation of phospholipase A2-mediated pathways, increased sensitivity to transformation with a ras gene, and greatly increased sensitivity to growth factors. The biological properties associated with the transfection of the ras gene include morphological transformation, anchorage-independent growth, tumorigenicity, increased phosphatidylinositol metabolism, the induction of growth-factor processing and secretion, which leads to (exogenous) growth factor-independent tumor growth, and a marked resistance to normal inhibitors of growth such as TGF-beta. It is proposed that the complementary actions of the myc and ras genes in cellular transformation may be related to the ras-induced secretion of autocrine growth factors by cells sensitized to their effects by the myc gene. The increased stimulus for growth coupled to a ras-induced insensitivity to growth inhibitors may lead to clonal expansion of these cells and tumor development. 
Necrolytic migratory erythema: dyskeratotic dermatitis, a clue to early diagnosis. A 57-year-old woman with a 6-year history of a dermatitis that evolved into typical necrolytic migratory erythema is reported. Four biopsy specimens were obtained in 5 years. The early lesions revealed superficial perivascular inflammation in the dermis, minor epidermal spongiosis, and scattered dyskeratotic cells in the upper epidermis. The differential diagnosis of this pattern of dyskeratotic dermatitis, particularly in a chronic eruption, should include consideration of hyperglucagonemia and the possibility of an associated pancreatic islet cell tumor. 
Correlation of occult clonogenic leukemia drug sensitivity with relapse after autologous bone marrow transplantation. Despite initial complete remission rates exceeding 70%, the majority of patients with acute myeloid leukemia (AML) and adults with acute lymphocytic leukemia (ALL) eventually relapse. Improving the therapeutic results in acute leukemia requires detecting, and understanding the biology of, the minimal residual leukemia remaining after therapy and responsible for relapse. To investigate the biologic relevance of an in vitro assay for clonogenic leukemia (leukemia colony-forming units [CFU-L]) as a measure of minimal residual leukemia, we studied 58 consecutive patients with acute leukemia in complete remission undergoing autologous bone marrow transplantation (BMT) with cyclophosphamide-based therapy. CFU-L were cultured from the pretransplant remission marrows in 45 of 58 patients: 35 of 43 patients with AML and 10 of 15 with ALL. Clonal rearrangements, identical to the patients' overt leukemia when available, were detected in the occult CFU-L from four of the eight patients with ALL in whom adequate DNA for analysis could be obtained from the CFU-L. None of the uncultured pretransplant remission marrows from the 15 ALL patients showed clonal gene rearrangements. We also determined the in vitro sensitivity of the occult CFU-L to 4-hydroperoxycyclophosphamide (4HC), and correlated these results with the outcome of the patients. The sensitivity of the occult CFU-L to 4HC was the only factor that predicted relapse following BMT. The actuarial probability of relapse was 18% in the 23 patients whose CFU-L were sensitive to 4HC compared with 77% in the 22 patients whose CFU-L were resistant (P less than .001). The only factor that influenced the CFU-L sensitivity to 4HC was the type of leukemia. The CFU-L from the AML patients were more sensitive to 4HC than the CFU-L from the ALL patients (P = .001). Occult CFU-L genetically and functionally represent occult leukemia. Therefore, the CFU-L assay should provide a means for studying the biology of minimal residual leukemia and improving the therapeutic results in patients with acute leukemia. 
Intraoperative colonic lavage and primary anastomosis in nonelective colon resection. In selected individuals requiring emergency colon resection, intraoperative colonic lavage with primary anastomosis represents a safe alternative to staged reconstruction. This procedure achieves excellent mechanical preparation of the colon, facilitates safe anastomosis, and avoids the disadvantages associated with multistaged operations. At our institution, 25 patients requiring urgent segmental resection of the left colon have undergone intraoperative colonic lavage. Primary anastomosis without fecal diversion has been performed in 21 of these patients. Obstruction of the large intestine was the indication for operation in 56 percent of the patients in this series. Ten patients (40 percent) required laparotomy for an acute intra-abdominal inflammatory process. No post-operative deaths have occurred in our series, and no patient has sustained clinically evident anastomotic leakage. A pelvic abscess developed in one patient after sigmoid colectomy for diverticulitis. Three patients required treatment for wound infection. Based on our results, we recommend resection with intraoperative colonic lavage and primary anastomosis as the preferred treatment for the majority of patients requiring nonelective segmental left colon resection. 
Scrapie-infected spleens: analysis of infectivity, scrapie-associated fibrils, and protease-resistant proteins. Scrapie-associated fibrils (SAF) and protease-resistant proteins (PrP) were isolated from spleens and brains of clinical animals (mice and hamsters) from three scrapie agent-host strain combinations, and their concentrations were compared with infectivity levels. The spleens of infected animals contained lower levels of infectivity, PrP, and SAF than did brains. Regardless of the route of infection, both SAF and infectivity were detected in spleen before brain. Infectivity increased in brains and spleens of 139A-infected mice before the detection and increase in SAF, suggesting that the synthesis of SAF and PrP may not be the limiting factor in agent replication. In contrast to those in ME7- and 263K-infected animals, the Western blot profiles for PrP from brain and spleen of 139A-infected mice exhibited distinct differences. Results indicate that SAF and PrP found in the spleens are both organ- and scrapie strain-specific. 
Randomized study on the effect of collagen impregnation of knitted Dacron velour aortoiliac prostheses on blood loss during aortic reconstruction. Intraoperative blood loss is an important factor in reconstructive surgery for aortoiliac disease because it is clearly associated with an increase in the operative morbidity and mortality rates. To minimize intraoperative blood loss, a blood-tight vascular prosthesis has been developed by impregnating a knitted Dacron prosthesis with bovine collagen. To study a potential reduction of intraoperative blood loss using these collagen-impregnated prostheses, we conducted a prospective randomized trial involving the collagen-impregnated prosthesis and its non-impregnated substrate, the Dacron knitted non-impregnated prosthesis. During a 2.5-year period, 123 consecutive patients (undergoing 81 procedures for aneurysmal disease and 43 procedures for occlusive disease) were admitted for elective aortic reconstructive surgery. Equal numbers of the two prostheses were randomly implanted. Various parameters were monitored: intraoperative blood loss before aortic cross-clamping (phase 1), during implantation of the prosthesis (phase 2) and after release of aorta cross-clamping (phase 3); the number of intraoperative and postoperative blood transfusions; and, finally, all preoperative and intraoperative factors that might contribute to intraoperative blood loss. A significant overall difference in intraoperative blood loss between the collagen-impregnated (2425 ml) and the non-impregnated (1907 ml) group was found (P = 0.003). However, this difference could not be attributed to collagen impregnation because no statistically significant difference in blood loss was found in the relevant period of operation (phase 3). Similar results were observed in patients operated on for both aneurysmal and occlusive disease (2600 versus 2195 ml and 2105 versus 1344 ml respectively). 
Profound hypothermia (less than 10 degrees C) compared with deep hypothermia (15 degrees C) improves neurologic outcome in dogs after two hours' circulatory arrest induced to enable resuscitative surgery. Deaths from uncontrollable hemorrhage might be prevented by arresting the circulation under protective hypothermia to allow resuscitative surgery to repair these injuries in a bloodless field. We have shown previously that in hemorrhagic shock, circulatory arrest of 60 minutes under deep hypothermia (tympanic membrane temperature, Ttm = 15 degrees C) was the maximum duration of arrest that allowed normal brain recovery. We hypothesize that profound cerebral hypothermia (Ttm less than 10 degrees C) could extend the duration of safe circulatory arrest. In pilot experiments, we found that the cardiopulmonary system did not tolerate arrest at a core (esophageal) temperature (Tes) of less than 10 degrees C. Twenty-two dogs underwent 30-minute hemorrhagic shock (mean arterial pressure 40 mm Hg), rapid cooling by cardiopulmonary bypass (CPB), blood washout to a hematocrit of less than 10%, and circulatory arrest of 2 hours. In deep hypothermia group 1 (n = 10), Ttm was maintained at 15 degrees C during arrest. In profound hypothermia group 2 (n = 12), during cooling with CPB, the head was immersed in ice water, which decreased Ttm to 4 degrees-7 degrees C. The Tes was 10 degrees C in all dogs during arrest. Reperfusion and rewarming were by CPB for 2 hours. Controlled ventilation was to 24 hours, intensive care to 72 hours. In the 20 dogs that followed protocol, best neurologic deficit scores (0% = normal, 100% = brain death) at 24-72 hours were 23% +/- 19% in group 1 and 12% +/- 8% in group 2 (p = 0.15). Overall performance categories and histologic damage scores were significantly better in group 2 (p = 0.04 and p less than 0.001, respectively). We conclude that profound cerebral hypothermia with CPB plus ice water immersion of the head can extend the brain's tolerance of therapeutic circulatory arrest beyond that achieved with deep hypothermia. 
A clinicopathologic study of 153 cases of complete hydatidiform mole (1980-1990): histologic grade lacks prognostic significance. Although the significance of histologic grading in hydatidiform mole has previously been investigated, most studies evaluated patients treated before 1975. Since 1975, many advances have been made in the understanding and treatment of hydatidiform mole, including the division of molar pregnancy into complete and partial hydatidiform mole. We retrospectively studied 153 cases of complete hydatidiform mole diagnosed and treated at the Brigham and Women's Hospital between 1980-1990 to determine the current prognostic significance of histologic grading in this disease. The histologic grade (based on the criteria of Hertig and Sheldon) was compared with the subsequent clinical course, including the rates of spontaneous remission, persistent gestational trophoblastic tumor, metastatic disease, "high-risk" metastatic disease, chemotherapy resistance, and survival. The histologic grade of the original complete hydatidiform mole did not correlate significantly with any index of clinical outcome evaluated. 
Granulomatous vasculitis occurring after cutaneous herpes zoster despite absence of viral genome. Granuloma annulare, sarcoidal and other granulomatous dermatitides, pseudolymphoma, lymphoplasmacytoid lymphoma, and Kaposi's sarcoma have been described as sequelae of herpes zoster. We report a new postzoster reaction, granulomatous vasculitis, that caused flat-topped papules restricted to the affected dermatome. Polymerase chain reaction failed to detect varicella-zoster virus in a biopsy specimen. These results suggest that granulomatous vasculitis occurs without persistence of the viral genome and, perhaps, is a reaction to minute amounts of viral proteins. 
The endocrine effects of long-term treatment with mifepristone (RU 486). Mifepristone (RU 486) is a compound with progesterone as well as cortisol-blocking activities. We investigated the endocrine effects of long-term therapy of 10 patients with meningiomas with 200 mg mifepristone daily for 1 yr. Most patients initially complained of nausea, vomiting, and/or tiredness. In four patients prednisone (7.5 mg/day) had to be given simultaneously in order to overcome these side-effects. In retrospect those patients who presented with the most severe side-effects showed the most rapidly occurring activation of the hypothalamo-pituitary-adrenal-axis, as measured by an increase of circulating cortisol levels as well as of urinary cortisol excretion. Therapy with RU 486 activated the hypothalamo-pituitary-adrenal axis, resulting in a resetting of this system at a higher level at which the diurnal rhythm and the responsiveness to CRH stimulation were maintained, whereas the sensitivity to dexamethasone had diminished. Secondarily the production of androstenedione and estradiol increased considerably. These endocrine changes were caused by the induction of partial cortisol receptor resistance during therapy with RU 486. The compensatory overproduction of androgens and consequently of estrogens during long-term RU 486 therapy might limit its use as a single treatment in the treatment of estrogen-dependent cancer. 
Acute pandysautonomic neuropathy. Acute pandysautonomic neuropathy is characterized by severe postganglionic sympathetic and parasympathetic dysfunction, with relative or complete sparing of motor and sensory function. Of four reported cases with sural nerve biopsies, two were normal and two abnormal, revealing loss of small myelinated and unmyelinated fibers. We present a patient with pandysautonomic neuropathy and elevated CSF protein whose sural nerve biopsy showed active axonal degeneration. 
A spectrum of bilateral squamous conjunctival tumors associated with human papillomavirus type 16. Three patients with bilateral tumors presenting as multiple keratinizing and verrucous lesions of the bulbar and tarsal conjunctiva were determined by DNA amplification and hybridization studies to harbor human papillomavirus type 16 (HPV-16). Results of biopsy in two patients showed infiltrating squamous cell carcinoma in one eye and dysplasia or carcinoma in situ in the fellow eye. In the third patient, focal, inflamed, hypertrophic, papillary lesions with pseudoglandular invaginations of the surface epithelium were found in the tarsal conjunctivae of both eyes. These are the first documented cases of bilateral conjunctival tumors associated with human papillomavirus. 
Exaggerated and prolonged thyrotrophin releasing hormone (TRH) test responses in tertiary hypothyroidism. A 60 year old man with panhypopituitarism due to a large meningioma and prolonged and exaggerated thyroid stimulating hormone (TSH) responses is described. Initial investigations showed a subnormal urinary free cortisol concentration, a low serum cortisol taken at 0900 hours, and a low free T4 concentration. The TSH was towards the upper end of the normal range. Subsequently pituitary function tests showed subnormal production of luteinising hormone in response to luteinising hormone releasing hormone (LHRH) and a short synacthen test with a low 30 minute cortisol value. Long synacthen testing showed a normal response at four days, confirming that the abnormalities were due to a pituitary or hypothalamic cause. A computed tomogram showed a large meningioma compressing the hypothalamus, pituitary, and temporal lobe. TRH testing showed a prolonged and exaggerated response, consistent with tertiary hypothyroidism. 
Treatment of antenatal myasthenia gravis. Maternal myasthenia gravis has been associated with the presence of neonatal myasthenia and sometimes fatal congenital anomalies. As a result, antenatal therapy directed at fetal sequelae may be indicated. We present the case of a pregnant myasthenic woman whose two previous pregnancies had ended in neonatal deaths from fetal deformations that were presumably due to maternal myasthenia. Serial plasmaphereses and oral prednisone therapy were used in an attempt to depress maternal anti-acetylcholine receptor antibody titers. As anti-acetylcholine receptor antibody titers fell, fetal breathing movements became apparent by ultrasound, and as these titers rose, no fetal breathing movements were apparent. Our patient delivered an infant with transient neonatal myasthenia but normal pulmonary development and no deformations. We suggest that the therapy given may have improved the outcome of this pregnancy compared with her two previous pregnancies. 
Gastrointestinal mucosal injury in experimental models of shock, trauma, and sepsis. BACKGROUND AND METHODS: The mucosa of the GI tract serves as an important barrier limiting the systemic absorption of luminal microbes and microbial products. Two methods commonly used to assess the integrity of the GI mucosal barrier are assessment of the extent of microbial translocation and measurement of mucosal permeability to hydrophilic probes. RESULTS: Studies using these methods have provided convincing evidence that the barrier function of the intestinal mucosa is deranged in numerous animal models of shock, trauma, and sepsis. CONCLUSIONS: Although the mechanisms underlying mucosal injury under these circumstances remain incompletely understood, current evidence suggests that mucosal damage in shock, trauma, and sepsis is likely due to various combinations of intracellular hypoxia due to ischemia, tissue injury caused by reactive oxygen metabolites, the deleterious effects of various lipid mediators (e.g., platelet-activating factor) and/or cytokines (e.g., tumor necrosis factor), and deficient utilization or supply of key nutritional substrates (e.g., glutamine). 
Pneumatic retinopexy. A two-year follow-up study of the multicenter clinical trial comparing pneumatic retinopexy with scleral buckling. The authors report 2-year follow-up information on 179 of 198 eyes (90%) enrolled in a previously published multicenter, randomized, controlled clinical trial comparing pneumatic retinopexy (PR) with scleral buckling (SB) for the management of selected retinal detachments. Scleral buckling was compared with PR with regard to redetachment after the initial 6-month follow-up period (1% versus 1%), overall attachment (98% versus 99%), subsequent cataract surgery (18% versus 4%; P less than 0.05), preoperative visual acuity (no significant difference), and final visual acuity of 20/50 or better in eyes with macular detachment for a period of 14 days or less (67% versus 89%; P less than or equal to 0.05). Reoperations after a failed PR attempt did not adversely affect visual outcome. After 2 years, PR continues to compare favorably with SB. 
Prophylaxis against venous thromboembolism in surgical patients. Venous thromboembolic disease is a common, potentially life-threatening, but preventable complication of surgery. Venographic studies have shown a high incidence of deep vein thrombosis in patients who do not receive prophylaxis. The long-term sequelae of deep vein thrombosis in these patients can be disabling, but the exact prevalence of post-thrombotic complications has not been well documented. Fatal pulmonary embolism has been reported in 0.5% to 1% of patients after major abdominal surgery and in 2% to 6% after total hip replacement. Several methods of prophylaxis against venous thromboembolism have demonstrated efficacy, but a surprising number of patients still do not receive prophylaxis. A medical record review in 16 hospitals recently disclosed that only 32% of high-risk patients received prophylaxis, with a range from 9% in a community hospital to 56% in a major teaching hospital. The possible reasons for this comparatively low rate of utilization are discussed. Current issues and future trends in the prophylaxis of venous thromboembolism are briefly summarized. 
Certified cause of death in children and young adults with cerebral palsy. The status of 732 children suffering from cerebral palsy from the South East Thames region (births from 1970-9) was ascertained at the end of 1989, and copies of death certificates of the 73 children who have died, aged 4 weeks to nearly 16 years, were obtained. Infantile cerebral palsy (ICD Code 343-) was coded as the underlying cause of death in only 16 (22%) cases. On 28 (38%) certificates there was no mention of any form of cerebral palsy, the proportion in which it was not mentioned increasing with age. In 20 (28%) cases the coded underlying cause of death was respiratory, hence in published national statistics the number of deaths from respiratory causes is inflated. A postmortem examination was known to have been performed in 23 cases, but the recorded information was in some cases limited to a 'terminal event'. The importance of good data on the death certificate, and the significance of published national statistics, need to be communicated to all those involved in the certification process if cerebral palsy and other chronic conditions, which raise the relative risk of death, are not to be under-represented. 
Repair of aortic coarctation in infants. Fifty-three consecutive infants younger than 2 years underwent coarctation repair. A recoarctation occurred in 11 infants (21%). To determine variables associated with recoarctation, we entered preoperative and operative data into a multivariate stepwise logistic regression analysis. Patient weight was an incremental risk factor for recoarctation instead of age, in contrast to previously published studies. Furthermore, the residual gradient after the operation was a strong incremental risk factor. This risk factor was even more significant when expressed as a ratio of the systolic arm pressure, which takes background hemodynamics into account. Because weight is a more significant risk factor than age, we conclude that deferring operation is indicated only when the infant gains weight. Furthermore, a residual gradient is more important in the hemodynamic setting of a lower systolic arm pressure. 
Dose response characteristics of hypertonic saline dextran solutions. In an effort to find the best hypertonic saline-dextran solution (HSD) for prehospital use, 33 chronically catheterized sheep were bled using a fixed pressure shock model (50 mm Hg x 2 hours) and resuscitated with 4 ml/kg of HSD solution (2-minute bolus). In the first set of experiments colloid was varied and sodium chloride was held constant, as 7.5% NaCl was paired with either 0%, 6%, or 12% dextran 70. A dose-response relationship existed, with cardiac output increasing 20% with each sequential dextran 70 concentration. Mean arterial blood pressure was higher in animals that were resuscitated with either the 7.5% NaCl/6% dextran 70 or 7.5% NaCl/12% dextran 70 solution (p less than 0.05). Using the optimal dextran 70 concentration from the first set of experiments (i.e., 12%), solute was varied in a second set of experiments comparing 0.9%, 3.8%, 7.5%, or 10% NaCl/12% dextran 70. Again, dose-response features were demonstrated, as cardiac output increased as a function of NaCl concentration. However, this response plateaued with the 7.5% NaCl concentration and no advantage was obtained by increasing the NaCl concentration to 10%. We conclude that a 4-ml/kg bolus of 7.5% NaCl/12% dextran 70 solution may be a more effective form of therapy than those previously evaluated. This new solution is now being included in our ongoing clinical trials. 
Diminishment of respiratory sinus arrhythmia foreshadows doxorubicin-induced cardiomyopathy. BACKGROUND. The development of a microcomputer-based device permits quick, simple, and noninvasive quantification of the respiratory sinus arrhythmia (RSA) during quiet breathing. METHODS AND RESULTS. We prospectively and serially measured the radionuclide left ventricular ejection fraction and the RSA amplitude in 34 cancer patients receiving up to nine monthly bolus treatments with doxorubicin hydrochloride (60 mg/m2). Of the eight patients who ultimately developed symptomatic doxorubicin-induced congestive heart failure, seven (87.5%) demonstrated a significant decline in RSA amplitude; five of 26 subjects without clinical symptoms of cardiotoxicity (19.2%) showed a similar RSA amplitude decline. On average, significant RSA amplitude decline occurred 3 months before the last planned doxorubicin dose in patients destined to develop clinical congestive heart failure. CONCLUSION. Overall, RSA amplitude abnormality proved to be a more specific predictor of clinically significant congestive heart failure than did serial resting radionuclide ejection fractions. 
Plasma endothelin in coronary venous blood from patients with either stable or unstable angina. STUDY OBJECTIVE--To test the hypothesis that the active coronary endothelial lesions in unstable angina raise the endothelin concentration in coronary venous blood. DESIGN--Systemic and coronary venous blood samples were obtained from unselected patients with the clinical syndromes of either stable or unstable angina at the time of cardiac catheterisation and coronary arteriography. Control venous blood samples were obtained from healthy laboratory workers and from patients with chronic renal failure treated by intermittent haemodialysis. PATIENTS--Twelve patients with angina: seven with stable symptoms and five with unstable angina. RESULTS--The mean coronary venous endothelin concentration in unstable angina was 2.32 ng/l (range 1.7-3.2 ng/l). In stable angina it was 2.77 ng/l (range 2.1-4.4 ng/l). These values were not significantly different from one another nor from the values obtained in systemic venous blood from either group or from the healthy controls. Circulating endothelin concentrations were much higher in venous blood from the patients treated by haemodialysis. CONCLUSIONS--These data do not support the hypothesis that raised endothelin concentrations in coronary blood in patients with unstable angina may modulate variations in coronary arterial tone thereby contributing to the clinical syndrome of chest pain and electrocardiographic changes at rest. The raised endothelin concentrations seen in systemic venous blood after myocardial infarction may be part of the systemic response to myocardial infarction. 
Effects of an increase in intracellular free [Mg2+] after myocardial stunning on sarcoplasmic reticulum Ca2+ transport. BACKGROUND. Myocardial stunning has been associated with a greater than twofold increase in intracellular free [Mg2+] from 0.6 to 1.5 mM. The effect of this increase in free [Mg2+] on the function of the sarcoplasmic reticulum (SR) Ca2+ pump was assessed in SR isolated from Langendorff perfused, isovolumic rabbit hearts after 15 minutes of global ischemia. METHODS AND RESULTS. Our results indicate that myocardial stunning results in a shift in the Ca2+ sensitivity of oxalate-supported, Ca2+ transport over the entire range of free [Ca2+] associated with the cardiac cycle. Using 0.6 mM free Mg2+ as control, maximal rates of Ca2+ transport occurred at 1 microM free Ca2+ (control, 519 +/- 32; stunned, 337 +/- 37 nmol Ca2+.min-1.mg-1). At 0.56 microM free Ca2+, SR Ca2+ transport was reduced from a control of 351 +/- 49 to 263 +/- 12 nmol Ca2+.min-1.mg-1 at 0.6 mM free [Mg2+]. Moreover, an increase in the free [Mg2+] from 0.6 to 1.5 mM results in a greater shift in the Ca2+ activation curve with no change in the level of maximal activation. Ca2+ transport at 0.56 microM free Ca2+ was shifted in the stunned SR from 263 +/- 12 to 138 +/- 29 nmol Ca2+.min-1.mg-1 at 0.6 and 1.5 mM free Mg2+, respectively. CONCLUSIONS. These results indicate that an increase in free [Mg2+] after stunning in combination with the inherent defect in the SR Ca2+ ATPase may reduce the ability of the cell to regulate Ca2+ to a greater extent than previously observed. This impairment in Ca2+ regulatory function may contribute directly to the increase in diastolic tone and indirectly to the reduced systolic function characteristic of the stunned myocardium. 
Sarcomas of soft tissue and bone. Sarcomas arise primarily from mesenchymal structures at any site in the body, even within visceral stroma and neurovascular bundles. Sarcomas have been associated with prior radiation therapy, toxic exposures, and genetic conditions and soft tissue sarcomas have been distinguished from bone sarcomas. For localized soft tissue sarcoma, tumor grade is the most important prognostic variable. Low-grade tumors are generally cured by wide surgical excision, but there is a significant rate of both local recurrence and development of distant metastasis in high-grade lesions. The treatment of soft tissue sarcoma histologic subtypes is generally similar grade-for-grade, with the exception of rhabomyosarcoma, Kaposi's sarcoma, and mesothelioma. Tumor location strongly influences resectability. Radiation therapy has been used successfully in conjunction with conservative surgery to improve local control rates for soft tissue sarcomas, particularly in extremity lesions. Currently, adjuvant chemotherapy remains unproven for most adult soft tissue sarcomas, but is established in the treatment of rhabdomyosarcomas, osteosarcomas, and Ewing's sarcomas. 
Otolaryngologic aspects of Lyme disease. Lyme disease is a systemic illness caused by the spirochete Borrelia burgdorferi and transmitted by the bite of a tick in the Ixodes ricinus complex. While the illness is often associated with a characteristic rash, erythema migrans, patients may also present with a variety of complaints in the absence of the rash. The otolaryngologist may be called upon to see both groups of patients, with any number of signs and symptoms referable to the head and neck, including headache, neck pain, odynophagia, cranial nerve palsy, head and neck dysesthesia, otalgia, tinnitus, hearing loss, vertigo, temporomandibular pain, lymphadenopathy, and dysgeusia. We review our institutional experience with 266 patients with Lyme disease, 75% of whom experienced head and neck symptoms. We also summarize the diagnostic and treatment modalities for this illness. 
Duplex Doppler sonography of the carotid artery: false-positive results in an artery contralateral to an artery with marked stenosis. Anecdotal reports have described a false-positive "jet effect" or velocity increase in the carotid artery contralateral to an artery with significant stenosis or occlusion when using duplex Doppler sonography. In this study, the frequency, significance, and possible reasons for this finding were evaluated by a retrospective comparison of duplex sonography and angiography. Twenty-three patients with unilateral 81-100% carotid artery stenosis who underwent both duplex sonography (16 Acuson, seven Quantum) and angiography were evaluated. In 14 patients, there was an accurate or slight underestimate (less than 20%) of stenosis present in the internal carotid artery contralateral to an artery with tight stenosis/occlusion. In nine, a velocity increase in the internal carotid artery resulted in overestimation (10-80%) of the actual degree of stenosis. In one of these nine patients, real-time images were sufficient to explain the velocity increase on the basis of vessel tortuosity. In one, falsely elevated velocity resulted from inaccurate assignment of the Doppler angle of incidence in a patient in whom real-time visualization of a distal internal carotid lesion was poor. In four of the nine patients, cross filling via the circle of Willis toward the side of greater stenosis occurred. However, seven of 14 patients in whom there was duplex sonography/angiography agreement or slight duplex sonography underestimation also had cross filling. Vertebral artery patency did not correlate well with the presence of a "jet effect." These findings suggest that an increase in blood flow velocity with duplex Doppler sonography in the internal carotid artery on the side opposite an artery with a tight stenosis is a common source of error and is not readily explained by angiographic evidence of collateral flow. 
Influence of isradipine on the maternal and fetal cardiovascular system in hypertensive disorders in pregnancy. Nine pregnant women (aged 28.7 +/- 6.9 years) who had developed hypertension (blood pressure greater than 140/90 mm Hg) took part in an open pilot study with the new calcium antagonist isradipine. Dosage was started with 1.25 mg twice daily and was increased weekly to 2.5 mg and 5 mg twice daily until a diastolic blood pressure of less than or equal to 80 mm Hg was achieved. By the time of the last visit before term, blood pressure was significantly reduced to 129/79 mm Hg and heart rate had not altered. External cardiotocography indicated fetal well-being throughout the entire study. Doppler flow measurements showed no deterioration in A:B ratio, resistance index, and pulsatile index. All measurements in the newborn were within normal ranges. In conclusion, isradipine is a safe and effective drug for pregnant women and their fetuses in the management of hypertensive disorders in pregnancy. 
Abdominal CT findings after liver transplantation in 66 patients. CT scanning is used frequently to assess the condition of patients after liver transplantation. The CT records of 174 adult patients who underwent liver transplantation were studied retrospectively to determine the number and timing of CT studies as well as the frequency and significance of the findings. One-hundred seventy CT scans were obtained in 66 (38%) of the 174 patients, with a mean of 2.6 scans/patient. The interval between transplantation and scanning was 1 day to 24 months; in 59 (89%) of 66 patients, the first CT scan was obtained within 30 days. The acute indications for CT scanning were fever or leukocytosis in 54 (92%) of 59 patients and abnormal liver function tests in five (8%) of 59 patients. CT scans obtained more than 30 days after transplantation were repeat scans in all but seven patients. Indications in this latter group were the same as for the acute group, plus evaluation of hepatic neoplasia in three patients. CT findings included periportal low attenuation in 41 (62%) of 66 patients; ascites in 25 (38%); splenomegaly in 19 (29%); loculated intraperitoneal noninfected fluid collections in 13 (20%); intrahepatic, splenic, pancreatic, or perihepatic abscesses in seven (11%); hepatic infarction in six (9%); splenic infarction in three (4%); and hepatic calcification in two (3%). Other major abnormalities included inferior vena caval thrombosis (one patient), pseudoaneurysm of the hepatic artery with rupture (one patient), and recurrent hepatocellular carcinoma (one patient). CT scanning after liver transplantation is used predominantly in the acute setting to evaluate for liver infarction or intraabdominal abscess. In this setting, CT showed these abnormalities, in addition to tumor recurrence or vascular abnormalities, in 15 (23%) of 66 patients. 
Protein-tyrosine-phosphatase CD45 is phosphorylated transiently on tyrosine upon activation of Jurkat T cells. The leukocyte common antigen (CD45) is an abundant lymphocyte surface antigen that has been reported to be involved in signaling through the T-cell antigen receptor. CD45 is a transmembrane protein-tyrosine-phosphatase. An internal segment comprises two domains each of which is homologous to other protein-tyrosine-phosphatases; the extracellular segment has the hallmarks of a ligand-binding motif. Since tyrosine phosphorylation is an early signal resulting from stimulation of the T-cell antigen receptor and CD45 is required for proper activation through the receptor, we explored whether CD45 might be regulated by tyrosine phosphorylation. Treatment of a T-cell leukemia line (Jurkat) with either phytohemagglutinin or anti-CD3 antibodies induced phosphorylation of tyrosine residues in CD45; treatment with phorbol 12-myristate 13-acetate did not. Phosphorylation of CD45 was transient, disappearing within 40 min after phytohemagglutinin treatment. The requirement for stringent conditions of phosphatase inhibition suggests that CD45 is capable of autodephosphorylation in vivo. These observations support recent reports indicating CD45 is involved in an early step in the T-cell activation cascade. They also suggest that phosphorylation/dephosphorylation of tyrosine residues in CD45 should be explored further as a possible regulatory mechanism. 
Headache in the use and withdrawal of opiates and other associated substances of abuse. The incidence and character of headache were retrospectively studied in 40 opiate addicts and 40 control subjects. The relationships between headache and use and withdrawal of opiates or other associated substances of abuse were investigated. In the opiate-dependent patients, the effects of opiate intake and withdrawal on headache were also investigated during detoxification treatment. A higher (p less than 0.001) incidence of headache was found in the opiate addicts (60%), particularly those with a longer history of addiction, than in the control subjects. A history of different types of headache (tension type headache, migraine-like headaches), which seemed respectively to be associated with the use of certain types of heroin, cocaine intake, and opiate withdrawal, was reported by the addicts who suffered from headache. Out of the 24 patients who completed the detoxification therapy, a migraine-like headache occurred in 37.5% of the subjects after opiate withdrawal. 
Treatment of ulcerated hemangiomas with the pulsed tunable dye laser. Hemangiomas are the most common tumor of infancy and are characterized by rapid growth during the first 6 months of life. During the rapid growth phase, approximately 5% to 10% of the hemangiomas ulcerate. Ulcerated lesions are painful, may bleed, and are at risk for bacterial infection. Previous therapy has included daily local wound care, topical antibiotics, and local and systemic steroids. We treated nine infants (eight female and one male) with ulcerated hemangiomas by means of a vascular-specific (585-nm) pulsed (450-microsecond) tunable dye laser. Eight of the nine patients had a single ulceration, whereas one patient had two ulcerations within a large hemangioma. Six of the ulcerations healed with a single laser treatment. One ulceration required two treatments to heal, and the remaining two required three treatments. Pain was subjectively decreased within 2 to 3 days in all patients after a single treatment. The pulsed tunable dye laser should be considered in the treatment of all ulcerated hemangiomas. 
Pathophysiology of myocardial perfusion in hypertension. Chronic and acute hypertension have multiple untoward effects on the coronary circulation, several of which may either mimic or markedly worsen the clinical manifestations of coronary artery disease. Early after the onset of left ventricular hypertrophy secondary to hypertension, coronary vasodilator reserve is significantly impaired. During cardiac hypertrophy secondary to hypertension, the coronary arteries fail to enlarge in concert with ventricular enlargement. This failure results in a relative decrease by approximately 50% in the ratio of epicardial vessel diameter to the mass of myocardium perfused. The lower range of coronary subendocardial autoregulation is altered by chronic renovascular hypertension. A variety of vascular smooth muscle homeostatic mechanisms are abnormal in genetic models of hypertension, as is endothelium-dependent vascular relaxation. Acute hypertension may enhance constriction to serotonin, most likely through the release of potent vasoconstrictor substances from leukocytes and platelets that adhere to the endothelium as a result of endothelial damage. Finally, many of the consequences of myocardial infarction are worsened in the setting of hypertension and left ventricular hypertrophy. 
Kistrin, a polypeptide platelet GPIIb/IIIa receptor antagonist, enhances and sustains coronary arterial thrombolysis with recombinant tissue-type plasminogen activator in a canine preparation BACKGROUND. Kistrin is a 68-amino acid polypeptide from the venom of the Malayan pit viper Agkistrodon rhodostoma, which inhibits the platelet GPIIb/IIIa receptor. Its effect on thrombolysis, reocclusion, and bleeding associated with administration of recombinant tissue-type plasminogen activator (rt-PA) was studied in a canine model of coronary artery thrombosis. METHODS AND RESULTS. Coronary patency was monitored for 2 hours by ultrasonic flow probe and repeated coronary angiography. The rt-PA was given as 0.45-mg/kg bolus injections at 15-minute intervals until recanalization or to a maximum of four boluses. Four groups of four or five dogs were studied: a control group that received intravenous heparin (4,000-unit bolus and 1,000 units each hour) and three groups that received heparin and 0.48, 0.24, or 0.12 mg/kg kistrin, administered as a 10% bolus injection and an infusion during a 60-minute period. In the control group, reflow occurred in four of five dogs within 37 +/- 47 minutes but was followed by cyclic reflow and reocclusion. Kistrin at a dose of 0.48 and 0.24 mg/kg reduced the time to reflow to 6 +/- 5 and 10 +/- 3 minutes, respectively, and abolished reocclusion. With 0.12 mg/kg kistrin, reflow occurred in all four animals, within 27 +/- 23 minutes, and reocclusion occurred in two animals. Kistrin induced a dose-related prolongation of the template bleeding time: with 0.48 mg/kg kistrin, the bleeding time was prolonged from 3.8 +/- 1.3 minutes before infusion to 29 +/- 2 minutes during infusion, but it was shortened to 8.3 +/- 2.6 minutes at 90 minutes after the end of infusion. Kistrin also caused a dose-related inhibition of platelet aggregation with ADP and collagen: with 0.48 mg/kg kistrin, platelet aggregation was abolished during the infusion but had partially recovered toward the end of the observation period. Pathological examination of recanalized coronary arterial segments of dogs given 0.48 or 0.24 mg/kg kistrin revealed widely patent arteries with some platelets layered on the damaged intimal surface. CONCLUSIONS. Kistrin increases the rate and extent of thrombolysis with a reduced dose of rt-PA, and it prevents reocclusion. At an effective dose, it is associated with a transient prolongation of the bleeding time and inhibition of platelet aggregation. Kistrin may offer promise as adjunctive treatment to thrombolytic agents in patients with acute myocardial infarction. 
Massive hemorrhage from a ruptured enteric varices of an augmented bladder. Intestinal varices are uncommon and usually occur secondary to portal hypertension. We report a case of variceal rupture in the intestinal segment of an augmentation colocystoplasty. The patient presented in shock from exsanguinating hemorrhage per urethram, and diagnosis was established at laparotomy. Although the bleeding was controlled with excision of the involved intestinal segment, the patient died of multiple organ failure. The diagnosis and treatment of this rare but fatal condition are discussed. 
Intracerebral temperature in neurosurgical patients. Recent laboratory results have indicated that the ischemic brain is very sensitive to minor variations in temperature. This has created new interest in hypothermia and brain temperature. There is, however, very little information available regarding human intracerebral temperature and its relation to body core temperature during normal and pathological circumstances. We therefore made continuous measurements of the temperature of the lateral ventricle in 15 neurosurgical patients utilizing a newly developed technique with copper-constantan thermocouples introduced through a plastic catheter also used for monitoring intracranial pressure. The intraventricular temperature was higher than the rectal temperature during approximately 90% of all measurements. The largest temperature gradient measured was 2.3 degrees C. Usually the difference between the temperature of the rectum and the brain was much smaller, the mean value being 0.33 degrees C. For the patients in the most severe condition, the rectal temperature was sufficiently close to the brain temperature to afford a reliable basis for adequate clinical judgment. 
Complications of the Heitz-Boyer urinary diversion: case report of late development of malignancy. We report on 3 patients with bladder exstrophy followed for more than 15 years after having undergone Heitz-Boyer urinary diversion. One patient had adenocarcinoma at the ureterocolonic anastomoses 16 years after diversion. To our knowledge this is the first reported case of a malignancy developing after a Heitz-Boyer procedure. The other 2 patients had significant problems with urinary incontinence and recurrent urinary tract infections. Initial success with this form of urinary diversion can be followed by significant long-term complications. 
Clear cell squamous cell carcinoma. A histologic, immunohistologic, and ultrastructural study. Squamous cell carcinomas (SCCs) usually show a standard histopathologic picture only varying with regard to their degree of differentiation. The authors describe a case of clear cell SCC that was studied by light and electron microscopy. The clear cells showed an empty cytoplasm that was periodic acid-Schiff and alcian blue negative. By electron microscopy these cytoplasms consisted of empty spaces and were not surrounded by membranes, which would be consistent with lipid vacuoles. The differential diagnosis of this uncommon variant of SCC requires consideration of other clear cell tumors. 
Phrenic neural output during hypoxia in dogs: constant-flow ventilation vs. spontaneous breathing. We studied the effects of removing cyclic pulmonary afferent neural information on respiratory pattern generation in anesthetized dogs. Phrenic neural output during spontaneous breathing (SB) was compared with that occurring during constant-flow ventilation (CFV) at several levels of eucapnic hypoxemia. Hypoxia caused an increase in both the frequency and the amplitude of the moving time average (MTA) phrenic neurogram during both SB and CFV. The change in frequency as arterial saturation was reduced from 90 to 60% during SB was significantly higher than that during CFV [SB, 32.3 +/- 10.9 (SD) breaths/min; CFV, 10.3 +/- 5.8 breaths/min; P = 0.001]. By contrast, the increase in the amplitude of the MTA phrenic neurogram was smaller (SB, 0.62 +/- 0.68 units; CFV, 1.35 +/- 0.81 units; P = 0.01). The changes in frequency with hypoxia during both modes of ventilation resulted primarily from a shortening of expiratory time. Both inspiratory time and expiratory time were greater during CFV than during SB, but their change in response to hypoxia was not significantly different. We conclude that the amplitude response of the MTA phrenic neurogram to hypoxia is similar to that seen during hypercapnia; in the presence of phasic afferent feedback the MTA amplitude response is decreased and the frequency response is increased relative to the response observed in the absence of phasic afferents. 
Captopril improves neurologic outcome from incomplete cerebral ischemia in rats. We investigated the effects of the angiotensin-converting enzyme inhibitor captopril on neurologic outcome in a rat model of incomplete cerebral ischemia. Twenty male Sprague-Dawley rats were anesthetized with 70% nitrous oxide in oxygen and fentanyl (10 micrograms x kg-1 i.v. bolus, 25 micrograms x kg-1 x hr-1 i.v. continuous infusion). Animals in group 1 (n = 10) received no angiotensin-converting enzyme inhibitor while animals in group 2 (n = 10) were given 10 mg x kg-1 i.v. captopril 30 minutes prior to the ischemic period. Ischemia was produced by unilateral carotid artery ligation and hemorrhagic hypotension to 35 mm Hg for 30 minutes. Body temperature, arterial blood gases, and arterial pH were maintained constant. Neurologic outcome was evaluated every 24 hours for 3 days using a graded deficit score (0, normal; 18, stroke-related death). On the third day after ischemia, captopril significantly improved neurologic outcome (median deficit score = 4) compared with controls (median deficit score = 18) (p less than 0.05). These results suggest that reduced angiotensin II levels or increased tissue kinin concentrations may decrease ischemic brain injury. 
Ability of high-intensity ultrasound to ablate human atherosclerotic plaques and minimize debris size. To investigate whether high-intensity ultrasound can destroy atherosclerotic plaques while sparing the normal arterial wall, 279 normal human aortic sites and 119 fibrous and 193 calcified plaques, obtained from 24 necropsies, were insonified in a water tank, at 20 kHz and at 5 different power intensities, ranging from 68 W/cm2 (P1) to 150 W/cm2 (P5). These intensities were associated with a total excursion of the ultrasound irradiation apparatus tip from 90 to 268 microns, respectively. Time to perforate normal aortic sites and fibrous and calcified plaques was recorded at each intensity. There was no difference in perforation time between normal aortic sites and fibrous and calcified plaques when high-power levels (P2 to P5) were used. However, at the lowest power (P1), perforation time for the normal aortic wall was significantly longer than for fibrous and calcified plaques: 30 +/- 18 seconds (166 observations), 14 +/- 7 seconds (p less than 0.001) (78 observations) and 12 +/- 8 seconds (p less than 0.001) (115 observations), respectively. When perforation times for normal vessel wall versus fibrous plaque and normal vessel wall versus calcified plaque from the same necropsy specimen were compared in a pairwise manner, the results were: 29 +/- 13 vs 16 +/- 7 (p less than 0.001) (48 paired observations) and 26 +/- 9 vs 10 +/- 5 seconds (p less than 0.001) (55 paired observations), respectively. Regardless of whether paired or unpaired comparison was applied, no significant difference was found in perforation time between fibrous and calcified plaques. The debris did not differ in size as measured separately for normal sites and fibrous and calcified plaques by a computer-interfaced Channelizer and Coulter Counter system. 
The effect of radiation therapy on the fixation strength of an experimental porous-coated implant in dogs. Radiation therapy prevents heterotopic ossification after cemented total hip arthroplasty, but its effect on the fixation of porous-coated devices is not known. The purpose of this study was to determine the effect of irradiation on the pullout strength of a porous implant in the canine model. A custom-designed titanium fiber metal-coated cylinder was implanted into the distal femurs of 12 dogs. One femur of each dog was irradiated with 10 Gy, given in four 2.5-Gy daily fractions beginning one day after surgery. Serial bone scans were performed at one, two, four, and six weeks postoperatively. At six weeks, the femurs were harvested, and eight were randomly selected for mechanical testing. Scintigraphic evaluation showed a significant reduction in uptake at one and two weeks in the irradiated limb, but this had returned to normal at four and six weeks. The failure to pullout was significantly less in the irradiated limb compared with the control limb six weeks postoperatively. In this canine model, the pullout strength of the titanium fiber implant was significantly reduced by a dose of radiation commonly used in the prevention of heterotopic ossification. If irradiation is chosen for prophylaxis, either the porous implant should be adequately shielded or a cemented implant should be utilized. 
Disability, residential mobility, and changes in living arrangements. The extent of mobility and changes in living arrangements associated with disability were studied using data from the 1984-86 Longitudinal Study of Aging. It was hypothesized that persons with significant limitations in their ability to perform normal daily activities (ADLs and IADLs) in 1984 would be more likely to move, more likely to be living with others in 1986, and more likely to have entered an institution between 1984 and 1986 than those without limitations. When only those variables that were measured in 1984 were used as predictors, this turned out to be true for institutionalization and for living with others in 1986. However, among those remaining in households, residential mobility showed little relationship to disability when other variables were controlled. When the change in disability between 1984 and 1986 was added to the prediction equation, there were strong relationships between changes in disability and both residential mobility and adjustment in living arrangement, suggesting that people respond quickly to significant changes in disability. However, because we cannot be sure that the changes in disability preceded the mobility or changes in living arrangements, we cannot claim to have established a causal link between these events. 
Change in the expression of a nuclear matrix-associated protein is correlated with cellular transformation. We have identified a monoclonal antibody that recognizes a nuclear matrix-associated protein in NIH 3T3 cells. The immunofluorescence pattern consists predominantly of bright nuclear granule clusters distributed throughout the nucleoplasm, with the exclusion of nucleoli. It recognizes a protein of 190 kDa that is down-regulated to various degrees in a panel of single-oncogene-transformed NIH 3T3 cells. Its localization is similar, but not identical, to the spliceosomal speckles. p190 shows a coordinate expression during the growth cycle of nontransformed NIH 3T3 cells; it is synthesized at the highest level under growth arrest conditions. It is expressed in adult mouse brain and is also present in human IMR-90 fibroblasts. 
Small, deep pelvic abscesses: definition and drainage guided with an endovaginal probe. Four small, deep pelvic abscesses were easily drained transvaginally by using an endovaginal transducer for guidance, support, and continuous monitoring of catheter placement. Collections that could not be drained percutaneously or at surgery were effectively managed with this technique. An inexpensive guide (estimated cost, $1.65) facilitated control of the catheter. All four abscesses resolved without further intervention. 
Exercise thallium-201 perfusion scintigraphy in the assessment of coronary artery disease. Exercise thallium-201 perfusion scintigraphy has been used extensively over the last decade for the detection and localization of coronary artery disease. Single-photon emission computed tomography (SPECT) is a refinement of presently available techniques, offering improved identification over planar imaging of individual vessel stenosis and quantification of the extent of abnormally perfused myocardium. In this review, the planar and SPECT techniques are discussed in light of the most recently published large patient series, and with regard to the many factors that affect the sensitivity and specificity of perfusion imaging in identifying coronary artery disease. The clinical implications of exercise perfusion scintigraphy and its future applications in cardiology practice are discussed. 
Obstructive sleep apnea complicating negative-pressure ventilatory support in patients with chronic paralytic/restrictive ventilatory dysfunction. The purpose of this study was to determine the incidence and severity of obstructive events and oxyhemoglobin desaturation (dSaO2) in 37 patients with paralytic/restrictive ventilatory insufficiency during use of nocturnal ventilatory assistance provided by means of negative-pressure body ventilators (BVs). Thirteen of the 37 patients had mean oxyhemoglobin saturation (SaO2) less than 95 percent and a mean of ten or more episodes per hour when the dSaO2 was greater than or equal to 4 percent (4%dSaO2/h). In all, 26 of the 37 patients had evidence of significant multiple episodes of dSaO2 while asleep on BVs. Polysomnography performed on three of these patients substantiated the obstructive nature of the dSaO2. Twenty-two of the 37 patients who had a mean SaO2 of 90.6 +/- 7.2 percent and a mean of 17.7 +/- 16.1 4%dSaO2/h on BVs were switched to noninvasive ventilatory assistance by intermittent positive airway pressure (NV-PAP). Their mean SaO2 improved to 96.0 +/- 2.2 percent, and the 4%dSaO2/h decreased to 1.2 +/- 1.8 per hour. All symptoms similar to those of obstructive sleep apnea were relieved. We conclude that BV use is associated with significant dSaO2 in over 50 percent of patients. The dSaO2 is predominantly obstructive in nature but may be due to chronic underventilation in patients using less effective BVs. Patients with a mean SaO2 less than 95 percent or 10 or more 4%dSaO2/h may benefit from conversion to NV-PAP via the nose, the mouth, or an oral-nasal interface. 
Intrahepatic hematoma: a rare complication of exchange transfusion. A four-day-old male neonate who underwent three exchange transfusions for jaundice owing to ABO incompatibility on three consecutive days is presented. A large intrahepatic hematoma developed as a complication of the third exchange transfusion. The baby fully recovered. 
Partial motor epilepsy with "negative myoclonus". Three children had both nocturnal unilateral motor seizures and daytime ipsilateral "negative myoclonus" which occurred so frequently that it resembled asterixis. Neurophysiologic studies demonstrated lateralized spike discharges that were time-locked to postural lapse in the contralateral outstretched arm. The clinical course was characterized by good seizure control with benzodiazepines. 
Treatment of acute migraine with subcutaneous sumatriptan. Sumatriptan succinate, a 5-HT1D receptor agonist, constricts human cranial arteries. Two parallel-group trials for treatment of acute migraines were conducted in the United States. Adult patients were randomized and given either 6 mg of sumatriptan succinate subcutaneously (n = 734) or placebo (n = 370). At 1 hour, sumatriptan was significantly more effective than placebo in reducing moderate or severe headache pain to mild or no pain (70% vs 22%), in completely relieving headaches (49% vs 9%), and in improving clinical disability (76% vs 34%). Sumatriptan also reduced nausea and photophobia significantly better than placebo. Patients with residual migraines received another injection; those who had originally received sumatriptan received either a second active injection (n = 187) or placebo (n = 178), while those who had received placebo received a second placebo injection (n = 335). Statistical evidence for benefit of second sumatriptan injection is absent. Adverse events associated with sumatriptan were tingling, dizziness, warm-hot sensations, and injection-site reactions. Sumatriptan is effective and well tolerated in patients with acute migraine. 
Deletion of sequences upstream of the proteinase improves the proteolytic processing of human immunodeficiency virus type 1. Human immunodeficiency virus type 1 expresses structural proteins and replicative enzymes within gag and gag-pol precursor polyproteins. Specific proteolytic processing of the precursors by the viral proteinase is essential for maturation of infectious viral particles. We have studied the activity of proteinase in its immature form, as part of a gag-pol fusion protein, in an in vitro expression system. We found that deletion of p6*, the region in pol upstream of proteinase, resulted in improved processing of the precursor. A modified proteinase is released, but it functions less efficiently than wild type. Improved autoprocessing correlates with increased accessibility of the active site region in the polyprotein carrying the p6* deletion. Our results suggest that p6* is involved in the regulation of proteinase activation, perhaps as a region limiting the interaction of the active site and substrate binding domain with the remainder of the polyprotein. Release of p6* inhibition may be an activation step necessary for infectious particle maturation. 
Dipyridamole echocardiography stress testing in hypertensive patients. Targets and tools. Arterial hypertension can provoke a reduction in coronary flow reserve through several mechanisms that are not mutually exclusive, namely, coronary artery disease, left ventricular hypertrophy, and microvascular disease. These different targets of arterial hypertension should be explored with different diagnostic markers. The transient dyssynergy detected by two-dimensional echocardiography and evoked during dipyridamole infusion is a marker of coronary disease that is equally reliable in normotensive and hypertensive individuals. On the contrary, dipyridamole-induced ST segment depression is frequently elicited in hypertensive patients when angiographically assessed coronary disease is absent. This ischemiclike electrocardiographic response can be found in echocardiographically assessed left ventricular hypertrophy. However, even when left ventricular mass is normal, dipyridamole-induced ST segment depression is associated with an impaired coronary flow response to pacing, which is consistent with microvascular disease. Whether echocardiographically silent electrocardiographic changes are simply diagnostic noises transmitting a misleading false positive response or a potentially important clinical marker of early myocardial damage remains a pivotal though still unanswered question. 
Response characteristics of a dual transcutaneous oxygen/carbon dioxide monitoring system. We tested the response characteristics of a dual transcutaneous (tc) PO2/PCO2 monitoring system in healthy subjects who breathed various gas mixtures, and we compared steady-state tc readings to simultaneous arterial blood gas analysis in 20 stable respiratory outpatients. The electrodes were simple to apply, required very little skin preparation, and had trivial signal drift. In healthy subjects, tcPCO2 lag time during CO2 rebreathing was 16.8 seconds, with a 90 percent response time of 77.9 seconds after CO2 breathing was discontinued. The 90 percent response times of the O2 electrode when subjects breathed a hypoxic mixture was 257 seconds after a lag of 31 seconds. When inhaled gas mixtures were changed from hypoxia to room air, the lag time was shorter (12.5 seconds), but 90 percent response time exceeded 5 minutes. In stable patients with respiratory disease, tcPCO2 and tcPO2 were linearly related to PaCO2 (range, 19 to 53 mm Hg) and PaO2 (range, 45 to 99 mm Hg), respectively (tcPCO2 = 1.4 PaCO2-9.44, with r = 0.90 and SEE = 5.35 mm Hg; tcPO2 = 0.56 PaO2 + 20.4, with r = 0.53 and SEE = 11.7 mm Hg). We conclude that the response of the dual transcutaneous monitoring system is more rapid for the CO2 than the O2 electrode and may be rapid enough to be useful in some clinical settings; however, the O2 system fails to offer the response characteristics and accuracy that would allow it to be substituted for arterial gas tensions in unstable clinical situations. 
Risk factors for stroke as predictors of platelet membrane fluidity in Alzheimer's disease. We have previously reported that increased platelet membrane fluidity identifies a subgroup of patients with Alzheimer's disease who have distinct clinical features including an earlier age of symptomatic onset, a more rapidly progressive cognitive decline, and a decreased prevalence of focal electroencephalographic findings. In the current study, these patients also exhibited a decreased prevalence of risk factors for stroke compared with patients who had normal platelet membrane fluidity. Our findings suggest that the platelet membrane abnormality describes a clinical subgroup of patients with Alzheimer's disease who are less likely to have coexisting cerebrovascular disease than the remaining patients who meet clinical consensus criteria for probable Alzheimer's disease. 
Enhancement of mammary carcinogenesis by high levels of dietary fat: a phenomenon dependent on ad libitum feeding Female 55-day-old Sprague-Dawley rats were treated with a single intravenous dose of 7,12-dimethylbenzanthracene (DMBA), 2 mg/100 g of body weight each. At 60 days of age, the rats were divided into four dietary groups (41-42 rats/group):I, 5% corn oil diet fed ad libitum; II, 20% corn oil diet fed ad libitum; III, 5% corn oil diet fed 12% less than group I; and IV, 20% corn oil diet fed 12% less than group II. The 5% and 20% corn oil diets were purified semisynthetic diets that were isonutrient on a caloric basis. All animals were housed individually in single cages; food consumption of each animal was computed daily throughout the study. Sixteen weeks after carcinogen treatment, mean numbers of mammary carcinomas per rat (+/- SE) in groups I, II, III, and IV were 4.1 +/- 0.6, 6.8 +/- 0.7, 3.0 +/- 0.3, and 4.1 +/- 0.5, respectively. Mean weight of mammary carcinomas per rat (g +/- SE) in groups I, II, III, and IV were 3.5 +/- 0.7, 8.0 +/- 1.3, 3.0 +/- 1.1, and 4.6 +/- 1.3, respectively. Mammary carcinoma number and weight were significantly (P less than .01) increased in the animals fed the 20% corn oil diet ad libitum when compared with those fed the 5% corn oil diet ad libitum; however, no significant differences in mammary tumor number or weight were observed between the animals fed a restricted, 20% corn oil diet and those fed a restricted, 5% corn oil diet. The study involving the animals fed the 12%-restricted diets was repeated (38-42 rats/group), with virtually identical results, i.e., the mean number of mammary carcinomas per rat in the groups fed the restricted 5% fat and 20% fat diets at termination of the study was 3.1 +/- 0.4 and 3.7 +/- 0.3, respectively, and the mean weight (g) of mammary carcinomas per rat was 4.3 +/- 1.2 and 4.0 +/- 1.1, respectively (no significant differences). Thus, high levels of dietary fat can significantly enhance mammary carcinogenesis in female rats, but only in animals on an ad libitum feeding protocol. A slight restriction in amount consumed (12% less than ad libitum) abolished the mammary carcinogenic differential between a high-fat and a low-fat diet. 
Recombinant interferon alfa given before and in combination with standard chemotherapy in children with acute lymphoblastic leukemia in first marrow relapse: a Pediatric Oncology Group pilot study. Recombinant interferon alfa (rIFN-alpha) was given to 31 children with acute lymphoblastic leukemia (ALL) in first on-therapy marrow relapse as the sole treatment (30 megaunits/m2/d intravenously x 10 days) before standard four-drug reinduction and during multiagent continuation therapy (30 megaunits/m2 subcutaneously x 3 consecutive days every 3 weeks). After 10 days of rIFN-alpha, there were two partial remissions (PRs); seven additional patients had either greater than or equal to 25% reduction in the percentage of marrow blast cells or hypoplastic marrow. Two patients had progressive disease with an increase in leukocyte counts. All patients experienced influenza-like symptoms, and there were isolated instances of severe abdominal pain and personality change. Dose-limiting toxicity comprised grade III/IV transaminase elevation (two patients) and syncope with personality change (one patient). Twenty-three of 31 children (74%) subsequently achieved marrow remission using standard agents. One patient was taken off study during teniposide (VM-26) and cytarabine (ara-C) consolidation due to toxicity. Continuation therapy including rIFN-alpha pulse was well tolerated in the remaining children; only one patient required rIFN-alpha dosage reduction (for CNS toxicity). rIFN-alpha toxicity did not necessitate reductions in doses of standard chemotherapy agents or significant delays in therapy. Five patients remain in remission at 26+ to 36+ months; 13 patients relapsed in marrow, one in the meninges (7 months), and one in meninges, mediastinum, and lymph nodes (2 months). Two children were removed from study for marrow transplant. In summary, high-dose rIFN-alpha alone had a modest antileukemic effect. In contrast to the clinical experience with combined rIFN-alpha and chemotherapy in adults, rIFN-alpha given in a pulse-like manner throughout continuation therapy did not compromise the intensity of the standard chemotherapy regimen. 
Enhanced gastric mucosal haemostasis after upper gastrointestinal haemorrhage. An endoscopic technique for the measurement of gastric mucosal bleeding time has been developed to study gastric haemostasis in patients with acute upper gastrointestinal haemorrhage. The relation of gastric mucosal bleeding time to skin bleeding time and nonsterodial anti-inflammatory drug usage was examined in 61 control patients and in 47 patients presenting with bleeding peptic ulcers or erosions. Gastric mucosal bleeding time was shorter in patients with haemorrhage (median 2 minutes, range 0-5 minutes) than in the control group (median 4 minutes, range 2-8 minutes) (p less than 0.001). Skin bleeding times were similar in the two groups (medians 4 minutes in patients with haemorrhage and 4.5 minutes in controls). In 21 patients with haemorrhage who were taking non-steroidal anti-inflammatory drugs, the median gastric mucosal bleeding time (2.5 minutes, range 1.0-5.0 minutes) was similar to that in 26 patients with haemorrhage not associated with these drugs (2.0 minutes, range 0.0-5.0 minutes). These results show that gastric mucosal haemostasis is accelerated in response to haemorrhage in the upper gastrointestinal tract, even in patients taking nonsteroidal anti-inflammatory drugs. This enhanced gastric haemostasis probably reflects a local protective response to minimise blood loss from the bleeding lesion. 
Prognostic value of serum proteins synthesized by breast carcinoma cells. Several breast carcinoma cell lines or explants of such tumors, as well as examples of lactating or dysplastic breast tissue, synthesized three serum proteins (alpha 2-Zn-glycoprotein, alpha 1-antichymotrypsin, and alpha-lipoprotein) in vitro. These proteins were detected by immunoperoxidase techniques in 126 breast carcinomas that had been evaluated clinically for more than six years. Alpha-2-Zn-glycoprotein was present in 58% of the carcinomas, whereas alpha 1-antichymotrypsin was seen in 55% and alpha-lipoprotein in 52%. These markers showed a relationship with clinical outcome. Alpha-1-antichymotrypsin and alpha-lipoprotein were unfavorable determinants, whereas alpha 2-Zn-glycoprotein was detected in lesions with a favorable evolution. Taken individually, these markers have similar but rather weak associations with five-year survival rates; roughly 20% of patients in the "favorable" group died, compared with 33% in the "unfavorable" group. Alpha-2-Zn-glycoprotein in grade 1 tumors was a marker with marginally favorable significance, but alpha 1-antichymotrypsin significantly worsened the prognosis of grade 2 and 3 tumors. Furthermore, stratification of patients according to the number of positive unfavorable markers yielded striking results. Eight percent of patients with none of the unfavorable markers were dead at five years, compared with 55% of those whose lesions expressed three unfavorable markers. 
Total replacement for post-traumatic arthritis of the elbow. Fifty-three of 55 consecutive elbow replacements for post-traumatic arthritis were followed for a minimum of two years (mean 6.3, range 2 to 14.4). The patients presented difficult management problems, having undergone an average of two previous operations per joint; 22 joints had suffered prior complications; 18 had less than 50 degrees of flexion and six were flail. One of three versions of the Coonrad prosthesis was employed in all. During the follow-up period, 10 patients underwent 14 revision procedures for aseptic loosening; 38 elbows are currently without progressive radiolucent lines. In two patients an elbow had to be resected, one for deep infection and the other for bone resorption following a foreign-body reaction to titanium. The current design of the Coonrad prosthesis offers a reliable option for the treatment of post-traumatic arthritis but should be used only in carefully selected patients over the age of 60 years. 
Cardiac rehabilitation services: what are they and are they worth it? The objectives of cardiac rehabilitation include lowering mortality but, more importantly, increasing functional capacity so reducing disability and potentially improving quality of life. The data suggest that cardiac rehabilitation services are worth the patient's costs and efforts and as such, they should be considered an integral component of comprehensive cardiovascular care by cardiologists and primary care physicians. While there is considerable agreement on the roles of exercise testing and training in the three position stands, there are also substantiated, and important, differences in their recommendations on other cardiac rehabilitation services, such as counseling and risk factor management. The challenge for the 1990's is not only to continue to better define the effectiveness of cardiac rehabilitation services, but more urgently, how to deliver effective services most efficiently. This will help physicians provide optimum care for their patients, will improve the patient's likelihood of regaining for themselves an active and productive life, and should generate a more equitable and accountable reimbursement system for quality health care. 
Risk stratification for arrhythmic events in postinfarction patients based on heart rate variability, ambulatory electrocardiographic variables and the signal-averaged electrocardiogram. The value of heart rate variability, ambulatory electrocardiographic (ECG) variables and the signal-averaged ECG in the prediction of arrhythmic events (sudden death or life-threatening ventricular arrhythmias) was assessed before hospital discharge in 416 consecutive survivors of acute myocardial infarction. During the follow-up period (range 1 to 1,112 days), there were 24 arrhythmic events and 47 deaths. The initial relation between several prognostic factors and arrhythmic events was explored with use of the Kaplan-Meier product limit estimates of survival function. Impaired heart rate variability less than 20 ms (p less than 0.0000), late potentials (p less than 0.0000), ventricular ectopic beat frequency (p less than 0.0000), repetitive ventricular forms (p less than 0.0000), left ventricular ejection fraction less than 40% (p less than 0.02) and Killip class (p less than 0.02) were identified as significant univariate predictors of arrhythmic events. When these variables were analyzed by using a stepwise Cox regression model, only impaired heart rate variability, followed by late potentials and repetitive ventricular forms remained independent predictors of arrhythmic events. The combination of impaired heart rate variability and late potentials had a sensitivity of 58%, a positive predictive accuracy of 33% and a relative risk of 18.5 for arrhythmic events and was superior to other combinations including those incorporating left ventricular function, exercise ECG, ventricular ectopic beat frequency and repetitive ventricular forms. These results suggest that a simple method of assessment based on heart rate variability and the signal-averaged ECG can select a small subgroup of survivors of myocardial infarction at high risk of future life-threatening arrhythmias and sudden death. 
Hemianesthesia, sensory neglect, and defective access to conscious experience. We report a patient with an ischemic stroke in the vascular territory of the right middle cerebral artery who had left spatial neglect and left hemianesthesia. The patient showed a dissociation between defective verbal reporting of somatosensory stimuli delivered to the left hand and physiologic evidence from an autonomic index. This indicates that there was processing of undetected stimuli without the patient's awareness, and suggests that the hemianesthesia was due, at least in part, to somesthetic hemi-inattention. 
Pathogenesis of thrombosis in unstable angina. Plaque rupture of the thinned, weak fibrous cap infiltrated by macrophages and overlying a pool of lipid in the arterial wall initiates the acute thrombotic event of unstable angina. Thrombosis may be advanced within minutes. Most lesions that precede plaque rupture are minor (less than 50% stenosis); thus, thrombus greatly contributes to sudden flow limitation and onset of symptoms. If thrombosis can be totally blocked (not possible with current antithrombotic agents), clinical events should be preventable, and endogenous thrombolysis may be possible within days. Local and systemic factors contribute to arterial thrombosis. With type III injury (fissure into plaque or media) platelet-rich thrombus anchors in the fissure, tracks along the site of deep injury, extends into the lumen, and requires the highest blood level of specific thrombin inhibition (a molar concentration that inhibits the total concentration of prothrombin in circulating blood). Thus, the thrombin content requiring inhibition in type III injury is highest. Local factors for thrombosis associated with type III injury include the rheology of blood flow (increased shear rate forces platelets to the periphery) and substrates in the arterial wall. Plaque substrates include the more thrombogenic collagens (types I and III and diabetic or glycosylated collagen), tissue thromboplastin, lipid gruel, thrombin bound to arterial wall matrix, and decreased prostacyclin. There is a direct relation between platelet deposition (thrombus) and local vasoconstriction, which may perpetuate each other. Thrombus as a substrate is more thrombogenic than type III arterial injury. 
Ossified mucin-secreting choroid plexus adenoma: case report. This is the first report of a fully documented case of an ossified mucin-producing benign choroid plexus tumor. This was a chance finding in a man who complained only of posttraumatic low back discomfort. The ossification of the tumor appears to have been therapeutic. Mucin production may be a defense mechanism. 
Increased incidence of lymphoproliferative disorder after immunosuppression with the monoclonal antibody OKT3 in cardiac-transplant recipients BACKGROUND. A sudden increase in the incidence of post-transplantation lymphoproliferative disorder among the patients in our cardiac-transplantation program was temporally related to introduction of the immunosuppressive drug OKT3. This monoclonal antibody has come to be widely used in recent years both to prevent and to treat rejection after cardiac transplantation. METHODS. In order to identify variables that predict the development of post-transplantation lymphoproliferative disorder, we analyzed retrospectively a series of 154 consecutive cardiac-transplant recipients at a single institution. Univariate analyses and multivariate analysis by logistic regression were performed. RESULTS. Among 75 patients who did not receive OKT3, post-transplantation lymphoproliferative disorder developed in 1 (1.3 percent), as compared with 9 of 79 patients who received the drug (11.4 percent); the incidence among the OKT3-treated patients was ninefold higher (odds ratio, 9.5; 95 percent confidence interval, 1.6 to 54.7). According to multivariate analysis, the only factor significantly associated with the development of post-transplantation lymphoproliferative disorder was the use of OKT3 (P = 0.001). A significant increase in risk with increasing doses was also apparent: 4 of 65 patients who received a cumulative dose of 75 mg of OKT3 or less (6.2 percent) had post-transplantation lymphoproliferative disorder, whereas 5 of 14 patients who received more than 75 mg had the disorder (35.7 percent; P less than 0.001). CONCLUSION. The addition of OKT3 to the immunosuppressive regimen increases the incidence of post-transplantation lymphoproliferative disorder after cardiac transplantation, and the risk increases sharply after cumulative doses greater than 75 mg. We suggest that the risks and benefits of prophylactic OKT3 administration be reassessed in the light of these findings, particularly since the value of prophylactic immunotherapy in cardiac-transplant recipients remains to be clearly established. 
Non-steroidal anti-inflammatory drugs and complicated diverticular disease: a case-control study. Fifty patients with severe complications of diverticular disease were compared with two groups of 50 controls, matched for age and sex. The first control group (A) was randomly selected from all emergency hospital admissions, and the second group (B) from patients with uncomplicated diverticular disease. Of the 50 study patients, 24 (48 per cent) were taking non-steroidal anti-inflammatory drugs (NSAIDs) at the time of admission compared with nine (18 per cent) of control group A and ten (20 per cent) of control group B. Both of these differences were statistically significant, indicating a strong association between the ingestion of NSAIDs and the development of severe complications of diverticular disease. 
Is there a link between fluoridated water and osteosarcoma? To test the hypothesis that fluoride is a risk factor for osteosarcoma, a case control study compared the complete residential fluoride histories of osteosarcoma patients with matched hospital-based controls. Fluoridation was not found to be a risk factor for osteosarcoma in the study population. The trend in the data from this small sample study suggests the hypothesis that a protective effect may exist against the formation of osteosarcoma for individuals consuming fluoridated water. 
Postoperative computed tomography study of pterygomaxillary separation during the Le Fort I osteotomy. Computed tomography (CT) was used postoperatively to assess the pterygomaxillary region in 12 orthognathic surgery patients who had had a Le Fort I osteotomy. Although pterygomaxillary separation was successful in all cases, in only 41.6% of the sides did fractures of the plate not occur. The incidence of low pterygoid plate fracture was 37.5% and that of high pterygoid plate fracture was 25%; 4.2% of sides showed a maxillary tuberosity fracture. Multiple fractures were observed in 8.3% of separated plates. Of 17 pterygoid plates judged clinically to be intact, only 10 were intact as assessed by CT. The significance of these findings and application of CT to evaluation of modifications to the Le Fort I osteotomy is discussed. 
Inhibition of interferon-inducible gene expression by adenovirus E1A proteins: block in transcriptional complex formation. Infection with wild-type adenovirus 5, but not with a mutant lacking the E1A gene, prevented the induction by interferon (IFN) alpha of chloramphenicol acetyltransferase (CAT) activity in HeLaM cell lines that had been permanently transfected with chimeric CAT reporter genes driven by the transcriptional regulatory regions of the IFN-responsive genes 561 and 6-16. Similar inhibition of IFN-inducible CAT activity was observed in cells that were cotransfected with the same reporter genes and plasmids expressing either the E1A 289- or 243-amino acid protein. These proteins also prevented the induction of CAT activity by IFN-gamma from a cotransfected HLA-DR alpha-CAT gene. Experiments with E1A mutants mapped the inhibitory activity to amino acid residues 38-65 of these proteins. In a HeLa cell line permanently expressing the E1A 289-amino acid protein, the replication of vesicular stomatitis virus and encephalomyocarditis virus was not inhibited by IFN-alpha, suggesting a global blockade of IFN responses. In accord with this theory, induction of 561, 1-8, and (2'-5')oligoadenylate synthetase mRNAs by IFN was blocked in these cells at the transcriptional level. The observed transcriptional inhibition could be attributed to the lack of formation of the crucial IFN-stimulated gene factor 3 (ISGF3) transcriptional complex. As shown by mobility shift assays, this complex was not formed in the nuclear extracts of IFN-treated adenovirus-infected cells or IFN-treated E1A-producing cells. These nuclear extracts were deficient in both ISGF3 alpha and ISGF3 gamma subunits. However, they did not block the formation of ISGF3 complex from exogenously added components. 
Acute airway obstruction in relapsing polychondritis: treatment with pulse methylprednisolone. We describe 2 adolescents with relapsing polychondritis who developed acute airway obstruction. Both were successfully treated with intravenous steroids for this complication following failure with oral steroids. Early respiratory tract involvement in younger patients seems predictive of a poor outcome and aggressive therapy with intravenous high dose steroids and/or immunosuppressive drugs appears to be indicated. 
Screening dyspepsia by serology to Helicobacter pylori. Owing to limited endoscopy resources, various screening strategies for endoscopy have been proposed. Helicobacter pylori can be detected with high sensitivity and specificity by serology, and therefore we assessed the effects on diagnostic accuracy and endoscopic workload of a policy of screening clinic patients with dyspepsia before endoscopy by a strategy based on age, Helicobacter pylori serology, and use of non-steroidal anti-inflammatory drugs. 1153 patients were studied, of whom 842 were of known histological H pylori status (histology group) and 293 had serum assessed prospectively by in-house and commercial ELISAs for detection of IgG antibodies to H pylori. Overall, the screening strategy would have reduced endoscopy workload by 23.3% (95% confidence interval 20.9-25.8%) and would have had a sensitivity for detection of peptic ulcer of 97.4% (94.5-99.1%). No peptic ulcer or malignant disease was missed in the patients studied prospectively, but 6 of 192 peptic ulcers in the histology group would have been missed. A policy of screening young dyspeptic patients for H pylori by serology is more sensitive than symptom-based screening strategies, and may have an important role in reducing endoscopy workload. 
Use of secondary prophylaxis against myocardial infarction in the north of England OBJECTIVE--To record the use of secondary prophylactic drugs in patients discharged from hospital having had a myocardial infarction. DESIGN--Prospective postal questionnaire survey of a random one in two sample of general practitioners in the region. SETTING--The nine family practitioner committee areas within the Northern Regional Health Authority. PATIENTS--Patients who had had a myocardial infarction and were discharged to their general practitioner. MAIN OUTCOME MEASURE--Whether beta blockers or aspirin, or both, were given on discharge. RESULTS--Of 267 patients, 158 (59%) were treated suboptimally in that they did not receive a secondary prophylactic drug to which they had no contraindication. For most patients this entailed underuse of one drug, but 17 (6%) of patients received no treatment. beta Blockers were 2.5 times less likely to be used than aspirin. Treatment was not associated with the age or sex of the patient, risk of further infarction, or hospital of discharge. CONCLUSIONS--Secondary prophylaxis after myocardial infarction is practised haphazardly. It should be offered to all patients who can tolerate it, after a trial period to assess any side effects of the drugs if necessary. 
Management of the medial canthal tendon in nasoethmoid orbital fractures: the importance of the central fragment in classification and treatment. The medial canthal tendon and the fragment of bone on which it inserts ("central" fragment) are the critical factors in the diagnosis and treatment of nasoethmoid orbital fractures. The status of the tendon, the tendon-bearing bone segment, and the fracture pattern define a clinically useful classification system. Three patterns of fracture are appreciated: type I--single-segment central fragment; type II--comminuted central fragment with fractures remaining external to the medial canthal tendon insertion; and type III--comminuted central fragment with fractures extending into bone bearing the canthal insertion. Injuries are further classified as unilateral and bilateral and by their extension into other anatomic areas. The fracture pattern determines exposure and fixation. Inferior approaches alone are advised for unilateral single-segment injuries that are nondisplaced superiorly. Superior and inferior approaches are required for displaced unilateral single-segment injuries, for bilateral single-segment injuries, and for all comminuted fractures. Complete interfragment wiring of all segments is stabilized by junctional rigid fixation. All comminuted fractures require transnasal wiring of the bones of the medial orbital rim (medial canthal tendon-bearing or "central" bone fragment). If the fracture does not extend through the canthal insertion, the canthus should not be detached to accomplish the reduction. 
PAF-induced bowel necrosis. Effects of vasodilators. Ischemic bowel necrosis in the rat is produced by injecting platelet-activating factor (PAF) intravenously. Since intestinal hypoperfusion is observed after PAF injection, we hypothesize that mesenteric vasoconstriction is the mechanism of bowel injury. We thus studied the effects of vasodilators in this model. We found that: (1) Phenoxybenzamine, prazosin, ICI 198615 (leukotriene antagonist) and PGE1 counteracted the PAF-induced mesenteric flow reduction and ameliorated the bowel injury. However, phenoxybenzamine and prazosin were relatively ineffective in correcting PAF-induced hypotension, showing that bowel injury can be prevented independently of the hypotensive state. (2) Nitroglycerin failed to prevent bowel injury, although it improved the mesenteric blood flow. Thus, in opposition to our initial hypothesis, correction of the mesenteric flow reduction induced by PAF does not always prevent intestineal necrosis. (3) Only phenoxybenzamine, prazosin, ICI 198615, and PGE1 ameliorated PAF-induced hemoconcentration and bowel injury. This suggests a correlation between vascular injury (expressed by "leaky" vessels and the consequent hemoconcentration) and bowel necrosis. (4) Although both nitroglycerin and hydralazine relax smooth muscle, hydralazine seemed to aggravate bowel necrosis. The mechanism remains unclear. 
Greater loop chloride uptake contributes to blunted pressure natriuresis in Dahl salt sensitive rats. A blunted pressure natriuretic response is present in Dahl salt sensitive rats. To determine whether this results from tubular or glomerular mechanisms, late proximal, early distal, and late distal micropuncture were performed in salt resistant (R), salt sensitive (S), or salt sensitive rats with renal perfusion reduced to that of R rats (S-AC). Differences in neuro-endocrine background between groups were eliminated by renal denervation and by fixing plasma aldosterone, norepinephrine, and vasopressin levels by infusion. Renal perfusion pressure was greater (P less than 0.05) and inulin clearance less (P less than 0.05) in S than R rats. Urinary sodium excretion, however, was not different. S-AC had renal perfusion pressures that were similar to R rats and inulin clearance similar to S rats. Urinary NaCl excretion was less (P less than 0.05) than either group. Single nephron inulin clearance, fluid, and chloride delivery to late proximal sites were not different between groups. Absolute and fractional chloride delivery to early distal sites was less (P less than 0.05) in S-AC than R or S but not different between R and S. Late distal chloride delivery was not different between any group. Calculated loop chloride reabsorption was greater in S-AC than R or S. Thus, the lower urinary NaCl excretion in S-AC rats is in part due to increased loop chloride reabsorption. This effect is probably intrinsic to the S kidney as it occurs despite renal denervation when plasma levels of vasopressin, norepinephrine, and aldosterone are fixed. The increased loop chloride uptake is abolished when perfusion pressure increases. 
Fistula-in-ano in Crohn's disease. Results of aggressive surgical treatment. The outcome of aggressive surgical treatment of 64 symptomatic anal fistulas in 55 patients with Crohn's disease has been studied. Forty-one fistulas, in 33 patients, were treated by conventional fistulotomy (17 subcutaneous, 19 intersphincteric, 5 low transsphincteric fistulas). Thirty wounds (73 percent) healed within 3 months and eight more wounds (93 percent) healed within 6 months. Three wounds did not heal within 12-18 months. Two of these patients subsequently required proctocolectomy. Wound healing was not influenced by the presence of rectal Crohn's disease or granulomatous inflammation in the tract. No change in continence was experienced by 26 of the 33 patients who underwent fistulotomy. Three patients required proctocolectomy and the remaining four patients experienced minor degrees of incontinence postoperatively. Sixteen high transsphincteric, five suprasphincteric, and one extrasphincteric fistula in 22 patients were treated by laying open external tracts and placing a noncutting seton through the sphincter, which was left in place for prolonged periods to maintain drainage. During follow-up (6 months to 10 years, median 2.5 years), three fistulas healed and seven remained quiescent. Nine patients required further treatment by a new seton and three patients required proctocolectomy. Eight of the 22 patients who had a seton inserted had no change in continence, and six patients in this group developed minor changes in continence, mostly related to diarrhea associated with intestinal disease. Anal fistulas in Crohn's disease, which involve minimal sphincter muscle, can be successfully treated by fistulotomy. High fistulas should be treated with seton drainage to limit recurrent suppuration and preserve sphincter function. 
Clinical applications of carbon dioxide/digital subtraction arteriography. During an 18-month period 33 patients in whom there were contraindications to the use of iodinated contrast arteriography underwent 40 carbon dioxide/digital subtraction arteriograms for lower extremity ischemia (19), severe hypertension and renal insufficiency (12), or arterial aneurysm (2). Contraindications to iodinated contrast agents included renal insufficiency, congestive heart failure, and contrast hypersensitivity. Sixteen aortic, 15 iliac-femoral-popliteal-tibial, five aorta-iliac-femoral and four aorta-iliac-femoral-popliteal-tibial carbon dioxide/digital subtraction arteriography studies were performed. In 11 studies, imaging of selected arterial segments required the addition of 10 to 60 ml of dilute nonionic contrast. Guided by carbon dioxide/digital subtraction arteriography studies four femoral-tibial bypasses, three aneurysmorrhaphies, two aortorenal bypasses, one aortofemoral bypass and one femoral-femoral bypass were successfully performed in 11 patients. In addition, carbon dioxide/digital subtraction arteriography directed angioplasties of the common iliac (4), superficial femoral (6), popliteal (3), or tibioperoneal trunk (1) were performed in 10 patients. Complications of carbon dioxide/digital subtraction arteriography included transient deterioration in renal function in three patients in whom 20 ml of nonionic contrast was used, a nonfatal myocardial infarction after a popliteal percutaneous transluminal angioplasty in one patient, and transient tachypnea and tachycardia during a carbon dioxide/digital subtraction arteriography study in one patient. Diagnostic arteriograms are obtainable using carbon dioxide as the contrast agent. Carbon dioxide/digital subtraction arteriography permits patients with symptomatic arterial disease at high risk for contrast related complications to safely undergo arteriography and subsequent arterial reconstruction or endovascular intervention. 
Myocardial perfusion imaging with thallium-201 to evaluate patients before and after percutaneous transluminal coronary angioplasty. Thallium-201 imaging may be used to help determine the distribution and amount of myocardium in jeopardy and the success of revascularization after percutaneous transluminal coronary angioplasty. Single photon emission computed tomography is particularly advantageous because of its ability to differentiate vascular territories and thus evaluate patients with multivessel disease. Myocardial infarction resulting from complications such as distal embolization and side-branch occlusion can be detected. Thallium-201 imaging early after angioplasty may show abnormal results caused by transiently insufficient coronary flow reserve. However, studies performed 6 weeks or more after angioplasty accurately detect early restenosis and may identify those individuals likely to become symptomatic and eventually develop restenosis in the future. 
Comparative experience with smooth and polyurethane breast implants using the Kaplan-Meier method of survival analysis. Smooth-walled silicone implants have been widely used in breast surgery. Capsular contracture, causing undesirable firmness and spherical deformity, has been a common problem. Recent studies suggest that polyurethane-covered breast implants are associated with a lower incidence of capsular contracture. The statistical methodology employed in some of these studies, however, may be subject to criticism. Between July of 1984 and June of 1990 (72 months), 427 polyurethane breast implants were used in 279 patients and 439 smooth prostheses were used in 250 patients for a variety of aesthetic and reconstructive procedures. The occurrence of capsular contracture was carefully monitored and then analyzed using the Kaplan-Meier method of survival analysis. This method is particularly well suited to analysis of these types of clinical data because it allows for the fact that contractures occur at varying intervals after surgery and that follow-up of patients is incomplete. The probability of capsular contracture with smooth-walled prostheses was found to be significantly greater than with polyurethane-covered implants in each group of patients studied (p less than 0.05). Other complications occurred at a similar rate regardless of prosthesis type. This study supports the belief that polyurethane breast implants have a lower contracture rate; furthermore, it introduces the Kaplan-Meier method for analyzing the outcome of alternative plastic surgical therapies. 
Limb-sparing surgery in skeletally immature patients with osteosarcoma. The use of an expandable prosthesis. Limb-sparing surgery has a definite role in the treatment of osteosarcoma in children. Increased survival, however, raises problems of limb-length discrepancy and prosthetic longevity. The concept of an expandable adjustable prosthesis addresses the problem of leg-length discrepancy. The problem of prosthesis longevity will require further long-term evaluation of current designs and methods of fixation, as well as the development of a permanent prosthesis or biologic replacement. At skeletal maturity, the expandable prosthesis may either be maintained or substituted with another implant or biological alternative if warranted by the clinical situation. 
Idiopathic myointimal hyperplasia of mesenteric veins. Nonthrombotic occlusion or stenosis of the mesenteric veins is a rare cause of intestinal ischemia that usually occurs in association with systemic vasculitis. The current report includes four male patients with segmental ischemic colitis caused by idiopathic myointimal hyperplasia in the small mesenteric veins and their intramural branches; neither vasculitis nor arterial involvement were present. Three of the four patients were less than or equal to 38 years of age; the fourth was 67. All four patients were previously healthy and had no history of drug use of any kind. Clinical findings included abdominal pain, diarrhea, bloody stools, and colonic strictures discovered by barium enema. The intima of the mesenteric and intestinal mural veins was focally thickened by a marked increase in cells and matrix between the endothelium and internal elastic lamina, whereas the vessel walls external to the thickened intima appeared normal. Histochemistry and immunoreactivity with antibodies to muscle-specific actins (HHF-35) disclosed that the intimal thickening was caused by proliferation of smooth muscle cells in a proteoglycan matrix. All patients recovered completely after segmental resection of the ischemic portion of the colon and had no recurrence of intestinal symptoms on follow-up of up to 7 years. These unusual venous lesions do not appear to have been previously described; their etiology and pathogenesis remain unknown. 
In situ human papillomavirus (HPV) genotyping of cervical intraepithelial neoplasia in South African and British patients: evidence for putative HPV integration in vivo. In South Africa asymptomatic wart virus infection diagnosed by morphological criteria occurs in 16-20% of all ethnic groups; the incidence in black women is 66%. To identify human papillomavirus (HPV) types the prevalence of HPV in cervical intraepithelial neoplasia (CIN) in South African women (n = 72) with age matched British women (n = 73) was compared by non-isotopic in situ hybridisation (NISH) using digoxigenin labelled probes for HPV 6, 11, 16, 18, 31, 33 and 35 on archival biopsy specimens. A higher proportion of British biopsy specimens (68%) contained HPV than those from South Africa (50%) in CIN 2 and 3; this difference was due to HPV 16. Thirty six per cent of the positive biopsy specimens from South African women also contained HPV 33/35 compared with 16% in the United Kingdom. There was no difference in HPV detection with age in either group. These data indicate that HPV types vary geographically, with "minor" HPV types being more common in South Africa. Three qualitatively distinct NISH signals were observed; a diffuse (type 1) signal in superficial cells, mainly koilocytes; a punctate signal (type 2) in basal/"undifferentiated" cells in CIN 3; and combined type 1 and 2 signals in CIN with wart virus infection (type 3). The punctate signal may represent HPV integration. 
A controlled study of caudal epidural injections of triamcinolone plus procaine for the management of intractable sciatica. The management of sciatica due to lumbar nerve root compromise remains controversial, probably because few well-controlled studies of conservative management have been performed. This preliminary study assesses the efficacy of epidural injections of 80 mg triamcinolone acetonide plus 0.5% procaine hydrochloride in saline, administered via the caudal route, in a double-blind, placebo controlled trial with 1 year follow-up. Twenty-three patients were entered into the study: 12 received treatment and 11 placebo. The active group showed significant pain relief (P = 0.02) and a significant increase in mobility (P = 0.01) at 4 weeks, which resulted in improved quality of life (P = 0.02). At 1 year, subjective and objective measures improved in both groups. The improvement was greater in the actively treated group, but only the objective assessment (straight leg raise) was statistically significant. 
A prospective study of incisional time, blood loss, pain, and healing with carbon dioxide laser, scalpel, and electrosurgery. Carbon dioxide laser incisions are reported to be less painful, less bloody, and less prone to seroma formation and to heal better than scalpel or electrosurgical incisions. We compared all three modalities in a prospective randomized study of cholecystectomy incisions. Time required for the incision and incisional blood loss was less with electrosurgery than with the carbon dioxide laser or scalpel. Postoperative pain and wound healing, however, were the same for all three techniques. The carbon dioxide laser appears to offer no advantage over conventional means of making a standard incision. 
Glial swelling following human cerebral contusion: an ultrastructural study. The ultrastructural features of cerebral contusion seen three hours to 11 days after head injury were studied in 18 patients undergoing surgery. Massive astrocytic swelling ("cytotoxic" oedema) was seen three hours to three days after injury, maximal in perivascular foot processes, and compressing some of the underlying capillaries. The tight junctions were not disrupted. Neuronal damage was most marked three to 11 days after injury. The pathophysiological mechanisms leading to oedema formation and neuronal degeneration are discussed. 
Extraperitoneal approach for repair of inflammatory abdominal aortic aneurysm. Inflammatory abdominal aortic aneurysms are characterized by dense perianeurysmal fibrosis involving the adjacent organs. Attempts to isolate the aneurysm can lead to operative injuries of these structures, thus increasing the rates of complications and mortality. In the last 12 years 45 patients with inflammatory abdominal aortic aneurysms underwent aneurysm resection at the Department of Vascular Surgery of the University of Rome. The aneurysm was resected through a standard, midline transperitoneal approach in 39 patients, through a thoracophrenolaparotomy in two patients, and through a left-flank extraperitoneal approach in the last four patients. The extraperitoneal approach simplified aneurysm dissection and aortic clamping with no cases of postoperative morbidity or death. In addition, we reviewed the CT scan findings of 12 patients surgically treated for inflammatory abdominal aortic aneurysm. The amount of fibrosis in the anterior wall of the aneurysm was greater than in the left posterolateral aspect (p = 0.008). We conclude that the left-flank extraperitoneal approach is the most anatomically advantageous route for repair of inflammatory abdominal aortic aneurysm. 
Induction of sustained patency after clot-selective coronary thrombolysis with Hybrid-B, a genetically engineered plasminogen activator with a prolonged biological half-life. BACKGROUND. Despite the utility of tissue-type plasminogen activator (t-PA) in eliciting coronary thrombolysis clinically, early reocclusion remains a problem, occurring despite anticoagulation in 5-30% of patients with initially successful recanalization. This study evaluated the utility of Hybrid-B, a molecular variant of t-PA with a prolonged half-life in the circulation, in eliciting coronary thrombolysis and maintaining patency in the presence of a continuing thrombogenic stimulus. METHODS AND RESULTS. In intact, anesthetized dogs, either 18 mg Hybrid-B over 30 minutes (n = 15) or 50 mg t-PA (Activase) over 60 minutes (n = 8) was administered starting 60 minutes after left anterior descending coronary artery occlusion was induced with a thrombogenic copper coil. Time to lysis averaged 54 +/- 26 (means +/- SD) minutes and 64 +/- 34 minutes with Hybrid-B and t-PA, respectively (p = NS). When Hybrid-B was administered as a bolus (20 mg over 1 minute) to induce a high initial concentration in blood, time to lysis was shortened markedly and averaged 15 +/- 5 minutes. Dogs given Hybrid-B by either infusion or bolus exhibited prolonged time to reocclusion (337 +/- 192 minutes compared with 192 +/- 125 minutes in dogs given t-PA, p less than 0.03), reflecting maintenance of a subthrombolytic but persistently active concentration of activator in blood. Despite the persistence of Hybrid-B in blood, concentrations of fibrinogen and alpha 2-antiplasmin were not depleted markedly and remained at 77 +/- 25 and 56 +/- 24%, respectively, of control values. CONCLUSIONS. Thus, Hybrid-B, a novel variant of t-PA with unique pharmacokinetic properties, elicits prompt, sustained, and clot-selective coronary thrombolysis. 
The use of masseter electromyography with electroneurography in the evaluation of facial paralysis. In the evaluation of facial paralysis, electroneurography provides a quantitative assessment of the degree of degeneration. Near the endpoint of degeneration, the facial musculature compound action potential may be contaminated by masseter artifact resulting from supramaximal stimulation. We propose the use of both masseter electromyography and electroneurography in the evaluation of advanced degeneration to better define the current level for supramaximal stimulation, to eliminate masseter artifact, and to more accurately assess the degree of facial nerve degeneration. 
Usefulness of weightlifting training in improving strength and maximal power output in coronary artery disease. The effects of 10 weeks (20 sessions) of combined weightlifting and aerobic training (n = 10) were compared with the effects of aerobic training alone (n = 8) on indexes of strength and aerobic exercise capacity in 18 men with coronary artery disease (CAD). Initial test performance was similar between groups. After aerobic training, the maximal load that could be lifted once only (1-repetition maximum) in single-arm curl, single-leg press and single-knee extension exercises increased by 13% (11.8 to 13.3 kg; p less than 0.01), 4% (97.0 to 101.0 kg; difference not significant) and 5% (28.2 to 29.7 kg; difference not significant), respectively; corresponding gains with combined weightlifting and aerobic training were 43% (12.2 to 17.4 kg; p less than 0.01), 21% (99.0 to 120.0 kg; p less than 0.01) and 24% (29.0 to 36.0 kg; p less than 0.01). After aerobic training, the initial 1-repetition maximum could be lifted an average of 4 times, compared with 14 times after combined training. Maximal progressive incremental cycle ergometer power output increased by 2% in the aerobic control group (1,088 to 1,113 kpm/min; difference not significant) and by 15% (1,030 to 1,180 kpm/min; p less than 0.05) in the experimental group. Cycling time at 80% of initial maximal power before attaining a Borg (0 to 10) rating of perceived exertion of 7 (very severe) increased by 11% (604 to 672 seconds; difference not significant) and by 109% (541 to 1,128 seconds; p less than 0.05) in the control and weight-trained patients, respectively. 
Neoplasms associated with pulmonary eosinophilic granuloma. We found a high prevalence of pulmonary and extrapulmonary neoplasms in patients with pulmonary eosinophilic granuloma (PEG) who were studied at our institution. Among 21 patients with PEG, 10 (48%) had associated benign (one patient) or malignant (nine patients) tumors. Patients with tumors were older at the time of diagnosis of PEG (48.9 vs 34.5 years). Tumors included three lung carcinomas, one pulmonary carcinoid tumor, two lymphomas, five extrapulmonary carcinomas, and one mediastinal ganglioneuroma. Two malignant neoplasms developed in each of two patients. Six tumors preceded, three followed, and three occurred concomitantly with the diagnosis of PEG. Slides from eight PEG-associated tumors and 18 control neoplasms from patients without PEG were also stained immunohistochemically for S100 protein. Four PEG-associated (50%) and 11 control (61%) tumors contained S100 protein-positive interstitial cells. Our study suggests, but does not prove, that there may be more than a random association between PEG and neoplasms. Cigarette smoking, moreover, is an important risk factor for both PEG and lung carcinomas. Our immunohistochemical findings indicate that S100 protein-positive cells in tumors usually bear little or no relationship to PEG. In patients with an underlying malignant neoplasm, PEG simulates pulmonary metastases clinically and, occasionally, histopathologically. 
One hundred patients with hepatic metastases from colorectal cancer treated by resection: analysis of prognostic determinants. One hundred patients with hepatic metastases from colorectal cancer underwent 'radical' liver resection from 1980 to 1989. At least 1 cm of normal parenchyma surrounded the tumour and no microscopic invasion of resection margins was evident. The disease was staged according to our own staging system. Lobectomy was performed in 50 patients and non-anatomical resection in the remainder. The postoperative mortality rate was 5 per cent and the major morbidity rate was 11 per cent. The actuarial 5-year survival rate for patients in stages I, II and III was 42 per cent, 34 per cent and 15 per cent respectively (P less than 0.001). The overall actuarial 5-year survival rate was 30 per cent. The prognostic importance of various patient and tumour variables was evaluated by univariate analysis and then by multivariate analysis. Age of patient, site of primary, disease-free interval between treatment of primary and of hepatic metastases, preoperative carcinoembryonic antigen levels, and number of metastases, did not relate to prognosis, while sex (P = 0.024), stage of primary (P = 0.026), extent of liver involvement (P less than 0.001), distribution of metastases (P = 0.01) and type of surgery (P = 0.028) significantly affected prognosis as single factors. Multivariate analysis revealed that only the extent of liver involvement and stage of the primary tumour were independent predictors of survival. We conclude that liver resection is effective in selected patients with hepatic metastases from colorectal cancer. In resectable patients it is not yet possible to formulate a clear prognosis based on clinical factors. The extent of liver involvement and the staging system used may be significant, although not absolute, indicators of outcome. 
Secondary erythrocytosis due to a cerebellar hemangioblastoma: demonstration of erythropoietin mRNA in the tumor. Cerebellar hemangioblastoma is a rare cause of secondary erythrocytosis. Although the erythrocytosis is a result of erythropoietin (Ep) stimulation, direct evidence of Ep synthesis by the tumor has been lacking. In an erythrocytotic patient with a cerebellar hemangioblastoma we found elevated levels of Ep in the tumor cyst fluid and for the first time demonstrated Ep mRNA in the tumor by Northern blotting. This finding confirms cerebellar hemangioblastoma as a site of ectopic Ep production. 
Midazolam use in the emergency department. Midazolam is a new imidazobenzodiazepine derivative that is two to three times as potent as diazepam, is water-soluble, has a rapid onset and short duration of action, and produces a profound amnestic effect. These properties make it an extremely useful drug for outpatient sedation. We performed retrospective review of midazolam use in a general emergency department over a one-year period. Midazolam was used in 120 patients, 71 men and 49 women, with an average age of 46 years. The average dose given was 3.4 mg, with a range of 1 to 10 mg. In 69 of the cases (57%) other drugs were administered, most commonly an opiate. There were only four adverse reactions. One patient developed urinary retention, one patient vomited, and two patients were somnolent for a prolonged period of time. There were no serious cardiovascular or respiratory problems. We conclude that midazolam is a safe drug to use in the emergency department. Close monitoring of the patient and the availability of airway support equipment are mandatory. 
Risk factors for falls as a cause of hip fracture in women. The Northeast Hip Fracture Study Group. BACKGROUND. Although even in the elderly most falls are not associated with fractures, over 90 percent of hip fractures are the result of a fall. Few studies have assessed whether the risk factors for falls are also important risk factors for hip fracture. METHODS. To examine the importance of risk factors for falls in the epidemiology of hip fracture, we performed a case-control study of 174 women (median age, 80 years) admitted with a first hip fracture to 1 of 30 hospitals in New York and Philadelphia. Controls, matched to the case patients according to age and hospital, were selected from general surgical and orthopedic surgical hospital services. Information was obtained by direct interview. RESULTS. As measured by the odds ratio, increased risks for hip fracture were associated with lower-limb dysfunction (odds ratio = 1.7; 95 percent confidence interval, 1.1 to 2.8), visual impairment (odds ratio = 5.1; 95 percent confidence interval, 1.9 to 13.9), previous stroke (odds ratio = 2.0; 95 percent confidence interval, 1.0 to 4.0), Parkinson's disease (odds ratio = 9.4; 95 percent confidence interval, 1.2 to 76.1), and use of long-acting barbiturates (odds ratio = 5.2; 95 percent confidence interval, 0.6 to 45.0). Of the controls, 44 (25 percent) had had a recent fall. The case patients were more likely than these controls to have fallen from a standing height or higher (odds ratio = 2.4; 95 percent confidence interval, 1.0 to 5.7). Of those with hip fracture the younger patients (less than 75 years old) were more likely than the older ones (greater than or equal to 75 years old) to have fallen on a hard surface (odds ratio = 1.9; 95 percent confidence interval, 1.04 to 3.7). CONCLUSIONS. A number of factors that have been identified as risk factors for falls are also associated with hip fracture, including lower-limb dysfunction, neurologic conditions, barbiturate use, and visual impairment. Given the prevalence of these problems among the elderly, who are at highest risk, programs to prevent hip fracture should include measures to prevent falls in addition to measures to slow bone loss. 
Tumor markers in cancer of the colon and rectum. The primary role that tumor markers for cancer of the colon and rectum have at this time is for postoperative surveillance of those patients resected for cure who are at risk for recurrence of the disease. Carcinoembryonic antigen (CEA) serum levels are followed by most surgeons prospectively after the potentially curative resection. This tumor marker has not been advocated as a screening test for these cancers; however, a preoperative CEA serum level is determined in those patients before the initial surgery for colon or rectal cancer. The serum level of CEA is mainly determined by tumor differentiation and stage of disease. If the CEA serum level begins to increase during the postoperative surveillance period, the recurrence of colon or rectal cancer must be suspected. Further investigations are then performed to identify the location and resectability of the recurrent disease. Monoclonal antibodies labeled with radioisotope are presently being used clinically to identify recurrence of colon and rectal cancer. Used in conjunction with elevated serum CEA levels (or other determinants of recurrent disease) these tumor markers can specifically identify site(s) of cancer recurrence. Theoretically, by attaching cancer-fighting agents (i.e., chemotherapeutic agents) to the monoclonal antibody, the site of tumor recurrence can be potentially treated, too. Hence, these "tumor-seeking missiles" may one day be used to treat cancer recurrence. 
Fluid collections developing after pancreatic transplantation: radiologic evaluation and intervention. The usefulness of real-time sonography, duplex sonography, computed tomography (CT), cystography, diagnostic aspiration, and percutaneous drainage in the diagnosis and treatment of peri-pancreatic-transplant fluid collections was retrospectively assessed in 46 recipients of extraperitoneal pancreatic transplants. Forty-four abnormalities were identified in the extraperitoneal space at sonography, including four pancreatic pseudocysts associated with malfunction of the pancreatic duct, seven abscesses, six hematomas, nine urinomas, six early postoperative fluid collections that spontaneously resolved, six cases of pancreatitis, and six cases of vascular occlusion. Sonography (including pulsed Doppler sonography) was the procedure of choice in detecting fluid collections and diagnosing pancreatitis, rejection, vascular thrombosis, and pancreatic duct malfunction. CT was diagnostic in four of six hematomas; cystography was diagnostic in seven of nine urinomas. Sonographically guided percutaneous intervention enabled three patients to avoid surgery and allowed optimal surgical planning for six patients. 
Reversible symptomatic biliary obstruction associated with ceftriaxone pseudolithiasis. Ceftriaxone, a third-generation cephalosporin, has been associated with the development of sludge or stones in the gallbladders of some patients treated with this medication. Such precipitates, which are usually reversible upon discontinuation of the drug, sometimes cause symptoms, have simulated acute cholecystitis, and have even led to cholecystectomy in some cases. We report the first known instance of biliary obstruction and secondary pancreatitis in association with reversible ceftriaxone-induced pseudolithiasis. 
Serosal invasion as the single prognostic indicator in stage IIIA (T3N1M0) gastric cancer. Prognostic factors of gastric cancer with positive serosal invasion and regional lymph node metastasis were evaluated by multivariate analysis. Sixty-seven patients with the T3N1M0 subgroup of stage IIIA disease were evaluated, in which 34.9 +/- 13.4 nodes were dissected in extended lymph node dissection, and 6.5 +/- 6.2 were metastatic. Routine postoperative systemic chemotherapy with mitomycin C and N1-(2'-tetrahydrofuryl)-5-fluorouracil was administered. With this approach, the 5-year survival rate of stage IIIA disease was 47.6%. By Cox proportional hazards model, diameter of serosal invasion was the only significant determinant of prognosis in the T3N1M0 subgroup. The predicted 5-year survival rate for 24 patients with serosal invasion less than 3.0 cm in diameter was 59.5%, compared with 11.5% for 38 patients with invasion of 3.0 cm or larger in diameter. The number of metastatic nodes and the type of operation (total gastrectomy or less than total gastrectomy) did not affect the prognosis. When gastric cancer has both positive serosal invasion and metastatic regional lymph nodes, the diameter of serosal invasion is the more important factor for predicting prognosis. 
Typing of Pseudomonas aeruginosa ear infections related to outcome of treatment. Of 142 patients with Pseudomonas aeruginosa (PSA) ear infections, 88 (62 per cent) had chronic otitis media and 54 (38 per cent) external otitis. Following serotyping and pyocin typing of their bacteria, and relating the type to outcome, patients could be divided into three groups: (1) 120 patients who had no recurrence with isolation of only one PSA strain, (2) 13 patients who had recurrent infections and in whom the same PSA strain was isolated in repeated cultures, and (3) nine patients who had recurrent disease, but who had a change in their PSA strains. Most of the PSA strains isolated from patients in groups (1) and (2) were stable to pyocin, and resistent to gentamicin. Patients in the first group were all cured initially by medical management. Of the nine patients in group (3) who had a different serotype on repeated cultures, medical treatment was successful in eight (89 per cent), but of the 13 patients in group (2) who had the same Pseudomonas aeruginosa serotype cultured, medical therapy failed in six (46 per cent) and mastoid surgery was required. Serotyping of Pseudomonas aeruginosa otitis may be helpful in predicting the type of management in patients who have recurrent infections. 
Deep UV photochemistry of chemisorbed monolayers: patterned coplanar molecular assemblies. Deep ultraviolet (UV) irradiation is shown to modify organosilane self-assembled monolayer (SAM) films by a photocleavage mechanism, which renders the surface amenable to further SAM modification. Patterned UV exposure creates alternating regions of intact SAM film and hydrophilic, reactive sites. The exposed regions can undergo a second chemisorption reaction to produce an assembly of SAMs in the same molecular plane with similar substrate attachment chemistry. The UV-patterned films are used as a template for selective buildup of fluorophores, metals, and biological cells. 
Positron tomographic assessment of 16 alpha-[18F] fluoro-17 beta-estradiol uptake in metastatic breast carcinoma. The positron-emitting estrogenic steroid 16 alpha-[18F]fluoro-17 beta-estradiol (FES) has been shown to exhibit selective uptake in primary breast carcinomas; the uptake of tracer by positron emission tomography (PET) is strongly correlated with the tumor estrogen-receptor concentration. We have now extended the use of this radiopharmaceutical for imaging of metastases of breast carcinoma by PET in 16 patients with clinical or radiographic evidence of metastatic disease. Increased uptake of FES was identified on PET images in 53 of 57 metastatic lesions (93%); only two apparent false-positive foci of FES uptake were seen. In seven of the patients, evaluable PET studies were obtained both before and after initiation of antiestrogen therapy. In all cases, there was a decrease in FES uptake in the tumor deposits after initiation of antiestrogen therapy, and the mean (+/- standard deviation) uptake decreased from 2.22 (+/- 1.23) to 0.80 (+/- 0.42) x 10(3)+ dose/ml. These results indicate that PET with FES has high sensitivity and specificity for detecting metastatic breast carcinoma and provide additional confirmatory evidence that the tumor uptake of this ligand is a receptor-mediated process. 
Acute dacryocystic retention cured by inferior turbinate infracturing. A 30-year-old man with recurrent acute dacryocystic retention had successful infracturing of the inferior turbinate bone in association with probing of the lacrimal outflow system. Enlargement of the inferior nasal meatus by fracturing the turbinate is easy to do and would be indicated before recommending a dacryocystorhinostomy in cases of acute dacryocystic retention in which the causative cast is difficult to eliminate even by large probes that can be passed down the nasolacrimal duct. 
Anti-CD18 antibody attenuates neutropenia and alveolar capillary-membrane injury during gram-negative sepsis. Activated polymorphonuclear leukocytes (PMNs) are implicated in the pathogenesis of acute lung injury (ALI) associated with sepsis. Adhesion of activated PMNs to endothelial monolayers is mediated by the CD18 adhesion-receptor complex on the PMN cell surface. Monoclonal antibody 60.3 (MoAb 60.3) blocks CD18-dependent PMN-endothelial adhesion in vitro and in vivo. This study was designed to determine the role of CD18-dependent PMN adhesion in ALI associated with gram-negative sepsis. Anesthetized, ventilated (FiO2 0.5, positive end-expiratory pressure 5 cm H2O) pigs received sterile saline (control, n = 8) or live Pseudomonas aeruginosa, 5 x 10(8) colony-forming units/ml at 0.3 ml/20 kg/min (septic, n = 9) for 1 hour. A third group (n = 7) received MoAb 60.3, 2 mg/kg intravenously, 15 minutes before Pseudomonas infusion. Animals were studied for 300 minutes. MoAb 60.3 significantly (p less than 0.05) attenuated the neutropenia seen in sepsis (15 +/- 1 vs 6 +/- 1 x 10(3) PMNs/mm3 at 300 min). Alveolar-capillary membrane injury was assessed by bronchoalveolar-lavage protein content and extravascular lung water determination. MoAb 60.3 significantly (p less than 0.05) reduced BAL protein at 300 minutes (388 +/- 75 vs 1059 +/- 216 micrograms/ml in septic animals) and attenuated the increase in extravascular lung water to 240 minutes (7.1 +/- 2 vs 14.2 +/- 1.2 ml/kg in septic animals). Systemic hypotension, decreased cardiac index, pulmonary hypertension, and relative hypoxemia, all characteristic of this model, were not altered by MoAb 60.3. These data suggest that, in this model of septic ALI, neutropenia is, in part, CD18 dependent and that blocking CD18-dependent PMN adhesion protects the alveolar-capillary membrane independently of altered hemodynamic status. 
Evidence for central alpha-2 adrenoceptors, not imidazoline binding sites, mediating the ethanol-attenuating properties of alpha-2 adrenoceptor antagonists. The role of central adrenoceptors in the ethanol-attenuating effects of alpha-2 adrenoceptor blockers was investigated in mice; the centrally active antagonist atipamezole was compared with L 659,066, which penetrates the brain poorly. L 659,066 (1-10 mg/kg) had no effect on the hypothermia induced by ethanol (2 g/kg) or ethanol ataxia (2.4 g/kg), whereas atipamezole (1 mg/kg) significantly attenuated both ethanol-induced hypothermia and ataxia. Atipamezole (1-3 mg/kg) significantly attenuated the ethanol-induced reduction in exploratory head-dipping in a holeboard test whereas L 659,066 was only effective at a dose of 1 mg/kg, higher doses (3 and 10 mg/kg) and a lower dose (0.3 mg/kg) were ineffective. Atipamezole was without effect on ethanol's locomotor stimulant effect in the holeboard but L 659,066 attenuated this effect at doses less than 3 mg/kg Many alpha-2 adrenoceptor ligands also have affinity for nonadrenergic imidazoline-binding sites. The role these sites may play in attenuating ethanol's effects was investigated by comparing RX 821002 (methoxy idazoxan), which has little or no affinity for imidazoline-binding sites with atipamezole. Both atipamezo 1 e (1 mg/kg) and RX 821002 (0.06-0.2 mg/kg) significantly attenuated ethanol-induced hypothermia, ataxia and reduction in head-dipping, but were without effect on ethanol-induced locomotor stimulation. These results suggest that nonadrenergic imidazoline-binding sites are not implicated in the ethanol-attenuating properties of alpha-2 adrenoceptor antagonists. 
Pulmonary oedema following relief of upper airway obstruction in the Pierre-Robin syndrome: a consequence of early palatal repair? Pulmonary oedema occurred following relief of an acute upper airway obstruction in an infant with Pierre-Robin syndrome undergoing cleft palate repair. We anticipate an increased prevalence of this phenomenon in view of the present trend for early palatal repair, and would advocate the routine use of a nasopharyngeal airway after operation in infants with severe micrognathia. 
Assessing the denominator problem in community-oriented primary care. Determination of health care needs is an essential cornerstone of community-oriented primary care (COPC). Many physicians, lacking research resources, may generalize their own patient registry data to the community. But practice populations are likely to differ significantly from community populations. This study compared demographics, health status, and medical care utilization in a sample of 990 elderly living in the community and 250 elderly patients registered at the St. Elizabeth Hospital Family Health Center in Youngstown, Ohio. The community survey and patient registries were comparable on key demographic characteristics. But statistically significant differences were observed for functional status and a number of chronic medical conditions. Comparisons of symptomatology, use of health aides, subjective health status, depression, and stress produced no significant differences. Overall health care utilization patterns were similar. The elderly family health center patients were more representative of the non-institutionalized elderly in the community than expected. And although the clinical significance remains uncertain, these findings suggest that this practice sample may be used with caution for COPC planning. But considerably more research must be undertaken in a variety of practice settings before the use of practice populations for COPC planning is widely applied. 
Comparison of thermodilution and transthoracic electrical bioimpedance cardiac outputs. Current methods of measuring cardiac output require the invasive insertion of a thermodilution catheter with its concomitant risks and complications. We examined the noninvasive method of transthoracic electrical bioimpedance (TEB) in comparison with thermodilution cardiac outputs in a sample of 44 critically ill patients with poor left ventricular function (left ventricular ejection fraction less than 30%) and with either ischemic or idiopathic dilated cardiomyopathy. Dyspnea, mitral regurgitation, tricuspid regurgitation, and difference between real and ideal weight had the most marked effects on the correlation between the two methods, with lesser influence by left ventricular ejection fraction, height, weight, hemoglobin, hematocrit, and aortic regurgitation. TEB and thermodilution cardiac outputs were correlated, at r = 0.51 (p less than 0.00009), but the low reliability and low percentage of TEB readings within 0.5 L/min of thermodilution cardiac outputs (31%) renders TEB inadequate for clinical measurement of cardiac outputs in this patient population. 
Rationale for treatment. Based on substantial evidence, the 1984 NIH Consensus Development Conference concluded that the treatment of total and low-density lipoprotein (LDL) cholesterol elevations with diet and, when necessary, with drugs, can reduce the risk of coronary artery disease (CAD). Accordingly, in 1988 the National Cholesterol Education Program (NCEP) published guidelines for defining moderate-, borderline-high-, and high-risk categories for CAD. Many clinical trials have supported the benefits of antihyperlipidemic therapy. Evidence from the Coronary Primary Prevention Trial gave rise to the "2:1 ratio," i.e., that a 1% reduction in total cholesterol level is associated with a 2% decrease in CAD events. The Helsinki Heart Study results indicated that additional benefit may be obtained by raising high-density lipoprotein (HDL)-cholesterol levels. Dramatic reductions in LDL and total cholesterol were achieved by the Program on the Surgical Control of the Hyperlipidemias, which also achieved a 35% reduction in CAD events and a two-thirds reduction in both coronary bypass operations and angioplasties. Long-term benefits of cholesterol lowering in terms of cardiovascular and all-cause mortality have been shown in the Coronary Drug Project and the Multiple Risk Factor Intervention Trial. Two major studies that have documented angiographic changes as a result of cholesterol lowering are the Cholesterol-Lowering Atherosclerosis Study (CLAS) and the Familial Atherosclerosis Treatment Study (FATS). In both CLAS and FATS, there was a decrease in the development of new lesions and a lowering of the rate of progression of existing lesions. In FATS, there was also evidence that aggressive antihyperlipidemic therapy will decrease existing lesions in some CAD patients. 
Postoperative radiotherapy in the management of spinal cord ependymoma. Fifty-eight patients with histologically verified spinal cord ependymomas were treated at the Royal Marsden Hospital and Atkinson Morley's Hospital between 1950 and 1987. The median age in this series was 40 years (range 1 to 79 years) and the male:female ratio was 1.8:1. Ten patients had tumors in the cervical cord and 10 in the thoracic cord; 14 tumors involved the conus medullaris and 24 the cauda equina. Forty ependymomas were grade I and 13 were grades II to IV (in five patients there was insufficient material for grading). Eleven patients underwent biopsy only, 33 had partial or subtotal resection, and 14 had complete resection. Forty-three patients received postoperative radiotherapy. The median follow-up period was 70 months (range 3 to 408 months). Cause-specific survival rates were 74% and 68% at 5 and 10 years, respectively. On univariate analysis, age, histological grade, postoperative neurological function, and era of treatment were significant prognostic factors for survival. The histological grade was the only significant independent prognostic factor. The relative risk of death from ependymoma was 9.0 for patients with tumor grades II to IV compared to grade I (p less than 0.005, 95% confidence interval 2.7 to 30). The survival rates of patients following complete excision were significantly better compared to those after incomplete surgery (p less than 0.025). The majority of completely resected neoplasms were low-grade cauda equina tumors. Despite incomplete surgery, 5- and 10-year progression-free survival rates following radical radiotherapy were both 59%, and cause-specific survival rates were 69% at 5 years and 62% at 10 years. This suggests that radiotherapy may achieve long-term tumor control in over half of those patients with residual spinal ependymoma. 
The morphometric histopathology of undescended testes and testes associated with incarcerated inguinal hernia: a comparative study. The underlying injury to undescended testes may be hormonal, a transient perinatal form fruste of hypogonadotropic hypogonadism characterized by blunting of the surge in gonadotropins normally seen at age 60 to 90 days. Ischemia is the underlying injury to testes associated with incarcerated inguinal hernias. To determine if the histopathology of these 2 injuries is different histomorphometric analyses were performed on semithin microscopic sections of biopsies of 21 control testes, 17 undescended testes and 13 intrascrotal testes associated with incarcerated inguinal hernias. The infants in all groups were 30 to 120 days old. The results showed that, as in previous studies, undescended testes at this age are characterized by hypoplasia of Leydig cells, normal germ cell counts and defective maturation of gonocytes into adult dark spermatogonia. In contrast, testes associated with incarcerated inguinal hernias were characterized by hyperplasia of Leydig cells, reduced germ cell counts and normal maturation of gonocytes into adult dark spermatogonia. One might conclude that the underlying injury of undescended testes, presumably the blunted surge of gonadotropins, causes a primary hypoplasia and hypofunction of Leydig cells, which in turn causes a secondary defect in transformation of gonocytes into spermatogonia. In contrast, ischemia may primarily cause a tubular epithelial lesion leaving the hypothalamic-pituitary-gonadal axis intact and allowing normal transformation of gonocytes into spermatogonia. Reduced gonadotropins and ischemia appear to produce distinctly different primary and secondary pathophysiological effects on the testes. 
Laser-assisted angioplasty in the treatment of prosthetic graft stenosis. Late failure of peripheral bypass grafts has been treated primarily by secondary reconstruction. Laser-assisted angioplasty is an optional therapy that the authors investigated in 28 prosthetic grafts over a two-year period. Twenty-five symptomatic patients with 28 peripheral prosthetic arterial bypass grafts (25 polytetrafluoroethylene [PTFE] grafts and 1 each of knitted Dacron, Teflon, and umbilical vein) demonstrated graft occlusion (25) or high-grade stenoses (3). All patients underwent standard laser-assisted angioplasty using a continuous wave Nd:YAG laser source and hybrid probe. Twenty-one grafts (75%) were successfully recanalized with adequate restoration of flow through the conduit. All 7 failures were in occluded PTFE grafts that presented with either recalcitrant lesions (5) or perforations (2) at the distal anastomoses. There have been 3 long-term failures (14%) to date in the successfully treated group, all in PTFE grafts. Two patients suffered recurrent thrombosis and 1 developed an inexplicable graft infection five months after laser treatment. Laser-assisted angioplasty appears to be a clinically viable alternative treatment for prosthetic graft stenosis and recanalization of grafts occluded at their distal anastomosis. 
In vivo use of a radioiodinated somatostatin analogue: dynamics, metabolism, and binding to somatostatin receptor-positive tumors in man Somatostatin analogues, labeled with gamma-emitting radionuclides, are of potential value in the localization of somatostatin receptor-positive tumors with gamma camera imaging. We investigated the application in man of a radioiodinated analogue of somatostatin, 123I-Tyr-3-octreotide, which has similar biologic characteristics as the native peptide. The radiopharmaceutical is cleared rapidly from the circulation (up to 85% of the dose after 10 min) mainly by the liver. Liver radioactivity is rapidly excreted into the biliary system. Until 3 hr after injection, radioactivity in the circulation is mainly in the form of 123I-Tyr-3-octreotide. Thereafter, plasma samples contain increasing proportions of free iodide. Similarly, during the first hours after injection, radioactivity in the urine exists mainly in the form of the unchanged peptide. Thereafter, a progressive increase in radioiodide excretion is observed, indicating degradation of the radiopharmaceutical in vivo. Fecal excretion of radioactivity amounts to only a few percent of the dose. The calculated median effective dose equivalent is comparable with values for applications of other 123I-radiopharmaceuticals (0.019 mSv/MBq). 
Myocardial echinococcosis with perforation into the pericardium. Though rare, cardiac echinococcosis should be included in the differential diagnosis of cardiac tumors, particularly in patients originating from endemic areas or with manifestation of hydatid disease in other organs. Diagnosis and localisation of the cysts is best accomplished with non-invasive methods such as 2-D transthoracic and transesophageal echocardiography, computed tomography and NMR. Excision of the cardiac cyst from the interventricular septum in a 21 year old patient with polyvisceral echinococcosis was performed with cardiopulmonary bypass. Adjunctive medical therapy with mebendazol is being continued for 24 months postoperatively. Twelve months after surgery the patient is asymptomatic without echocardiographic signs of recurrence. 
Vitamin B6 is effective therapy for nausea and vomiting of pregnancy: a randomized, double-blind placebo-controlled study. Fifty-nine women completed a randomized, double-blind placebo-controlled study of pyridoxine hydrochloride (vitamin B6) for the treatment of nausea and vomiting of pregnancy. Thirty-one patients received vitamin B6, 25-mg tablets orally every 8 hours for 72 hours, and 28 patients received placebo in the same regimen. Patients were categorized according to the presence of vomiting: severe nausea (score greater than 7) or mild to moderate nausea (score of 7 or less). The severity of nausea (as graded on a visual analogue scale of 1-10 cm) and the number of patients with vomiting over a 72-hour period were used to evaluate response to therapy. Twelve of 31 patients in the vitamin B6 group had a pre-treatment nausea score greater than 7 (severe) (mean 8.2 +/- 0.8), as did ten of 28 patients in the placebo group (mean 8.7 +/- 0.9) (not significant). Following therapy, there was a significant difference in the mean "difference in nausea" score (ie, baseline - post-therapy nausea) between patients with severe nausea receiving vitamin B6 (mean 4.3 +/- 2.1) and placebo (mean 1.8 +/- 2.2) (P less than .01). In patients with mild to moderate nausea and in the group as a whole, no significant difference between treatment and placebo was observed. Fifteen of 31 vitamin B6-treated patients had vomiting before therapy, compared with ten of 28 in the placebo group (not significant). At the completion of 3 days of therapy, only eight of 31 patients in the vitamin B6 group had any vomiting, compared with 15 of 28 patients in the placebo group (P less than .05). 
Effect of otitis media on infrared tympanic thermometry. This study was designed to determine if temperature readings using a new tympanic thermometer are affected by otitis media. These readings were also compared to a rectal or oral temperature. Eighty-four children with unilateral suppurative or non-suppurative otitis media diagnosed clinically by their pediatricians were enrolled in the study. Temperatures were measured in both ears using the Thermoscan PRO-1 Instant Thermometer and rectally or orally by a glass or electronic predictive thermometer. For 67 children with unilateral suppurative otitis media the mean temperature in infected ears was 0.38 degrees Fahrenheit higher than in uninfected ears (p = .005). Neither temperatures measured in affected nor those from unaffected ears differed significantly from oral or rectal control readings. For 17 children with unilateral non-suppurative otitis media there was no statistically significant difference between temperatures in affected and unaffected ears or between the temperatures in either ear and the oral or rectal control. Our data show that temperatures taken in ears with suppurative otitis media are slightly higher than those in normal ears. This difference is of minimal clinical significance and does not affect the accuracy when compared to oral or rectal control readings. 
Electrophysiologic analysis of early Parkinson's disease. We have been interested in the application of quantitative measures of motor performance as a possible means of early detection of Parkinson's disease. To assess motor function, we have measured movement time (the physiologic correlate of bradykinesia) and reaction time (simple and directional choice) with an upper limb motor task, and tremor with accelerometry and electromyographic recordings. In this report we describe preliminary data from a Parkinson's disease patient group with symptoms of fewer than 2 years' average duration (compared with an age- and gender-matched normal control group) which indicate that precise, quantitative tests of motor function can detect the slight deviations from normal that are present in early Parkinson's disease. It appears that tests of bradykinesia are most sensitive, and detection of rest tremor is most specific. These tests may be applicable in screening individuals who are suspected of having or are "at risk for" Parkinson's disease and other related disorders. 
Inguinal endometriosis: pathogenetic and clinical implications. In six women with a preoperative diagnosis of incarcerated hernia, surgical exploration of the groin revealed inguinal endometriosis and no hernia. The affected structure was always the extraperitoneal portion of the round ligament. Six of the seven lesions were on the right. Intraperitoneal endometriosis was demonstrated in all patients. Catamenial pain was the pathognomonic symptom in the differential diagnosis of the inguinal mass. Gynecologists and surgeons should bear in mind the possibility that endometriosis may be the cause of symptoms of a suspected incarcerated inguinal hernia. Should this disease be detected at inguinal exploration, a laparoscopy is indicated during the same operation. 
Malignant hepatic tumors: P-31 MR spectroscopy with one-dimensional chemical shift imaging. To determine the clinical feasibility and applicability of phosphorus-31 magnetic resonance (MR) spectroscopy and to assess its potential for characterization of human hepatic tissue, one-dimensional chemical shift imaging (CSI) was performed in 37 patients with various malignant hepatic neoplasms (30 metastases from a variety of primary tumors and seven hepatocellular carcinomas) and seven healthy volunteers. Tumors were grouped according to the percentage of the analyzed section that was occupied by tumor: less than 50% (group A) or more than 50% (group B). In group B, all phosphomonoester/beta-adenosine triphosphate ratios were significantly higher than normal (P less than .001). Hepatocellular carcinomas and metastases from various primary neoplasms could not be differentiated on the basis of spectral characteristics and metabolite ratios. Limitations of one-dimensional surface coil CSI prevented separation of spectra of small tumors and tumors deep within the liver parenchyma from spectra of normal liver parenchyma. 
Monocyte zinc and in vitro prostaglandin E2 and interleukin-1 beta production by cultured peripheral blood monocytes in patients with Crohn's disease. This study investigated the relationship between zinc status and prostaglandin E2 and interleukin-1 beta production by cultured monocytes in patients with Crohn's disease. Monocyte zinc was significantly decreased in both 12 inpatients and 22 outpatients compared with controls (P less than 0.001) but lymphocyte and polymorphonuclear cell zinc were normal. When cultured monocytes from 10 outpatients with Crohn's disease were stimulated with lipopolysaccharide, prostaglandin E2 production increased markedly, coupled with a fall in monocyte zinc. In matched controls, prostaglandin E2 production was significantly less and monocyte zinc remained stable. No difference in interleukin-1 release was noted between patients and controls. The addition of prednisolone to cell cultures suppressed prostaglandin E2, interleukin-1 synthesis, and monocyte zinc did not change. Zinc chloride augmented prostaglandin E2 production in patients, but not controls, and interleukin-1 remained stable. These results demonstrate a link between low monocyte zinc concentration and excessive prostaglandin production in patients with Crohn's disease. 
Depression and chronic fatigue in the workplace. Workers' compensation and occupational issues. There is ample evidence that some forms of depression can be caused or aggravated by work. The relationship of work and chronic fatigue syndrome is questionable, but elements at work can aggravate the symptoms of chronic fatigue syndrome. The role of physicians who can support or discourage beliefs about physical illness is all important, both by what they say and how they treat. In the process of interaction, they can promote or discourage disability. The role of the physician in the workplace is to determine if an illness is work related, if it is disabling, if it requires treatment, and what treatment. The physician must advise if the worker can continue in his or her usual and customary employment and, if not, if he or she can be vocationally rehabilitated from a medical standpoint. Conditions in which physical symptoms are unsupported by physical findings and have diagnostic labels that describe the disorder without indicating either cause or pathology are especially troubling for the physician who must decide if the patient's job caused the symptoms. 
Practice patterns and costs of hospitalization for upper gastrointestinal hemorrhage. We conducted an observational study at three hospitals in Boston to examine the patterns of practice and the costs involved in the medical management of noncirrhotic, upper gastrointestinal bleeding. A total of 111 patients were identified and studied: 42 from hospital 1, 38 from hospital 2, and 31 from hospital 3. There were no significant differences in the management of the patients, except for the more frequent use of upper gastrointestinal radiography at hospital 3 and the more frequent use of cimetidine at hospital 2. Only a small percentage (3-7%) of patients required surgery, and overall mortality (0-8%) was low. The average cost of hospitalization, determined by using the New England Medical Center cost model, was calculated for direct costs ($3,180). The majority of costs incurred were for hospital bed or intensive care unit stay (63%) and transfusion of blood products (14%), with costs for physicians' services (9%), endoscopy (2%), and upper gastrointestinal radiography (1%) accounting for only a small percentage. This study demonstrates remarkable similarity in practice patterns and resource utilization at three different hospitals and provides data on the actual costs involved in hospitalization for noncirrhotic, upper gastrointestinal hemorrhage. 
Surgical correction of coarctation in early infancy: does surgical technique influence the result? Between 1979 and 1988, a total of 53 infants less than 1 year of age underwent repair of coarctation. Thirty-seven patients (70%) were younger than 3 months. Median age was 0.9 month. Four different surgical techniques were used: resection with end-to-end anastomosis, patch enlargement, subclavian flap aortoplasty, and subclavian displacement aortoplasty (Meier-Mendonca technique). Hospital mortality was 7.5% and was limited to patients with additional complex intracardiac defects. Neither age nor surgical technique had an influence on the operative risk. Follow-up averaged 15 to 43 months for the four different groups. Restenosis developed in 9 (19%) of 47 patients regularly followed up, 5 (11%) of whom have had reoperation. Age at operation was not a predictor for restenosis, which occurred in 17.4% of patients less than 1 month and 20.8% of those greater than 1 month of age at operation. Patch enlargement and the subclavian displacement technique demonstrated the highest restenosis rates (42% and 43%, respectively). However, patients who underwent patch enlargement had less favorable pathological conditions. It is concluded that results of coarctation repair in early infancy do not depend as much on the operative method itself as on the specific pathological aspect, which largely determines the method of treatment. Some reservation must be made in regard to the subclavian displacement technique. 
Characterization of target injury of murine acute graft-versus-host disease directed to multiple minor histocompatibility antigens elicited by either CD4+ or CD8+ effector cells. The precise identity of effector mononuclear cells capable of eliciting acute graft-versus-host disease (AGVHD) is controversial. In this study, highly purified subsets of donor T cells were used to produce AGVHD to multiple minor histocompatibility (H) antigens in two strain combinations of mice matched for the major histocompatibility complex (MHC). In the C3H.SW- greater than B6 strain combination, only CD8+ effector cells produced histologic evidence of AGVHD in skin and liver, which peaked 3 weeks after transplant. In the B10.D2- greater than DBA/2 strain combination, CD4+ effector cells, and to a lesser extent, CD8+ cells, mediated disease in skin, liver, and intestine, which peaked during the fourth week after transplant. Analysis of skin and liver from both combinations showed target cell injury that was phenotypically similar and resembled that previously described in human disease in other studies. In addition, prominent epithelial injury also was detected in oropharyngeal mucosa, esophagus, hepatobiliary ducts, and seminal vesicle in both transplant settings. These findings indicate that functionally different subsets of donor T cells may be capable of initiating common pathways of cellular injury in selected target sites in AGVHD, and have potential implications for strategies that seek to ablate disease development by manipulation of donor marrow before transplantation. 
Diarrhea, respiratory infections, and growth are not affected by a weekly low-dose vitamin A supplement: a masked, controlled field trial in children in southern India. Incidence, duration, and severity of diarrhea and respiratory symptoms were monitored weekly for 1 y in 15,419 children 6-60 mo of age in a randomized, placebo-controlled, masked clinical trial conducted in southern India. Half the children received weekly doses of 8.7 mumol (2500 microgram) vitamin A and 46 mumol (20 mg) vitamin E (treated) and the other half, 46 mumol vitamin E (control). Medical and ocular examinations and anthropometric measurements were obtained before and after 52 wk of intervention. Ocular examinations also were obtained after 26 wk. Supplements were delivered weekly from calibrated dispenser bottles by community health volunteers who also recorded each mother's recall of daily morbidity of her child during the previous week. Baseline characteristics of treated and control subjects were similar and documented a prevalence of 11% xerophthalmia and 72% undernutrition. Weekly treatment with the low-dose vitamin A supplement did not influence the incidence, severity, or duration of diarrhea or respiratory infections and did not influence linear or ponderal growth. 
Alcoholism in women. Women differ from men in their drinking patterns and in the biologic consequences of alcohol use. Women more often drink at home and conceal their drinking behavior. Because women have a higher percentage of body fat and a lower percentage of body water than men, the same amount of alcohol causes more severe toxic effects in women than in men. Heavy alcohol consumption in women is associated with gynecologic dysfunction and fetal alcohol syndrome. Depression, anxiety or other psychiatric illness is also common in women alcoholics. Family physicians should be alert to the subtle behaviors that suggest alcoholism and be familiar with the available community resources and treatment options. 
Transperineurial vessel constriction in an edematous neuropathy. The hypothesis that the accumulation of endoneurial edema can exert forces sufficient to occlude transperineurial vessels was tested using light microscopy and computer-assisted morphometry in rat sciatic nerve. Experimental nerves were exposed to a concentration of 10% procaine HCl, which from previous studies has been demonstrated to routinely produce an edematous neuropathy. For each vessel, a "constriction ratio" was defined by dividing its minimum intraperineurial lumen area by the average for minimum endoneurial and epineurial lumen cross-sectional areas. Constriction ratios were 0.91 +/- 0.26 (mean +/- SD) for control vessels and 0.28 +/- 0.25 for vessels in the procaine group (p less than 0.005). In addition, a strong negative correlation was observed between the morphologic demonstration of nerve edema and the transperineurial vessel constriction ratio (r = -0.85; p less than 0.002). It is concluded that in neuropathies characterized by widespread edema and increased endoneurial fluid pressures, the concomitant constriction of transperineurial vessels could diminish nerve blood flow and facilitate nerve injury. 
Successful long-term control of idiopathic hypereosinophilic syndrome with etoposide. A 38-year-old man with idiopathic hypereosinophilic syndrome had an inadequate response to steroids and severe side effects from hydroxyurea treatment, which necessitated withdrawal of the treatment. Successful control of clinical symptoms and eosinophil counts was obtained with etoposide (VP16-213) for 18 months. VP16-213 may be valuable in idiopathic hypereosinophilic syndrome treatment. 
Pediatric heart transplantation at Stanford: results of a 15-year experience. The long-term results of pediatric heart transplantation were evaluated in 53 patients, aged 0.25 to 18.94 years, who received transplants at Stanford University Medical Center between 1974 and 1989. Indications for transplantation were idiopathic cardiomyopathy (68%), congenital heart disease (21%), endocardial fibroelastosis (8%), and doxorubicin cardiomyopathy (3%). Immunosuppression was achieved with combinations of cyclosporine, prednisone, and azathioprine. Thirty-seven of 42 recipients leaving the hospital after transplantation were alive and in New York Heart Association class I at study's end. Cumulative survival was 79% at 1 year, 76% at 3 years, and 69% at 5 years. Fourteen recipients have survived more than 5 years (5.1 to 12.4 years). Hospital readmission for illness has been infrequent, decreasing from 6.8 days to 0.9 days per year over 5 years. Eleven patients have required no rehospitalization. Posttransplant deaths were due to infection (19%), rejection (4%), pulmonary hypertension (4%), coronary artery disease (2%), and lymphoproliferative disease (2%). Retransplantation was required for intractable rejection in 4 patients and advanced coronary artery disease in 2. Hypertension and elevated blood urea nitrogen and creatinine levels were common in individuals receiving cyclosporine. Growth was often impaired in prepubertal children receiving daily prednisone. Based on this 15-year experience, it is concluded that heart transplantation represents a reasonable alternative for selected young patients with end-stage cardiac disease. 
The noncemented porous-coated hip prosthesis. A three-year clinical follow-up study and roentgenographic analysis. This was a retrospective study reviewing 68 hip arthroplasties performed with noncemented, porous-coated components at three institutions in the period between December 1983 and June 1987. Fifty of these were available for follow-up study. The mean follow-up period was three years (range, 18-56 months). Thirty-seven patients were treated by total hip arthroplasty (THA) with porous-coated components, and thirteen were implanted with porous-coated femoral stems with bipolar endoprostheses using a porous-coated femoral stem and a universal head. The mean Harris hip score at follow-up evaluation for the entire group was 85.7 points. Eighty percent of the patients had either a good or excellent result. Those patients implanted with a porous femoral stem with bipolar acetabular components had only 54% good or excellent results compared with 90% good or excellent results for those having THA. Roentgenographic findings included a 59% rate of femoral neck cortex osteopenia, an 80% rate of medial or lateral distal cortical hypertrophy, and an 80% rate of distal bone bridging. All of these roentgenographic changes were secondary to changes in stress transference to the proximal femur. There was no correlation between thigh pain or the degree of bone-prosthesis radiolucencies and the fit of the femoral stem. 
General moderate hypothermia in the surgical treatment of descending thoracic aortic aneurysms. The diagnosis and surgical treatment of aneurysms of the descending thoracic aorta is difficult and some aspects of management remain controversial. We report 53 patients treated in the period 1983-1988; 25.9% of them had previously been erroneously diagnosed as having mediastinal cysts or tumours. Duplex scanning and computerised tomography were valuable adjuncts in establishing the correct diagnosis, which was confirmed by aortography in 52 patients. Of 49 patients operated upon electively three died with a mortality rate of 6.1%; of the 4 patients operated upon as emergencies 2 died. Fifty patients survived the operative procedure and of the 3 operated upon under normothermia 1 developed paraplegia, whereas of the 47 patients operated upon under moderate hypothermia (30 degrees-31 degrees C) only 1 developed paraplegia. 
Concentration of cefuroxime in serum and middle ear effusion after single dose treatment with cefuroxime axetil. Antimicrobial agents play an important role in the treatment of patients with acute otitis media and otitis media with effusion (OME). The study was undertaken to determine the concentrations of cefuroxime in the blood and middle ear effusions (MEE) of children between 6 and 12 years of age with acute otitis media and chronic OME after a single oral dose administration of cefuroxime axetil, the ester prodrug of cefuroxime. Cefuroxime axetil (250 mg) was administered 2 to 6 hours before either myringotomy for acute otitis media or myringotomy and tube insertion for chronic OME. Blood samples and middle ear aspirates were obtained from 31 children and the samples were analyzed by high performance liquid chromatography. Cefuroxime was recovered in measurable concentrations in all serum samples and in 15 (79%) of the 19 MEE specimens analyzed. No correlation was seen between cefuroxime MEE concentrations and effusion type, bacteriology or serum concentrations. This study shows that cefuroxime does penetrate into MEE when OME is present and that therapeutic concentrations can be achieved in some patients. 
Symptom reporting in wanted and unwanted pregnancies. This study examined the association between unwanted pregnancy and the reporting of pregnancy symptoms in a sample of 99 pregnant women drawn from an urban, medical school based family practice residency. Of these women, 51 had unwanted pregnancies, and 48 had wanted pregnancies. Women with wanted pregnancies were more likely than women with unwanted pregnancies to report three pregnancy symptoms (amenorrhea, breast tenderness, and morning sickness). This association of symptoms with a wanted pregnancy persisted after controlling for age, race, marital status, contraceptive use, menstrual irregularity, and days since last menses through multiple logistic regression. Findings suggest that symptoms may be underreported by women with unwanted pregnancies. 
Current treatment for Wolff-Parkinson-White syndrome: results and surgical implications. From July 1986 to January 1991, 123 patients with Wolff-Parkinson-White syndrome underwent operation for ablation of aberrant conduction pathways. There were 85 male and 38 female patients ranging in age from 11 months to 68 years. Associated anomalies included Ebstein's anomaly, sudden death syndrome, coronary artery disease, cardiomyopathy, abdominal aortic aneurysm, neurofibromatosis, other arrhythmias, or other complex congenital heart disease. Forty-one patients had multiple accessory pathways. Operative results showed a 7% initial failure rate, which dropped to 3% after reoperation. One patient had undergone previous operation for Wolff-Parkinson-White syndrome at another institution. Procedures performed concomitantly included mitral or tricuspid valve repair or replacement (6), right ventricular conduit replacement, subaortic resection, Fontan repair, corrected transposition repair, coronary artery bypass, and placement of an automatic internal cardioverter defibrillator. There was no operative mortality. Late follow-up is 27 +/- 16 months, and complications included mitral regurgitation and myocardial infarction. By comparison, in the last 12 months 124 patients with the Wolff-Parkinson-White syndrome underwent catheter ablation using radiofrequency current. There were 9 patients with multiple pathways. One hundred twelve patients (90%) had all accessory atrioventricular connections ablated and have remained free of symptomatic tachycardia. There have been 12 failures (10%), of which 5 have had operation and 7 are being treated medically. Mean follow-up is 7 +/- 5 months, and complications included circumflex coronary artery occlusion, excessive bleeding, valve perforation, and cerebral vascular accident. 
Assessment of aortic and pulmonic stenosis by echocardiography. Doppler and imaging echocardiography are highly useful methods of identifying and quantifying both aortic and pulmonic stenosis. The presence of valve stenosis and associated regurgitation is based on detecting abnormal intracardiac velocity patterns near the affected valve. Defining the specific valve involved and the type of lesion present is based on determining the location and timing of the abnormal velocities. Both color flow imaging and duplex pulsed Doppler with two-dimensional echocardiographic imaging are highly accurate in identifying the lesions present. Quantification of the severity of stenotic lesions requires calculation of the pressure gradient across the valve and estimation of valve area; quantification of volume flow rate is frequently helpful. The pressure gradient is calculated from high velocity data acquired in the stenotic valve orifice by using the Bernoulli equation. Volume flow rate through the valve can be estimated by using Doppler velocity data and two-dimensional echocardiographic imaging data acquired at sites upstream from the stenotic valve. The continuity equation allows calculation of valve area that is based on this noninvasive stroke volume and pressure gradient data. This review characterizes flow patterns present near stenotic valves, discusses the equations required to quantify aortic and pulmonic stenosis, and then describes the clinical approach to the noninvasive quantification of both stenotic lesions. 
Pearly penile papules: absence of human papillomavirus DNA by the polymerase chain reaction. Pearly penile papules clinically resemble the sexually transmitted papular variant of genital condylomata. Histologically, however, pearly penile papules consist of fibropapillomata that lack the characteristic morphologic features of human papillomavirus (HPV) infection. To study the possible association of HPV infections with pearly penile papules, we examined tissue specimens from 13 men with pearly penile papules with and without associated penile condylomata. Biopsy specimens were tested for the presence of HPV DNA by the polymerase chain reaction. None of the pearly penile papules contained HPV DNA sequences, whereas four of seven cases clinically suspected of being condylomata associated with pearly penile papules contained HPV DNA. These results confirm that pearly penile papule lesions do not contain HPV DNA; therefore, the distinction between pearly penile papules and penile condylomata is clinically significant. 
Decreased plasticity of glucoregulatory responses in aged rats: effects of chronic stress. These experiments were conducted to determine the effects of age and chronic stress on the ability of rats to attenuate stimulus-induced glucose and insulin responses during repeated exposure to a mild stressor. Young (5-month) and old (21-month) Fischer 344 male rats were either exposed to intermittent sessions of an escapable footshock stress for 3 months, or to no chronic stress. Afterwards, blood samples were obtained from each rat before, during, and after the first and fourth exposure to a novel motion stimulus. Between the first and the fourth exposure to the motion stimulus a pronounced attenuation of glucose and insulin responses was seen in both groups of young rats, and in old chronically stressed rats, but not in old control animals. Thus, it appears that the adverse effects of aging on plasticity of glucoregulatory response processes were significantly diminished by exposure of the animals to periodic challenges from their external environment. 
Prognostic significance of atrial fibrillation in advanced heart failure. A study of 390 patients. BACKGROUND. Atrial fibrillation is common in advanced heart failure, but its prognostic significance is controversial. METHODS AND RESULTS. We evaluated the relation of atrial rhythm to overall survival and sudden death in 390 consecutive advanced heart failure patients. Etiology of heart failure was coronary artery disease in 177 patients (45%) and nonischemic cardiomyopathy or valvular heart disease in 213 patients (55%). Mean left ventricular ejection fraction was 0.19 +/- 0.07. Seventy-five patients (19%) had paroxysmal (26 patients) or chronic (49 patients) atrial fibrillation. Compared with patients with sinus rhythm, patients with atrial fibrillation did not differ in etiology of heart failure, mean pulmonary capillary wedge pressure on therapy, or embolic events but were more likely to be receiving warfarin and antiarrhythmic drugs and had a slightly higher left ventricular ejection fraction. After a mean follow-up of 236 +/- 303 days, 98 patients died: 56 (57%) died suddenly, and 36 (37%) died of progressive heart failure. Actuarial 1-year overall survival was 68%, and sudden death-free survival was 79%. Actuarial survival was significantly worse for atrial fibrillation than for sinus rhythm patients (52% versus 71%, p = 0.0013). Similarly, sudden death-free survival was significantly worse for atrial fibrillation than for sinus rhythm patients (69% versus 82%, p = 0.0013). By Cox proportional hazards model, pulmonary capillary wedge pressure on therapy, left ventricular ejection fraction, coronary artery disease, and atrial fibrillation were independent risk factors for total mortality and sudden death. For patients who had pulmonary capillary wedge pressure of less than 16 mm Hg on therapy, atrial fibrillation was associated with poorer 1-year survival (44% versus 83%, p = 0.00001); however, in the high pulmonary capillary wedge pressure group, atrial fibrillation did not confer an increased risk (58% versus 57%). CONCLUSIONS. Atrial fibrillation is a marker for increased risk of death, especially in heart failure patients who have lower filling pressures on vasodilator and diuretic therapy. Whether aggressive attempts to maintain sinus rhythm will reduce this risk is unknown. 
Limitation of no reflow injury by blood-free reperfusion with oxygenated perfluorochemical (Fluosol-DA 20%). This study was designed to assess the effects of blood-free reperfusion with oxygenated or unoxygenated intracoronary perfluorochemical (Fluosol-DA 20%) on myocardial perfusion and to determine its mechanism or mechanisms of limiting no reflow. Twenty-four dogs underwent 90 min of coronary occlusion followed by 210 min of reperfusion and were randomized to either: 1) blood-free reperfusion with intracoronary oxygenated perfluorochemical (20 ml/kg per min) for 20 min followed by blood reperfusion (n = 8); 2) intracoronary unoxygenated perfluorochemical administered as in those treated with oxygenated perfluorochemical (n = 8); and 3) blood reperfusion alone (control) (n = 8). Regional myocardial blood flow was serially determined and global myocardial perfusion was assessed by an intravenous injection of the fluorescent dye (thioflavin-S). Quantitative studies were performed to determine neutrophil infiltration and extent of endothelial injury. Hemodynamic variables were similar in all groups. The zone of impaired perfusion (thioflavin negative), expressed as a percent of the left ventricle, averaged 10 +/- 2%, 6 +/- 2% and 3 +/- 1%, in control and unoxygenated and oxygenated perfluorochemical groups, respectively (control versus oxygenated perfluorochemical p less than 0.004). The reduction in thioflavin-negative area with oxygenated perfluorochemical was associated with a notable recovery of endocardial blood flow (0.97 +/- 0.22 vs. control 0.39 +/- 0.08 ml/min per g; p less than 0.04) at 210 min of reperfusion. The number of capillaries plugged by neutrophils (per 200 capillaries) in thioflavin-negative areas was similar with both oxygenated (5.9 +/- 1.4) and unoxygenated perfluorochemical (5.4 +/- 0.8) treatment and was significantly less than that with the control group (18.9 +/- 3.2, p less than 0.003). 
Estrogen and estrogen receptors in thyroid carcinomas. Thyroid tissues, composed of normal thyroid (10 cases), Graves' thyroid (4), and papillary carcinoma (10), were measured for the presence of receptors for estrogen (ER) using an enzyme-immunoassay method. The mean value of ER in papillary carcinoma tissues (4.0 +/- 3.6 fmol/mg protein) was higher than that in normal thyroid tissues (0.8 +/- 0.4 fmol/mg protein) or that in Graves' thyroids (2.6 +/- 0.9 fmol/mg protein). In 10 papillary carcinomas, 3 were from male patients and 7 were from females. The mean value of ER in the tumors from male patients (7.2 +/- 5.1 fmol/mg protein) was higher than that from female patients (2.6 +/- 1.7 fmol/mg protein). Another set of 100 thyroid tissues from normal (20 cases), Graves' disease (10), follicular adenoma (8), and papillary carcinoma (62) was also examined for the presence of estradiol (E2) using an immunohistochemical method on formalin-fixed paraffin-embedded sections. E2-positive tissues were found in 4 (40%) of 10 Graves' thyroids, 4 (50%) of 8 adenomas, and 47 (76%) of 62 papillary carcinomas. In 62 papillary carcinomas, E2-positive tissues were found in 37 (73%) of 51 female patients and 10 (91%) of 11 male patients. In relation to relapse of the carcinomas, E2-positive carcinomas were found in 10 (71%) of 14 patients with relapse of the disease and in 14 (54%) of 26 patients with no relapse (the difference was not significant). The findings indicate that thyroid carcinomas may be estrogen-dependent, but no definite conclusions could be drawn between the biological behavior of the tumors and the E2-positivity. 
Urinary cotinine measurement in patients with Buerger's disease--effects of active and passive smoking on the disease process. Although Buerger's disease is known to be closely related to smoking, no objective analysis of the smoke-associated problems has been performed. In this study, cotinine, the major metabolite of nicotine, was used as a sensitive marker to measure levels of active smoking and the exposure of nonsmokers to tobacco smoke because it has a relatively long half-life and because cotinine levels can be determined by noninvasive means in urine. According to urinary cotinine levels, 40 patients with Buerger's disease were classified as (1) smokers: those with urinary cotinine levels above 50 ng/mg creatinine; (2) passive smokers: those with levels between 10 and 50 ng/mg creatinine; and (3) nonsmokers who did not experience noticeable passive smoking: those with levels below 10 ng/mg creatinine. There were 10 smokers, 9 passive smokers, and 21 nonsmokers. The course of the disease, after the initial treatment at our hospital, was studied retrospectively. Seven of the 10 smokers, none of the 9 passive smokers, and 4 of the 21 nonsmokers experienced aggravation of the disease. Of the four nonsmokers who experienced aggravation, three had still been smokers and one had been exposed to tobacco smoke in the workplace at the time of relapse. There was a significant difference in the aggravation rate between the smokers' group and the other two groups. Among the smokers, the seven patients whose conditions worsened showed significantly higher cotinine levels than the three remaining patients who were in the stage of remission. 
Incidence and outcome of surgery for benign prostatic hyperplasia among residents of Rochester, Minnesota: 1980-87. A population-based study. The incidence and outcome of surgery for benign prostatic hyperplasia (BPH) was studied in Rochester, Minnesota, during the period 1980-1987. Three hundred thirty Rochester men without a diagnosis of prostate or bladder cancer underwent prostatectomy for BPH for the first time. Mean and median ages were both seventy (range: 46-95). The incidence of initial prostatectomy for BPH among men forty-five years of age and older age-adjusted to the 1980 U.S. white male population was 642 cases per 100,000 persons per year (py). Among the 330 men undergoing initial prostatectomy for BPH, 14 (4.2%) had serious intraoperative complications, 32 (9.7%) were rehospitalized for urologic complications within thirty days of surgery, and 13 (3.9%) had other serious complications within thirty days after surgery, including 1 death (surgical mortality 0.3%). Forty-five patients (14%) required blood transfusions within thirty days of surgery. The likelihood of reoperation within six years of the initial surgery was 15.1 percent (95% CI 9.7, 20.6). Short- and long-term postoperative mortality was not statistically significantly different than expected based on age- and sex-specific mortality statistics for Rochester, Minnesota. 
Cerebral haemorrhage in a French prospective population study. The incidence of cerebral haemorrhage was studied from a population-based stroke registry. The incidence was 12.3 per 100,000 per year in women and 13.9 per 100,000 per year in men, with a peak in the eighth decade and a male preponderance. Haemorrhages were deep seated and mostly due to hypertension. Recognised clinical characteristics of haemorrhage are acute onset, convulsion, vomiting, and disturbed consciousness. This study showed that cerebral haemorrhage may present with pure motor deficit or transient deficit preceding the stroke. The mortality was 51% in the first month, and 61% by two years. 
Torticollis in children. Torticollis is a common clinical sign that is found in a variety of disorders. Childhood torticollis differs from the adult form in that congenital types are common and many frequently encountered disorders found in adults are unusual. Pediatric torticollis related to otolaryngologic conditions is reviewed, and three illustrative cases are presented. 
Peritonitis due to Rhizopus in a patient undergoing continuous ambulatory peritoneal dialysis. A 61-year-old man who had end-stage renal disease secondary to diabetes mellitus and hypertension developed peritonitis due to infection with Rhizopus as a complication of receiving continuous ambulatory peritoneal dialysis (CAPD). At the onset of infection, the patient was neither acidemic nor hyperglycemic; in addition, deferoxamine had not been administered and Elastoplast dressings had not been applied. The infection occurred after the technique for disinfection of the catheter used for CAPD had been changed. The catheter was removed, and therapy with amphotericin B was initiated. Although the patient died of apparently unrelated causes, an autopsy revealed active fungal infection with multiple abscesses and superficial invasion of the ileal wall. 
Pouchitis--is it a wastebasket diagnosis? Pouchitis is a poorly defined syndrome that is unique to patients with an ileal reservoir. During a prospective follow-up review of 215 patients who underwent ileal pouch-anal anastomosis, pouchitis was diagnosed in 30 patients (14 percent). Based on the clinical course, two distinct patterns of pouchitis were recognized: patients who experienced two or fewer episodes (Group 1-18 patients) and patients who experienced at least three episodes (Group 2-12 patients). Histopathologic review of resected colons revealed a preponderance of indeterminate colitis in patients in Group 2 (58.3 percent) compared with patients in Group 1 (0 percent). In Group 1; 88.9 percent of patients responded to therapy with metronidazole. Only 25 percent of patients in Group 2 responded to metronidazole alone. Most patients in Group 2 required sulfasalazine, topical steroids, or both. Of the 30 patients with pouchitis, four (13.3 percent) had a distinct endoscopic pattern of distal inflammation. This subset of patients with short strip pouchitis was successfully treated with topical steroid preparations. The clinical differences suggest different causes of pouchitis in these two groups. 
Capillary haemangiomas: an approach to their management. Twenty-five children with eyelid haemangiomas were reviewed. Fifteen patients with enlarging lesions thought to be at risk of causing amblyopia were treated with intralesional steroids as soon after presentation as possible. This appeared to reduce significantly the incidence of amblyopia. Surgery was reserved for older children in whom no further involution of the lesion was expected. 
Snoring and the risk of ischemic brain infarction. To determine if a history of snoring is a risk factor for brain infarction, I conducted a case-control study of risk factors for ischemic stroke using 177 consecutive male patients aged 16-60 (mean 49) years with acute brain infarction. For each patient I chose an age-matched (+/- 6 years) male control. Arterial hypertension, coronary heart disease, snoring (habitually or often), and heavy drinking (greater than 300 g/wk) were risk factors in the stepwise multiple logistic regression analysis. The odds ratio of snoring for brain infarction was 2.13. By McNemar's test this association increased strongly if a history of sleep apnea, excessive daytime sleepiness, and obesity were all present with snoring (odds ratio 8.00). My study indicates that snoring may be a risk factor for ischemic stroke, possibly because of the higher prevalence of an obstructive sleep apnea syndrome among snorers than nonsnorers. 
Temperature-dependent modulation of lipopolysaccharide-induced interleukin-1 beta and tumor necrosis factor alpha expression in cultured human astroglial cells by dexamethasone and indomethacin. In bacterial meningitis, LPS induces production in cerebrospinal fluid of the cytokines IL-1 beta and tumor necrosis factor alpha (TNF alpha), which are the principle mediators of meningeal inflammation. IL-1 beta and TNF alpha induce fever, and elevated temperature may affect cytokine expression. Dexamethasone treatment improves outcome in bacterial meningitis possibly by inhibiting IL-1 beta and TNF alpha. In this report, the effects of elevated temperature and dexamethasone on LPS-stimulated IL-1 beta and TNF alpha mRNA gene expression and protein synthesis were studied in human astrocytoma cell lines and primary cultures of human fetal astrocytes. Cells cultured at 40 degrees C exhibited smaller peaks of IL-1 beta and TNF alpha transcription and protein synthesis compared with cells cultured at 37 degrees C. The addition of dexamethasone before, during, or after exposure of the cells to LPS resulted in temperature-dependent inhibition of IL-1 beta transcription and protein synthesis. The most extensive inhibition occurred in pretreated cells cultured at 37 degrees C. Cotreatment with LPS and dexamethasone also inhibited TNF alpha mRNA transcription at both temperatures. The effects of another antiinflammatory agent, indomethacin, on LPS induction of IL-1 beta and TNF alpha mRNA were temperature and cell line dependent. These findings provide a possible explanation for the efficacy of dexamethasone treatment of bacterial meningitis and support the proposal that fever may be beneficial to the host in this disease. 
Anal tonometry: a quick method of anal manometry. Evaluation of anal sphincter tonic activity is important in the proctologic clinic. However, manometric techniques are expensive, complex, and only available in some centers. Because there is often an in-office need for having objective measurements of anal tonic activity, in our clinic we introduced a simple method for measurement of anal pressures. This method is based on the flow of air in an open circuit by using a rubber probe with a side opening at one end. Pressure is assessed by an ordinary manometric gauge for arterial pressure. With this simple instrument, the following parameters are measured: 1) anal resting pressure, 2) squeeze pressure, 3) functional length of the anal canal, and 4) descent of the perineum on staining. After testing the technique in 100 healthy persons, it was applied to 130 patients with several proctologic disorders. Differences in pressures were found between controls and patients with anal fissure (high resting pressures), and patients with anal incontinence (low resting and/or squeeze pressures). A correlation was also found between the descending perineum measured by this method and by defecography. This simple instrument is useful in the office as the first approach to the function of the anal sphincters and the pelvic floor. Nowadays, so-called anal tonometry is part of the proctologic examination in our department, because it is simple, reliable, and takes only a few minutes. 
Analysis of inflammatory cells and complement C3 in bupivacaine-induced myonecrosis. Immunohistochemical analysis of the inflammatory cells and complement C3 in the rat skeletal muscle was performed chronologically in bupivacaine-induced myonecrosis. At 30 minutes after injection, polymorphonuclear leukocytes appeared and increased in number, with a peak value at 12 hours, while macrophages reached the highest level at 2 days. In contrast, T cells comprised only a small population. Two weeks after the injection, all types of the inflammatory cells returned to the normal level. Deposition of complement C3 was recognized at 60 minutes at the surface membrane of degenerating muscle fiber. Our observation suggests the importance of both polymorphonuclear leukocytes and complement C3 in the early stage, and macrophages in the later stage of bupivacaine-induced myonecrosis. In addition, our findings cast doubt on the pathological significance of T cells in this model. 
Anterior urethral polyp associated with hematuria in six-year-old child. Anterior urethral polyps are rare, occur only in male patients, and have been associated with obstruction, terminal hematuria, and enuresis. We believe this is the fifth reported case of anterior urethral polyp associated with terminal hematuria. The radiographic findings, treatment, and pathology are reviewed. 
Toward an integrated understanding of fibromyalgia syndrome. II. Psychological and phenomenological aspects. The present paper is the second of a 2-part series in which extant empirical literature concerning fibromyalgia syndrome (FS) is reviewed in order to provide a preliminary approach to forming an integrated understanding of the syndrome. Research on psychological disturbance in FS is reviewed with particular emphasis on affective dysfunction among FS patients. The phenomenology of FS is then described. We attempt to suggest that FS represents a quantitatively and qualitatively experience distinct from similar chronic pain syndromes. Substantive findings in FS research are summarized in the final section and potential ways in which these findings might be integrated to provide a more cohesive model for future research are suggested. 
Protracted outbreak of severe delta hepatitis: experience in an isolated Amerindian population of the Upper Orinoco basin. In an investigation of a 21-year-old epidemic of severe hepatitis, 80 serum samples were studied from two isolated Yanomami Amerindian populations of the Upper Orinoco basin in Venezuela. Of the assayed samples, 30.6% were positive for hepatitis B surface antigen (HBsAg), 53.7% were considered to reflect immunity to infection with hepatitis B virus (HBV), and only 16.2% were believed to reflect susceptibility to HBV infection; 82.5% of the samples tested positive for any marker of HBV infection. Thirty-one (39.7%) of 78 samples were also positive for antibody to delta antigen, including 91.6% of those positive for HBsAg and 20.9% of those immune to HBV. Our findings provide evidence of a high prevalence of HBV infection in this population. Furthermore, the high prevalence of antibody to delta antigen strongly suggests that coinfections with HBV or superinfections with hepatitis delta virus (HDV) in HBV carriers may be an important factor in the occurrence of an unusually high number of cases of fulminant hepatitis and of chronic liver disease. Serum samples obtained at the beginning of the outbreak 13 years earlier from 36 selected cases in the same population revealed a high rate of HBV infection (96.5%). All six HBsAg carriers from whom enough serum remained to be assayed were positive for antibody to delta antigen. Our findings indicate that the outbreak coincided with the introduction of HDV into a population with an already-high prevalence of HBV infection. 
Hepatobiliary cryptosporidiosis and cytomegalovirus infection mimicking metastatic cancer to the liver. A cholestatic syndrome caused by sclerosing cholangitis and papillary stenosis has been described in patients with the acquired immunodeficiency syndrome and hepatobiliary cryptosporidiosis and cytomegalovirus infection. The case of a 41-year-old homosexual man with the acquired immunodeficiency syndrome who presented with abdominal pain, diarrhea, fever, and cholestasis is reported. A percutaneous transhepatic cholangiogram showed that the extrahepatic and right-sided intrahepatic ducts were normal. Computerized tomography of the abdomen showed multiple hypodense lesions in the liver. Guided needle biopsies of several of these lesions showed severe confluent necrotizing pericholangitis with cytomegalovirus-infected cells. Numerous cryptosporidia were seen attached to biliary epithelium. The unique histopathologic and radiographic features of this case should be added to the spectrum of hepatobiliary manifestations of the acquired immunodeficiency syndrome. 
Obstructed central venous catheters. Restoring function with a 12-hour infusion of low-dose urokinase. Thrombotic obstruction frequently prohibits infusion through or withdrawal of blood from central venous catheters and can occur in conjunction with symptomatic thrombosis of the subclavian vein. Thirty catheters were radiographically proved to be obstructed by thrombus and had not responded to at least one instillation of 5000 units of urokinase. All catheters were treated with a 12-hour infusion of urokinase at the rate of 40,000 units/hour. The obstructing thrombus was either eliminated or reduced in size in all instances and full function was restored in all but one catheter. No bleeding complications were seen. Six patients with obstructed catheters also had symptoms of subclavian vein thrombosis. All patients with symptoms of subclavian vein obstruction became asymptomatic on anticoagulant therapy even though no attempt at dissolving the thrombus obstructing the subclavian vein was made. A 12-hour infusion of low doses of urokinase can safely salvage function of obstructed catheters that otherwise may require replacement. Patients with concomitant subclavian vein thrombosis become asymptomatic on anticoagulant therapy without need to dissolve the obstructing thrombus. 
Enhanced tumor growth of both primary and established human and murine tumor cells in athymic mice after coinjection with Matrigel. Previously we found that the reconstituted basement membrane matrix Matrigel, when premixed with human small-cell lung carcinoma cells and injected subcutaneously into athymic mice, permitted tumor growth, whereas cells injected in the absence of Matrigel did not form tumors. In the present study, we examined additional cell types and determined some of the underlying mechanisms involved in the promotion of tumor formation by Matrigel. The tumor cell lines that we studied included transformed mouse Englebreth-Holm-Swarm tumor cells (T-EHS), human submandibular carcinoma A253 cells, mouse melanoma B16F10 cells, human epidermoid carcinoma KB cells, and human primary renal cell carcinoma cells. When coinjected subcutaneously with Matrigel, these cell lines formed rapidly proliferating tumors. Primary biopsy specimens of human colon carcinoma, when dispersed and coinjected with Matrigel, also formed tumors. Only A253, KB, and B16F10 cells formed small tumors in the absence of Martrigel, but a fivefold to tenfold increase in tumor size was observed in the presence of Matrigel. These data demonstrate a useful method for improving the growth of human tumors in athymic mice. 
GM2-gangliosidosis B1 variant: analysis of beta-hexosaminidase alpha gene mutations in 11 patients from a defined region in Portugal. The GM2-gangliosidosis B1 variant occurs at an exceptionally high frequency in the northern part of Portugal. In most patients, the disease manifests itself as a juvenile form, as opposed to the late-infantile form described for many patients from other parts of the world. We have analyzed the beta-hexosaminidase alpha gene in 11 patients, as well as in some relatives, in order to characterize the underlying abnormalities. They were screened for the two previously identified mutations responsible for the B1 variant phenotype (G533----A, also designated as the "DN allele," and C532---T) by PCR amplification of an 800-bp DNA fragment and subsequent dot-blot hybridization with allele-specific oligonucleotides. The fragment amplified from one patient was also subcloned and sequenced. Ten patients, constituting a clinically and biochemically homogeneous group, were found to be homozygous for the DN allele. The other, whose clinical profile more resembled the late-infantile phenotype often described in the literature, was a compound heterozygote carrying the DN allele and another, as yet unidentified, abnormal allele. Our results, corroborated by previously published data, suggest that homozygotes and compound heterozygotes for the DN allele may be distinguishable at the phenotypic level, depending on the nature of the abnormality in the other allele. A common ancestral origin for the DN allele can also be postulated. 
Total cavopulmonary anastomosis versus conventional modified Fontan procedure. The total cavopulmonary anastomosis, lateral tunnel Fontan, has been advocated as a preferred method for Fontan type repair. From 1987 to July 1990, 39 patients underwent total cavopulmonary anastomoses (group 1) and 39 patients underwent modified Fontan procedures (group 2); patients receiving adjustable atrial septal defects were excluded. Diagnoses in group 1 included tricuspid atresia in 5 patients, single ventricle in 32, and pulmonary atresia and intact ventricular septum in 2. Diagnoses in group 2 included tricuspid atresia in 20, single ventricle in 17, hypoplastic left heart syndrome in 1, and pulmonary atresia and intact ventricular septum in 1. There were no significant differences in age, weight, cross-clamp time, duration of inotropic support, postoperative effusions, or hospital stay between the two groups. Early mortality in group 1 was 7.7% (3/39) and in group 2, 2.6% (1/39). There was no difference in the incidence of early dysrhythmias or early pacemaker placement. Late mortality was 2.8% in group 1 and 8% in group 2 with a mean follow-up of 18 and 25 months, respectively. Follow-up in group 1 revealed 33 patients in normal sinus rhythm and 1 patient with episodes of supraventricular tachycardia; no additional patients have required pacemakers. Follow-up in group 2 revealed 27 patients in normal sinus rhythm and supraventricular tachycardia in 4 patients; 5 additional patients have required pacemaker placement. There is no apparent difference in early outcome between the total cavopulmonary anastomosis and the conventional modified Fontan. However, there appears to be an increased incidence of late dysrhythmias and the need for pacemaker placement in the conventional modified Fontan group compared with the lateral tunnel group. 
Is adult-onset coeliac disease due to a low-grade lymphoma of intraepithelial T lymphocytes? Enteropathy-associated T-cell lymphoma commonly presents with malabsorption, and debate continues as to whether adult-onset coeliac disease (CD) is itself a form of low-grade lymphoma. A 59-year-old man with adult-onset CD required resection of a segment of oedematous jejunum. Histological examination of this tissue revealed an intense intraepithelial lymphocytosis. Immunophenotypic (CD3-, CD4-, CD8-, CD34-, and CD45 RO-) and cytogenetic (deletion of the Y chromosome and chromosome 9) abnormalities were found, together with monoclonal T-cell-receptor gene rearrangements. Some patients with adult-onset CD may have low-grade lymphoma from the outset of their illness. 
Treatment of pancreatic pseudocysts with octreotide. Pancreatic pseudocysts are a common and painful complication of chronic pancreatitis. Seven patients (six male, one female; mean age 49.9 years) with chronic pancreatitis complicated by pseudocysts and persistent pain were treated with the pancreatic anti-secretory drug octreotide for 2 weeks. Octreotide caused no notable changes in the size of the pseudocysts of three patients. In the remaining four patients, the pseudocysts decreased in size by a mean of 42% (range 29-52%), and pain disappeared completely. These findings suggest a role for octreotide in the treatment of pancreatic pseudocysts. 
Intussusception in cystic fibrosis. Two cases of acute intussusception in older children with cystic fibrosis are reported. Both cases presented with symptoms and signs consistent with meconium ileus equivalent, which delayed the final diagnosis. Both cases required abdominal surgery but made full and uneventful recoveries. 
Home monitoring of transcutaneous oxygen tension in the early detection of hypoxaemia in infants and young children. Twenty three patients (age range 0.5-40 months) with recurrent cyanotic episodes underwent physiological recordings, including transcutaneous oxygen tension (TcPO2) from a monitor modified for use at home (Kontron 821S). Of 69 episodes in which the arterial oxygen saturation (SaO2, Nellcor N200) was less than or equal to 80% for greater than or equal to 20 seconds and/or central cyanosis was present, the TcPO2 monitor alarmed (less than or equal to 20 mmHg or 2.67 kPa) in every episode. The pulse oximeter identified hypoxaemia in 62 out of 69 episodes, failing in seven episodes due to signal loss from movement artefact. In only seven of 69 episodes was there an accompanying apnoeic pause (greater than or equal to 20 seconds), and heart rate fell to less than or equal to 80 beats/minute in only five of 28 episodes in which an electrocardiogram was recorded. In 32 episodes in which SaO2 fell to less than or equal to 60%, the TcPO2 monitor alarmed after a median time interval of 16 seconds (maximum time interval 30 seconds). The TcPO2 monitor was then used in an uncontrolled trial at home in 350 patients at increased risk of sudden death and/or hypoxaemia. Indications for monitoring included apparent life threatening events or cyanotic episodes (n = 163), prematurity and prematurity related disorders (n = 86), and sudden unexpected death in one or more siblings (n = 122). The TcPO2 monitor detected cyanotic episodes at home in 81 patients, 52 of whom received vigorous stimulation and/or mouth to mouth resuscitation. Twenty one of these 52 patients had further hypoxaemic episodes documented in hospital with pulse oximetry. 
How AIDS forces reappraisal of hepatitis B virus control in sub-Saharan Africa For developing countries the cost-benefit of vaccination in the control of hepatitis B virus (HBV) infection is great since the acute infection is generally subclinical and the benefit is the prevention of small numbers of cases of cirrhosis and hepatocellular carcinoma. Since the pattern of HBV infection in Africa is such that, compared with south-east Asia, infection occurs later in childhood and spread is horizontal rather than vertical, investigation of the method of spread of HBV may result in a means of control other than by vaccination. In the meantime, because of the overlap in the means by which HBV and human immunodeficiency virus (HIV) are spread, it could be worthwhile taking advantage of existing AIDS prevention programmes to educate people about how to avoid both HBV and HIV infections. 
Treatment of oesophageal perforation: a multivariate analysis. Perforation of the oesophagus was retrospectively analysed in 59 patients. Cause and extent of perforation, localization, quality of the oesophageal wall and therapeutic modes were subjected to univariate analysis. The perforations of the intrathoracic oesophagus (39) were also subjected to multivariate analysis. Perforation of the cervical oesophagus is seldom lethal and can be adequately treated conservatively in the majority of cases. Perforations of the intrathoracic oesophagus can be divided into two groups, with or without simultaneous perforation of the parietal pleura. The optimal treatment for the group with pleural perforation seems to be resection of the oesophagus and secondary reconstruction, although primary closure is indicated in selected early cases. Perforations of the intrathoracic oesophagus confined to the mediastinum can be adequately treated conservatively in most patients. Perforation of the intra-abdominal oesophagus should be treated like any other intra-abdominal visceral perforation, by closure or diversion, even if this results in resection of the oesophagus. 
Comparison of the Finapres and direct arterial pressure monitoring during profound hypotensive anaesthesia. The Finapres was compared with direct intraarterial pressure monitoring in 10 patients undergoing local resection of choroidal melanoma, an operation that requires a period of profound hypotension. Good agreement was recorded for systolic arterial pressure and heart rate over a range of pressures. However, agreement of mean and diastolic pressures was poor, with the Finapres tending to overestimate these values. In cases requiring profound hypotension, direct arterial pressure monitoring remains the method of choice. 
The kissing balloon technique with two over-the-wire balloon catheters through a single 8-French guiding catheter. Some of the newer over-the-wire coronary angioplasty catheters have shaft sizes of 3.0 French (F) or less. The inner diameter of modern 8-F guiding catheters is large enough to accommodate two of such balloon catheters. We report a kissing balloon procedure with two over-the-wire catheters through a single 8-F guiding catheter. 
Superior vena caval thrombosis detected by transesophageal echocardiography. Three patients with clinical suspicion of bacterial endocarditis, induced by either pacemaker or indwelling catheter, underwent transesophageal echocardiography. High short-axis cuts through the great vessels, however, revealed the presence of superior vena caval thrombus in all three patients. Transesophageal echocardiography is more sensitive in establishing the diagnosis of superior vena caval thrombus than surface echocardiography. Comparison of transesophageal echocardiography with other diagnostic modalities is needed in assessing its overall sensitivity and specificity. 
Antibody to hepatitis C virus in post-transfusion hepatitis. OBJECTIVE: To evaluate the prevalence of antibodies to hepatitis C virus (anti-HCV), their relation to outcome, and the seroconversion rate in patients with post-transfusion non-A, non-B hepatitis. DESIGN: Retrospective analysis of prospectively collected serum specimens. SETTING: A referral-based university hospital. PATIENTS: Sixty-three consecutive patients who developed non-A, non-B post-transfusion hepatitis after open-heart surgery. All patients had follow-up with serial serum testing and clinical evaluation. The mean (+/- SD) duration of follow-up after hepatitis onset was 81 +/- 33 months (range, 13 to 132 months). Seventeen patients recovered after acute-phase illness, whereas 46 developed chronic disease which, in 30 cases, was confirmed histologically. MAIN RESULTS: Of 32 patients tested before transfusion, 1 (3.1%) had anti-HCV. Fifty-nine (93%) patients were anti-HCV positive during acute-phase hepatitis: Patients with "early" seroconversion (less than 15 days after hepatitis onset) did not differ from those with "late" seroconversion (greater than 60 days after onset) in epidemiologic, clinical, and biochemical features. The rate of anti-HCV positivity during acute-phase illness was not significantly different among patients who recovered (76%) compared with those who developed chronic disease (95%). At 6 to 12 months, patients whose disease resolved had lower antibody activity than those with progressive disease. Further, during long-term follow-up (1 to 9 years), 53% of patients whose disease resolved but only 6.9% of patients who had progressive disease became anti-HCV negative. CONCLUSIONS: Hepatitis C virus is the major cause of post-transfusion hepatitis in Italy. The time to anti-HCV seroconversion varies widely after hepatitis onset and is not significantly associated with acute-phase features or outcome of disease. 
Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. The SOLVD Investigators BACKGROUND. Patients with congestive heart failure have a high mortality rate and are also hospitalized frequently. We studied the effect of an angiotensin-converting-enzyme inhibitor, enalapril, on mortality and hospitalization in patients with chronic heart failure and ejection fractions less than or equal to 0.35. METHODS. Patients receiving conventional treatment for heart failure were randomly assigned to receive either placebo (n = 1284) or enalapril (n = 1285) at doses of 2.5 to 20 mg per day in a double-bind trial. Approximately 90 percent of the patients were in New York Heart Association functional classes II and III. The follow-up averaged 41.4 months. RESULTS. There were 510 deaths in the placebo group (39.7 percent), as compared with 452 in the enalapril group (35.2 percent) (reduction in risk, 16 percent; 95 percent confidence interval, 5 to 26 percent; P = 0.0036). Although reductions in mortality were observed in several categories of cardiac deaths, the largest reduction occurred among the deaths attributed to progressive heart failure (251 in the placebo group vs. 209 in the enalapril group; reduction in risk, 22 percent; 95 percent confidence interval, 6 to 35 percent). There was little apparent effect of treatment on deaths classified as due to arrhythmia without pump failure. Fewer patients died or were hospitalized for worsening heart failure (736 in the placebo group and 613 in the enalapril group; risk reduction, 26 percent; 95 percent confidence interval, 18 to 34 percent; P less than 0.0001). CONCLUSIONS. The addition of enalapril to conventional therapy significantly reduced mortality and hospitalizations for heart failure in patients with chronic congestive heart failure and reduced ejection fractions. 
Impact of diagnosis-related groups on the quality of postoperative care of patients with neck dissections. Two hundred eighty patients underwent neck dissection over a 10-year period: 138 during the 5-year period before the institution of Diagnosis-Related Group (DRG) reimbursement and 142 during the 5 years after DRG regulations. A comparison of these two groups by site of tumor, stage of disease, histopathology, previous treatment, type of neck dissection, whether neck dissection was carried out alone or in combination with another procedure, presence of preexisting disease, postoperative complications, and mortality revealed no significant differences. A 35% reduction in the length of hospital stay from 16 to 10 days was identified in the post-DRG group with no detrimental effects on patient care. The variables found to have the greatest impact on length of hospital stay were the extent of operation and postoperative complications. 
The long distance effects of brain lesions: visualization of axonal pathways and their terminations in the human brain by the Nauta method. This study aims at determining the reliability and the optimal post-injury survival time for the application of the Nauta technique to the analysis of the human brain. The Nauta method reveals the degeneration not only of nerve fibers, myelinated and unmyelinated, but also of their terminations. Immunohistochemical and ultrastructural observations appear to prove that the Nauta technique indeed stains axons in human autopsy material. The optimal survival time for the use of the Nauta method was found to be between nine days and five months. In cases with longer survival times--up to 20 months--the Nauta technique and a previously proposed polarizing technique (showing birefringent breakdown products of myelin) can be used as complementary methods. Applying these techniques to the human brain may help define the anatomical basis of neurological and neuropsychological symptoms important for man. 
Amino acid alterations and encephalopathy in the sepsis syndrome. OBJECTIVE: To evaluate the role of amino acid profiles in septic encephalopathy. DESIGN: Retrospective analysis. SETTING: Medical wards and medical ICU of a university hospital. PATIENTS: Patients with infections and normal mental status were compared with patients with septic shock and altered sensorium. INTERVENTIONS: Plasma amino acid levels and Acute Physiology and Chronic Health Evaluation (APACHE II) scores were determined. MEASUREMENTS AND MAIN RESULTS: Patients with septic shock and altered sensorium had higher circulating concentrations of ammonia (425 +/- 55 vs. 127 +/- 7 mmol/L) and the aromatic amino acids phenylalanine (122 +/- 19 vs. 74 +/- 3 mmol/L) and tryptophan (97 +/- 7 vs. 32 +/- 13 mmol/L), and lower levels of the branch-chain amino acid isoleucine (48 +/- 7 vs. 68 +/- 5 mmol/L) than patients with infections and normal sensorium (p less than .05). Aromatic amino acid levels correlated with APACHE II scores (R2 = .4, p less than .001) and mortality. APACHE II scores were higher in the septic shock patients (30 +/- 2 vs. 8 +/- 1, p less than .001), and these patients had a higher mortality rate (71% vs. 12%, p less than .01). Patients with septic shock who died had higher levels of ammonia (524 +/- 58 vs. 227 +/- 40 mmol/L, p less than .05) and sulfur-containing amino acids (172 +/- 31 vs. 61 +/- 7 mmol/L, p less than .05) than patients who survived. CONCLUSIONS: Plasma amino acid profiles appear to be important in septic encephalopathy and the severity of septic disease. 
Clinical significance of two forms of IgM antibody to hepatitis delta virus. Separation of 7-8 S and 19 S forms of serum IgM antibodies to the hepatitis delta virus by rate-zonal centrifugation was carried out on serum from 24 patients with hepatitis delta virus infection: 4 patients with acute, self-limited hepatitis; 5 patients with hepatitis delta virus superinfection progressing to chronicity; and 15 patients with chronic hepatitis delta virus. The high molecular weight IgM form (19 S) was predominantly detected in acute hepatitis delta virus cases, whereas the low molecular weight (7 S) form was found in chronic hepatitis delta virus cases. The serological profile of these two forms of IgM antibody to hepatitis delta virus was investigated in serial samples from five patients with acute hepatitis delta virus superinfection that evolved to chronic hepatitis delta virus. We found that, in the acute stage of the disease, the 19 S form was predominant, whereas 6 mo later a predominance of 7-8 S IgM was observed. These results suggest that IgM antibody to hepatitis delta virus antibody forms are different in acute and chronic hepatitis delta virus infection and that their detection only helps in differentiating an acute infection from a chronic infection but not a hepatitis delta virus-hepatitis B virus-HBV coinfection from hepatitis delta virus superinfection in the acute stage of the disease. 
Combined surgical and interventional radiological approach for complex benign biliary tract obstruction. In patients with complicated high benign biliary strictures surgical technique alone cannot exclude the possibility of recurrent problems, and hepatic atrophy/hypertrophy, portal hypertension and intrahepatic stones may all complicate surgical management. A multidisciplinary approach to these complex cases, which minimizes the need for repeated surgical interventions, has been pursued. Roux-en-Y hepaticojejunostomy was performed and an extended limb of the jejunum brought to the abdominal wall to allow access for later radiological intervention. Over a 30-month period 58 biliary-enteric anastomoses for benign disease were performed. Seventeen of these 58 patients were managed using the combined approach. Ten of these 17 patients had complex postcholecystectomy strictures and seven had strictures resulting from inflammatory disease, hepatic resection or congenital problems. A new classification of results of management of bile duct strictures is proposed. Seven patients were classified as 'excellent', six 'good', two 'fair' and two 'poor'. Results were obtained at a mean follow-up of 16 months and it seems likely that in some patients major surgical reinterventions were avoided. 
Hereditary unstable DNA: a new explanation for some old genetic questions? Fragile X syndrome, associated with the fragile X chromosome, is the most common cause of familial mental retardation. The condition is characterised by a heritable DNA sequence that consists of an abnormal number of CCG repeats, and which is unstable in both mitosis and meiosis. We suggest that such heritable unstable DNA sequences could be present in other parts of the genome and that these might explain a number of genetic events that are not well understood in terms of classic genetic mechanisms. Such poorly explained observations include anticipation, incomplete penetrance, variable expression, and possibly imprinting, variegation, and multifactorial inheritance. 
Significance of elevated levels of serum creatine phosphokinase in febrile diseases: a prospective study. The incidence and significance of elevated serum levels of creatine phosphokinase (CPK) in febrile diseases were studied prospectively in all patients admitted with fever to a department of medicine during 1 year. High serum CPK levels were detected in 70 (28%) of 247 febrile patients but in only six (6%) of 105 afebrile control patients (P = .0001). Elevated CPK levels were not related to any specific diagnosis. Logistic regression analysis identified five factors that correlated both significantly and independently with elevation of CPK values: increased blood urea nitrogen level, low serum phosphate level, a stuporous or comatose state, tremor, and muscle tenderness. Myoglobinuria, detected in 14 patients, was predictive of a fatal outcome, but a high CPK level by itself was not an independent correlate of mortality. In summary, CPK elevation is not uncommon in febrile diseases, but because it does not reflect a specific etiology it does not necessarily indicate that an extensive diagnostic work-up is required. 
Asymmetrical ocular pursuit with posterior fossa tumors. We report two patients with posterior fossa neoplasms who demonstrated asymmetrically impaired horizontal ocular pursuit documented with electrooculography. One patient had impaired pursuit contralateral to a pontomedullary lesion, whereas the second patient had impaired pursuit ipsilateral to a pontocerebellar lesion. These patients demonstrate that posterior fossa lesions may impair ocular pursuit either contralaterally or ipsilaterally unlike cerebral hemispheric lesions, which impair ocular pursuit ipsilaterally or bilaterally. 
Effects of a minimally supervised exercise program for mentally retarded adults. Previous exercise studies that attempted to improve the cardiovascular fitness (CVF) of mentally retarded (MR) adults were flawed with methodological shortcomings that prevented conclusive results. At issue in these training studies were fitness test validity and reliability, exactness of duration and intensity of training, and an inordinate amount of supervision. Therefore, we sought to determine whether moderately MR adults (seven males, five females; IQ = 61 +/- 3, age = 25 +/- 3 yr) could improve their CVF through a minimally supervised 16-wk training program. Each subject repeated exercise tests twice on two different modes of exercise, the treadmill (TM) and Schwinn Air-Dyne ergometer (SAE), before training to ensure validity and reliability of initial CVF levels. Intensity and frequency of exercise were closely monitored. An observer was present during the training bouts, but, following initial instructions, no additional encouragement or instructions were given. Although the training program significantly increased peak VO2 (29.2 +/- 8 to 33.5 +/- 9 ml.kg-1.min-1) and peak ventilation (73 +/- 26 to 81 +/- 231.min-1) when assessed on the TM, significant changes in these same parameters were not seen when assessed on the SAE. The importance of these results was discussed. 
Cardiac pacemaker in high spinal cord injury. Bradycardia followed by cardiac arrest is well documented as a complication of acute injury to the cervical spinal cord. This life-threatening bradycardia is attributed to an imbalance in the autonomic nervous system resulting from dissociation of the parasympathetic from the sympathetic responses during the stage of spinal shock. A patient with a C2 complete quadriplegia secondary to birth trauma who experienced symptomatic bradycardia, continuing for 21 months after injury despite intensive medical management, is reported. Clinical improvement followed insertion of a cardiac pacemaker. Possible etiologies for the continuation of abnormal bradycardia episodes after the resolution of spinal shock are discussed. Cardiac pacemaker implantation is advocated for patients with high cervical spinal cord injuries and continuing symptomatic bradycardia not responding to medical measures. 
The risk of dying of prostate cancer in patients with clinically localized disease. From 1966 to 1979, 360 patients with clinical stages A2, B and C1 prostate cancer underwent staging pelvic lymphadenectomy, and completed a course of combined interstitial radioactive gold seeds and external beam radiotherapy. All patients had a normal serum prostatic acid phosphatase level and a bone scan negative for metastases. All patients were followed until death or for a mean of 7.3 years (range 1.2 to 18.25 years) for those alive at analysis. To determine the risk of dying of prostate cancer we reviewed the records of the 142 patients (39%) who died. At analysis 21% of the patients had died of prostate cancer and 17% of other known causes. The cause of death could not be determined in 4 patients (1%). Cardiovascular disease accounted for a fifth of all deaths. The actuarial risk of death of prostate cancer for all patients was 8 +/- 3% (+/- 2 standard errors) at 5 years and 30 +/- 7% at 10 years. The risk of death of all causes was 16 +/- 4% at 5 years and 46 +/- 7% at 10 years. An increased risk of cancer death was associated with established risk factors, including advanced local disease, poorly differentiated histology, pelvic nodal metastases and distant recurrence. We also noted a substantial risk of cancer death in patients who had local tumor recurrence. While previous studies have reported a relatively low incidence of cancer deaths (4 to 17%) in patients initially diagnosed with localized disease, our data suggest that prostate cancer is the major cause of mortality in such patients. Aggressive curative therapy, regardless of treatment modality, should be considered for localized prostate cancer in men with a life expectancy of 10 or more years. 
Self-inflicted eye injuries. Five cases of self-inflicted eye injury are described and discussed. A review of the literature shows that several psychiatric diagnoses have been assigned to people who damage their eyes. A variety of mechanisms to explain this phenomenon are described. 
Dry beriberi: unusual complication of prolonged parenteral nutrition. An adult with Crohn's disease on home total parenteral nutrition (TPN) for 8 months presented with peripheral neuropathy and ataxia. The patient was found to be deficient of thiamine. A prompt symptomatic response to intravenous thiamine suggests that the patient had the chronic form of dry beriberi. To our knowledge, this variety of beriberi in a patient on TPN has not previously been reported. 
Double-blind investigation of the effects of propranolol and placebo on the pressure of esophageal varices in patients with portal hypertension. This study was aimed at investigating the effects of propranolol on esophageal variceal pressure in patients with portal hypertension. Variceal pressure was measured at endoscopy using a miniature pressure-sensitive gauge in 20 patients with portal hypertension. Measurements were obtained under baseline conditions and 20 min after double-blind administration of propranolol (0.15 mg/kg; n = 10) or an identical amount of placebo (normal saline, 0.3 ml/kg; n = 10). Under baseline conditions, variceal pressure was similar in propranolol and placebo groups (14.1 +/- 5 mm Hg vs. 14.9 +/- 6.6 mm Hg, respectively; not significant). Placebo had no significant effect on variceal pressure (baseline = 14.9 +/- 6.6 mm Hg; placebo = 15.5 +/- 6.6 mm Hg; not significant), and values after placebo administration were closely correlated with baseline values (r = 0.98; y = 1.1 + 0.97 x; p less than 0.0001). In contrast, propranolol caused a significant decrease in the pressure of esophageal varices (from 14.1 +/- 5 mm Hg to 11.3 +/- 4.4 mm Hg; p less than 0.0002). No significant changes in the size of esophageal varices were observed after propranolol or placebo administration. This study shows (a) the endoscopic pressure-gauge technique has a low variability and may be used to assess acute drug-induced changes in variceal pressure; and (b) propranolol causes significant decreases in variceal pressure in patients with portal hypertension and esophageal varices. 
Acute polyhydramnios associated with chorioangioma. A case report. A case of acute polyhydramnios occurred at 26 weeks' gestation. Prenatal sonography demonstrated a placental chorioangioma. Acute polyhydramnios is clinically distinct from nonacute polyhydramnios and carries a high perinatal mortality rate. As in our case, fetal death often results from complications of prematurity. 
Aortic thrombosis after umbilical artery catheterization in neonates: prevalence of complications on long-term follow-up. We previously reported the early natural history of aortic thrombosis occurring after umbilical artery catheterization in 21 neonates. Ten of those neonates were reevaluated at 36-42 months of age for evidence of hypertension, renal abnormalities, and leg-growth disturbances. They were compared with an age-matched control group of seven infants. Blood pressures were greater than the 95th percentile in three infants and between the 50th and the 95th percentile in six of the 10 infants. Height was less than the fifth percentile for age in four infants with aortic thrombosis. One child had a 1.0-cm discrepancy in leg-length measurements, and seven of nine patients exhibited a 0.5-2.0 cm discrepancy between legs in either thigh or calf circumference. Sonography showed no evidence of residual clot in the aorta or renal vessels. Doppler flow was normal in all cases. Despite resolution of neonatal aortic thrombosis, complications resulting in renovascular hypertension (three of 10 patients) and leg-growth abnormalities (eight of nine) can occur. Hypertension (one of seven) and leg-growth discrepancy (four of seven) were less frequent in the 3-year follow-up of the seven matched control infants. We suggest that infants with known aortic thrombosis receive long-term follow-up to detect these potential problems. 
Light reflection rheography: an effective non-invasive technique for screening patients with suspected deep venous thrombosis. Light reflection rheography is a simple non-invasive technique for assessing venous function in the leg. One hundred and twenty-four patients referred for venography with a clinically suspected deep venous thrombosis were investigated by light reflection rheography to determine the accuracy of the technique in diagnosing acute thrombosis. In half of the patients venography confirmed a deep venous thrombosis. Light reflection rheography had a sensitivity of 92 per cent and a specificity of 84 per cent in detecting acute thrombosis. The technique had a negative predictive value of 92 per cent in selecting those patients with no thrombosis. Light reflection rheography can be performed at the bedside or in the radiography department which makes it a suitable technique for screening patients with suspected deep venous thrombosis. 
Wildervanck or cervico-oculo-acoustic syndrome and MRI findings. In 1952, Wildervanck described the first case of what he styled the cervico-oculo-acoustic (COA) syndrome. This comprises Klippel Feil's (KF) anomaly (congenitally fused cervical vertebrae), congenital sensorineural deafness and Duane's retraction syndrome (deficient abduction with retraction on adduction). Since that original paper, there have been further reports describing this triad, either completely or incompletely. A further case of this syndrome is reported and the first report of MRI head scan findings in this condition is presented. In addition, the origin of mirror movements observed as part of the KF syndrome are discussed. 
Asymptomatic blastomycosis of the central nervous system with progression in patients given ketoconazole therapy: a report of two cases. Ketoconazole (KTZ) has largely replaced amphotericin B as first-line therapy for blastomycosis. However, KTZ penetrates poorly into the central nervous system (CNS), and therapeutic failure may be caused by initially unrecognized CNS infection. Two patients (22% [2/9] of all culture-proven cases of blastomycosis at Grady Memorial Hospital, Atlanta, over 15 years) developed CNS blastomycosis while receiving KTZ. Neither initially had CNS symptoms; both had cutaneous and pulmonary disease that responded to KTZ. If KTZ or other fungistatic imidazoles are to continue as primary therapy for blastomycosis, studies are needed to improve the ability to identify patients likely to experience treatment failure or develop CNS disease. Possibly all patients with disseminated blastomycosis, even those without CNS symptoms, should have lumbar puncture and computed tomography of the head before therapy. Critical evaluation of their immune function also may be required before making a therapeutic decision to use KTZ or amphotericin B. 
Treatment of rat prostatic adenocarcinoma with medroxyprogesterone acetate (MPA): effects on growth and morphology. Rats bearing the Dunning R3327H prostatic carcinoma were castrated and supplemented with testosterone propionate. These rats were then treated with estradiol benzoate or medroxyprogesterone acetate alone or in combination with estradiol. During the treatment period of six weeks, the growth rate of the prostatic tumors was measured. At the end of the treatment period the morphology of the tumors was also studied. It was found that medroxyprogesterone acetate is as effective as estradiol in inhibiting the growth of the Dunning prostatic carcinoma and that the combination of medroxyprogesterone acetate and estradiol was more efficient in that respect than estradiol alone. Morphometric evaluation of the tumor epithelium and stroma showed a decrement of epithelial growth in all treatment groups, while the groups treated with medroxyprogesterone acetate, both alone or in combination with estradiol, also showed an inhibited growth of the tumor stroma. It was concluded that medroxyprogesterone acetate probably has direct inhibitory effects on prostatic tumor cells in the Dunning model and that medroxyprogesterone acetate may act in an additive manner with estradiol. 
Pharmacokinetics of activated protein C in guinea pigs. Protein C is a vitamin K-dependent zymogen of the serine protease, activated protein C (APC), an important regulatory enzyme in hemostasis. In view of the potential of human APC as an anticoagulant and profibrinolytic agent, the pharmacokinetics and tissue distribution of APC were studied in guinea pigs. The plasma elimination of a trace dose of 125I-APC was biphasic following an initial rapid elimination of approximately 15% of the injected dose within 1 to 2 minutes. This rapid removal of 125I-APC from the circulation was found to be a result of an association with the liver regardless of the route of injection. Essentially identical results were obtained with active site-blocked forms of APC generated with either diisopropylfluorophosphate or D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone, which indicates that the active site was not essential for the liver association. Accumulation of all three forms of APC in the liver peaked at 30 minutes and then declined as increasing amounts of degraded radiolabeled material appeared in the gastrointestinal tract and urine. Removal of the gamma-carboxyglutamic acid (gla) domain of diisopropylphosphoryl-APC resulted in a 50% reduction in the association with liver and an accumulation in the kidneys. Protein C and protein S were cleared from the circulation at rates approximately one-half and one-fourth, respectively, that of APC. Both in vitro and in vivo, APC was found to form complexes with protease inhibitors present in guinea pig plasma. Complex formation resulted in a more rapid disappearance of the enzymatic activity of APC than elimination of the protein moiety. These findings indicate two distinct mechanisms for the elimination of APC. One mechanism involves reaction with plasma protease inhibitors and subsequent elimination by specific hepatic receptors. The other mechanism involves the direct catabolism of APC by the liver via a pathway that is nonsaturable over a substantial dose range and independent of the active site. This pattern of elimination is distinctly different from that observed with the homologous coagulation enzymes thrombin, factor IXa, and factor Xa. 
Intracarotid chemotherapy with etoposide and cisplatin for malignant brain tumors. Chemotherapy for tumors of the central nervous system has a limited efficacy presumably because of restricted blood-brain barrier permeability. The advantage of regional intra-arterial administration of anticancer drugs is an increased uptake during the first passage of the drugs through tumor capillaries. Twenty patients with high-grade astrocytomas (HGA) and 28 patients with metastatic brain tumors (MBT) received intracarotid/intravertebral infusion of etoposide and cisplatin. Eight patients with HGA who underwent incomplete resection responded to chemotherapy alone. Four additional patients had complete resection of the tumor. Median survival time of the group (responders and nonresponders) has been 14 months. Twelve patients with MBT responded to chemotherapy alone (six had complete response [CR], and six had partial response [PR]) with a median survival time of 7 months. Intra-arterial chemotherapy (IAC) appears to be effective with acceptable toxicities. Accrual of additional patients is required before a final conclusion can be reached. 
High mebendazole doses in pulmonary and hepatic hydatid disease. Thirty nine children with 71 hydatid cysts were given mebendazole orally in a dose of 100-200 mg/kg/day for 12 weeks and were followed up for a mean (SD) of 63 (24) months. Twenty children (three of them after a second course) were cured and another two avoided at least one operation. No serious side effects of the drug were observed. 
Concomitant lymphangioma and arteriovenous malformation of the orbit. An 8-year-old girl had an orbital-adnexal lymphangioma and ipsilateral orbital and middle cranial fossa arteriovenous malformations. High-resolution magnetic resonance image scanning, orbital ultrasonography, and digital subtraction angiography were used for diagnosis and preoperative assessment. Complications related to this vascular neoplasm included amblyopia, acute hemorrhage with proptosis, exposure keratitis, cosmetic deformity, and recurrent preseptal cellulitis. The girl was treated with both embolization and orbital surgery for recurrent hemorrhage and proptosis. We postulated that the coexistence of a lymphangioma and arteriovenous malformation represents an unusual and extensive maldevelopment of vascular embryogenesis. 
Importance of 6-mercaptopurine dose in lymphoblastic leukaemia. To explore the possibility that higher total dosage of 'maintenance' treatment may have contributed to the recent improvement in outlook of children in the United Kingdom with lymphoblastic leukaemia, details of the amount of 6-mercaptopurine prescribed during the first two years of treatment were studied in an unselected cohort of children diagnosed between 1973 and 1987. Eighty five patients were studied, 30 diagnosed before and 55 after 1980. The group diagnosed after 1980 showed an 18% improvement in relapse free survival at five years. Their median total dose of 6-mercaptopurine had increased by 22%, whereas according to the protocol it should have risen by an average of only 9%. After 1980 boys were prescribed significantly more 6-mercaptopurine than girls, and had fewer dose reductions because of myelosuppression. These findings support the clinical impression that after 1980 an important therapeutic difference resulting from the new United Kingdom acute lymphoblastic leukaemia protocols was an increase in the amount of 6-mercaptopurine that children actually received as a result of changes in prescribing guidelines rather than dose. They also provide further evidence that boys tolerate 6-mercaptopurine better than girls, which may be related to the still unexplained difference in prognosis between the sexes. 
The National Heart, Lung, and Blood Institute Workshop on antihypertensive drug treatment. The benefits, costs, and choices. Implications for research. Selected portions of the workshop's closing discussion are summarized. Major ongoing clinical trials of antihypertensive drug treatment are described. Some recommendations offered by workshop participants for future research directions are summarized. 
Hypercholesterolemia: the cost of treatment in perspective. Would the money spent on treating hypercholesterolemia save more lives if spent elsewhere? How many dollars must be spent on a treatment to make one person live 1 year longer? This cost-effectiveness analysis uses the cost per year of life gained to compare a wide variety of health care interventions ranging from carcinogen research to screening tests to liver transplants. The comparison calls into question some popular trends. 
Oral ketamine. Its use for mentally retarded adults requiring day care dental treatment. Four cases of severely mentally handicapped young adults requiring day care dental treatment are reported. All had required varying degrees of restraint during previous dental treatments, which had been distressing for the patient, the relatives and the ward staff. In all cases, administration of oral ketamine 10 mg/kg, 30-60 minutes before the procedure, facilitated subsequent induction of anaesthesia. 
Laparoscopic cholecystectomy: evolution, early results, and impact on nonsurgical gallstone therapies Laparoscopic cholecystectomy, a surgical technique first performed in France, has gained widespread acceptance among surgeons in the United States. The abdominal cavity is inflated by carbon dioxide, a video monitor is inserted via a laparoscope placed periumbilically, and the gallbladder is freed and removed from the liver bed by using small subcostal ports for access and dissection. Intraoperative cholangiography is routinely performed, but uncertainty exists about how best to manage choledocholithiasis. Compared with traditional cholecystectomy, initial reports describing laparoscopic cholecystectomy cite shorter recovery times because no large incisions are made, thus potentially reducing the cost and morbidity of cholecystectomy. A survey of 614 early cases supports these claims, with a reported complication rate of 1.5% and quick resumption of normal activities by patients. Because of its promise for reduced morbidity, laparoscopic cholecystectomy is challenging open cholecystectomy as the therapeutic gold standard for symptomatic cholelithiasis. Thus, the standard to which the nonsurgical gallstone therapies, such as lithotripsy and contact dissolution, will be compared may shift to laparoscopic cholecystectomy. As the laparoscopic complications are similar to those of traditional cholecystectomy, such as abscesses and bile leaks, their percutaneous treatment should not change. 
Renal abscess in childhood: diagnostic and therapeutic progress. During the past decade new techniques such as computed tomography (CT) and ultrasonography have been reported to have changed the diagnostic investigation and treatment of renal abscess in adults. To evaluate whether similar changes have taken place in the pediatric age group, a retrospective study of all patients seen between 1979 and 1989 was performed. Seven patients, 0.8 to 14 (mean, 9) years old, with renal abscesses in eight kidneys were identified. Ultrasound and computed tomography proved to be the most valuable diagnostic tools, revealing the diagnosis by showing a hypoechoic or hypodense mass. All patients had an initial trial of intensive antibiotic treatment, which led to resolution of the abscesses in two of the eight kidneys. In all other cases the abscesses were additionally drained, which was done surgically in two and by ultrasonography- or CT-guided percutaneous drainage in four patients. Abscess cultures grew Staphylococcus aureus (three), Escherichia coli (one) and Salmonella Group B (one) and were sterile in one case. Drainage was unsuccessful in only one patient, who subsequently underwent nephrectomy for uncontrolled infection of a diffusely damaged kidney. We conclude that the diagnosis of renal abscesses is greatly facilitated by ultrasonography and CT and that most patients can be cured without operation by antibiotics and, if necessary, by additional percutaneous drainage. 
Potassium accumulation in the globally ischemic mammalian heart. A role for the ATP-sensitive potassium channel. We investigated the contribution of opening of the ATP-sensitive K+ channel to extracellular accumulation of K+ during ischemia with the use of glibenclamide, a specific blocker of this K+ channel. To characterize the electrophysiological effects of glibenclamide during metabolic inhibition (by either application of dinitrophenol or hypoxia) we performed patch-clamp studies in isolated membrane patches of guinea pig myocytes and in intact guinea pig myocytes and studied action potential parameters in isolated superfused guinea pig papillary muscle. We studied the effect of glibenclamide on extracellular accumulation of K+ and H+ in isolated retrogradely perfused globally ischemic hearts of rat, guinea pig, and rabbit. Experimental evidence is presented that supports the conclusions that glibenclamide 1) effectively blocks open K+ATP channels, 2) reverses the dinitrophenol-induced increase of the outward current and prevents the hypoxia-induced shortening of the action potential, 3) decreases the rate of K+ accumulation during the first minutes of ischemia in stimulated hearts, an effect which was entirely absent in quiescent hearts, and 4) does not influence the rate and extent of ischemia-induced extracellular acidification. 
Percutaneous endoscopic gastrostomy and early mortality. To assess morbidity, mortality, and benefit associated with percutaneous endoscopic gastronomy (PEG), we retrospectively studied 42 patients who had had PEG. Mortality was exceptionally high during the first 60 days after PEG (43%), and then stabilized. In nearly half of the cases (20/42) the PEG tube was removed during the first 60 days because of either death or improvement. Patients with malignancy had a significantly higher morbidity and 60-day mortality than the neurologically impaired. We concluded that patients should be carefully selected for PEG because early mortality is high; a 60-day trial of soft nasogastric feedings should be considered before PEG, and could reduce by nearly half the number of patients failing to receive long-term benefit; and patients with malignancy have significantly greater morbidity and mortality after PEG and may not receive the same advantage from the procedure. 
Urologic sarcoma in adults. Memorial Sloan-Kettering Cancer Center experience based on a prospective database between 1982 and 1989. Urologic sarcoma is a group of rare tumors with a generally poor prognosis. These sarcomas share prognostic characteristics with soft-tissue sarcomas arising from other sites. A staging system that incorporates tumor grade and size is valuable in identifying patients at high risk of dying of disease. Patients with sarcomas that are high-grade, greater than 5 cm in diameter, or metastatic at the time of presentation (MSKCC stages 3 and 4) have a combined 3-year relapse-free survival rate of 26%. Complete surgical resection, preferably with negative margins, still offers the best chance of cure. For reasons that are not clear, multimodality therapy in rhabdomyosarcoma is less effective in adult than in pediatric disease. Present-day chemotherapeutic regimens are ineffective in controlling disseminated sarcoma. The adoption of a uniform staging system coupled with multi-institutional collaboration may allow progress to be made in this otherwise deadly form of genitourinary cancer. 
von Willebrand factor and factor VIII in renal transplant recipients under immunosuppression with cyclosporine and steroids. Sequential measurements over 4 months in 17 patients. In 17 consecutive cadaver kidney transplant recipients treated with cyclosporine (CsA) and steroids, the median of antigenic and functional levels of von Willebrand factor (vWF) and factor VIII (FVIII) before transplantation were elevated (vWF:Ag: 206%, vWF:RCof: 202%; FVIII:Ag: 248%, FVIII:C: 224%; normal values 50-150%). Sequential measurements after transplantation and during CsA treatment revealed a transient significant increase of median values with highest amounts of vWF:Ag of 362% (2 p less than 0.0001), FVIII:Ag of 398% (2 p less than 0.001) and FVIII:C of 360% (2 p less than 0.0001) (Friedman test). vWF:RCof did not show statistically significant changes. After 4 months, levels of vWF and FVIII comparable to those obtained before transplantation were observed. In univariate statistical analysis no correlation was found between vWF of FVIII on the one hand and plasma creatinine levels, CsA dose or CsA whole blood through levels on the other hand. However, multivariate statistics revealed to some extent a positive influence of CsA blood levels on vWF:Ag levels. Patients with vascular rejection or chronic CsA nephrotoxicity showed significantly lower levels of vWF:Ag as compared with patients without endothelial cell damage in the kidney (2 p less than 0.05). However, the difference in vWF:Ag levels already existed before transplantation. In contrast to recent reports, plasma vWF levels were not indicative of vascular injury in kidney graft recipients nor was the marked elevation of vWF and FVIII associated with thromboembolic complications ascribed to CsA treatment. 
The relationship between locomotor disability, autonomic dysfunction, and the integrity of the striatal dopaminergic system in patients with multiple system atrophy, pure autonomic failure, and Parkinson's disease, studied with PET. 18F-dopa and S-11C-nomifensine (NMF) are positron emitting tracers whose caudate and putamen uptake reflects striatal dopamine storage capacity and the integrity of dopamine reuptake sites, respectively. Using these two tracers, the integrity of the presynaptic striatal dopaminergic system has been studied with positron emission tomography (PET) in 10 subjects with multiple system atrophy (MSA, Shy-Drager syndrome) who had an akinetic-rigid syndrome that was poorly responsive to L-dopa, autonomic failure, and cerebellar ataxia. PET findings for the 10 MSA patients were compared with those for 13 age-matched controls, 8 subjects with L-dopa responsive Parkinson's disease (PD), and 7 subjects with pure autonomic failure (PAF). Influx constants, Ki, reflecting specific 18F-dopa uptake into striatal tissue, were severely reduced in the putamen and caudate of the 10 MSA subjects (mean putamen Ki 0.005 min-1 MSA vs 0.013 min-1 controls; mean caudate Ki 0.007 min-1 MSA vs 0.013 min-1 controls). Reduction of putamen, but not caudate, 18F-dopa uptake correlated with severity and duration of locomotor disability. Eight patients with PD, and a similar degree and duration of locomotor disability to the patients with MSA, demonstrated equal impairment of mean putamen 18F-dopa uptake, but significant preservation of mean caudate function. The 7 PAF patients had normal mean levels of putamen and caudate 18F-dopa uptake, although 1 individual PAF patient had significantly impaired striatal function. The MSA and PD groups of subjects both showed significantly reduced levels of specific striatal S-11C-NMF binding, again caudate function being relatively preserved in PD. It is concluded that in both MSA and PD there is a parallel decline of striatal dopamine storage capacity and reuptake site integrity, probably reflecting a loss of nigrostriatal nerve terminals. Caudate function is relatively preserved in PD compared with MSA. The majority of PAF patients have an intact nigrostriatal dopaminergic system, suggesting that PAF is a condition distinct from PD and MSA in spite of some pathological similarities. PET is capable of detecting subclinical nigrostriatal involvement in PAF patients when this is present. 
Muscle regeneration following segmental necrosis in tenotomized muscle fibers. The aim of this study was to determine how the new myotendinous junctions were re-established at the proximal and distal ends of the soleus muscle after tenotomy. Both proximal and distal tendons of the soleus muscle in mature female rats were severed. The animals were killed and the soleus muscles were removed and prepared for light and electron microscopic examination 1, 3, 5, 7, 14, 21, 28, and 42 days after the operation. It was found that segmental fiber destruction followed by removal by macrophages occurred at the ends of the soleus muscle fibers. This resulted in the liberation and myogenic activation of satellite cells. By 3 days after tenotomy the fusion of myoblasts to form myotubes could be seen. The myotubes developed within the original basal lamina and reattached to the surviving non-necrotic segments and grew in both length and width so that by 6 weeks postoperation, normal myotendinous junctions had been reformed. This study is the first to show that re-establishment of the myotendinous junction following tenotomy is accomplished by regeneration of the necrotic ends of the tenotomized fibers. 
Composition of atherosclerotic plaques in coronary arteries in women less than 40 years of age with fatal coronary artery disease and implications for plaque reversibility. This study analyzes the composition of atherosclerotic plaques in the 4 major epicardial coronary arteries in 8 women less than 40 years of age (mean 34) with fatal coronary artery disease (CAD) and compares these data to previous studies of 37 adults greater than 45 years of age (mean 59) with fatal CAD. Histologic sections were taken at 5-mm intervals from the entire lengths of the right, left main, left anterior descending and left circumflex coronary arteries. With the use of a computerized morphometry system, analysis of the 4 major epicardial coronary arteries showed the major component of plaque to be a combination of cellular (mean percent total plaque area = 65%, standard error = 6%) and dense (19%, standard error = 6%) fibrous tissue. Arterial segments narrowed greater than 75% in cross-sectional area from these young women were compared with similarly narrowed arteries from 37 older patients (32 men [86%]) with fatal CAD previously reported by this laboratory, and showed significantly more cellular fibrous tissue and lipid-rich foam cells, and lesser amounts of dense fibrous and heavily calcified tissue. The large amount of lipid-containing foam cells and relative lack of acellular scar tissue in coronary plaques in these young women suggests a greater potential for reversibility of these plaques in this subset of patients with CAD. 
Orbit-related variation in spatial resolution as a source of artifactual defects in thallium-201 SPECT The cause of 180-degree diametrical artifactual defects in clinical thallium-201 SPECT imaging was investigated using phantom simulation. This artifact was observed on SPECT images acquired with a "body contour" or "peanut" orbit. It was hypothesized that this artifact was caused by differences in spatial resolution that occur when the heart-to-detector distance changes employing noncircular orbits. To test this hypothesis, a series of planar static images of a normal cylindrical phantom was obtained at varying distances from the camera detector head. From these images, tomographic acquisition files were created that simulated tomographic data acquired with circular orbits and elliptical orbits. The reconstructed phantom short-axis slices showed no artifacts for circular orbits. However, for various elliptical orbits, significant regional nonuniformity, similar to the artifacts noted in patients, was observed. The degree of nonuniformity correlated with the long-short axis ratio of elliptical orbits (r = 0.98). In addition, circular orbits with the phantom in an eccentric position resulted in similar nonuniformities. It is concluded that a noncircular tomographic orbit can create characteristic artifacts on thallium-201 SPECT images. For rotational thallium 201 SPECT, a circular orbit with the heart in the center of rotation should be employed. 
Bowel obstruction: evaluation with CT Eighty-four computed tomographic (CT) scans from patients referred for bowel obstruction between January 2, 1988, and December 31, 1989, were retrospectively evaluated. A pair of radiologists without knowledge of patient histories determined the presence or absence of bowel obstruction. Sixty-four patients ultimately proved to have intestinal obstruction, and 20 did not. Diagnosis was established by means of surgery (n = 39), barium studies (n = 17), and clinical course (n = 28). Causes of obstruction included adhesions (n = 37), metastases (n = 6), primary tumor (n = 7), Crohn disease (n = 4), hernia (n = 3), hematoma (n = 2), colonic diverticulitis (n = 2), and other (n = 3). In addition, 83 CT examinations in patients with no history or indication of intestinal obstruction were simultaneously reviewed. The overall sensitivity was 94%, specificity was 96%, and accuracy was 95%. The cause of obstruction was correctly predicted in 47 of 64 cases (73%). Intestinal obstruction was not diagnosed in any of the 83 control patients. CT is most useful in patients with a history of abdominal malignancy and in patients who have not been operated on and who have signs of infection, bowel infarction, or a palpable abdominal mass. 
Postheparin plasma diamine oxidase values in the follow up of patients with small bowel Crohn's disease. Measurement of postheparin plasma diamine oxidase (PHD) activity has been proposed to assess mucosal integrity in several diseases of the small intestine. In Crohn's disease, PHD values identify a group of patients with predominantly small bowel mucosal damage. To determine the role of mucosal involvement in the progression of small bowel Crohn's disease and whether different PHD values can predict different outcomes the changes in PHD values in 41 patients with small bowel Crohn's disease admitted consecutively to our department were investigated. The test was performed during periods of active disease and after either medical or surgical treatment had resulted in improvement. PHD values were significantly lower than in normal subjects (normal range 3.7-7.7 U/ml). In 35 patients with active disease (Crohn's disease activity index (CDAI) greater than 150) two groups were identified by choosing a cut off value of 2 U/ml: 93% of the 15 patients with PHD values lower than 2 U/ml (mean (SD) 1.36 (0.46) U/ml) relapsed at least once in the following year, while only the 20% of the 20 whose values were higher than 2 U/ml (mean (SD) 3.69 (1.50)) relapsed in the same period. The data were statistically significant (Yates's corrected chi 2 = 15.63; p less than 0.0001). The positive and negative predictive values of the test were 93% and 80%, respectively. During relapses, PHD values were consistently lower than previous values, and increased significantly after effective medical or surgical treatment. In the six patients in whom there were no changes in disease activity (CDAI persistently less than 150), there was no change in PHD values. 
The renal growth hormone/insulin-like growth factor I axis. Collecting duct is a major site of insulin-like growth factor-I (IGF-I) synthesis within kidney. Production of IGF-I at this site is stimulated by growth hormone (GH). IGF-I produced in collecting duct is likely to act on glomerulus and proximal tubule via IGF-I receptors present at these locations. Renal IGF-I may be causative of the glomerular and proximal tubular hypertrophy that occurs in hypersomatotropic states, of compensatory renal hypertrophy, and of renal regeneration following acute ischemic injury. 
Thermochemotherapy in inoperable head and neck cancer. A combined hyperthermia and chemotherapy approach was used to treat five patients with locally advanced or recurrent squamous cell carcinoma of the head and neck whose tumors had failed to respond to chemotherapy. In two patients, tumor had recurred after initial combined modality therapy (surgery/radiation) and had failed to respond to one course of cisplatin/5-fluorouracil (cisplatin/5-FU) chemotherapy. The three remaining patients were enrolled onto a phase II evaluation of induction chemotherapy with cisplatin/fluorouracil for advanced head and neck carcinomas and had failed to achieve a partial remission after one treatment cycle. Palpable cervical tumors were heated to 40 degrees to 42 degrees C for 30 to 40 minutes, during which time cisplatin (100 mg/m2) was infused intravenously. A 5-day infusion of 5-fluorouracil (1000 mg/m2/d) followed. Despite less than a partial response to previous cisplatin/fluorouracil chemotherapy alone, two patients had complete clinical resolution of the heated tumor volume with two cycles of the combined thermochemotherapy approach. One patient achieved a partial remission with this approach. The remaining two patients died shortly after the initial thermochemotherapy treatment, as a result of progressive tumor growth. The two complete responders were subsequently treated with radiation (1 patient) and radical neck dissection (1 patient) and remained without evidence of disease 2 and 26 months after the completion of therapy, respectively. The toxicity of this combined modality approach was acceptable and appeared to be no greater than had been experienced during earlier treatment with chemotherapy alone. Further studies using a combination of these treatment modalities for locally advanced head and neck carcinomas are warranted. 
Cytomegalovirus infection in Gambian mothers and their babies. A 15 month longitudinal study of cytomegalovirus (CMV) infection in 178 Gambian mothers and their babies was undertaken. Twenty five (14%) of the babies were congenitally infected despite the fact that 87% of their mothers were antibody positive to the virus. Two of the 25 congenitally infected infants had evidence of severe neurological damage; skin sepsis was also a prominent feature in congenitally infected infants. The other children soon became infected. At 6 months of age, 53% of the infants were shedding virus either in urine or saliva. By the age of 12 months 86% of the infants had serological evidence of CMV infection. Preliminary evidence suggests that sibling to sibling infection in crowded compounds might be a major route of transmission. 
Acid secretory responses and parietal cell sensitivity following duodenal ulcer healing with omeprazole, sucralfate, and Maalox. Acid secretory responses and parietal cell sensitivity (PCS) have been studied in 21 duodenal ulcer patients before and after successful treatment with omeprazole (n = 7), sucralfate (n = 7), or Maalox (n = 7). The second study was carried out 3 days after documented healing and withdrawal of treatment in the sucralfate- and Maalox-treated groups and 14 days after documented healing and withdrawal of treatment in the omeprazole-treated patients. Acid output (mmol/hour) was measured as basal secretion, and in response to 0.1 microgram/kg/hour pentagastrin (low-dose) and 6.0 micrograms/kg/hour pentagastrin (high-dose) stimulation. PCS was calculated as the ratio of low dose:high dose acid output (expressed as a percentage). Ulcer healing with sucralfate resulted in significant (p less than 0.05) decreases in low-dose acid output from 36.4% (13.2-51.0) (median [range]) to 8.4% (3.2-45.4) mmol/hour and PCS from 69.1% (44.9-91.4) to 22.0% (16.0-85.6), whereas no significant decreases in any of the measured parameters were noted following ulcer healing with Maalox. Ulcer healing with omeprazole resulted in significant (p less than 0.05) decreases in basal acid output from 6.3 (1.5-22.9) (median [range]) to 2.2 (0-6.9) mmol/hour, and low-dose acid output from 31.0 (6.0-58.0) to 23.0 (1.4-44.8) mmol/hour. These findings suggest that acid secretory responses following ulcer healing vary according to the therapeutic agent used. 
Selective versus routine predischarge coronary arteriography after therapy with recombinant tissue-type plasminogen activator, heparin and aspirin for acute myocardial infarction. TIMI II Investigators. To ascertain whether predischarge arteriography is beneficial in patients with acute myocardial infarction treated with recombinant tissue-type plasminogen activator (rt-PA), heparin and aspirin, the outcome of 197 patients in the Thrombolysis in Myocardial Infarction (TIMI) IIA study assigned to conservative management and routine predischarge coronary arteriography (routine catheterization group) was compared with the outcome of 1,461 patients from the TIMI IIB study assigned to conservative management without routine coronary arteriography unless ischemia recurred spontaneously or on predischarge exercise testing (selective catheterization group). The two groups were similar with regard to important baseline variables. During the initial hospital stay, coronary arteriography was performed in 93.9% of the routine catheterization group and 34.7% of the selective catheterization group (p less than 0.001), but the frequency of coronary revascularization (angioplasty or coronary artery bypass surgery) was similar in the two groups (24.4% versus 20.7%, p = NS). Coronary arteriograms showed a predominance of zero or one vessel disease (stenosis greater than or equal to 60%) in both groups (routine catheterization group 73.1%, selective catheterization group 61.3%). During the 1st year after infarction, rehospitalization for cardiac reasons and the interim performance of coronary arteriography were more common in the selective catheterization group (37.9% versus 27.6%, p = 0.007 and 28.6% versus 11.6%, p less than 0.001, respectively); however, the interim rates of death, nonfatal reinfarction and performance of coronary revascularization procedures were similar. At the end of 1 year, coronary arteriography had been performed one or more times in 98.9% of the routine catheterization group and 59.4% of the selective catheterization group (p less than 0.001), whereas death and nonfatal reinfarction had occurred in 10.2% versus 7.0% (p = 0.10) and 8.6% versus 9.0% (p = 0.87), respectively. Because the selective coronary arteriography policy exposes about 40% fewer patients to the small but finite risks and inconvenience of the procedure without compromising the 1 year survival or reinfarction rates, it seems to be an appropriate management strategy. 
Safety and efficacy of oral flecainide therapy in patients with atrioventricular re-entrant tachycardia. OBJECTIVE: To assess the short- and long-term safety and efficacy of oral flecainide therapy in patients with symptomatic tachycardia and an extranodal accessory pathway. DESIGN: Open-label, uncontrolled trial with a mean follow-up of 24 months. SETTING: Referral-based, teaching medical center. PATIENTS: Sixty-three patients with symptomatic tachycardia and an extranodal accessory pathway. INTERVENTIONS: Patients had electrophysiologic testing before and after the initiation of oral flecainide therapy and were followed long-term for the presence of symptoms, new physical limitations, and adverse effects of therapy. MEASUREMENTS AND MAIN RESULTS: Flecainide therapy prevented or slowed (324 +/- 59 ms to 398 +/- 55 ms; P less than 0.001) inducible sustained atrioventricular reciprocating tachycardia in 44 of 63 patients (70%). Of the 44 patients discharged from the hospital, 33 (75%) have continued to receive flecainide therapy and have shown no adverse effects (mean follow-up, 24 +/- 10 months). Adverse cardiac reactions (proarrhythmia or sinus node suppression) attributable to flecainide occurred in 11 of 63 patients (17%); in 9 (82%) of these 11 patients, events were detected during either in-hospital monitoring or the electrophysiologic study done before discharge. Structural heart disease was detected by two-dimensional echocardiography in 8 of 11 patients who had adverse cardiac events and in 6 of 52 patients who did not have such events (P less than 0.001). Isoproterenol reversed the effects of flecainide therapy in 11 of 21 patients; 7 of the 11 patients had spontaneous clinical recurrences of tachycardia or palpitations during the follow-up period, but these symptoms occurred in only 1 of 10 patients who did not show isoproterenol-induced reversal (P = 0.02). CONCLUSIONS: Oral flecainide therapy was effective in 33 of 63 patients who had tachycardia and an extranodal accessory connection. Hospital monitoring during initial therapy is recommended, and flecainide should be used with caution, if at all, in patients with structural heart disease. An isoproterenol challenge appears to be helpful in predicting late recurrence of tachycardia. 
Motor unit firing rates in postpolio and control subjects during submaximal contraction. Postpolio patients have a deficit in strength recovery after isometric activity. The cause for this is unknown, but may be the result of higher motor unit firing rates during the activity, which leads to excessive fatigue of the motor units. The purpose of this study was to determine whether postpolio subjects recruited motor units at higher firing rates than control subjects. Twelve control and seven postpolio subjects were tested for maximal voluntary contraction of the quadriceps isometrically. Randomly, subjects performed isometric contractions for five 10-s periods freely against gravity (threshold) and at 20% and 40% of maximal voluntary contraction. Decompositional motor unit electromyographic analysis was used to measure motor unit amplitude, motor unit firing rate and counted number of motor units identified. Analysis was by univariate analysis of variance. Motor unit firing rate was not significantly greater (P greater than 0.05) in postpolio subjects than control subjects at all three levels of contraction. Thus, it is unlikely that an increased motor unit firing rate leads to the deficit in recovery of strength in postpolio subjects. 
Nutritional support in Crohn's disease: which route? Nutritional and clinical responses to three nutritional regimens were retrospectively evaluated in 81 Crohn's patients with active disease. Group 1 (n = 42) received a low residue oral diet, group 2 (n = 15) received chemically defined diets, and group 3 (n = 24), parenteral nutrition (PN). Weight gain was observed in a similar percentage of patients, whereas serum albumin increase was significant only in group 3: 3.15 +/- 0.66 versus 3.54 +/- 0.61 g/100 ml (p less than 0.05). Mean activity index decreased significantly in all groups (p less than 0.001), and length of stay in hospital was similar. Patients with intestinal obstruction had a better immediate response when submitted to PN: clinical remission was achieved in 75% of those in group 3, but in only 50% in groups 1 and 2 (p less than 0.05). Otherwise, short- and long-term outcome was similar. 
Multicenter evaluation of a new fixed-wire coronary angioplasty catheter system: clinical and angiographic characteristics and results. Coronary angioplasty is increasingly used as an attempt to revascularize patients with severe coronary artery disease. To determine the efficacy of such treatment, a new fixed wire angioplasty catheter was evaluated by a multicenter group in a non-randomized fashion in 50 patients, average 58 +/- 11 years (+/- 1 SD), 58% men. Forty-four percent had a prior revascularization procedure (28% angioplasty, 16% coronary bypass surgery), 38% had a prior Q-wave myocardial infarction, 43% had grade 4 angina, and 60% multiple vessel disease. Angioplasty was attempted in 63 lesions which were located in a mid to distal location in 69%, with a proximal tortuosity score of 1.8 (2 = 45-60 degrees entrance angle), and lesion angulation of 1.4 (1 = 45 degrees lesion bend). In 88%, the device was the primary catheter used and in 6%, it was chosen when another system failed. The balloon was able to successfully cross 94% of all lesions attempted. Six lesions were crossed and dilated but significant residual stenoses remained. There were no significant device malfunctions, or angiographic or clinical complications. This feasibility evaluation of this new fixed wire system yielded excellent angiographic results. Although not a comparative study, this analysis suggests that this new generation of angioplasty catheter may improve the safety and efficacy of complex coronary angioplasty. 
Magnetic resonance imaging of vertebrobasilar ectasia in tic convulsif. Case report. A patient with trigeminal neuralgia and hemifacial spasm was evaluated using multiplanar magnetic resonance (MR) imaging with gadolinium enhancement. Preoperative images demonstrated massively ectatic vertebral and basilar arteries and their distortion of the brain stem and the trigeminal and facial nerves. Surgical manipulation included selective trigeminal rhizotomy, cushioning of the residual nerve at the point of maximal distortion by the underlying basilar artery, and microvascular decompression of the seventh nerve from the anterior inferior cerebellar artery which was being pushed dorsomedially by the vertebral artery. Postoperatively, the patient had neither trigeminal neuralgia nor facial spasm. Gadolinium-enhanced MR imaging not only excludes other etiologies such as tumor or arteriovenous malformation, but also demonstrates cranial nerve compression by ectatic vertebral and basilar arteries. The choice of preoperative imaging modality is discussed and the literature concerning the etiology of tic convulsif is reviewed. 
Anatomic correction of transposition of the great arteries with ventricular septal defect. Experience with 118 cases. One hundred eighteen patients, 100 with transposition of the great arteries plus ventricular septal defect and 18 with double-outlet right ventricle and subpulmonary ventricular septal defect have undergone arterial switch and patch closure of the ventricular septal defect since February 1983. In transposition of the great arteries the ventricular septal defect was perimembranous in 70 cases, trabecular in 28, and infundibular in 10. Eleven patients had multiple ventricular septal defects. In addition to 18 patients with double-outlet right ventricle, malalignment of the conal septum was present in 19 cases. Coronary type A distribution was recognized in 79 cases, type C in one, type D in 24, and type E in 14. Great arteries were side by side in 19% of cases. Aortic coarctation was present in 31 cases, and subaortic obstruction in 9. Age at operation ranged from 4 days to 4 years (mean, 3.5 +/- 8.3 months), and mean weight was 4.0 +/- 1.6 kg. Thirty-seven infants were younger than age 1 month. Thirty-six patients underwent previous operations: pulmonary artery banding alone (n = 13), pulmonary artery banding and coarctation repair (n = 13), and coarctation repair alone (n = 10). Mean time between the first procedure and the switch was 2.2 months. Six patients with aortic coarctation underwent one-stage repair, through median sternotomy, aortic reconstruction, closure of the ventricular septal defect, and arterial switch. Perioperative mortality was 13.5% (70% confidence limit 10% to 17.6%, n = 16). It was directly related to coronary artery kinking in 50% of deaths and to anatomy and size discrepancy of the great arteries in the remaining deaths. Univariate analysis could not find any significant risk factor of in-hospital mortality. Mean follow-up of 30.3 +/- 23.5 months was achieved in all but 2 survivors. There was one late death. Ten patients underwent 11 reoperations for recoarctation (n = 1), pulmonary stenosis (n = 7), residual ventricular septal defect (n = 2), and stenosis of superior vena cava (n = 1). Two patients needed a permanent pacemaker. Actuarial survival and freedom from reoperation at 5 years were 84.5% +/- 3.6% and 85.7% +/- 4.6%, respectively. We conclude that anatomic correction of complex transposition is a safe method that offers good early and midterm results. 
Progressive deterioration of auditory evoked potentials after excision of an acoustic neurinoma: case report. The authors report the case of a 17-year-old girl who underwent excision of bilateral neurinomas of the cerebellopontine angle. Although her auditory evoked potentials were well maintained during the operation, they deteriorated gradually and progressively for the following 2 months. This seemed to reflect degeneration of the cochlear nerve fibers initiated by operative manipulation in the cerebellopontine angle in a patient who had no hearing when she awoke from surgery. 
von Hippel-Lindau disease: inadequacy of angiography for identification of renal cancers. Selective renal angiograms were retrospectively evaluated for the identification of renal cell cancers in patients with von Hippel-Lindau disease (VHL). Seven patients underwent angiography and surgery because of solid or complex renal masses identified at cross-sectional imaging. Nine kidneys underwent detailed examination by the surgeon and by a pathologist. There were 31 renal cancers. Angiography had enabled identification of only five cancers (16%), and six others (19%) had been suspected. Cancers detected angiographically were larger than those not detected (P less than .05). Solid tumors tended to appear less hypervascular than expected and occasionally had the angiographic appearance of atypical cysts. There were no false-positive angiograms. Angiography revealed only one cancer not previously suspected and changed the surgeon's approach for only one kidney (11%). The sensitivity and specificity of angiography were 35% and 100%, respectively. In these patients, selective renal angiography is not helpful for the detection or exclusion of cancer in a kidney. It does not have a limited role for vascular mapping prior to partial nephrectomy or tumor enucleation. 
Abnormal hormonal and renal responses to saline load in hypertensive patients with parental history of cardiovascular accidents. BACKGROUND. Acute cardiac and cerebrovascular accidents are more frequent in hypertensive subjects with a family history of acute vascular accidents. The mechanisms underlying the susceptibility to vascular disease in these subjects are unknown. We investigated whether a parental history of premature heart attack or stroke in hypertensive subjects is associated with abnormalities of sodium handling. METHODS AND RESULTS. Patients with mild, uncomplicated essential hypertension were divided into two subgroups according to family history: a subgroup with a parental history of premature heart attack or stroke (FV+, n = 18) and a subgroup with a family history completely negative for vascular accidents (FV-, n = 14). The two subgroups were comparable with respect to age, weight, sex distribution, blood pressure, duration of hypertension, cardiovascular risk factors, renal function, and organ damage. Baseline plasma renin activity (PRA), concentrations of aldosterone (PA), atrial natriuretic factor (ANF), and norepinephrine, and urinary electrolyte excretion were also comparable in the two subgroups. Despite these similarities, the responses to an acute saline load, measured under controlled metabolic and experimental conditions, were different in the two subgroups. In the FV+ subgroup at 60 minutes of saline load, PRA fell by 1.0 +/- 0.2 ng/ml/hr and PA concentration by 89.4 +/- 26 pg/ml and ANF concentration increased by 38 +/- 9 pg/ml, whereas in the FV- subgroup the corresponding responses were -2.3 +/- 0.3 ng/ml/hr (p less than 0.005), -190 +/- 43 pg/ml (p less than 0.05), and 80 +/- 13 pg/ml (p less than 0.005), respectively. Urinary sodium excretion was delayed in the FV+ subgroup (270 +/- 67 mu eq/min at 60 minutes) compared with the FV- subgroup (555 +/- 157 mu eq/min at 60 minutes, p less than 0.05). At 120 minutes of saline load, significant (p less than 0.005) differences in PRA and ANF concentration were still observed. In a control group of eight normal subjects the responses to a saline load were comparable to those in the FV- subgroup but greater than those in the FV+ subgroup at 60 minutes. CONCLUSIONS. These results provide evidence that the hormonal and renal adjustments to an acute salt load are impaired in hypertensive patients with a parental history of vascular accidents. We speculate that abnormalities of sodium handling may represent markers of a more rapid development of vascular injury in human hypertension. 
Rare intrathoracic complications in acute pancreatitis. Ascites and pleural effusions may complicate pancreatitis but pericarditis with pericardial effusion and tamponade is rare and necrosis of mediastinal fat has not been described before. All these complications occurred in the case reported here. 
Gentamicin and vancomycin removal by continuous venovenous hemofiltration. The dispositions and dose requirements for vancomycin and gentamicin were investigated in a 58-year-old man who was receiving long-term continuous venovenous hemofiltration. Estimates of clearance were obtained using a Bayesian parameter estimation program and stayed remarkably consistent throughout the therapy. Single daily doses of both vancomycin and gentamicin generally maintained the profiles for both drugs around the target ranges of peak 5-10 mg/L (gentamicin) and 25-40 mg/L (vancomycin) and trough less than 2 mg/L (gentamicin) and less than 10 mg/L (vancomycin). 
Spinal cord herniation associated with an intradural spinal arachnoid cyst diagnosed by magnetic resonance imaging. Two rare cases of spinal cord herniation associated with intradural spinal arachnoid cyst are reported. A preoperative magnetic resonance imaging scan demonstrated the presence of spinal cord herniation, identified as a protrusion continuous with the spinal cord. Surgery upon the intradural spinal arachnoid cyst improved progressive neurological dysfunction. The authors postulate that spinal cord herniation occurred for the following reason: The pressure of the intradural arachnoid cyst on the dorsal aspect of the spinal cord caused thinning of the dura, leading to a tear and, thus, the development of an extradural arachnoid cyst. Along with the enlargement of intradural arachnoid cyst, the spinal cord herniated through the tear in the dura into the extradural arachnoid cyst. 
Spinal cord schistosomiasis: a pediatric case mimicking intrinsic cord neoplasm. We present the clinical, myelographic, MRI, and histologic data on a 7-year-old girl with confirmed Schistosoma mansoni infection of the spinal cord. MRI of the granulomatous spinal lesion revealed extensive enlargement of the cord in the T11-12 area, with some intramedullary swelling extending to T-5 through T-7. The clinical manifestations of spinal schistosomiasis can be diverse, and there should be a high index of suspicion for all patients from endemic areas. 
Collagen stability and collagenolytic activity in the normal and aneurysmal human abdominal aorta. Two issues were addressed in this study. The first was whether a bona fide collagenase exists within the wall of the aorta. The second was whether the activity of this putative collagenase is greater in aneurysmal tissue. No collagenase could be extracted from the wall of the aorta under nondenaturing conditions. However, hydroxyproline was liberated from tissue samples allowed to autolyze at neutral pH under reaction conditions favoring the activity of collagenase. Such an activity was probably enzymic as it occurred in a time- and temperature-dependent fashion and was suppressed by chelators. In normal and stenotic tissue, activity was increased by adding aminophenylmercuric acetate, an activator of latent collagenase. Examination of the blanks revealed that the collagen of aneurysmal aorta was more soluble than normal. Furthermore, its digestion kinetics differed in a way that suggested that aneurysmal aorta possessed a labile component that was absent from normal tissue. Although the activity of the putative aortic collagenase was higher than normal in the aneurysmal tissue, our assays do not distinguish between changes in the amount or activity of the enzyme and alterations in the collagen. 
Late follow-up after repair of left ventricular aneurysm and (usually) associated coronary bypass grafting. This study assesses clinical and operative data (LV) aneurysm was repaired to determine factors that might predict in-hospital and long-term outcome. Long-term follow-up study was obtained in 296 of 298 patients undergoing LV aneurysm repair with or without coronary artery bypass grafting between 1974 and 1986. No patient had sustained a myocardial infarction within 2 weeks of surgery or was undergoing other concurrent cardiac surgery. The average age of the study patients was 57 +/- 9 years and the average ejection fraction was 35 +/- 13%. Ninety percent of the patients underwent concurrent bypass grafting, with an average of 2.2 +/- 1.3 grafts placed. Fourteen (5%) patients died in the hospital, with most deaths attributable to LV dysfunction. Advanced age and less extensive revascularization were correlates of in-hospital mortality. The 10-year survival was 57%, myocardial infarction-free survival 43%, and freedom from death, myocardial infarction and reoperative coronary surgery 41%. Advanced age, systemic hypertension, significant left main coronary artery narrowing and emergent operative status were multivariate correlates of long-term mortality. A low-risk population was defined by the absence of these risk factors, and high-risk by the presence of greater than or equal to 1 risk factors. The 10-year survival was 71% in the low-risk and 41% in the high-risk groups (p = .0006). The 10-year myocardial infarction free survival was 55% in the low-risk and 31% in the high-risk groups (p = 0.0017). LV aneurysm repair may be performed with acceptable in-hospital mortality, and the long-term risk may be stratified. 
Insulin resistance after surgery: normalization by insulin treatment. 1. Injury is known to be associated with variable degrees of tissue insensitivity to insulin. We measured insulin resistance in a group of non-obese, glucose-tolerant patients undergoing major elective surgery with an uncomplicated post-operative course. 2. Shortly after surgery, hyperglycaemia (7.3 +/- 0.6 versus 4.2 +/- 0.3 mmol/l glucose pre-surgery, mean +/- SEM, P less than 0.01) with normal insulin concentrations (73 +/- 15 versus 64 +/- 18 pmol/l) suggested the presence of insulin resistance. Counter-regulatory hormones were raised, whole-body protein oxidation was doubled (P less than 0.01) and energy expenditure was up by 18% (P less than 0.01). 3. Insulin sensitivity was quantified by clamping plasma glucose concentrations at 5.6 mmol/l during 24 h of total parenteral nutrition (15% protein, 55% glucose and 30% fat, supplying 1.25 times the measured resting energy expenditure) with a variable infusion of exogenous insulin. After surgery, eight times more insulin was needed than before surgery (14.14 +/- 1.15 versus 1.78 +/- 0.29 pmol min-1 kg-1, P less than 0.001) to maintain euglycemia. 4. After surgery, stimulation of net carbohydrate oxidation (18.8 +/- 1.4 versus 17.2 +/- 1.8 mumol min-1 kg-1 preoperatively, not significant), suppression of lipolysis and lipid oxidation and inhibition of ketogenesis occurred to the same extent as before surgery. Of the infused nutrients, the glucose was all oxidized, amino acids replaced endogenous protein losses (= neutral nitrogen balance) and lipids were stored. Insulin administration caused no further increment in oxygen consumption or energy expenditure. 
Renal effects of ANF (95-126), a new atrial peptide analogue, in dogs with experimental heart failure. Atrial natriuretic factor 95-126 [ANF (95-126)] is a novel 32 amino acid peptide which is thought to originate from the kidney. The systemic hemodynamic and renal effects of equimolar doses of intravenous synthetic ANF (95-126) and synthetic alpha ANF (99-126) were examined in normal dogs (n = 6) and in dogs with an arteriovenous (AV) fistula and chronic compensated high-output heart failure (n = 5). ANF (95-126) and alpha ANF (99-126) were infused at 5 and 10 pmol/kg/min for 75-min periods each. In the normal and AV fistula dogs the two peptides similarly decreased mean arterial pressures and right atrial pressures (P less than .05). Creatinine clearance and urinary volume excretion increased (P less than .05) in the normal dogs with both peptides, but only ANF (95-126) produced significant elevations (P less than .05) of these two parameters in the AV fistula animals. With the highest infusion dose, ANF (95-126) increased urinary sodium excretion to at least twice the levels observed with alpha ANF (99-126) in both groups of dogs (P less than .05). The decreases in plasma renin and aldosterone were comparable for the two peptides in both groups of animals. These results indicate that ANF (95-126) is more potent than alpha ANF (99-126) for the promotion of a natriuresis, particularly in AV fistula dogs with compensated high-output heart failure, in which the sodium excretory actions of alpha ANF (99-126) were attenuated markedly. 
Percutaneous biopsy of left adrenal masses: prevalence of pancreatitis after anterior approach. Acute pancreatitis is an unusual but recognized complication of percutaneous aspiration biopsy of the pancreas. As the pancreatic tail is located anterior to the left adrenal gland, percutaneous biopsy of a left adrenal mass via the anterior approach may result in needle passage through the tail of the pancreas with subsequent potential development of pancreatitis. To evaluate this risk, we retrospectively reviewed 48 CT-directed percutaneous aspiration biopsies of left adrenal masses done between 1984 and 1989 at two institutions. Positioning of the patient, the course of the needle, the number of needle passes, and the size of the needle were analyzed. Thirty-three (69%) of 48 biopsies of a left adrenal mass were performed by using the anterior approach. The pancreas was traversed by one or more needles in 32 of 33 cases. Biopsies were performed with 20- to 22-gauge needles, and the number of needle passes varied widely. The medical records of the 33 patients in whom the anterior approach was used also were reviewed for complications. Acute pancreatitis, which required 11-13 days of hospitalization, developed in two patients (6%). None of the other 31 patients suffered a complication. We conclude that the pancreatic tail is routinely traversed by the biopsy needle when biopsy of a left adrenal mass is done via the anterior approach and that severe acute pancreatitis can occur as a result. 
Changes of DNA methylation and chromatin structure in the human myeloperoxidase gene during myeloid differentiation. Expression of the myeloperoxidase (MPO) gene is tightly regulated in a tissue- and development-specific manner. Accumulation of MPO messenger RNA (mRNA) occurs only at the late myeloblastic and promyelocytic stages of myeloid differentiation and is negligible at other stages of myeloid development and in other tissues. The goal of our studies was to begin to understand the events that occur to control MPO gene expression during normal granulocytopoiesis. Chromatin structure of the MPO gene was evaluated by DNase I treatment of isolated nuclei and Southern blot analysis. No detectable DNase I hypersensitive sites were found in the region of the MPO gene in non-myeloid cells. One site was present in the 5' upstream region in myeloid cells that are developmentally too immature to transcribe MPO. Three sites of hypersensitivity in the regions of the putative MPO promoter and upstream region occurred in MPO-expressing promyelocytes. These sites were markedly reduced in terminally differentiated, non-expressing myeloid cells. Analysis of DNA methylation of the MPO gene using methylation-sensitive restriction enzymes showed that the gene was highly methylated in non-myeloid cells. Stepwise demethylation occurred in myeloid cells developmentally too immature to transcribe MPO. Maximal demethylation in the 5' gene region occurred in MPO-expressing promyelocytes. This methylation pattern did not change in terminally differentiated, MPO non-expressing myeloid cells. A somatic hybrid cell formed by fusion of HL-60 (MPO-expressing cells) and PUT (MPO non-expressing lymphoid cells) extinguished expression of MPO and showed a chimeric pattern of MPO gene methylation, suggesting that demethylation is necessary but not sufficient for expression of the MPO gene. Our studies show that demethylation and DNase I hypersensitivity of the MPO gene were associated with a tissue-dependent potential for MPO gene expression that preceded the developmental ability to express MPO mRNA. 
Genetic susceptibility to Parkinson's disease. Genetic factors clearly cause Lewy-body Parkinson's disease (PD) in a subset of autosomal-dominant families. However, most cases of PD are sporadic. The two most likely models of four discussed for sporadic PD are the reduced penetrance model and the multifactorial model. Sporadic PD is likely to be caused by the combined effect of environmental precipitating factors and genetic susceptibility factors. Because the number of major genetic factors is likely to be small, these hypotheses can be tested and genetic factors located using linkage mapping techniques. The affected pair analysis methods are especially suited to PD. Finding the genetic susceptibility factors for PD is important because this may be the fastest way to identify the environmental precipitating factors and because it may lead to prevention of PD. Because of the usefulness of identifying genetic susceptibility factors for PD, we are carrying out linkage studies in a group of 16 large autosomal-dominant families with PD and more than 300 living affected PD pairs. 
Tardive dyskinesia and chronic pain. Psychotropic drugs are frequently used to treat chronic pain. Tardive dyskinesia is a serious complication of such therapy, but is not mentioned in the pain literature. Two cases are reported and the implications discussed. 
Fracture line in post head injury optic nerve damage. Diminution of vision following head injuries involving the optic canal is not uncommon. In order to find out how a blunt trauma to the frontotemporal region produced damage to the optic nerve in its canalicular portion, this study was conducted on cadaveric skulls and its results are described. 
Auscultation with an esophageal stethoscope. A new test for pneumoperitoneum. Auscultation for the tympanic sound characteristic of developing pneumoperitoneum during insufflation of the abdomen at laparoscopy was performed with an esophageal stethoscope. Such auscultation detected pneumoperitoneum as soon as or sooner than did the other, standard methods to which it was compared. This test requires no additional maneuvers beyond those routine in standard laparoscopic and anesthetic procedures, providing a useful adjunctive test for pneumoperitoneum acquisition. 
Benign arterial dissections of the posterior circulation. Four young adults with spontaneous dissection of the vertebrobasilar system are reported. Clinically, two patients presented with subarachnoid hemorrhage and two with brain-stem ischemia. In two cases of ruptured arterial dissection of the posterior cerebral artery, angiography demonstrated fusiform and "sausage-like" dilatation of the involved vessel. In two cases of occlusive dissection of the basilar artery, angiography revealed the typical "string sign." All four patients were treated conservatively: three survive in good clinical condition and one remains disabled. Follow-up angiograms showed spontaneous healing of the lesion with return to an almost normal arterial configuration in two cases; residual narrowing corresponding to the dissection was the most notable finding in the other two. It is recommended that, in a subset of neurologically stable patients, angiographic monitoring is undertaken to assess the tendency for spontaneous repair before surgical intervention is planned. 
Presence of PAF-acether in stool of patients with pouch ileoanal anastomosis and pouchitis. Platelet-activating factor is an endogenous phospholipid produced by a wide variety of inflammatory cells. Platelet-activating factor induces severe pathological changes in various organs and, among numerous potent effects, causes bowel necrosis. Pouchitis is a poorly understood complication of ileoanal pouch anastomosis which occurs in patients who undergo surgery for ulcerative colitis. The aim of this study was to measure ileal or fecal platelet-activating factor and lyso platelet-activating factor contents in normal volunteers (n = 12), in patients with terminal ileostomy (n = 7), and in patients with ileoanal anastomosis (n = 15) (8 patients have pouchitis defined by the presence of ulcerations on the reservoir). Fecal samples were processed and assessed for platelet-activating factor by platelet aggregation assay. The aggregating material was further characterized as platelet-activating factor by the following: inhibition of the platelet aggregation it induced by specific platelet-activating factor receptor antagonist (BN 52021; IHB, Le Plessis Robinson, France); abolition of platelet aggregation after incubation with phospholipase A2 but not with lipase A1; and retention time on high-performance liquid chromatography. Stool platelet-activating factor content (in nanograms per gram of stool, mean +/- 1SD) was significantly increased in patients with pouchitis (22.2 +/- 16 ng/g) compared with patients with normal reservoir (1.59 +/- 0.63 ng/g, P less than 0.01), terminal ileostomy (0.59 +/- 0.43 ng/g, P less than 0.01), and healthy controls (0 +/- 0 ng/g of stool, P less than 0.001). Lyso platelet-activating factor (nanograms per gram of stool) was increased in patients with pouchitis (10,704 +/- 5499 ng/g) compared with patients with normal reservoir (4721 +/- 4549 ng/g of stool, P less than 0.05), terminal ileostomy (3042 +/- 4019 ng/g, P less than 0.02), and healthy volunteers (128 +/- 107 ng/g, P less than 0.001). In patients with ileoanal anastomosis and pouchitis, increased platelet-activating factor production could be implicated in the inflammation and ulcerations observed in the reservoir. 
Quinine-induced immune thrombocytopenia associated with hemolytic uremic syndrome: a new clinical entity. Three patients are described who developed severe thrombocytopenia, microangiopathic hemolytic anemia, and acute renal failure after ingestion of quinine. In one patient, the same clinical findings recurred several months later after another exposure to quinine. Serum from one patient contained quinine-dependent IgG antibodies reactive with the platelet glycoprotein (GP) Ib/IX complex. In the second and third cases, serum contained IgG and IgM antibodies reactive with both the GP Ib/IX and IIb/IIIa complexes in the presence of quinine. Quinine appears to have induced both immune thrombocytopenia and the hemolytic uremic syndrome (HUS) in these individuals. Findings made in these cases may have implications for the pathogenesis of some forms of HUS. 
Managing the care of patients with dementia. How to maximize level of functioning and minimize behavior problems. Effective treatment of patients with dementia involves supporting and educating the primary caregiver, uncovering and correcting the underlying cause of any decompensation that may occur, and deciding when drug therapy is appropriate. Caregivers must be taught how to cope with the patient's denial and how to modify the patient's environment so that it is safe and easy to understand. Pharmacologic therapy for depression accompanying dementia can improve a patient's quality of life and independence considerably; drugs may also be of help in dealing with patients who resist care. Psychotic symptoms usually do not require pharmacologic treatment, and hypnotics should, if possible, be avoided as a solution to sleep problems. 
Revision osteoarticular allograft transplantation in weight-bearing joints. A clinical review. The early results of revision osteoarticular allografts in weight-bearing joints are reported. Sixteen consecutive patients underwent surgery over a six-year period between 1982 and 1988. At the time of review eight patients (50%) had surviving second allografts with an average follow-up time of 48 months (range 12 to 87). Five patients were graded excellent according to the Mankin scale, one good and two fair. Eight patients (50%) required further surgery, but only two patients came to amputation. 
Inorganic mercury transport in the proximal tubule of the rabbit. Inorganic mercury transport was studied in the S1, S2, and S3 segments of the isolated perfused proximal tubule of the rabbit. The concentration of mercury in the perfusate was 18.4 microM. At this concentration all three segments of the proximal tubule underwent degenerative changes that proceeded to cellular necrosis at the end of the tubule which was attached to the perfusion pipet. This pathological process progressed along the tubule for approximately 200 microns. The remainder of the tubule, to the collection pipette, remained intact and free of any pathological changes. In examining the transport of mercury under these condition, it was found that, on average, the S1, S2, and S3 segments all removed inorganic mercury from the luminal fluid at approximately 140 fmol min-1 mm-1. The transport of mercury, as measured by the appearance of 203Hg in the bathing solution, was 80% lower than the removal of 203Hg from the luminal fluid. The mercury appearing in the bath could be accounted for by passive leakage through the necrotic portion of the tubule in the S1 and S2 segments, but not in the S3 segment. Leakage could account for only 16.2% of the transepithelial movement of inorganic mercury in the S3 segment. Inorganic mercury taken up by the tubule (92%) was primarily associated with the structural proteins of the tubular epithelial cells, while very little (8%) was found in the tubular extract. The toxicity of inorganic mercury was determined by titration. Perfusion with 1 microM inorganic mercury produced necrosis. The pathological features appeared to be the same as those resulting with 18.5 microM inorganic mercury. 
Colorectal ornithine decarboxylase activity in human mucosa and tumors: elevation of enzymatic activity in distal mucosa. To examine the value of ornithine decarboxylase (ODC) assay as a biological marker of potential malignancy in large bowel, we harvested 43 colorectal carcinoma, 7 adenoma, 6 polyps, and 77 normal-appearing mucosa at surgery from patients with colorectal carcinoma. In addition, 13 normal rectal mucosa were obtained at biopsy from patients with benign diseases or diseases unrelated to colorectal carcinoma as normal control. ODC activity was significantly higher in polyps and adenocarcinomas than in normal-appearing mucosa from patients with colorectal carcinoma. ODC activity in normal-appearing mucosa varied throughout the large intestine, with significantly higher activities in the distal segment of the large bowel. The higher ODC activity detected in the sigmoid colon and rectum correlates with the larger incidence of tumor development in this region of the large bowel. This observation needs to be taken into consideration when ODC activities of the colorectal mucosa are measured as biological markers of potential malignancies. 
Pheochromocytoma of the urinary bladder. A case of pheochromocytoma of the bladder involving a ureteral orifice is presented, with a review of the literature. We discuss general management principles of bladder pheochromocytoma and factors specific to the management of our case, which allowed complete removal of the benign tumor while preserving bladder and ureteral function. Imaging modalities for localizing extraadrenal pheochromocytomas are reviewed. 
The concept of uterine preservation with ovarian malignancies. A 30-year-old woman with bilateral, recurrent, borderline papillary serous cystadenocarcinoma of the ovary was treated with bilateral oophorocystectomy and omentectomy with uterine preservation. Ten years later, through induction of an artificial endometrial cycle and ovum donation, she conceived twins and delivered two healthy infants. Staging exploratory laparotomy at the time of cesarean delivery was negative for malignancy. This case illustrates the value of uterine preservation for cases in which classical teaching has indicated hysterectomy with bilateral salpingoophorectomy. 
Comparison of the effects of atenolol and nifedipine on glucose, insulin, and lipid metabolism in patients with hypertension. Various aspects of carbohydrate and lipid metabolism have been studied in two groups of patients with mild hypertension before and after four months of treatment with either nifedipine (n = 12) or atenolol (n = 12). Mean (+/- SEM) blood pressure fell to the same degree following treatment with either nifedipine (147 +/- 3/98 +/- 2 to 134 +/- 2/85 +/- 2 mm Hg) or atenolol (149 +/- 3/99 +/- 2 to 135 +/- 2/86 +/- 3 mm Hg). Circulating plasma glucose, insulin, and triglyceride concentrations were measured at hourly intervals from 8:00 AM to 4:00 PM, before and after breakfast (8:00 AM), and at lunch time (noon). The response to treatment was different in the two groups. Specifically, plasma glucose concentration were unchanged and insulin concentrations were higher in association with atenolol treatment. In contrast, nifedipine-treated patients had similar plasma insulin, but lower plasma glucose and triglyceride concentrations after four months of therapy. The changes in day-long plasma glucose and insulin responses suggested that resistance to insulin-stimulated glucose uptake had increased in association with atenolol treatment and decreased following nifedipine. This conclusion was supported in that measurement of insulin-stimulated glucose disposal showed a decrease in atenolol-treated patients and an increase in nifedipine-treated patients. Finally, plasma lipoprotein cholesterol concentrations did not change following atenolol therapy, whereas plasma high density lipoprotein cholesterol increased in association with nifedipine administration. These data show that changes in carbohydrate and lipid metabolism observed with treatment of mild hypertension can vary significantly as a function of the drug used, despite similar beneficial effects on blood pressure. 
Toxicity and immunomodulatory effects of interleukin-2 after autologous bone marrow transplantation for hematologic malignancies. Autologous bone marrow transplantation (ABMT) for advanced hematologic malignancies is associated with high relapse rates. Interleukin-2 (IL-2) and lymphokine-activated killer (LAK) cells represent a potentially non-cross-resistant therapeutic modality that might prevent or delay relapses if used early after ABMT at a time when the tumor burden is minimal. However, high-dose chemoradiotherapy and ABMT might increase patients' susceptibility to IL-2 toxicity, and might interfere with immunologic responses to IL-2 in vivo. Therefore, to determine safety, tolerance, and immunomodulatory effects of IL-2 therapy early after ABMT, IL-2 was administered by continuous intravenous infusion to 16 patients 14 to 91 days (median, 33) after ABMT for acute leukemia, lymphoma, or multiple myeloma. Patients were sequentially assigned to escalating IL-2 "induction" doses (0.3 to 4.5 x 10(6) U/m2/d, days 1 to 5), and all patients received a nonescalating IL-2 "maintenance" dose (0.3 x 10(6) U/m2/d, days 12 to 21). Most patients exhibited mild to moderate fever, nausea, diarrhea, and/or skin rash with IL-2 infusions. The maximum tolerated "induction" dose was 3.0 x 10(6) U/m2/d; dose-limiting toxicities were hypotension and thrombocytopenia. All toxicities reversed on stopping the IL-2 infusions, and all patients completed "maintenance." Postinfusion lymphocytosis was exhibited by patients at all IL-2 dose levels. With the higher IL-2 doses, increased percentages of patients' PBMC expressed CD16 and CD56, with augmented lysis of K562 and Daudi, reflecting the induction of natural killer and circulating LAK effector activities. Increased LAK precursor activity was exhibited by patients at all IL-2 dose levels. Thus, the IL-2 therapy regimen was safely tolerated after ABMT, and pronounced immunomodulatory effects were observed with the higher IL-2 doses. These studies support the planned use of IL-2 and LAK cells after ABMT in an attempt to reduce relapses of advanced hematologic malignancies. 
Evaluation of indium-111-labeled antifibrin monoclonal antibody for the diagnosis of venous thrombotic disease The potential advantage of using 111In-antifibrin (111In-AF) monoclonal antibody for the diagnosis of deep venous thrombosis (DVT) was studied in 44 patients with suspected DVT (27 underwent heparin therapy before 111In-AF injection). All patients had contrast venography (considered as the gold standard) and 111In-AF scintigraphy within 24 hr. Two to 3 mCi of 111In-AF were injected intravenously, and planar scintigraphy of the limbs was recorded within 10 min (17 times), 3 hr (44 times), and 18 hr (39 times). Indium-111-AF images were then interpreted without knowledge of the results of the other examinations. The DVT diagnostic accuracy of 111In-AF was greater when interpretation was based on images recorded at different time periods after injection. Indium-111-AF sensitivity for diagnosis of DVT was 85% (29/34) and was not apparently decreased by heparin therapy. None of the 10 patients with negative contrast venography had a positive 111In-AF scan. The results demonstrate the importance of recording serial images and the excellent accuracy of 111In-AF for diagnosing DVT. 
The stomach in liver cirrhosis. Endoscopic, morphological, and clinical correlations. The stomachs of cirrhotic patients are frequently subject to a number of alterations, detectable by endoscopy, the presence of which indicates a disturbance in the mucosa. Several investigators believe that portal hypertension plays an etiopathogenetic role. Three groups of subjects were studied prospectively: 83 cirrhotic patients with portal hypertension, 53 cirrhotic patients without portal hypertension, and 135 control subjects. Snake skin, scarlatina rash, and petechia were the most frequent endoscopic findings in the cirrhotic patients with portal hypertension (P less than 0.001); these findings were also most frequently present in association with each other in this group. There was no correlation between the endoscopic findings, the clinical gravity of liver cirrhosis (Child-Pugh grade), and the gravity of esophageal varices (Beppu score). There were no characteristic inflammatory findings in the gastric mucosa. Hypergastrinemia was often observed in cirrhotic patients with and without angiodysplasias. 
Different lectin-binding patterns in primary breast cancers and their metastases. The expression of glycoconjugates in primary tumors and their metastases in 18 consecutive cases of metastasized breast cancer was studied by use of lectin histochemistry. Paraffin sections were stained with a panel of seven fluorochrome-labeled lectins with defined sugar specificities. The study revealed variation in the lectin binding patterns of individual cancers. In the primary tumors the lectin reactivity was diversified, whereas in their respective metastases it was rather homogeneous. This finding indicates that there is intratumoral heterogeneity in the primary cancers, whereas the selected subclones of malignant cells with restricted glycoconjugate expression seem to give rise to metastases. 
Pyridostigmine used as a nerve agent pretreatment under wartime conditions. OBJECTIVE. To determine the adverse effects of pretreatment with pyridostigmine bromide for nerve agent exposure during wartime. DESIGN. A retrospective study. SETTING. Southwest Asia. PARTICIPANTS. Personnel who provided medical support to the XVIII Airborne Corps. These medical officers supplied information pertaining to symptoms and disposition of 41,650 soldiers who received pyridostigmine at the onset of hostilities of Operation Desert Storm. INTERVENTION. Pyridostigmine bromide, 30 mg orally, was self-administered every 8 hours while under the threat of nerve agent attack (for 1 to 7 days). MAIN OUTCOME MEASURE. Physiologic changes attributable to pyridostigmine that resulted in need for medical attention, discontinuation of the drug, hospitalization, and/or evacuation from Southwest Asia. RESULTS. About half of the population noted physiologic changes that were not incapacitating, such as increased flatus, abdominal cramps, soft stools, and urinary urgency. Approximately 1% of the soldiers believed they had effects that warranted medical attention, but fewer than 0.1% had effects sufficient to discontinue the drug. Nonincapacitating symptoms often occurred; however, military mission performance was not impaired. CONCLUSION. While under the threat of nerve agent attack, pyridostigmine can be administered to virtually all soldiers. 
Phase I/II trial of recombinant human granulocyte-macrophage colony-stimulating factor following allogeneic bone marrow transplantation. Forty-seven patients with hematologic neoplasia received recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) by daily 2-hour infusion following allogeneic bone marrow transplantation from HLA-identical sibling donors in a phase I-II dose-escalation trial. Dose levels ranged from 30 to 500 micrograms/m2/d. At doses at or below 250 micrograms/m2/d, toxicity felt to be caused by rhGM-CSF was negligible. However, three of five patients treated with 500 micrograms/m2/d had unacceptable side effects caused by rhGM-CSF. Two different graft-versus-host disease (GVHD) prophylactic regimens were administered. Twenty-seven evaluable patients were administered regimens that did not contain methotrexate (MTX) (Group I) and reached an absolute neutrophil count of 1,000/microL by a median of day 14. In contrast, 18 patients who received GVHD prophylactic regimens containing MTX (Group II) reached an absolute neutrophil count of 1,000/microL on a median of day 20. Patients in Group I had fewer febrile days and, of those discharged, had shorter initial hospitalizations than patients in Group II. The overall incidence of severe acute GVHD (grade 2 or greater) in the rhGM-CSF-treated patients was 28% and was similar to that in historical "good risk" patients who did not receive rhGM-CSF. These preliminary data suggest rhGM-CSF is unlikely to exacerbate GVHD in HLA-identical sibling donor transplants and indicate the need for randomized trials of rhGM-CSF in allogeneic marrow transplant patients. 
Diffusion-weighted MR imaging of the brain: value of differentiating between extraaxial cysts and epidermoid tumors. This study demonstrates the use of diffusion-weighted MR imaging in improving the specificity of the diagnosis of extraaxial brain tumors. Three surgically proved lesions (one arachnoid cyst and two epidermoid tumors) and two nonsurgically proved lesions (arachnoid and ependymal cysts) were evaluated with T1- and T2-weighted spin-echo studies followed by intravoxel incoherent motion (IVIM) MR imaging. The IVIM images of the lesions were displayed as an apparent diffusion coefficient (ADC) image obtained at 0.65 G/cm (maximum gradient b value = 100 sec/mm2) and compared with external oil and water phantoms. The ADC of arachnoid cysts was similar to stationary water whereas the ADC of epidermoid tumors was similar to brain parenchyma, indicating the solid nature and the slower diffusion rate of the epidermoid tumors. Cisternal CSF demonstrated uniformly high ADC, primarily because of bulk flow, which enhanced image contrast. Improved delineation of postsurgical changes was also possible. Our preliminary results show that diffusion-weighted MR imaging can be useful in distinguishing between arachnoid cysts and epidermoid tumors. 
Invasive Chrysosporium infection of the nose and paranasal sinuses in an immunocompromised host. Aggressive fungal rhinosinusitis with Chrysosporium sp. occurred in a patient with acute lymphocytic leukemia. The infecting organism is an exceedingly rare human pathogen. Usually, human chrysosporial infections are mild and unmarked by symptoms. Most case reports appear in the pathology literature and describe the incidental finding of adiaspores in the pulmonary parenchyma at autopsy. Clinical disease from active growth of chrysosporial mycelia in human tissues has been noted on a porcine aortic valve prosthesis and in a tibial abscess. Hyphal elements were not recovered from any other body parts of these patients. Histopathologic and microbiologic studies permitted the identification of this rarely encountered organism. Our patient experienced systemic spread of Chrysosporium organisms. Treatment of this pathogen is the same as for other opportunistic fungal infections. 
Conventional versus laparoscopic cholecystectomy and the randomized controlled trial. Cholecystectomy Study Group We considered using a randomized trial to assess the value of laparoscopic cholecystectomy in the treatment of symptomatic gallstones. The pros and cons for the timing of such a trial were in favour of not beginning the trial until surgeons learned to use the new procedure safely and effectively, and until key endpoints and outcome indices could be identified and assessed using valid measures. Instead an observational study was implemented to monitor the learning curve of surgeons as they mastered the laparoscopic equipment and procedures, and to assess the responses of the patients to the procedure. In the first 100 patients, the procedure proved to be as safe and feasible to use as conventional surgery, and there were strong benefits in terms of quicker recovery of the patients with less pain, discomfort, and a reduced length of hospital stay. The responses of the surgeons and the patients to the new procedure now place ethical constraints on the planning of a randomized controlled trial. Currently, comprehensive surveillance and monitoring of laparoscopic cholecystectomy is the only realistic method with which to assess the impact of this new technology in our clinic. 
The radiology of headache. The patient who presents with a severe and acute headache should be evaluated radiographically with CT. The key diagnosis to make in this situation is hemorrhage, either subarachnoid or intraparenchymal. Computed tomography is more sensitive to acute hemorrhage than is MRI. When the patient is stable, MRI frequently contributes information to narrow the diagnostic possibilities, because vascular malformations and certain parenchymal lesions have a characteristic appearance on MRI. Hydrocephalus may also present acutely and is easily seen on CT or MRI. In a patient may show WMF and atrophy. The patient with trigeminal neuropathy may demonstrate central or peripheral lesions. In temporomandibular joint dysfunction, conventional tomography and MRI are frequently used. Magnetic resonance imaging shows excellent detail of the disk and surrounding soft tissues, whereas tomography better demonstrates bony changes. When a history of trauma is present, MRI may show a subacute subdural hematoma. These collections are easily seen on MRI, even when isodense on CT. Evidence of old shear injury is also well seen on MRI. Finally, neoplastic, inflammatory, congenital, and idiopathic sources of headache may be demonstrated by either MRI or CT, depending on presentation. MRI will generally show superior characterization. 
Successful removal of massive intragastric gallstones by endoscopic electrohydraulic lithotripsy and mechanical lithotripsy. We describe a case of massive gallstones discharged into the stomach through a cholecystoduodenal fistula and the successful removal of these stones by endoscopic electrohydraulic lithotripsy (EEHL) and endoscopic mechanical lithotripsy (EML) for the prevention of gallstone ileus. A 60-yr-old woman was admitted with epigastric pain and nausea. Upper gastrointestinal tract examination demonstrated backflow of contrast medium from the duodenal bulb into the gallbladder. Endoscopic examination revealed a large fistula on the anterior wall of the duodenal bulb, and two brown stones (about 3 cm in diameter) were found in the stomach. To prevent gallstone ileus, removal of these stones was attempted. They were broken into pieces by EEHL, then crushed into smaller pieces by EML and removed orally. Chemical analysis showed the composition of the gallstones to be at least 98% cholesterol. The patient was discharged one month after removal of the gallstones and has remained asymptomatic. 
Reactive arthritis due to hidradenitis suppurativa mimicking osteomyelitis. We have reported a case of erosive arthritis of the hand preceding the appearance of hidradenitis suppurativa in the ipsilateral axilla, which was mistaken for osteomyelitis. Recognition of this presentation is important to avoid unnecessary invasive diagnostic procedures and to initiate prompt treatment directed at the underlying cause. 
Ovarian cancer screening. For populations in which preventive measures have been applied for the more common causes of death, the early detection of ovarian cancer becomes the next focus of efforts to reduce premature death among women. Data regarding the effectiveness of ultrasonography in detecting early-stage ovarian cancer are reviewed. Ultrasonography is more sensitive than pelvic examination in detecting ovarian abnormalities but lacks specificity in distinguishing benign from malignant ovarian lesions. Combined with serum CA 125 levels, ultrasonography may provide an effective screening tool, although cost-effectiveness has not been demonstrated and its effectiveness in reducing mortality from ovarian cancer has not been completely evaluated. Guidelines are presented for the use of ultrasonography in evaluating the postmenopausal ovary. 
Histiocytes in Sweet's syndrome. The histological features of biopsies from 18 previously unreported cases of Sweet's syndrome are reported. The dermal infiltrate in the majority of the cases contained numerous histiocytes that at first sight appeared to mimic neutrophils. The immunophenotype of these histiocytes was consistent with monocytes that have freshly infiltrated into the lesions. Only two of the cases in this series, associated with leukaemia, displayed the histological features of Sweet's syndrome with a predominant neutrophilic infiltration. We suggest that the initiating mechanisms in Sweet's syndrome are that monocyte/histiocyte-derived cytokines such as the interleukins IL-1 and IL-8, secreted either by infiltrating histiocytes in the non-leukaemia-associated cases of Sweet's syndrome or by tumoural myelomonocytic cells in those associated with leukaemia, are responsible for the systemic manifestations and the infiltration with neutrophils in the skin lesions. 
Elevated circulating interleukin-6 is associated with an acute-phase response but reduced fixed hepatic protein synthesis in patients with cancer. It has been suggested that, as part of the inflammatory response to the presence of a tumor, various cytokines are produced and these induce hepatic synthesis of acute-phase proteins (APP). Under these circumstances it is not known what changes occur in the fixed component of hepatic protein synthesis. The aim of this study was to compare circulating interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor (TNF) concentrations and fixed hepatic protein synthesis rates in a group of healthy controls (n = 6) with a group of patients with an established APP response secondary to hepatic metastasis from colorectal cancer (n = 6). Fixed hepatic protein synthesis rates were measured following a primed, constant 20-hour infusion of 15N-glycine. The liver was biopsied at laparotomy. The APP response was assessed by serum C-reactive protein concentration and cytokines were assayed by a combination of immunoassay and bioassay. The patients with advanced cancer and an on-going APP response had elevated circulating IL-6 concentrations (p less than 0.01). Rates of fixed hepatic protein synthesis were 30% lower than those observed in controls (p less than 0.01). These findings demonstrate that in patients with hepatic metastasis, although the synthesis of certain acute-phase export proteins can be increased, fixed protein synthesis is reduced. Whether these changes in the distribution of hepatic protein synthesis are mediated by IL-6 will require further investigation. 
Experience with a third-generation implantable cardioverter-defibrillator. A Medtronic 7216A pacemaker cardioverter-defibrillator was implanted in 16 patients (mean age 56 years) with sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) and organic heart disease with a mean left ventricular ejection fraction of 33%. Endocardial and epicardial defibrillation shock efficacy was evaluated before or at implant using 1 to 3 shock patterns, i.e., monophasic single, sequential or simultaneous shocks with dual and triple electrode configurations. Endocardial leads used a common right ventricular cathode and dual anodes, whereas epicardial leads used 2 or 3 helical coil patches. VT termination was evaluated using pacing or shock therapy, or both, whereas only shocks were used in VF. Programmable bradycardia pacing, individual zones for VT and VF detection and individualized pacing and shock therapy for VT and VF were used. Monophasic shocks had epicardial defibrillation thresholds ranging from 3 to 18 (mean 10) J and were comparable for sequential and simultaneous shocks (p greater than 0.2). VT detection rates ranged from 340 to 470 ms and VF detection rates from 270 to 330 ms. VT or VF induction, or both, was performed noninvasively in 13 patients after implant and was reproducibly terminated by rapid pacing alone (5 patients), low-energy shocks (2 patients), high-energy shocks (3 patients) and combined therapy (3 patients). Intermediate or high-energy shocks terminated all induced VF episodes. During follow-up (2 to 12 months), there have been 2 noncardiac deaths. Electrical therapy was delivered in 7 patients, for VT (3 patients), VT and VF (3 patients) and indeterminate tachyarrhythmia (1 patient). All VT/VF episodes were successfully terminated, with 78 of 96 (81%) spontaneous VT episodes terminated by pacing. Follow-up reprogramming was required in 5 patients. It is concluded that successful application of individualized electrical therapy prescriptions in patients with VT/VF is feasible. Pacing therapies, which are effective for induced VT, can be reliably used for effective long-term spontaneous VT termination in conjunction with shock therapy and can permit reduced patient exposure to shock therapy. Thus, a programmable hybrid pacemaker cardioverter-defibrillator system provides nonthoracotomy implantation, effective VT/VF termination, demand ventricular pacing and noninvasive modes for arrhythmia induction, event monitoring and clinical trouble-shooting. 
Laparoscopic treatment of painful perihepatic adhesions in Fitz-Hugh-Curtis syndrome. This report illustrates a case of Fitz-Hugh-Curtis syndrome associated with pelvic inflammatory disease in which the clinical symptom of right upper quadrant pain was severe and persistent despite appropriate antibiotic therapy. Because of the atypical course, an extensive work-up was performed to rule out other possible etiologies for the pain. In this context, a laparoscopy was performed and identified dense adhesions between the liver and the anterior abdominal wall. These adhesions were safely and successfully lysed using a KTP/532 laser through a second puncture site. After surgery the pain was completely resolved, with no further recurrence after 6 months of follow-up. 
Severely injured geriatric patients return to independent living: a study of factors influencing function and independence. Our previous work demonstrated that geriatric trauma patients (age greater than 65 years) consume disproportionate amounts of health care resources. In the past we hypothesized that late mortality is high, long-term outcome is poor, and return to independence is low in a severely injured geriatric population. Of 6,480 trauma admissions over 5 years, geriatric patients (n = 495) with blunt trauma injury (n = 421) and an ISS greater than 16 (n = 105) who survived until discharge (n = 61) underwent long-term follow-up (mean = 2.82 years). We surveyed 20 measures of functional ability; 10 measures of independence; availability and use of rehabilitation resources; employment history; alcohol use; support systems; and nursing home requirements. Of the 105 patients, 7 were subsequently lost to follow-up. Among the remaining 98, 44 (44.9%) died in hospital and 54 (55.1%) were discharged and interviewed. The mean age of the contacted patients was 72.6; their mean ISS was 23.3. Forty eight of 54 (88.9%) were alive at the time of interview, while 6/54 (11.1%) had died. Although only 8/48 patients regained their preinjury level of function, 32/48 (67%) returned to independent living. The 32 independent patients, those with "acceptable" outcome, were compared with an "unacceptable" outcome group composed of the 44 in-hospital deaths, the 6 late deaths, and the 16 dependent patients. Factors associated with poor outcome include a GCS score less than or equal to (p = 0.001), age greater than or equal to 75 (p = 0.004), shock upon admission (p = 0.014), presence of head injury (p = 0.03), and sepsis (p = 0.03). 
Coronary bypass surgery improves global and regional left ventricular function following thrombolytic therapy for acute myocardial infarction. TAMI Study Group. Coronary bypass surgery was performed prior to hospital discharge in 303 (22%) of 1387 consecutive patients enrolled in the TAMI 1 to 3 and 5 trials of intravenous thrombolytic therapy for acute myocardial infarction. Bypass surgery was of emergency nature (less than 24 hours from treatment with intravenous thrombolytic therapy) in 36 (2.6%) and was deferred (greater than 24 hours) in 267 (19.3%) patients. The indications for bypass surgery included failed angioplasty (12%); left main or equivalent coronary disease (9%); complex or multivessel coronary disease (62%); recurrent postinfarction angina (13%); and refractory pump dysfunction, mitral regurgitation, ventricular septal rupture or abnormal predischarge functional test (1% each). Although patients having bypass surgery were older (59.5 +/- 9.8 versus 56.0 +/- 10.2 years, (p less than 0.0001), had more extensive coronary artery disease (46% with three-vessel disease versus 11%, (p less than 0.0001), had more frequent diabetes mellitus (19% versus 15%, (p = 0.048), had more prior infarctions (p less than 0.0001), had more severe initial depression in global left ventricular ejection fraction (48.0 +/- 11.9% versus 51.8 +/- 11.9%, p = 0.0002), and regional infarct zone (-2.7 +/- 0.94 versus -2.5 +/- 1.1 SD/chord, p = 0.02) and noninfarct zone function (-0.36 +/- 1.8 versus 0.43 +/- 1.6 SD/chord, p less than 0.0001) than patients not having coronary bypass surgery, no difference in the incidence of death in hospital (7% surgical versus 6% nonsurgical) or death at long-term follow-up of hospital survivors (7% surgical versus 6% nonsurgical) was noted between groups. Surgical patients demonstrated a greater degree of recovery in left ventricular ejection fraction (3.4 +/- 9.8% versus 0.16 +/- 8.5%, p = 0.036) and infarct zone regional function (0.71 +/- 1.1 versus 0.34 +/- 0.99 SD/chord, p = 0.001) when immediate (90 minutes following initiation of thrombolytic therapy) and predischarge (7 to 14 days after treatment) contrast left ventriculograms were compared than did patients who received only intravenous thrombolytic therapy with or without coronary angioplasty. These data suggest a beneficial influence of coronary bypass surgery on left ventricular function and possibly on the clinical outcome of patients initially treated with intravenous thrombolytic therapy for acute myocardial infarction. 
Mechanism of inhibitory action of prostaglandins on the growth of human gastric carcinoma cell line KATO III. Prostaglandins (PGs) play important roles in the regulation of various gastric functions. In this study, the effects of various PGs on the growth of the human gastric carcinoma cell line KATO III were investigated. All the PGs tested inhibited KATO III cell growth with a relative potency order of PGE2 greater than PGE1 greater than 17S,20-dimethyl-6-oxo PGE1-methyl ester (ornoprostil) greater than PGF2 alpha. This inhibition was accompanied by an increase of cyclic adenosine monophosphate production. Furthermore, in the presence of guanosine triphosphate, these PGs stimulated adenylate cyclase activity in the plasma membrane of KATO III cells, followed by enhancement of membrane guanosine triphosphatase activity. The relative potencies of these PGs for increasing cyclic adenosine monophosphate levels, activating adenylate cyclase, and enhancing guanosine triphosphatase activity were all comparable to those for inhibiting cell growth. On the other hand, the proliferation of KATO III cells was also inhibited by forskolin as well as dibutyryl cyclic adenosine monophosphate, whereas none of the agents that did not increase cyclic adenosine monophosphate levels had any effect. These results suggest that PGs inhibit KATO III cell growth by stimulating cyclic adenosine monophosphate production via a guanosine triphosphate-dependent process, suggesting the involvement of guanosine triphosphate-binding stimulatory protein, probably coupled to PGE2 receptors, in the action of PGs. 
Successful percutaneous closure of a complex coronary-to-pulmonary artery fistula using a detachable balloon: benefits of intra-procedural physiologic and angiographic assessment. A 48-yr-old woman presented with a loud continuous precordial murmur and symptoms of fatigue. Color-flow doppler imaging and nuclear magnetic resonance imaging failed to show the cause of the murmur. Diagnostic catheterization showed a large left anterior descending coronary artery to pulmonary artery fistula with impaired left ventricular wall motion. Two detachable balloons were deployed in the fistula with complete abolition of flow in the main fistula channel. A small parallel channel of the fistula, previously not appreciated due to vessel overlap, remained patent but had trivial flow as assessed by green-dye and oximetric techniques. The patient had immediate resolution of her symptoms and return of normal ventricular wall motion. 
Bilateral gluteus maximus transposition for anal incontinence. Seven patients (five men and two women) ranging in age from 26 to 65 years (means = 44) underwent bilateral gluteus maximus transposition for complete anal incontinence. The indications for operation were sphincter destruction secondary to multiple fistulotomies (n = 4), bilateral pudendal nerve damage (n = 2), and high imperforate anus (n = 1). The procedure is performed without the use of a diverting colostomy. The inferior portion of the origin of each gluteus maximus is detached from the sacrum and coccyx, bifurcated, and tunneled subcutaneously to encircle the anus. The ends are then sutured together to form two opposing slings of voluntary muscle. Postoperatively, six patients regained continence to solid stool, two to liquid stool as well, and only one patient in this group was able to control flatus. Although resting pressures remained unchanged, voluntary squeeze pressures were restored by this operation. In addition, rectal sensation was markedly improved, which helps make this a worthwhile procedure for properly selected patients. 
Effects of hemoperfusion during percutaneous transluminal coronary angioplasty on left ventricular function. The effect of autologous blood perfusion, delivered through an angiographic power injector, on alleviating left ventricular (LV) hemodynamic deterioration during percutaneous transluminal coronary angioplasty (PTCA) was examined. LV systolic and diastolic pressures, LV peak positive and peak negative first derivative of LV pressure (dP/dt), and ST-segment shift were recorded in 9 patients with and without hemoperfusion. Hemoperfusion resulted in an improved LV hemodynamic profile during balloon occlusion, as reflected in LV systolic pressure (127 +/- 14 vs 120 +/- 15 mm Hg, p = 0.01), LV end-diastolic pressure (17 +/- 14 vs 25 +/- 6 mm Hg, p less than 0.001), peak positive (1,237 +/- 240 vs 1,149 +/- 225 mm Hg/s, p less than 0.05) and peak negative (1,666 +/- 357 vs 1,485 +/- 385 mm Hg/s, p = 0.003) dP/dt. Hemoperfusion provides substantial protection for significant LV dysfunction induced by conventional PTCA in 1-vessel angioplasty and is a feasible option to protect against potential cardiovascular collapse in high-risk PTCA. 
Cisplatin and fluorouracil chemotherapy does not yield long-term benefit in locally advanced head and neck cancer: results from a single institution. Fifty-one patients with locally advanced head and neck cancer were treated with three cycles of cisplatin at 100 mg/m2 followed by 5-day continuous infusion fluorouracil (5-FU) at 1,000 mg/m2/d as induction chemotherapy. Subsequent local therapy consisted of surgery for patients with resectable disease and/or radiotherapy. Three cycles of adjuvant chemotherapy were administered to patients with partial response (PR) or complete response (CR) to induction chemotherapy. Twenty-two patients (43%) had a clinical CR that was pathologically confirmed in 12 patients (24%), and 24 patients (47%) had a PR for an overall response rate of 90%. Local therapy included surgery in 24 patients (47%) and radiotherapy alone in 22 patients (43%). Adjuvant chemotherapy was administered to 32 patients (63%) frequently at great dose reduction. At a median follow-up of 90 months, the median survival is 22 months (95% confidence interval, 15 to 36 months), and the 5-year survival is 25%, with only five patients known to be alive and disease-free at this time. The median time to progression is 14 months, with 29 patients (57%) having documented progression of their head and neck cancer and eight (16%) having progression of a second neoplasm. Seven patients died of intervening medical events. This high incidence of second malignancies supports the continued investigation of chemoprevention for patients in CR. Despite the known high response rates achieved with cisplatin and 5-FU induction chemotherapy, the overall poor survival data reported here should lead to a thorough reexamination of the frequent administration of this regimen in the community. 
Periorbital necrobiotic xanthogranuloma and stage I multiple myeloma. Ultrastructure and response to pulsed dexamethasone documented by magnetic resonance imaging. We observed a 40-year-old woman with necrobiotic xanthogranuloma from the inception of indurated eyelid and periorbital infiltrates and concurrent stage I multiple myeloma to resolution of infiltrates in skin and bone marrow after pulsed high-dose oral dexamethasone therapy. Ultrastructural studies revealed lipid vacuoles in epidermal keratinocytes, in dermal histiocytic macrophages, and in vascular and lymphatic endothelial cells. The presence of lipid vacuoles in epidermal keratinocytes has not been reported previously in xanthogranuloma. 
Basal and maximum acid output after continuous overnight gastric aspiration. Basal and maximum acid outputs were measured on two occasions in a group of 15 duodenal ulcer (DU) patients in remission. The initial study was carried out after a nocturnal acid collection, whereas the second was carried out in the conventional manner without preceding nocturnal aspiration. No difference in the basal acid output, concentration, or volume of secretion was found between the two study days. Maximum acid output on the other hand, was significantly (p less than 0.02) reduced from 30.9 (14.2-41.2) mmol/h, median (+range), to 23.7 (8.1-33.7) mmol/h after overnight aspiration. The reduction in maximum acid output was attributable to a fall in the volume of gastric secretion from 280 (170-371) ml to 230 (142-280) ml. No fall in acid concentration was seen. We conclude that overnight gastric aspiration does not affect basal gastric secretion, but reduces the maximum acid output as a result of a reduced secretory volume. 
Helicobacter pylori infection and the risk of gastric carcinoma BACKGROUND. Infection with Helicobacter pylori has been linked with chronic atrophic gastritis, an inflammatory precursor of gastric adenocarcinoma. In a nested case-control study, we explored whether H. pylori infection increases the risk of gastric carcinoma. METHODS. From a cohort of 128,992 persons followed since the mid-1960s at a health maintenance organization, 186 patients with gastric carcinoma were selected as case patients and were matched according to age, sex, and race with 186 control subjects without gastric carcinoma. Stored serum samples collected during the 1960s were tested for IgG antibodies to H. pylori by enzyme-linked immunosorbent assay. Data on cigarette use, blood group, ulcer disease, and gastric surgery were obtained from questionnaires administered at enrollment. Tissue sections and pathology reports were reviewed to confirm the histologic results. RESULTS. The mean time between serum collection and the diagnosis of gastric carcinoma was 14.2 years. Of the 109 patients with confirmed gastric adenocarcinoma (excluding tumors of the gastroesophageal junction), 84 percent had been infected previously with H. pylori, as compared with 61 percent of the matched control subjects (odds ratio, 3.6; 95 percent confidence interval, 1.8 to 7.3). Tumors of the gastroesophageal junction were not linked to H. pylori infection, nor were tumors in the gastric cardia. H. pylori was a particularly strong risk factor for stomach cancer in women (odds ratio, 18) and blacks (odds ratio, 9). A history of gastric surgery was independently associated with the development of cancer (odds ratio, 17; P = 0.03), but a history of peptic ulcer disease was negatively associated with subsequent gastric carcinoma (odds ratio, 0.2; P = 0.02). Neither blood group nor smoking history affected risk. CONCLUSIONS. Infection with H. pylori is associated with an increased risk of gastric adenocarcinoma and may be a cofactor in the pathogenesis of this malignant condition. 
The noncemented porous-coated hip prosthesis. A three-year clinical follow-up study and roentgenographic analysis. This was a retrospective study reviewing 68 hip arthroplasties performed with noncemented, porous-coated components at three institutions in the period between December 1983 and June 1987. Fifty of these were available for follow-up study. The mean follow-up period was three years (range, 18-56 months). Thirty-seven patients were treated by total hip arthroplasty (THA) with porous-coated components, and thirteen were implanted with porous-coated femoral stems with bipolar endoprostheses using a porous-coated femoral stem and a universal head. The mean Harris hip score at follow-up evaluation for the entire group was 85.7 points. Eighty percent of the patients had either a good or excellent result. Those patients implanted with a porous femoral stem with bipolar acetabular components had only 54% good or excellent results compared with 90% good or excellent results for those having THA. Roentgenographic findings included a 59% rate of femoral neck cortex osteopenia, an 80% rate of medial or lateral distal cortical hypertrophy, and an 80% rate of distal bone bridging. All of these roentgenographic changes were secondary to changes in stress transference to the proximal femur. There was no correlation between thigh pain or the degree of bone-prosthesis radiolucencies and the fit of the femoral stem. 
Rupture of low transverse cesarean scars during trial of labor We report eight cases of rupture of low transverse cesarean scars occurring during trials of labor. The cases occurred in five hospitals in the Denver metropolitan area during a 13-month period. The estimated incidence was 0.7% of planned trials of labor. Complications of rupture included one neonatal death, two cases of severe neonatal asphyxia, three maternal bladder lacerations, and one hysterectomy. 
The influence of diazepam or lorazepam on the frequency of endotracheal intubation in childhood status epilepticus. Anticonvulsant management of status epilepticus (SE) may result in respiratory depression, often requiring endotracheal intubation (ETI). By examining rates of ETI in childhood SE after intravenous diazepam or lorazepam, when administered alone or in combination with phenytoin, the influence of anticonvulsants on the frequency of ETI during SE was determined. The medical records of 142 consecutive children younger than 16 years of age admitted from a university hospital ED with seizures during a 28-month period were retrospectively reviewed. SE was identified in 38 (27%) of cases. Records of children with SE were reviewed for demographic, seizure severity, and management variables. Twelve patients were excluded, ten of whom received concomitant phenobarbital. Patients receiving lorazepam had ETI rate of 27% (4/15), compared to 73% (8/11) in the diazepam group (P = 0.026, Fisher's exact). The groups were not significantly different in age, weight, sex, seizure type, seizure duration, and appropriate anticonvulsant dosage. A prospective, randomized trial comparing lorazepam and diazepam is warranted to confirm the apparent advantage of lorazepam in reducing respiratory depression. 
Opercular cheiro-oral syndrome. Perioral and distal upper limb sensory dysfunction (cheiro-oral syndrome) has classically been attributed to cortical involvement. In previously reported cases of the syndrome, caused by stroke, however, the thalamus or brain stem has been the actual site of the lesion. We have studied two patients with infarct in the superficial middle cerebral artery territory involving the parietal operculum. Sensory involvement was purely subjective in the face, but severe hypoesthesia was present in the distal upper limb, involving mainly position sense, stereognosis, and graphesthesia. Temperature and pain sensation were involved in one patient. These findings correlated with involvement of the lower part of the postcentral gyrus, more caudal parts of the parietal operculum, and underlying white matter. This opercular cheiro-oral syndrome seems more uncommon than faciobrachiocrural hemihypesthesia associated with anterior parietal artery territory infarct. A double supply to the parietal opercular region through branches of the temporal arteries and anterior parietal artery may explain the rarity of cheiro-oral syndrome resulting from hemisphere stroke, because simultaneous and partial compromise to two different pial artery networks is uncommon. 
Prevalence of simple adnexal cysts in postmenopausal women. This prospective study was performed with ultrasound (US) to determine the prevalence of unilocular, nonseptated adnexal cysts ("simple cysts") in healthy postmenopausal women and the relationship between cyst occurrence and both hormone replacement and length of time since onset of menopause. Transabdominal and transvaginal US were performed on 149 volunteers aged 50 years or older. Patients were classified according to hormone regimens (no hormones, unopposed estrogen, continuous daily estrogen and progesterone, and sequential estrogen and progesterone) and time since onset of menopause (less than 5 years, 5-10 years, and greater than 10 years). Simple adnexal cysts were found in 22 women with the aid of transvaginal and/or transabdominal US, yielding a relative frequency of 14.8% +/- 5.7% and a prevalence of 14,800 patients with cysts per 100,000 patients. No statistical relationship was found between cyst frequency and type of hormone replacement or length of time since onset of menopause. 
Rare presentation of a parapharyngeal schwannoma. Schwannoma, or neurilemmoma, is included in the differential diagnosis of masses in the parapharyngeal space. Schwannomata do not usually cause acute inflammation, and therefore do not tend to present as emergencies as in this case, in which there was acute respiratory embarrassment. 
Ventricular fibrillation complicating endomyocardial biopsy of a cardiac allograft. Transvenous endomyocardial biopsy remains the most useful diagnostic aid in assessing rejection in the transplanted heart. Although invasive, the complications associated with endomyocardial biopsy are few, and the procedure is generally regarded as safe. We report a case of apparent ventricular fibrillation complicating transvenous endomyocardial biopsy. Histologic section revealed evidence of moderate acute rejection. This case represents the first report of a life threatening ventricular dysrhythmia following routine endomyocardial biopsy in a cardiac transplant recipient. 
Fetal choroid plexus cysts in the second trimester of pregnancy: a cause for concern. Controversy surrounds the issue of recommending cytogenetic studies in second-trimester fetuses with fetal choroid plexus cysts. To assist in clarifying this issue, a prospective study was designed to describe the association between fetal choroid plexus cysts and aneuploidy in a large population. During a 3-year period 7350 women at 15 to 22 weeks' gestation underwent an ultrasonographic evaluation. Fetal choroid plexus cysts were diagnosed in 71 (0.96%) of these pregnancies. Sixty-two of the 71 patients elected to undergo amniocentesis. An abnormal karyotype was identified in four (6.4%) of these fetuses. One fetus had trisomy 21, and three fetuses were diagnosed with trisomy 18. These data indicate that it is reasonable to offer genetic counseling and cytogenetic studies in those patients identified as having a fetal choroid plexus cyst. 
Head-up tilt for the evaluation of syncope of unknown origin in children. Fifteen patients aged 10 to 18 years with syncope of unknown origin, and 10 healthy control children aged 11 to 18 years, were evaluated by head-up tilt to 60 degrees for 60 minutes. Six patients (43%) reproduced symptoms of syncope during the examination. Four had a typical vasovagal reaction; two had marked hyperventilation. None of the children in the control group had syncope. The head-up tilt test offers a simple, noninvasive, high-yielding diagnostic tool for evaluation of syncope in children. 
Endoscopic therapy for gastric cancer in patients more than 80 years old. We prospectively studied 17 gastric cancer patients who were more than 80 yr old, in whom endoscopic therapy was performed. The patients were divided into two groups: the first group included 13 patients in whom curative treatment was attempted, and in 11 (85%) a curative response was achieved. Two patients in this group showed a positive gastric biopsy after 1 and 2 yr, respectively, of therapy: one patient is under current treatment with laser therapy, and the other patient underwent surgery with resection of the stomach. The second group included four patients in whom treatment was aimed at prolonging survival or palliation, and in all four patients, a successful response was obtained. Therefore, our results demonstrate that endoscopic therapy is effective for the treatment of gastric cancer patients over 80 yr old. 
Expression and amplification of the HER-2/neu (c-erbB-2) protooncogene in epithelial ovarian tumors and cell lines. Amplification of the c-erbB-2 protooncogene has been associated with a poor prognosis in human breast and ovarian cancers. Our study was undertaken to examine whether amplification, rearrangement, or overexpression of c-erbB-2 and other protooncogenes was frequently observed in epithelial ovarian cancers. c-erbB-2 was expressed in 87% of 22 ovarian cancers analyzed, but expression was significantly increased in only one of the 22 tumor specimens. In this case elevated c-erbB-2 expression was associated with dramatic amplification of the gene. In another tumor a 3.8 kb EcoRI fragment was found, in addition to the usual 4.4 and 6.0 kb fragments; this is consistent with a possible gene rearrangement or a restriction fragment length polymorphism. To place these results in perspective, expression of several other protooncogenes has been examined in ovarian carcinomas. The c-fos, c-myc, n-myc, c-fms, and c-Ha-ras protooncogenes were expressed in different fractions of tumors, but expression of l-myc, c-erbB, c-myb, c-sis, and c-mos was not detectable. Aside from c-erbB-2, neither amplification nor rearrangement was observed among the other protooncogenes studied. Expression of c-erbB-2, c-fms, c-myc, n-myc, c-fos, and c-Ha-ras deserves further evaluation as a prognostic factor in ovarian cancer. 
Serum pepsinogen I concentrations in peptic ulcer patients in relation to ulcer location and stage. To investigate the relation of the serum group I pepsinogen (PG I) concentration to the location of gastric ulcers and chronicity of peptic ulcers, ulcer patients (n = 322) were compared with endoscopically normal subjects (n = 174). The mean PG I concentration was significantly higher in male control subjects (n = 90) than in female control subjects (n = 84). In male patients with ulcers in the duodenum (n = 69), antrum (n = 34), or angulus portion (the lower third of the body; n = 83), the mean serum PG I concentration was significantly higher than in the control subjects but in patients with an ulcer in the upper body (n = 49) it was similar to control values. Men with active or healing ulcers (n = 149) showed a significantly higher serum PG I concentration than those with scarred lesions (n = 86) when the abnormality was located in either the upper body or in the angulus portion. For female patients (n = 87), the results were similar. These results suggest that serum PG I concentrations reflect the stages of activity of peptic ulcer. 
Abnormal perception of visceral pain in response to gastric distension in chronic idiopathic dyspepsia. The irritable stomach syndrome. Sensory and pressure responses to gastric distension were evaluated in 24 consecutive patients suffering from chronic idiopathic dyspepsia and 20 healthy subjects. A latex balloon was placed in the proximal stomach and inflated by increments of 100 ml of air up to a maximal volume of 800 ml. Symptom response and intragastric pressure-volume curve were recorded during the gradual balloon distension. Thirteen of the 24 patients experienced pain at a distension volume less than or equal to 400 ml of air, but only one of the 20 controls (P less than 0.001). Intragastric pressure-volume curves were similar in patients and controls, and in patients with and without abnormal pain threshold, suggesting that a compliance defect was not the cause of the sensory anomaly. Gastric emptying of solids and liquids was measured in 20 of the 24 patients using a dual isotopic technique; psychological status was also evaluated in 18 patients using the Mini-Mult test. The frequency of the sensory anomaly was not different in patients with (7/14) or without (4/6) gastric stasis, but was lower in patients with (5/13) than in those without psychological disturbances (5/5, P less than 0.01). Thus, a primary visceral sensory anomaly, either alone or in conjunction with motility disturbances, can play an important role in chronic idiopathic dyspepsia and must be taken in account for further therapeutic research. 
Association of nm23-H1 allelic deletions with distant metastases in colorectal carcinoma. A prospective study analysed the prognostic value of nm23-H1 allelic deletions in colorectal cancer. Of 21 patients with no evidence of distant metastases at initial operation, 11 showed nm23-H1 allelic deletions (including 1 homozygous deletion); 10 had no nm23-H1 deletions. After median follow-up of 25 months, distant metastases had developed in 8 of 11 (73%) patients with nm23-H1 deletions but in only 2 of 10 (20%) without nm23-H1 deletions (p less than 0.03). Tests with probe YNZ 22.1, near p53, showed no significant association with distant metastases. nm23-H1 may be, or may be located near, a late-acting suppressor gene in colorectal carcinoma, in which deletions may have prognostic value. 
Blood and liver-infiltrating lymphocytes in primary biliary cirrhosis: increase in activated T and natural killer cells and recruitment of primed memory T cells. We used two-color and three-color flow cytometric analysis to study phenotypical activation and functional subsets of T and natural killer cells in the blood and liver tissue of patients with primary biliary cirrhosis, other chronic liver diseases and the blood of healthy subjects. The changes in blood lymphocyte phenotype in patients with primary biliary cirrhosis and other chronic liver diseases were similar and comprised elevated relative or absolute numbers of activated human leukocyte antigen-DR + T subset (CD4+ and CD8+) cells and DR+ natural killer-like (CD16+) cells. B cell (CD19+) numbers were normal. In primary biliary cirrhosis a selective reduction in T cells of suppressor-inducer (CD45RA + CD4 + ) type was registered. The human leukocyte antigen-DR expression among CD4+ T cell subsets was investigated further in primary biliary cirrhosis and healthy controls using triple antibody flow cytometric analysis. Phenotypical cell activation was confined to helper T cells of the primed, memory (CD45RO + CD4+) type. The decrease in suppressor-inducer T cells in primary biliary cirrhosis was paralleled by a reciprocal increase in primed memory T cells. Several significant differences were observed when blood and liver-infiltrating cells from primary biliary cirrhosis patients were compared. In the liver tissue, the CD4/CD8 ratio was decreased, the relative activation of T-subset cells and NK cells was further increased, the suppressor-inducer T subset was further depressed and the primed memory T subset was increased. The cytotoxic T-cell subset (CD11b-) dominated within the CD8+ population. In liver tissue from other chronic liver disease subjects, a lower CD4/CD8 ratio was found compared with primary biliary cirrhosis. 
Familial amyloid polyneuropathy: alanine-for-threonine substitution in the transthyretin (prealbumin) molecule. A previously reported family with amyloid polyneuropathy (FAP) was reinvestigated to determine the type of mutation in the transthyretin (prealbumin) molecule. Transthyretin was isolated from amyloid-laden myocardium and serum, and tryptic peptides were resolved by high-performance liquid chromatography. Amino acid sequencing of an anomalous peptide revealed an alanine-for-threonine substitution corresponding to position No. 60 of the transthyretin monomer. Detection of the FAP gene in asymptomatic carriers was accomplished by hybrid isoelectric focusing of transthyretin in the presence of dithiothreitol and high concentrations of urea, and by Southern blotting of Pvull-digested leukocyte deoxyribonucleic acid. This type of FAP was found to be identical to the previously described Appalachian amyloid. Patients with FAP and their asymptomatic gene-carrying offspring had significantly reduced levels of serum transthyretin and retinol-binding protein. 
MRI of the facial nerve during paralysis. Gadolinium-enhanced MRI was used to evaluate 10 patients with Bell's palsy and one patient with facial paralysis secondary to Lyme disease. Nine of the eleven patients showed increased signal intensity of their facial nerve with gadolinium-enhanced MRI. In all nine patients, the facial nerve was involved at the labyrinthine, geniculate ganglion and proximal tympanic portions of the facial nerve, while two of the nine patients also had involvement of the mastoid segment of the facial nerve. Patients whose facial nerve enhancement was limited to the labyrinthine, geniculate ganglion and proximal tympanic facial nerve ultimately had complete return of facial function. Patients whose facial nerve enhanced in the mastoid segment experienced incomplete return of facial function. Gadolinium is effective in localizing the site of inflammation during facial paralysis. Those patients with enhancement localized to the labyrinthine, geniculate ganglion and proximal tympanic segments were more likely to regain complete facial function. In contrast, patients who had enhancement of the mastoid segment of the facial nerve had poorer prognoses for complete return of facial function. 
Necrotizing fasciitis: 10 years' experience in a district general hospital. Of 14 patients with necrotizing fasciitis who presented between 1979 and 1988, six (43 per cent) died. The deaths were associated with delays in diagnosis, poor surgical technique and diabetes. Prompt diagnosis, resuscitation and early radical surgery are essential to the successful management of necrotizing fasciitis. 
Primary intracerebral osteosarcoma. A 64-year-old man was admitted because of a rapidly progressive left side hemiparesis. A computed tomography scan showed a right side intrathalamic mass, partially calcified. Surgical specimen proved to be an osteosarcoma. The patient died 3 days later from an acute myocardial infarct. Autopsy failed to discover any other significant lesion. A review of the literature disclosed that this case might be the second published primary intracerebral osteosarcoma and the first with immunocytochemical analysis. 
Morphological changes of hepatic microcirculation in experimental rat cirrhosis: a scanning electron microscopic study. Morphological changes of hepatic microcirculation, especially peribiliary plexus, in experimental rat cirrhosis that resulted from the repeated intraperitoneal injections of N-diethylnitrosamine, 100 mg/kg body weight/one shot/week, were examined by scanning electron microscope. Control rats were treated with saline. Whole blood vessels of the rats were perfused by saline and stuffed with methylmethacrylated resin. Multiple nodular changes were seen in the livers after the five injections (5 wk) of N-diethylnitrosamine, and diffuse nodular transformations mimicking human cirrhosis after six injections (6 wk) were also seen. Overall changes in experimental rats were numerous vascular channels mainly composed of venous branches around the parenchymal nodules, increased arterioportal anastomoses and flattening of veins, especially hepatic vein branches. Peribiliary plexuses of the experimental rats were much richer in the vessels than those of the controls, and many dilated veins, ramified from portal vein branches, were present in the former. Direct connections between peribiliary plexuses and sinusoids or between peribiliary plexuses and portal veins increased in the experimental rats. Studies concerning microcirculatory changes of peribiliary plexuses in experimental rat cirrhosis are rare. It was concluded that the abnormal peribiliary plexuses in this experimental series might participate in a collateral circulation under a state of portal hypertension. 
Prognostic value of lymphocyte surface markers in acute myeloid leukemia. We studied the expression of cell surface antigens associated with myeloid and lymphoid leukemias on bone marrow-derived blast cells from 339 patients with newly diagnosed de novo acute myeloid leukemia (AML) enrolled on Cancer and Leukemia Group B (CALGB) chemotherapy protocols. Surprisingly, of 211 cases studied for the expression of CD2 (T-cell marker, sheep erythrocyte binding receptor for T lymphocytes) 45 were positive (21%). In addition, of 298 patients studied for CD19 (B-lymphocyte marker), 41 were positive (14%). Overall, of 170 patients studied for both CD2 and CD19, 56 (33%) were positive. Interestingly, central review of the French-American-British (FAB) morphology of the CD2- and CD19-positive cases showed that FAB M3 was twice as frequent, and M4E eight times as frequent compared with the CD2- and CD19-negative cases. Of 22 lymphocyte antigen-positive cases in which cells were available for studies of Ig or T-cell antigen receptor (TCR) gene rearrangement, 20 were germline, one had a rearranged Ig heavy chain gene, and one had rearranged TCR beta and Ig heavy chain genes. The presence of messenger RNA for CD2 was demonstrated in four CD2 surface antigen-positive cases, thus validating the cell surface data. Lymphocyte antigen-positive cases had karyotypes commonly seen in AML; 71% of cases with an abnormal clone had t(8;21)(q22;q22), inversion 16(p13q22), t(15;17)(q22;q12), or t(9;11)(p22;q23). The patients with lymphocyte markers had a significantly higher incidence of these karyotypic abnormalities compared with patients with lymphocyte antigen-negative AML (34% v 15%, P less than .02). When the outcome to therapy of the lymphocyte antigen-positive cases was compared with that for the CD2, CD19-negative cases, we found that the CD2, CD19-positive cases actually had higher complete remission rates (75% v 59%, P = .04), and significantly longer time to failure (P = .02; 32.4% +/- 6.0% v 18.0% +/- 4.1% at 2 years) and overall survival (P = .02; 43.5% +/- 6.3% v 26.0% +/- 4.5% at 2 years). CD2 antigen-positive cases also had a significantly superior survival (P = .02; 43.8% +/- 7.9% v 29.8% +/- 3.8% at 2 years). There were no significant differences (P less than or equal to .05) between the two groups in age, leukocyte count at diagnosis, incidence of extramedullary disease, or FAB classification.(ABSTRACT TRUNCATED AT 400 WORDS). 
Bleeding peptic ulcer after abdominal aortic aneurysm surgery. A retrospective study of 112 patients with abdominal aortic aneurysm (AAA) and 232 with arteriosclerosis obliterans (ASO) demonstrated that 16.7% of those with AAA and 1.6% of those with ASO had a history of gastroduodenal ulcer; 83% of these lesions with AAA were gastric ulcers. Ulcer bleeding after vascular reconstruction developed in seven patients with AAA and one with ASO. Serum fibrinogen levels and platelet counts were significantly lower in patients with AAA than in those with ASO or controls. A prospective study showed that 25 (52.1%) of 48 patients with AAA and six (20.0%) of 30 patients with ASO had endoscopically proved gastroduodenal lesions before vascular reconstruction. None of them developed postoperative bleeding after treatment of both their gastroduodenal lesions and coagulopathy. Furthermore, the significant decrease in blood flow and prostaglandin content of gastric mucosa was demonstrated in patients with AAA. 
Severity of obstructive sleep apnea. A four-level severity scale for obstructive sleep apnea is offered using four criteria: maximum oxygen desaturation, apnea/hyponea index, symptoms of excessive day-time sleepiness, and symptoms of related cardiac disease. Oxygen desaturation and the apnea/hyponea index for 175 patients, all having had uvulopalatopharyngoplasty surgery, showed 19% mild, 33% moderate, 17% moderately severe, and 31% severe obstructive sleep apnea. There was a very poor correlation between oxygen desaturations and number of obstructive events, which demands that both be used in any estimation of disease severity. 
Bilateral symmetrical striopallidodentate calcification associated with pseudohypoparathyroidism demonstrated in a patient with cerebellar astrocytoma. A case of calcification in the striopallidodentate system associated with pseudohypoparathyroidism, clinically manifested after operation for a cystic astrocytoma of the cerebellar vermis, is reported. Bilateral symmetrical striopallidodentate calcification accompanying a disturbance in calcium metabolism is rare. Only a few cases have been described previously in the literature, of which only six were accompanied by pseudohypoparathyroidism. The importance of identifying hypoparathyroidism, especially pseudohypoparathyroidism, early in the course of investigation is discussed. 
Washed human platelets prevent ischemia-reperfusion edema in isolated rabbit lungs. Washed human platelets prevent edema formation in isolated rabbit lungs infused with xanthine oxidase, an enzyme that injures endothelial membranes by generating extracellular oxidants. We hypothesized that platelets would similarly preserve membrane permeability in isolated lungs exposed to ischemia-reperfusion injury, a model that perturbs endothelial cells by the generation of intracellular oxidants. Isolated perfused rabbit lungs (IPL) were exposed to warm ischemia-reperfusion to cause lung edema. The infusion of washed human platelets (1.05 +/- 0.02 x 10(10) cells) prevented edema formation as measured by lung weight gain, wet-to-dry lung weight ratios, histological edema, and preservation of paraendothelial cell tight junctions. Inhibition of the platelet glutathione redox cycle with 1,3-bis(2-chloroethyl)-1-nitrosourea, dehydroepiandrosterone, or 1-chloro-2,4-dinitrobenzene interfered with platelet protective effects. In contrast, inhibition of platelet catalase with aminotriazole and H2O2 had no effect on platelet protection. Lung tissue malonyldialdehyde concentrations were similar in isolated lungs exposed to ischemia-reperfusion with or without the infusion of platelets. These results indicate that platelet attenuation of ischemia-reperfusion lung edema depends on platelet glutathione redox cycle antioxidants but not platelet catalase. 
Hypermetabolism in arthrogryposis multiplex congenita. Two patients who developed hypermetabolic reactions during anaesthesia and surgery and who were suffering from arthrogryposis multiplex congenita are reported and it is proposed that the reaction is distinct from malignant hyperthermia and independent of the anaesthetic agents used. The implications for anaesthetists involved in the management of patients with arthrogryposis multiplex congenita are discussed. 
Nonaspiration fine-needle cytology of the liver: a new technique for obtaining diagnostic samples. We studied a new method of obtaining diagnostic cytology samples from the liver that differs from fine-needle aspiration cytology in that no suction is used to obtain the sample. This method is simpler to perform than traditional aspiration biopsy and yields concentrated cell smears that are easier to interpret. The sample enters the needle because of capillary action, a physical property of fluid that causes it to flow into the lumen of a narrow channel. This nonaspiration technique was used in 40 consecutive patients undergoing fine-needle biopsy of mass lesions of the liver. A 22-gauge spinal needle was used in all procedures. The cytology smears obtained were prepared, stained, and interpreted by the same methods used for conventional fine-needle cytology specimens. Specific diagnoses were rendered in 36 patients (90%) and in 32 (94%) of those patients with malignant tumors. An average of 1.7 needle passes (range, 1-4) was needed per patient. We conclude that the results from nonaspiration fine-needle cytology of the liver are as good as those from conventional aspiration technique, and the nonaspiration technique is easier to perform and results in smears that are easier to interpret. 
Public Health Service inter-agency guidelines for screening donors of blood, plasma, organs, tissues, and semen for evidence of hepatitis B and hepatitis C. Several infectious agents transmit through infected blood and blood products. To decrease the potential for disease transmission, donors are screened for risk factors by medical history and for evidence of infection by specific testing. The Food and Drug Administration (FDA) currently requires that all donations of whole blood and transfusable components as well as plasma for fractionation into injectable derivatives be subjected to a serologic test for syphilis, hepatitis B surface antigen (HBsAg), and antibody to the human immunodeficiency virus (anti-HIV). The FDA also currently recommends testing donations of whole blood and components for transfusion for antibody to human T lymphotropic virus type I (anti-HTLV-I) and antibody to hepatitis C virus (anti-HCV), and is considering recommending testing for antibody to hepatitis B core antigen (anti-HBc). Blood banks in the United States voluntarily began testing donations for anti-HBc and alanine aminotransferase (ALT) in 1986 and 1987 and for anti-HCV in 1990. 
Pharmacokinetics, neuromuscular effects, and biodisposition of 3-desacetylvecuronium (Org 7268) in cats. The pharmacokinetics, biodisposition, and neuromuscular blocking properties of 3-desacetylvecuronium were studied in 17 adult cats. Animals were divided into three groups: five cats with kidney failure induced by bilateral ligation of the renal pedicles, six cats with galactosamine-induced fulminant hepatitis, and six control cats. An intravenous bolus of 300 micrograms.kg-1 of 3-desacetylvecuronium was rapidly injected into the jugular vein. Arterial blood, urine, and bile samples were collected at regular intervals for 6 h in control cats and for 8 h in cats with kidney or liver failure. The liver was excised for analysis at the end of the experiment. In cats with renal failure, 3-desacetylvecuronium pharmacokinetic and pharmacodynamic variables did not differ from those in control cats. In cats with liver failure, plasma clearance was significantly less and mean residence time greater than in control cats (2.8 +/- 0.6 vs. 14.1 +/- 6.5 ml.kg-1.min-1 and 334 +/- 225 vs. 49 +/- 29 min, mean +/- SD, respectively). Volume of distribution at steady state in cats with liver failure and in control cats was not different. Also, in cats with liver failure, the duration of action and recovery index of 3-desacetylvecuronium was significantly greater than in control cats (168 +/- 62 vs. 82 +/- 32 min, and 39 +/- 19 vs. 10 +/- 4 min, respectively). Onset time of neuromuscular blockade was similar in all three groups. Total recovery of 3-desacetylvecuronium, for all three groups, in urine, bile, and liver was 90 +/- 11% (mean +/- SD). In control cats, 70 +/- 18% of 3-desacetylvecuronium was recovered in bile and liver and 19 +/- 14% in urine. No 3,17-bidesacetylvecuronium (a putative 3-desacetylvecuronium metabolite) was detected. 
Increased thrombin levels during thrombolytic therapy in acute myocardial infarction. Relevance for the success of therapy. BACKGROUND. It has been suggested that thrombolysis in a feedback reaction may generate pro-coagulant activities. METHODS AND RESULTS. Fifty-five patients were treated with urokinase-preactivated prourokinase (n = 35) or tissue-type plasminogen activator (n = 20) for acute myocardial infarction and underwent coronary angiography at 90 minutes and at 24-36 hours into thrombolysis, and fibrinogen (Ratnoff-Menzie), D-dimer (ELISA) and thrombin-antithrombin III complex levels (ELISA) were measured. Primary patency was achieved in 39 patients (70.9%), 13 of whom (33.3%) suffered early reocclusion. Nonsignificant decreases in fibrinogen levels were observed while D-dimer levels increased +3,008 +/- 4,047 micrograms/l (p less than 0.01), differences not being significant in respect to the thrombolytic agents or to the clinical course. In contrast, while thrombin-antithrombin III complex levels decreased -4.4 +/- 13.0 micrograms/l in patients with persistent patency, they increased +7.5 +/- 13.6 micrograms/l in case of nonsuccessful thrombolysis (p less than 0.02) and +11.9 +/- 23.8 micrograms/l in case of early reocclusion (p less than 0.001). For patients with thrombin-antithrombin III complex levels greater than 6 ng/l 120 minutes into thrombolysis, the unfavorable clinical course was predicted with 96.2% sensitivity and 93.1% specificity. CONCLUSION. Generation of thrombin, occurring during thrombolysis, is a major determinant for the success of therapy and thrombin-antithrombin III levels may serve as predictors for the short-term prognosis. 
Vulnerability of nerve fibres to ischaemia. A quantitative light and electron microscope study. In order to learn more about the vulnerability of nerve fibres to ischemia, a quantitative study of nerve fibre abnormalities was performed on biopsy specimens of the superficial branch of the peroneal nerve from 26 patients with vasculitic neuropathy: 20 had necrotizing arteritis, 5 a lymphocytic, and 1 a leucocytoclastic vasculitis on nerve and/or muscle biopsy. The density of myelinated fibres ranged from 25 to 7880 per mm2 (n = 8470 +/- 706 (SD]. There was a marked inequality in the density of nerve fibres between the fascicles of individual nerves with a mean coefficient of variation of 41 +/- 37 (SD) % versus 7.4 +/- 3.0% in controls. Loss of myelinated fibres, which was greater for fibres larger than 7 microns in diameter, was more severe than that for unmyelinated axons. Regeneration, which was assessed by the number of clustered axons, decreased when the density of myelinated fibres decreased, suggesting that severe nerve ischaemia precludes axonal regeneration. Wallerian degeneration affected on average 58% (range 5-100%) and segmental demyelination, mainly of the secondary type, on average 1.94% (range 1-10%) of teased fibres. It was concluded that (1) myelinated fibres are more vulnerable to ischaemia than unmyelinated axons; (2) large myelinated fibres are affected before the smaller ones; (3) segmental demyelination is uncommon in this context; (4) severe nerve ischaemia precludes axonal regeneration. 
Five-year results of the first 159 consecutive phakic chronic open-angle glaucomas treated by argon laser trabeculoplasty. 159 phakic eyes with chronic open-angle glaucoma were treated by argon laser trabeculoplasty and followed for 5 years. According to our criteria of failure, 31 eyes were failures at 1 year (19%), 47 eyes at 2 years (30%), 66 eyes at 3 years (41%), 77 eyes at 4 years (48%) and 82 eyes at 5 years (52%). In the 77 eyes still controlled at 5 years, the intraocular pressure drop was 6.57 mm Hg and the initial medical treatment could be tapered or stopped in only 33 of the cases (43%). In the 82 failures, there was a greater percentage requiring surgery for pressure control during the first year after laser treatment: 16 trabeculectomies in 31 failures (52%). The initial mean intraocular pressures of 7 failures needing surgery during the first 2 months (27.22 mm Hg) and of the 27 failures needing surgery during the 5 year follow-up (24.41 mm Hg) were higher than the initial mean intraocular pressure of the 77 successful cases (22.67 mm Hg). In the 159 eyes followed for 5 years, 19% (31 eyes) to 6% (5 eyes) new failure cases per year were encountered and the initial good results obtained by argon laser trabeculoplasty persisted for about 5 years in half of the cases. 
Long-term response of recurrent respiratory papillomatosis to treatment with lymphoblastoid interferon alfa-N1. Papilloma Study Group. BACKGROUND. We earlier reported that patients with recurrent respiratory papillomatosis responded to six months of treatment with lymphoblastoid interferon alfa-n1. Because another study of patients treated for one year with leukocyte interferon alfa-n3 found that the growth rate of papillomas was slowed in the first six months but returned to base line during months 7 through 12 despite persistent interferon treatment, we now report the long-term results in our original study patients who were followed for a median of four years after the original one-year crossover study. METHODS. After the patients in our study had completed the first study year, their physicians could continue or recommence treatment with lymphoblastoid interferon alfa-n1 in a dose of either 2 MU per square meter of body-surface area per day or 4 MU per square meter every other day. The extent of disease was measured by endoscopy when clinically indicated. RESULTS. Data on late-follow-up were obtained for 60 of the 66 patients. There were 22 complete remissions and 25 partial remissions; 13 patients had no response. The median duration of the complete remissions was 550 days, and 15 patients continued to be in complete remission. The median duration of partial remissions was 400 days and seven patients were still in partial remission. Thirteen of 28 patients responded to a second course of interferon after an interruption in treatment of at least one month. The rate of response in the 11 of 53 patients who had neutralizing antibody to interferon was the same as in the patients without the antibody. CONCLUSIONS. Patients with severe recurrent respiratory papillomatosis may have a sustained or repeated response to treatment with lymphoblastoid interferon alfa-n1. We recommend that patients with recurrent respiratory papillomatosis who require surgery every two to three months be given a six-month trial of interferon alfa-n1. 
Left anterior fascicular block: an ischaemic response during treadmill testing. A patient in whom exercise induced reversible ischaemic left anterior fascicular block is reported. Glyceryl trinitrate relieved the fascicular block. Coronary angiography showed a 90% obstruction of the left anterior descending artery. The left anterior fascicular block induced by exercise disappeared after a successful coronary angioplasty. 
Pleomorphic xanthoastrocytoma. Ultrastructural, immunohistochemical, and DNA cytofluorometric study of a case. A case of right frontal pleomorphic xanthoastrocytoma that occurred in a 7-year-old boy is reported clinicopathologically. The patient underwent surgery on September 29, 1988. Histologic diagnosis of pleomorphic xanthoastrocytoma was made because, in addition to the unique pleomorphic histologic features, positive glial fibrillary acidic protein in immunohistochemical staining and characteristic ultrastructural features, i.e., cytoplasmic intermediate fibrils and lipid vacuoles, basal lamina, and abundant reticulin networks were demonstrated. The DNA cytofluorometric analysis of the nuclei of the tumor cells disclosed the main mode to be diploid with polyploid classes (4, 8, 16, and 32C) without any aneuploidy. Despite the presence of many pleomorphic nuclei, DNA histogram of the tumor disclosed very few DNA synthetic cells indicating a biologically inactive nature of the tumor. The patient is still alive and totally asymptomatic 20 months postoperatively. 
Osteomyelitis in children with sickle cell disease: early diagnosis with contrast-enhanced CT. Two children with sickle cell disease and osteomyelitis were treated. In one child, definitive treatment was delayed until computed tomography (CT) revealed a subperiosteal abscess. Early performance of CT in the other child resulted in prompt diagnosis and treatment. Before the appearance of the characteristic plain radiographic findings, diagnosis of osteomyelitis in patients with sickle cell disease can be difficult because the clinical manifestations of infarction and osteomyelitis can be similar. Radionuclide scans have yielded mixed results. In equivocal cases, early performance of CT can help establish the diagnosis of osteomyelitis to avoid significant morbidity. 
Cyclosporin A modulates the course of woodchuck hepatitis virus infection and induces chronicity. Immunosuppression is known to influence the state of chronic hepatitis B virus infection, and is thought to increase the risk of developing chronic infection in newly exposed individuals. Cyclosporin A (CsA), an immunosuppressive agent that inhibits Th cell function, was administered to woodchucks chronically infected with woodchuck hepatitis virus (WHV), and resulted in a decreased severity of chronic hepatitis and an increased viremia during the treatment. Adult woodchucks inoculated with WHV and given CsA for 14 wk had increased viremias, decreased acute phase liver injury, and developed chronic infections at a higher rate compared with immunocompetent woodchucks given virus alone (chronicity in seven of seven WHV + CsA + vs zero of nine WHV + CsA-; p less than 0.001). These results in a relevant animal model of hepatitis B virus infection indicate: 1) that liver injury in acute hepadnavirus infections is immune-mediated and not a direct cytopathic effect of virus replication; 2) that Th cells function in the inflammatory response and in the immunologic control of hepadnavirus infection; and 3) that suppression of Th cell function in acute hepadnavirus infection decreases liver injury but alters the outcome of infection in favor of chronicity. These results also suggest continued challenges in the application of CsA in liver transplantation for hepatitis B virus-induced diseases. 
Occurrence of resting tremor in Parkinson's disease. Several previous studies have noted that resting tremor (RT) is absent in 10% to 30% of idiopathic Parkinson's disease (IPD) patients. We report our 22-year observations in 47 pathologically verified parkinsonian patients. In all the IPD cases with median follow-up of 3.7 years, RT was noted on at least one evaluation. Among other parkinsonian syndrome variants characterized by widespread subcortical pathology with median follow-up of 2.86 years, RT was seen in 31% of the cases. Our data indicate that the sites typically involved in IPD are sufficient to produce RT. 
The spectrum of molecular alterations in the evolution of chronic myelocytic leukemia. DNA from 135 patients with chronic myelogenous leukemia (CML) at various clinical stages and Philadelphia (Ph1) chromosome positive acute lymphoblastic leukemia was investigated for alterations in a variety of proto-oncogenes which have been implicated in the evolution of CML from its chronic phase to blast crisis. The most common genetic change found in the evolution of typical Ph1 chromosome positive CML to blast crisis was an alteration of the p53 gene involving either a rearrangement, a deletion, or a point mutation in the coding sequence of the gene. Alterations of the p53 gene were found in the myeloid and the rare megakaryocytic variant of blast crisis but were absent in the lymphoid leukemic transformants. Gross structural alterations were seen in 11 of 54 (20%) of myeloid or unknown phenotypes of blast crisis and in only 1 of 44 chronic phase cases. Eight examples of mutations in the open reading frame of the p53 gene at codons 49, 53, 60, 140, 202, 204, 238, and 239 were observed in blast crisis patients. Mutations in the N-RAS gene were rare in typical blast crisis (2 of 27 cases) but were found in megakaryocytic and Ph1 negative myeloid blast crisis. We concluded that heterogeneous alterations in the p53 gene and occasionally in the N-RAS genes accompany the evolution of chronic phase CML to blast crisis. 
Effect of peripheral cardiopulmonary bypass on left ventricular size, afterload and myocardial function during elective supported coronary angioplasty. Although cardiopulmonary bypass support has been increasingly used for high risk coronary angioplasty, few data exist regarding its effects on left ventricular function. Accordingly, in 20 patients changes in left ventricular size, afterload and myocardial function were assessed by continuous hemodynamic monitoring and simultaneous two-dimensional echocardiography during cardiopulmonary bypass-supported high risk angioplasty. The cross-sectional left ventricular area during bypass support remained unchanged during diastole, whereas during systole it decreased (from 29.6 +/- 11.4 to 27.6 +/- 10.4 cm2, p less than 0.05). Global left ventricular function expressed as fractional area change remained unchanged from baseline to bypass support but decreased during balloon inflation (from 0.27 +/- 0.11 to 0.17 +/- 0.09, p less than 0.001). The end-systolic meridional wall stress decreased during bypass support (from 141 +/- 75 to 110 +/- 58 x 10(3) dynes/cm2, p less than 0.02). Regional myocardial function was assessed by a wall motion score (0 = normal, 1 = hypokinesia, 2 = akinesia and 3 = dyskinesia). Regions supplied by a stenotic (greater than or equal to 50% diameter) vessel deteriorated during bypass support (score from 0.9 +/- 0.8 to 1.06 +/- 0.8, p less than 0.01), whereas regions supplied by a nonstenotic vessel did not. Regions supplied by the target vessel deteriorated further during balloon inflation (score from 0.7 +/- 0.6 to 1.7 +/- 0.75, p less than 0.001). Thus, although left ventricular size and global function remain unchanged and afterload decreases during bypass support, myocardial dysfunction in regions supplied by a stenotic vessel may occur. Furthermore, regional and global left ventricular dysfunction still occur with angioplasty balloon inflation during cardiopulmonary bypass support. 
Clinical evaluation of circulating serum sialyl Tn antigen levels in patients with epithelial ovarian cancer. Sialyl Tn antigen (NeuAc alpha 2----6GalNac alpha 1----0-Ser/Thr [STN]) with antigenic specificity in the core structure of mucin-type carbohydrate chains has been determined. In the present study, we evaluated the clinical significance of this new carbohydrate antigen, STN, in patients with epithelial ovarian cancer. With the use of a radioimmunoassay developed to detect STN antigen in serum, elevated (greater than or equal to 32.6 U/mL) antigen levels were observed in 50.0% of patients with ovarian cancer. In contrast, 3.8% of healthy individuals had STN antigen levels greater than or equal to 32.6 U/mL. In 9.6% of patients with benign gynecologic diseases and 0% of pregnant women, there were elevated levels of STN antigen. There was a significant difference (P less than .001) in STN antigen levels between patients with ovarian cancer and patients with benign gynecologic diseases, pregnant women, or the controls. The mean +/- SD for all evaluated samples of ovarian cancer was 109.2 +/- 146.8 U/mL. Both the mean values and the positive rate increased as the stage advanced. Classified according to the histologic type, the highest positive rate (61.0%) was observed in mucinous adenocarcinoma. The usefulness of STN antigen as a circulating tumor marker in ovarian cancer was estimated as follows: sensitivity 50.0%, specificity 93.5%, positive predictive value 72.2%, negative predictive value 84.7%, and diagnostic value 46.8%. Serum STN antigen levels were elevated in 12 of 33 patients with ovarian cancer who had serum CA 125 antigen levels less than 35 U/mL. While CA 125 antigen levels were elevated in 74.6% and STN antigen levels were elevated in 50.0% of the same population, the use of both assays indicated the sensitivity of detection of 83.8% in the population studied. 
Acid peptic disease in adolescents. How to avoid misdiagnosis and undertreatment. Acid peptic disease in adolescents may be more common than previously recognized. However, appropriate medical attention is often delayed because of misdiagnosis and undertreatment. Thorough questioning of adolescent patients is important to elicit a complete description of symptoms. Endoscopy or intraluminal pH monitoring may be necessary to establish a diagnosis of gastroesophageal reflux disease or peptic ulcer. Therapy with histamine receptor antagonists, especially ranitidine (Zantac), is recommended. Antireflux surgery may be needed to prevent potential long-term gastrointestinal damage. Patients with duodenal ulcer should also be advised to make life-style changes to avoid recurrence of disease later in life. 
In-flight esophageal variceal bleeding en route for liver transplantation: a case report and review of the literature. Esophageal variceal bleeding owing to portal hypertension is a potential threat in pediatric patients awaiting liver transplantation. We report a case of a three-year-old boy with severe congenital hepatic fibrosis, Caroli's disease, and portal hypertension who developed a life-threatening variceal hemorrhage for the first time in his life during commercial air transport to a liver transplantation center. Factors precipitating variceal bleeding are discussed, particularly those resulting from changes in altitude. It is recommended that prophylactic treatment for variceal bleeding be at least considered in children awaiting liver transplantation prior to prolonged air transportation. Because of differences in capabilities of treatment providers in various locales, and because there are as yet no conclusive data, the treatment of choice must be decided on an individual basis. Equipment for treating in-flight hemorrhage should be available. 
Increased calcium influx in caudal artery of rats made hypertensive with pyridoxine deficiency. Moderate pyridoxine deficiency in rats has been shown to induce hypertension, which can be corrected by pyridoxine supplementation. In this study, calcium handling by isolated caudal arteries from pyridoxine-deficient and age-matched control rats was evaluated. We found 45Ca influx into the intracellular compartment to be significantly elevated in deficient rats. This increased influx could be attenuated with nifedipine, a calcium channel blocker, in a dose-dependent manner, suggesting alterations in the calcium channels that would make them leaky. The pyridoxine-deficient arterial segments maintained a higher resting tone; removal of extracellular calcium by EGTA or entry blockade by nifedipine decreased the tone significantly in the deficient arteries, compared with little or no effect in controls. 
Quantitative testicular biopsy in spinal cord injured men: comparison to fertile controls. Spermatogenic abnormalities have been reported in the majority of spinal cord injured men on routine testicular biopsy. However, given the interim advances in their urological and rehabilitative care, a quantitative assessment of the germinal epithelium after spinal cord injury and comparison of these parameters to normal controls are warranted. Incisional testicular biopsy was performed in 14 spinal cord injured men. Quantitative micrometric techniques were applied to assess spermatogenesis and the results were compared to a normative data base of testicular biopsies previously obtained from a group of 15 fertile volunteers. From a minimum of 10 randomly selected round seminiferous tubules per subject the mean number of Sertoli cells, mature spermatids, tubular diameter and tubular wall thickness were determined in both groups and statistically analyzed. In the spinal cord injury group the mean number of spermatids per tubule was significantly lower and the mean number of Sertoli cells per tubule was significantly higher than in fertile controls (p less than 0.05). Moreover, the mean Sertoli cell-to-spermatid ratio per seminiferous tubule was significantly higher in the spinal cord injury group and discriminated between spinal cord injured men and controls, with a sensitivity of 93% and specificity of 100% (p less than 0.0001). Half of the spinal cord injury group showed a mean tubular spermatid density of less than 10. Compared to the fertile population, spinal cord injured men show significant differences in quantitative parameters of the germinal epithelium that may contribute to the reproductive dysfunction. 
Mesalamine in ulcerative colitis. Sulfasalazine has been used for many years in the management of ulcerative colitis. As many as 20 percent of patients treated with it experience intolerable adverse effects usually attributed to its sulfapyridine component. The other active component is 5-aminosalicylic acid (5-ASA); the only 5-ASA enema preparation currently available in the U.S. is mesalamine (Rowasa, Reid-Rowell) containing 5-ASA 4 g in 60 mL. In clinical trials, mesalamine has proved efficacious in treating refractory cases of distal ulcerative colitis, proctitis, and proctosigmoiditis. Because of its high cost compared with more conventional treatment modalities, it should be reserved for cases that are either refractory or intolerant to conventional treatment. 
Intractable heart failure despite angiotensin-converting enzyme inhibitors, digoxin, and diuretics: long-term effectiveness of add-on therapy with pimobendan. In 25 patients whose chronic congestive heart failure (CHF) had recently worsened to New York Heart Association class IV, pimobendan (5 to 20 mg/day) was added to maximum conventional therapy consisting of digoxin, diuretics, angiotensin-converting enzyme inhibitors, coumadin derivatives to prevent thromboembolic complications, and amiodarone to suppress serious ventricular rhythm disturbances. CHF was fatal in less than 1 month in five patients (two had shown some initial improvement). The other 20 had sustained improvement by at least one functional class, interrupted by episodes of CHF that usually responded to intravenous therapy. Median survival was 12 months (range 10 days to greater than 3 years); five patients died suddenly, 12 died of intractable CHF, and two died of other causes. Six patients were alive 3 years after the onset of treatment with pimobendan. Add-on therapy with pimobendan produced a sustained improvement in many patients with severe CHF that was no longer responding to a combination of digoxin, diuretics, and angiotensin-converting enzyme inhibitors. 
Anatomy of the tricuspid annulus. Circumferential myofibers as the structural basis for atrial flutter in a canine model. BACKGROUND. Little anatomic information is available on the annular myocardium. This study was conducted to determine the anatomic substrate for atrial flutter due to circus movement around the tricuspid annulus in the Y-shaped incision canine model of atrial flutter. METHODS AND RESULTS. We studied photographs of the annular myocardium serial histological sections, made in either of three different planes, and compared these with photographs of the intact and blocked gross heart specimens. We found that the annulus is the most caudal region of the atrial wall. The epicardial aspect of the annulus abuts the ventricular septum or the aortic root in the medial region; in other regions, it is covered by the fat of the coronary sulcus. Its endocardial aspect is delimited by the tricuspid leaflets inferiorly and by the pectinate muscle bundles superiorly, except in the medial region where the pectinate muscle bundles are absent. The annular myocardium is bilaminated. A continuous subepicardial circumferential lamina is the most prominent and is robust in the anterior, lateral, and posterior regions, but it attenuates to a fine muscular connection in the medial region. Myofibers of its superior border merge with the pectinate muscle bundles or are admixed in the medial region with myocardium at the base of the medial atrial wall. Its inferior border makes little contact with the annulus fibrosus about the ring; however, in the medial region, these myofibers insert into fibrous tissue superior to the septal leaflet. A discontinuous, subendocardial perpendicular lamina contains myofibers that descend from the atrium; most of these myofibers insert into the annulus fibrosus about the ring, but the lamina is absent in the anteromedial region. CONCLUSIONS. We conclude that the continuous circumferential lamina provides the anatomic substrate for circus movement of excitation in this model. 
Correlation of circulating von Willebrand factor levels with cardiovascular hemodynamics. BACKGROUND. Valvular heart disease is associated with a decreased platelet circulating time and a thrombotic tendency. The possibility that these events are related to changes in von Willebrand factor (vWF), a multimeric glycoprotein released from endothelial cells and platelets that mediates platelet adhesion to the vascular subendothelium, has not been examined. METHODS AND RESULTS. We measured the vWF antigen (vWF:Ag) concentration in 43 patients undergoing cardiac catheterization for the evaluation of mitral (n = 17) or aortic (n = 10) stenosis or nonvalvular heart disease (n = 16). Mean vWF:Ag concentration was significantly higher in patients with mitral stenosis than in those without (212 +/- 84 versus 150 +/- 79 units/dl, p less than 0.02); this elevation was associated with a significant elevation of pulmonary vascular resistance (PVR) in the patients with mitral stenosis (186 +/- 49 versus 133 +/- 81 dynes-sec-cm-5, p less than 0.02). The vWF:Ag levels in the entire group of patients (regardless of the presence or type of valvular disease) varied directly with PVR (r = 0.72, p less than 0.0001) and with pulmonary artery pressure (r = 0.60, p less than 0.0001) and inversely with cardiac output (r = 0.64, p less than 0.0001). Changes in PVR, pulmonary artery pressure, or cardiac output could not be correlated with circulating levels of fibrinogen or beta-thromboglobulin, which may be released from activated platelets, nor with the endothelial cell product tissue plasminogen activator. CONCLUSIONS. The association of high vWF:Ag levels with increased PVR and decreased cardiac output in patients both with and without mitral stenosis suggests a hemodynamically induced increase in the endothelial release of vWF, which might contribute to a thrombotic tendency in these patients. 
Fifteen-year results of ambulatory compression therapy for chronic venous ulcers. A nonoperative approach to venous stasis ulceration of the lower extremity, consisting of initial bedrest, ulcer cleansing, dressing changes, and ambulatory elastic compression stocking therapy, has been maintained for over 15 years. All patients had class III, severe chronic venous insufficiency. One hundred five of 113 patients (93%) experienced complete ulcer healing in a mean of 5.3 months. One hundred two patients were compliant with elastic compression stockings, and 11 patients were noncompliant. Complete ulcer healing occurred in 99 of 102 patients (97%) who were compliant versus six of 11 patients (55%) who were noncompliant (p less than 0.0001). The influence of noncompliance, previous venous ulceration, previous venous surgery, previous known deep venous thrombosis, peripheral arterial insufficiency (ankle brachial systolic blood pressure index less than or equal to 0.60), pretreatment ulcer duration, ulcer size, age, sex, diabetes, smoking, and photoplethysmography venous refill time on ulcer healing was determined by logistic regression analysis. Only noncompliance with elastic compression stockings (p less than 0.0001) and a pretreatment ulcer duration of more than 9 months (p = 0.02) significantly decreased initial ulcer healing. Posthealing follow-up was available in 73 patients for a mean of 30 months. Fifty-eight patients (79%) continued to be compliant with stockings; 15 patients were noncompliant. Total ulcer recurrence in patients who were compliant was 16%. Five-year lifetable recurrence was 29%. All patients who were noncompliant had recurrent ulceration by 36 months. Previous ulceration, previous venous surgery, and peripheral arterial insufficiency had no effect on ulcer recurrence (p greater than 0.05). 
Endothelial dysfunction and subendothelial monocyte macrophages in hypertension. Effect of angiotensin converting enzyme inhibition. Hypertension is associated with an impairment of endothelium-dependent relaxation. The angiotensin converting enzyme inhibitors captopril and cilazapril can prevent this endothelial dysfunction. We recently observed that long-term treatment with cilazapril could also prevent subendothelial infiltration by mononuclear cells in spontaneously hypertensive rats. This prompted us to examine whether, in spontaneously hypertensive rats, endothelial dysfunction and subendothelial infiltration by mononuclear cells are associated. These cells were characterized as monocyte macrophages. Infiltration by monocyte macrophages was quantified by morphometry. Endothelial function was estimated by calculating serotonin ratio (maximal contraction to serotonin on isolated arterial rings with endothelium over maximal contraction on paired rings without endothelium). The regional distribution of endothelial dysfunction and subendothelial monocyte macrophages was similar. Both were maximal in the carotid artery, less in the aorta, and nonexistent in the renal artery. A 2-week treatment with cilazapril decreased both endothelial dysfunction (serotonin ratio decreased by 32%) and the number of subendothelial monocyte macrophages in the aorta, which decreased by 38%. We conclude that in spontaneously hypertensive rats, endothelial dysfunction and subendothelial monocyte macrophage infiltration are associated and that cilazapril can decrease both. The observation that angiotensin converting enzyme inhibitors affect subendothelial accumulation of monocyte macrophage may lead to a better understanding of the mechanism of action of this class of drugs. 
Comparison of four subarachnoid solutions in a needle-through-needle technique for elective caesarean section. We have used both spinal and extradural anaesthesia with a 26-gauge, long spinal needle through a 16-gauge Tuohy needle for elective Caesarean section. Four different subarachnoid solutions of bupivacaine were compared: 0.5% heavy bupivacaine alone, or with adrenaline, fentanyl or adrenaline and fentanyl. The incidence of complications and time of regression of the sensory block were analysed. The technique is recommended because it allows rapid onset of anaesthesia and the advantages of an extradural catheter. The subarachnoid solution of choice was 0.5% heavy bupivacaine 12.5 mg with fentanyl 10 micrograms. 
Severe congestive heart failure. How successful are drug and transplant therapies? Severe congestive heart failure is a fatal illness. Aggressive use of proven medical regimens, including vasodilators and angiotensin-converting enzyme inhibitors, may prolong survival time for some patients. Those with refractory symptoms and seriously reduced left ventricular function, impaired exercise capacity, and complex or frequent ventricular arrhythmias should be considered for cardiac transplantation. Candidacy for transplantation is based on the absence of other illnesses that would limit survival or diminish the likelihood of success of the transplant. With the introduction of potent immunosuppressive agents, particularly cyclosporine (Sandimmune), survival rates after transplantation have improved to 90% at 1 year. Major problems include organ rejection, serious infection, development of coronary artery disease in the transplanted heart, and the limited donor organ supply. 
Enhancement of ischaemic rabbit skin flap survival with the antioxidant and free-radical scavenger N-acetylcysteine. 1. The burst of damaging oxygen free-radicals at the time of reperfusion is one of the crucial factors affecting skin flap survival after an ischaemic interval. In these experiments the efficacy of the antioxidant and free-radical scavenger N-acetylcysteine in improving the survival of ischaemic rabbit epigastric skin flaps was tested. 2. At the time of reperfusion flaps were given: (1) balanced salt solution by intravenous whole-body administration, (2) N-acetylcysteine (200 mg/kg) by intravenous whole-body administration, (3) balanced salt solution by intra-arterial infusion into the flap, (4) N-acetylcysteine (20 mg/kg) by intra-arterial infusion into the flap, or (5) N-acetylcysteine (200 mg/kg) by intra-arterial infusion into the flap. Flap survival at 1 week, and tissue levels of parameters related to free-radical production, blood levels of thromboxane B2 and peripheral resistance during reperfusion were determined. 3. Compared with controls (groups 1 and 3) which had flap survival rates (expressed as percentage surface area surviving) of 27.1% and 31.6%, respectively. N-acetylcysteine treatment in group 2 (55.2%) and group 4 (51.9%) resulted in significant (P less than 0.05) improvements in flap survival. The survival rate in group 5 (37.7%) was not significantly better than that of the controls. 4. N-Acetylcysteine significantly reduced parameters related to free-radical production in the skin flap after 30 min of reperfusion, determined as tissue levels of malonyldialdehyde and protein oxidation products. There was also a significant decrease in peripheral resistance when low-dose N-acetylcysteine (group 4) was infused intra-arterially into the flap. 
Interference between gastroesophageal reflux and sleep in near miss SIDS. GER may be considered as one of the triggering factors in some apparently life-threatening events or even SIDS. Also at the present time, many teams perform 24-h pH monitoring in at-risk infants and treat those with abnormal scores. However, further investigations are needed to answer the question: Which unknown additional factor(s) is present when a specific episode of GER causes apnea and/or bradycardia either during sleep or wakefulness?. 
Evaluation and treatment of aneurysms of the vertebral artery: different strategies for different lesions. Aneurysms of the vertebral artery and its branches are relatively uncommon lesions. Their anatomy and presentation can be quite variable. A spectrum of aneurysms of the vertebral artery is presented to illustrate the neuroradiological evaluation, surgical treatment, and perioperative management of these complex lesions. 
Bladder compliance in myelodysplastic children: effect of anti-reflux surgery and conservative treatment. Paediatric urology. Little is known about changes in bladder compliance and bladder capacity in myelodysplastic patients following anti-reflux surgery. A study group of 70 patients was divided as follows: group A included 20 myelodysplastic patients who had been operated on for reflux and whose subsequent treatment was conservative. Group B comprised 31 myelodysplastic patients who had been treated conservatively; a third group of 19 non-myelodysplastic patients, treated by anti-reflux surgery because of primary reflux, formed the control group. The follow-up period for group A averaged 61 months (extending from a urodynamic study 3 months after surgery to the most recent test). In group B the mean follow-up period between the initial test and the latest test was 86 months. Bladder compliance in group A patients did not increase significantly (from 5.5 to 6.9), but patients in group B did show a significant increase (from 5.9 to 10.7). Compliance in the 19 non-myelodysplastic patients decreased only marginally 6 months after surgery (from 29.6 to 26.3). Changes in bladder capacity showed a similar trend. In their most recent test, however, the bladder capacity of group A patients increased to the same volume as that of group B. A high correlation between radiological bladder deformity and bladder compliance was found. We propose a bladder compliance of 10.0 as the lower limit for myelodysplastic patients' preferred range. It was concluded that anti-reflux operations prevent any improvement in bladder compliance (but not in bladder capacity) compared with conservative treatment. 
The opacity of portal hypertension-related ascites correlates with the fluid's triglyceride concentration. To determine if an elevated triglyceride concentration can explain the opacity of some cirrhotic ascites specimens, the authors measured triglyceride concentration by Coulter DACOS (Hialeah, FL) on 133 paired serum and ascitic fluid specimens. The specimens were categorized as clear or cloudy by coded visual inspection. In addition, the ascitic fluid specimens were inspected for a lipid supernatant after 48 hours of refrigeration at 4 degrees C. The ascitic fluid triglyceride concentration of the 87 clear specimens was 1.9 +/- 1.0 mmol/L compared with 7.0 +/- 4.6 mmol/L for the opalescent specimens (P less than 0.001). Only 17% of the clear specimens demonstrated any lipid layer after refrigeration, compared with 94% of opalescent specimens (P less than 0.001). The triglyceride concentrations were not significantly different between the serum samples obtained from patients with clear compared with opalescent ascites. The opacity of portal hypertension-related ascites appears to be related to the triglyceride concentration of the fluid. 
Spinal cord pial metastases: MR imaging with gadopentetate dimeglumine. The purpose of this investigation was to describe gadopentetate-dimeglumine-enhanced MR findings in metastatic disease to the pial lining of the spinal cord. Correlation was made with clinical data, other radiologic studies, and pathologic findings. Eighty-six patients with a known malignancy and unexplained neurologic signs or symptoms were studied with pre- and postcontrast T1-weighted images. In seven of these patients, abnormal enhancement of the pial lining of the cord was seen on the sagittal postcontrast T1-weighted images. This appeared as a thin rim of enhancement along the surface of the cord in six patients and as a focal, thick rim of enhancement in addition to the thin rim of enhancement in the seventh patient. Axial images confirmed the location along the pial lining in each case. Precontrast T1-weighted images in all seven cases and precontrast T2-weighted images in five cases failed to detect any focal abnormalities of the pial lining of the cord. Pathologic confirmation was available in five of the seven patients. Primary malignancies in these patients included breast carcinomas (two), lymphoma (one), leukemia (one), adenocarcinoma of the lung (one), prostate carcinoma (one), and malignant melanoma (one). Three of seven patients had metastatic disease evident only within the CNS, while four patients had widespread disease outside the CNS. We conclude that contrast-enhanced MR imaging is useful in the diagnosis of pial spread of metastatic disease in patients with a known primary malignancy and unexplained neurologic signs or symptoms. 
Facial nerve monitoring in acoustic tumor surgery. Anatomic and functional preservation of the facial nerve during acoustic tumor surgery remains a primary goal. Intraoperative electromyographic facial nerve monitoring with auditory feedback has enabled the surgeon to more readily achieve this goal. We compared a group of monitored translabyrinthine acoustic tumor removals (N = 89) to a similar unmonitored group (N = 155) in regard to facial nerve function. Function was assessed immediately postoperatively, at time of discharge, and at 1 year postoperatively using the House six-point scale. Results were grouped as satisfactory, intermediate, or poor and were analyzed by tumor size. Facial nerve results were better at all time intervals in the monitored groups, although the difference was not statistically significant at the 1-year interval. There was no difference between monitored and unmonitored patients in the subgroups with tumors smaller than 2.5 cm in diameter. This study supports the usefulness of intraoperative facial nerve monitoring in improving facial nerve results, particularly in larger tumors. 
Fatal persistent pulmonary hypertension presenting late in the neonatal period. Two cases of fatal idiopathic persistent pulmonary hypertension presented late in the neonatal period. Lungs were examined histologically by light and electron microscopy, and immunocytochemical studies were used to identify nerves. There was extension of medial smooth muscle distally along the arterial pathway so that most precapillary arteries had completely muscular walls, which in some cases completely obliterated the vessel lumen. Enlarged endothelial cells also contributed to the reduction in the size of the lumen. Nerve fibres accompanying muscular arteries were found in the alveolar region, more distal than is normal. The predominant neuropeptide was the vasoconstrictor tyrosine. Possible aetiological factors in persistent pulmonary hypertension of the newborn are increased muscularity of the peripheral pulmonary arteries antenatally, an increase in the number of vasoconstrictor nerves, or an imbalance in the production of leukotrienes and prostacyclins in the perinatal period. 
False aneurysm of the right internal mammary artery. False aneurysm of the internal mammary artery is an uncommon complication of median sternotomy. Clinical and radiological findings of 2 such cases are presented. At operative exploration neither was directly related to the presence of a sternal wire. 
Continuous extrapleural intercostal nerve block after pleurectomy. A randomised, double blind trial was carried out in 16 patients undergoing pleurectomy to assess the effect of continuous extrapleural intercostal block on postoperative pain and pulmonary function. Subjective pain relief was assessed on a linear visual analogue scale. Pulmonary function was measured on the day before operation and daily for five days after surgery. Eight patients received bupivacaine and eight placebo (saline). The mean pain scores at 4, 8, 16, and 24 hours were 13.3, 8.5, 6.1, and 10 mm respectively in the bupivacaine group compared with 56.3, 41, 46.7, and 35 in the control group; in addition, the bupivacaine group required less papaveretum. Twenty four hours after surgery mean values of peak expiratory flow, forced expiratory volume in one second, and forced vital capacity were reduced to 82%, 76%, and 76% of preoperative control values in the bupivacaine group, and to 39%, 32%, and 36% in the control group. The speed of recovery of pulmonary function was superior in the bupivacaine group. There were no complications related to the infusion. Continuous extrapleural intercostal nerve blockade with bupivacaine provides safe and effective postoperative analgesia and improves respiratory mechanics after pleurectomy. 
Oral contraceptive-associated liver cell adenoma and hepatocellular carcinoma. Cytomorphology and mechanism of malignant transformation. From January 1976 to May 1990, 1673 patients with a liver mass or masses detected by imaging techniques underwent percutaneous fine-needle aspiration biopsy of the liver. Of these, 99 were diagnosed cytologically as "hepatocellular carcinoma" and 9 as "consistent with liver cell adenoma." The cytologic diagnoses were confirmed in the follow-up of all cases. Among the 99 patients with hepatocellular carcinoma, 3 had taken oral contraceptives for a period of 10, 11, and 12 years, respectively. The nine patients with liver cell adenoma were all users of oral contraceptives over a period ranging from 5 to 10 years. Of these, two who had taken oral contraceptives for a period of 8 and 10 years, respectively, had foci or areas of liver cell dysplasia within the adenomas. The cytologic criteria for the diagnosis of liver cell dysplasia included cytoplasmic and nuclear enlargement, nuclear pleomorphism together with prominent nucleoli, hyperchromasia and multinucleation. The cytologic features of liver cell dysplasia strikingly mimic hepatocellular carcinoma. From this study, the foci or areas of liver cell dysplasia arising within the liver cell adenomas appear to be the missing link responsible for the transformation of liver cell adenoma to carcinoma. It is believed that liver cell adenomas are not premalignant and may undergo reversible change after withdrawal of causative agents, whereas liver cell dysplasia is an irreversible, premalignant change and will eventually progress to hepatocellular carcinoma. 
Turbinate hypertrophy in habitual snorers and patients with obstructive sleep apnea: findings of acoustic rhinometry. Forty-five habitual snorers (mean respiratory disturbance index = 6) and 22 patients with obstructive sleep apnea syndrome (mean respiratory disturbance index = 36) were examined by polysomnography, radiocephalometry, rhinomanometry, nasopharyngeal videoendoscopy, and acoustic rhinometry. In 97% of these patients, hypertrophy of the inferior nasal turbinates was found by acoustic rhinometry, while increased nasal resistance of various degrees was measured in 93% of all patients by active anterior rhinomanometry. Acoustic rhinometry demonstrated that the most resistive segment was located in the anterior parts of the nasal cavity and was built up by two compartments: the region of the isthmus nasi and the region of the head of the inferior turbinate. In our snoring patients, the cross-sectional areas at the head of the inferior turbinate were always smaller than the cross-sectional areas in the isthmus nasi, which in normal controls presented the minimal cross-sectional values of the whole nasal cavity. While rhino-manometry can only measure the amount of nasal resistance, acoustic rhinometry can clearly determine the exact size and location of the different stenoses in the nasal cavity that contribute to the increased nasal resistance. 
The human hematopoietic progenitor cell antigen (CD34) in vascular neoplasia. The human hematopoietic progenitor cell antigen CD34 is synthesized and expressed by early normal hematopoietic progenitor cells and by many acute leukemias. Anti-CD34 antibodies also have been reported to stain blood vessels in tissue sections, and, more recently, CD34 mRNA has been detected in vascular endothelial cells. Therefore, the authors studied the diagnostic utility of immunohistochemical CD34 antigen detection in tumors of endothelial cell derivation and compared the results with stains for von Willebrand (vW) factor. A wide variety of epithelial and mesenchymal neoplasms also were examined to assess the specificity of CD34 for vascular neoplasia. Seven cases of angiosarcoma (seven of seven), five cases of Kaposi's sarcoma (five of five), and eight cases of epithelioid hemangioendothelioma (eight of eight) were moderately to strongly positive for CD34. This reactivity was equally intense in frozen sections, alcohol-fixed tissue, and formalin-fixed specimens. In many cases, the malignant endothelial cells stained more strongly than adjacent benign endothelium. Moreover, in most cases CD34 positivity was quantitatively and qualitatively stronger than staining for vW factor. Two cases of hemangiopericytoma (two of two) were CD34 positive but stained less intensely than the angiosarcomas, Kaposi's sarcomas, or hemangioendotheliomas. Five of six cases of hemangioma also stained positively for CD34; the nonreactive tumor in this group was the only one among 28 vascular neoplasms studied that was not reactive for CD34. In comparison, 9 of the 28 vascular tumors did not stain for vW factor. Three hundred fifty-seven tumors of nonvascular derivation also were examined for CD34 antigen expression. Focal light staining was seen in one pulmonary squamous cell carcinoma; moderate to intense staining was observed in half of the epithelioid sarcomas studied (8 of 16) and in a minority of leiomyosarcomas (3 of 22). These findings indicate that CD34 is a sensitive and relatively specific marker for neoplasms of vascular origin. 
A case of vesical paraganglioma behind the symphysis pubis. We report on a 15-year-old boy with a vesical paraganglioma behind the symphysis pubis. Magnetic resonance imaging and transurethral intravesical ultrasonography were helpful in the preoperative localization of the lesion. 
Non-specific aorto-arteritis (Takayasu's disease) in children. Digital subtraction panaorto-arteriography was performed in 32 consecutive children (21 females, mean age 10.8 years) with non-specific aorto-arteritis to assess digital subtraction angiography (DSA) in imaging these children and to study the patterns of involvement in the Indian sub-continent. Diagnostic quality DSA images were obtained in 21 out of 27 intravenous and nine out of 11 intra-arterial studies. Obstructive lesions were present in all the patients and commonly involved the abdominal aorta (24 patients) and renal arteries (20 patients). Aneurysms were seen in five patients and predominantly involved the descending thoracic aorta. Pulmonary artery involvement was uncommon (five out of 20 patients) and clinically silent. Based on clinical and angiographic features, percutaneous transluminal angioplasty was performed for the management of uncontrolled hypertension in eight patients (10 lesions). Initial success was obtained in eight procedures (80%). Re-stenosis occurred after 5.5 months in one patient, but was successfully re-dilated. The follow-up period ranged between 5 and 16 months (mean 9 months). Long-term efficacy of transluminal angioplasty in the management of these children is awaited. 
Compulsive overeating. Compulsive overeating is a behavior used in an attempt to numb or nurture feelings that are threatening to the person. Emotional states are soothed by use of food. Treatment is designed to respond to internal, biologic causes of hunger and satiety while simultaneously allowing feelings to surface and be dealt with. Work on the inner child enables the person to identify and deal with unmet needs and correct distortions from childhood. The secondary gain realized from the extra weight is examined, and direct means of dealing with these needs explored. The focus of recovery is on learning to nurture the self, physically and emotionally. 
Intralesional interferon alfa-2b in the treatment of basal cell carcinoma. Immunohistochemical study on cellular immune reaction leading to tumor regression. Four patients with basal cell carcinomas were treated with intralesional injections of interferon alfa-2b (1.5 million IU per injection) three times a week for 2 weeks. Histopathologic examination of biopsy specimens of the lesions confirmed the absence of basal cell carcinoma in all cases 4 weeks after completion of therapy. A dense mononuclear cell infiltrate and numerous ectatic blood vessels were present in the dermis at the sites of previous basal cell carcinoma. Immunohistologic analysis of the dermal infiltrate revealed a marked increase of Leu-4+ T cells with a slight predominance of Leu-3+ helper/inducer T cells over Leu-2+ suppressor/cytotoxic T cells. Most of the dermal infiltrate expressed HLA-DR antigen. In addition, Leu-11+ natural killer cells were observed in the dermal infiltrate. Immunohistologic changes in the skin lesions at the sites of previous basal cell carcinoma suggest that intralesional interferon alfa-2b acts on tumor cells by enhancement of local T-cell-mediated immune responses. 
Recurrent pericarditis and cardiac tamponade in a patient with hypocomplementemic urticarial vasculitis syndrome. We describe a patient with hypocomplementemic urticarial vasculitis syndrome complicated by recurrent pericarditis and cardiac tamponade. The episodes of pericarditis were associated with urticarial vasculitis, hypocomplementemia, and circulating IgG antibodies to the collagen-like region of Clq. Histopathologic examination of the skin and pericardium demonstrated vasculitis associated with immunoglobulin and complement deposition suggesting an immune complex mediated etiology. Recurrent pericarditis should be included in the clinical spectrum of hypocomplementemic urticarial vasculitis syndrome. 
Gonococcal endocarditis complicating pregnancy: a case report and literature review. The incidence of gonorrhea has decreased substantially in the past decade. Disseminated gonorrhea is more common in women than in men, although gonococcal endocarditis is more common in men. Disseminated gonorrhea is most commonly described in women during menses or pregnancy. Only two cases of gonococcal endocarditis during pregnancy have been reported in the literature since 1942. We report a patient who experienced sudden hemodynamic decompensation at 30 weeks' gestation, resulting in fetal death. Aortic valve replacement was performed, but extensive involvement of the aortic root made complete eradication of infection impossible and eventually resulted in maternal death. 
Survival and management considerations in postirradiation osteosarcoma and Paget's osteosarcoma. Postirradiation and Paget's osteosarcomas are high-grade malignancies. The five-year survival was only 10% in recent experience at the author's institution. Progressive pain is an important clinical feature in both conditions. Careful roentgenographic studies demonstrate cortical destruction and a soft-tissue mass in virtually all patients. Metastasis was present in 25% of both groups of patients at presentation. In contrast to previous series, more than 80% of the patients with postirradiation osteosarcoma had had irradiation for malignant entities and more than 70% had been treated with modern radiotherapy regimens (cobalt-60 or linear accelerator). Twice as many patients with postirradiation osteosarcoma were evaluated and treated in the 1980s than in the previous decade. The initial indication for irradiation often was carcinoma of the breast, uterus, or cervix, or lymphoma. Two-thirds of the patients had progressive disease that was not controllable within six months after diagnosis. Early detection may be the only effective means of improving survival with postirradiation or Paget's osteosarcoma. These patients require lifelong follow-up evaluations. 
Routine computed tomographic scans, selective mediastinoscopy, and other factors in evaluation of lung cancer. Routine computed tomographic scan is advocated as the best noninvasive method of evaluating mediastinal nodes for cancer spread. Positive studies should be confirmed histologically. Large size, central location, unfavorable cell type, poor cellular differentiation of the primary cancer, and weight loss also correlate with increased likelihood of mediastinal involvement. 
Toxic shock syndrome after pilonidal cystectomy. Report of a case. Toxic shock syndrome is an uncommon disease associated with staphylococcal infections. Although most frequently reported in menstruating women and associated with tampon use, toxic shock syndrome has been described following many types of surgical procedures. In this report we describe a case of toxic shock syndrome occurring in a previously healthy young man after elective surgery for a pilonidal cyst. 
Recovery after intense chronic stimulation: a physiological study of cat's fast muscle. Adult cats were used to study the recovery of muscles that had become altered by long-term electrical stimulation. Chronic activation was delivered to the deafferented common peroneal nerve (no pain, no reflexes), and contractile properties were measured for peroneus longus muscle. After 4 wk of great daily amounts of treatment at moderately high pulse rates (30-40 Hz delivered during 50% of daily time), the peroneus longus became considerably weaker, demonstrated a longer time course of twitches and a slower rate of rise of tetanic force, and became less fatigable. Furthermore, its twitch-to-tetanus ratio decreased, and there was no longer any depression of electromyogram (EMG) amplitude during fatigue tests. After 4 wk of subsequent rest it was found that 1) twitch speed and maximum tetanic force had returned to nearly normal values, 2) fatigue resistance showed some return toward normal but was still significantly enhanced, and 3) no significant recovery had yet occurred of the altered twitch-to-tetanus ratio, the abolished EMG depression, or the slowed rate of rise of tetanic tension. During the poststimulation recovery period, the progressive increase of isometric twitch speed was not promoted by the administration of small daily amounts of high-rate stimulation (100-Hz bursts). The results support the conclusions that 1) the time course of recovery differs among physiological properties, 2) the EMG and force reactions that occur during a fatigue test are not strongly coupled, as demonstrated by the alterations of their relationship during poststimulation recovery, and 3) in cat's fast muscles, there is still no evidence for rate-specific effects of chronic stimulation on isometric twitch speed. 
POEMS syndrome with idiopathic flushing mimicking carcinoid syndrome. POEMS syndrome, a rare multisystem disease, is a variant of osteosclerotic myeloma and is characterized by polyneuropathy, organomegaly, endocrinopathy, monoclonal proteins, and skin changes. Presented herein is a case of POEMS syndrome with flushing. The flushing was intermittent, involving the face and upper third of the trunk, and was associated with hypotension and bronchospasm. Final diagnosis was made by biopsy examination of an axillary lymph node, which showed angiofollicular hyperplasia that stained strongly and selectively for lambda light chains. The patient had most of the typical features of POEMS syndrome but was unique in that her most striking finding was carcinoid-like flushing. The flushing improved with steroid therapy, as did some of the other clinical features of her disease. This case suggests that idiopathic flushing can be added to the skin changes observed in POEMS syndrome. 
Magnetic resonance imaging shows specific abnormalities in the MELAS syndrome. The MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) can be difficult to identify. We report MRI abnormalities that we believe are specific to this disorder in three patients with complete or partial MELAS syndrome. The patients all showed an unusual pattern on T2-weighted MRI with multifocal areas of hyperintense signal confined to the cortex of the cerebrum, cerebellum, and adjacent white matter. Some images suggested selective cortical involvement of deeper layers only. Deep white matter was relatively spared, distinguishing this from usual cerebrovascular disease or the edema after status epilepticus. Specificity of these findings is further suggested by a good correlation of these findings with the previously described unique postmortem brain pathology of MELAS. 
Examination of cardiorespiratory changes during upper gastrointestinal endoscopy. Comparison of monitoring of arterial oxygen saturation, arterial pressure and the electrocardiogram. Critical events including hypoxaemia, arrhythmias and myocardial ischaemia may occur more frequently during endoscopic procedures than during anaesthesia. A study was undertaken to assess the cardiovascular changes and to evaluate suitable monitoring techniques to detect critical events during sedation and endoscopy. Twenty patients scheduled to undergo a prolonged endoscopic procedure which required deep sedation were studied. Continuous recordings of electrocardiogram, heart rate and arterial oxygen saturation were made and arterial pressure was recorded at one-minute intervals. The study commenced immediately before administration of sedatives, continued for the duration of the examination and for one hour following the examination. Oxygen saturation decreased in all patients during the examination to a mean of 82.9% (SD 11.9), and remained below baseline for the duration of the examination and into the recovery period. Statistically significant increases and reductions of systolic arterial pressure and rate-pressure product were found during the procedures compared with baseline values recorded before administration of sedatives. Sixteen of the 20 patients developed tachycardia during the examination. Ten patients developed ectopic foci which were supraventricular, ventricular or both in origin. Electrocardiogram changes resolved during the recovery period. Myocardial ischaemia was assessed by S-T segment depression and a significant correlation was found between S-T segment depression and hypoxaemia, although the magnitude of the S-T depression was small and may not have been detected clinically. No correlation was found between S-T segment depression and arterial pressure, heart rate or rate-pressure product. 
Childhood epidermolysis bullosa acquisita. Report of three cases and review of literature. Epidermolysis bullosa acquisita is an acquired subepidermal blistering disease with variable clinical, pathologic, and immunologic features. The disease has been reported infrequently in adults and only rarely in children. We describe three new cases of childhood epidermolysis bullosa acquisita, review three previously reported cases, and contrast the features of the disease in children with those in adults. The results suggest that both children and adults with epidermolysis bullosa acquisita have variable clinical and pathologic features that may mimic other bullous diseases. Epidermolysis bullosa acquisita is characterized by a chronic course, poor response to therapy, and occasional clinical remissions. 
Digitalis and beta-blocking agents: effects on depression following myocardial infarction. Depression is frequently seen in patients following myocardial infarction (MI), many of whom are receiving digitalis glycosides, beta-blockers, or other agents that may exert central nervous system (CNS) effects. In a prospective study of the clinical significance of post-MI depression, 335 patients were assessed using a standardized diagnostic interview for depression at 8 to 10 days, and 190 were reinterviewed at 3 to 4 months. Patients prescribed digitalis, beta-blockers, or other cardioactive medications at hospital discharge were identified. Logistic regression analyses were performed to determine the contribution of these agents to depression at 3 to 4 months, controlling for medical and sociodemographic factors as well as for baseline depression. Treatment with digitalis predicted depression at 3 to 4 months (p less than 0.05); no other medications, including beta-blockers, predicted depression (p greater than 0.10). Digitalis may have CNS effects that contribute to depression post-MI and this finding should be considered in the differential diagnosis of depression in cardiac patients. 
Older age and elevated blood pressure are risk factors for intracerebral hemorrhage after thrombolysis. Intracerebral hemorrhage is an important concern after thrombolytic therapy for acute myocardial infarction, but risk factors are controversial. Accordingly, we assessed risk factors in 107 treated patients of whom 4 had intracerebral hemorrhage. Intracerebral hemorrhage occurred at a mean of 25 hours (range 3.5 to 48) after therapy and was fatal in 2 patients. Significant differences were found between patients with and without intracerebral hemorrhage for age (77 +/- 7 vs 62 +/- 11 years, p less than or equal to 0.01), and initial (161 +/- 23 vs 135 +/- 23 mm Hg, p less than or equal to 0.03) and maximal (171 +/- 30 vs 146 +/- 20, p less than or equal to 0.02) systolic blood pressures. Initial and maximal diastolic blood pressures also tended to be higher (101 +/- 25 vs 86 +/- 16, p less than or equal to 0.07; 104 +/- 24 vs 90 +/- 13, p less than or equal to 0.06). Differences did not achieve significance for comparisons of gender, height, weight, site of infarction, time to therapy, specific thrombolytic agent used, concomitant therapy, interventions and partial thromboplastin time. It is concluded that age (greater than or equal to 70 years) and elevated blood pressure (greater than or equal to 150/95 mm Hg) are important risk factors for intracerebral hemorrhage. The overall balance of benefit and risk of thrombolysis should continue to be assessed by large mortality trials. 
Extended aortic root replacement with cryopreserved allografts: do they hold up? The extended aortic root replacement technique is used for the surgical repair of left ventricular outflow tract obstruction complicated by concurrent hypoplastic aortic annulus, multiple levels of obstruction, or aortic insufficiency. Extended aortic root replacement incorporates the concepts of aortic root replacement and aortoventriculoplasty to create a comparatively simple procedure. Unique features of the technique include the implantation of an allograft, which makes the need for anticoagulation obsolete, and use of the donor mitral leaflet to enlarge the outflow tract. Since 1985, 32 patients in Denver have undergone placement of a cryopreserved aortic valve allograft as part of extended aortic root replacement. There were four hospital deaths (13%), and 1 child underwent cardiac transplantation 30 hours after operation. In 6 months to 4.8 years of follow-up, a 14-year-old boy with familial hyperlipidemia required coronary artery bypass grafting, and 3 children experienced allograft calcification with progressive insufficiency, which prompted allograft replacement. The other 23 patients are clinically well. 
Non-antireflux versus antireflux ureteroneocystostomy in adults. A retrospective analysis of ureteric reimplantation in adults showed that a high proportion (71%) had been treated by non-antireflux procedures. Analysis of the ureteroneocystostomy success rate in aetiological groups where either antireflux or non-antireflux techniques were used indicated the superiority of antireflux surgery in the prevention of reflux. The risk of stenosis at the site of anastomosis was equal in both groups. No significant difference in the preservation of renal function was detected in the 2 groups. It was concluded that antireflux procedures offered no advantage over non-antireflux ureteric reimplantation in adults. 
Acute cor pulmonale secondary to metastatic tumor to the heart: a case report and literature review. Metastatic tumors to the heart are becoming more common due to improved survival afforded by advanced treatment of malignancies. Their presence should be sought in a cancer patient who develops new primary cardiac symptoms. We present a case of a 50-year-old woman who succumbed to acute cor pulmonale secondary to metastatic laryngeal carcinoma to the right ventricle with subsequent tumor emboli to the pulmonary vasculature. 
Tentorial subdural hemorrhage in term newborns: ultrasonographic diagnosis and clinical correlates. Tentorial subdural hemorrhage with its supratentorial and infratentorial extensions were diagnosed by cranial ultrasonography and computed tomography in 9 term newborns. Vacuum extraction or forceps delivery was used in 6 patients. Abnormal neurologic manifestations developed after a period of normality in 8 patients. Increased intracranial pressure was the most common presentation. All patients had hemorrhage at the falcotentorial junction near the incisura; 5 also had hemorrhage around the tentorial leaflet. Posterior fossa retrocerebellar subdural hemorrhage developed in 5 patients and posterior interhemispheric subdural hemorrhage developed in 4. All 6 patients who received conservative treatment had normal neurodevelopmental outcomes. Of the other 3 patients upon whom suboccipital craniotomies were performed, only 1 had a normal outcome. Although it localized the tentorial subdural hemorrhage either at the incisura area or at the tentorial leaflet, ultrasonography failed to identify all patients with retrocerebellar or posterior interhemispheric subdural hemorrhage. Parturitional tentorial subdural hemorrhage may not be uncommon. Ultrasonography and computed tomography are complementary in the diagnosis. Surgical decompression of the posterior fossa subdural hematoma is necessary only in the presence of acute hydrocephalus or signs of brainstem compression. 
Efficacy of a postoperative regimen of enoxaparin in deep vein thrombosis prophylaxis. Venous thromboembolism is a common complication in patients undergoing elective hip replacement, in whom the incidence of calf vein thrombosis is 40% to 60%; proximal vein thrombosis, 20%; and fatal pulmonary embolism, 1% to 2% when prophylaxis is not used. A double-blind, randomized trial comparing low-molecular-weight heparin (enoxaparin) with placebo for the prevention of venous thrombosis in patients undergoing elective hip surgery was carried out. Prophylactic treatment with a fixed dose was begun postoperatively and continued for 14 days. Fifty patients in each treatment group underwent surveillance with 125I-fibrinogen leg scanning and impedance plethysmography. In the first 24 patients, venography was performed only if their surveillance test was positive. Venography was requested in the remaining 76 patients even if the screening tests were negative; in this latter group, venous thrombosis occurred in 4 patients (10.8%) given enoxaparin and 20 patients (51.3%) given placebo (p = 0.0002). The corresponding rates for proximal vein thrombosis were 5.4% and 23.1%, respectively (p = 0.029). In the entire group of 100 patients, venous thrombosis occurred in 12% of those given enoxaparin and 42% of those given placebo (p = 0.0007). The corresponding rates for proximal vein thrombi were 4% and 20%, respectively (p = 0.014). The observed hemorrhagic rate was 5% in each treatment group. The results of this study show that prophylaxis with fixed-dose enoxaparin is effective and safe for patients undergoing elective hip replacement. 
Liposarcoma of the esophagus. Liposarcoma is one of the most common soft tissue sarcomas found in adults, yet it rarely develops in the alimentary tract. This report describes the pathological features and management of a liposarcoma of the esophagus. 
Testing for association between disease and linked marker loci: a log-linear-model analysis. One approach frequently used for identifying genetic factors involved in the process of a complex disease is the comparison of patients and controls for a number of genetic markers near a candidate gene. The analysis of such association studies raises some specific problems because of the fact that genotypic and not gametic data are generally available. We present a log-linear-model analysis providing a valid method for analyzing such studies. When studying the association of disease with one marker locus, the log-linear model allows one to test for the difference between allelic frequencies among affected and unaffected individuals, Hardy-Weinberg (H-W) equilibrium in both groups, and interaction between the association of alleles at the marker locus and disease. This interaction provides information about the dominance of the disease susceptibility locus, with dominance defined using the epidemiological notion of odds ratio. The degree of dominance measured at the marker locus depends on the strength of linkage disequilibrium between the marker locus and the disease locus. When studying the association of disease with several linked markers, the model becomes rapidly complex and uninterpretable unless it is assumed that affected and unaffected populations are in H-W equilibrium at each locus. This hypothesis must be tested before going ahead in the analysis. If it is not rejected, the log-linear model offers a stepwise method of identification of the parameters causing the difference between populations. This model can be extended to any number of loci, alleles, or populations. 
Comparison of image analysis and flow cytometric determination of cellular DNA content. A good correlation (r = 0.94) was obtained between the DNA indices (DI) using flow cytometry and image analysis of nuclei cytospins extracted from paraffin wax embedded tumour sections. Some of the limitations and problems associated with image analysis which came to light included an unacceptably high coefficient of variation (CV) and a "left-shift" in the DI in most DNA histograms obtained when using image analysis of 5 microns sections. In contrast, the DNA histograms generated using image analysis of cytospun nuclei from paraffin wax blocks were of good quality and similar to those obtained using flow cytometry. Variability in Feulgen staining was common and an important source of error despite rigorous control of the staining technique. This could be overcome by using internal controls such as fibroblasts rather than external controls (rat hepatocytes) to determine the diploid DI with image analysis. A thorough understanding and appreciation of the methodological problems associated with image analysis and flow cytometric determination of DNA content is required before these methods find widespread clinical application. 
Exercise radionuclide angiocardiography predicts cardiac death in patients with coronary artery disease. The purpose of this investigation was to document the relative importance of three clinical and three radionuclide variables for prediction of cardiac death in a consecutive group of patients evaluated for coronary artery disease. During a 6 1/2-year period, beginning in January 1978, 2,042 consecutive patients underwent radionuclide angiocardiography, with a clinical diagnosis of coronary artery disease, at Duke University Medical Center. A subgroup of 318 patients who underwent surgical myocardial revascularization near the time of initial study were excluded from later analysis. Clinical follow-up information was complete in a group of 1,663 patients who did not undergo interventional therapy. The 141 cardiac deaths in these 1,663 patients were the study end point. Cox proportional hazards models analyzed the prognostic information contained in three clinical variables (pain type, age, and sex) and three radionuclide angiocardiogram variables (exercise ejection fraction, resting end-diastolic volume, and change in heart rate with exercise). One-variable models confirmed the prognostic importance of each of these six variables. A multivariable model in which all six variables were used showed clinical variables to contain only 5% and the radionuclide variables 95% of the prognostic information. The exercise ejection fraction was the single most important variable, which alone contained 85% of the total information in the model. Curves relating probability of no cardiac death to the exercise ejection fraction identified a value of 0.50 as an inflection point. Patients with exercise ejection fractions below 0.50 demonstrate a probability of cardiac death that increases as the ejection fraction decreases. 
Interferon therapy for acute posttransfusion non-A, non-B hepatitis: response with respect to anti-hepatitis C virus antibody status. To assess the effect of interferon therapy on posttransfusion non-A, non-B acute hepatitis, we examined the appearance of serum hepatitis C virus antibody (anti-HCV) and abnormal serum aminotransferase levels after the onset of hepatitis in 12 patients treated with interferon and in 46 patients treated conservatively. Eleven patients were given 3 million units of human fibroblast beta-interferon three times weekly for 4 wk and 1 was given one million units of human lymphoblastoid alpha-interferon daily for 3 months. In the interferon-treated patients, the effect of therapy on hepatic histology was also assessed. Detection of anti-HCV within 6 and 12 months after the onset of hepatitis was less common in interferon-treated patients than in control patients (6/12 vs 35/46 and 5/12 vs 35/46, both p = NS). At 24 months after the onset of hepatitis, anti-HCV levels were significantly lower in interferon-treated patients (0/10, p less than 0.05), but had not changed significantly in control patients (34/46). Abnormal serum aminotransferase levels at 6, 12, and 24 months after the onset of hepatitis were significantly less common in interferon-treated patients than in controls (25% vs 78.3%, p less than 0.005; 25% vs 71.7%, p less than 0.01; and 0% vs 67.4%, p less than 0.001). The percentage of abnormal serum aminotransferase levels at 6, 12, and 24 months after onset of hepatitis was also less in interferon-treated patients than in control patients, both among anti-HCV-positive patients (50% vs 85.7%, p = NS; 50% vs 80%, p = NS; and 0% vs 77.1%, p less than 0.01) and among anti-HCV-negative patients (0% vs 54.5%, p = NS; 0% vs 45.5%, p = NS; and 0% vs 27.3%, p = NS). Immediately after interferon therapy, the histological activity index dropped from 6.0 +/- 4.2 to 4.8 +/- 2.5 in anti-HCV-positive patients (p = NS) and from 4.2 +/- 4.3 to 2.6 +/- 1.7 in anti-HCV-negative patients (p = NS). Biopsy specimens obtained from four patients 12-23 months after interferon therapy revealed normal histology in one anti-HCV-positive patient and two anti-HCV-negative patients, and marked improvement in the other anti-HCV-positive patient. These results indicate that short-term, low-dose interferon therapy may be effective for posttransfusion non-A, non-B acute hepatitis (both anti-HCV-positive and anti-HCV-negative). 
Diagnosis and treatment of oral candidosis. Oral candidosis is a common opportunistic infection that manifests in a variety of forms. It is also recognized as one of the earliest manifestations of human immunodeficiency virus (HIV) infection. Although a number of antifungal agents are available for the treatment of this condition, a newly introduced triazole group of drugs appears to be highly effective in treating oral candidosis. This article reviews the clinical presentation and management of oral candidosis, particularly with reference to the latter group of drugs and HIV-induced disease. 
Experimental cardiac tamponade: a hemodynamic and Doppler echocardiographic reexamination of the relation of right and left heart ejection dynamics to the phase of respiration. A hallmark of cardiac tamponade is pulsus paradoxus. However, the exact mechanism of pulsus paradoxus and the relation of left and right ventricular ejection dynamics remain controversial, with some studies suggesting an inverse relation in ventricular filling and ejection and others citing a more important role for the effects of right heart ejection dynamics delayed by transit through the pulmonary artery bed. To specifically reexamine this issue, six sedated but spontaneously breathing dogs were studied during experimental cardiac tamponade with use of extensive hemodynamic instrumentation and Doppler methods. During cardiac tamponade, left ventricular systolic pressure decreased from 125.8 +/- 12.1 to 81.7 +/- 26.7 mm Hg (p less than 0.01) and cardiac output from 5.86 +/- 1.48 to 2.34 +/- 0.98 liters/min (p less than 0.001); mean pericardial pressure increased from -1.2 +/- 0.8 to 10.5 +/- 3 mm Hg (p less than 0.001) and pulsus paradoxus from 4.3 +/- 1.6 to 10.7 +/- 1.2 mm Hg (p less than 0.001) compared with baseline values. An inverse relation in left and right ventricular ejection dynamics that was very close to 180 degrees out of phase was seen throughout the respiratory cycle in multiple hemodynamic and Doppler variables including peak systolic pressures, aortic and pulmonary flow velocities and ventricular ejection times. Simultaneous recording of the transmitral pressure gradient provided indirect evidence that the ventricular ejection dynamics were directly related to changes in ventricular filling. However, the magnitude of ventricular pressure or output flow velocity for each respiratory cycle was variable, depending on the exact timing of filling and ejection in relation to the phase of respiration. Variation in left ventricular output due to changes in right ventricular output delayed by transit through the pulmonary vasculature was not recognized in any animal. It is concluded that in spontaneously breathing dogs with acute cardiac tamponade, peak ventricular pressures, ventricular ejection times and pulmonary and aortic flow velocities have an inverse relation that is very close to 180 degrees out of phase. 
Pyogenic vertebral osteomyelitis with paralysis. Prognosis and treatment. In the interval between 1983 and 1988, 14 patients were treated for pyogenic spondylitis complicated by neurologic compromise. There were nine males and five females aged 39-80 years. The average time between onset of symptoms and diagnosis was 2.8 months. Predisposing factors were diabetes mellitus in four patients and urinary tract infections in five patients. The infection was blood borne in all 14 patients. In two patients, the infection was superimposed on a recent vertebral fracture. The cervical spine was involved in one patient; the thoracic spine in seven; and the lumbar spine in six patients. Six patients presented with a Frankel B paralysis, six with a Frankel C paralysis, and two with grade D paralysis. The neurologic symptoms lasted between one day and six weeks before surgery. Twelve patients had anterolateral decompression. Two of the 12 patients had a second stage posterior stabilization. Two patients were deemed inoperable. All surviving patients were managed by parenteral antibiotics for three to six weeks followed by enteral route for a total of three to six months. All 12 operated patients had a significant neurologic improvement (one grade or more on the Frankel scale) with solid interbody fusion. 
Cell kinetics of gastrointestinal tumors after different nutritional regimens. A preliminary report. Forty-four cases of different untreated gastrointestinal tumors were studied with regard to cell kinetic activity. As a pilot experiment, we also determined the 3H-TdR Labeling Index (LI) in 28 patients in basal conditions and after 15 days of nutritional manipulation with prevalently lipid-based or glucose-based feeding to ascertain whether selective nutritional regimens could affect tumor proliferation. Preliminary results from this study indicate that a kinetic perturbation is induced in tumor cells by nutritional manipulation. Lipid-based feeding seems to produce effects similar to those of chemical or physical anticancer agents, thus suggesting a possible supporting role of nutritional manipulation in cancer treatment strategy. 
Direct correlation of cytogenetic findings with cell morphology using in situ hybridization: an analysis of suspicious cells in bone marrow specimens of two patients completing therapy for acute lymphoblastic leukemia. Bone marrow cells from two pediatric patients completing therapy for acute lymphoblastic leukemia were studied using in situ hybridization with an alpha-satellite DNA probe specific for chromosome 17. Morphologic analysis of the end-therapy specimens from each patient had shown small numbers (7.5%, 8.5%) of cells that were suspicious for residual or recurrent disease. These cells could not be morphologically or immunophenotypically distinguished with certainty from immature lymphoid cells (hematogones), which may be present normally, sometimes in increased numbers, in the bone marrow specimens of children. In situ hybridization with a probe to chromosome 17 was used because the leukemic cells from each patient had originally been shown to have an extra copy of this chromosome. In one patient, in situ studies showed a population of cells (106 of 1,000 cells) with three hybridization signals indicating trisomy 17, and thus residual/recurrent leukemia. In the other patient trisomy 17 could not be detected. Additional hybridizations to previously stained bone marrow aspirate smears permitted a direct correlation of the cytogenetic findings with the suspicious cells on a cell-to-cell basis. The questionable cells were identified, photographed, and then re-examined after hybridization. In one patient, 13 of 18 (72%) of the suspicious cells were found to have trisomy 17, whereas in the other patient 0 of 24 (0%) demonstrated an extra copy of this chromosome. These cases illustrate a clinical application of interphase cytogenetic analysis and demonstrate how this technology can be used for direct correlation of cytogenetic findings with cell morphology. This technique should prove useful for the detection of minimal residual disease and for lineage studies in leukemia and myelodysplasia. 
Genesis of arrhythmias in the failing heart and therapeutic implications. Between 50 and 70% of patients with heart failure die suddenly and unexpectedly before they have deteriorated to New York Heart Association class IV symptoms. It has long been known that ventricular ectopy predicts sudden cardiac death in coronary heart disease, and this has also been shown in dilated cardiomyopathy. It is less certain whether antiarrhythmic drugs reduce this risk and improve prognosis. Supraventricular arrhythmias frequently develop in heart failure of all causes. They nearly always cause symptoms, and the establishment of atrial fibrillation may mark a permanent deterioration. Except for sustained ventricular tachycardia, ventricular arrhythmias are often occult. Hypokalemia and digitalis toxicity may have been precipitated by diuretics or interaction with antiarrhythmic drugs. In coronary heart failure, arrhythmias may be related to scar tissue or ischemia, which may also be responsible in dilated cardiomyopathy. Use of inotropes and inodilators may precipitate arrhythmias, whereas drugs that conserve energy or potassium, such as beta blockers and angiotensin-converting enzyme inhibitors, may prevent them. Since suppression of ventricular arrhythmias has not been shown to prevent sudden death or prolong life in patients with heart failure, it may be that such arrhythmias do not directly presage ventricular fibrillation except in so far as they are markers of a poor prognosis with a risk of sudden death. If so, such arrhythmias are most likely to be suppressed by agents that result in improvement of left ventricular function and, through that, prolongation of life. 
Nutritional supplementation, psychosocial stimulation, and mental development of stunted children: the Jamaican Study. There is little unequivocal evidence that nutritional supplementation of undernourished children has a beneficial effect on their mental development. The effects of nutritional supplementation, with or without psychosocial stimulation, of growth-retarded (stunted) children aged 9-24 months were assessed in a study in Kingston, Jamaica. 129 children from poor neighbourhoods were randomly assigned to four groups--control, supplemented only, stimulated only, and supplemented plus stimulated. A group of matched non-stunted children (n = 32) was also included. The supplement comprised 1 kg milk-based formula per week for 2 years, and the stimulation weekly play sessions at home with a community health aide. The children's development (DQ) was assessed on the Griffiths mental development scales. Initially the stunted groups' DQs were lower than those of the non-stunted group, and those of the control group declined during the study, increasing their deficit. Stimulation and supplementation had significant independent beneficial effects on the children's development. Estimates of the supplementation effect ranged from 2.2 (95% confidence limits-1.4, 5.7) for the hand and eye subscale to 12.4 (5.4, 19.5) for the locomotor subscale and those for the stimulation effect from 6.4 (2.8, 10.0) for hand and eye to 10.3 (3.3, 17.3) for locomotor. The treatment effects were additive, and combined interventions were significantly more effective than either alone. These findings suggest that poor mental development in stunted children is at least partly attributable to undernutrition. 
Limitations of the electrocardiogram in estimating infarction size after acute reperfusion therapy for myocardial infarction. OBJECTIVE: To assess the ability of the 12-lead electrocardiogram to estimate infarction size after reperfusion therapy for acute myocardial infarction. DESIGN: The presence or absence of Q waves and the Selvester QRS score obtained before and after hospital discharge were compared with radionuclide estimates of infarction size and ejection fraction at discharge and 6 weeks later, regional wall motion at discharge and 6 weeks later, and myocardial perfusion defect size quantitated with Tc-99m-sestamibi at discharge. SETTING: A tertiary referral center. PATIENTS: A consecutive series of 43 patients with acute myocardial infarction who received acute reperfusion therapy and were assessed using 12-lead electrocardiography, radionuclide angiography, and Tc-99m-sestamibi tomographic imaging before discharge. INTERVENTIONS: All 43 patients received acute reperfusion therapy: 21 patients received intravenous tissue plasminogen activator, and 22 patients underwent primary percutaneous transluminal coronary angioplasty. MAIN OUTCOME MEASURE: The correlation of QRS score and Q waves with three radionuclide estimates of infarction size. RESULTS: A significant correlation was found between myocardial perfusion defect size at discharge and both left ventricular ejection fraction and regional wall motion at discharge and 6 weeks later (r = -0.71 to -0.81; all comparisons, P less than 0.001). Little correlation was found between electrocardiographic findings and radionuclide measurements of left ventricular function and perfusion. Presence or absence of Q waves at discharge was not associated with any difference in ejection fraction, regional wall motion, or perfusion defect at discharge. No correlation was found between QRS score and ejection fraction or myocardial perfusion defect size at discharge. The QRS score at discharge correlated only weakly with regional wall motion at discharge and 6 weeks later. This lack of correlation was unchanged when electrocardiograms obtained after hospital discharge were analyzed. CONCLUSION: Although inexpensive and readily available, the 12-lead electrocardiogram does not appear to provide a reliable estimate of infarction size after reperfusion therapy for acute myocardial infarction. 
Beneficial effects of alpha 1-adrenoceptor activity on myocardial stunning in dogs. This study was undertaken to elucidate whether alpha-1 adrenoceptor activity is beneficial to contractile dysfunction during reperfusion after a brief period of ischemia (stunned myocardium) in 54 open-chest dogs. Contractile dysfunction assessed by fractional shortening (FS) was observed 3 hours after the onset of reperfusion following 15 minutes of complete occlusion of the left anterior descending coronary artery. Pretreatment with prazosin (4 micrograms/kg/min i.c.) further deteriorated contractile dysfunction compared with the untreated condition (12.7 +/- 0.6% versus 6.9 +/- 0.4% with prazosin treatment, p less than 0.001). Conversely, alpha 1-adrenoceptor agonists, methoxamine (1.0 microgram/kg/min i.c.) and norepinephrine (0.24 microgram/kg/min i.c.) with rauwolscine and propranolol, significantly attenuated contractile dysfunction (FS in the methoxamine-treated group, 17.3 +/- 0.3%, p less than 0.001 versus the untreated group; FS in the norepinephrine-treated group, 18.0 +/- 0.9%, p less than 0.05 versus 13.6 +/- 1.1% in the propranolol group). Both adenosine release and hyperemic coronary flow response during the early reperfusion period were significantly attenuated in the prazosin-treated group, and both were enhanced in the alpha 1-adrenoceptor stimulation groups. These results suggest that beneficial effects of alpha 1-adrenoceptor activity may be due to the enhanced release of adenosine. To test the cause-effect relation between the extent of adenosine release and contractile dysfunction during reperfusion, 8-phenyltheophylline was infused to block adenosine receptors in the methoxamine-treated group. The treatment with 8-phenyltheophylline completely abolished (FS, 7.4 +/- 0.3%) the beneficial effect of the enhanced adenosine release by alpha 1-adrenoceptor stimulation. Furthermore, in the prazosin-treated group, adenosine (9 micrograms/kg/min) was additionally infused into the left anterior descending coronary artery 5 minutes before and 2 hours after the onset of reperfusion. Both hyperemic coronary flow and contractile dysfunction (FS, 17.3 +/- 0.3%) recovered to the levels of the alpha 1-adrenoceptor stimulation groups. However, treatment with papaverine could not prevent deleterious effects of prazosin despite the fact that comparable hyperemic flow was obtained. Instead, lactate production up to 10 minutes after the onset of reperfusion was significantly larger (p less than 0.01) despite augmented contractile function in the prazosin-treated and the 8-phenyltheophylline with methoxamine-treated groups compared with the untreated group. The electron microscopic examination revealed no irreversible myocardial injury with and without pharmacological interventions. Thus, we conclude that alpha 1-adrenoceptor activity can reduce the magnitude of myocardial stunning and that its cellular mechanism is due to enhanced adenosine release by alpha 1-adrenoceptor activity.(ABSTRACT TRUNCATED AT 400 WORDS). 
Grafting of perfused adrenal medullary tissue into the caudate nucleus of patients with Parkinson's disease. Clinica Puerta de Hierro Neural Transplantation Group. The authors report results obtained in 20 severely affected patients with Parkinson's disease (Grade IV or V) who received an autotransplant of perfused adrenal medullary tissue. This study seems to indicate that these autoimplants can improve the parkinsonian symptomatology and induce amelioration in the patients' performance of routine activities. All the symptoms analyzed showed improvement, although it differed in intensity and time of onset. Moreover, this improvement was accompanied by a reduction in the daily intake of L-dopa, with discontinuance of dopamine agonists and amantadine. A number of medical complications were encountered, including three deaths, probably related to performing abdominal surgery in seriously affected parkinsonian patients who were unable to tolerate the discontinuance of their medication. The transient psychiatric disorders observed appeared to be related to the postoperative dose of L-dopa and/or anticholinergic agents administered, and diminished or disappeared when the doses were reduced. The reasons for improvement, which was bilateral, remain unknown, although one cause may be the surgical trauma (minicaudotomy) together with the implantation of adrenal medullary tissue, which may promote the sprouting of surviving dopaminergic fibers. Moreover, in this series, perfusion of adrenal medulla increased the capacity for revascularization of the tissue and may have reduced the damaging effects of warm ischemia on the cells. This, together with the existence of fenestrated vessels, could hypothetically have served as an access point for drugs, and if the implanted cells were viable, they might have served to store and manufacture different factors and/or transmitters. These results as well as those of other groups justify the development of a controlled international clinical trial. 
Isradipine: overall clinical experience in hypertension in the United States. Isradipine is a new dihydropyridine calcium antagonist shown to be efficacious, safe, and well tolerated in the treatment of hypertension, regardless of patient age or race. There has been no evidence of negative inotropism, atrioventricular conduction delay, nor clinically significant changes in laboratory parameters associated with isradipine treatment. A total of 934 patients have been treated with isradipine in double-blind hypertension trials (involving 297 patients treated with placebo and 414 treated with active controls, such as hydrochlorothiazide and enalapril). Both the mean changes from baseline in diastolic and systolic blood pressures and the percentage of patients responding to treatment (blood pressure decrease of at least 10 mm Hg) were greater with isradipine than with placebo or active controls. Blood pressure response increases with increases in isradipine dose up to 10 to 15 mg daily; higher doses do not, on average, result in greater blood pressure reduction. The incidence of adverse reactions with isradipine is similar to that for active controls and slightly more than for placebo. There were fewer discontinuations with isradipine and, in addition, a decrease in the incidence of new adverse reactions with increasing duration of treatment, down to 1% at 24 months. 
Chronic neurologic manifestations of Lyme disease BACKGROUND AND METHODS. Lyme disease, caused by the tick-borne spirochete Borrelia burgdorferi, is associated with a wide variety of neurologic manifestations. To define further the chronic neurologic abnormalities of Lyme disease, we studied 27 patients (age range, 25 to 72 years) with previous signs of Lyme disease, current evidence of immunity to B. burgdorferi, and chronic neurologic symptoms with no other identifiable cause. Eight of the patients had been followed prospectively for 8 to 12 years after the onset of infection. RESULTS. Of the 27 patients, 24 (89 percent) had a mild encephalopathy that began 1 month to 14 years after the onset of the disease and was characterized by memory loss, mood changes, or sleep disturbance. Of the 24 patients, 14 had memory impairment on neuropsychological tests, and 18 had increased cerebrospinal fluid protein levels, evidence of intrathecal production of antibody to B. burgdorferi, or both. Nineteen of the 27 patients (70 percent) had polyneuropathy with radicular pain or distal paresthesias; all but two of these patients also had encephalopathy. In 16 patients electrophysiologic testing showed an axonal polyneuropathy. One patient had leukoencephalitis with asymmetric spastic diplegia, periventricular white-matter lesions, and intrathecal production of antibody to B. burgdorferi. Among the 27 patients, associated symptoms included fatigue (74 percent), headache (48 percent), arthritis (37 percent), and hearing loss (15 percent). At the time of examination, chronic neurologic abnormalities had been present from 3 months to 14 years, usually with little progression. Six months after a two-week course of intravenous ceftriaxone (2 g daily), 17 patients (63 percent) had improvement, 6 (22 percent) had improvement but then relapsed, and 4 (15 percent) had no change in their condition. CONCLUSIONS. Months to years after the initial infection with B. burgdorferi, patients with Lyme disease may have chronic encephalopathy, polyneuropathy, or less commonly, leukoencephalitis. These chronic neurologic abnormalities usually improve with antibiotic therapy. 
Menstrual cycle factors related to increased gastric contractile response to tube feeding. Evidence exists that the ovarian hormones have a modulating effect on gastrointestinal (GI) motility, yet details are sketchy and little attention has been paid to the effect that fluctuating hormone levels might have on women who are receiving enteral feedings. This study compared gastric motility indices in response to tube feedings at two points in the menstrual cycle, concurrently measured ovarian hormone levels, and described three potentially related factors (ie, GI symptoms, uterine cramping pain, reports of daily stressors). Intragastric motility responses to enteral feedings were obtained on 28 women (aged 19-37) during menses and midfollicular phases of two menstrual cycles. Intragastric pressure changes were monitored by an open-tipped cannula method at rest, during and after tube feeding (Ensure, 240 ml at 8 ml/min). Serum estradiol and progesterone levels were measured by radioimmunoassay. Women completed a daily diary of symptoms and stressors throughout the two menstrual cycles. Results showed that intragastric pressure amplitudes and frequencies were higher at menses compared with midfollicular recordings. At menses, prefeeding and feeding gastric pressure amplitudes were positively correlated with uterine cramping pain and GI symptoms (ie, nausea). At menses, postfeeding contraction frequencies were also correlated with uterine cramping pain. At midfollicular phase, progesterone levels correlated with gastric motility indices; number of stressors indirectly correlated with gastric motility indices. These data suggest that gastric responses to enteral feeding are influenced by menstrual cycle phase. 
Nd:YAG laser-induced hyperthermia treatment of spontaneously occurring veterinary head and neck tumors. Conventional hyperthermia treatment of superficial tumors in the oral cavity is troublesome due to difficulty in accessing the lesion. A new hyperthermia technique employing near-infrared radiation delivered through a flexible silica optical fiber is described. The system consisted of an Nd:YAG laser for tissue heating, a He-Ne laser for aiming beam, a computer-controlled optical shutter, an interstitial thermometer, computer, and a printer. A 3-m-long 600-microns silica fiber delivered laser energy to the tumor via surface illumination. Using the aiming beam, the spot size was adjusted to include 5 mm of surrounding normal tissue. A thermocouple implanted in the tumor base provided temperature feedback to maintain desired hyperthermic temperature within the lesion. Three spontaneously occurring canine (two squamous cell carcinomas on the gum, one pigmented melanoma on the hard palate) and one feline tumor (squamous cell carcinoma on the nose) have been treated with Nd:YAG laser hyperthermia. Hyperthermia was delivered at 43.5 degrees C for 1 h. All animals received standard radiation treatment prior to hyperthermia. Nd:YAG laser hyperthermia allowed effective and efficient delivery of heat to veterinary nasal and oral lesions otherwise not treatable with conventional heating techniques. 
Pulmonary function tests in bronchopleural fistula. A 53-year-old white man underwent a left pneumonectomy for alveolar cell carcinoma. His postoperative course was complicated by pneumonia. At a follow-up clinic visit, the patient complained of a "roaring sound" during respiration. A follow-up PFT did not show the expected loss of volume (nitrogen washout) from a preoperative PFT, suggesting a bronchopleural fistula. A chest x-ray film and xenon lung scan confirmed the diagnosis. The fistula was surgically repaired. 
End-to-end repair of aortic coarctation using absorbable polydioxanone suture. Based on previous laboratory work, we have used polydioxanone absorbable suture in a variety of vascular and cardiac repairs in pediatric patients. However, some investigators have expressed concern about the potential for aneurysm formation at the anastomotic site. Between March 1983 and June 1989, 15 patients (7 male, 8 female) aged 2.5 months to 9.2 years (mean, 3.7 years) had resection of coarctation of the aorta and end-to-end anastomosis with polydioxanone absorbable suture. Thirteen patients have returned for routine postoperative evaluation, the follow-up time ranging from 11 to 49 months (mean, 23 months). Noninvasive two-dimensional, pulsed-wave Doppler and color echocardiography and magnetic resonance imaging studies demonstrated good anatomical repair and no anastomotic aneurysm formation or residual coarctation of the aorta in any patient after end-to-end anastomosis with polydioxanone. In summary, this intermediate follow-up study has revealed no vascular complications related to the repair of coarctation with absorbable polydioxanone suture. 
A life-threatening sexually transmitted Haemophilus influenzae in septic abortion: a case report. Haemophilus influenzae infections of the genitourinary tract are rare. A case of a life-threatening Haemophilus influenzae bacteremia associated with a septic abortion is presented. Sexual transmission of bacteria after orogenital contact is proposed as a possible source of this uncommon infection. 
Thoracic epidural analgesia in a patient with bilateral phaeochromocytoma undergoing coronary artery bypass grafting. A patient suffering from phaeochromocytoma and coronary artery stenoses needed coronary artery bypass grafting before adrenalectomy. High thoracic epidural analgesia (T1-T2) with bupivacaine and sufentanil in combination with general anaesthesia was used. Plasma adrenaline and noradrenaline concentrations decreased during the period before bypass grafting compared to the baseline value and no important haemodynamic changes were seen during this period. Thoracic epidural analgesia failed to suppress the release of catecholamine during the bypass period. After the operation, the plasma catecholamine concentrations returned to the baseline value. Excellent analgesia (visual analogue scale = 1-2) was achieved with a postoperative epidural, but the plasma catecholamine concentration increased considerably. 
Serum and tissue alpha-L-fucosidase activity in the pre-clinical and clinical stages of hepatocellular carcinoma. 1. To assess the value of serum alpha-L-fucosidase (EC 3.2.1.51) as a marker for hepatocellular carcinoma, the activity was measured in patients with hepatocellular carcinoma and in control subjects. 2. Mean serum alpha-L-fucosidase activity was significantly greater in 35 patients with hepatocellular carcinoma (225 +/- 69 nkat/l) than in 35 patients with cirrhosis and 20 normal subjects (134 +/- 30 and 93 +/- 28 nkat/l, respectively). The overlap between hepatocellular carcinoma and cirrhosis, however, was such as to severely limit any value of the enzyme as a diagnostic test. 3. In four cirrhotic patients with hepatocellular carcinoma, an increased enzyme activity was detectable in samples taken up to 66 months before the tumours were diagnosed clinically. 4. The serum activity of alpha-L-fucosidase fell to within the reference range after liver transplantation for hepatocellular carcinoma in three patients and in one of these a subsequent rise was associated with tumour recurrence which was diagnosed at 8 months after the rise in activity. Ineffective cytotoxic chemotherapy was also associated with a progressive rise in serum alpha-L-fucosidase activity. 5. alpha-L-fucosidase activity in tumour tissue was significantly lower than that seen in non-tumour tissue from cirrhotic patients. These reductions may represent increased transport from the tissue and may partly account for the increased serum activity found in some patients with hepatocellular carcinoma. 
Generalized pustular psoriasis. A review of 63 cases. BACKGROUND--Sixty-three patients with generalized pustular psoriasis were hospitalized during a 29-year period. They were classified into four subgroups on the basis of onset and morphologic pattern of disease: acute (von Zumbusch), subacute annular, chronic (acral), and mixed. This division provides a better understanding of the variability of the disease and helps in choosing treatment. OBSERVATIONS--The average age at onset was 50 years; male and female patients were affected about equally. In 11 patients, flares were precipitated by localized infections. Approximately one fourth of the patients had complications; most were superinfections. The average stay in the hospital was 30 days; factors correlating with a long hospitalization were hypocalcemia, female sex, and a previous history of psoriasis vulgaris or pustular psoriasis. CONCLUSIONS--Whereas topical therapy was helpful, systemic medications were often needed. Coal tar, ultraviolet light, and psoralen-ultraviolet A may be effective; however, they must be used with caution, because they may exacerbate the disease. 
Cardiovascular reflexes and autonomic dysfunction in Parkinson's disease. Cardiovascular reflexes were analysed in a group of 20 patients suffering from Parkinson's disease and in 12 age-matched healthy subjects, in order to ascertain the incidence and degree of autonomic dysfunction. The following were measured: heart rate variation during normal breathing, postural change (30/15 ratio) and during the Valsalva manoeuvre: blood pressure variation after standing. These measurements were taken at least 12 h after therapy had been withdrawn and were repeated after therapy had been resumed. Significant changes in the different heart rate variation indices were found in the parkinsonian patients which correlated with the duration and severity of the extrapyramidal symptomatology. After standing the patients showed a significant drop in blood pressure, when compared respectively with their base values and with the response in controls. Anticholinergic drugs had no significant effect on the heart rate variation indices, whereas antiparkinsonian therapy seems to have contributed to the drop in blood pressure after standing. 
Transformation suppressor activity of a Jun transcription factor lacking its activation domain. The oncoprotein c-Jun is thought to be a mediator of ras transformation as both its synthesis and activity as a transcription factor are stimulated by ras expression. But c-Jun co-operates with ras in transformation assays, suggesting that they act along different pathways (reviewed in ref. 4). Here we show by means of a dominant-negative mutated transcription factor that c-Jun potentially in conjunction with other factors that interact with it is necessary for transformation by ras. The mutant Jun lacks an activation domain and blocks stimulation of transcription by several oncoproteins, including Ras, v-Src, polyoma middle T, c-Jun and c-Fos, as well as by the tumour promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). The inhibition is specific for motifs that bind Jun: activation of an NF-kappa B/Rel motif is not affected. This Jun mutant acts as an anti-oncogene in ras-transformed cells, generating non-transformed revertants that have acquired anchorage and density-dependent growth, as well as reduced tumorigenicity in vivo. Mutants of other transcription factors designed to inhibit transformation will enable us to study their role in signal transduction. 
Plasticity of central motor pathways in children with hemiplegic cerebral palsy. To obtain neurophysiologic evidence for a reorganization of central motor pathways in children who had suffered a cerebral lesion at birth, we performed cross-correlation analyses of multiunit EMG recordings obtained from children with hemiplegic cerebral palsy and marked mirror movements. We found that the motoneuron pools of homologous left and right hand muscles received common synaptic input from abnormally branched presynaptic axons. The results of electromagnetic brain stimulation, cutaneomuscular, and tendon reflex testing suggested that these common inputs are provided by abnormally branched corticospinal tract fibers whose origin is the undamaged motor cortex. 
Complex segregation analysis of primary hepatocellular carcinoma in Chinese families: interaction of inherited susceptibility and hepatitis B viral infection. Primary hepatocellular carcinoma (PHC) is extremely common in eastern China, where it is both associated with chronic infection with hepatitis B virus (HBV) and often familial. Complex segregation analysis of 490 extended families was undertaken with liability classes defined by age, sex, and HBV infection status. The maximum-likelihood model suggests that a recessive allele with population frequency approximately .25 yields lifetime risk of PHC, in the presence of both HBV infection and genetic susceptibility, of .84 for males and .46 for females. The model further predicts that, in the absence of genetic susceptibility, lifetime risk of PHC is .09 for HBV-infected males and .01 for HBV-infected females and that, regardless of genotype, it is virtually zero for uninfected persons. Complex segregation analysis therefore provides evidence for the interaction of genotype, environmental exposure, sex and age in determining the occurrence of PHC in this population. 
Biomagnetic localization of ventricular arrhythmias. The magnetic fields caused by electrical activity of the human heart can be coherently measured with a highly sensitive, multichannel, superconducting quantum interference-device system and can enable noninvasive localization of the underlying electrical activity. The magnetocardiograms (MCGs) of 10 patients with spontaneous premature ventricular complexes (PVCs), three patients with ventricular tachycardia (VT), and four healthy subjects with induced paced beats were recorded for 2-15 minutes. After correction for superimposed repolarization activity, the site of origin of the arrhythmias was localized from the magnetic field distribution at the onset of the ectopic beats. The localization results of paced beats showed an error of a few millimeters in relation to the position of the catheter tip. The results of spontaneous PVC and VT were confirmed with endocardial mapping or associated with ischemic lesions. The authors conclude that multichannel magnetocardiographic studies enable the completely noninvasive localization of ventricular arrhythmias. 
Intraperitoneal contrast material improves the CT detection of peritoneal metastases. The preoperative detection of peritoneal metastases from gynecologic malignancies is difficult; in particular, CT often fails to detect peritoneal implants. This study was designed to determine if the administration of intraperitoneal iodinated contrast media would increase the CT detection of such peritoneal metastases. Prospectively, both standard and intraperitoneal contrast-enhanced CT studies of the abdomen and pelvis were performed in 16 patients with suspected gynecologic tumors. All patients then underwent operative staging, with the location and number of metastases documented. The intraperitoneal enhanced CT studies were more sensitive in the detection of peritoneal metastases than standard CT examinations. Whereas routine CT detected peritoneal metastases in seven (64%) of 11 patients with surgically proved implants, the intraperitoneal enhanced CT studies detected peritoneal metastases in all 11 patients. Depending on the specific intraperitoneal compartments involved, the sensitivity of intraperitoneal enhanced CT in the detection of peritoneal metastases was two- to fourfold greater than that of standard CT examinations. Our results suggest that intraperitoneal enhanced CT is superior to standard CT in the detection of peritoneal metastases. 
Abscesses of the neck in infants and young children. A review of 112 cases. A review of 112 patients 5 years of age and younger with cervical abscesses is reported. Staphylococcus aureus and group A beta-hemolytic Streptococcus were cultured most often: in 39% and 17% of patients, respectively. Sixteen patients (14%) had unusual abscesses such as infected congenital cysts, cat-scratch disease, or myocobacterial abscesses. One patient had a necrotizing infection with group A streptococci and anaerobic streptococci. Intravenous antibiotic therapy was used in 104 patients, with 94% of these patients receiving a penicillin derivative, usually an antistaphylococcal penicillin. Ninety-six percent of the patients had incision and drainage of their abscesses; 8 patients required more than one incision and drainage. Two patients required airway intervention, 1 by intubation and 1 by trachetomy. Most pediatric cervical abscesses respond well to appropriate intravenous antibiotic therapy and incision and drainage. 
Effects of EAP follow-up on prevention of relapse among substance abuse clients. Clients entering an employee assistance program (EAP) of a large manufacturing plant in 1985 who were assessed as having an alcohol or drug abuse problem (N = 325) were randomized into an experimental "special follow-up" group and a control "regular care" group. The regular care group received follow-up only as needed (following the usual practice of the EAP), while a follow-up counselor was hired to make routine contacts with the special follow-up group. Study intake continued through 1985, and follow-up continued through the end of 1986. Data collected on study subjects included EAP participation data, absenteeism, number of hospitalizations, health care claims paid and disability claims paid. The major study hypothesis was that EAP clients randomly allocated to special follow-up would show better results than regular care clients (i.e., would have fewer relapses, better job attendance and lower health benefit utilization during the follow-up year). The follow-up intervention was incompletely implemented due to a variety of organizational problems. Differences between the two groups on the six outcome measures were not statistically significant, although clients in the special follow-up group did show better results than clients in the regular care group on the three measures related to substance abuse. Differences on these three measures were marginally significant in regression analyses after controlling for the effects of number of follow-up visits, age, race and chronicity. 
Naloxone-sensitive, pregnancy-induced changes in behavioral responses to colorectal distention: pregnancy-induced analgesia to visceral stimulation. This study examined the feasibility of using colorectal distention as a noxious visceral stimulus in rat pregnancy-induced analgesia studies as well as the influence of naloxone on the pregnancy-induced changes in the behavioral response to a noxious visceral stimulus. In the first part of the study, we compared the effects of pregnancy on several forms of noxious stimulation (colorectal distention, hypertonic saline induced writhing, tail flick, and hot plate). After determination of prepregnant baseline values, one group of rats (n = 35) was mated and retested on days 7 and 21 of gestation and 1, 3, 5, 7, and 14 days after parturition. After baseline determinations on day 21 and postpartum day 1, the animals received a subcutaneous injection of naloxone 1.0 mg/kg and were retested. A nonpregnant control group of animals (n = 7) was tested in the same manner. On day 21 of gestation and postpartum days 1 and 3, significant changes (higher threshold or longer latency to response) were observed after all but the writhing test. High-dose naloxone (1.0 mg/kg) significantly reduced the increases observed on day 21 and post-partum day 1. Nonpregnant rats demonstrated no significant change on any test day. The second part of the study evaluated a possible influence of low-dose naloxone on pregnancy-induced analgesia to visceral stimulation (colorectal distention) in another group of pregnant rats (n = 44). The significant increase in threshold on day 21 of gestation was not changed by intravenous (i.v.) naloxone 1.0, 2.3, or 3.0 micrograms/kg, whereas 5.0 and 20.0 micrograms/kg naloxone significantly decreased the observed pregnancy-induced analgesia. 
Treatment of acute myeloid leukaemia in a renal allograft recipient: implications of cyclosporin immunosuppressive treatment. The clinical effects of cyclosporin were evaluated during cytotoxic treatment in a 61 year old man with acute myeloid leukaemia. He had required a renal transplant 18 months before presenting with acute myeloid leukaemia (FAB subtype M4). He had received cyclosporin 3.5-4.0 mg/kg daily to maintain a plasma cyclosporin concentration of 75-150 ng/ml. Cyclosporin was continued during induction chemotherapy with daunorubicin, cytarabine, and 6-thioguanine (DAT). He had fever and oropharyngeal candidiasis that was unresponsive to anti-bacterial drugs but responsive to systemic amphotericin. Bone marrow examination 14 days after chemotherapy showed complete haematological remission. Subsequently he tolerated consolidation treatment with DAT with no serious complications. Unfortunately he developed fatal septicaemia following a second consolidation with mitozantrone and cytarabine. Inhibition of P-glycoprotein activity by cyclosporin may not significantly increase the toxicity of aggressive chemotherapeutic regimens, and as benefit may be achieved by this approach further clinical evaluation is justified. 
Renal transplant arterial thrombosis: association with cyclosporine. Of 136 patients who received a renal transplant between January 1984 and August 1988, there were six cases (4.4%) of allograft arterial thrombosis (AAT) occurring a mean of 23 days after transplantation. All were maintained on cyclosporine A(CsA) in addition to prednisone and azathioprine. All transplants were performed by the same transplant surgeon. Five of the six episodes (83%) were in allografts that had multiple renal arteries (MRA), giving an incidence of AAT in that group of 36%. Only one of 122 (0.8%) allografts with a single renal artery experienced thrombosis. CsA was started a mean of 9 days after transplantation (range, 16 to 33 days). There was no correlation of AAT to CsA levels. AAT appears to be an early complication of allografts with MRA in patients maintained on CsA. 
Phase I-II study of advanced head and neck squamous cell carcinoma patients treated with recombinant human interferon gamma. The association of immunodeficiency with head and neck squamous cell carcinoma has generated the concept of supplying immunologically active agents as a means of treating these cancers. One of the most active immunologic messengers is interferon gamma, which has been observed in our laboratories to also have a direct cytotoxic effect on cultures of squamous cell carcinoma derived from the head and neck. To test the feasibility of treating patients with advanced but resectable head and neck cancer with this agent, we designed a phase I-II trial of recombinant human interferon gamma using a 24-hour infusion repeated weekly for four times. In this study, both tumor and immunologic parameters were studied before and after treatment. Eight patients were entered into the study with the highest recombinant human interferon gamma dose attempted being 0.25 mg/m2 per 24 hours. Minimal side effects were observed. Three patients had clinically measurable responses, four had stabilization of disease, and one had progression while receiving treatment. Histopathologic results of treatment were similar to in vitro observations. Necrosis, as well as differentiation of tumor cells, was observed. In some tumors there was a marked decrease in cellularity without a change in tumor volume due to increased extracellular keratin deposition. Our study indicates that evaluation of adoptive immunotherapy trials in head and neck cancer needs to include parameters other than simple tumor regression as an end point, otherwise therapeutically important lymphokine-induced changes may be missed. Further evaluation of recombinant human interferon gamma and agents that induce human interferon gamma are warranted. 
Incremental prognostic accuracy of clinical, radionuclide and hemodynamic data in acute myocardial infarction. A logical sequence of testing in evaluating prognosis early in acute myocardial infarction (AMI) would be to use clinical data first, then add noninvasive data and finally add invasive data. The incremental prognostic information concerning 1-year survival obtained from such a sequence in 107 patients with AMI was studied using logistic regression and receiver-operating characteristic curves. Cardiac mortality was 24% at 1 year. Clinical data obtained soon after admission (prior myocardial infarction, heart rate, blood pressure, age) were 78 +/- 5% accurate in the prediction of 1-year survival. The addition of radionuclide-estimated left ventricular ejection fraction or invasive hemodynamic data to the clinical model at this time improved prognostic accuracy to 84 +/- 5% (p = 0.05) and 87 +/- 4% (p = 0.007), respectively. The further addition of invasive data to the model containing clinical and left ventricular ejection fraction data provided a further increment in prognostic accuracy to 89 +/- 4%, whereas no significant increase in accuracy was seen on addition of left ventricular ejection fraction to the model containing clinical and invasive data. It is concluded that clinical data provide important prognostic information concerning late survival early in the course of AMI. This may be improved by the logical application of noninvasive and invasive studies at this time. 
Dietary manipulation of methotrexate-induced enterocolitis. Administration of chemotherapy is limited by host toxicity, which is often manifested by severe enterocolitis. This study evaluated the effects of a liquid, elemental, chemically defined diet (ED) supplemented with 2% glutamine (Glu-ED) compared with a polypeptide diet (PPD) on the morbidity and mortality after methotrexate (MTX) administration. Fischer 344 rats (n = 80) were fed either a regular rat chow diet (RD), a 2% glycine supplemented elemental diet (Gly-ED), a 2% glutamine-supplemented elemental diet (GLU-ED), and a glycine-supplemented polypeptide diet(Gly-PPD) for 7 days prior to administration of MTX (20 mg/kg, ip). After 72 hours, eight rats per group were killed; portal vein and vena cava blood, mesenteric lymph nodes (MLN), liver, small intestine, and cecum were sampled for bacterial culture. Remaining animals were followed to calculate survival. One hundred percent of the Gly-PPD and 25% of the Glu-ED animals survived compared with 0% of the Gly-ED animals. Our data showed that ED resulted in an increased quantity of intestinal Gram-negative bacteria and diminished intestinal mucosal height and mucosal DNA/protein content. The polypeptide diet prevented intestinal mucosal atrophy, avoided MTX-induced enterocolitis and significantly improved animal survival compared with an elemental diet with or without glutamine supplementation. 
Contribution of regional vascular responses to whole body autoregulation in conscious areflexic rats. We designed studies to evaluate the autoregulation response during volume expansion in three major circulation regions (intestine, kidney, and hind limb) during simultaneous determination of whole body autoregulation in conscious areflexic rats. Cardiac output was measured with chronically implanted electromagnetic flow probes on the ascending aorta. Regional blood flow velocity was measured with pulsed Doppler flow probes on the superior mesenteric (n = 7), left renal (n = 7), and right iliac (n = 7) arteries. Doppler flow probes were calibrated in situ in each rat to determine regional blood flow values. Neurohumoral reflex control of pressure was removed pharmacologically, and blood pressure and cardiac output were returned to resting control values with intravenous norepinephrine infusion, which was maintained at that constant level throughout the study. Hemodynamic changes were measured in response to blood volume expansion with infusion of 0.9 ml blood over 6 minutes. This small change in blood volume resulted in significant increases in vascular resistance of 15% in the whole body, 8% in the intestine, 18% in the kidney, and 15% in the hind limb. The pressure-flow slope, used as an index of autoregulation (slope = 0, perfect autoregulation; slope = 1, rigid vasculature), averaged 0.34 in the whole body, 0.52 in the intestine, 0.19 in the kidney, and 0.39 in the hind limb. When compared with the whole body, blood flow autoregulation was less in the intestine, greater in the kidney, and the same in the hind limb. 
MRI in cerebral toxocaral disease. Toxocara canis, the common roundworm in the dog, can cause "visceral larva migrans" syndrome in humans, which may include generalised illness, eosinophilia, and symptoms arising from larval invasion of different organs. Of these, the clinically most important are liver, lungs, eyes and CNS. Involvement of the different parts of the CNS in human toxocaral disease has been described, but not the CT or MRI appearances of the cerebral lesions. In one case with a single focal epileptic fit, CT was described as normal. In the Toxocara canis case described, the cerebral lesions on MRI, before and after therapy, are shown. 
Treatment of hypertensive urgencies with oral nifedipine, nicardipine, and captopril. Sixty-five patients with uncomplicated hypertensive urgencies were treated in the emergency and cardiology departments with 20 mg nifedipine, 20 mg nicardipine, or 25 mg captopril in a randomized study. The study population consisted of 65 patients ranging in age from forty-one to seventy-one. Blood pressure and heart rate were assessed for six hours after intake of the antihypertensive agents. Within sixty minutes nifedipine reduced blood pressure by an average of 74.7 mmHg for the systolic and 35.4 mmHg for the diastolic. Average heart rate increased significantly by 11.6 beats/min at within thirty minutes. Nicardipine and captopril produced equivalent falls in systolic (-81.6 and -79.4 mmHg) and diastolic (-37.3 and -33 mmHg) blood pressure respectively, but did not increase heart rate significantly. The antihypertensive effect of each drug was maintained until six hours after medication. In conclusion, nifedipine, nicardipine, and captopril show similar efficacy in the treatment of hypertensive urgencies. The authors believe that these drugs can be used as first-line therapy in the treatment of hypertensive urgencies safely and effectively. 
Emergency department stabilization of pediatric patients with bacterial meningitis. Current advances. The infant or child who presents to the Emergency Department with bacterial meningitis may have nonspecific vague symptoms with few signs of serious illness. However, the disease is often rapidly progressive and life-threatening, and may be associated with respiratory failure, circulatory failure, increased intracranial pressure, disseminated intravascular coagulation, or convulsions, any of which may lead to a fatal outcome. It is important for the triage technician in an Emergency Department to cautiously inspect each young patient who presents with illness, carefully considering whether the presenting syndrome of symptoms and signs might be consistent with early meningitis. If the young patient is triaged in a nonemergent category, then periodic assessments of the patients waiting to be seen may ensure that, when the infant or child with an obscure presentation develops evidence suggesting this diagnosis, the triage technician will promptly notify the appropriate definitive care providers who assume responsibility for immediate definitive evaluation and stabilization. Changes in delivery of lifesaving care to the life-threatened child are being impacted by current advances in the understanding of the biochemical basis of disease at the cellular and subcellular levels. Endotoxin release into the blood causes increased production of kinins, which results in vasodilatation and increased vascular permeability. Members of the leukotriene family may also enhance vascular permeability as well as produce augmented leukocyte aggregation to vascular endothelium, vasoconstriction, and bronchoconstriction. Endotoxin activates the complement cascade and induces platelets to form reversible aggregates that may be trapped in the pulmonary microcirculation; and endotoxemia-activated platelets release serotonin, which may be associated with pulmonary hypertension. Now that we have antibiotics that are effective against organisms whose degradation produces endotoxin, there is interest in lessening the host inflammatory response to endotoxin through use of dexamethasone as an anti-inflammatory agent. Clinical trials have revealed that patients who received dexamethasone became afebrile earlier and were less likely to acquire deafness after bacterial meningitis. Because administration of antibiotics is the current specific medical therapy for this life-threatening microbial invasion, it is reasonable to continue to strive to shorten the interval between recognition of disease and specific therapy. However, new studies suggest that consequences of the complex host inflammatory response (at the cellular and subcellular level) to microbial invasion and endotoxin release from bacterial degradation are increasingly important in determining survival or severity of morbidity. Therapeutic intervention with specific antibiotics and steroid anti-inflammatory agents for modulating host responses enhances outcome. 
A short plasma exchange protocol is effective in severe myasthenia gravis. Plasma exchange has been reported to be a successful therapeutic procedure for the treatment of severely compromised myasthenic patients, but the optimal regimen in terms of costs or clinical benefit has not so far been determined. We have investigated the efficacy of a short plasmapheresis protocol of two exchanges 1 day apart in a series of 70 patients with severe forms of myasthenia gravis. Patients were evaluated before and 7 days after the first exchange. A positive outcome was observed in 70% of the plasma exchange cycles performed. Disease severity did not seem to be a negative prognostic factor for the efficacy of this short protocol, which was well tolerated by patients. In only 1 case were major side-effects observed. In spite of its short duration, the exchange treatment plus concomitant immunosuppressive drug therapy was not followed by early clinical deterioration. 
Visceral leishmaniasis: a difficult diagnosis and unusual causative agent. In a young man who had a prolonged fever of unknown origin, hepatosplenomegaly, and progressive pancytopenia, stained smears, blood-agar cultures of bone marrow, and serologic testing for antileishmanial antibodies were negative. Biopsies from liver and bone marrow were uninformative. Visceral leishmaniasis was diagnosed only after splenectomy, when amastigotes were finally cultured from the spleen. The parasite was shown to be an unusual leishmanial parasite, possessing a mixture of intrinsic biochemical and serologic characteristics displayed independently by Leishmania tropica and Leishmania donovani sensu lato, the latter being the usual cause of visceral leishmaniasis. After splenectomy, parasites were also demonstrated in stained bone marrow aspirate smears. Recovery was uneventful after treatment with antimony for 28 days. Visceral leishmaniasis can be a cause of fever of unknown origin and should be considered in its differential diagnosis in endemic areas. 
Ultrasonography in the diagnosis of acute appendicitis. Ultrasonography with graded compression was performed in 525 patients with clinical signs of acute appendicitis. Of 207 patients with surgically proven appendicitis the inflamed appendix (diameter greater than or equal to 6 mm) had been visualized sonographically in 177 (86 per cent). The score for non-perforated appendicitis (91 per cent) was higher than for perforated appendicitis (55 per cent). Twenty-four patients in whom an inflamed appendix was seen on ultrasonography did not undergo surgery because of rapidly subsiding symptoms ('abortive appendicitis'). Four of these 24 developed recurrent appendicitis warranting surgery. Two underwent elective appendectomy and 18 have remained symptom-free. Of 155 patients with a subsequently confirmed alternative condition, ultrasonography made the correct diagnosis in 140: bacterial ileocaecitis (69), mesenteric lymphadenitis (eight), gynaecological conditions (34), urological conditions (eight), caecal diverticulitis (six), perforated peptic ulcer (six), Crohn's disease (two) and miscellaneous conditions (seven). Of 139 patients in whom no definite diagnosis was made ultrasonography showed no abnormalities in 138. In four patients a false positive sonographic diagnosis of appendicitis was made and in two patients with appendicitis an alternative condition was incorrectly diagnosed. During the last 3 years of the study the negative appendicectomy rate was 7 per cent and delay beyond 6 h after admission occurred in only 2 per cent of patients with surgically proven appendicitis. When used to complement the clinical diagnosis ultrasonography improves the diagnostic accuracy and patient management in those suspected of having acute appendicitis. 
Proportionate mortality trends: 1950 through 1986 Mortality trends in the United States from 1950 through 1986 were analyzed for the conditions that are or have recently been among the six leading causes of death. The age-adjusted mortality rate for all causes has decreased from 841.5 to 541.7 per 100,000 population. Cause-specific, age-adjusted mortality rates have declined from 1950 through 1986 for cerebrovascular disease, injuries, perinatal conditions, heart disease, and influenza and pneumonia. Time trends in the proportion of persons dying of each of these diseases, however, have varied; the proportion dying of cerebrovascular disease, injuries, and perinatal conditions has decreased, and the proportion of persons dying of heart disease and influenza and pneumonia has remained fairly stable from 1950 through 1986. During this same time, age-adjusted death rates have increased for chronic obstructive pulmonary disease and have remained fairly stable for malignant neoplasms, while the proportions of persons dying of chronic obstructive pulmonary disease and malignant neoplasms have increased dramatically. For people aged 35 to 64 years, malignant neoplasms have now overtaken heart disease as the leading cause of death. For those aged 65 years and older, heart disease remains the leading cause of death, accounting for almost 50% of all deaths in persons 85 years and older. 
Postsepsis bradycardia in children with leukemia. OBJECTIVE: We observed sinus bradycardia in a small number of children with hematologic malignancies who were recovering from sepsis. Our objective was to define this symptom complex and attempt to delineate its etiology. DESIGN: Retrospective chart review. SETTING: A pediatric ICU in a children's oncology hospital. PATIENTS: Children admitted to the ICU over a 24-month period who developed persistent bradycardia (heart rate less than 5% for age for greater than 1 hr) after an episode of sepsis. MEASUREMENTS AND MAIN RESULTS: Seven children developed postsepsis bradycardia. Six patients had a primary diagnosis of acute myelogenous leukemia and one patient had acute lymphocytic leukemia. All patients had positive blood cultures (Streptococcus mitis, n = 4; Escherichia coli, n = 2; and Klebsiella pneumoniae, n = 1). All seven children were clinically recovering from sepsis when the bradycardia developed. Neither hypotension nor other symptom was associated with the bradycardia. No therapy was given for the bradycardia. Echocardiograms and ECGs were normal in all patients, except for the presence of bradycardia. Bradycardia persisted for 24 to 72 hrs. After that time, heart rates slowly increased to the normal range for age. CONCLUSIONS: We speculate that this syndrome may result from alterations in beta-adrenergic receptor function or an unidentified humoral factor produced by the invading organism or as part of the host's response to sepsis. Prior drug therapy or the underlying illness may predispose to this condition, since all the patients had acute leukemia. As the bradycardia was clinically insignificant, invasive therapeutic or diagnostic strategies were not indicated. 
The use of an intraluminal shunt for bypass grafts of the cavernous internal carotid artery. Technical note. The authors describe an indwelling intraluminal shunt for use during graft bypass procedures of the cavernous internal carotid artery. The clinical use of this shunt in a patient with meningioma invading the right cavernous sinus is described. This shunt has also been found applicable during carotid endarterectomy, and should prove to be a useful addition to the neurosurgical armamentarium for skull-base surgery. 
Exaggerated and prolonged thyrotrophin releasing hormone (TRH) test responses in tertiary hypothyroidism. A 60 year old man with panhypopituitarism due to a large meningioma and prolonged and exaggerated thyroid stimulating hormone (TSH) responses is described. Initial investigations showed a subnormal urinary free cortisol concentration, a low serum cortisol taken at 0900 hours, and a low free T4 concentration. The TSH was towards the upper end of the normal range. Subsequently pituitary function tests showed subnormal production of luteinising hormone in response to luteinising hormone releasing hormone (LHRH) and a short synacthen test with a low 30 minute cortisol value. Long synacthen testing showed a normal response at four days, confirming that the abnormalities were due to a pituitary or hypothalamic cause. A computed tomogram showed a large meningioma compressing the hypothalamus, pituitary, and temporal lobe. TRH testing showed a prolonged and exaggerated response, consistent with tertiary hypothyroidism. 
High energy neutron treatment for pelvic cancers: study stopped because of increased mortality. OBJECTIVE--To compare high energy fast neutron treatment with conventional megavoltage x ray treatment in the management of locally advanced pelvic carcinomas (of the cervix, bladder, prostate, and rectum). DESIGN--Randomised study from February 1986; randomisation to neutron treatment or photon treatment was unstratified and in the ratio of 3 to 1 until January 1988, when randomisation was in the ratio 1 to 1 and stratified by site of tumour. SETTING--Mersey regional radiotherapy centre at Clatterbridge Hospital, Wirral. PATIENTS--151 patients with locally advanced, non-metastatic pelvic cancer (27 cervical, 69 of the bladder, seven prostatic, and 48 of the rectum). INTERVENTION--Randomisation to neutron treatment was stopped in February 1990. MAIN OUTCOME MEASURES--Patient survival and causes of death in relation to the development of metastatic disease and treatment related morbidity. RESULTS--In the first phase of the trial 42 patients were randomised to neutron treatment and 14 to photon treatment, and in the second phase 48 to neutron treatment and 47 to photon treatment. The relative risk of mortality for photons compared with neutrons was 0.66 (95% confidence interval 0.40 to 1.10) after adjustment for site of tumour and other important prognostic factors. Short term and long term complications were similar in both groups. CONCLUSIONS--The trial was stopped because of the increased mortality in patients with cancer of the cervix, bladder, or rectum treated with neutrons. 
Cardiovascular evaluation in blunt thoracic trauma using transesophageal echocardiography (TEE). Blunt chest trauma can result in significant cardiothoracic injury, which can include cardiac contusion, aortic injury, and myocardial valvular injury. Nineteen patients with no prior history of cardiac abnormalities who sustained severe blunt chest trauma and had widening of the mediastinum on chest radiographs were prospectively evaluated using transesophageal echocardiography (TEE). In each instance TEE was performed without difficulty, excellent images were obtained of the aorta and heart, and no complications were noted. Abnormalities were seen in 12 (63%) patients, with hypokinetic regional wall motion consistent with cardiac contusion demonstrated in five (26%) patients. Tricuspid regurgitation was found in three (16%) patients, and aortic and mitral regurgitation in one (5%) patient each. Aortic wall hematomas were seen in two patients, one of whom had an intimal tear on aortography, and a pericardial effusion was seen in one patient with an aortic intimal tear confirmed angiographically. Thus TEE can be performed safely in the acute setting of patients sustaining severe blunt chest trauma and yield useful information with respect to cardiovascular function and the aorta. 
Treatment of voiding complaints and incontinence in painful bladder syndrome. The treatment of voiding complaints and incontinence in painful bladder syndrome requires careful attention to detail. As the exact nature of these conditions is unknown, no single modality is effective, and multiple treatments may be required. A sympathetic and supportive physician is necessary in all these cases. 
Listeriosis in patients infected with human immunodeficiency virus. Although resistance to Listeria monocytogenes infection requires intact T cell-mediated immunity, only 20 patients with human immunodeficiency virus (HIV) infection and listeriosis (including one patient described herein) have been reported to date. Listeriosis developed before AIDS in five cases. Syndromes included meningitis in nine cases, bacteremia in nine, brain abscess in one, and endocarditis in one. Eighteen patients were treated with ampicillin, penicillin, or amoxicillin with or without aminoglycosides. Clinical and microbiologic responses were obtained in one patient with bacteremia treated with vancomycin and in one patient with meningitis treated with trimethoprim-sulfamethoxazole. Three of the nine patients with meningitis died, as did the patient with brain abscess. All nine patients with bacteremia and the patient with endocarditis survived. No case of relapse was documented. L. monocytogenes, although uncommon, should be considered in the differential diagnosis of febrile illness, meningitis, and brain abscess in patients with HIV infection. 
Management of hypertensive crises. The availability of potent antihypertensive drugs that will decrease markedly elevated blood pressure within minutes to hours has changed the concepts of definition and therapy of hypertensive emergencies and urgencies. Intravenous infusion of sodium nitroprusside can be used in the truly emergent situation and is effective, reliable, and safe. While oral therapy is more convenient, it is not as consistently effective as parenteral administration and can lead to excessive reductions in blood pressure that are more difficult to manage than when short-acting agents are given intravenously. 
Postmortem studies of the heart in three fatal cases of the eosinophilia-myalgia syndrome. OBJECTIVE: To examine the hearts of individuals who died from the eosinophilia-myalgia syndrome associated with ingestion of L-tryptophan, with particular attention paid to the coronary arteries, the neural structures, and the conduction system of the heart because of reported terminal disturbances of cardiac rhythm and conduction. STUDY MATERIAL: Three hearts fixed in neutral formalin and well preserved with all the relevant areas of conduction system intact. METHODS: Light microscopic examination of subserial sections of the sinus node, atrioventricular node and His bundle, coronary chemoreceptor and regional nerves, ganglia, and small coronary arteries. Routine stains used were Goldner trichrome and Verhoeff-van Gieson. RESULTS: Arterial abnormalities were numerous and primarily of two types: focal fibromuscular dysplasia causing moderate to severe narrowing, as well as endarteritis and panarteritis. Extensive examples of neuritis and ganglionitis were present throughout the heart, including the conduction system, where arterial abnormalities were also abundant. In the coronary chemoreceptor there were both old and new lesions comprising focal inflammation with degeneration as well as older areas of fibrotic destruction. Within the sinus node, areas of dense fibrosis replaced all nodal tissue. These abnormalities were similar in nature and extent in all three hearts. CONCLUSIONS: The pathologic lesions present in the coronary arteries, neural structures, and conduction system of the heart in patients who died from the eosinophilia-myalgia syndrome provide a suitable anatomic substrate for substantial cardiac electrical instability, including the occurrence of sudden death. In cases of unexplained cardiac electrical instability or sudden unexpected death an inquiry should be made about previous use of L-tryptophan. In patients with the eosinophilia-myalgia syndrome, the possibility of cardiac electrical instability should be considered as part of long-range clinical management. 
The use of an intraluminal shunt for bypass grafts of the cavernous internal carotid artery. Technical note. The authors describe an indwelling intraluminal shunt for use during graft bypass procedures of the cavernous internal carotid artery. The clinical use of this shunt in a patient with meningioma invading the right cavernous sinus is described. This shunt has also been found applicable during carotid endarterectomy, and should prove to be a useful addition to the neurosurgical armamentarium for skull-base surgery. 
Contemporary management of neurofibromatosis. The neurofibromatoses are two distinct entities with different genetic origins. The phenotypic expressions and required treatments are different. The devastating nature of neurofibromatosis-2 may be more effectively controlled through the application of advanced imaging techniques and contemporary neurotologic procedures. The most common manifestation of neurofibromatosis-2 is that of bilateral acoustic neuromas. The eventual total bilateral sensorineural deafness associated with this condition can be obviated in selected cases if the diagnosis is established early. Follow-up data are reported for three patients in whom hearing was preserved in at least one ear. When removal with hearing preservation is not possible, subtotal tumor removal with decompression of the internal auditory canals may delay progression of hearing loss. A new approach to tumors of the pterygomaxillary fossa that have extended to the middle cranial fossa has been successfully applied and is described. 
Sex cord tumor with annular tubules associated with endometriosis of the fallopian tube. Sex cord tumor with annular tubules (SCTAT) is a distinctive ovarian sex cord-stromal tumor. The authors describe a case of SCTAT arising outside the ovaries, in the fallopian tube. The authors are aware of only one other case of extra-ovarian SCTAT, in an umbilical hernia sac in an adult woman. The case reported was an incidental finding in a hysterectomy specimen, obtained because of carcinoma in situ of the uterine cervix in a 32-year-old woman. The patient is alive and disease-free two years after surgery. The 1-cm tumor in the right fallopian tube was composed of typical ring-shaped tubules encircling hyalinized basement membrane-like material. In addition, glands and stroma of endometriosis were intimately admixed with the nests of tumor. The implications of these findings for the origin of SCTAT and ovarian sex cord structures are discussed. 
Clinical features and circulating gonadotropin, insulin, and androgen interactions in women with polycystic ovarian disease. OBJECTIVE: To investigate the interactions of hyperinsulinemia and inappropriate gonadotropin secretion in women with polycystic ovarian disease (PCOD). DESIGN: Comparative study of endocrinologic parameters in subjects with PCOD. SETTING: Open patient clinic of reproductive endocrinology at University Central Hospital of Turku, Finland. PATIENTS: Fourteen nonobese and 10 obese patients with PCOD. Seven healthy women for reference data collection. Normal thyroid function, serum prolactin concentration, normal diurnal cortisol variation, euglycemia in all subjects. MAIN OUTCOME MEASURES: Serum concentrations of insulin, testosterone, androstenedione, dehydroepiandrosterone sulfate, sex hormone-binding globulin, immunoreactive luteinizing hormone (LH), bioactive LH, and follicle-stimulating hormone (FSH). RESULTS: The concentration of insulin was higher and that of bioactive LH was lower in obese than in nonobese PCOD women in whom the levels were also above the upper reference value. There was a negative correlation between insulin and bioactive LH levels (r = -0.57). Bioactive LH correlated inversely with the body mass index (BMI) (r = -0.50). After eliminating the effect of the BMI, the correlation between bioactive LH and insulin was no longer significant (r = -0.37). The bioactive LH and immunoreactive LH/FSH ratio correlated significantly (r = 0.68). CONCLUSIONS: These data demonstrate that hyperandrogenic women can be divided into two subgroups: those with insulin resistance, normal or minimally elevated LH, and markedly elevated insulin levels; and those with elevated LH levels, no insulin resistance, and normal insulin concentrations. Obesity is associated with the former, and high bioactive LH levels with the latter subgroup. 
Acute respiratory infections. During the past decade, recognition of the significance of pneumonia for childhood mortality has greatly increased. Etiologic studies have clarified the role of Streptococcus pneumoniae and H. influenzae as the pathogens most responsible for childhood pneumonia in developing countries. Case management intervention strategies using community health workers to identify cases of pneumonia by counting respiratory rate and observing chest indrawing have been shown to reduce ARI-related mortality. Although research is underway to develop more effective vaccines against Streptococcus pneumoniae and non-type b H. influenzae, effective case management will remain the most realistic method of reducing mortality in the next decade. Important gaps remain in our understanding of the pathogenesis, etiology, and epidemiology of acute respiratory infections. Our understanding is complicated by the multiplicity of viral and bacterial agents and their interrelationships, by an abundance of interacting host risk factors, and by diverse social, cultural, and environmental factors. However, sufficient knowledge is available to support the implementation of the WHO case management intervention strategies, which will save the lives of the many children now dying because of pneumonia. 
Sclerotherapy of bleeding esophageal varices using a thrombogenic cocktail. The short- and long-term efficacy of a thrombogenic sclerosant (1% tetradecyl sulfate, thrombin, and cefazolin) was studied in 101 patients. The majority of patients had alcoholic cirrhosis with Child's C classification (84/101). Bleeding was controlled in 94 per cent of patients with the first sclerotherapy. In-hospital and early (within 6 weeks) mortality were 14 per cent and 19 per cent, respectively. There was a strong correlation with hospital mortality and the severity of hepatic disease. Long-term follow-up in 70 patients (mean of 16 months) showed that survival correlated with compliance to follow-up sclerotherapy and abstention from further alcohol intake. Mortality in patients compliant with follow-up was 5 per cent (1/19), as compared with 24 per cent (12/51) in patients who were not compliant with follow-up sclerotherapy. The mortality in alcoholic cirrhotic patients who abstained from further alcoholic intake was 6 per cent (1/17), as compared with 23 per cent (10/44) in those who continued to abuse alcohol. No systemic thrombotic or allergic events related to the use of bovine thrombin were noted during a total of 349 sclerotherapy sessions. 
Compartment syndrome complicating prolonged use of the lithotomy position. Two patients with three postoperative calf compartment syndromes, which followed prolonged lithotomy positioning, will be presented. Potential physiologic mechanisms are described, and a review of current cases in literature are summated. 
Levels of morphine and metabolites in CSF during respiratory depression after intraventricular morphine injection. We report a case of respiratory depression after intracerebroventricular morphine administration of a dose inadvertently 10 times greater than the typical daily dose. At the time of the respiratory dysfunction, the concentrations of morphine and its metabolites in cerebrospinal fluid (CSF) and plasma samples were determined. On comparison of these results with previous clinical studies in which there was no respiratory depression, no relationship was found between the occurrence of respiratory depression and the concentration of morphine or its metabolites in the CSF. The occurrence and characteristics of respiratory depression may be related to the concentrations of morphine and its metabolites in bulbar tissue. 
Vaginal adenosis and clear cell carcinoma after 5-fluorouracil treatment for condylomas. Vaginal adenosis and clear cell adenocarcinoma of the vagina occurred in a 44-year-old woman after treatment for condylomata acuminata. She had no known exposure to diethylstilbestrol (DES) in utero. Biopsy-proven vaginal adenosis appeared 8 months after intravaginal 5-fluorouracil application for recurrent urogenital condylomata acuminata. Forty months later, biopsies showed residual adenosis with foci of clear cell adenocarcinoma. Although clear cell adenocarcinoma is associated with vaginal adenosis and cervical ectropion in DES-exposed women, its occurrence in adenosis after 5-fluorouracil therapy has not been reported to the authors' knowledge. In this report, this rare but serious complication of treatment of condylomata acuminata is highlighted, and the literature regarding the development of non-DES-associated vaginal adenosis is discussed. 
Study of brain electrolytes and organic osmolytes during correction of chronic hyponatremia. Implications for the pathogenesis of central pontine myelinolysis. Osmotic injury induced by rapid correction of severe chronic hyponatremia has been implicated in the development of central pontine myelinolysis. Organic osmolytes known previously as "idiogenic osmoles" accumulate intracellularly to protect cells from osmotic injury. We investigated the changes of these organic osmolytes as well as electrolytes in the brain during the induction and correction of chronic hyponatremia. Using 1H-nuclear magnetic resonance spectroscopy and HPLC, we found that in rats with chronic hyponatremia (3 d, serum sodium = 109 +/- 3 meq/liter), brain concentrations of myoinositol (41%), glycerophosphorylcholine (45%), phosphocreatine/creatine (60%), glutamate (53%), glutamine (45%), and taurine (37%) were all significantly decreased compared with control values (percentage control value shown, all P less than 0.01). The contribution of measured organic osmolytes and electrolytes to the total brain osmolality change was 23 and 72%, respectively. With rapid correction by 5% NaCl infusion, significant brain dehydration and elevation of brain Na and Cl levels above the normal range occurred at 24 h. These changes were not seen with slow correction by water deprivation. Reaccumulation of most organic osmolytes except glycerophosphorylcholine is delayed during the correction of hyponatremia and is independent of the correction rate of serum sodium. It is concluded that: most of the change of brain osmolality in chronic hyponatremia can be accounted by the changes in organic osmolytes and brain electrolytes; and rapid correction of hyponatremia is associated with an overshoot of brain sodium and chloride levels along with a low organic osmolyte level. The high cerebral ion concentrations in the absence of adequate concentrations of organic osmolytes may be relevant to the development of central pontine myelinolysis. 
Simulated aggressive skull base erosion in response to benign sinonasal disease. Benign sinonasal masses and slow-growing neoplasms tend to remodel the nasal vault and facial bones, and this is particularly true of nasal polyps and inverted papillomas. However, when such benign masses press against the floor of the anterior cranial fossa and the walls of the sphenoid sinuses, simulated aggressive bone destruction rather than bone remodeling usually occurs. This type of bone destruction implies to the radiologist that a carcinoma may also be present, and this information could dissuade a surgeon from operating with an attempt at cure. In fact, about 90% of the time with inverted papillomas and in virtually all cases of nasal polyposis, no carcinoma is present. The computed tomographic (CT) scans and magnetic resonance images of 14 patients are used to demonstrate these changes. In addition, the CT scans of three patients with malignancies are shown to illustrate the similarity in the bony skull base changes. 
Improved treatment results in boys with overt testicular relapse during or shortly after initial therapy for acute lymphoblastic leukemia. A Pediatric Oncology group study. Boys with acute lymphoblastic leukemia (ALL) who have overt testicular relapse (OTR) during initial continuation chemotherapy or within 6 months thereafter have poor outcomes, with long-term survival similar to patients with marrow relapse during treatment. In April 1983, the Pediatric Oncology Group (POG) adopted for these patients an intensive treatment protocol (POG 8303) consisting of a four-drug systemic reinduction (prednisone, vincristine, daunorubicin, and asparaginase), a brief intensive consolidation phase with teniposide and cytarabine, and a 2-year program of continuation chemotherapy with weekly rotating drug pairs (vincristine/cyclophosphamide and teniposide/cytarabine) with or without (by randomization) four-drug reinforcement pulses every 16 weeks. Bilateral testicular radiation (2600 cGy) was administered during reinduction, and intrathecal chemoprophylaxis was given every 4 to 6 weeks. Among 38 eligible study patients with OTR, 5 had prior or concominant extramedullary relapse in other sites. The median duration of complete remission before OTR was 27 months (range, 10 to 42 months). All 38 patients achieved clinical remission after reinduction. Three patients withdrew while in remission, 22 had another relapse (12 marrow, 5 central nervous system (CNS), 2 testicular, 1 retroperitoneal, 1 prostate, and 1 eye), and 13 (34%) remain in complete remission from 32+ to 74+ months after OTR (median, 53+ months). Eighteen patients had their therapy electively discontinued, and five relapses occurred thereafter. These results are superior to those observed in patients with first marrow relapse treated with the same protocol. Approximately one third of patients with OTR treated with POG protocol 8303 exhibit prolonged second remissions with the potential for cure. 
Confirmation of endosonographic detection of external anal sphincter defects by simultaneous electromyographic mapping. Anal endosonography was performed in 13 consecutive patients with post-traumatic faecal incontinence. Thirteen acoustic defects in the external anal sphincter (two hyperechoic, four of mixed echogenicity and seven hypoechoic) were analysed electromyographically by locating under ultrasound guidance the tip of a concentric needle within the defect. The electromyographic activity in this zone was compared with ultrasonically normal muscle. Eleven of 13 sonographic defects showed no electrical activity on electromyography, there was one technical electromyography failure, and one defect was too deep to be reached by the electromyography needle. The electromyographic response was normal in each case within ultrasonically normal muscle. Anal endosonography is recommended as the initial investigation to locate defects, which may be confirmed electromyographically thereby limiting the number of painful needle insertions required for complete mapping of the external anal sphincter. 
Spirochetes in atrophic skin lesions accompanied by minimal host response in a child with Lyme disease. Acrodermatitis chronica atrophicans, which has rarely been observed in the United States, is a late skin manifestation of Lyme borreliosis. A 12-year-old girl who spent summers on Cape Cod presented with a 2-year history of hyperpigmentation and atrophy of the skin on the hands, wrists, and ankles. The skin biopsy specimen of an affected area showed mild dermal fibrosis, a few inflammatory cells, and spirochetes morphologically compatible with Borrelia burgdorferi. An IgG antibody response to B. burgdorferi could be elicited by immunoblotting, but not by enzyme-linked immunosorbent assay. We conclude that this patient had chronic Lyme borreliosis manifested only by indolent infection of the skin. 
Deletional switch recombination occurs in interleukin-4-induced isotype switching to IgE expression by human B cells. There is controversy as to whether deletional rearrangement occurs between the IgM and IgE switch regions (S mu and S epsilon, respectively) during switching to the IgE isotype. We have addressed the issue by stimulating normal human B cells, sorted for lack of expression of surface IgE, to produce IgE by infection with Epstein-Barr virus (EBV) in the presence of interleukin 4 (IL-4). Genomic DNA was amplified for S mu/S epsilon switch junction fragments by utilizing the nested-primer polymerase chain reaction. Switch junction fragments were amplified from B cells infected with EBV in the presence of IL-4 but not from B cells infected with EBV alone. The DNA sequence of these "switch fragments" revealed direct joining of S mu to S epsilon in each case. The recombination sites within S mu were clustered within 900 base pairs at the 5' end of the switch region, suggesting that there are "hot spots" for recombination within S mu. The S epsilon recombination sites were scattered throughout the S epsilon region. These findings indicate that IL-4-induced isotype switching to IgE production in human B cells is accompanied by DNA rearrangements with joining of S mu to S epsilon. 
Intercostal-to-pulmonary arterial anastomosis, complicated by high-output heart failure: case report. A patient who had high-output heart failure resulting from anastomosis of the intercostal and bronchial arteries to the right pulmonary artery is reported. The patient was a fifty-one year-old man who was admitted to our hospital with left heart failure. A radionuclide angiocardiogram revealed blood flow from the aorta to the right pulmonary artery. A descending aortogram revealed abnormally dilated right intercostal and bronchial arteries, which formed the anastomosis. The right pulmonary artery was visualized via that anastomosis. Tuberculous pleurisy in the patient's history was considered to be the cause of the anastomosis. The therapeutic procedure used was embolization via a catheter for the anastomosis, but most anastomoses could not be embolized. The present report is considered the first on anastomosis of the intercostal artery to the pulmonary artery to the extent that high-output heart failure occurs. 
Tissue plasminogen activator release and plasminogen activator inhibitor levels in coronary artery disease. Unstable angina and Q wave myocardial infarction are associated with intraluminal coronary thrombosis, a process to which impaired fibrinolysis may contribute. The authors examined the extrinsic fibrinolytic system, including tissue plasminogen activator antigen, plasminogen activator inhibitor activity and antigen, and euglobulin clot lysis time before and after venous occlusion in 56 patients undergoing coronary angiography for chest pain syndromes and in 16 healthy controls. Fibrinolysis variables were similar (with greater than 95% confidence) in the patients with thrombus-associated coronary syndromes as compared with those with chest pain syndromes not due to coronary thrombosis. These fibrinolytic variables were also similar to those in patients without coronary artery disease and in healthy controls. Their data suggest that defective fibrinolysis is not involved, at least systemically, in the pathogenesis of thrombus-associated coronary artery syndromes. 
Influence of allopurinol on cardiac complications in open heart operations. During cardiac operations, the heart is subjected to total ischemia and reperfusion, causing serious operative and postoperative complications such as arrhythmias, heart failure, and infarctions that may be partly due to free radical generation. Thus, allopurinol was tested to see if it could reduce cardiac complications during open heart operations. Ninety patients undergoing elective coronary artery bypass grafting were studied prospectively. Fortyfive patients were treated with allopurinol and 45 patients acted as controls. Treatment requiring arrhythmias in the allopurinol group was 6.6% compared with 33.3% in the control group (p less than 0.01). The percentage of patients requiring inotropes was significantly lower in the allopurinol group than in the control group (4.4% versus 26.6%; p less than 0.01). Perioperative myocardial infarction did not occur in the allopurinol group but was seen in 8 patients (17.7%) in the control group. Intraaortic balloon pumping was used in 5 control patients (11.1%) but not in the allopurinol group. This study shows that allopurinol decreases significantly the incidence of cardiac complications in open heart operations. 
Cerebral hemodynamics in ischemic cerebrovascular disease. During the past decade, technological advances have made it possible to measure regional cerebral hemodynamics in individual patients. Studies performed with these techniques have demonstrated that the degree of carotid stenosis correlates poorly with the hemodynamic status of the ipsilateral cerebral circulation. The primary determinant of cerebral perfusion pressure and blood flow under these circumstances is the adequacy of collateral circulatory pathways. Since collateral circulation varies from patient to patient, there is no critical degree of carotid stenosis that consistently produces hemodynamic compromise of the cerebral circulation. It is, thus, time to abandon the concept of the hemodynamically significant carotid stenosis as it relates to the pathogenesis and treatment of cerebrovascular disease. Measurements of regional cerebral hemodynamics have provided new insight into the pathogenesis of transient ischemic attacks and generated some preliminary data on the prognostic and therapeutic importance of chronic reductions in regional cerebral perfusion pressure. Further investigations into the importance of hemodynamic factors in ischemic stroke can now be based on accurate assessment of cerebral (not carotid or vertebrobasilar) hemodynamics in the context of other coexisting epidemiological, clinical, hematological, and angiographic risk factors. 
The impact of breast cancer on sexuality, body image, and intimate relationships. For women, breast cancer remains a common and dreaded experience. It is normal for a diagnosis of breast cancer to evoke grief, anger, and intense fear. Most women, however, face this crisis and master it without developing major psychiatric disorders or severe sexual dysfunction. The options of breast conservation and reconstruction give women a new sense of control over their treatment and are quite successful in helping women feel comfortable with their bodies again. The effectiveness of breast conservation and reconstruction in preventing or ameliorating sexual problems after breast cancer diagnosis is less clear, however. Any impact these options have on sexuality is subtle and may relate more to a woman's feelings of being desirable than to how often she has sex, her lovemaking practices, or how much she enjoys sex. We need more information on how chemotherapy and hormonal therapy affect women's sex lives. As clinicians, we should pay more attention to our patients' complaints of vaginal pain, dryness, and overall loss of sexual desire during systemic treatment. Practical advice on lovemaking techniques and a clinician's open attitude towards discussing sexual issues can prevent a great deal of anxiety and sadness as women with breast cancer search for ways to keep their sex lives satisfying. 
Natural anticoagulants in systemic lupus erythematosus. Deficiency of protein S bound to C4bp associates with recent history of venous thromboses, antiphospholipid antibodies, and the antiphospholipid syndrome. The association of thrombosis with antiphospholipid antibodies (aPL) in patients with systemic lupus erythematosus (SLE) could be due to their interference with natural phospholipid dependent anticoagulant mechanisms. We studied antigenic protein C (APC), functional protein C (FPC), free protein S (FPS), protein S bound to C4 binding protein (C4bp-S), antithrombin III (ATIII), as well as IgG and IgM anticardiolipin antibodies (aCL) in 38 patients with SLE with a history of thromboses and 70 patients with SLE without such history. We found a high frequency of deficiencies of natural anticoagulants in both groups of patients with SLE but, because of patient selection, we could not determine the actual prevalence of these defects. Patients having had a venous thrombosis in the previous year had low C4bp-S more frequently than patients with older or no thromboses. When we divided our patients with SLE into those who had a definite, probable, questionable or no antiphospholipid syndrome (aPS) we found the frequency of C4bp-S deficiency to be significantly higher in those with definite aPS than in those without aPS. Intermediate proportions were found in patients with probable and questionable aPS. The levels of C4bp-S decreased as the levels of aCL, particularly IgG, increased. Stepwise discriminant analysis of natural anticoagulants selected deficiencies of C4bp-S and FPC with increased ATIII as a set of variables with highest predictive power for classification of patients with and without aPS. Thus, deficiencies of natural anticoagulants may occur frequently in patients with SLE. 
Parathyroid adenoma in a cancer center patient population. The association of parathyroid adenoma and antecedent events or relationships was examined retrospectively in 103 patients with parathyroid adenoma drawn from a cancer institute patient population. Patients were divided into two study groups by the referral pattern-intramural or community. The major contrast between the two groups was that the intramural patients had cancer diagnoses. The factors of advanced age, female gender, and prior regional irradiation appeared to be associated with the development of parathyroid adenoma. An interrelationship of incidental cancer and parathyroid adenoma, however, was not supported. Breast and differential thyroid cancers were most frequently associated with parathyroid adenoma, but age, gender, and irradiation were bias influences. 
Correlations between fibrinolytic function and acute myocardial infarction. The diurnal variation of tissue plasminogen activator and plasminogen activator inhibitor--2 important factors in regulation of fibrinolysis--is well established, but its clinical implications are not yet fully understood. Fibrinolytic function was measured in a group of 133 patients less than 45 years of age, 3 months after they presented with myocardial infarction, and they were compared with an equal group of carefully matched control subjects. A sub-sample of 71 patients and 50 control subjects was examined 3 years later. Tissue plasminogen activator inhibitor plasma levels were higher in patients versus control subjects at 3 months and at 3 years after myocardial infarction, with a high degree of correlation between the 2 determinations (r = 0.87). Of all hemostatic parameters studied, only low tissue plasminogen activator activity and increased tissue plasminogen activator inhibitor levels were significantly different between patients with and without recurrent infarction during the 3-year period. In those patients with a second infarction greater than 3 years later, however, tissue plasminogen activator inhibitor concentration was not significantly related to reinfarction. 
Intractable heart failure despite angiotensin-converting enzyme inhibitors, digoxin, and diuretics: long-term effectiveness of add-on therapy with pimobendan. In 25 patients whose chronic congestive heart failure (CHF) had recently worsened to New York Heart Association class IV, pimobendan (5 to 20 mg/day) was added to maximum conventional therapy consisting of digoxin, diuretics, angiotensin-converting enzyme inhibitors, coumadin derivatives to prevent thromboembolic complications, and amiodarone to suppress serious ventricular rhythm disturbances. CHF was fatal in less than 1 month in five patients (two had shown some initial improvement). The other 20 had sustained improvement by at least one functional class, interrupted by episodes of CHF that usually responded to intravenous therapy. Median survival was 12 months (range 10 days to greater than 3 years); five patients died suddenly, 12 died of intractable CHF, and two died of other causes. Six patients were alive 3 years after the onset of treatment with pimobendan. Add-on therapy with pimobendan produced a sustained improvement in many patients with severe CHF that was no longer responding to a combination of digoxin, diuretics, and angiotensin-converting enzyme inhibitors. 
A successful murine model for contact sensitization to a sesquiterpene-alpha-methylene-gamma-butyrolactone: sensitization to alantolactone in four strains of mice. Induction of allergic contact hypersensitivity to a sesquiterpene lactone, alantolactone, was studied in four strains of mice: C3H/He, DBA/2, Balb/b, and Balb/c. The last three were successfully sensitized. A significant dose/response was demonstrated in these species, as well as an experimental "overload effect" in Balb/c and Balb/b strains. Histologic studies confirmed the allergic nature of the reaction. From the overall results, alantolactone can be considered a moderate sensitizer in mouse as well as in guinea pig. This study shows that the murine model can be used for experimental contact sensitization with moderate allergens, without the use of Freund's adjuvant for induction. 
Lumbar regional anaesthesia and prophylactic anticoagulant therapy. Is the combination safe? A survey has been carried out in all Danish anaesthetic departments (n = 80) regarding the attitude towards the use of epidural/spinal lumbar analgesia in patients who were receiving prophylactic anticoagulant therapy for the prevention of thromboembolism. About 60% of the departments used the techniques in patients receiving low-dose heparin and no side effects had been experienced. Spinal and epidural anaesthesia were in general regarded as being contraindicated in patients fully anticoagulated with vitamin K antagonists. In the world literature, the attitude towards the combination is conflicting. No randomised trial has been performed and complications are almost entirely confined to patients fully anticoagulated with vitamin K antagonists. Only one case of an epidural haematoma has been recorded when subcutaneous low-dose heparin was used as thromboprophylaxis. 
Eyelid necrosis and periorbital necrotizing fasciitis. Report of a case and review of the literature. Necrotizing fasciitis is an uncommon and severe soft tissue infection characterized by cutaneous gangrene, suppurative fasciitis, and vascular thrombosis. The disease is usually preceded by trauma in patients that have systemic problems, most commonly diabetes and alcoholism. Streptococcus pyogenes and Staphylococcus aureus are the most frequent bacterial etiologies; however, combinations of numerous facultative and anaerobic organisms have also been isolated. Involvement of the face and periocular region is rare. A case is presented here, as well as a review of the clinical features of 15 other patients previously described, in whom eyelid necrosis due to periorbital necrotizing fasciitis developed. Early surgical debridement and drainage of necrotic tissues and appropriate parenteral antibiotics are the mainstay of therapy. The mortality rate in patients with periorbital spread was 12.5%, with the prognosis known to be adversely affected by delay in diagnosis and treatment and/or extension of infection from the face to the neck. Reconstruction of the eyelids with skin grafts was necessary in most cases to avoid such complications as cicatricial lid retraction, lid malpositions, and lagophthalmos. 
Relative kindling effect of detoxification and non-detoxification admissions in alcoholics. We reviewed the histories of 340 men and 60 women who were admitted for alcohol detoxification to determine if hospitalizations unrelated to detoxification increased the prevalence of seizures observed in these patients. Previous investigations on this cohort suggested that recurrent detoxification admissions increased the probability of seizure histories. Detoxification and non-detoxification hospitalizations were calculated from patient reports and chart reviews on patients admitted for alcohol detoxification. Discriminant analysis of each type of hospitalization and total hospitalizations for each sex revealed an increased risk of seizure activity correlating with non-detoxification hospitalizations, but the correlation was weaker than that observed for detoxification admissions and for total admissions. This correlation between hospitalizations and seizure prevalence supports the hypothesis that recurrent alcohol withdrawal may have a kindling effect. 
Effects of protein size on the rate of import of the precursors of aldehyde dehydrogenase and ornithine transcarbamylase into rat liver mitochondria. It is known that a signal peptide is required for the import of a protein into mitochondrial matrix. It is also known that a signal peptide can be attached to any protein and allow it to be imported. We recently reported that the rate of import of rat liver mitochondrial aldehyde dehydrogenase precursor was slower than that of ornithine transcarbamylase precursor (Wang TTY, Farres J, and Weiner H. Arch Biochem Biophys 272, 440-449, 1989). It was not known if the difference in the rate of import was related to the fact that the mature portion of aldehyde dehydrogenase is larger (500 amino acids compared with 322 amino acids) or because the signal peptides were different. We further showed that treatment of the mitochondria with alcohols caused an inhibition of the import of the precursor of aldehyde dehydrogenase but not that of ornithine transcarbamylase. In the present study we constructed chimeric proteins that contained the signal peptide from one precursor protein and the mature portion from the other. We found that the rate of import was related to the overall size of the precursor protein. Consistent with this observation was finding that a truncated aldehyde dehydrogenase precursor, which contained 317 amino acids, was imported more rapidly than was the authentic precursor. Consistent with this finding was the fact that butanol caused the inhibition of only the large precursor proteins. Thus, it appears that size of the protein being imported is a major determinant of the rate at which a precursor protein is imported into mitochondria. 
Orthotopic cardiac transplantation in two patients with previous malignancy. This report presents 2 patients with previous malignancy in whom congestive cardiomyopathy developed secondary to doxorubicin toxicity. Both patients underwent orthotopic cardiac transplantation 3 and 5 years ago and are now in functional class I with no evidence of malignant recurrence. 
Weight-loss experience of black and white participants in NHLBI-sponsored clinical trials. We examined race-specific weight-loss results from two randomized, multicenter trials; the Hypertension Prevention Trial (HPT) and the Trials of Hypertension Prevention (TOHP). Mean weight change from baseline averaged 2.2 kg less in black women than in white women during 18 mo of follow-up in TOHP and 2.7 kg less during 36 mo of follow-up in HPT. Mean weight loss averaged 2.0 kg less in black than in white men in TOHP and 1.4 kg less in HPT. Because of greater weight gain in black control subjects, a comparison of net weight loss (change in intervention minus change in control participants, within-race) showed a less marked difference than did black-white differences in weight loss within the actively treated group. Thus, relative to weight that would have been gained without the intervention, the experience of blacks and whites was more similar. Racial differences in weight loss may result from a combination of behavioral, sociocultural, biological, and programmatic factors. 
Angioscopically directed valvulotomy: a new valvulotome and technique. Despite a large experience with "blind" retrograde valvulotomy in in situ vein bypass grafting, the incidence of residual competent valves remains high, and valvulotome-induced injury is common. In this study we describe a new valvulotome and technique of angioscopically directed valvulotomy and review the video tape recordings of 85 completion angioscopies of in situ femorodistal bypasses. Fifty-three vein grafts were prepared with the blind retrograde valvulotomy technique and 32 vein grafts with the new valvulotome and angioscopy. The use of the new valvulotome and technique is compared with that of the standard blind retrograde valvulotomy technique, and the normal endoluminal anatomy and incidence of primary disease in saphenous vein grafts was noted. The incidence of valvulotome-induced injury was 5/32 (15.6%) and 45/53 (85%) in vein grafts prepared with angioscopically directed valvulotomy and blind retrograde valvulotomy, respectively. Residual competent valves were found in 10/53 (18.9%) in blind retrograde valvulotomy and 0/25 of angioscopically directed valvulotomy vein grafts (p = 0.0114). In 22/53 vein grafts unsuspected primary disease was detected. Angioscopically directed valvulotomy with the new valvulotome and technique is feasible, reliable, and safe. It avoids residual competent valves, minimizes valvulotome-induced injury, and allows the detection and correction of unappreciated primary vein graft abnormalities. The new valvulotome and technique is a first step in the complete endoluminal preparation of the in situ vein graft. 
Predictors of death from aortic aneurysm among middle-aged men: the Whitehall study. Among 18,403 male civil servants examined at age 40-64 years there were 99 deaths attributed to aortic aneurysm during 18 years of follow-up. Each case was matched by age to ten controls who survived longer than the case. The risk of all types of fatal aneurysm was substantially increased for current smokers of manufactured cigarettes (rate ratio compared with lifelong non-smokers = 6.5; 95 per cent confidence interval 2.3-18.7), pipe or cigars (6.7; 1.7-26.5) and hand-rolled cigarettes (25.0; 7.5-83.3). Diastolic blood pressure was strongly associated with dissecting aneurysm (rate ratio per 10 mmHg increase = 2.4; 95 per cent confidence interval 1.7-3.2) and abdominal aneurysm (1.5; 1.2-1.9) but not other aneurysms (1.0; 0.7-1.5). The independent effects of height, adiposity, plasma cholesterol, glucose intolerance, reported angina and intermittent claudication were not significant. Hypertension and smoking, particularly of hand-rolled cigarettes, are confirmed as major and potentially remediable risk factors for fatal aortic aneurysm. 
Endothelial cell seeding. Endothelial cell seeding is a technique that has developed over the past 15 years in response to the need for a high performance synthetic vascular graft. This review details our present knowledge of seeding and examines the various problems that have hampered its introduction into clinical practice. 
Smoking and hypertension: risk factors for carotid stenosis. The prevalence of smoking, hypertension and diabetes mellitus was assessed in 221 patients suffering from internal carotid stenosis and compared with the prevalences in two sex- and age-matched control groups composed of subjects having normal Doppler findings and from non-neurological outpatients. Of the subjects with carotid stenosis 27.6% were hypertensive smokers in comparison with 9.5% and 17.2% in the two control groups. The difference of the stenosis cohort from the two control groups was significant (P less than 0.01 and P = 0.016 respectively). There was no statistically significant differences between the occurrence of diabetes and hypertension in non-smokers and patients who smoked. In 394 investigated patients suffering from carotid stenosis or occlusion an obstruction index, based on the Doppler shift frequency, was calculated. This index was lowest in the normotentive non-smokers. It was only insignificantly higher in the hypertensive non-smokers but significantly so in the normotensive smokers. The index was highest in the hypertensive non-smokers. It was concluded that cigarette smoking, especially if associated with hypertension, is a determinant risk factor for carotid stenosis and occlusion. 
Frequency of abnormal sphincter of Oddi manometry compared with the clinical suspicion of sphincter of Oddi dysfunction. Patients with pancreaticobiliary pain or idiopathic pancreatitis have been classified as having definitive (type I), presumptive (type II), or possible (type III) sphincter of Oddi dysfunction (SOD) based on clinical, laboratory, and ERCP data. This study was undertaken to determine the frequency of abnormal sphincter of Oddi manometry (SOM) when patients are classified by this system. Two hundred and thirteen patients with pancreaticobiliary pain were evaluated clinically; SOM, ERCP, and ductal contrast drainage time tests were performed. For biliary types I, II, and III, the frequency of abnormal SOM was 85.7%, 55.1%, and 28.1%, respectively. Similarly, for pancreatic types I, II, and III, an elevated basal sphincter pressure occurred in 92.3%, 58.2%, and 35.1%, respectively. When patients with an abnormal basal sphincter pressure were characterized by the magnitude of the elevation, the manometric profiles were similar for types I, II, and III. These data suggest that elevated sphincter pressure occurs more frequently in type III patients than previously reported, and supports consideration of SOM when evaluating and treating type II and type III patients. 
Gastroesophageal reflux, as measured by 24-hour pH monitoring, in 509 healthy infants screened for risk of sudden infant death syndrome. Continuous long-term esophageal pH monitoring has become the preferred test to quantify acid gastroesophageal reflux. Because reflux to a limited extent is physiologic, the determination of optimal thresholds to separate normal from abnormal reflux is mandatory. Esophageal pH was measured during 24 hours in 509 healthy thriving infants, aged 3 days to 1 year, using a glass microelectrode with an external reference electrode connected to a portable recorder. Percentiles of the four parameters studied (reflux index or percent of the investigation time with a pH less than 4, number of episodes with a pH less than 4 during 24 hours, number of episodes lasting greater than 5 minutes, the duration of the longest episode (in minutes) are presented. A percentile curve of the reflux index regarding the age distribution shows that the normal range for the reflux index during the first 12 months of life is about 10% (95 percentile), decreasing from 13% at birth to 8% at 12 months. Application of an age-related percentile curve offers a close-to-reality possibility of data interpretation and illustrates that there is inevitably an overlap of data between normal and abnormal populations, because reflux is a phenomenon occurring to some extent in every human being. 
Abnormal hormonal and renal responses to saline load in hypertensive patients with parental history of cardiovascular accidents. BACKGROUND. Acute cardiac and cerebrovascular accidents are more frequent in hypertensive subjects with a family history of acute vascular accidents. The mechanisms underlying the susceptibility to vascular disease in these subjects are unknown. We investigated whether a parental history of premature heart attack or stroke in hypertensive subjects is associated with abnormalities of sodium handling. METHODS AND RESULTS. Patients with mild, uncomplicated essential hypertension were divided into two subgroups according to family history: a subgroup with a parental history of premature heart attack or stroke (FV+, n = 18) and a subgroup with a family history completely negative for vascular accidents (FV-, n = 14). The two subgroups were comparable with respect to age, weight, sex distribution, blood pressure, duration of hypertension, cardiovascular risk factors, renal function, and organ damage. Baseline plasma renin activity (PRA), concentrations of aldosterone (PA), atrial natriuretic factor (ANF), and norepinephrine, and urinary electrolyte excretion were also comparable in the two subgroups. Despite these similarities, the responses to an acute saline load, measured under controlled metabolic and experimental conditions, were different in the two subgroups. In the FV+ subgroup at 60 minutes of saline load, PRA fell by 1.0 +/- 0.2 ng/ml/hr and PA concentration by 89.4 +/- 26 pg/ml and ANF concentration increased by 38 +/- 9 pg/ml, whereas in the FV- subgroup the corresponding responses were -2.3 +/- 0.3 ng/ml/hr (p less than 0.005), -190 +/- 43 pg/ml (p less than 0.05), and 80 +/- 13 pg/ml (p less than 0.005), respectively. Urinary sodium excretion was delayed in the FV+ subgroup (270 +/- 67 mu eq/min at 60 minutes) compared with the FV- subgroup (555 +/- 157 mu eq/min at 60 minutes, p less than 0.05). At 120 minutes of saline load, significant (p less than 0.005) differences in PRA and ANF concentration were still observed. In a control group of eight normal subjects the responses to a saline load were comparable to those in the FV- subgroup but greater than those in the FV+ subgroup at 60 minutes. CONCLUSIONS. These results provide evidence that the hormonal and renal adjustments to an acute salt load are impaired in hypertensive patients with a parental history of vascular accidents. We speculate that abnormalities of sodium handling may represent markers of a more rapid development of vascular injury in human hypertension. 
Total knee arthroplasty for osteoarthrosis in patients who have Paget disease of bone at the knee. Thirteen patients who had had sixteen total knee arthroplasties for pagetic gonarthrosis were followed for a mean of seven years (range, two to fifteen years). Involvement of the femur or tibia with Paget disease was associated with multiple technical difficulties at operation and with a final position in suboptimum varus or valgus alignment (ten limbs) or suboptimum alignment of the mechanical axis (nine limbs). The presence of bone with Paget disease did not affect the amount of blood lost during the operation, the postoperative course, or the rate of loosening of the prostheses. At the most recent evaluation, nine patients had no pain, three had mild pain, and one had moderate pain. The mean Knee Society pain score improved from 42 points preoperatively to 88 points and the mean functional score, from 33 to 86 points. 
Management of traumatic injuries to the facial nerve. Penetrating and nonpenetrating trauma to the head and neck produces myriad injuries to the facial nerve. This article presents a rationale of management of neural injury, emphasizing extracranial and intratemporal trauma and techniques of neurorrhaphy. 
Anterior plate fixation in spine tumor surgery. Indications, technique, and results. Anterior decompression by vertebrectomy is now well established as the procedure of choice to optimize neurologic recovery in patients with a deficit due to tumor involvement of the vertebral body. Fifteen patients with tumor involvement of the cervical or thoracic spine and neurologic deficit were treated by single-stage anterior decompression and AO plate stabilization. No patient suffered neurologic deterioration after surgery. All patients with thoracic lesions who were unable to walk on presentation and who managed to survive their primary disease improved to a level that allowed independent ambulation with a frame. There were no problems, such as loss of fixation or deformity. It is concluded that standard AO plates provide adequate stabilization of the cervical and thoracic spine after vertebrectomy for tumor involvement. 
PAF-induced bowel necrosis. Effects of vasodilators. Ischemic bowel necrosis in the rat is produced by injecting platelet-activating factor (PAF) intravenously. Since intestinal hypoperfusion is observed after PAF injection, we hypothesize that mesenteric vasoconstriction is the mechanism of bowel injury. We thus studied the effects of vasodilators in this model. We found that: (1) Phenoxybenzamine, prazosin, ICI 198615 (leukotriene antagonist) and PGE1 counteracted the PAF-induced mesenteric flow reduction and ameliorated the bowel injury. However, phenoxybenzamine and prazosin were relatively ineffective in correcting PAF-induced hypotension, showing that bowel injury can be prevented independently of the hypotensive state. (2) Nitroglycerin failed to prevent bowel injury, although it improved the mesenteric blood flow. Thus, in opposition to our initial hypothesis, correction of the mesenteric flow reduction induced by PAF does not always prevent intestineal necrosis. (3) Only phenoxybenzamine, prazosin, ICI 198615, and PGE1 ameliorated PAF-induced hemoconcentration and bowel injury. This suggests a correlation between vascular injury (expressed by "leaky" vessels and the consequent hemoconcentration) and bowel necrosis. (4) Although both nitroglycerin and hydralazine relax smooth muscle, hydralazine seemed to aggravate bowel necrosis. The mechanism remains unclear. 
Benign intrinsic tectal "tumors" in children. A specific group of intrinsic dorsal midbrain tumors was identified in six children by computerized tomography (CT) and magnetic resonance (MR) imaging. Each patient presented with raised intracranial pressure as a result of hydrocephalus due to obstruction of the sylvian aqueduct. No patient had brain-stem signs referable to the tectal tumor initially or subsequently. All six children underwent cerebrospinal fluid (CSF) diversionary procedures. The radiological features were consistent and specific, with all patients showing tectal calcification or primary increased attenuation of the tectal plate on CT scans. In addition, lack of contrast enhancement was noted initially in four patients and eventually in all six patients. In all patients MR imaging showed a focal tectal tumor distorting the collicular plate with no cystic component and increased signal intensity on T2-weighted images. There has been no evidence of progression in these six patients in the follow-up period ranging from 8 months to 17 years (8 months and 2 1/2, 4 1/2, 8, and 17 years). Diversion of CSF has been the only surgical treatment and no patient underwent deep x-ray therapy. Five patients have had normal intellectual development. In contrast to the majority of previously described periaqueductal and tectal tumors, this group of lesions appeared to be truly benign. The authors suggest that patients presenting with these clinical and radiological features may be managed by CSF diversion, serial examination, and MR imaging. 
Appearance of thrombosis-inducing activity in the plasma of patients undergoing pulmonary resection. Thrombosis-inducing activity (TIA) was detected in the peripheral blood of patients with lung cancer who had undergone pulmonary resection. TIA was examined by intravenously injecting plasma from the patients into BALB/c mice. The plasma containing TIA induced multiple thromboses in the lung and caused the mice to die 3 to 30 minutes after injection. The subjects were 19 patients whose plasma contained no TIA before operation. TIA was detected in 5.3 percent (1/19) on the first postoperative day (POD), 47.4 percent (9/19) on the seventh POD, 47.1 percent (8/17) on the 14th POD, 26.7 percent (4/15) on the 21st POD, and 20 percent (2/10) on the 28th POD. Plasma fibrinogen levels and peripheral platelet counts increased postoperatively and reached a maximum on the seventh and 14th POD, respectively. Peripheral blood with TIA had a significant elevation of plasma fibrinogen levels and platelet counts as compared to that without TIA. These observations suggest that TIA is present in blood in a hypercoagulable state in patients after pulmonary resection. Since tumor necrosis factor and interleukin 1 are known to induce hypercoagulable states both in vitro and in vivo, we tried to determine whether it was possible to detect both cytokines in blood indicated as hypercoagulable state by the presence of TIA. They did not, however, reach detectable levels in the blood. 
Hepatocellular carcinoma, alcohol, and cirrhosis: facts and hypotheses. Despite the epidemiological evidence of a correlation between ethanol abuse and hepatocellular carcinoma, some of the results of experimental and clinical studies remain controversial. Apart from inducing cirrhosis, which may be viewed as a precancerous liver lesion, ethanol may act as a cocarcinogen. Most investigations on this topic have focused on two aspects: ethanol's capacity to induce the cytochrome P-450-dependent microsomal biotransformation system and its interference with at least one DNA repair mechanism. Ethanol exposure enhances the capacity of mixed function oxidases to activate many chemical carcinogens, such as dimethylnitrosamine (DMN). On the other hand, ethanol exposure fails to influence DMN-induced liver carcinogenesis. The capacity of alcohol to inhibit DMN-demethylase activity has not been clearly demonstrated in experiments carried out with human tissue. In conclusion, both the effects of ethanol and their underlying mechanisms as regards liver carcinogenesis are open to debate. The link between ethanol abuse and hepatocellular carcinoma appears to be mediated mainly by its capacity to induce cirrhosis. 
Finger tremor after carbon disulfide-based pesticide exposures. Index finger tremor accompanying voluntary movement was studied in 19 age-matched control subjects and in 19 grain industry employees chronically exposed to carbon disulfide-based fumigants. Visual judgments of tremor amplitude made by neurologists during clinical examinations equaled the sensitivity of computerized tremor amplitude measurements. Tremor frequency variations detectable only with computerized measurement were present in grain workers with and without increased tremor amplitudes. Frequency differences discriminated between normal subjects and 74% of the grain workers. The distribution of tremor frequency power in the grain workers was often sequestered at 5 to 7 Hz, reminiscent of tremor in idiopathic Parkinson's disease. These findings suggest that the measurement of subtle tremor frequency changes may provide an early indication of chronic carbon disulfide poisoning. 
Chronic diarrhea. A practical approach for the pediatrician. Despite the high prevalence of chronic diarrhea there is no universal approach to its diagnosis and treatment. This article summarizes the pathophysiologic processes that result in chronic diarrhea and presents a diagnostic and therapeutic approach to this often distressing problem. 
Long-term complications of polyurethane-covered breast implants. The authors's personal experience using an earlier manufactured polyurethane-covered gel prosthesis is presented. Very long-term follow-up did not validate the author's initial enthusiasm. It is to be hoped that the newer polyurethane-covered implants will give more satisfactory long-term results. 
Transformed mammalian cells are deficient in kinase-mediated control of progression through the G1 phase of the cell cycle. To investigate the role of kinase-mediated mechanisms in regulating mammalian cell proliferation, we determined the effects of the general protein kinase inhibitor staurosporine on the proliferation of a series of nontransformed and transformed cultured rodent and human cells. Levels of staurosporine as low as 1 ng/ml prevented nontransformed cells from entering S phase (i.e., induced G1 arrest), indicating that kinase-mediated processes are essential for commitment to DNA replication in normal cells. At higher concentrations of staurosporine (50-75 ng/ml), nontransformed mammalian cells were arrested in both G1 and G2. The period of sensitivity of nontransformed human diploid fibroblasts to low levels of the drug commenced 3 hr later than the G0/G1 boundary and extended through the G1/S boundary. Interference with activity of the G1-essential kinase(s) caused nontransformed human cells traversing mid-to-late G1 at the time of staurosporine addition to be "set back" to the initial staurosporine block point, suggesting the existence of a kinase-dependent "G1 clock" mechanism that must function continuously throughout the early cycle in normal cells. The initial staurosporine block point at 3 hr into G1 corresponds to neither the serum nor the amino acid restriction point. In marked contrast to the behavior of nontransformed cells, neither low nor high concentrations of staurosporine affected G1 progression in transformed cultures; high drug concentrations caused transformed cells to be arrested solely in G2. These results indicate that kinase-mediated regulation of DNA replication is lost as the result of neoplastic transformation, but the G2-arrest mechanism remains intact. 
Lineage-restricted clonality in biphasic solid tumors. Cytogenetic analysis of two pulmonary chondroid hamartomas and nine breast adenofibromas revealed clonal chromosome aberrations in both hamartomas and in four breast tumors. To determine lineage of the cells with chromosome aberrations, a combined immunohistochemical/cytogenetic approach was developed that enabled simultaneous ascertainment of cytogenetic aberrations and immunohistochemical features in individual cells. Immunohistochemical/cytogenetic evaluation of one hamartoma and two adenofibromas demonstrated that neoplastic proliferation, in each case, was confined to the mesenchymal (stromal) component, whereas epithelial cells appeared to be reactive. Cytogenetically abnormal short-term cultures of the remaining hamartoma and another of the breast adenofibromas were composed entirely of mesenchymal elements, indicating mesenchymal clonality in those tumors as well. Our findings support redesignation of pulmonary chondroid hamartomas as 'pulmonary chondromas' and suggest that carcinomas developing within fibroadenomas arise from reactive epithelial proliferation. Combined immunohistochemical/cytogenetic analysis might be useful in the development of novel therapeutic approaches that selectively target neoplastic populations within solid tumors. 
Instability of a 550-base pair DNA segment and abnormal methylation in fragile X syndrome. The fragile X syndrome, a common cause of inherited mental retardation, is characterized by an unusual mode of inheritance. Phenotypic expression has been linked to abnormal cytosine methylation of a single CpG island, at or very near the fragile site. Probes adjacent to this island detected very localized DNA rearrangements that constituted the fragile X mutations, and whose target was a 550-base pair GC-rich fragment. Normal transmitting males had a 150- to 400-base pair insertion that was inherited by their daughters either unchanged, or with small differences in size. Fragile X-positive individuals in the next generation had much larger fragments that differed among siblings and showed a generally heterogeneous pattern indicating somatic mutation. The mutated allele appeared unmethylated in normal transmitting males, methylated only on the inactive X chromosome in their daughters, and totally methylated in most fragile X males. However, some males had a mosaic pattern. Expression of the fragile X syndrome thus appears to result from a two-step mutation as well as a highly localized methylation. Carriers of the fragile X mutation can easily be detected regardless of sex or phenotypic expression, and rare apparent false negatives may result from genetic heterogeneity or misdiagnosis. 
Lichen planus and mesalazine. Lichen planus is a recognized complication of sulfasalazine therapy. Two patients developed typical oral and cutaneous lichen planus on sulfasalazine and their skin lesions recurred when they were subsequently changed to mesalazine. Lichen planus only resolved on withdrawal of both drugs. It seems likely that the aminosalicylic acid moiety is responsible for this reaction and that lichen planus is a true complication of mesalazine therapy. 
Bacteremia in febrile patients. A clinical model for diagnosis. Among 244 patients aged 18 to 98 years who were consecutively hospitalized in a department of internal medicine because of a febrile disease, 52 (21%) were bacteremic. On a logistic regression analysis, five variables known within 24 hours of admission were found to be associated both significantly and independently with bacteremia: low serum albumin level, low premorbid performance status, chills, renal failure, and an assumptive diagnosis of urinary tract infection on admission. The logistic model was used to divide patients into three groups. In group 1, the percentage of bacteremic patients was 5%, in group 2, 40%, and in group 3, 83%. The percentage of deaths in the three groups was 0%, 23%, and 50%, respectively. The model was validated in a second group of 257 patients. The percentage of bacteremia was 1% in group 1, 23% in group 2, and 65% in group 3. The death rate in three groups was 3%, 4%, and 35%, respectively. The accuracy of the attending physician in diagnosing bacteremia within 24 hours of hospitalization was compared with that of the model. Use of the model could have improved the diagnostic accuracy in 5% of the patients in group 1 and in 18% of patients in group 3. 
Pharmacologic roles of heparin and glucocorticoids to prevent restenosis after coronary angioplasty. Restenosis after successful percutaneous transluminal coronary angioplasty is the major clinical problem limiting the long-term efficacy of this treatment for coronary atherosclerosis. Recent advances in the understanding of the biology of restenosis indicate that intimal hyperplasia of smooth muscle cells is the predominant cause for restenosis. Therefore, therapeutic agents that inhibit vascular smooth muscle cell proliferation should be candidate drugs to prevent restenosis. Heparin has documented antiproliferative effects on smooth muscle cells, and the availability of low molecular weight heparins that lack anticoagulant properties makes them ideal agents. Glucocorticoids have wide effects on inflammatory and wound healing events and inhibit smooth muscle cell growth in culture and in animal models of arterial injury. Recent laboratory data suggest that combination therapy with both low molecular weight heparin and hydrocortisone may be a powerful treatment regimen to limit restenosis. 
Haemodynamic interactions of muscle relaxants and sufentanil in coronary artery surgery. The haemodynamic interactions between sufentanil (S) and muscle relaxants (MR) were studied in 40 ASA physical status III or IV patients (four groups of ten) scheduled for coronary artery bypass grafting (ABG). Group I received pancuronium (P) 0.08 mg.kg-1, Group II received vecuronium (V) 0.1 mg.kg-1, Group III received atracurium (A) 0.5 mg.kg-1 and Group IV metocurine 0.1 mg.kg-1 plus pancuronium 0.02 mg.kg-1 (M-P). Sufentanil, 20 micrograms.kg-1 was administered before sternotomy, 10 micrograms.kg-1 being injected before tracheal intubation and 10 micrograms.kg-1 afterwards. Heart rate (HR), ECG leadII and V5, systolic, diastolic and mean arterial and pulmonary blood pressures, central venous pressure (CVP) and pulmonary capillary wedge pressure (W) were measured and recorded at the time of seven strategic events between the pre-induction of anaesthesia period and sternotomy. Cardiac output (CO) and systemic vascular resistances (SVR) were also measured before induction of anaesthesia and after the administration of S 10 micrograms.kg-1 plus the MR. The HR decreased from baseline values in the post-tracheal intubation period in all groups except in P group. The mean arterial pressure also decreased significantly in all groups except in the P group. The CO did not change from baseline values but SVR decreased in all groups. There was no evidence of new myocardial ischaemia according to the ECG monitoring and there was no significant difference in the HR changes between patients who had or who had not received beta-blockers in any group. We conclude that within the present study conditions and design, HR and blood pressure changed least with pancuronium. 
Coronary artery vasoregulation and left ventricular function in patients with angina pectoris-like pain and normal coronary angiograms. Twenty patients with angina pectoris-like pain, normal coronary angiography and abnormal exercise 201Tl scans were investigated by means of haemodynamic, coronary sinus blood flow and lactate determinations before and after cold provocation, pacing and dipyridamole infusion. Radionuclide angiography, a new exercise 201Tl scan and noninvasive hyperventilation and ergonovine tests were performed. Intracoronary infusions of acetylcholine were given in increasing doses and a second coronary angiogram in combination with a 201Tl scintigram was performed. Despite a previously pathological 201Tl scintigram, with reversible perfusion defects, only ten of the patients had reversible perfusion defects at the second investigation. Hyperventilation and ergonovine tests did not result in ECG signs indicative of coronary spasm. Intracoronary infusion of acetylcholine resulted in a diffuse coronary constriction in 3 of 14 patients, and in one patient a perfusion defect was observed on thallium scintigram. In conclusion, although most of the common methods for inducing coronary vasospasm were used, no consistent pattern of reaction was found to explain the chest pains experienced in this group of patients. 
Atrial natriuretic peptide-induced relaxation of pre-constricted isolated rat perfused lungs: a comparison in control and hypoxia-adapted animals. 1. To further understand the vasodilator actions of atrial natriuretic peptide and its role in hypoxic pulmonary hypertension, we studied the effects of atrial natriuretic peptide in the isolated perfused rat lung during normoxic ventilation and after elevation of pulmonary artery pressure by either hypoxic ventilation or infusion of prostaglandin F2 alpha. Control animals were compared with littermates that had become adapted to a 10% O2 environment for 3 weeks. Atrial natriuretic peptide was compared with atriopeptin I and atriopeptin III in order to study its structure-activity relationship. 2. Five experiments, each involving six control and six chronically hypoxic rats, were performed. During normoxic ventilation, atrial natriuretic peptide (30 ng-3 micrograms) produced a dose-dependent reduction in pulmonary artery pressure in chronically hypoxic rats, but had no action in the control animals. 3. Atrial natriuretic peptide dose-dependently abolished hypoxic pulmonary vasoconstriction to a greater extent in chronically hypoxic rats (EC50 98 ng) than in control rats (EC50 298 ng; P less than 0.001). Bolus atrial natriuretic peptide (100 ng) produced a plasma concentration of 22.6 pmol/l at 1 min, which is within the pathophysiological range. Initial plasma atrial natriuretic peptide levels were 9.4 pmol/l in control animals and 27.4 pmol/l in chronically hypoxic rats. 4. Chronically hypoxic rats were more sensitive to atriopeptin I, atriopeptin III and atrial natriuretic peptide than were the control rats (P less than 0.05). Atrial natriuretic peptide and atriopeptin III were equipotent and were 10 times more potent than atriopeptide I in both groups (P less than 0.001). 
Midazolam improves electrophysiologic recovery after anoxia and reduces the changes in ATP levels and calcium influx during anoxia in the rat hippocampal slice. Since blockers of excitatory transmission have been shown to reduce anoxic and ischemic neuronal damage, augmentation of inhibitory transmission by agents such as midazolam might have a similar protective effect. Rat hippocampal slices were maintained in vitro and used to determine whether and by what mechanism midazolam improves recovery of evoked responses after anoxia. The Schaffer collateral pathway in the slice was stimulated electrically, and an extracellular potential, the evoked population spike, was recorded from the CA1 pyramidal cells, which are postsynaptic. The slices were made anoxic by substituting artificial cerebrospinal fluid aerated with 95% nitrogen-5% carbon dioxide for fluid aerated with 95% oxygen-5% carbon dioxide. Percentage recovery was expressed as the amplitude of the evoked population spike 60 min after anoxia divided by its preanoxic amplitude. Protection in this model is defined as a significant (P less than 0.05) improvement in percentage recovery compared to the recovery of untreated slices. There was no recovery of the response recorded from CA1 pyramidal cells after 5 min of anoxia (4 +/- 2%) (mean +/- standard error of the mean [SEM]). Slices were treated with midazolam 10 min before, during, and 10 min after anoxia. Midazolam (1 microM) did not enhance recovery after anoxia when dissolved either in water (3 +/- 3%) or in dimethyl sulfoxide (DMSO) (1 +/- 1%). A higher concentration of midazolam (100 microM) did enhance recovery when dissolved in DMSO (27 +/- 7%) but not when dissolved in water (5 +/- 2%). To test whether prolonged pretreatment with midazolam dissolved in water would enhance recovery, slices were treated for 30 min prior to anoxia. 
Selective microscopic examination of gallbladders, hernia sacs, and appendices. The usefulness of many "routine" medical procedures is being challenged in the health care atmosphere of today. This study was undertaken to determine the utility of routine microscopic pathologic examination of three frequently submitted surgical specimens. Pathology reports of 39,568 consecutive specimens, 17,105 appendices, 14,654 hernia sacs, and 7,809 gallbladders, submitted over a 49-year period, were reviewed. Microscopic examination of these tissues detected few unexpected findings. In those instances in which unexpected findings were discovered the primary surgery was curative or additional surgery would not have altered the prognosis. When careful, thorough gross examination by the surgeon and pathologist failed to disclose significant abnormalities or confirmed obvious disease such as inflammation, microscopic examination of these tissues might have been eliminated without a change in patient outcome. Although it could be argued that this microscopic pathologic correlation may be helpful for quality control and/or feedback of surgical decision making, the data indicate that gross examination alone may be sufficient in most cases, since unexpected microscopic findings are rare. The indications for microscopic examination of appendices, hernia sacs, and gallbladders are listed. Substantial savings of resources and time may be expected when selective microscopic examination is used. 
Deletions within the pseudoautosomal region help map three new markers and indicate a possible role of this region in linear growth. Short stature is consistently found in individuals with terminal deletions of Xp. In order to refine the localization of a putative locus affecting height, we analyzed two patients with a partial monosomy of the pseudoautosomal region at the molecular level. Eight pseudoautosomal probes were used for the genetic deletion analysis through dose evaluation. Three of them represent new markers (DXS415, DXS419, and DXS406) which were positioned on the pseudoautosomal map by pulsed field gel electrophoresis. Our data suggest that a locus affecting height maps in a region of about 1.5 Mbp, distal to the DXS406 locus and proximal to the DXS415 locus, a region which includes two CpG islands, and rule out an involvement of very distal sequences at the X/Y telomeres. 
Sleep apnea in acromegaly. OBJECTIVE: To provide information on the nature, prevalence, and severity of sleep apnea in patients with acromegaly. DESIGN: Consecutive case series. SETTING: Tertiary referral hospital. PATIENTS: Fifty-three patients with acromegaly were consecutively referred: 33 patients were referred because of clinical suspicion of sleep apnea and 20 patients were referred without suspected apnea. MEASUREMENTS: Sleep studies as well as growth hormone and insulin-like growth factor 1 (IGF-1) measurements were done. MAIN RESULTS: Thirty-one patients (93%; 95% Cl, 85% to 100%) referred because of suspicion of sleep apnea had sleep apnea compared with 12 patients (60%; Cl, 37% to 83%) referred without suspected sleep apnea. Patients with sleep apnea did not have biochemical evidence of increased disease activity (random growth hormone, 12.7 +/- 4.4 micrograms/L; mean growth hormone at 24-hour sampling, 10.8 +/- 8.4 micrograms/L; IGF-1, 90.0 +/- 7.5 nmol/L) compared with patients without sleep apnea (random growth hormone, 14.2 +/- 4.9 micrograms/L, P greater than 0.2; mean growth hormone, 12.4 +/- 3.5 micrograms/L, P greater than 0.2; IGF-1, 90.0 +/- 10.0 nmol/L, P greater than 0.2). Central sleep apnea was the predominant type of apnea in 33% (Cl, 18% to 47%) of patients and was associated with higher random growth hormone and IGF-1 levels than was obstructive apnea (random growth hormone, 23.4 +/- 3.9 compared with 8.8 +/- 3.1 micrograms/L, P less than 0.001; IGF-1, 126 +/- 17.5 compared with 72.5 +/- 7.5 nmol/L, P less than 0.01). CONCLUSIONS: Sleep apnea is common in acromegaly. The rate of central sleep apnea was unexpectedly high in patients with acromegaly, and biochemical evidence of increased disease activity was associated with the presence of central apnea rather than with the degree of sleep apnea. Altered respiratory control is a possible mechanism producing sleep apnea in acromegaly. 
Paraganglioma of urethra. Paraganglioma of the urethra is a rare tumor; only 4 cases have been reported previously. We report a fifth case of urethral paraganglioma and review the literature. 
Localization of metallothionein in hair follicles of normal skin and the basal cell layer of hyperplastic epidermis: possible association with cell proliferation. Metallothionein is a low-molecular-weight metal-binding protein. Although it is inducible by a variety of agents and ubiquitously present in many tissues, its physiologic functions are still not clear. The present study was undertaken to determine the possible functions of metallothionein in both the proliferation and differentiation of epidermal keratinocytes. Metallothionein was detected immunohistochemically in hair matrix cells of the bulb and cells of the outer root sheath of anagen hair follicles, but not in dermal papillae in normal skin in the back of mice. In hyperplastic epidermal tissue, induced by either a phorbol ester tumor promoter or cholera toxin, the basal cells of the interfollicular epidermis stained strongly for metallothionein. Elevated expression of mRNA of the metallothionein gene was also demonstrated when the skin was stimulated by agents that induced hyperplasia. Papillomas produced by two-stage carcinogenesis protocols also stained for metallothionein. These observations suggest that metallothionein is involved in the proliferation of epidermal keratinocytes. 
Hemostatic wrapping of ruptured liver in two postpartum patients. A variety of surgical techniques with variable success rates have been reported in the management of the spontaneously ruptured liver in pregnancy. We managed two cases of postpartum ruptured liver by wrapping the liver in hemostatic material. Hemostatic encapsulation effectively controlled massive bleeding of ruptured livers in two postpartum patients. 
Middle ear adenoma: tumour of mixed mucinous and neuroendocrine differentiation. Two cases of progressive hearing loss due to middle ear tumours are described. The histological characteristics numbered intraluminal mucin production and neuroendocrine features, as shown by argyrophilia and ultrastructural demonstration of dense core granules. These tumours have been known by many different names, reflecting the controversies relating to their presumed histogenesis and differentiation. The currently preferred designation is middle ear adenoma, and these two cases provide further evidence for dual lines of differentiation. 
Suture technique affects perianastomotic colonic crypt cell production and tumour formation. Suture line recurrence is an important cause of failure after potentially curative resection for colonic carcinoma. Our aim was to determine whether suture technique affected the incidence of perianastomotic tumours in experimentally induced colonic cancer. Sprague-Dawley rats were randomized into three groups. A 1 cm longitudinal colotomy was repaired with four interrupted 6/0 polypropylene monofilament sutures, using either a transmural technique (n = 18) or a seromuscular technique (n = 18). Control animals (n = 18) had a sham laparotomy. All animals received nine, weekly, subcutaneous injections of azoxymethane (total dose 90 mg/kg) starting 6 weeks after laparotomy. Surviving animals were killed 32 weeks after laparotomy. Five animals from each group were given intraperitoneal bromodeoxyuridine (100 mg/kg) 1 h before being killed. At death, perianastomotic tumours occurred more frequently in animals with transmural sutures than in either controls or those with seromuscular sutures. This difference was associated with a greater mucosal bromodeoxyuridine crypt cell labelling index in the transmural suture group. We conclude that a transmural anastomotic suture technique promotes the development of experimental perianastomotic colonic tumours. 
Recurrent deletion in the human antithrombin III gene. Eight unrelated patients with recurrent thromboembolism, a family history of thrombosis, and plasma antithrombin III (ATIII) activity/antigen levels consistent with a diagnosis of heterozygous type I ATIII deficiency were studied by polymerase chain reaction/direct sequencing of ATIII gene exon-coding regions. Frameshift mutations of one base and two bases, respectively, were found to have occurred in two unrelated patients at the same GAG codon (Glu 245) within exon 4 of the ATIII gene. A literature search showed six further hitherto unrecognized deletion "hotspots" in four other human genes. These deletion-prone sites exhibited sufficient sequence homology with each other to derive a consensus sequence (T G A/G A/G G A/C), suggesting that deletion in human genes may not only be non-random but also sequence-directed. 
Detection of polyadenylated RNA in hepatitis B virus-infected peripheral blood mononuclear cells by polymerase chain reaction. Polymerase chain reaction (PCR) with a reverse transcriptase step characterized a specific transcription activity in hepatitis B virus (HBV)-infected peripheral blood mononuclear cells (PBMC) in two patients (1 and 2) with chronic hepatitis positive for antibody to hepatitis B core antigen (HBc). Patient 1 was also coinfected with human hepatitis delta virus. A patient who cleared HBV replication after antiviral treatment with vidarabine served as negative control. HBV-specific RNA poly A sequences were detected by PCR in PBMC of patients 1 and 2 even without detectable HBV DNA (patient 2) as shown by dot blot and PCR assays. RNA sequences were found in both the nucleus and cytoplasm. The demonstration of HBV mRNA sequences within PBMC suggests the transcription of viral DNA, in agreement with the findings of HBV surface antigen in PBMC. The results in patient 1 demonstrated HBV mRNA sequences in leukocytes even without PCR-detectable HBV DNA sequences, likely due to ongoing hepatitis delta virus replication. 
Gold weight lid load as a secondary procedure. This paper discusses the use of gold weight lid load as a secondary procedure. By using three representative patients, I emphasize the following points: First, the dominance of the eye must be determined so that postoperative changes in the eyelid height can be anticipated. Second, in order to obtain an accurate weight of the implant needed, the restrictive effect on the eyelid from the previous surgery (a tarsorrhaphy or an encircling band) must first be eliminated. Third, to ensure the best result and the patient's comfort, lacrimal function, Bell's phenomenon, and levator function must be assessed. 
Effect of intracoronary diltiazem on infarct size and regional myocardial function in the ischemic reperfused canine heart This study was designed to investigate whether intracoronary diltiazem given before reperfusion could enhance myocardial salvage in the canine heart. Twenty-five dogs were subjected to 90 min of coronary occlusion followed by 4 h of reperfusion. The dogs were assigned to one of three experimental groups. The early diltiazem group received intracoronary diltiazem into the distal coronary bed at the onset of coronary occlusion and for 60 min after reperfusion. The late diltiazem group received the same amount of drug beginning 15 min before reperfusion and the control group received saline solution for 90 min of occlusion and 60 min of reperfusion. Infarct size expressed as a percent of the area at risk was significantly smaller in the early and late diltiazem groups (15.6 +/- 3.6% and 21.2 +/- 5.1%, respectively) than in the control group (49 +/- 4.6%) (p less than 0.05). Intracoronary diltiazem restored systolic function of the stunned, previously ischemic tissue to essentially normal preocclusion values. Segmental shortening after reperfusion averaged 21.6% in the early diltiazem group versus 0 +/- 1.7% and 7.3 +/- 4% for the control and late diltiazem groups, respectively (p less than 0.05). Low dose intracoronary diltiazem did not alter hemodynamic variables or myocardial blood flow but did improve segmental shortening 2 and 6 h after reperfusion. These data indicate that intracoronary diltiazem given during occlusion or just before reperfusion increases the salvage of myocardium compared with the salvage achieved by reperfusion alone. These results also suggest that intracoronary diltiazem given during the ischemic period enhances systolic contractile function of postischemic stunned myocardium. 
Influence of the site of tumor growth on the capacity of a low tumorigenic line of Friend erythroleukemia cells to differentiate. Friend erythroleukemia cells (FLC) passaged in mice are highly tumorigenic and multiply extensively in the livers of suckling DBA/2 mice without differentiating. In contrast, in vitro passaged FLCs injected intravenously were of low tumorigenicity, multiplied to a limited extent in the livers of suckling mice, and underwent marked differentiation from the proerythroblast to the orthochromatic erythroblast stage in the liver. The presence of characteristic C-type virions budding from the cell surface in various stages of erythroid differentiation served as a marker of the injected FLCs. When the same in vitro passaged FLCs that differentiated in the liver were injected subcutaneously in suckling mice, they formed large subcutaneous tumors consisting of sheets of undifferentiated tumor cells. It is concluded that the tumorigenicity of FLCs depended on the site of tumor growth and that there is an inverse correlation between the tumorigenic capacity and the capacity to differentiate. 
Gallstone fragmentation during biliary lithotripsy: effect of stone composition and structure. In vitro lithotripsy with the Siemens Lithostar was conducted on 36 radiolucent or minimally calcified gallstones housed in an anthropomorphic phantom. The ease and pattern of fragmentation were correlated with global composition for the entire stone, regional or microcomposition (determined by Fourier-transform infrared spectroscopy), and microstructure (determined by scanning electron microscopy). Stones made up of more than 62% cholesterol required 50% more shock waves to pulverize all fragments to 0.3 cm or less than did stones of less than 62% cholesterol (p less than .01). An inverse relationship was found between the number of shock waves needed for fragmentation and the cholesterol content (r = .77). Although a broad range of fragmentation responses occurred, little variation was seen in the ease of fragmentation within stone families. The majority of stones fractured along radially oriented cholesterol plates, but one third of stones treated showed initial chipping or flaking at the periphery before radial fracture. This type of peripheral erosion most often occurred in stones with peripheral pigment rims. These stones required more shock waves and lagged in pulverization compared with more homogeneous cholesterol stones. The efficiency of fragmentation during biliary lithotripsy correlates with the stones' global cholesterol content. A stone's architecture, as reflected by its regional composition and microstructure, partially predicts the mechanism of fragmentation. These in vitro data may be useful in further refining criteria for selecting patients and understanding the fragmentation process. 
Prognostic value of raised prostatic acid phosphatase and negative skeletal scintigraphy in prostatic cancer. Of 438 consecutive cases of newly diagnosed prostate cancer, 178 (41%) had skeletal metastases (T0-4 M1) at the time of diagnosis according to skeletal scintigraphy; 139 men had serum prostatic acid phosphatase (PAP) greater than twice the upper limit of normal on 2 separate occasions at the time of diagnosis and 65% of them had metastases on bone scan. However, 49 men with normal bone scans were found to have similarly raised serum PAP. (Such patients are defined as having skeletal metastases in the current Medical Research Council immediate versus deferred orchiectomy study and stratified accordingly). The actuarial survival of this group was calculated by life table methods and was compared with that of 2 other subgroups: those patients having metastases demonstrated on bone scan, and those patients having both normal bone scans and normal serum PAP. The survival of the "metastatic by acid phosphatase" group was significantly better than that of the "metastatic by bone scan" group but did not differ from that of patients having both normal scans and PAP. For patients with no scintigraphic evidence of skeletal metastases at diagnosis, those with a raised PAP were at a significantly greater risk of scan conversion, although this was more powerfully predicted by high histological grade. 
Cancer occurrence in a cohort of patients surgically treated for peptic ulcer. A cohort of 4107 patients treated surgically for peptic ulcer between 1955 and 1960 was followed up to determine the incidence of cancer by record linkage to the Danish Cancer Registry. A total of 930 cases of cancer were observed during 76,634 person-years. Relative risks of cancer were computed by comparison with the recorded cancer incidence in the Danish population. During the first five years after surgery the relative risk of gastric cancer was slightly increased (RR = 1.43), but 5-15 years after the operation the risk was lower than expected (RR = 0.55). Thereafter, the relative risk of gastric cancer increased steadily and increased more than twofold after 25 years. Lung cancer occurred more frequently in the cohort members than expected (RR = 1.66), but the relative risk was independent of time since surgery. Malignancies other than gastric cancer and cancers related to tobacco smoking were close to the expected numbers. The results do not support the findings of a recent British study of similar size in which increased risks were reported for cancer at other sites. 
Proteinase trapping: screening for viral proteinase mutants by alpha complementation. Many virally encoded proteinases cleave themselves out of a polyprotein, with cleavage occurring usually at their own N terminus. This property was used to develop an in vivo screening system using the lacZ gene fragment of M13mp18. When a fusion protein of the alpha fragment of beta-galactosidase and an active 2A proteinase of human rhinovirus 2 was expressed, alpha complementation was not affected, as the 2A proteinase cleaved itself off the alpha fragment. However, fusion of an inactive 2A prevented alpha complementation, as the 2A polypeptide remained fused to the alpha fragment. After random mutation of the 2A gene by PCR amplification, mutants were screened; M13 phage defective in alpha complementation were obtained at an efficiency of 5% and were shown to contain mutated 2A genes. Intermolecular cleavage was then examined by expressing an alpha fragment-inactive proteinase fusion protein as substrate for an active 2A proteinase expressed from an M13 vector. alpha complementation indicated intermolecular processing of the 2A cleavage site on the alpha fragment-inactive proteinase fusion protein. This versatile system thus allows the high-density screening of both active and inactive proteinase mutants, cleaving either intramolecularly or intermolecularly, and should be applicable to other proteinases of high specificity. 
Excimer laser ablation of fibrocartilage: an in vitro and in vivo study. To date, lasers have found only limited applications in orthopedics. We employed a 308 nm XeCl excimer laser for ablation of fibrocartilage, in order to investigate the feasibility of excimer laser assisted meniscectomy. Experiments were conducted both in vitro and in vivo. For the in vitro study, human menisci, obtained during surgery and autopsy, were irradiated via a 600 microns core fiber at radiant exposures ranging between 20 mj/mm2 and 80 mj/mm2, at 20 Hz. Ablation rate measurements and histological analysis of the samples were performed. The ablation rates were found to range from 3 microns/pulse to 100 microns/pulse depending on the radiant exposure and/or the applied pressure on the fiber delivery system. Thermographic analysis was also performed during pulsed excimer as well as CW Nd:Yag and CW CO2 laser irradiation. Temperatures were lower for excimer laser (Tmax less than 65 degrees) than CW ND: Yag (Tmax less than 210 degrees) or CW CO2 (Tmax less than 202 degrees) laser. For the in vitro study, medial meniscectomy was performed in 15 rabbits with the excimer laser and a CW Nd:Yag laser in the right and left knee respectively. Excimer laser irradiation was performed at 70 mj/mm2. Nd:Yag irradiation was performed via a 600 microns core fiber at power outputs between 20 to 40 W for 10 and 20 seconds duration. The healing response to injury was investigated by histological analysis of the menisci after 1 day, 1, 2, 4, and 8 weeks following the laser procedure. Excimer laser treated menisci showed less inflammatory reaction and noticeable repair with minimal inflammatory response. 
Palliation of malignant tracheal strictures using silicone T tubes. The use of silicone T tubes for intubation of malignant tracheobronchial strictures may provide some degree of palliation of this distressing condition. It was used in seven patients with malignant lesions and two with benign strictures (resulting from tracheal trauma and lung transplantation). Four patients (two with cancer) are still alive and well with the tube in position. All patients noted improvement in dyspnoea and stridor. The main problems were tube migration (one patient), tracheo-oesophageal fistula (one patient), and blockage of the tube by tumour (two patients) or encrusted secretions (three patients). Airway patency was restored when the tube was blocked by cleaning or by laser resection of the tumour. With careful supervision and education of the patient intubation can give useful palliation to patients with distressing upper airways obstruction. 
The effect of intravesical bacillus Calmette-Guerin therapy on the upper urinary tract. A total of 66 patients with low grade, low stage transitional cell carcinoma of the bladder who were treated with intravesical bacillus Calmette-Guerin (BCG) underwent cystourethrography to detect vesicoureteral reflux. BCG was instilled weekly for 6 weeks and monthly thereafter for up to 24 months. Whenever vesicoureteral reflux was found or morphological abnormalities were detected on excretory urography (IVP) an isotope renal scan was performed to evaluate the relative renal function. Vesicoureteral reflux was found in 13 patients (19.7%): 10 had grades 1 and 2A, and 3 had grade 2B reflux. The number of BCG instillations ranged from 8 to 22. IVPs were normal in 11 patients. In 2 patients mild unilateral dilatation was present before BCG instillations, and this remained unchanged during and after therapy. None of the 13 patients with vesicoureteral reflux had IVP features suggestive of urinary tuberculosis. In 11 patients the refluxing renal systems had normal relative renal function (50 to 55%). Two patients had a decrease to 40% of the relative renal function with normal IVPs, suggesting a nonBCG related cause. We conclude that BCG therapy is safe in patients with minimal reflux. 
Intraoperative evaluation of intestinal ischemia: a comparison of methods. Methods for evaluating intestinal ischemia include standard clinical criteria, Doppler ultrasonography, and intravenous fluorescein injection. Each has disadvantages, and a combination of methods is often used. The purpose of this study was to determine whether surface oximetry could be used to assess perfusion in an animal whose intestinal diameter approximates that of infants. Reversible arterial, venous, and arteriovenous occlusion was studied in rabbit intestines. After 6 to 8 hours of occlusion, intestinal vascularity was evaluated by the four methods listed. Doppler ultrasonography and surface oximetry were found to be unreliable tools for assessing perfusion in this animal model. We conclude that standard clinical criteria and fluorescein remain the standards for intraoperative evaluation of intestinal perfusion. 
Ventricular tachycardia with congenital ventricular diverticulum. A 24-year-old man presented with symptomatic, recurrent, sustained ventricular tachycardia (VT). He was found to have a basal inferior left ventricular diverticulum. His sustained VT was reproduced by programmed electrical stimulation and was unresponsive to procainamide, tocainide, propafenone, and flecainide. Endocardial mapping followed by resection and cryoablative surgery was performed. The patient had only one recurrence after 18 months, with subsequent control with procainamide for over 14 months. 
Clinical parameters predictive of malignancy of thyroid follicular neoplasms. Needle aspiration biopsy is commonly employed in the evaluation of thyroid nodules. Unfortunately, the cytologic finding of a "follicular neoplasm" does not distinguish between a thyroid adenoma and a follicular cancer. The purpose of this study was to identify clinical parameters that characterize patients with an increased risk of having a thyroid follicular cancer who preoperatively have a "follicular neoplasm" identified by needle aspiration biopsy. A total of 395 patients initially treated at Vancouver General Hospital and the British Columbia Cancer Agency between the years of 1965 and 1985 were identified and their data were entered into a computer database. Patients with thyroid adenomas were compared to patients with follicular cancer using the chi-square test and Student's t-test. Statistically significant parameters that distinguished patients at risk of having a thyroid cancer (p less than 0.05) included age greater than 50 years, nodule size greater than 3 cm, and a history of neck irradiation. Sex, family history of goiter or neoplasm, alcohol and tobacco use, and use of exogenous estrogen were not significant parameters. Patients can be identified preoperatively to be at an increased risk of having a follicular cancer and accordingly appropriate surgical resection can be planned. 
Metabolic markers of stress-induced myocardial ischemia. The human heart in the fasting state extracts free fatty acids (FFA), glucose, lactate, pyruvate, and ketones from circulating blood. The utilization of FFA accounts for most of the oxygen consumed and energy produced at rest. Patients with angiographically demonstrable coronary artery disease and stable angina pectoris have a resting myocardial metabolism similar to that of normal individuals. During atrial pacing in normal persons, there is a significant enhancement of glucose uptake but that of FFA is unchanged, and the oxidation of carbohydrates accounts for more than 60% of the energy produced. In patients with stable angina, myocardial perfusion becomes regionally inadequate during stress. Despite the increase of myocardial glucose utilization, carbohydrate oxidation is negligible. Pyruvate will not be oxidized but in the presence of increased amounts of reduced coenzymes will be reduced to lactate. In addition, a greater amount of alanine will be released by the myocardium through the transamination of pyruvate, with a concomitantly greater uptake of glutamate that serves as the NH2 donor. In addition, glutamate may be used as an anaerobic fuel through conversion to succinate coupled with GTP formation. Although coronary hemodynamics, including myocardial perfusion, return to baseline within a few minutes after stress, a longer time course is needed for myocardial metabolism to become normal. In particular, myocardial utilization of exogenous glucose remains higher well after the normalization of hemodynamic parameters. This is more pronounced in postischemic myocardium, but it also occurs in nonischemic muscle, and glucose is presumably used for rebuilding glycogen stores that were depleted during ischemia. 
Orthotopic liver transplantation for incurable alveolar echinococcosis of the liver: report of 17 cases. Between 1986 and 1989, orthotopic liver transplantations were performed in our unit for 17 patients with incurable alveolar echinococcosis. Ten patients had hilar involvement (group I), and seven patients had posterior localization (five of them had chronic Budd-Chiari syndrome) (group II). The delay between diagnosis and the orthotopic liver transplantation was more than 48 mo in group Ia (six patients), less than 24 mo in group Ib (four patients) and less than 48 mo in group II. Previous operations were more common in group Ia than in group Ib and II. Five patients have died-four in group I and one in group II. The actuarial survival rate at 15 mo was 75%. Early reoperations were frequent (69%), mainly caused by rebleeding. Bacterial and fungal infections occurred only in group Ia (four cases) and group II (three cases). In eight patients (palliative group), residual foci of infected nonhepatic tissue occurred after surgery. The titer of specific antibodies decreased during the first 3 mo in all the patients but one. In patients with radical liver transplantation, the complete disappearance of specific antibodies occurred within 2 yr in four cases. In the remaining five patients, specific antibodies remained detectable, but no evidence of recurrence has been obtained up to now. In the palliative group, a peak of specific IgM occurred at 3 mo; an increase of specific IgG was observed later. The growth of residual parasitic foci was relatively slow, and all these patients remained asymptomatic with a mean follow-up of 19 mo. We conclude that orthotopic liver transplantation is feasible in incurable alveolar echinococcosis and could be proposed without delay to patients with parasitic Budd-Chiari syndrome or complicated secondary biliary cirrhosis. In the other cases, the best time to perform an orthotopic liver transplantation is more difficult to determine. Nevertheless, in the perspective of an orthotopic liver transplantation, the management of these patients has to change, and repetitive laparotomies for palliative surgical procedures have to be replaced by interventional radiology. 
Avoiding the blanket approach to insomnia. Targeted therapy for specific causes. A systematic approach to the common complaint of insomnia usually results in a specific clinical diagnosis with clear therapeutic implications. Use of effective treatment strategies tailored to the situation can make treating insomnia a gratifying experience instead of a frustrating one. 
Transformation of T lymphocytes by the v-fos oncogene. Activation of T lymphocytes through the T cell antigen receptor has been shown to stimulate a rapid and transient accumulation of c-fos mRNA and protein. Transfection of a normal murine T lymphocyte clone with the FBJ-v-fos oncogene resulted in generation of a cell line that was morphologically transformed, had lost the requirement for IL-2 for proliferation, and was tumorigenic in adult syngeneic mice; however, the transformed cells retained the ability to proliferate in response to IL-2. The transformed cells did not show constitutive expression of IL-2 or c-fos mRNA, although the promoter regions of both IL-2 and c-fos genes contain AP-1 sites that are expected to be targets for binding of Fos/Jun complexes. In contrast, the transformed T cells showed increased constitutive expression of IL-2R alpha and c-myc mRNA; these genes may represent cellular targets for transformation by v-fos and physiologic activation by c-fos. We discuss the possibility that these transformed cells behave as cells partially activated through the TCR, and that transformation occurs through a mechanism independent of IL-2. 
Laparoscopic cholecystectomy. Treatment of choice for symptomatic cholelithiasis. Our initial experience with laparoscopic cholecystectomy (LC) for symptomatic cholelithiasis has involved 152 patients. Patient age ranged from 17 to 83 years; most were female (78%). Their average weight was 170 pounds (range, 75 to 365 lbs.). Twenty-two per cent had a single gallstone, while 9% had two to three stones and 64% had more than three stones. Exclusion criteria initially included upper abdominal scarring, severe acute cholecystitis, choledocholithiasis, and inability to tolerate general anesthesia. The first two of these are now only relative contraindications with increased experience. Thirteen of the one hundred fifty-two procedures (8.5%) required conversion to an open operation. Average time of operation was 138 minutes. Intraoperative cholangiography was attempted in 78% of cases and was completed successfully in 66% of those attempted. There have been no deaths. The complication rate has been low: 4% major, 0% life-threatening, and 7.2% minor complications. Postoperative analgesic requirements are remarkably low: 36% of patients required no narcotics after leaving the recovery room. Eighty-seven per cent of patients successfully undergoing LC were discharged by the first postoperative day. Most patients resumed normal activities within 1 week after discharge. Laparoscopic cholecystectomy offers the majority of patients with symptomatic cholelithiasis an improved treatment option, resulting in significantly less postoperative pain, hospitalization, and recuperation time. 
Sucralfate versus antacids or H2-antagonists for stress ulcer prophylaxis: a meta-analysis on efficacy and pneumonia rate. OBJECTIVES AND METHODS: Histamine2 (H2)-receptor antagonists and antacids have been the basic drugs for the prevention of stress bleeding in ICU patients during the past decade. Recently, drugs without major influence on gastric pH have been investigated in stress bleeding prophylaxis. Therefore, a meta-analysis (Mantel-Haenszel test) was undertaken to determine the efficacy of sucralfate in the prevention of macroscopically visible stress bleeding, as well as the influence of sucralfate on the frequency of pulmonary infections. RESULTS: The efficacy of sucralfate was compared with H2-antagonists in nine studies and with antacids in eight studies. Sucralfate was significantly more effective than H2-antagonists (typical odds ratio 0.532, 95% confidence interval 0.303 to 0.933) and equally as effective as antacids (typical odds ratio 0.868, 95% confidence interval 0.452 to 1.667). The pneumonia rates of those patients who were administered sucralfate were compared with the rates of those patients who were given H2-antagonists in five studies and with those patients who were given antacids in four studies. Pneumonia was a significantly more frequent occurrence under prophylaxis with H2-antagonists (typical odds ratio 0.498, 95% confidence interval 0.316 to 0.783) as well as with antacids (typical odds ratio 0.402, 95% confidence interval 0.235 to 0.687). CONCLUSION: Sucralfate is an effective drug for the prevention of stress bleeding that minimizes the risk of nosocomial pneumonia in long-term ventilated ICU patients. 
Helicobacter pylori infection and the risk of gastric carcinoma BACKGROUND. Infection with Helicobacter pylori has been linked with chronic atrophic gastritis, an inflammatory precursor of gastric adenocarcinoma. In a nested case-control study, we explored whether H. pylori infection increases the risk of gastric carcinoma. METHODS. From a cohort of 128,992 persons followed since the mid-1960s at a health maintenance organization, 186 patients with gastric carcinoma were selected as case patients and were matched according to age, sex, and race with 186 control subjects without gastric carcinoma. Stored serum samples collected during the 1960s were tested for IgG antibodies to H. pylori by enzyme-linked immunosorbent assay. Data on cigarette use, blood group, ulcer disease, and gastric surgery were obtained from questionnaires administered at enrollment. Tissue sections and pathology reports were reviewed to confirm the histologic results. RESULTS. The mean time between serum collection and the diagnosis of gastric carcinoma was 14.2 years. Of the 109 patients with confirmed gastric adenocarcinoma (excluding tumors of the gastroesophageal junction), 84 percent had been infected previously with H. pylori, as compared with 61 percent of the matched control subjects (odds ratio, 3.6; 95 percent confidence interval, 1.8 to 7.3). Tumors of the gastroesophageal junction were not linked to H. pylori infection, nor were tumors in the gastric cardia. H. pylori was a particularly strong risk factor for stomach cancer in women (odds ratio, 18) and blacks (odds ratio, 9). A history of gastric surgery was independently associated with the development of cancer (odds ratio, 17; P = 0.03), but a history of peptic ulcer disease was negatively associated with subsequent gastric carcinoma (odds ratio, 0.2; P = 0.02). Neither blood group nor smoking history affected risk. CONCLUSIONS. Infection with H. pylori is associated with an increased risk of gastric adenocarcinoma and may be a cofactor in the pathogenesis of this malignant condition. 
Differential effects on right ventricular function of transient right, left anterior descending and left circumflex coronary occlusions during percutaneous transluminal coronary angioplasty. Right ventricular function was studied by means of a thermodilution catheter before, during and after percutaneous transluminal angioplasty of the proximal right (group 1, n = 8), left anterior descending (group 2, n = 8) or left circumflex (group 3, n = 8) coronary artery. All patients had evidence of myocardial ischemia, with single-vessel disease affecting the proximal segment of one of the three major coronary arteries; no patient had had a previous myocardial infarction and all had normal cardiac function at baseline study. Cardiac index decreased during balloon inflation. Mean pulmonary artery pressure was unaffected in group 1 but increased in group 2 (from 19 +/- 5 to 31 +/- 11 mm Hg, p less than 0.01) and in group 3 (from 19 +/- 2 to 22 +/- 5 mm Hg, p less than 0.05). Right ventricular ejection fraction decreased from 62 +/- 9% to 52 +/- 10% (p less than 0.01) in group 1 and from 64 +/- 7% to 44 +/- 10% (p less than 0.005) in group 2, and returned to normal within 2 min after balloon deflation in both groups. In group 3, right ventricular ejection fraction was unchanged during balloon inflation (58 +/- 5% at baseline, 58 +/- 9% at 60 s, p = NS). Therefore, brief occlusion of the proximal segments of the left anterior descending or right coronary artery results in marked alteration of right ventricular performance that is probably caused by right ventricular free wall ischemia in the right coronary group and by the concomitant effects of septal ischemia and increased right ventricular afterload in the left anterior descending artery group. 
The presence in experimental animals of a colon specific Mr 40,000 protein(s) with relevance to ulcerative colitis. In patients with ulcerative colitis a colon tissue bound IgG and serum antibodies against an Mr 40,000 colonic protein(s) has been identified. Using an anti-Mr 40,000 protein monoclonal antibody, 7E12H12, by an immunocytochemical method, the protein was localised in human tissue exclusively to colonic epithelial cells. In this study the presence of the Mr 40,000 protein was assessed in experimental animals by the direct and inhibition enzyme linked immunosorbent assays (ELISAs) using the anti-Mr 40,000 protein monoclonal antibody, 7E12H12 (IgM isotype). In addition, a total of 129 specimens including colon, small intestine, gall bladder, biliary tract, and kidney from nine strains of rats and mice, and from human tissue were studied by the immunocytochemical method using 7E12H12. All colon specimens from both humans and animals reacted with 7E12H12 in the immunocytochemical and ELISA assays. None of the non-colonic organs reacted with 7E12H12. While in human colon 7E12H12 recognised the absorptive epithelial cells, in all the animals it recognised mainly the colonic goblet cells. Extracts of animal colon but not of small intestine inhibited the binding of 7E12H12 to the human colon extract. This study shows the presence of an organ specific Mr 40,000 colonic epithelial protein(s) in humans and experimental animals. A differing cellular localisation of the Mr 40,000 protein(s) in human v animal tissue was also shown. Further characterisation of the Mr 40,000 protein(s) may provide important clues regarding the autoimmune mechanisms in ulcerative colitis. 
Lymphatic abnormalities in Alagille's syndrome. Chylous pleural effusions developed in a patient with Alagille's syndrome who had dysplasia of the lymphatic system. Lymphatic abnormalities are not a recognised feature of Alagille's syndrome. 
Endoscopic contact Nd:YAG laser resectional vaporization (ECLRV) and esophageal dilatation (ED) in advanced malignant obstruction of the esophagus. Malignant esophageal obstruction in patients with advanced and metastatic carcinoma is unsuitable for surgery. Palliative treatment must provide adequate swallowing with minimum complications in these often seriously ill patients. Twenty consecutive patients underwent endoscopic Nd:YAG contact laser resection and vaporization (ECLRV) and esophageal dilatation (ED) for advanced esophageal carcinoma since August, 1985. Average duration of the disease when first referred was 7.2 months. Tumor cell type was either squamous cell carcinoma (n = 11) or adenocarcinoma (n = 9). Tumor location was distal (n = 14), middle (n = 5), or upper (n = 2). Mean tumor length was 7.5 cm. Mean preoperative luminal diameter was 1 mm, with total obstruction in ten (50%) patients. The operative procedure in all patients was under general anesthesia with endotracheal tube intubation. Rigid and flexible endoscopes were both used as indicated. Mean postoperative luminal diameter was 15 mm. All but four were able to swallow fluids on the first postoperative day, followed by semisolids the next day without discomfort. Minor perforation was noted in three cases and managed in two conservatively. One more patient had difficulty in swallowing due to extra-esophageal compression, in spite of a technically successful laser therapy. Percutaneous endoscopic gastrostomy (PEG) was carried out in eight cases. Eleven patients were retreated successfully for recurrent obstruction and two were treated more than twice, at a mean of six-week intervals. Endoscopic contact laser resectional vaporization with esophageal dilatation was relatively safe and provided an improved quality of life in this preliminary study group, providing a mean survival of 18.5 weeks (range 2-50 weeks). 
Orbital lesions with granulomatous inflammation. Orbital lesions characterized by granulomatous inflammation are a heterogeneous group of diseases of various causes with a common histopathological substrate involving aggregates of epithelioid cells. Forty-one patients (27 females and 14 males) with biopsy-proven granulomatous inflammation were seen at an orbital clinic between 1978 and 1989. The mean age at presentation was 40.2 (extremes 6 and 77) years. Two main clinical presentations were noted: painless, subacute or chronic mass effect, and tender, subacute inflammatory process. Six patients had secondary features that were infiltrative in character. The lesions were primarily located in the anterior superior orbit. In nearly half the patients the granulomatous reaction was confined to the orbit (predominantly ruptured dermoid and localized orbital sarcoid), and the remainder had either regional involvement (Wegener's granulomatosis or fibro-osseous process) or systemic involvement (sarcoidosis). 
Spontaneous recovery of renal function after resection of contralateral hypernephroma. We report a case of nonfunction of an anatomically normal kidney associated with a contralateral hypernephroma. X-ray and radionuclide imaging suggested a disturbance of the contralateral renal blood flow at the microvascular level. Normal function resumed after tumor resection. The implications for management are discussed. 
Gastrointestinal transit of solid-liquid meal in chronic alcoholics. Gastric emptying, mouth-to-cecum transit, and whole-gut transit of a solid-liquid meal were measured in 46 chronic alcoholics and in 30 control subjects by using scintigraphic techniques, hydrogen breath test, and stool markers. In the alcoholics various parameters such as ethanol consumption, gastrointestinal symptoms, and alcoholic neuropathy were determined and related to gastrointestinal transit times. Although there was no significant overall difference of gastric emptying, abnormally delayed gastric emptying was detected in 23.9% of the alcoholics but no control subject (P less than 0.005). Mouth-to-cecum transit was significantly prolonged in the alcoholics (P less than 0.001) with 14 alcoholics (37.8%) disclosing delayed mouth-to-cecum transit. No significant differences between both groups were detected concerning whole gut transit. In the alcoholics there was a significant correlation of dyspeptic symptoms with delayed gastric emptying (P less than 0.006), and alcoholics with diarrhea had an accelerated mouth-to-cecum transit as compared to those without diarrhea (P less than 0.05). Neither the presence of autonomic or peripheral neuropathy nor the presence of liver cirrhosis or ascites was significantly related to gastrointestinal transit times. However, the daily ethanol ingestion significantly correlated with gastric emptying (P less than 0.005). It is concluded, therefore, that in chronic alcoholics the small intestine and the stomach are most likely to be affected by gastrointestinal transit disorders and that these transit abnormalities are potentially related to toxic damage of gastrointestinal smooth muscle. 
Treatment of accidental digital injection of epinephrine. The use of epinephrine auto-injectors for prehospital treatment of severe allergic reactions has become increasingly popular in recent years. Anxiety when patients are called on to use these spring-loaded devices may lead to complications. We present the case of a 28-year-old woman who accidentally injected epinephrine 1:1,000 solution 0.3 mL into her right index finger with an automatic epinephrine injector. The approach to the treatment of these complications has been varied in the literature, including local sympathectomy, topical nitrates, and either local or intra-arterial phentolamine. This potentially disabling case of epinephrine-induced vasospasm of digital arteries was treated successfully with local infiltration of phentolamine. 
The porcine model for the understanding of thrombogenesis and atherogenesis. The hypothesis originated by Carl Rokitansky a century ago that thrombosis contributes substantially to atherosclerosis has been rekindled by accumulating experimental and clinical evidence. On the basis of our experience with the experimental porcine model, several important biologic determinants of thrombosis have been identified. The degree of vascular injury seems to be the primary determinant of the thrombotic response. In addition, hemodynamic shear stress and the presence of the von Willebrand factor have important roles in the process of thrombosis. Although there is little evidence that thrombosis is a factor in the initiation of spontaneous, or naturally occurring, atherosclerosis, substantial evidence suggests that thrombosis has an essential role in the progression of spontaneous atherosclerosis and also in the early pathogenic process of the syndromes of accelerated atherosclerosis-namely, heart transplant atherosclerosis, vein graft disease, and coronary restenosis after angioplasty. Advances in the understanding of vascular injury and of the interactions of blood cells with the vascular wall have allowed development of new experimental antithrombotic strategies and subsequent clinical applications in the prevention of these vascular diseases. 
Complex ventricular ectopic activity in patients less than 20 years of age with or without syncope, and the role of ventricular extrastimulus testing. To assess the potential for ventricular tachycardia (VT), ventricular extrastimulus testing was performed in 33 young patients with complex ventricular ectopic activity defined as multiform ventricular premature complexes (VPCs), couplets or nonsustained VT, or a combination, found during electrocardiographic monitoring. There were 21 male and 12 female patients with a mean age of 11 years (range 1 to 18). Patients were divided into 2 groups based on the presence (14 patients) or absence (19 patients) of syncope. Patients with syncope had ostensibly normal hearts (9 patients) or miscellaneous heart disease (5 patients). Patients without syncope had ostensibly normal hearts (8 patients) or miscellaneous heart disease (11 patients). Ventricular stimulation protocol consisted of burst pacing and 1 to 4 programmed extrastimuli decreasing to refractoriness at 3 drive-train cycle lengths, and at 2 pacing sites (right ventricular apex and outflow tract) during the drug-free baseline state and isoproterenol infusion. No patient had VT induced with 1 or 2 extrastimuli. VT was induced in 13 of 14 patients (93%) with syncope, and in 9 of 19 patients (47%) without syncope (p less than 0.05). Using a 3-extrastimuli protocol, 8 of 14 patients (57%) with and 3 of 19 patients (16%) without syncope had VT induced (p less than 0.05). These findings suggest that VT may be the cause of syncope in young patients with complex ventricular ectopic activity. 
Clinical benefits of structural and functional changes with calcium antagonists. Calcium antagonists have a large variety of pharmacologic effects in addition to those exploited clinically. All drugs used in the management of hypertension, including calcium antagonists, are coming under increasing scrutiny for the possible beneficial and adverse effects they may have on the circulation and risk factor profile. This is particularly because of concern about the relative resistance of coronary heart disease to antihypertensive drug treatment and the increasing interest in evaluating the impact of blood pressure-lowering drugs on surrogate endpoints such as left ventricular hypertrophy. Given the pharmacokinetic and pharmacodynamic heterogeneity of calcium antagonists, it may be wise to keep in mind the subtypes as exemplified by the prototypes nifedipine, diltiazem, and verapamil and to extrapolate from one type to another with great caution. The increased understanding of the diversity among calcium antagonists as well as the pathophysiology of hypertension and other vascular diseases promises an exciting future for calcium antagonists in cardiovascular therapeutics. 
Risk of peritonitis and fatal septicaemia and the need to defunction the low anastomosis. The aim of this study was to investigate the need to defunction the low anastomosis after anterior resection of the rectum with total mesorectal excision for rectal cancer. Two hundred consecutive patients (125 defunctioned, 75 non-defunctioned) undergoing low anterior resection for carcinoma were included in the study. Peritonitis requiring emergency laparotomy occurred in 8 per cent of the patients who did not have a defunctioning stoma compared with less than 1 per cent of those patients who had a defunctioning stoma (P less than 0.01). There was no mortality related to closure of the stoma but seven patients developed a faecal fistula and ten developed an incisional hernia. Despite current trends to avoid the defunctioning stoma, these results suggest that after total mesorectal excision the faecal stream should be temporarily diverted away from the anastomosis that is 6 cm or less from the anal verge to protect against potentially life-threatening anastomotic leakage. 
Acute and sustained changes in sodium balance during nifedipine treatment in essential hypertension. PURPOSE: To assess the changes in sodium excretion and sodium balance after initiation of nifedipine treatment and after withdrawal of nifedipine. PATIENTS: Eight patients with uncomplicated mild to moderate essential hypertension were entered in a single-blind, placebo-controlled study of 39 days' duration. METHODS: Two 7-day periods while on a fixed sodium intake of 150 mmol/day approximately 3 weeks apart. After 4 days of a placebo and fixed sodium intake, patients were given nifedipine GITS (gastrointestinal therapeutic system) once a day and carefully studied for the following 4 days. Thereafter, patients continued to receive nifedipine GITS, and approximately 3 weeks later they were studied again for a week while on a fixed sodium intake. Nifedipine administration was stopped and changes occurring after withdrawal were studied. RESULTS: Nifedipine caused a significant increase in sodium excretion with a cumulative loss of sodium of 38 mmol per subject within the first 4 days of treatment. The withdrawal of nifedipine treatment caused a significant decrease in sodium excretion and a cumulative retention of sodium of 42 mmol per subject within the first 4 days of withdrawal. CONCLUSION: Nifedipine causes an acute and a sustained reduction in sodium balance in patients with essential hypertension. This prolonged effect may contribute to the mechanism whereby nifedipine lowers blood pressure. 
The interaction of proinsulin with the insulin-like growth factor-I receptor in human liver, muscle, and adipose tissue. Because of the sequence homology and tertiary structure similarities between proinsulin (PI) and insulin-like growth factor-I (IGF-I), it is possible that PI interacts with the IGF-I receptor with higher affinity than insulin. To test this hypothesis in man, we have partially purified IGF-I receptors from liver, muscle, and adipose tissue and studied their interaction with PI, insulin, IGF-I, and IGF-II. With some tissue to tissue variation, [125I]insulin binding was 4- to 8-fold greater than IGF-I binding. Unlabeled IGF-I at about 1 x 10(-9 M, IGF-II at about 1 x 10(-8) M, and insulin at about 1 x 10(-6) M displace 50% the binding of [125I]IGF-I to its receptor, whereas PI at 1 x 10(-6) M displaces less than 20% of the binding of [125I]IGF-I to its receptor. We conclude that in human liver, muscle, and adipose tissue, PI does not interact with the IGF-I receptor at a higher affinity than insulin, and the affinity of IGF-I receptors is several-fold lower than that of insulin receptors. It is, therefore, unlikely that if PI were to be administered to man any of its biological effects would be by interacting with the IGF-I receptor. 
The yield of barium enema in patients undergoing inguinal hernia repair or abdominal hysterectomy. It is the practice of some gynecologists and general surgeons to preoperatively evaluate the colon with a barium enema (BE) examination to exclude potential intestinal involvement or coexistent disease in patients undergoing pelvic or hernia operations. This practice appears to be based on anecdotal data with few studies specifically evaluating its usefulness. We retrospectively evaluated the records of 190 patients at William Beaumont Army Medical Center during 1986 to 1987 who received a preoperative BE prior to total abdominal hysterectomy (TAH) or inguinal hernia repair (IHR). The tumor registry charts of 59 patients diagnosed with carcinoma of the colon and rectum during the same period were also cross-checked to determine if any were detected during preoperative evaluation for TAH or IHR. BE findings were considered significant if they altered surgical management or asymptomatic carcinoma was detected. Of 86 patients screened before TAH by BE, eight had abnormal findings with subsequent colonoscopy revealing four with adenomatous polyps, one of which required surgical resection. Of 104 patients screened before IHR by BE, 15 had abnormal findings with subsequent colonoscopy revealing five patients with adenomatous polyps and two with adenocarcinoma. Screening preoperative BE had a low yield of clinically significant findings, which was even lower in the subgroup with carcinoma. There was no apparent relationship between findings and age in our study. Our results suggest that the use of routine preoperative BE has a low yield and should be performed only if clinical symptoms or findings suggest a need for this study. 
Does tremor pace repetitive voluntary motor behavior in Parkinson's disease? In patients with Parkinson's disease and in normal subjects, the influence of tremor on repetitive voluntary movement was investigated in the index finger by comparing frequency of isometric force tremor with frequency of voluntary alternating isometric contractions. Tremor frequency, measured over the range from 0 to 70% maximum voluntary force, usually increased with force. The tremor frequency band was lower and more often overlapped with the upper voluntary frequency range in patients than in normal subjects. Normal subjects could accurately produce voluntary contractions at all cue frequencies from 1 to 5 Hz. Patients could produce auditory-paced frequencies of 1 and 2 Hz, but at higher cue frequencies, their voluntary contractions were often faster or slower than the cue. The faster or "hastened" voluntary frequencies were within the tremor frequency band, whereas the slowed voluntary frequencies were below it. Maximal voluntary frequency was often greater than the lowest but always less than the highest tremor frequency. It is concluded that parkinsonian tremor may pace voluntary repetitive movements to go faster than intended with the highest tremor frequency being an upper limit for voluntary frequency. Similar mechanisms may underlie the hastened repetitive vocal responses that were also observed in the parkinsonian patients. 
Serum alpha-L-fucosidase. A more sensitive marker for hepatocellular carcinoma? Forty-nine liver disease patients (7 chronic persistent hepatitis, CPH; 10 chronic active hepatitis, CAH; 13 liver cirrhosis, LC; 9 primary hepatocellular carcinoma, PHC, without LC; and 10 PHC with associated LC) and 20 controls were assessed for their serum alpha-L-fucosidase (ALF) and alpha-fetoprotein (AFP) levels and several routine liver injury parameters. Tumor diameter in those with hepatic cancer was assessed by angio-CT. Only ALF and AFP were significantly greater in patients with PHC and PHC + LC patients as compared to patients with LC alone. At an accepted cutoff level of 500 ng/ml, the AFP level provided 43% false negative tests. On the other hand, an ALF level exceeding 740 mumol/hr/ml provided a sensitivity of 84% with a specificity of 94%. No relationship between the ALF level and Child's criteria or with any liver injury parameter was evident. Considering all individual values, the ALF, rather than the AFP, correlated with tumor size. This finding suggests the ALF level may be of value in the early detection of PHC as well as in the follow-up of patients treated for PHC. 
Postoperative protein metabolism: effect of nursing elderly patients for 24 h after abdominal surgery in a thermoneutral environment. We have studied the effect of intraoperative body heat conservation and 24-h thermoneutrality on postoperative whole body protein turnover using stable isotope methodology in a group of elderly patients undergoing colorectal surgery for rectosigmoid adenocarcinoma. Two groups of eight patients were studied. One group (control, or cold) received routine intraoperative and postoperative care. All patients in the second group (warmed) were maintained at normothermia during anaesthesia and surgery; these patients were nursed after surgery in a warm room (ambient temperature 28-30 degrees C) for a period of 24 h. General anaesthesia, surgical care and nutritional support were similar in both groups. A constant nutritional intake, based on nitrogen 0.1 g kg-1 day-1 and energy 20 kcal kg-1 day-1, was provided orally for 7 days before surgery and i.v. after operation for 4 consecutive days. Whole body protein breakdown and synthesis, as assessed by stable isotope methodology, increased significantly 2 and 4 days after surgery in both groups (P less than 0.01), but the increase in protein breakdown in the warmed group on day 2 was significantly less than that in the cold group (P less than 0.05). The increase in leucine oxidation in the warmed group on the 2nd day after surgery was not significant, and was less than the increase observed in the cold group (P less than 0.05). However, by the 4th day, leucine oxidation was enhanced significantly in both groups (P less than 0.01). 
Nasal haemangiopericytoma. Haemangiopericytoma is an uncommon vascular tumour frequently diagnosed with difficulty. The immunohistochemical findings of strong positivity to vimentin together with other diagnostic features (histological and ultrastructural) improves the certainty of its diagnosis. We report a case arising in the nose and outline diagnostic problems especially relating to histopathology. 
Elevated intraoperative blood carboxyhemoglobin levels in surgical patients--Georgia, Illinois, and North Carolina. In October 1990, three hospitals, one each in Georgia, Illinois, and North Carolina, reported 26 episodes of elevated blood carboxyhemoglobin (COHb) levels (normal: less than 3% in a nonsmoker, less than 10% in a smoker) during surgery in patients with no known carbon monoxide (CO) exposure. All three hospitals are large, medical-school-affiliated, training institutions. Hospital A (Georgia) reported 15 episodes from January 1987 through September 1989; hospital B (North Carolina), eight episodes from January through October 1990; and hospital C (Illinois), three episodes from January through September 1990. All of the episodes were detected during routine blood gas analyses that included COHb measurements (co-oximetry). In eight episodes, peak COHb levels were greater than 20%. Usually, when an elevated COHb level was detected intraoperatively, 100% oxygen was administered, an alternate gas source was instituted, and COHb levels returned to normal. No deaths or serious complications were reported. 
Neurotrophic protein S100 beta stimulates glial cell proliferation. Nervous system development involves a coordinated series of events, including regulation of cell proliferation and differentiation by specific extracellular factors. S100 beta is a neurotrophic protein that has been implicated in regulation of cellular proliferation, but direct evidence was lacking. In this report, nanomolar concentrations of S100 beta are shown to stimulate proliferation of rat C6 glioma cells and primary astrocytes. An S100 mutant with a single amino acid change was inactive. S100 beta also stimulated increases in the steady-state levels of c-myc and c-fos protooncogene mRNAs and complemented the effects of platelet-derived growth factor. Two neuroblastoma cell lines did not proliferate in response to S100 beta, suggesting that the mitogenic activity of S100 beta is selective for astroglial cells. These results suggest that S100 beta may be involved in the coordinate development and maintenance of the central nervous system by synchronously stimulating the differentiation of neurons and the proliferation of astroglia. 
Overnight studies in severe chronic left heart failure: arrhythmias and oxygen desaturation. Overnight studies were performed in 10 patients with severe chronic left heart failure (New York Heart Association grades III and IV) without pulmonary disease and in eight controls. Transcutaneous oxygen (Po2) and carbon dioxide tensions (Pco2) and oxygen saturation were measured and the electro-cardiogram was recorded. During sleep mean oxygen saturation fell to 92.7% (minimum 86.1%) from 95.1% when awake. During the night oxygen saturation was below 95% for 62% of the time, below 90% for 6% of the time, and below 85% for 1% of the time. In four patients there were oxygen desaturation dips (a fall of greater than 4% in oxygen saturation from a stable baseline that lasted greater than 30 s) with concurrent increases in Pco2. Two patients had bradycardia during the dips: in one there was non-sustained ventricular tachycardia during the dips and in the other there was ST depression (greater than 0.1 mV at 80 ms after the J point) during a dip. In the controls the fall in mean oxygen saturation from 95.4% when they were awake to 94.4% when they were asleep was less than the fall in patients with heart failure and there were no desaturation dips or arrhythmias. Thus patients with severe heart failure had episodes of oxygen desaturation during sleep, some of which were associated with arrhythmia. Such episodes may be related to the increased risk of sudden death in chronic heart failure. 
Phase I trial of tissue plasminogen activator for the prevention of vasospasm in patients with aneurysmal subarachnoid hemorrhage. Recent laboratory studies have demonstrated that intracisternal administration of recombinant tissue plasminogen activator (rt-PA) can facilitate the normal clearing of blood from the subarachnoid space and prevent or ameliorate delayed arterial spasm. The results of a preliminary Phase I trial of intracisternal rt-PA in 10 patients are reported with documented aneurysmal subarachnoid hemorrhage (SAH). All patients enrolled were classified as clinical Grade III or IV (according to Hunt and Hess) with thick clots or layers of blood in the basal cisterns and major cerebral fissures (Fisher Grade 3). Ventriculostomy and surgery for clipping of the aneurysms were performed within 48 hours of hemorrhage. In one patient, 10 mg rt-PA was instilled into the subarachnoid cisterns prior to closing the dura. In the remaining nine patients, a small silicone catheter was left in the subarachnoid space and rt-PA (5 mg in four cases or 1.5 mg (0.5 mg every 8 hours for three infusions) in five cases) was instilled 12 to 24 hours after surgery. Minor local bleeding complications were noted in all patients receiving 5 or 10 mg rt-PA. Oozing was noted at the operative incision site in four of five patients and at the ventriculostomy site in two patients. One patient developed a small epidural hematoma that was treated by delayed drainage. No bleeding complications were noted in the patients receiving the lower regimen of rt-PA (three infusions of 0.5 mg each). Serial coagulation studies demonstrated no evidence of systemic fibrinolysis. Analysis of cisternal cerebrospinal fluid samples revealed thrombolytic tissue plasminogen activator (t-PA) levels for 24 to 48 hours. Follow-up cerebral angiography 7 to 8 days after rupture disclosed mild to moderate spasm in nine patients, while one patient with hemorrhage from a posterior inferior cerebellar artery aneurysm had severe focal spasm of the vertebral arteries that was not symptomatic. These results suggest that postoperative treatment with rt-PA may be effective in reducing the severity of delayed cerebral vasospasm. The results of serial t-PA levels suggest that the lower dosage regimen with divided dosages at 8-hour intervals is well tolerated and that even lower dosages may be effective. Further studies are clearly indicated. 
The long distance effects of brain lesions: visualization of axonal pathways and their terminations in the human brain by the Nauta method. This study aims at determining the reliability and the optimal post-injury survival time for the application of the Nauta technique to the analysis of the human brain. The Nauta method reveals the degeneration not only of nerve fibers, myelinated and unmyelinated, but also of their terminations. Immunohistochemical and ultrastructural observations appear to prove that the Nauta technique indeed stains axons in human autopsy material. The optimal survival time for the use of the Nauta method was found to be between nine days and five months. In cases with longer survival times--up to 20 months--the Nauta technique and a previously proposed polarizing technique (showing birefringent breakdown products of myelin) can be used as complementary methods. Applying these techniques to the human brain may help define the anatomical basis of neurological and neuropsychological symptoms important for man. 
Brain natriuretic peptide as a novel cardiac hormone in humans. Evidence for an exquisite dual natriuretic peptide system, atrial natriuretic peptide and brain natriuretic peptide. Using a specific radioimmunoassay for human brain natriuretic peptide (hBNP) with a monoclonal antibody, we have investigated its synthesis, secretion, and clearance in comparison with those of atrial natriuretic peptide (ANP) in normal subjects and patients with congestive heart failure (CHF). Mean BNP-like immunoreactivity (-LI) levels in normal atrium and ventricle were 250 and 18 pmol/g, respectively. The plasma BNP-LI level in normal subjects was 0.90 +/- 0.07 fmol/ml, which was 16% of the ANP-LI level. In contrast, the plasma BNP-LI level markedly increased in patients with CHF in proportion to its severity, and surpassed the ANP-LI level in severe cases. There was a significant step-up of the plasma BNP-LI level in the coronary sinus (CS) compared with that in the aortic root (Ao) and the difference between these BNP-LI levels, delta(CS-Ao)BNP, also increased with the severity of CHF. In addition, the step-up of the BNP-LI level in the anterior interventricular vein [delta(AIV-Ao)BNP] was comparable to delta(CS-Ao)BNP, indicating that BNP is secreted mainly from the ventricle. Predominant BNP synthesis in the ventricle was also confirmed by Northern blot analysis. Catheterization and pharmacokinetic studies revealed that hBNP is cleared from the circulation more slowly than alpha-hANP; this was in part attributed to lower (about 7%) binding affinity of hBNP to clearance receptors than that of alpha-hANP. A predominant molecular form of BNP-LI in the heart and plasma was a 3-kD form corresponding to hBNP. These results indicate that BNP is a novel cardiac hormone secreted predominantly from the ventricle, and that the synthesis, secretion and clearance of BNP differ from those of ANP, suggesting discrete physiological and pathophysiological roles of BNP in a dual natriuretic peptide system. 
A pair of monozygotic twins who are concordant for myasthenia gravis but became discordant for systemic lupus erythematosus post-thymectomy. We describe a pair of monozygotic twins who are concordant for myasthenia gravis but discordant for systemic lupus erythematosus (SLE). SLE developed in twin 1 18 years post-thymectomy and has been characterized by recurrent transverse myelitis and optic neuritis. Twin 2 remains well post-thymectomy, except for a skin rash and persistent leukopenia. Both twins have developed autoimmune thyroid disease. We review genetic and environmental factors of importance in the pathogenesis of SLE and discuss the possible role of thymectomy in the etiology of the disease. 
Incidence of pneumonia in mechanically ventilated patients treated with sucralfate or cimetidine as prophylaxis for stress bleeding: bacterial colonization of the stomach. Retrograde colonization of the oropharynx from the stomach by microaspiration of gastric fluid is a recently recognized phenomenon associated with increased gastric pH that may result in pneumonia during ventilation therapy. In a prospective study we investigated 104 mechanically ventilated patients in the intensive care unit who were receiving sucralfate (n = 49) or cimetidine (n = 55) for stress ulcer prophylaxis. The incidence of pneumonia was 45.5% (25 patients) in the cimetidine group and 26.5% (13 patients) in the sucralfate group (95% confidence interval 0.98 to 6.97; odds ratio 2.61; p = 0.0549). Mortality rates were 18.4% (9 patients) in the sucralfate group versus 25.5% (14 patients) in the cimetidine group (p = 0.48). The mean pH values of gastric aspirates were significantly lower in patients treated with sucralfate than in patients receiving cimetidine (p = 0.044). The number of colony-forming units of Enterobacteriaceae in gastric aspirates was also significantly lower in the sucralfate group (p = 0.0037). 
A randomized trial of a single bolus dosage regimen of recombinant tissue plasminogen activator in patients with acute pulmonary embolism. Experiments in animals have demonstrated that recombinant tissue plasminogen activator (rt-PA) produces continuing thrombolysis after it is cleared from the circulation and that thrombolysis is both increased and accelerated, and bleeding is reduced when rt-PA is administered over a short period. In previous studies in patients with thrombotic disease, rt-PA has been shown to be an effective thrombolytic agent when administered by continuous infusion over a period between 90 minutes and 8 hours. To determine whether a short course regimen of rt-PA can achieve thrombolysis, a double-blind randomized trial has been conducted in which patients with objectively established acute symptomatic pulmonary embolism who were receiving heparin were allocated to either a 2-minute infusion of rt-PA at a dose of 0.6 mg/kg (33 patients) or saline placebo (25 patients). Perfusion lung scanning was used to assess the change in pulmonary perfusion at 24 hours and seven days post-study drug administration. Thirty-four percent of the rt-PA patients had a greater than 50 percent resolution in the perfusion defect at 24 hours compared to 12 percent of placebo patients (p = 0.026). At 24 hours, the mean relative improvement in the perfusion defect was 37.0 percent in rt-PA treated patients compared to 18.8 percent in the placebo group (p = 0.017). By day 7, no difference in lung scan resolution was detected between the groups. There were no major bleeds in either group nor were there any differences in transfusion requirements between groups. Minor bleeding occurred in 15 of the rt-PA patients mainly at angiogram-catheter insertion and venipuncture sites. These results suggest that a bolus regimen of rt-PA produces accelerated thrombolysis and provides an alternative and convenient approach to thrombolytic therapy in patients with pulmonary embolism. 
Endoscopic surgery for lacrimal obstruction. Intranasal access to the lacrimal drainage system has been greatly enhanced with the advent of endoscopic nasal surgery. This technique has been used for the treatment of recurrent lacrimal obstruction after failed external dacryocystorhinostomy (DCR) in 12 patients. Improved intranasal visualization with the endoscope allowed easy identification and opening of the lacrimal sac, with no need for a skin incision. Obstructing intranasal pathology, including adhesions from previous DCR, an enlarged middle turbinate, and ethmoid sinus disease, was readily identified and corrected. There were no intraoperative complications. Lacrimal obstruction was completely relieved in nine of 12 patients (75%), with a followup of 7 to 25 months. Endoscopic revision DCR should be considered in patients with recurrent epiphora after external DCR. 
Composition of atherosclerotic plaques in the four major epicardial coronary arteries in patients greater than or equal to 90 years of age. The composition of atherosclerotic plaques in 733 five-mm segments of the 4 major (left main, left anterior descending, left circumflex and right) epicardial coronary arteries of 18 patients greater than or equal to 90 years of age was determined by computerized planimetric analysis. By analysis of all coronary segments of all patients greater than 90, the plaques consisted primarily of fibrous tissue (87 +/- 8%) with calcific deposits (7 +/- 6%), pultaceous debris (5 +/- 4%) and foam cells (1 +/- 1%) occupying a much smaller percentage of plaque area. Analysis of composition according to the 4 degrees of luminal cross-sectional area narrowing revealed marked step-wise increases in pultaceous debris (from 0 +/- 0% at 0 to 25% narrowing to 18 +/- 22% at 76 to 100% narrowing, p = 0.0001) and calcific deposits (from 0 +/- 0 to 10 +/- 15%, p = 0.002), and decreases in fibrous tissue (from 99 +/- 3 to 71 +/- 23%, p = 0.0001) and area occupied by the media (from 35 +/- 8 to 16 +/- 8%, p = 0.0001). When the analysis was restricted to sections narrowed greater than 75%, no significant differences were found in plaque components or medial area between patients with (11 patients) and without (7 patients) myocardial infarcts at necropsy. 
Adenosquamous carcinoma of the pancreas: a clinicopathologic study. A total of eight patients with adenosquamous carcinoma of the pancreas were studied clinicopathologically. Histochemical and immunohistochemical studies were also done. The 8 patients were composed of 4 men and 4 women with a mean age of 56 years, which was 9 years younger than for other pancreatic carcinoma. The site of origin and size of the tumors were similar to those of usual pancreatic carcinoma. Histopathologically, all eight tumors showed an abrupt transition between adenocarcinoma and squamous cell carcinoma. Squamous cell carcinoma was located at the periphery of the tumors. Histochemistry and immunohistochemistry disclosed a different nature for both components. The cumulative 1-year survival rate of the 8 patients was 21.4%, compared to 42.1% of 72 with adenocarcinoma of the pancreas. The survival curve of the 8 patients with adenosquamous carcinoma was significantly less favorable than that of 36 patients with well-differentiated adenocarcinoma of the pancreas. These facts support the view that squamous cell carcinoma in adenosquamous carcinoma of the pancreas is squamous cell metaplasia of the pre-existing adenocarcinoma. The clinical course of adenosquamous carcinoma of the pancreas was unfavorable. 
Unexplained chest pain and breathlessness. Complaints of chest pain and breathlessness are common in both primary care and medical outpatient settings. A subgroup of these patients who find their way into tertiary care settings and subsequently are found to have no relevant organic pathology are at risk of continuing morbidity. One possible reason for this is that diagnostic strategies often focus on establishing an organic cause of pain and ignore psychosocial factors. In this article I have attempted to describe not only the prevalence but also the clinical characteristics of patients with medically unexplained cardiorespiratory symptoms. A method of establishing a positive diagnosis of noncardiac chest pain has also been outlined. This is based on an interactive and overlapping model that takes into account not only a number of psychological and social factors but also current physical and cardiac risk factors. It is important for nonpsychiatric physicians to diagnose noncardiac pain at an earlier stage in the evolution of the disorder. This would have major beneficial effects for patients, including (1) fewer unnecessary investigations; (2) less distress and functional disability; (3) reduced cost to the hospital; and (4) fewer iatrogenic complications. 
Trial of flecainide acetate in the management of tinnitus. A two-phase trial of flecainide acetate in the management of tinnitus has been carried out in 22 patients with severe long-term tinnitus resistant to other treatments. Although 5 (23%) patients reported some limited benefit the results are not conclusive but suggest that, for such patients, flecainide deserves a place as a drug worth considering as a last resort, with the prospect of it occasionally giving a worthwhile degree of relief. 
Primary Raynaud's phenomenon in early childhood. Three young children, aged 17 months, 26 months and 29 months, presented with primary Raynaud's phenomenon. One was treated with nifedipine. Raynaud's phenomenon is rare in children and as a result experience in its treatment limited. Previously reported cases of childhood Raynaud's are reviewed, and approaches to management discussed. 
Six-year follow-up of early physiotherapy intervention in very low birth weight infants. Eighty very low birth weight infants assigned to neurologically normal or at-risk groups on the basis of a neurodevelopmental score were previously described. Infants were assigned to physiotherapy or control groups, and the effect of physiotherapy was assessed at 1 year. At-risk infants had a significantly lower developmental quotient than the normal group and no beneficial effect of physiotherapy was shown. Of the original 80 subjects, 49 were reassessed at a mean age of 74.7 months. As observed previously, physiotherapy until 1 year did not influence subsequent outcome in either normal or at-risk children. At-risk and normal children had similar mean developmental quotients at 6 years, but the locomotor score of at-risk children was significantly below that of normal children. Cerebral palsy occurred in 6 of 24 at-risk vs 0 of 25 normal subjects (P less than .01) and remedial therapy was recommended in 17 of 24 at-risk subjects vs 6 of 25 normal subjects (P less than .001). These results confirm that the neurodevelopmental score predicts a risk for either cerebral palsy or soft neurological problems, and early physiotherapy is of questionable benefit in preventing such problems. 
Dextran-70 versus albumin as plasma expanders in cirrhotic patients with tense ascites treated with total paracentesis. Results of a randomized study To investigate whether albumin can be substituted by less expensive plasma expanders in cirrhotic patients with tense ascites treated with total paracentesis, 88 patients (16 with renal failure) submitted to this therapeutic procedure were randomly assigned to receive IV albumin (43 patients) or dextran-70. Both substances were given at a dose of 8 g/L of ascitic fluid removed. Patients were discharged from the hospital with diuretics, and cases developing tense ascites during follow-up were treated according to their initial schedule. Total paracentesis was effective in eliminating the ascites in all but two cases in each group. Neither paracentesis plus IV albumin infusion nor paracentesis plus IV dextran-70 infusion was associated with significant changes in renal and hepatic function or serum electrolytes. The incidence of renal impairment (one case in each group), hyponatremia (three and four cases, respectively), and other complications (hepatic encephalopathy, gastrointestinal hemorrhage, bacterial infections) after paracentesis, and the clinical course of the disease as estimated by the probability of readmission to hospital during follow-up, causes of readmission, probability of survival, and causes of death were similar in the two groups of patients. The effect of paracentesis on effective intravascular volume was indirectly assessed by measuring plasma renin activity and aldosterone concentration before and 2 and 6 days after treatment, the patients being without diuretics. In patients treated with albumin, no significant changes in renin and aldosterone were observed during the entire period of observation. In contrast, both parameters increased significantly on the 6th day of treatment in patients receiving dextran-70. A significant increase in plasma renin activity and aldosterone concentration (30% over baseline values) was observed in 51% of patients treated with dextran-70 and in only 15% of those treated with albumin (x2 = 10.4; P = 0.0012). These results indicate that although dextran-70 is less efficacious than albumin in protecting cirrhotic patients treated with total paracentesis from the decrease in effective intravascular volume, it appears to be capable of preventing the renal and electrolyte complications induced by this therapeutic procedure. 
Diarrhea in children newly enrolled in day-care centers in Houston. Diarrhea is a common illness among children in day-care centers (DCC). We hypothesized that the incidence of diarrhea was greater among children in their first 1 or 2 months after enrollment in a DCC than in any subsequent period in day care. We followed 442 children younger than 2 years of age enrolled in 13 randomly selected DCCs for the occurrence of diarrhea during a 14 1/2-month period. Parents completed standardized baseline questionnaires and research nurses visited the DCC twice weekly to record the occurrence of diarrhea and to collect stool specimens. Incidence rates, rate ratios, chi square statistics and 95% confidence intervals were calculated for crude and stratified analyses. The diarrheal incidence rate of 4.4 cases/child-year in the first 4 weeks in the centers was significantly (rate ratio, 1.6; confidence interval, 1.3 to 2.1; P less than 0.01) higher than the 2.7 cases/child-year incidence rate of diarrhea in subsequent weeks. The effects of gender, ethnicity, age, DCC size, previous DCC attendance and season were examined and did not account for the association observed between recent enrollement and risk of diarrheal illness. Rotavirus was identified in 18% of cases of diarrhea, but no association was seen with recent enrollment in DCC. A significantly higher incidence of diarrhea occurred in males compared with females (P less than 0.002) and in younger children (P less than 0.001) compared with older children. Diarrhea is common in children in DCCs and occurs significantly more frequently in children during their first 4 weeks in a DCC. 
The influence of zinc status and malnutrition on immunological function in Crohn's disease. Cellular immunity is likely to be important in the pathogenesis of Crohn's disease; whether it is abnormal is not clear. The heterogeneity of patients with Crohn's disease probably underlies the disparity of reports, but attempts to determine which clinical features influence cellular immunity have been largely unsuccessful. This is probably caused by the omission of nutritional status as a potential factor, even though zinc deficiency has frequently been linked with abnormal immunity. Therefore, a detailed study of nutritional and tissue zinc status, nonspecific cellular immunity, and a measure of phagocytic function was performed in 32 patients with Crohn's disease and in a control group of 18 normal subjects and 12 patients with anorexia nervosa. Fourteen patients with Crohn's disease, all patients with anorexia nervosa, but none of the normal controls were malnourished. Peripheral blood lymphocyte population levels were normal in patients with Crohn's disease and in normal controls, but there was a small decrease in the levels of patients with anorexia nervosa. In vivo delayed hypersensitivity skin test responses were profoundly depressed in patients with anorexia nervosa and decreased in patients with Crohn's disease who were malnourished or receiving systemic glucocorticoids. In vitro lymphocyte transformation was reduced in malnourished patients with Crohn's disease, but there were only minor changes in patients with anorexia nervosa. There were alterations of in vitro immunoregulation in Crohn's disease, but they were not responsible for the abnormal lymphocyte transformation responses in malnourished patients. In vitro phagocytic function was reduced in patients with active Crohn's disease. These findings suggest that depressed in vivo and in vitro cellular immunity in malnourished patients with Crohn's disease is caused by a qualitative lymphocyte defect and that depressed in vivo but normal in vitro cellular immunity in anorexia nervosa is caused by a quantitative defect. Thus, malnutrition in Crohn's disease resembles kwashiorkor; in anorexia nervosa, it resembles marasmus. Tissue zinc status was mostly normal in Crohn's disease and anorexia nervosa, and zinc deficiency was not responsible for depressed nonspecific cellular immunity in either condition. 
Prealbumin in the diagnosis of bronchopulmonary carcinoid tumours. The reliability of prealbumin as a diagnostic marker was studied in 60 cases of bronchopulmonary carcinoid tumours. There were differences in the incidence of positivity between typical and atypical carcinoids (well differentiated neuroendocrine carcinomas). Seventy five per cent of the carcinoid tumours were positive for prealbumin; (86.7% typical and 63.3% atypical carcinoids). In 15 cases, which were Grimelius negative, 10 were prealbumin positive. Only 8.3% carcinoids were negative with both prealbumin and Grimelius stains. Ten squamous, 10 adeno- and 10 small cell carcinomas showed only occasional scattered prealbumin positive cells. It is concluded that prealbumin is a useful marker for bronchopulmonary carcinoid tumours. It is cheap, readily available, and should be considered part of routine diagnostic procedures for the diagnosis of carcinoid tumours. 
Hemifacial spasm in an infant due to fourth ventricular ganglioglioma. Case report. The case of an infant is reported in which hemifacial spasm due to a ganglioglioma of the fourth ventricle was relieved by surgery. Previously described causes of hemifacial spasm are summarized, and the relevance of this case to theories on the pathogenesis of the condition is discussed. 
Economies of scale, physician volume for urology patients, and DRG prospective hospital payment system. Diagnosis Related Group (DRG) hospital payment has begun to squeeze hospitals financially and is likely to do so in the future. This study analyzed the relationship between the volume of urologic procedures by an individual urologist, hospital costs per patient, and outcome. We used a three-year DRG database of urology patients (N = 2,980) at an academic medical center to analyze these. Low-volume urologists (arbitrarily defined by us) had higher hospital costs per patient, financial losses versus profits under DRGs, and a poorer outcome when compared with high-volume urologists. Pearson correlation showed a positive relationship between cost per patient and physician volume for nonemergency patients (-0.129, p less than 0.0001) and emergency patients (-0.368, p less than 0.0001). This may have been explained (in part) by a greater severity of illness for patients of low-volume urologists. These findings suggest, however, that the volume of urologic procedures per urologist may be related to hospital resource consumption. The health care financing environment of the future should provide substantial interest in this finding for those involved in the consumption of urologic services. 
Cerebrospinal fluid tumour markers in patients treated for meningeal malignancy. The results of cerebrospinal fluid (CSF) biochemical markers were compared with conventional CSF cytology in patients treated for leptomeningeal metastases from extra cranial malignancies. For lumbar CSF, before treatment, no statistically significant difference of the probabilities of being positive was found between CSF cytology and a classification by linear discriminant analysis, based on patient's age, of beta-glucuronidase and beta 2-microglobulin. During treatment, classification by linear discriminant analysis was found more often positive than cytology. Possible mechanisms for this difference are discussed. For ventricular CSF a correlation was found between CSF cytology and beta-glucuronidase for solid tumours, and between CSF cytology and beta 2-microglobulin for haematological malignancies. Reference values for ventricular protein, CEA beta-glucuronidase and beta 2-microglobulin were obtained for cytological negative samples. 
Blood pressure dysregulation associated with alcohol withdrawal. Alcoholics' blood pressures (BP) are typically elevated during withdrawal. Do such elevations predict future blood pressure dysregulation or are they simply a transitory effect of alcohol toxicity? Thirty-two patients admitted to the hospital for alcohol detoxification were tested to examine the relationship between admission BP and response to isometric handgrip administered 4 to 5 days (session 1) and 3 to 4 weeks (session 2) postdetoxification. Alcoholics were divided into three groups based on admission BPs: Hypertensive (HT, greater than or equal to 160/95 mmHg), Borderline Hypertensive (BHT, 140/90-159/94 mmHg), and Normotensive (NT, less than 140/90 mmHg). In sessions 1 and 2, the groups no longer differed on resting BP or heart rate (HR) but did differ on BP and HR response to handgrip: Compared with the NT group, the HT and BHT groups had greater rises in systolic and diastolic BP and HR. There was a trend for HT alcoholics to report a positive parental history of hypertension (91%) compared to BHT and NT alcoholics (64% and 60%, respectively), suggesting the existence of premorbid factors to this exaggerated cardiovascular response. Further, alcohol consumption, based on a quantity-frequency index, was significantly higher in the HT group than in the NT group. The results suggest that transitory elevations in blood pressure observed during alcohol withdrawal may predict future BP abnormalities. 
Lichen sclerosus et atrophicus, morphea, and coexistence of both diseases. Histological studies using lectins. Histological studies using three lectins, lens culinaris agglutinin, soybean agglutinin, and Ulex europaeus agglutinin-I, were carried out in a case of coexistent lichen sclerosus et atrophicus and morphea, five cases of morphea, and two cases of lichen sclerosus et atrophicus. The lectin staining patterns of the formaldehyde-fixed epidermis of patients with morphea were not different from those of normal epidermis, but epidermis of patients with lichen sclerosus et atrophicus showed different staining patterns. Lens culinaris agglutinin stained the basal and the spinous layers of the normal epidermis and that of patients with morphea but stained only the basal cells of the epidermis from patients with lichen sclerosus et atrophicus; epidermal Ulex europaeus agglutinin binding was observed only in the cases of lichen sclerosus et atrophicus. Moreover, in the patient with coexistent diseases, the morphea lesion showed the staining profiles of morphea and the lichen sclerosus et atrophicus lesion showed the staining patterns of lichen sclerosus et atrophicus, respectively. 
Transient porphyrinemia in a liver transplant recipient. We report a case of acquired porphyrinemia in a liver transplant recipient. Thrombosis of the portal vein and hepatic artery led to massive necrosis of the patient's first donor liver, necessitating its removal. After an 18-hour anhepatic period, a second donor liver was transplanted. During this interval, the patient was warmed with an infrared heat lamp that emitted bright visible light. Following the anhepatic period, a photodistributed cutaneous erythema was noted. The level of total serum porphyrins during the anhepatic period was significantly elevated at 1.548 mumol/L (normal, less than 0.018 mumol/L). Fractionation showed that the levels of the hydrophobic porphyrins, coproporphyrin and protoporphyrin, were elevated, while the levels of the hydrophilic porphyrins remained normal. Following the successful second liver transplantation, the patient's porphyrin levels declined. This is the first reported case of acquired porphyrinemia in a liver transplant recipient. 
Thrombus within a submitral left ventricular aneurysm: diagnosis on cross sectional echocardiography. Subvalvar left ventricular aneurysms are rare and occur predominantly in black Africans. A submitral left ventricular aneurysm was diagnosed on cross sectional echocardiography in a black woman born in the United Kingdom. The left parasternal long axis view showed a highly echogenic mass apparently attached to the wall of a dilated left atrium, but the apical two-chamber view showed that this was thrombus in the apex of a left ventricular aneurysm. The patient subsequently underwent surgical correction. 
Interaction between methotrexate, "rescue" agents and cell proliferation as modulators of homocysteine export from cells in culture. Clinical studies on cancer and psoriasis patients have shown that plasma and urinary homocysteine (Hcy) responds to methotrexate (MTX) therapy, indicating that Hcy in extracellular fluids may be an indicator of the antifolate effect. However, the clinical data indicate that the burden of proliferating cells, cytotoxicity and the folate status are also determinants of extracellular Hcy. To evaluate this further, we investigated the modulation of cellular Hcy egress by MTX, rescue agents, cell proliferation and cytotoxicity. Nontransformed and chemically transformed fibroblasts and murine lymphoma cells, which are characterized by different growth behavior and MTX response, were used. The Hcy export rate was correlated positively with the proliferation rate in all cell types. 5-Formyltetrahydrofolate or 5-methyltetrahydrofolate added to fibroblasts not exposed to MTX reduced the Hcy export rate, whereas the export from the lymphoma cells was not affected. All cells types exposed to MTX were rescued by thymidine + hypoxanthine, and this allowed the assessment of Hcy export during MTX exposure without interference from cytotoxicity. In the fibroblasts, MTX with thymidine + hypoxanthine rescue induced a marked increase in Hcy export, and the dose-response paralleled the cytotoxicity curves obtained for MTX without rescue. Nontoxic concentrations of MTX without rescue enhanced the Hcy export. When MTX concentration was increased further, Hcy export was stimulated initially, and then declined rapidly as cell death ensued. MTX did not enhance the Hcy export from the lymphoma cells and, in the absence of rescue, the Hcy export from these cells declined in proportion to inhibition of cell growth. 
The causes of esophageal symptoms in human immunodeficiency virus infection. A prospective study of 110 patients. STUDY OBJECTIVES.--To determine the prevalence of infectious agents in patients with human immunodeficiency virus infection and odynophagia or dysphagia; the utility of endoscopic, histologic, cytologic, and virologic testing for the diagnosis of esophagitis; and the yield of blind brushings of the esophagus in this setting. DESIGN.--Prospective clinical case study. SETTING.--Urban county hospital. PATIENTS.--One hundred ten consecutive patients with esophageal symptoms and documented human immunodeficiency virus infection. INTERVENTION.--Blind brushing of the esophagus via orogastric tube followed by endoscopy with esophageal brushing for fungal stain, Papanicolau smear, and viral cultures and esophageal biopsies for histologic examination and viral culture. MAIN RESULTS.--Seventy-two (65%) of the 110 patients had a total of 100 esophageal infections. Thirty-three (30%) had Candida alone, 22 (20%) had Candida and cytomegalovirus, two (1.8%) had Candida with cytomegalovirus and herpes simplex virus, seven (6%) had cytomegalovirus alone, six (5%) had herpes simplex virus alone, and two (1.8%) had both viruses. Fifty of 55 patients with plaques alone had Candida, and two (4%) had only viral infection. Of 19 patients with erosions or ulcers, 11 (58%) had a viral infection, two (11%) had Candida alone, and six (30%) had no etiologic agent identified. The sensitivity of endoscopic brushings (95%) was better than that of histologic examination (70%) in the diagnosis of Candida esophagitis. Likewise, viral cultures of brushings or biopsy specimens were more sensitive (67%) than histologic examination (35%) for viral esophagitis. Blind brushing of the esophagus had a sensitivity and specificity for infectious esophagitis of 84% and 75%, respectively. Oral thrush had a sensitivity of 53% and a positive predictive value of 77% for Candida esophagitis. 
Effect of intra-arterial tissue plasminogen activator and urokinase on autologous arterial emboli in the cerebral circulation of rabbits [corrected] [published erratum appears in Stroke 1991 Feb;22(2):285] We conducted a randomized, blinded controlled trial to test the efficacy of fibrinolytic therapy with tissue plasminogen activator and urokinase in the treatment of acute embolic stroke. Embolic stroke was simulated in rabbits by injecting three 0.5 x 0.5 mm fragments of autologous arterial thrombus harvested from a traumatized auricular artery. Thirty minutes after embolization the rabbits were blindly treated with tissue plasminogen activator (n = 21), urokinase (n = 20), or 0.9% saline (n = 20). At 6 hours the rabbits were sacrificed, and the cerebral vasculature was inspected for the location and number of emboli. The brain was then cut into 0.5-cm-thick coronal sections and stained with triphenyltetrazolium chloride to define areas of infarction. Treatment with either tissue plasminogen activator or urokinase significantly reduced the number of emboli present in the cerebral circulation (p less than 0.05). The area of ischemic injury was also significantly reduced (p less than 0.05) by acute fibrinolytic therapy with either tissue plasminogen activator or urokinase. However, only treatment with tissue plasminogen activator significantly reduced (p less than 0.05) the incidence of infarction. There was no evidence of intracerebral hemorrhage in any rabbit. Early fibrinolytic therapy improved outcome in this model of acute embolic stroke. 
Characterizing organic delusional syndrome. We present a first comprehensive description of the clinical features of patients with organic delusional syndrome. This description is based on information from 39 patients with organic delusional syndrome among 14,889 patients who presented for initial evaluation over a 5-year period at our institution. This description includes an enumeration of the common clinical symptoms of this syndrome and the respective prevalence and mean severity of each symptom. The severity of the symptoms of organic delusional syndrome are compared with those of schizophrenia to determine which symptoms distinguish between these two diagnostic categories. Patients with organic delusional syndrome demonstrated significantly more symptoms of "acquired intellectual impairment," "impaired sensorium," and "hallucinations of smell, taste, or touch," while schizophrenic patients demonstrated more "flat affect," "emotional coldness," and "thought disorganization." In addition, associated factors are presented concerning demographics, modes of treatment, level of functioning, and current physical problems associated with organic delusional syndrome. 
Correlation between histology and nerve excitability after reinnervation of paralyzed strap muscles in the rabbit. We have recently shown that the mean muscle chronaxie for nerve pedicle implanted into denervated rabbit strap muscle is comparable to that of normal nerve. This study correlates excitability with histologic characteristics of muscles reinnervated via nerve-muscle pedicles (NMP) and direct nerve implants (DNI). Strength duration curves were measured in 13 rabbits 3.5 to 5 months after reinnervation by NMP (n = 6) and DNI (n = 7). Following this, control (n = 5) and reinnervated straps were harvested immediately before the animals were killed and frozen in liquid nitrogen. The material was submitted for hematoxylin-eosin stains as well as trichrome stains for general morphology, myofibrillar ATPase and NADH for fiber typing, and cholinesterase for determination of denervated fibers. In all animals with low chronaxie, expected type grouping from reinnervation was noted (n = 10). By contrast, the three animals in which chronaxie was abnormally elevated demonstrated fibrosis, inflammation, and absence of or poor type grouping. This suggests that type grouping is necessary for excitability after reinnervation of paralyzed striated muscles. 
Clenbuterol plus acivicin decrease tumor growth and increase muscle mass in rats maintained on total parenteral nutrition. Two problems associated with supplemental nutrition of tumor-bearing organisms are control of tumor growth and reduction of cachexia. To investigate these problems, rats bearing methylcholanthrene-induced sarcomas were maintained on total parenteral nutrition (TPN) for 10 to 12 days beginning 23 days after tumor inoculation. Combined treatment of one group of these rats with the glutamine antimetabolite, acivicin, and the beta 2-adrenergic agonist, clenbuterol, arrested tumor growth, increased skeletal muscle mass and protein content, increased gut mass, and decreased total plasma lipid levels. Resting energy expenditure and cardiac mass were increased by TPN and were increased further by acivicin plus clenbuterol. These results demonstrate that tumor growth and muscle wasting can be controlled during TPN of tumor-bearing organisms. Therefore, cachectic depletion of lean body tissue may not be obligatory in neoplastic disease. 
Jaw pain and tenderness levels during and after repeated sustained maximum voluntary protrusion. Eight normal male volunteers performed 4 repeated sustained voluntary isometric protrusive jaw muscle contractions of 25, 50, 75 and 100% of maximum effort. Each contraction was sustained until maximum pain tolerance was reached, and all 4 contractions were completed within a single 120-min experimental period. A 30-min rest period followed each sustained contraction. The following measurements were made before and 1, 2, 3, and 7 days after the experiment: (1) superficial masseter and anterior temporalis muscle pain threshold; (2) maximum active pain-free jaw opening and lateral excursion; and (3) current overall jaw pain level. None of these measurements showed any significant post-experimental changes. Contrary to common clinical belief, these results suggest that in healthy male subjects, significant jaw pain and tenderness following repeated sustained isometric protrusion efforts are difficult to induce. 
CT-guided percutaneous transpedicular biopsy of the spine. Occasionally, vertebral body lesions are encountered that are ill suited to the standard posterolateral approach to biopsy. The authors used a transpedicular approach to spine biopsy in six such cases. The authors suggest that this approach be used when the location of the lesion does not allow easy access by means of the posterolateral approach. 
A review of hemoglobin and the pathogenesis of cerebral vasospasm. We believe that current experimental and clinical evidence can be most satisfactorily interpreted by assuming that oxyhemoglobin is the cause of cerebral vasospasm that follows subarachnoid hemorrhage. We review the pathogenetic mechanisms by which oxyhemoglobin affects cerebral arteries. The relative importance of each of these mechanisms in the genesis of vasospasm, the biochemical pathways of oxyhemoglobin-induced smooth muscle contraction, and the intracellular actions of oxyhemoglobin on smooth muscle and on other cells in arteries are still not definitely established. 
Incidence of pneumonia in mechanically ventilated patients treated with sucralfate or cimetidine as prophylaxis for stress bleeding: bacterial colonization of the stomach. Retrograde colonization of the oropharynx from the stomach by microaspiration of gastric fluid is a recently recognized phenomenon associated with increased gastric pH that may result in pneumonia during ventilation therapy. In a prospective study we investigated 104 mechanically ventilated patients in the intensive care unit who were receiving sucralfate (n = 49) or cimetidine (n = 55) for stress ulcer prophylaxis. The incidence of pneumonia was 45.5% (25 patients) in the cimetidine group and 26.5% (13 patients) in the sucralfate group (95% confidence interval 0.98 to 6.97; odds ratio 2.61; p = 0.0549). Mortality rates were 18.4% (9 patients) in the sucralfate group versus 25.5% (14 patients) in the cimetidine group (p = 0.48). The mean pH values of gastric aspirates were significantly lower in patients treated with sucralfate than in patients receiving cimetidine (p = 0.044). The number of colony-forming units of Enterobacteriaceae in gastric aspirates was also significantly lower in the sucralfate group (p = 0.0037). 
Effect of heparin on coronary arterial patency after thrombolysis with tissue plasminogen activator in acute myocardial infarction. Infarct artery patency rates at 90 minutes after coronary thrombolysis using recombinant tissue-type plasminogen activator (rt-PA) with and without concurrent heparin anticoagulation have been shown to be comparable. The contribution of heparin to efficacy and safety after thrombolysis with rt-PA is unknown. In this pilot study, 84 patients were treated within 6 hours of onset of acute myocardial infarction (mean of 2.7 hours) with the standard dose of 100 mg of rt-PA over 3 hours. Forty-two patients were randomized to receive additionally immediate intravenous heparin anticoagulation (5,000 U of intravenous bolus followed by 1,000 U/hour titrated to a partial thromboplastin time of 1.5 to 2.0 times control) while 42 patients received rt-PA alone. Coronary angiography performed on day 3 (48 to 72 hours, mean 57) after rt-PA therapy revealed infarct artery patency rates of 71 and 43% in anticoagulated and control patients, respectively (p = 0.015). Recurrent ischemia or infarction, or both, occurred in 3 (7.1%) anticoagulated patients and 5 (11.9%) control patients (difference not significant). Mild, moderate and severe bleeding occurred in 52, 10 and 2% of the group receiving anticoagulation, respectively, and 34, 2 and 0% of patients in the control group, respectively (p = 0.006). These data indicate that after rt-PA therapy of acute myocardial infarction, heparin therapy is associated with substantially higher coronary patency rates 3 days after thrombolysis but is accompanied by an increased incidence of minor bleeding complications. 
Predictors of left atrial thrombus in mitral valve disease OBJECTIVE: To determine the risk factors for left atrial thrombus (LAT) and the prevalence of thrombi in cases of mitral valve disease whose severity was judged to necessitate surgical intervention. DESIGN: Hospital record review of all operative cases from 1982 to 1985. SETTING: A community serving a referral population encompassing 1.5 million people. Only two hospitals in the geographic area performed cardiac surgery, and both hospitals' records were reviewed. PATIENTS: All 372 patients who underwent either mitral valve replacement or open mitral commissurotomy. MAIN RESULTS: Twenty-six patients (7%) were noted to have LAT at surgery. Five preselected factors were significantly (p less than 0.05) associated with LAT in univariate analysis: female gender, prior history of embolism, prior anticoagulant therapy, mitral stenosis (MS), and atrial fibrillation (AF). In logistic regression analysis, only MS and AF remained as significant independent predictors of LAT. Mitral stenosis patients in sinus rhythm had a relatively low [2.4 +/- 3.3% (observed +/- 95% confidence interval)] likelihood of having an LAT. Likewise, mitral regurgitation patients in sinus rhythm (n = 139) had an extremely low (0.7 +/- 1.4%) prevalence of LAT. In contrast, MS patients in AF (n = 122) had a prevalence of LAT of 18.0 +/- 6.8%. CONCLUSIONS: These findings indicate that, overall, LAT in mitral valve disease may be less common than previous studies have suggested. In addition, mitral valve disease patients who remain in sinus rhythm appear to have a low risk of harboring an LAT. Conversely, MS patients, especially those in AF, appear to be at high risk of harboring an LAT. These results may be helpful in formulating strategies for the use of prophylactic anticoagulation in categories of patients with clinically severe mitral valve disease, or perhaps in estimating the likelihood of a cardiac source of embolism in mitral valve disease patients with suspected cerebral or peripheral emboli. 
Stereotactic radiosurgery for squamous cell carcinoma of the nasopharynx. Stereotactic radiosurgery using the gamma unit represents a unique neurosurgical treatment method for the management of selected intracranial vascular malformations and tumors. During a closed-skull single-session procedure that focuses 201 individual beams of gamma irradiation, a high-radiation dose is delivered to the lesion, with a steep dose fall-off peripherally. In order to maintain accuracy of delivery, the target must remain fixed in space; hence the skull is engaged by rigid external fixation during treatment. In this report, we document the first extracranial lesion treated with radiosurgery, a recurrent squamous cell carcinoma of Rosenmuller's fossa, and discuss the possible role of radiosurgery in carefully selected head and neck malignancies. 
The association of IgA glomerulonephritis and thin glomerular basement membrane disease in a hematuric patient: light and electron microscopic and immunofluorescence investigation. A double glomerulopathy (IgA glomerulonephritis [IgAGN] associated with thin glomerular basement membrane disease [TGBMD]) is reported in a 39-year-old woman presenting with macroscopic-microscopic hematuria. Her 3-year-old daughter was also affected by microhematuria of probable glomerular origin. The diagnosis of IgAGN was made by means of immunofluorescence investigation, which showed generalized diffuse mesangial deposits. TGBMD was identified by electron microscopic investigations, which disclosed thinning (up to 160 nm) of basement membrane of several capillary loops and prominence of the lamina densa. Bearing in mind the known frequencies of the two glomerulopathies, their association may not be coincidental, and, therefore, is worthwhile researching in hematuric patients. 
Chronic calcific pancreatitis in a patient with Waldenstrom's macroglobulinemia. We report on a patient with chronic calcific pancreatitis associated with Waldenstrom's macroglobulinemia, and we have hypothesized a possible relationship between these two entities. The hyperviscosity of serum in Waldenstrom's macroglobulinemia may be associated with a viscous pancreatic juice that leads to stone formation. 
Adjusting the dose to the individual response of the patient during the induction of ovulation with pulsatile gonadotropin-releasing hormone. To identify the effective dose of intravenous pulsatile gonadotropin-releasing hormone necessary to induce ovulation in patients with chronic anovulation of diverse etiology, 40 women were subdivided into four groups: idiopathic hypogonadotropic hypogonadism (IHH), functional hypothalamic amenorrhea, normoandrogenic oligomenorrhea, and polycystic ovarian syndrome (PCOS). During 90 treatment cycles, the dose was the only parameter that was progressively adjusted. The overall ovulation rate per cycle was 100% in IHH, functional hypothalamic amenorrhea, and normoandrogenic oligomenorrhea, using only 5 micrograms/90 minutes in functional hypothalamic amenorrhea and normoandrogenic oligomenorrhea and up to 7.5 micrograms/90 minutes in IHH. In PCOS, the ovulation rate was 67.6%, using up to 20 micrograms/90 minutes. The lesser degree of effectiveness observed in PCOS can probably be explained by the different basal endocrine profile presented by these subjects. 
Epileptic palatal myoclonus. Palatal myoclonus (PM) is usually caused by lesions of the brainstem. We report a case of PM of focal cortical origin in a patient with epilepsia partialis continua. The PM sometimes occurred in isolation, and at other times was accompanied by unilateral face, neck, and arm twitching. This was documented by both EEG and SPECT. 
Nutrition and alcoholic liver disease. While the rate of malnutrition is relatively modest in alcoholic patients without alcoholic liver disease, the rate of malnutrition is virtually 100% in patients with alcoholic hepatitis and/or alcoholic cirrhosis. The reasons for malnutrition in the alcoholic hepatitis patient include various factors such as anorexia, poor diet, malabsorption, and altered metabolic state. When the patient is hospitalized, the malnutrition frequently worsens because of fasting for tests, continued anorexia, and complications such as gastrointestinal bleeding. Patients with severe acute hepatitis appear to be both hypermetabolic and hypercatabolic, whereas data are much more conflicting concerning patients with more stable liver disease. Most studies suggest that patients with alcoholic liver disease require at least 60 g of protein per day to maintain positive nitrogen balance. Consistent alterations in plasma amino acid profiles occur in alcoholic liver disease, and specialized nutritional formulations have been devised to correct this amino acid profile with the intent of improving overall nutritional status, hepatic encephalopathy, and mortality. The effects of nutritional support (including use of specialized products) on outcome, on acute hepatic encephalopathy, and on chronic or latent portal systemic encephalopathy are reviewed. 
Comparison of mastectomy and lumpectomy for medial carcinoma of the breast. The recurrence and five year disease-free survival rates of 86 patients with carcinoma of the breast located in the medial quadrants who had either lumpectomy and radiotherapy or mastectomy were compared. Patients who had lumpectomy and mastectomy were comparable with respect to variables reflecting extent of the disease. One of 54 patients who had lumpectomy had a local recurrence and five had a recurrence regionally or at distant sites. In the group of 32 patients who had a mastectomy, one patient had a local recurrence and an additional four patients had a recurrence at other sites. The five year study disease-free survival rate was 83 per cent for the lumpectomy group and 78 per cent for the mastectomy group. These data suggest that, for medial quadrant lesions, there may be a disease-free survival advantage associated with lumpectomy and radiotherapy over mastectomy. Further study of this treatment modality for this subset of patients seems indicated. 
Mechanisms of gastro-oesophageal reflux in cystic fibrosis. Abnormal degrees of gastro-oesophageal reflux (GOR) were detected by 24 hour intraoesophageal pH measurement in 12 of 14 children (mean age 7.9 years; range 5 months-16 years) affected by cystic fibrosis and complaining of symptoms suggesting GOR. These patients underwent combined recording of distal oesophageal motility and intraluminal pH in order to investigate mechanisms of GOR. Inappropriate lower oesophageal sphincter relaxation was the most common mechanism of reflux in all patients. Other mechanisms (appropriate relaxation or lowered pressure of the lower oesophageal sphincter, increased intragastric pressure) were detected less frequently. Frequency of inappropriate lower oesophageal sphincter relaxations was significantly higher in patients with cystic fibrosis than in other study groups (symptomatic GOR, GOR disease complicated by respiratory complaints). Inappropriate lower oesophageal sphincter relaxations occurred with the same frequency in patients with cystic fibrosis and in a group of children with GOR disease complicated by oesophagitis. Abnormalities of distal oesophageal contractions such as decreased amplitude or uncoordinated waves were also recorded in cystic fibrosis patients. Seven patients with cystic fibrosis completed a therapeutic trial for eight weeks consisting of postural treatment and oral cisapride, a new prokinetic drug. The oesophageal acid exposure improved in only three patients. We conclude that pathologic GOR is commonly associated with cystic fibrosis. The predominant reflux mechanism in these patients is a transient inappropriate lower oesophageal sphincter relaxation rather than a low steady state basal lower oesophageal sphincter pressure. 
Effects of phosphatidylserine in age-associated memory impairment. We treated 149 patients meeting criteria for age-associated memory impairment (AAMI) for 12 weeks with a formulation of phosphatidylserine (100 mg BC-PS tid) or placebo. Patients treated with the drug improved relative to those treated with placebo on performance tests related to learning and memory tasks of daily life. Analysis of clinical subgroups suggested that persons within the sample who performed at a relatively low level prior to treatment were most likely to respond to BC-PS. Within this subgroup, there was improvement on both computerized and standard neuropsychological performance tests, and also on clinical global ratings of improvement. The results suggest that the compound may be a promising candidate for treating memory loss in later life. 
The benefit to cost ratio of work-site blood pressure control programs. Reduction in the cost of health care claims among hypertensive employees was examined over a 4-year period after exposure to a 3-year blood pressure control program, to see whether work-site monitoring and counseling produced a subsequent benefit. Hypertensive employees at three experimental sites (N = 183 to 367 subjects) were compared with subjects at a control site (N = 169) who had received no postscreening follow-up or monitoring, and with matched normotensive employees. The cost of subsequent health care claims for hypertensive employees at the experimental sites was lower than claims for those at the control site, but there was no significant difference across the sites in claims for normotensive employees. After adjusting to a standard 1982 dollar, the data showed from $1.89 to $2.72 in reduced health care claims per dollar spent operating the hypertension control program. 
Aqueduct block markedly reduces mortality and hypertension in post-deoxycorticosterone acetate Dahl salt-resistant rats. When Dahl salt-resistant (DR) rats are given mild post-deoxycorticosterone acetate (DOCA) hypertension, they will have, within 8 weeks, a 53% mortality on a high NaCl diet, without a rise of blood pressure. Forty-two DR rats were given DOCA in silicone (250 mg/kg) and 1% NaCl to drink. After 4 weeks, the DOCA and 1% saline were removed and replaced with a low NaCl diet and tap water. One week later, they were divided into two groups perfectly matched for blood pressure (154 mm Hg). One group had the aqueduct of Sylvius blocked with silicone and epoxy materials; the other group had a sham block. After 4 more recovery weeks on a low NaCl diet, blood pressure averaged 171 mm Hg in sham rats and 147 mm Hg in truly blocked rats (p less than 0.0001). Thus, the aqueduct block prevented most of the post-DOCA hypertension and permitted a strong post-DOCA recovery from the acute DOCA hypertension. The rats with the sham block had an actual rise in blood pressure during the post-DOCA recovery period. The vicious cycle leading to permanent post-DOCA NaCl hypertension was broken by the aqueduct block. Then both groups began an 8% high NaCl diet, and after 4 weeks, blood pressure averaged 184 mm Hg in sham and 155 mm Hg in truly blocked rats (p less than 0.0001). After 12 weeks on 8% NaCl, all sham rats had died (28 of 28), whereas only one of 14 truly blocked rats had died (93% reduction in mortality, p less than 0.0001). 
Animal models for arterial thrombolysis and prevention of reocclusion. Erythrocyte-rich versus platelet-rich thrombus. Experimental animal models for erythrocyte-rich (ER) and platelet-rich (PR) arterial thrombosis were developed in dogs and rabbits and used for the evaluation of the effect of antithrombin and antiplatelet agents on thrombolysis with recombinant tissue-type plasminogen activators (rt-PA). The canine models consist of a whole blood clot produced in the left anterior descending coronary artery (ER thrombus) or a 1-cm everted (inside-out) segment graft in the circumflex coronary artery that predisposes to occlusion with PR material (PR thrombus). The rabbit models consist of a femoral arterial whole blood clot (ER thrombus) or a femoral arterial eversion graft (PR thrombus). The whole blood clot models are sensitive to recanalization with rt-PA but are consistently associated with reocclusion, notwithstanding the concomitant use of heparin and/or aspirin. Clot lysis is accelerated and reocclusion is prevented by the administration of F(ab')2 fragments of a monoclonal antibody 7E3 directed against the platelet glycoprotein IIb/IIIa receptor; of Argatroban, a synthetic thrombin inhibitor; or of kistrin, a glycoprotein IIb/IIIa-blocking polypeptide from the Malayan pit viper venom. The PR thrombus models are very resistant to recanalization with rt-PA, but this resistance can be overcome by the concomitant use of the platelet glycoprotein IIb/IIIa-blocking antibody. Thus, selective platelet glycoprotein IIb/IIIa inhibitors are more effective than aspirin, heparin, or both in accelerating arterial thrombolysis with rt-PA; in preventing reocclusion after clot lysis; and in overcoming the resistance of PR thrombus to dispersion with rt-PA. These experimental animal models may be useful in the development of improved thrombolytic strategies using plasminogen activators in conjunction with specifically targeted antiplatelet and anticoagulant agents. 
Increasing incidence of coeliac disease in Sweden. Changes in the incidence of coelic disease was studied among children born in Goteborg, Sweden, between 1970 and 1988. A total of 188 patients with coeliac disease were found. Of these, 83% were less than 2 years old at the time of their first duodenal biopsy and 74% of them have so far been verified according to the criteria of the European Society for Gastroenterology and Nutrition (ESPGAN). The cumulative incidence at 2 years of age/1000 liveborn infants increased significantly from 0.31 in the first birth cohort to 2.93 in the last. This increase could only partly be explained by improvements in detection. Weight for age at diagnosis was generally considerably below the reference value, but was slightly less affected towards the end of the period. The increase in incidence of coeliac disease is the first reported since the middle 1970s and makes the disease one of the most common chronic diseases among Swedish children. 
Fatal theophylline poisoning with rhabdomyolysis. A potential role for dantrolene treatment. A fatal case of theophylline poisoning is described. The patient developed rhabdomyolysis, renal failure and compartment syndrome, as well as the more usual features of severe theophylline poisoning. Dantrolene appeared to be useful in controlling the hypermetabolic state associated with the overdose and may have a role in future treatment. 
Unusual cause of intranasal injury. Intranasal injury without external involvement is not common. To our knowledge this is the first reported case of such an injury, caused by an assailant's two fingers forced up the nostrils of our patient causing severe mucosal laceration and excessive bleeding. The patient died two weeks later. 
Delayed cardiac rupture due to blunt chest trauma. A 7-year-old boy fell from a 2.5-m height and suffered contusion of the thorax with hematoma in the soft tissues of the lateral chest wall. The rib cage itself remained intact. After 3 days, there was only local pressure sensitivity of the left hemithorax. On day 8 after the trauma, the child, who up to then had seemed to be in good health, suddenly died during lessons at school. Autopsy revealed a full-thickness rupture of the left ventricle with resultant cardiac tamponade. The macroscopic and histopathologic findings are presented and discussed. 
Mechanism of the enhanced epidermal growth factor-induced growth response of genetically hypertensive vascular myocytes. Although enhanced growth of the vascular myocyte is believed to play a role in hypertensive cardiovascular disease, the cellular basis of altered growth regulation is not completely understood. The present study demonstrates that in the presence of 10% fetal calf serum, the logarithmic growth rate of cultured mesenteric artery myocytes of the spontaneously hypertensive rat (SHR) is similar to that of the normotensive Wistar-Kyoto (WKY) control rat. However, in the presence of low levels of fetal calf serum, SHR myocytes respond to epidermal growth factor (EGF) with increased growth, whereas WKY cells do not. This difference does not result from different numbers or affinities of EGF receptors in these cell lines. Examination of EGF-induced growth responses of SHR and WKY myocytes in the presence of varying levels of insulin or fetal calf serum indicates that, compared with WKY myocytes, SHR myocytes have a lower requirement for factors that confer competence to respond to EGF. Another property of the SHR myocytes is an elevation of free intracellular Ca2+. To determine whether a difference in cellular Ca2+ metabolism might play a role in the differential growth response, growth of myocytes in medium containing 0.25, 0.75, or 1.25 mM extracellular Ca2+ and 5% fetal calf serum was examined. Myocytes of SHR showed enhanced growth in the presence of 5% fetal calf serum at all levels of extracellular Ca2+. It is concluded that, although vascular myocytes of SHR and WKY rats have the capacity to grow at similar rates, under limiting conditions, the SHR myocyte growth response is enhanced. 
Nursery Neurobiologic Risk Score: important factor in predicting outcome in very low birth weight infants. We developed a nursery Neurobiologic Risk Score (NBRS) based on potential mechanisms of brain cell injury in preterm infants and correlated it with developmental outcome at the corrected ages of 6, 15, and 24 months. The NBRS was determined at 2 weeks of age and at the time of discharge from intensive care in 58 preterm infants with birth weights less than or equal to 1500 gm. The NBRS correlated significantly with the Bayley Scales of Infant Development, Mental Development Index (MDI) (r = -0.61 to -0.40) and Psychomotor Development Index (PDI) (r = -0.59 to -0.46), and with abnormal neurologic examination findings (r = 0.59 to 0.73) at the three testing periods. Although 12 of the 13 items composing the NBRS individually correlated with one or more outcome variables, seven items (infection, blood pH, seizures, intraventricular hemorrhage, assisted ventilation, periventricular leukomalacia, and hypoglycemia) accounted for almost all of the explained variance. Logistic regression of individual items demonstrated intraventricular hemorrhage to be the most important item for predicting the MDI at 24 months; pH was the most influential item for predicting the PDI at every testing period. A shorter, revised NBRS that included only the seven significant items demonstrated as strong a correlation with developmental outcome as the original NBRS. A revised 2-week score of greater than or equal to 5 or a discharge score of greater than or equal to 6 demonstrated 100% specificity and had a 100% positive predictive value for an abnormal outcome at 24 months of age in this group of infants. We conclude that the NBRS identifies during the intensive care nursery stay those infants at highest risk for an abnormal outcome related to nursery events. In addition, analysis of NBRS items provides insight into the relative importance of individual factors for influencing mental, motor, and neurologic outcome. 
The role of corticosteroids in infants and children with bacterial meningitis. Bacterial meningitis continues to be a cause of substantial morbidity in infants and children. Hearing impairment is the most common sequela of this disease. Corticosteroids have been used in an attempt to reduce the incidence of meningitis-induced hearing loss. Some studies have demonstrated a decrease in the incidence of hearing impairment in patients treated with cefuroxime plus dexamethasone compared with cefuroxime alone. Similar data are lacking for other frequently used antibiotics. Based on these studies, the use of dexamethasone should be considered in infants and children greater than two months of age with suspected bacterial meningitis. Critical issues including the timing of steroid initiation in relation to antibiotic therapy and the appropriate antibiotic-corticosteroid regimen must be addressed. Studies should be performed to define the exact role of corticosteroids in the treatment of bacterial meningitis. Until additional data are available, we recommend the use of dexamethasone in pediatric patients older than two months of age with bacterial meningitis. 
Selection bias in the use of thrombolytic therapy in acute myocardial infarction. The SAVE Investigators. OBJECTIVE. To determine whether clinical selection for thrombolytic therapy for acute myocardial infarction results in a skewed population for subsequent adverse cardiovascular events. DESIGN. A comparison of the clinical features of the patients in the Survival and Ventricular Enlargement Study who either had or had not received thrombolytic therapy was conducted in both univariate and multiple logistic regression analyses. SETTING. Hospitalized patients experiencing acute myocardial infarction from 112 broadly representative, private, academic, and government hospitals in the United States and Canada. PATIENTS. All patients in the Survival and Ventricular Enlargement Study had had a recent myocardial infarction (less than 16 days) and had a left ventricular ejection fraction of 40% or less. INTERVENTION. Thrombolytic therapy was administered to 733 patients and was not given to 1498. MAIN OUTCOME MEASURES. The comparisons with respect to use of thrombolytic therapy were formulated after the completion of enrollment and indicated that the majority of patients did not receive thrombolytic therapy. RESULTS. The 1498 (67.1%) patients who did not receive thrombolytic therapy were at higher risk (older age, lower functional capacity, greater likelihood of a history of prior myocardial infarction, angina, diabetes, and hypertension) for subsequent cardiovascular events and, as anticipated, were more likely to have concomitant gastrointestinal and neurological diseases. A multiple logistic regression analysis indicated that older age, prior myocardial infarction, impaired functional status, employment status, diabetes, and neurological diseases were predictors of use of thrombolytic therapy. CONCLUSION. Although the Survival and Ventricular Enlargement Study population was selected for left ventricular dysfunction, the majority of patients who currently are judged clinically as unsuitable for thrombolytic therapy have a higher risk for adverse cardiovascular events. 
SCID mice: a suitable model for experimental studies of urologic malignancies. In vivo studies on human malignant tumors are limited because of a lack of suitable animal models. In this study, the usefulness of SCID (severe combined immunodeficiency) mice, deficient in functions of both T- and B-lymphocytes, was evaluated. Inbred SCID mice were kept in isolated cages and 2 x 10(7) cells of KU-7, an established bladder carcinoma cell line, were inoculated in the subcutaneous tissue of the flank region of six SCID mice. Athymic nude mice were inoculated by the same method and served as the controls. The KU-7 cells were taken within 14 days in the injected region in all six SCID mice, while in only five out of eight nude mice. Tumors subsequently formed at the site of inoculation in these mice were confirmed to be transitional cell carcinomas histologically and intra-abdominal metastases were noted in two SCID mice. We conclude that SCID mice provide an ideal in vivo model for experimental studies of human urologic malignant tumors. 
Bilateral anterior cerebral artery infarction resulting from explosion-type injury to the head and neck. A 43-year-old woman suffered a blast-type injury to the head and neck. She subsequently developed bilateral internal carotid artery occlusion and bilateral anterior cerebral artery infarction not demonstrated by magnetic resonance imaging scan 24 hours after the explosion, but confirmed by a second scan 8 days after the explosion. In patients with blast-type injury to the head and neck who develop coma with a nonfocal neurological exam, the possibility of bilateral carotid artery occlusion and bilateral ischemic infarction should be considered. 
Synthesis of chondrocytic keratan sulphate-containing proteoglycans by human chondrosarcoma cells in long-term cell culture [published erratum appears in J Bone Joint Surg [Am] 1991 Sep;73(8):1274] Keratan sulphate is an integral component of the large aggregating proteoglycans of mature human articular cartilage. The keratan sulphate content of chondrocytic proteoglycans increases during maturation, and it is a useful marker of mature-type chondrocytic proteoglycans. Ordinarily, in cell culture, chondrocytes from non-neoplastic tissues dedifferentiate, diminish or cease to synthesize aggregating proteoglycans with the same amount of keratan sulphate as those formed in vivo, and do not maintain their in vivo phenotype. In tissue culture, this down-regulation of synthesis of keratan sulphate is irreversible. The study of the metabolism of mature human chondrocytes has been hampered by the absence of stable models. We report a cell-line, 105KC, derived from a human chondrosarcoma, that has maintained a stable proteoglycan phenotype during more than three years of culture. Analysis with immunofluorescence suggested that 105KC cells continued to synthesize keratan sulphate in long-term culture. Biochemical analysis demonstrated that 105KC cells maintained the production of chondrocytic large-aggregating proteoglycans and that keratan sulphate composed 13 per cent of their glycosaminoglycan content. To our knowledge, 105KC represents the first model to have maintained the post-fetal chondrocytic proteoglycan phenotype in stable culture. This study documents the feasibility of the development of mature chondrocytic cell-lines and sheds light on the biological characteristics of chondrosarcomas. 
Doppler and echocardiographic characteristics of patients having an Austin Flint murmur. BACKGROUND. The purpose of this study was to investigate the genesis of the Austin Flint murmur using Doppler and echocardiographic imaging. METHODS AND RESULTS. A total of 51 patients having significant aortic insufficiency and an anatomically normal mitral valve were evaluated. They were divided into two groups; 30 patients had an audible Austin Flint murmur (AFM+) and 21 did not (AFM-). All patients had a complete M-mode, two-dimensional, and Doppler echocardiographic examination to characterize left ventricular size and function, motion of the mitral valve, transmitral flow velocities, direction of the aortic insufficiency jet, and severity of aortic insufficiency. There was no significant difference in severity of aortic insufficiency between groups. There was, however, a significant difference in direction of the insufficiency jet. In the AFM+ group compared with the AFM- group, for the parasternal long-axis view 24 (80%) versus eight (38%) had their insufficiency jet directed at the mitral valve, for the apical five-chamber view the values were 25 (83%) versus five (24%), and for the apical long-axis view the values were 27 (90%) versus five (24%); for all comparisons p less than 0.01. There was also a greater frequency of localized anterior mitral leaflet distortion by two-dimensional echocardiography (AFM+:23 [77%] versus AFM-:five [24%]; p less than 0.001) and a greater frequency of Doppler striations overlying the aortic insufficiency jet (AFM+:25 [83%] versus AFM-:seven [33%]; p less than 0.001). Regarding transmitral flow velocities, there was no significant difference in filling patterns or absolute velocities during early or late diastole between groups. There was no gradient by Doppler analysis or by hemodynamics (n = 26) across the mitral valve in either group. There also was no difference in the frequency of preclosure of the mitral valve (AFM+:two versus AFM-:three). Systolic function was similar in both groups, but the left ventricular end-diastolic dimension was significantly greater in the AFM+ group (6.8 +/- 0.8 cm) than in the AFM- group (6.2 +/- 0.7 cm, p = 0.008). CONCLUSIONS. The results of this study suggest that the primary factor responsible for the Austin Flint murmur is the presence of an aortic insufficiency jet directed at the anterior mitral leaflet. This, combined with the biphasic pattern of transmitral flow, distorts the shape of the anterior mitral leaflet as it opens and closes during diastole, making it shudder. The leaflet's shuddering sets up vibrations and shock waves that distort the aortic insufficiency jet, causing the observed Doppler striations and probably the sound of the murmur. There is no evidence from this study to support prior theories that have proposed functional mitral stenosis or diastolic mitral regurgitation as the source of the murmur. 
Acoustic discrimination of three types of infant cries. The ability of acoustic characteristics, both separately and in linear combination with others, to differentiate among procedural pain-induced, hungry, and fussy crying was explored using audiorecordings of cries from healthy 2 to 4-month-old infants. Fussy cries were less tense than hungry or pain-induced cries and pain-induced cries had significantly stronger second formant amplitudes than fussy or hungry cries. Formants and tenseness were important contributors to a linear combination of acoustic measures, derived from discriminant function analysis, which correctly classified 74% of the procedural pain-induced crying specimens. The inability of this linear combination of acoustic measures to identify correctly approximately one-third of the cry specimens suggests that the discrete acoustic differences among the three situationally defined types of crying is not large. 
Hemorrhage and intracranial hypertension in combination increase cerebral production of thromboxane A2. BACKGROUND AND METHODS: To determine the effects of reduced cerebral perfusion pressures produced by hemorrhage alone or in combination with intracranial hypertension on thromboxane A2 (TxA2) production, we undertook a randomized study in 38 anesthetized, mongrel dogs. Animals were subjected to 30 mins of hemorrhagic shock with normal (group 1) or increased (group 2) intracranial pressure (ICP). Group 1 animals (n = 22) were hemorrhaged to reduce cerebral perfusion pressure to 40 mm Hg for 30 mins. In group 2 (n = 16), cerebral perfusion pressure was reduced by the combination of less severe hypotension and intracranial hypertension (20 mm Hg). Cerebral and systemic hemodynamic measurements were recorded, including cerebral blood flow (sagittal sinus outflow method); ICP; cerebral perfusion pressure; and arterial and cerebral venous concentrations of TxB2 (double-antibody radioimmunoassay technique), the major metabolite of TxA2. Data were obtained at baseline and at the beginning and end of the 30-min shock period. RESULTS: Hemorrhagic shock significantly (p less than .05) decreased cerebral blood flow in both groups. At the beginning of the shock period, cerebral blood flow was higher in group 1 than in group 2 (p less than .05) and venous-arterial differences in TxB2 increased significantly (p less than .05) in group 2, but not in group 1. At the end of the 30-min shock period, venous-arterial levels of TxB2 remained significantly (p less than .05) higher in group 2. CONCLUSIONS: Increased cerebral production of TxA2 during hypotension accompanied by intracranial hypertension may contribute to the severity of neural damage produced by the combination of head trauma and shock. 
Morphine-augmented cholescintigraphy: its efficacy in detecting acute cholecystitis Cholescintigrams were performed in 158 patients suspected of having acute cholecystitis after administration of 185 Mbq (5 mCi) of 99mTc-mebrofenin or disofenin. Morphine sulfate, 0.04 mg/kg was given intravenously if there was nonvisualization of the gallbladder at 40-60 min provided that radiotracer was seen within the small bowel. Acute cholecystitis was deemed present if there was nonvisualization of the gallbladder 30 min post-morphine administration; no cystic duct obstruction was present if the gallbladder was demonstrated pre- or post-morphine administration. A final diagnosis was estimated in 51 postoperative patients histologically, the remainder having their final diagnosis gleaned from their medical records. The sensitivity, specificity, positive and negative predictive value of morphine-augmented cholescintigraphy in detecting acute cholecystitis was 94.6, 99.1, 97.2, and 98.3%, respectively. These findings indicate that morphine-augmented cholescintigraphy detects acute cholecystitis with as high a degree of accuracy as conventional hepatobiliary scintigraphy, yet requires only 1.5 hr to establish the diagnosis. 
The sleep apnoea syndrome in obesity: risk of sudden death. A total of 34 severely obese men with a history of heavy snoring and excessive daytime sleepiness indicative of obstructive sleep apnoea syndrome (OSAS) were studied prospectively. Their mean age was 46 years, and mean body mass index was 41.6 kg m-2. During a 4-year follow-up, 15% (5/34) of these subjects died (three cases of acute myocardial infarction and two cases of pulmonary oedema), all of them suddenly and unexpectedly, outside hospital. On autopsy the degree of atherosclerosis was found to be moderate in all cases. In 68% (15/22) of the men a pathological apnoea index (mean value 46 +/- 20) confirmed the OSAS diagnosis. Exercise tests and neurological examinations did not reveal any other causes of daytime sleepiness. Mean blood pressure at rest and during exercise was normal, and mean serum lipid and blood glucose levels were normal. Spirometry revealed intrapulmonary restrictive changes that could not be attributed to the heavy thoracic wall. Compliance was reduced to about 50% of reference values, and the mean pCO2 level (5.8 kPa) was close to the upper reference limit. Blood tests suggested that high alcohol consumption may be an important factor contributing to OSAS. These results demonstrate that morbidly obese men with a history of OSAS have a high risk of sudden cardiovascular death, despite the absence of other conventional risk factors. 
Pathologic changes associated with androgen deprivation therapy for prostate cancer. Prostate glands exposed to androgen deprivation with leuprolide +/- flutamide were evaluated for pathologic changes which might be related to therapy. Comparing pretreatment and posttreatment tissue by visual discrimination using light microscopic study revealed treatment-related alterations in the size and distribution of neoplastic glands in 60% of cases. Quantitative measurements documented glandular changes in an even greater percentage of cases. Although distinctive, the histologic pattern was not specific for leuprolide/flutamide. The absence of appreciable degeneration and necrosis in tumor cells suggests that this type of androgen deprivation may act through suppression rather than ablation of prostatic cancers. The relationship between treatment-related histologic effects and initial tumor grade and clinical stage as well as expression of prostate-specific antigen was studied. Accurate histologic assessment of leuprolide/flutamide-treated prostate glands should not be a problem so long as specimens are thoroughly examined and drug-related variations in tumor morphologic features are appreciated. 
Defective Fc receptor-mediated clearance in patients with primary biliary cirrhosis. Fc receptor-mediated clearance of immunoglobulin G-coated autologous erythrocytes was studied in patients with primary biliary cirrhosis (n = 14), alcoholic liver cirrhosis (n = 5) and healthy reference individuals (n = 14). The mean half-life of the sensitized erythrocytes was significantly prolonged in patients with primary biliary cirrhosis (85 +/- 25 minutes; P less than 0.001) compared with the corresponding value in patients with alcoholic cirrhosis (16 +/- 2 minutes) and healthy reference individuals (20 +/- 5 minutes), respectively. No correlation between clearance rate and age, liver histopathology, or serum levels of bilirubin, aminotransferases, immunoglobulin G, immunoglobulin A, and Clq binding or C3-containing immune complexes was found. The results presented here indicate a profound disturbance of Fc receptor-mediated immune clearance function in patients with primary biliary cirrhosis. 
Competitive control of myosin expression: hypertrophy vs. hyperthyroidism. The competition between two opposing influences on the phenotypic expression of skeletal muscle myosin were studied to determine which was the dominant regulator. Experimental hyperthyroidism, which induces fast myosin expression, was produced by subcutaneous implantation of a 40-day constant-time-release triiodothyronine pellet. Compensatory hypertrophy, which induces slow myosin expression, was produced by surgical removal of a synergistic hindlimb muscle. Hyperthyroidism increased the percentage of type II fibers and the fast myosin isoforms in both the plantaris and soleus muscles. Hypertrophy significantly increased the percentage of type I fibers and the slow myosin type in the plantaris and soleus muscles. However, with the simultaneous introduction of hyperthyroidism and hypertrophy, only the hyperthyroid effects were observed. Hyperthyroidism and not physiological demand was found to be the dominant regulator of skeletal muscle myosin expression. 
The double-stapled ileal reservoir and ileoanal anastomosis. A prospective review of sphincter function and clinical outcome. Fifteen consecutive patients (nine males and six females) who underwent construction of a double-stapled ileoanal reservoir (DS-IAR) were prospectively evaluated. Mean and maximal resting pressures preoperatively, before ileostomy closure, and at 12 months, were 53 and 84 mm Hg, 39 and 62 mm Hg, and 62 and 81 mm Hg. Mean and maximal squeeze pressures at those same time periods were 96 and 153 mm Hg, 111 and 173 mm Hg, and 95 and 168 mm Hg. There were no significant decreases in either resting or squeeze pressure between preoperative values and those obtained 12 months after surgery. However, the length of the high pressure zone decreased from 3.8 cm preoperatively to 2.3 cm at 12 months. This reflects the sacrifice of the cephalad 1.5 cm of the internal anal sphincter necessary to effect this anastomosis at a mean of 1.4 cm from the dentate line. However, this maneuver did not result in poor continence. Eleven patients whose ileostomies were closed for a mean of 9 months, ranging from 3 to 15 months, were evaluated regarding functional outcome. Only one patient had any incontinence and this patient had incomplete circular-stapled tissue rings, which necessitated transanal suture repair of the anastomotic defect. Similarly, three of the four patients who sometimes or rarely use a pad at night had transanal-suture reinforcement. Ten of the 11 patients never wear a pad during the day. No pelvic or perianal sepsis occurred. Stratified squamous epithelium was found in 6 of the 13 distal stapler "donuts" that were examined. In addition, 10 patients underwent biopsy of the tissue immediately caudad to the circular staple line at the time of ileostomy closure; in five, only stratified squamous epithelium was noted. The DS-IAR is associated with excellent objective physiologic and subjective functional results. 
Effect of ketanserin on intraoperative blood loss during total hip arthroplasty in elderly patients under general anaesthesia. We have studied the effect of ketanserin, a selective serotonin S2-receptor antagonist, on surgical bleeding in a double-blind, placebo-controlled study in elderly patients undergoing total hip arthroplasty. One group of patients (n = 9) received ketanserin 10 mg i.v. followed by an infusion of 0.075 mg kg-1 h-1. The second group (n = 8) received placebo. Both groups were comparable with regard to age, height and body weight. Mean intraoperative blood loss was 454 ml with ketanserin and 894 ml with placebo (P = 0.004; Wilcoxon two-sample test). Mean duration of the operation was less with ketanserin (112 min) than with placebo (134 min) (P = 0.004), but rate of blood loss was also less with ketanserin (4.1 vs 6.7 ml min-1; P = 0.03). In the ketanserin group, mean arterial pressures tended to be less than in the placebo group. Reductions in central venous pressure were similar in both groups. There were no complications in relation to the use of ketanserin. 
Clinical follow-up and immunogenetic studies of 32 patients with eosinophilia-myalgia syndrome 31 patients with L-tryptophan-associated eosinophilia-myalgia syndrome (EMS) that developed during the United States outbreak in 1989 were followed up prospectively at a university hospital outpatient rheumatology clinic for 16 to 24 months from the onset of their illness. Another patient with EMS associated with L-tryptophan in 1988 was followed up for 30 months. 93% of the 28 survivors from the 1989 cohort continue to have symptoms affecting 1-4 organ systems (median 3) and 3 have died, so the disorder produces considerable morbidity and mortality. The chronic sequelae most often associated with long-term disability are sclerodermatous skin thickening (54%), sensorimotor polyneuropathy (61%), proximal myopathy (36%), and severe episodic myalgias (64%). Thrombocytopenia developed in 1 patient. HLA-class II typing revealed a non-significant trend towards an association with HLA-DR4. Early therapy with corticosteroids did not seem to prevent the development of chronic manifestations. 
Growth hormone treatment of growth failure secondary to total body irradiation and bone marrow transplantation. Growth hormone was given to 13 children (nine boys, four girls) with acute leukaemia who had undergone treatment with cyclophosphamide and total body irradiation before bone marrow transplantation. Mean age at total body irradiation and bone marrow transplantation was 9.0 years (range 3.7-15.8). Endocrinological investigation was carried out at a mean of 2.0 years (range 0.4-4.0) after bone marrow transplantation. Peak serum growth hormone responses to hypoglycaemia were less than 10.0 micrograms/l (less than 20.0 mU/l) in 10, 10.5 micrograms/l (21.0 mU/l) in one, greater than 16.0 micrograms/l (greater than 32.0 mU/l) in two patients. Mean age of the patients at the start of growth hormone treatment was 12.2 years (range 5.8-18.2). The mean time between total body irradiation and bone marrow transplantation and the start of growth hormone treatment was 3.2 years (range, 1.1-5.0). Height velocity SD score (SD) increased from a mean pretreatment value of -1.27 (0.65) to + 0.22 (0.81) in the first year, +0.16 (1.11) in the second year, and +0.42 (0.71) in the third year of treatment. Height SD score (SD) changed only slightly from -1.52 (0.42) to -1.50 (0.47) in the first year, to -1.50 (0.46) in the second year, and -1.74 (0.92) in the third year. Measurement of segmental proportions showed no significant increase in subischial leg length from -0.87 (0.67) to -0.63 (0.65) in the first year, to -0.58 (0.70) in the second year, and -0.80 (1.14) in the third year of treatment. 
Sympathetically maintained pain of the digits in porphyria cutanea tarda relieved by i.v. regional guanethidine. A case of a sympathetically maintained pain of the tips of the fingers in a 39-year-old man with porphyria cutanea tarda is presented. Occupational vibrating trauma is the presumed cause. The successful treatment with intravenous regional guanethidine is reported. 
Coronary heart disease in rhesus monkeys with diet-induced coronary artery atherosclerosis. Diet-induced coronary artery atherosclerosis develops in rhesus monkeys (Macaca mulatta). The goal of this study was to establish the rhesus monkey as an animal model of coronary heart disease (CHD). From a colony of 160 rhesus monkeys fed an atherogenic diet, we identified 14 monkeys with electrocardiographic and echocardiographic evidence of CHD. When compared with 14 rhesus monkeys matched for age, gender, and dietary history with normal electrocardiograms and echocardiograms, monkeys with CHD had higher arterial blood pressures (mean +/- SEM, 92 +/- 4 mm Hg vs 75 +/- 5 mm Hg, respectively), lower high-density lipoprotein cholesterol concentrations (mean +/- SEM, 1.70 +/- 0.25 mmol/L vs 2.32 +/- 0.28 mmol/L [66 +/- 10 mg/dL vs 90 +/- 11 mg/dl]), and lower A-l apolipoprotein concentrations (mean +/- SEM, 200 +/- 17 mg/dL vs 252 +/- 15 mg/dL). Monkeys with CHD tended to have higher total plasma cholesterol concentrations (mean +/- SEM, 11.6 +/- 1.55 mmol/L vs 9.36 +/- 0.93 mmol/L [450 +/- 60 mg/dL vs 362 +/- 36 mg/dL]) and higher low-density lipoprotein cholesterol concentrations (mean +/- SEM, 8.71 +/- 1.75 mmol/L vs 6.12 +/- 0.90 mmol/L [337 +/- 68 mg/dL vs 237 +/- 35 mg/dl]) than monkeys with normal electrocardiograms and echocardiograms. We conclude that rhesus monkeys, like human beings, develop CHD as a complication of coronary artery atherosclerosis. Furthermore, risk factors for CHD in rhesus monkeys and human beings are similar. 
Primary chest wall tumor appearing as frozen shoulder. Review and case presentations. The term frozen shoulder may apply to a primary, common, recognizable entity with a predictable course to a painful stiff condition with periarthritis secondary to trauma, rotator cuff or arthritic source. We studied 140 cases of frozen shoulder, referred to a surgical clinic for manipulation when conservative care was not effective. Investigations showed only 40 cases had "primary" frozen shoulder and among these were 3 patients with a local primary invasive neoplasm mimicking the exact features of the common condition. The attending physician and surgeon should be suspicious of tumor in younger patients with progressive pain among the other features of primary frozen shoulder. 
Acute cor pulmonale secondary to metastatic tumor to the heart: a case report and literature review. Metastatic tumors to the heart are becoming more common due to improved survival afforded by advanced treatment of malignancies. Their presence should be sought in a cancer patient who develops new primary cardiac symptoms. We present a case of a 50-year-old woman who succumbed to acute cor pulmonale secondary to metastatic laryngeal carcinoma to the right ventricle with subsequent tumor emboli to the pulmonary vasculature. 
Impaired suppression of plasma norepinephrine during head-down tilt in patients with congestive heart failure. Neurohumoral activation is present in congestive heart failure and may contribute to vasoconstriction in this syndrome. The mechanisms leading to and maintaining neurohumoral activation in long-standing congestive heart failure are as yet undefined. The present study addresses the possibility that baroreceptor-mediated suppression of plasma norepinephrine may be abnormal in patients with long-standing congestive heart failure. Eight normal subjects and 12 patients with long-standing congestive heart failure were studied during 15 minutes of 30 degrees head-down tilt. There were no significant changes in heart rate or arterial blood pressure in either group during these maneuvers. In normal subjects, plasma norepinephrine declined from 257 +/- 38 pg/ml at control to 208 +/- 39 pg/ml during head-down tilt (p less than 0.005). Plasma norepinephrine was elevated in the patients with congestive heart failure, 475 +/- 189 pg/ml, and did not change during head-down tilt. These observations suggest that baroreflex loading maneuvers, which in this study included increased central blood volume and hydrostatic effects on the sinoaortic baroreceptor, do not suppress increased plasma norepinephrine in patients with long-standing congestive heart failure. Impaired baroreflex responsiveness could therefore contribute to either the generation or maintenance of high plasma norepinephrine in this syndrome. 
Aprotinin reduces intraoperative and postoperative blood loss in membrane oxygenator cardiopulmonary bypass. To determine whether aprotinin can provide a significant improvement of hemostasis in cardiopulmonary bypass using a membrane oxygenator, we tested this drug in a prospective, randomized, double-blind, placebo-controlled clinical trial. The subjects were 80 male patients undergoing cardiopulmonary bypass for coronary artery bypass grafting. Forty patients received aprotinin and 40 patients served as placebo controls. Aprotinin (4 x 10(6) KIU) was given as a continuous infusion, starting before operation and continuing until after cardiopulmonary bypass; additionally, 2 x 10(6) KIU aprotinin was added to the pump prime. Intraoperative and postoperative bleeding, respectively two thirds and one third of the total perioperative blood loss, were both significantly reduced in the aprotinin-treated group (p less than 0.01). The total average perioperative blood loss, corrected to a hemoglobin concentration of 7 mmol/L, was 550 mL in the aprotinin-treated patients versus 900 mL in the control patients. This reduction in blood loss, furthermore, significantly decreased the amount of postoperative blood transfusions (p less than 0.05) and increased the percentage of patients who did not receive postoperative donor blood from 42% to 68%. Aprotinin increased the activated clotting time significantly during cardiopulmonary bypass, which led to a reduction in heparin usage. The improved hemostasis during operation, despite the prolonged activated clotting time, might even abolish the need for heparin conversion with protamine at the end of cardiopulmonary bypass, thus allowing retransfusion through cardiotomy suction to be continued, which saves the blood that is currently lost with vacuum suction. 
Quality assurance for patients with head injuries admitted to a regional trauma unit. The efficacy of trauma systems in reducing preventable deaths has been established but the methods of auditing care are still evolving. Various "audit filters" to identify which patients' charts should be reviewed have been proposed. An analysis of all patients admitted to the Regional Trauma Unit (RTU) over a 19-month period was conducted. Of 729 patients, 135 were identified as having suffered a traumatic intracranial hemorrhage (TICH). On review, neither delay in transfer from the emergency room to the operating room nor increasing time from the incident to the operating room correlated with increasing mortality. In contrast to delay, the Glasgow Coma Scale (GCS) score on admission correlated well with outcome. The charts of patients with anomalous outcomes based on admission GCS score were reviewed, and two possibly preventable deaths were identified. There were 48 patients with TICH who had no operations but there were no deaths attributable to a missed operation. There were 76 patients for whom the GCS score at the referring hospital and the GCS score on admission to the RTU were available. Seven of 19 patients who worsened on transfer declined because of significant pulmonary injuries. Anomalous outcomes based on admission GCS score and declining GCS scores are recommended as quality assurance filters. 
Protein kinase C plays a role in the induction of tyrosine phosphorylation of lymphoid microtubule-associated protein-2 kinase. Evidence for a CD3-associated cascade that includes pp56lck and that is defective in HPB-ALL. Ligation of the CD3 receptor induces multiple signal transduction events that modify the activation state of the T cell. We have compared two lines that express biologically active CD3 receptors but differ in their biochemical activation pathways during ligation of this receptor. Jurkat cells respond to anti-CD3 with Ca2+ mobilization, PKC activation, induction of protein tyrosine phosphorylation, and activation of newly characterized lymphoid microtubule associated protein-2 kinase (MAP-2K). MAP-2K itself is a 43-kDa phosphoprotein that requires tyrosine phosphorylation for activation. Although ligation of the CD3 receptor in HPB-ALL could stimulate tyrosine phosphorylation of a 59- kDa substrate, there was no associated induction of [Ca2+]i flux, PKC, or MAP-2K activation. A specific PKC agonist, PMA, which bypasses the CD3 receptor, could, however, activate MAP-2K in HPB-ALL cells. This implies that defective stimulation of PKC by the CD3 receptor is responsible for its failure to activate MAP-2K in HPB-ALL. The defect in PKC activation is likely distal to the CD3 receptor as A1F14- failed to activate MAP-2K in HPB-ALL but was effective in Jurkat cells. The stimulatory effect of PMA on MAP-2K activity in HPB-ALL was accompanied by tyrosine phosphorylation of this kinase which implies that PKC may, in some way, regulate tyrosine phosphorylation of MAP-2K. A candidate for this role is pp56lck which underwent posttranslational modification (seen as mobility change on SDS-PAGE) during anti-CD3 and PMA stimulation in Jurkat or PMA treatment in HPB-ALL. There was, in fact, exact coincidence between induction of PKC activity, posttranslational modification of lck and tyrosine phosphorylation/activation of MAP-2K. Lck kinase activity in an immune complex kinase assay was unchanged during PMA treatment. An alternative explanation is that modification of lck may alter its substrate profile. We therefore looked at the previously documented ability of PKC to dissociate lck from the CD4 receptor and found that PMA could reduce the stoichiometry of the lck interaction with CD4 in HPB-ALL and to a lesser extent in Jurkat cells. These results imply the existence of a kinase cascade that is initiated by PKC and, in the course of which, lck and MAP-2K may interact. 
Terminal axon pathology in infantile neuroaxonal dystrophy. In order to clarify the pathogenesis of infantile neuroaxonal dystrophy, ultrastructural studies of the terminal and nonterminal axons of motor and autonomic nerves in muscle and skin, of which structures are much simpler than those of the central nervous system, were performed in 5 patients affected by infantile neuroaxonal dystrophy. The primary lesion was located in the axon terminal; the majority of terminal axons were dystrophic with tubulo-membranous profiles, while there were only a few dystrophic axons in the nonterminal axons. According to these findings, it is logical to consider that interruption of axonal transport at the site of the "turnaround" process is a cause of dystrophic change of the terminal axon in infantile neuroaxonal dystrophy. 
Small bowel length in Crohn's disease. The length of the small intestine in patients with Crohn's disease who are referred for surgery has not been well studied. In this report, 25 patients with Crohn's disease who were being operated on for the first time had their small intestine measured at the time of surgery. The mean length of small intestine in this group was 501 cm, which was not different from a group of patients without Crohn's disease who were being operated on for other problems. In the group of patients with Crohn's disease, as well as the entire group, there was a correlation between increasing height and longer small bowel length. No other parameters investigated, including weight, surface area, age, sex, and duration of disease, correlated with bowel length. The results of this study are somewhat encouraging to patients with Crohn's disease, since these patients do not start off with a shortened bowel prior to surgery. 
Long-term health risks and benefits of oral contraceptive use. The contraceptive effect of oral contraceptive use provides an important health benefit, particularly in developing countries, where the risks of pregnancy and childbearing are increased. Several important noncontraceptive health benefits of oral contraceptive use include the prevention of endometrial and ovarian cancers. Data are generally reassuring concerning the risks of oral contraceptive use, which include cardiovascular disease and breast and cervical cancer. 
Mismatch of left ventricular function and infarct size demonstrated by technetium-99m isonitrile imaging after reperfusion therapy for acute myocardial infarction: identification of myocardial stunning and hyperkinesia. Quantitation of perfusion defect size using tomographic imaging with technetium-99m-hexakis-2-methoxy isobutyl isonitrile was performed at the time of hospital discharge in 32 patients with a first myocardial infarction who underwent successful coronary reperfusion within 8 h of the onset of chest pain. Reperfusion was accomplished with thrombolysis or primary coronary angioplasty. Radionuclide angiography was performed at discharge and 6 weeks later. There was a close correlation between perfusion defect size and values for ejection fraction and regional wall motion both at discharge (r = -0.80 and -0.75, respectively) and 6 weeks later (r = -0.81 and -0.81, respectively). There was no overall group difference in ejection fraction between the value at discharge and at 6 weeks; however, five patients had a significant increase (greater than or equal to 0.08) and six had a significant decrease (greater than or equal to 0.08) in ejection fraction. In patients with a significant increase at 6 weeks, ejection fraction was significantly lower at discharge than the value predicted from perfusion defect size (0.37 +/- 0.09 measured versus 0.47 +/- 0.13 predicted, p less than 0.05) and it improved at 6 weeks to near predicted values (0.51 +/- 0.07). In patients with a significant decrease at 6 weeks, ejection fraction was significantly higher at discharge than the value predicted from perfusion defect size (0.60 +/- 0.10 measured versus 0.50 +/- 0.10 predicted, p less than 0.05) and it decreased at 6 weeks to near predicted levels (0.51 +/- 0.09). Left ventricular ejection fraction at the time of hospital discharge is a potentially misleading index of the efficacy of reperfusion therapy for myocardial infarction. In a significant minority (34%) of patients this index does not accurately reflect perfusion defect size, apparently because of the effects of myocardial stunning and compensatory hyperkinesia. 
Management of valvular heart disease: an illustrative cases approach. As indicated by the 22 illustrative cases included in this monograph, a stepwise approach to the assessment of valvular heart disease provides the information necessary to make good clinical decisions. The ECG and chest x-ray add useful information to the history and physical examination. Echocardiography, Doppler, and color flow Doppler techniques have an important role in defining the presence and severity of valvular stenosis and regurgitation. Nuclear techniques provide useful information about global biventricular systolic function, regional wall motion, and myocardial perfusion. Exercise testing is most valuable in confirming objectively the patient's functional status and exercise tolerance. Newer imaging techniques, such as cine CT and MRI, are capable of displaying and measuring cardiac chamber size and myocardial thickness; however, visualization of the cardiac valves and demonstration of flow abnormalities are difficult, limiting the current usefulness of these techniques in patients with valvular heart disease. 
Dysphagia in psychiatric patients: clinical and videofluoroscopic study. Deaths due to airway obstruction are more common in psychiatric inpatients than in the normal population. A dysphagia program was started in a 400 bed Massachusetts psychiatric hospital after 4 patients in 1 year died from asphyxia. In the year after the program was started, there were no deaths; however, 28 patients experienced 32 choking incidents. The 28 patients received clinical evaluations by speech pathologists, neurologists, psychiatrists, and internists. Of the incidents, 55% required use of the Heimlich maneuver to open the airway. Choking incidents could be classified into five types based on results of clinical examination: bradykinetic, dyskinetic, fast eating syndrome, paralytic, and medical. Twenty-one of the 28 patients were studied by videofluoroscopy and 86% of the videos were abnormal, showing aspiration in eight, webs in five, and delay in the oral phase in five. Patients with bradykinetic dysphagia (secondary to neuroleptic-induced extra-pyramidal syndrome [EPS]) and paralytic dysphagia appeared to experience a more severe form of choking. 
Fatigue and depression in the patient in the intensive care unit. The recognition, management, and treatment of fatigue and depression in the patient in the intensive care unit has been presented in a framework to allow consideration of intrapsychic, interpersonal, environmental, and disease factors that can be altered by various means. It is rare that fatigue so seriously complicates the primary illness as to be life threatening itself. Depression and delirium are associated with increased morbidity and mortality on their own; therefore, prompt attention to major depressive disorders and organic effective disorders is necessary. Through it all, attention to the person who has the disease with fatigue, depression, or both is essential. 
Circadian variation in the frequency of onset of chest pain in acute myocardial infarction. The time of onset of chest pain was studied prospectively in 1154 consecutive patients admitted to a coronary care unit with myocardial infarction during a five year period. Statistical analysis confirmed a previous finding in a retrospective study of a bimodal frequency distribution with peaks in the time of onset of chest pain between 2330 and 0030 hours and between 0630 and 0830 hours. 
Bioelectric impedance analysis: experience with male patients with cirrhosis. Bioelectric impedance analysis is a new, convenient and portable method used to estimate total body water and to assess body composition in healthy people. We used the tetrapolar bioelectrical impedance analysis method in 58 cirrhotic patients to assess its clinical applicability. Whole-body resistance, reactance and impedance were measured and compared with those of 30 healthy volunteers matched for age and sex. The resistance and impedance values of ascitic cirrhotic patients (resistance = 461 +/- 80 omega; impedance = 462 +/- 80 omega) and nonascitic cirrhotic patients (resistance = 487 +/- 96 omega; impedance = 489 +/- 97 omega) were comparable with the resistance (488 +/- 44 omega) and impedance (491 +/- 44 omega) of controls. However, a significant (p less than 0.05) reduction in whole body reactance was found in patients with ascites and in those without ascites (34 +/- 9 omega vs. 47 +/- 12 omega) as compared with healthy subjects (56 +/- 7 omega). In 10 ascitic patients total body water was determined both before and after paracentesis; the volume of intraperitoneal fluid removed (7.9 +/- 3.8 L) could not be fully accounted for but only detected as an average volume of 1.9 +/- 1.0 L independently of the initial volume of the ascites. Our data clearly demonstrate that tetrapolar bioelectric impedance analysis is not adequate for measuring variations of "compartmentalized" fluid in the abdomen. 
Survival and valve failure after aortic valve replacement. A prospective evaluation of 412 consecutive patients undergoing isolated aortic valve replacement between January 1982 and December 1985 was performed in an attempt to identify the determinants of survival and valve failure. A variety of valves were inserted to permit a prospective evaluation of alternative valves including: Bjork-Shiley mechanical (n = 37), Ionescu-Shiley pericardial (n = 261), Hancock pericardial (n = 78), and Carpentier-Edwards porcine (n = 36). Thirteen patients died in the hospital (3.2%) and 47 patients died in the follow-up period producing an actuarial survival of 81% +/- 3% at 48 months. Survival was independently predicted by advancing age, preoperative New York Heart Association functional class, and the presence of endocarditis (p less than 0.05 by Cox regression analysis). The majority of patients were symptomatically improved (New York Heart Association class I or II: 21% preoperative, 88% postoperative). Freedom from structural valve dysfunction, prosthetic valve endocarditis, and reoperation for valve-related complications were 95% +/- 2%, 95% +/- 2%, and 92% +/- 2% at 48 months, respectively. These valve-related complications occurred more frequently in younger patients and in those with a Hancock pericardial valve (freedom from structural valve dysfunction, 89% +/- 5%; prosthetic valve endocarditis, 84% +/- 9%; reoperation, 78% +/- 10%; p less than 0.05 by Cox regression). Freedom from thromboembolism was 88% +/- 2% at 48 months; it was significantly lower in patients with a preoperative thromboembolic event and was not influenced by the type of prosthesis inserted. Freedom from anticoagulant-related hemorrhage was 85% +/- 8% at 48 months and was not influenced by any preoperative factors. 
National High Blood Pressure Education Program Working Group Report on High Blood Pressure in Pregnancy This consensus report focuses the presentation, pathophysiology, and management of the hypertensive disorders of pregnancy expanding on recommendations first presented in 1988 by the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. Practicing physicians should determine whether a patient's hypertension during pregnancy falls into the classification of (1) chronic hypertension, (2) preeclampsia, (3) preeclampsia superimposed on chronic hypertension, or (4) transient hypertension. The distinction, for management considerations, is made between hypertension that is present before pregnancy (chronic and preexisting) and that occurring as part of the pregnancy-specific condition preeclampsia. When maternal blood pressure reaches diastolic levels of 100 mm Hg or greater, treatment should be instituted to avoid hypertensive vascular damage. The report includes a discussion of antihypertensive therapy specific to the chronic or acute hypertension occurring concomitantly with pregnancy. The roles of calcium supplementation and low-dose aspirin to prevent preeclampsia and chronic and transient hypertension are under investigation. 
Clinical, physiologic, anatomic and procedural factors predictive of restenosis after percutaneous transluminal coronary angioplasty. In a recent prospective double-blind placebo-controlled trial, a combination of aspirin and dipyridamole was not associated with a reduction in the rate of restenosis within the 1st 6 months after coronary angioplasty. The purpose of this study was to determine whether clinical, anatomic or procedural factors were predictive of the observed restenosis rates in that prospective trial. A total of 247 patients and 280 segments underwent follow-up angiography and quantitative coronary angiographic analysis between 4 and 7 months after coronary angioplasty. Two baseline clinical characteristics--angina class and duration of angina in months--were related to the rate of restenosis by univariate analysis. Patient-related stepwise logistic regression analysis identified severity of angina as the only clinical predictor of restenosis. Three univariate baseline anatomic characteristics--percent diameter stenosis before angioplasty, stenosis greater than 10 mm in length and calcific stenosis--and two early postangioplasty characteristics--residual percent diameter stenosis and residual mean pressure gradient--were predictive of restenosis. Of these, only two--length of stenosis and residual percent diameter stenosis--were independently related to restenosis by multivariate analysis and only the former is identifiable before the procedure. It is concluded that in prospective studies in contrast to retrospective studies, few clinical and anatomic factors appear to be predictive of restenosis after coronary angioplasty. 
What is the role of the central nervous system in mineralocorticoid hypertension? The importance of the central nervous system (CNS) in the development of mineralocorticoid hypertension has been well documented. Type I receptors in adrenalectomized rats are concentrated in the hippocampus, amygdala, lateral septum, and hypothalamus, particularly in the periventricular regions, areas known to be or suspected of being important in the regulation of ACTH release, arousal, fluid and fluid osmolality equilibrium, and the maintenance of normal blood pressure. In the rat, ablation of the AV3V area and central, but not peripheral, sympathectomy prevent the development of DOCA-salt hypertension. The continuous intracerebroventricular (icv) infusion of aldosterone in rats or dogs at doses which do not affect the blood pressure when administered subcutaneously (sc) produces significant increases in resting blood pressure. In rats this effect is dose dependent, blocked by the concomitant icv infusion of prorenone, an aldosterone antagonist, and enhanced, but not completely dependent upon renal mass reduction and excess salt consumption. The icv infusion of RU28318, a selective mineralocorticoid antagonist, at doses which are ineffective when administered sc, inhibits the development of hypertension produced by the sc infusion of aldosterone or deoxycorticosterone, as well as that produced by the oral administration of a licorice derivative and of a high salt diet in the Dahl S/JR rat. It is assumed that this effect is mediated through the mineralocorticoid receptor because it is inhibited by mineralocorticoid antagonists and because the icv infusion of RU26988, a selective glucocorticoid agonist, has no effect. The concomitant icv infusion of corticosterone, which is thought to be the primary ligand of the brain mineralocorticoid receptor, antagonizes the effect of icv infusion of aldosterone. 
Epidemiology of pain in New Zealand. Information on the prevalence of pain in the general population has relevance for the allocation of health services and for understanding of chronic pain. In 1986 a sample of 1498 adults were interviewed using the Diagnostic Interview Schedule. Questions on pain were taken from the somatisation section of the interview schedule. These responses were used to determine the lifetime prevalence of pain in the urban population of New Zealand. The majority of subjects reported more than one life disrupting experience of pain. Pain was most common in the joints, back, head and abdomen. Women reported more pain than men. In general the prevalence of pain increased with age, however this was not true for headaches and abdominal pain. Most subjects related their pain symptoms to a physical cause. 
National High Blood Pressure Education Program Working Group report on hypertension and chronic renal failure. End-stage renal disease attributed to hypertension has increased annually for the last decade and will probably worsen through the year 2000. Patients with diabetic nephropathy and patients with hypertensive renal disease account for most new cases annually. Evidence reveals that all levels of untreated hypertension are associated with potentially declining renal function. Data from the Hypertension Detection and Follow-up Program and other studies show that antihypertensive treatment can prevent progressive renal failure. An ablation model demonstrates glomerular hyperfiltration as a possible mechanism for progressive renal failure. Human data on the renal effects of antihypertensive agents are limited and inconsistent. Despite the limitations, the Working Group on Hypertension and Chronic Renal Failure concludes that controlled hypertension to less than 140/90 mm Hg reduces the incidence of end-stage renal disease. Patients with established renal impairment may benefit from individualized treatment to 130/85 mm Hg or less. 
Myospherulosis. Complicating wound healing. Myospherulosis is a complication of wound healing which results from an action between lipids and extravasated erythrocytes. A case of myospherulosis of the mandible is reviewed with its history, histopathology and occurrence. 
Clinically significant pneumatosis intestinalis with postoperative enteral feedings by needle catheter jejunostomy: an unusual complication. We evaluated the incidence of clinically significant pneumatosis intestinalis and intestinal necrosis with the use of needle catheter jejunostomy in 217 consecutive patients who had undergone complicated abdominal operations or selected bariatric procedures. The needle catheter jejunostomy was used to deliver immediate postoperative nutrition, maintenance, and replacement fluids, and selected medications. In this group, no serious complications requiring surgical intervention were related to the use of needle catheter jejunostomies. Clinically significant pneumatosis intestinalis was encountered in two of 217 patients (1%). With the needle catheter jejunostomy in place, both patients improved rapidly when enteral feedings were discontinued and parenteral antibiotics were administered. None of the 217 patients developed ischemic intestinal necrosis. We conclude that 1) clinically significant pneumatosis is a rare complication of enteric feeding via needle catheter jejunostomy when the intrajejunal feeding is begun with a diluted, hypoosmolar solution with stepwise increases in osmolality, and 2) patients who do develop clinically significant pneumatosis (n = 2) seem to respond rapidly to a temporary stoppage of enteral feedings and administration of parenteral antibiotics. 
Cultured human bladder tumors for pharmacodynamic studies. Human bladder tumor fragments were cultured on collagen gel. In this system, the three dimensional architecture, cell-to-stroma and cell-to-cell interactions, and tumor heterogeneity were maintained. Cell viability and labeling index (LI) were determined by exposure to 3H-thymidine and autoradiography. Of the samples from 20 patients with transitional cell carcinoma, 14 (70%) were successfully cultured and had a mean LI of 32%. In addition, one specimen from a patient with squamous cell carcinoma was cultured and had a LI of 61%. Cultured samples were tested for chemosensitivity using a two hour exposure of mitomycin C in concentrations ranging from one to 50 micrograms./ml. A dose-dependent relationship was demonstrated; LI decreased as mitomycin C concentrations increased. The methodology described provides an alternative to suspension or monolayer techniques of culturing human bladder tumors for pharmacological studies. 
Experience with multiagent chemotherapy for osteosarcoma. Improved outcome. Clinical researches at the authors' institution have been treating patients with osteosarcoma with effective adjuvant chemotherapy for 18 years, including 14-years experience with limb-salvage surgery. The outlook for patients with nonmetastatic high-grade osteosarcoma has improved dramatically since 1972. Updated results of the single-agent adjuvant (postoperative) chemotherapy trial project a five-year disease-free survival (DFS) of 42% (95% confidence interval [CI], 14% to 70%) with follow-up periods of 5.7 to 13.8 years compared to a two-year DFS of 78% (60% to 95%) and follow-up periods of 0.6 to 6.8 years with six-agent, alternating, adjuvant postoperative chemotherapy. Additionally, since limb-salvage surgery began to be offered in 1976 to selected patients, 36 of 74 patients (49%) have had limb-salvage operations performed. The two-year DFS is 69% (52% to 85%) for patients having limb-salvage operations with follow-up periods of 0.6 to 10.3 years compared to 72% (57% to 87%) for amputees with follow-up periods of 0.3 to 10.3 years. It is concluded that patients receiving limb-salvage operations appear to be at no greater risk for relapse than patients receiving cross-bone amputation and that the administration of alternating, multiagent, adjuvant chemotherapy has significantly improved the DFS for patients who present with nonmetastatic high-grade osteosarcoma. 
Phase I-II trial of pentoxifylline for the prevention of transplant-related toxicities following bone marrow transplantation. Disease relapse and transplant related toxicities have limited the application of bone marrow transplantation (BMT) in the treatment for hematologic malignancies. Because elevated levels of tumor necrosis factor alpha (TNF-alpha) have been correlated with the development of transplant related complications, we conducted a phase I-II trial of pentoxifylline (PTX), a xanthine derivative capable of down-regulating TNF-alpha production, in patients with hematologic malignancies undergoing BMT. Thirty consecutive adult patients (median age, 34) were entered and received either an allogeneic (n = 26) or autologous (n = 4) BMT. Patients were enrolled at increasing dose levels (1,200, 1,600, and 2,000 mg/d) from day -10 through day +100 posttransplant. PTX was well tolerated with no significant adverse side effects noted at any of the dose levels administered. The actuarial day 100 survival for these 30 patients was 90% (95% confidence interval 79% to 100%). When compared with a good risk control group, PTX recipients experienced less mucositis (3.7 +/- 1.1 v 18.7 +/- 1.1 days, P = .004), less hepatic venocclusive disease (10% v 65%, P = .001), a lower incidence of renal insufficiency (3% v 65%, P = .0003), required less days of total parenteral nutrition (TPN) (24.0 +/- 1.3 v 35.0 +/- 2.4, P = .001) and were discharged from the hospital earlier than controls (day 26.0 +/- 1.8 v 37.0 +/- 3.8, P = .01). In addition the incidence of graft-versus-host disease (GVHD) greater than or equal to grade II was also reduced among the PTX recipients (35% v 68%, P = .03). PTX at doses in excess of 1,200 mg/d further reduced the severity of mucositis, and TPN requirements resulting in earlier hospital discharge than patients receiving 1,200 mg/d of PTX. In this study oral administration of PTX in doses up to 2,000 mg/d was well tolerated and associated with a reduction in morbidity and mortality in patients undergoing BMT. Prospective randomized trials are currently in progress to test these preliminary observations. 
Granulomatous renal mass during endovesical BCG therapy for bladder carcinoma. Diagnosis by fine-needle aspiration. One case of pseudotumoral granulomatous renal mass during endovesical bacillus Calmette-Guerin (BCG) therapy for superficial bladder neoplasm is reported. Such an adverse effect is exceptional and is clearly related to a vesicorenal reflux in our patient. In this case ultrasound-guided fine-needle aspiration was able to settle the diagnosis and avoid surgery. The patient responded to triple antituberculous therapy. 
Intranasal amphotericin B reduces the frequency of invasive aspergillosis in neutropenic patients. PURPOSE: To retrospectively study the prophylaxis of invasive aspergillosis in neutropenic patients and to relate the frequency of this fungal disease to any causal or modifying factors that could be identified. PATIENTS AND METHODS: Between 1977 and 1988, 130 patients underwent 158 intensive treatment episodes to control acute leukemia, lymphoma, and aplastic anemia, and the frequency of complicating aspergillus infection was determined. RESULTS: Proven invasive aspergillus infections occurred in 22 cases, 12 of which were fatal. Invasive aspergillosis was suspected in a further 16 cases and all these patients recovered with amphotericin B treatment. Colonization by Aspergillus in the absence of clinically significant infection was seen in 31 treatment episodes. Invasive aspergillosis involved mainly the upper and lower respiratory tract and skin. Control of the infection was closely related to the control of the underlying disease, with subsequent return of normal marrow function and resolution of neutropenia. The incidence of aspergillus infection has decreased dramatically since 1985, most probably due to the introduction of intranasal amphotericin B. This occurred despite the persistence of aspergillus spores in the hematology ward air during the 1986 to 1988 period. CONCLUSION: Intranasal aerosolized amphotericin B may protect against invasive aspergillosis, even when neutropenic patients are cared for in conventional wards without HEPA filtration. 
Hydronephrosis after aortofemoral bypass graft. A prospective study. This prospective study was designed to determine the frequency and natural history of hydroureteronephrosis (HUN) after placement of an aortobifemoral vascular graft. A total of 30 patients were evaluated by the study protocol, which included: pre and postoperative biological kidney function tests, preoperative and early postoperative (14th day) intravenous pyelograms and a late (mean 18th month) urologic examination by renal ultrasonic tomography. Four asymptomatic, early cases of HUN were observed in the 57 ureters examined (7%); all four complications regressed in less than 30 days. No cases of symptomatic early or late HUN were observed in this series. Asymptomatic early HUN was a frequent complication in our series (7%) but its benign course does not justify systematic screening. These asymptomatic complications contrast with the symptomatic cases of early or late HUN reported in the literature which necessitated urologic and vascular investigations. 
Listeria meningitis and pate. Listeria meningitis occurred in a 63 year old man who was in complete haematological remission following chemotherapy for acute myeloid leukaemia. The patient had followed Department of Health advice to immunocompromised patients and had avoided soft cheeses, cook-chill meals, and salads. He had, however, recently eaten pate produced in Belgium. This was no longer available for examination but a coincidental survey of pate in the Cardiff area found Listeria monocytogenes in 16 out of 73 samples. Pate should be included in the list of foods to be avoided by immunocompromised patients. 
Studies in autotomy: its pathophysiology and usefulness as a model of chronic pain. An interesting behavioral syndrome results in animals from the same or similar types of lesions that lead to deafferentation pain in humans; many neurectomized animals begin to scratch, bite, or self-mutilate their denervated limb, a phenomenon termed autotomy. The proposition that this behavior in animals is a response to the chronic pain of peripheral nerve injury has met with considerable controversy. If this issue were resolved, then a better understanding of the neurophysiology of autotomy might help elucidate the mechanisms of the human conditions. To determine the association between deafferentation and the autotomy behavior, we developed a pharmacologically induced functional deafferentation preparation using chronic perineural lidocaine infusion of the sciatic nerve. This 'chronic lidocaine' model's behavior was compared with that of the neurectomy model. While autotomy was noted in 80% of the latter group, no animal undergoing a chronic perineural infusion of lidocaine autotomized. We thus conclude that autotomy is not a response to non-painful sensory deafferentation, but rather that this behavior is a response to pain. We also studied the development of autotomy in a variety of other focal denervation preparations. On the basis of these data, we conclude that autotomy is not due to loss of sensory input on a functional basis nor to an action potential-mediated process. Rather, nerve damage which coincidentally involves sensory loss is necessary and sufficient for the development of this behavior. We suggest that interruption of a humoral feedback process homeostatically operating within the first order sensory neuron with its effect exerted post-synaptically leads to autotomy. The evidence supports the existence of a loss of a transportable, humoral autotomy inhibitory factor. 
Blood antibodies and uncrossmatched type O blood. The immediate transfusion of uncrossmatched type O blood in the initial resuscitation of the trauma victim remains controversial. To examine difficulties in crossmatching blood for later transfusions after use of uncrossmatched type O blood, we undertook a prospective 23-month study at a level I trauma center. One hundred thirty-five severely injured patients received uncrossmatched type O blood during the study period. Sixty-one patients (45%) died and 76 patients (56%) underwent emergent operation. There were no major transfusion reactions. Six patients had blood antigen-antibodies present on admission, and such antibodies developed in three patients during hospitalization. We conclude that uncrossmatched type O blood may be used safely in the exsanguinating patient, but blood antigen-antibodies, which may complicate later crossmatching, can develop after its use. 
A study of elastic tissue and actinic radiation in "aging," temporal arteritis, polymyalgia rheumatica, and atherosclerosis. The actinic storm in the modern world. Solar radiation provokes a lifelong series of destructive changes in the supporting elastic tissues of "exposed" skin. Called actinic elastosis/lysis (or actinic "aging"), the sequence begins in early life as simple elastic hyperplasia, converts in middle life to progressive actinic elastotic degeneration, and, in late life, typically ends with a stage of resorption (elastolysis) and atrophy ("aged" skin). Superficial "exposed" arteries such as the temporal artery participate in the same sequence of degenerative elastotic changes, which, as in the skin, may provoke granulomatous responses in a few of the many subjects affected. In the case of the temporal artery, a contingent outcome may be giant cell (temporal) arteritis and its recognized systemic vascular expression, polymyalgia rheumatica. Actinic commotion at the surface of the body is often massive in degree and extent and may be expected to exert a deleterious autoimmune impact on the essential elastic tissues of the arterial system. For this reason, solar radiation should be recognized as a risk factor for other elastic-related vascular diseases, including atherosclerosis and aneurysms. Man-made radiations may be exacerbating the effects of predominant solar radiation. Of the many radiant bands that make up the actinic (electromagnetic) spectrum, little is known for certain about the identity of those that cause these prevalent disorders of elastic tissue. Until this void is filled, more care should be taken with solar and the other "safe" radiations. 
The effects of recombinant human interferon-gamma on a panel of human bladder cancer cell lines. We have examined the Major Histocompatibility Complex class II antigen inducing capabilities of recombinant human interferon-gamma, on a panel of human transitional cell carcinoma lines which have been raised from original tumours of varying histological grades: RT4 (grade 1), RT112 (grade 2) and MGH-U1 (grade 3). Cells were examined for class II antigens using an indirect immunofluorescent staining method and analysed on a fluorescence activated cell sorter. Twenty percent of RT4 cells constitutively expressed class II antigen. Both RT112 and MGH-U1 were repeatedly found to be negative for this antigen prior to treatment with interferon-gamma. Following treatment with interferon-gamma all three lines showed an increase in class II antigen expression, which was consistently dependent on both the length of incubation and concentration of interferon-gamma. A differential susceptibility was found amongst the three cell lines which may relate to the histological grade of the parent tumor. 
Optochiasmal arachnoiditis following muslin wrapping of ruptured anterior communicating artery aneurysms. Optochiasmal arachnoiditis has been reported following treatment of ruptured intracranial aneurysms, particularly arising from the anterior communicating artery. It has been suggested that the accompanying loss of vision is due to a muslin-induced optic neuropathy. This paper considers five cases of this condition; the response to steroid therapy was beneficial in three cases. A review of the literature is included. The arachnoiditis is considered to be due to an inflammatory response to muslin gauze placed close to the optic nerves and chiasm. 
Potentially lethal complications of shigellosis. Complications that can lead to death during shigellosis include intestinal as well as systemic manifestations. The former include intestinal perforation, toxic megacolon, and dehydration, and the latter include sepsis, hyponatremia, hypoglycemia, seizures and encephalopathy, hemolyticuremic syndrome, pneumonia, and malnutrition. Data on the frequency of these complications come primarily from hospital-based studies, in which sepsis-either with Shigella or with other Enterobacteriaceae-and hypoglycemia are the most common causes of death. Management of these two complications requires broad-spectrum empiric antibiotic treatment of all severely ill, malnourished patients with shigellosis as well as frequent feedings to prevent hypoglycemia. Unfortunately, in developing countries, access to parenteral broad-spectrum antimicrobial agents is often limited, and frequent feedings are often precluded by the severe anorexia that is characteristic of shigellosis. Realistic approaches to the reduction of mortality from shigellosis must continue to focus on prevention and early antimicrobial therapy rather than on treatment of established complications. 
Acute diverticulitis. A complicated problem in the immunocompromised patient. We reviewed the records of 209 patients with acute diverticulitis treated from 1984 through 1989 to determine if immunocompromised patients have a worse prognosis than nonimmunocompromised patients. Forty immunocompromised patients and 169 nonimmunocompromised patients with acute diverticulitis were identified. Free perforation into the peritoneal cavity occurred in 43% (17/40) of immunocompromised patients and 14% (24/169) of nonimmunocompromised patients. Operations were performed in 58% (23/40) of immunocompromised patients and 33% (55/169) of nonimmunocompromised patients. Postoperative morbidity was 65% (15/23) in immunocompromised patients and 24% (13/55) in nonimmunocompromised patients; postoperative mortality was 39% (9/23) and 2% (1/55), respectively. We conclude that acute diverticulitis in the immunocompromised patient is a complicated problem; there is a greater risk of free perforation and need for surgery than in the nonimmunocompromised patient. Furthermore, the prognosis for immunocompromised patients who undergo surgery is worse than that for nonimmunocompromised patients. 
The effect of transcutaneous nerve stimulation on sphincter of Oddi pressure in patients with biliary dyskinesia. Vasoactive intestinal polypeptide (VIP) has been postulated as a neuropeptide with inhibitory neurotransmitter activity in nonadrenergic noncholinergic pathways. Transcutaneous electric nerve stimulation (TENS) relaxes the lower esophageal sphincter in patients with achalasia. Such response is accompanied by a 30% increase in VIP concentrations in the systemic circulation. Since the sphincter of Oddi (SO) receives a very dense VIP nerve supply, we evaluate the effect of TENS on SO motor activity and on VIP plasma concentrations in patients with biliary dyskinesia and in healthy volunteers. TENS was performed with a pocket stimulator for 45 min. SO pressure and VIP levels were obtained before and after 45 min of TENS. In patients with SO dyskinesia, TENS produced a significant decrease in SO pressure from 80.1 +/- 11.9 mm Hg to 58.3 +/- 9.7 mm Hg p less than 0.01); this was accompanied by a significant increase in VIP plasma levels from 21.1 +/- 0.5 pg/ml to 32.6 +/- 1.5 pg/ml (p less than 0.01). In healthy volunteers, TENS did not produce significant changes in SO pressure. However, a significant increase in VIP plasma values was observed (p less than 0.01). No significant changes in amplitude, duration and frequency of SO phasic contractions were observed in either of the two groups evaluated. We conclude that, in patients with SO dyskinesia, TENS decreases SO basal pressure, possibly by a direct action of the released VIP in the systemic circulation. In healthy volunteers, TENS increases VIP plasma values without significant effect on SO basal pressure. These findings suggest that the response to TENS may be mediated by VIP. It is also possible that the alterations seen in patients with biliary dyskinesia may be due to impairment of the VIP nerve supply at the level of the SO. 
The effect of diazepam enema on the rectal mucosa of rats. The use of undiluted intravenous diazepam solution administered as an enema has been recommended for the acute management of seizures when intravenous access cannot be obtained. It is well absorbed, rapidly effective, and generally accepted as being safe when used in this manner. The effect of intravenous diazepam solution on the rectal mucosa has not been studied. This study demonstrates that there are no acute changes in the rectal mucosa of adult rats after administration of 10 to 20 times the recommended human dose. 
Myocardial metabolic, hemodynamic, and electrocardiographic significance of reversible thallium-201 abnormalities in hypertrophic cardiomyopathy. BACKGROUND. Exercise-induced abnormalities during thallium-201 scintigraphy that normalize at rest frequently occur in patients with hypertrophic cardiomyopathy. However, it is not known whether these abnormalities are indicative of myocardial ischemia. METHODS AND RESULTS. Fifty patients with hypertrophic cardiomyopathy underwent exercise 201Tl scintigraphy and, during the same week, measurement of myocardial lactate metabolism and hemodynamics during pacing stress. Thirty-seven patients (74%) had one or more 201Tl abnormalities that completely normalized after 3 hours of rest; 26 had regional myocardial 201Tl defects, and 26 had apparent left ventricular cavity dilatation with exercise, with 15 having coexistence of these abnormal findings. Of the 37 patients with reversible 201Tl abnormalities, 27 (73%) had metabolic evidence of myocardial ischemia during rapid atrial pacing (myocardial lactate extraction of 0 mmol/l or less) compared with four of 13 patients (31%) with normal 201Tl scans (p less than 0.01). Eleven patients had apparent cavity dilatation as their only 201Tl abnormality; their mean postpacing left ventricular end-diastolic pressure was significantly higher than that of the 13 patients with normal 201Tl studies (33 +/- 5 versus 21 +/- 10 mm Hg, p less than 0.001). There was no correlation between the angiographic presence of systolic septal or epicardial coronary arterial compression and the presence or distribution of 201Tl abnormalities. Patients with ischemic ST segment responses to exercise had an 80% prevalence rate of reversible 201Tl abnormalities and a 70% prevalence rate of pacing-induced ischemia. However, 69% of patients with nonischemic ST segment responses had reversible 201Tl abnormalities, and 55% had pacing-induced ischemia. CONCLUSIONS. Reversible 201Tl abnormalities during exercise stress are markers of myocardial ischemia in hypertrophic cardiomyopathy and most likely identify relatively underperfused myocardium. In contrast, ST segment changes with exercise and systolic compression of coronary arteries on angiography are unreliable markers of inducible myocardial ischemia in hypertrophic cardiomyopathy. Apparent cavity dilatation during 201Tl scintigraphy may indicate ischemia-related changes in left ventricular filling, with elevation in diastolic pressures and endocardial compression. 
Structured lipid made from fish oil and medium-chain triglycerides alters tumor and host metabolism in Yoshida-sarcoma-bearing rats. The effects of structured lipid composed of fish oil and medium-chain triglycerides (Fish/MCT) on tumor and the host metabolism was compared with conventional long-chain triglycerides (LCTs) in Yoshida-sarcoma-bearing rats receiving TPN for 3 d. The two parenterally fed groups were divided into two treatments, saline or tumor necrosis factor (TNF), given intravenously at 20 micrograms/kg body wt. Changes in tumor volume, body weight, urinary nitrogen, whole-body and tissue protein kinetics, and fatty acid composition were measured. The study revealed that Fish/MCT feeding inhibited tumor growth, which could be attributed to decreased tumor protein synthesis. Body weight and nitrogen were better maintained by Fish/MCT feeding. In addition, the effects of Fish/MCT on tumor growth were synergistic with TNF treatment. The results demonstrate that dietary fat composition can influence fatty acid compositions of tumor tissue as well as tumor protein kinetics after a short period of TPN feeding. 
Sclerosing vasculopathy of the central nervous system in nonelderly demented patients. Three nonelderly patients without hypertension whose clinical and radiologic features otherwise resembled Binswanger's subcortical arteriosclerotic encephalopathy underwent biopsy of the hyperintense periventricular lesions seen on magnetic resonance imaging. The pathologic findings of the periventricular lesions consisted of gliosis with mild rarefaction and edema of the white matter. All patients had a sclerosing vasculopathy of unknown cause, which involved numerous small vessels within the periventricular lesions. The vessels stained negatively for amyloid, amyloid precursors, desmin, vimentin, keratin, immunoglobulin, and complement. On electron microscopy, small arteries, arterioles, venules, and capillaries were characterized by swollen astrocytic foot processes surrounding the vessels; dense, perivascular collagen packing; crystalline arrays of filaments within basement membrane; giant lipid-laden lysosomes within perivascular cells; and narrowing of the vascular lumina. Similar changes were not seen in a control group of 19 patients. The pathologic features of the vessels in these cases are distinct from the vasculopathy associated with Binswanger's subcortical arteriosclerotic encephalopathy. We suggest that a spectrum of vasculopathies may be associated with dementia and periventricular hyperintense lesions on magnetic resonance imaging. 
Carcinomas with metaplasia and sarcomas of the breast. The clinicopathologic, immunohistochemical, and flow cytometric characteristics of 34 cases of mammary carcinoma with metaplasia were compared with those of 20 cases of pure sarcoma of the breast. All 20 of the latter tumors showed the pattern of malignant fibrous histiocytoma. There were 20 cases of carcinoma with mesenchymal metaplasia, 7 cases of carcinoma with mixed epithelial (squamous) and mesenchymal metaplasia, and 7 cases of carcinoma with epithelial metaplasia (four mixed ductal/squamous and three pure squamous cell carcinomas). No patient with pure sarcoma had lymph node metastases develop; all nodal metastases were found in patients who had carcinoma with metaplasia, although in one case the carcinomatous component was seen only within a lymph node metastasis. Epithelial antigens were found not only within the epithelial elements of all cases of carcinoma, but also within the apparent mesenchymal elements of 44% of the carcinomas showing divergent differentiation. Flow cytometric analysis of eight cases of carcinoma with mesenchymal metaplasia showed aneuploidy/tetraploidy in six neoplasms. For patient management purposes, the distinction of pure sarcoma from carcinoma with metaplasia is important, but additional subclassification of carcinoma with metaplasia is of greater biologic than clinical interest. 
Very late recurrence of renal vasculitis. We report a case of renal vasculitis with a relapse occurring 9 and a half years after the original presentation. The plasma creatinine six months before relapse was only 118 mumol/l. During the initial illness there was histological evidence of glomerular damage but at the time of relapse renal biopsy showed the remaining glomeruli to be normal with the destructive process causing fibrinoid necrosis of arteries. 
Myasthenia gravis in mothers and their newborns. Myasthenia gravis is a complex autoimmune disorder. Anti-AChR antibodies destroy elements of the postsynaptic membrane of the myoneural junction in affected muscle groups. This results in decreased nerve-impulse transmission. Myasthenic patients have diminished skeletal muscle strength and tire rapidly with exercise. Pregnancy threatens maternal myasthenic exacerbation and crisis, particularly early in the puerperium. The medication requires frequent adjustment during pregnancy due to changing requirements and physiologic changes in absorption and excretion. Myasthenia results in an increase in maternal mortality, morbidity, pregnancy wastage, and premature labor. Anticholinesterase medications and corticosteroids are the mainstays of medical therapy of maternal MG. Thymectomy, plasmapheresis, immunosuppressant drugs, gamma globulin, and ACTH are adjuvants of varying usefulness. Enforced rest periods, a tranquil environment, and prompt treatment of intercurrent infections are important for myasthenic mothers. The management of myasthenic crisis requires hospital intensive care with mechanical respiratory support and careful monitoring of blood gases. Plasmapheresis is an effective means of controlling crises. It is usually combined with intensive steroid and or immunosuppressant therapy. The myasthenic mother undertakes pregnancy with increased risk to herself and her infant. There is a 40% chance of exacerbation of her MG during pregnancy and an additional 30% risk in the puerperium. Maternal mortality risk is approximately 40 per 1,000 live births. Perinatal mortality approximates 68 per 1,000 births, five times that of uncomplicated pregnancies. Modern management minimizes these risks to the extent that pregnancy is not precluded in myasthenic women. A good outcome depends on meticulous maternal and fetal prenatal surveillance and early detection and management of exacerbations. Facilities and trained personnel must be available to support labor and manage vaginal or operative delivery. Intensive care of myasthenic crises is critical to the prevention of maternal complications and death. 
Plexiform granular cell odontogenic tumor: unicystic variant. Plexiform granular cell odontogenic tumor of the mandible has recently been described. The cardinal histopathologic feature, as its name suggests, is a monophasic plexiform pattern of granular cells; the principal tumor in the differential diagnosis is granular cell ameloblastoma. Unlike the two previously reported cases of plexiform granular cell odontogenic tumor, which occurred as solid tumors in elderly men, the lesion reported here is a unicystic variant occurring in a middle-aged woman. 
The effects of neurokinin A, neurokinin B, and eledoisin on substance P analysis. Commercial sources for neuropeptide radioimmunoassays have made this sensitive tool available to clinical investigators for monitoring the potential involvement of neuropeptides in pain modulation. We measured substance P-like immunoreactivity in the plasma, saliva, and pericardial fluid of subjects with and without pain (chronic and acute) to determine if substance P levels are altered. Some recent studies have suggested that substance P in various body fluids may be a correlate of chronic pain. To test this correlation it is important to ensure that the assay is measuring what it was designed to measure. Therefore, the influence of three tachykinins on the analysis of substance P concentrations was assessed with a commercially available radioimmunoassay kit. A small (approximately 2 to 6%), apparently nonspecific elevation in measured substance P was found when alpha-neurokinin, beta-neurokinin, or eledoisin was incubated with substance P and its antibody. Our results also indicate an apparent specific affinity of the substance P antibody for alpha-neurokinin (above 1,000 pg/ml) and beta-neurokinin (above 5,000 pg/ml). Substance P levels in the body fluids we tested ranged from 0.47 to 62.88 pg/mg protein (47.4 to 230.8 pg/ml). Levels of the tested tachykinins have not been determined in body fluids. If alpha-neurokinin or beta-neurokinin is found to be present in high concentrations in these fluids, this commercially available substance P kit may overestimate substance P levels. The concentrations of tachykinins necessary to interfere specifically with the assay are 10- to 100-fold higher than substance P in body fluids. 
Hypoxemia is associated with mitochondrial DNA damage and gene induction. Implications for cardiac disease OBJECTIVE.--Oxidative phosphorylation (OXPHOS) deficiency due to hypoxemia or other causes was hypothesized to increase oxygen radical generation, damage mitochondrial DNA (mtDNA), and reduce adenosine triphosphate synthesis, resulting in compensatory OXPHOS gene induction. Therefore, we investigated the levels of mtDNA damage and OXPHOS transcripts in normal and ischemic hearts, and then in other forms of heart disease. DESIGN.--DNA was extracted from the heart and the levels of the common 4977 base pair mtDNA deletion were quantitated as an index for mtDNA damage. Total RNA was extracted from hearts and analyzed for OXPHOS transcript levels. RESULTS.--In control hearts, the 4977 base pair mtDNA deletion appeared at age 40 years and reached a maximum deletion of 0.0035%. Much higher levels were found in ischemic hearts (0.02% to 0.85%), as well as in three of 10 cases with other types of heart disease (0.017% to 0.16%). The OXPHOS transcripts were increased in all diseased hearts. CONCLUSION.--Ischemic hearts have increased mtDNA damage and OXPHOS gene expression, suggesting that mtDNA damage is associated with OXPHOS deficiency. Oxidative phosphorylation defects may also play a role in some other forms of cardiac disease. 
Stereotactic multiple arc radiotherapy. A radiotherapy technique is presented for delivering a concentrated pattern of absorbed dose to intracranial lesions. Treatment takes place on a conventional, isocentrically mounted linear accelerator, rotated in several planes around a single target site. A new, relocatable stereotactic frame is used which enables fractionated radiotherapy to be administered if required. Calculations of the absorbed dose distribution in three orthogonal planes are performed using specially prepared software on a computer used for standard treatment planning. In this way, the need for excessive computing power is avoided. 
Hypothermia in the summer. We have presented two cases of hypothermia associated with altered mental status occurring during the summer in the sunbelt. Both cases represent nonexposure hypothermia of multifactorial origin requiring prompt aggressive diagnostic and therapeutic intervention. The effects of phenothiazines, alcoholism, Wernicke's encephalopathy, Parkinson's disease, and altered mental status contributed to the development of hypothermia in these instances. Although both patients survived and were discharged from the hospital, it is likely that hypothermia in such situations has a higher mortality. Awareness of the broad differential of predisposing conditions is mandatory in treating such patients in a timely fashion. 
A quantitative approach to radiography of the lower limb. Principles and applications. A method is described which provides standardised reproducible radiographic images of the lower limb. Anteroposterior and lateral radiographs are digitised and processed by computer to provide graphic/numeric displays of angles and linear measurements, relating the centre points of the hip, knee, and ankle. Two cases illustrate how surgical planning is facilitated when standardised data are available. These data confirm the close relationship between postoperative limb alignment and positioning of prosthetic elements. 
The Edmonton injector: a simple device for patient-controlled subcutaneous analgesia. In a prospective open study we tested the Edmonton injector (EI), a device designed by our group for subcutaneous injection of narcotics. In 25 patients, the EI was used for patient-controlled analgesia (PCA); mean duration of treatment was 28 +/- 10 days. Mean equivalent daily dose of morphine was 160 +/- 85 mg. All patients found the EI safe and simple to operate. The main reason for discontinuation was death (10 cases) or return to oral narcotics (8 cases). In 20 patients who were admitted to the hospital and were too ill to learn PCA, the EI was used for regular s.c. administration by nurses. Narcotics were administered every 4 h and extra doses were administered on a 'PRN' basis. Waiting time for a 'PRN' dose in 8 patients before starting the EI was 18 +/- 7 min; after the EI was started, it was 3 +/- 4 min (P less than 0.01). We conclude that the EI is safe, effective and inexpensive, and that it will be particularly useful in smaller hospitals and developing countries. 
Liquid-propane freeze injury: a case history. Exposure of skin to liquid propane causes a severe freeze injury. This cutaneous injury has the appearance of a partial-thickness thermal injury of indeterminate depth, but the deep tissue damage is greater than is at first apparent. A case history is presented that illustrates the severity of this particular mechanism of injury and the need for adequate safety precautions. 
Acid secretory changes and early relapse following duodenal ulcer healing with ranitidine or sucralfate. Controversial aspects relating to acid secretory changes following duodenal ulcer healing, and the effect of histamine-2 (H2)-receptor blockers on such changes are discussed. Recent studies comparing the effects of ranitidine or sucralfate on changes in the acid secretory responses in the healing of duodenal ulcers are described, and the relevance of these changes to early relapse considered. The duration of therapy and timing of acid-secretory studies and endoscopies are standardized in all studies, but the acid-secretory parameters vary. These comprised acid secretory responses to graded doses of an intravenous infusion of pentagastrin or histamine, sham-feeding responses, and basal and nocturnal acid secretion. In all studies, healing with sucralfate was associated with a significant decrease in the various parameters of acid secretion. In the ranitidine-healed groups, no appreciable decrease was noted and there was, indeed, a significant increase in nocturnal acid secretion. Routine endoscopies performed 4-6 weeks after documented ulcer healing showed a recurrence of 3 of the 32 (9%) sucralfate-healed and in 14 of the 35 (40%) ranitidine-healed ulcers. Increased acid secretory responsiveness following duodenal ulcer healing was strongly correlated with subsequent early relapse. 
Selection of the approach to the distal internal carotid artery from the second cervical vertebra to the base of the skull. Although several approaches for exposure of distal internal carotid artery lesions have been reported, the precise anatomic levels for which each of these maneuvers are most appropriate have not been well described. Since these techniques may require preoperative preparation, it is useful to determine in advance how much exposure will be needed and to select the most suitable and effective technique. We used anatomic dissection in 12 human cadaver specimens (24 carotid bifurcations) to define the limits of distal internal carotid artery exposure by several commonly advocated methods. The standard anterior approach along the sternocleidomastoid muscle allowed exposure of the internal carotid artery to the level of the upper one third of the second cervical vertebra. The upper limit of this exposure was extended to the middle of the first cervical vertebra by division of the posterior belly of the digastric muscle. Anterior subluxation of the mandible increased the distal exposure of the internal carotid artery to the superior border of the first cervical vertebra. Styloidectomy in combination with the preceding maneuvers extended the exposure an additional 0.5 cm cephalad. Lateral mandibulotomy did not significantly extend exposure beyond that obtained with mandibular subluxation and styloidectomy. Exposure of the internal carotid artery in the 1 cm immediately below the base of the skull required a posterior approach with mastoidectomy. 
Effects of calcium antagonists on glomerular hemodynamics and structure in experimental hypertension. The RK, DS, and UNX SHR rats are related models of progressive renal disease characterized by the presence of severe systemic hypertension and reduction in renal mass. In these models, glomerular injury is related to increased glomerular pressure and to kidney and glomerular hypertrophy. As summarized in Table 1, administration of a calcium antagonist reduces the prevalence of glomerular sclerosis in all three models. Calcium antagonists have many effects that might tend to reduce renal injury. Similar to the ACE inhibitors, they may reduce PGC, although a protective effect has been observed in some models despite persistence of marked glomerular capillary hypertension. Calcium antagonists also appear to inhibit compensatory renal growth. The observation that these drugs lessen injury in experimental hypertension has important implications for the treatment of patients with hypertension and renal disease. However, widespread use of calcium antagonists specifically to prevent kidney damage should await the results of controlled clinical trials. 
Acute fulminant hepatic failure. Fulminant hepatic failure is the rapid onset of life-threatening hepatic decompensation in patients who have no previous history of liver disease. This condition has a multifactorial etiology, including viral hepatitis and drug toxicity. At this time there is no specific therapy for FHF. However, early diagnosis and treatment of the complications--in particular, cerebral edema--may prolong survival and prevent irreversible neurologic complications. Once the diagnosis has been made, patients with FHF should promptly be transferred to a specialized liver care unit where liver transplantation is available. Liver transplantation is now the treatment of choice for patients with clinical characteristics suggesting a poor chance of survival. 
Problems encountered with the Bethesda System: the University of Iowa experience. This paper provides a descriptive summary of 1 year's experience with the Bethesda Cytologic Classification System at the University of Iowa Hospitals and Clinics. Cytotechnologists and pathologists criticized the failure of the new classification system to provide microscopic criteria for the following categories: adequacy of the smear (satisfactory, less than optimal, unsatisfactory), atypical squamous cells of undetermined significance, atypical glandular cells of undetermined significance, and inflammation-associated changes. Clinicians criticized the "less than optimal" category and the reporting of koilocytosis, moderate dysplasia, and endometrial cells. Suggestions for modifying the Bethesda System include: eliminating the less than optimal response, defining what constitutes an unsatisfactory smear, eliminating the terms low-grade and high-grade squamous intraepithelial lesion, and changing the reporting of endometrial cells. 
Microglandular adenosis of the breast. An immunohistochemical comparison with tubular carcinoma. Microglandular adenosis (MA) of the breast is a benign, disorganized proliferation of glands lined by a single layer of cells. As such, differential diagnosis between MA and tubular carcinoma may be challenging in selected cases. A panel of antibodies was applied to 10 cases of MA and 10 of tubular carcinoma to investigate the potential benefit of immunohistochemistry in the separation of these lesions and the possible role of myoepithelial cells in MA. The luminal cells in nine cases of MA were surrounded by a cuff of muscle-specific actin-reactive cells, which also coexpressed cytokeratin and vimentin. The immunophenotype of these cells is characteristic of myoepithelial differentiation, which was heretofore thought to be lacking in MA. This finding demonstrates that myoepithelial cells are indeed present in MA subjacent to luminal epithelial cells; moreover, it distinghuishes MA from tubular carcinoma, all examples of which were actin negative in this analysis. In addition, circumferential type IV collagen deposition was observed around constituent glands of MA in nine cases but was lacking in all tubular carcinomas. Other markers included in this evaluation (S100 protein, gross cystic disease fluid protein 15, carcinoembryonic antigen, estrogen receptor protein) were of no differential diagnostic value. 
Propranolol in the prevention of the first hemorrhage from esophagogastric varices: A multicenter, randomized clinical trial. The Boston-New Haven-Barcelona Portal Hypertension Study Group. To assess the effectiveness of propranolol in the prevention of initial variceal hemorrhage, a double-blind, randomized trial was carried out in three centers. Patients with cirrhosis (78% alcoholic), hepatic venous pressure gradients greater than 12 mm Hg and endoscopically proven esophageal varices were randomly assigned to propranolol (51 patients) or placebo (51 patients). Of the 102 patients, 58% were Child's class A, 34% were Child's class B and 8% were Child's class C. Daily dosage was determined by the administration of progressively increasing doses of propranolol with the hepatic vein catheter in place to achieve a 25% decrease in hepatic venous pressure gradient, a decrease in hepatic venous pressure gradient to less than 12 mm Hg or a decrease in resting heart rate to less than 55 beats/min. During a mean follow-up period of 16.3 mo, 11 patients in the placebo group (22%) bled from esophageal varices compared with 2 in the propranolol group (4%) during a mean period of 17.1 mo (p less than 0.01). Three additional patients (6%) in the placebo group bled from portal hypertensive gastropathy compared with none in the propranolol group. Propranolol appeared effective in preventing bleeding from large varices. Eleven deaths (22%) occurred in the placebo group compared with eight deaths (16%) in the propranolol group (NS). The mean dose of propranolol was 132 mg/day, and the median dose was 80 mg/day. Using a compliance index (pill count, clinic attendance, alcohol and propranolol levels and alcohol history), 81% of the propranolol patients and 77% of the placebo patients were considered compliant. Complications severe enough to require cessation of therapy occurred in eight patients (16%) in the propranolol group and four in the placebo group (8%) (NS). We conclude that propranolol effectively prevents the first variceal hemorrhage in patients with alcoholic cirrhosis and large esophageal varices but does not improve survival. 
Stump pressure, the contralateral carotid artery, and electroencephalographic changes. Electroencephalographic (EEG) monitoring and measurement of stump pressure are the most widely employed methods of assessing the risk of cerebral ischemia during carotid endarterectomy. The status of the contralateral carotid artery has also been thought to influence the need for placing a shunt. The relationship of EEG monitoring, stump pressure, and the contralateral carotid artery has not been completely delineated. We retrospectively reviewed these three variables in 113 patients undergoing 124 carotid endarterectomies. The contralateral artery was classified as occluded, stenotic (greater than 50% decrease in diameter), or nonstenotic. There was a 48% incidence of EEG changes with contralateral occlusion, 18% with stenosis, and 21% with nonstenotic arteries (p = 0.014). There was a 73% incidence of EEG changes when the stump pressure was less than 25 mm Hg, 32% when the stump pressure was 25 to 50 mm Hg, and 2% when the stump pressure was greater than 50 mm Hg (p less than 0.001). There was no significant difference in the mean stump pressure for patients with occlusion (43.8 mm Hg), stenosis (44.7 mm Hg), or nonstenotic contralateral arteries (51.3 mm Hg). All patients with contralateral occlusion and a stump pressure less than 25 mm Hg had EEG changes. No patient with a stump pressure greater than 50 mm Hg and a patent contralateral artery had EEG changes. Although the incidence of EEG changes in the majority of patients was not accurately predicted by the stump pressure and the status of the contralateral carotid artery, stump pressure less than or equal to 50 mm Hg was sensitive, identifying 97% of patients with EEG changes. 
Malignant lymphoma of the urinary bladder. A case with signet-ring cells simulating urachal adenocarcinoma. We describe a malignant lymphoma involving the dome and anterior wall of the urinary bladder in an elderly woman. The initial biopsy showed a malignant neoplasm of uncertain cell type. Because the clinical presentation was most compatible with urachal adenocarcinoma, an extensive resection was performed. Microscopically, the excised tumor was composed of large lymphoid cells with isolated and clustered signet-ring cells. Immunohistochemical analysis established the B-cell phenotype of the neoplasm, and electron microscopy of the signet-ring cells revealed endoplasmic reticulum-bound inclusions consistent with immunoglobulin. Primary malignant lymphomas of the urinary bladder are rare, and, to our knowledge, we report the first example with signet-ring cells. We emphasize this histopathologic finding because of the potential for confusion with urachal adenocarcinoma. 
Is adult-onset coeliac disease due to a low-grade lymphoma of intraepithelial T lymphocytes? Enteropathy-associated T-cell lymphoma commonly presents with malabsorption, and debate continues as to whether adult-onset coeliac disease (CD) is itself a form of low-grade lymphoma. A 59-year-old man with adult-onset CD required resection of a segment of oedematous jejunum. Histological examination of this tissue revealed an intense intraepithelial lymphocytosis. Immunophenotypic (CD3-, CD4-, CD8-, CD34-, and CD45 RO-) and cytogenetic (deletion of the Y chromosome and chromosome 9) abnormalities were found, together with monoclonal T-cell-receptor gene rearrangements. Some patients with adult-onset CD may have low-grade lymphoma from the outset of their illness. 
Treatment of chronic pain by epidural spinal cord stimulation: a 10-year experience. Epidural spinal cord stimulation by means of chronically implanted electrodes was carried out on 121 patients with pain of varied benign organic etiology. In 116 patients, the pain was confined to the back and lower extremities and, of these, 56 exhibited the failed-back syndrome. Most patients were referred by a pain management service because of failure of conventional pain treatment modalities. Electrodes were implanted at varying sites, dictated by the location of pain. A total of 140 epidural implants were used: 76 unipolar, 46 Resume electrodes, 12 bipolar, and six quadripolar. Patients were followed for periods ranging from 6 months to 10 years, with a mean follow-up period of 40 months. Forty-eight patients (40%) were able to control their pain by neurostimulation alone. A further 14 patients (12%), in addition to following a regular stimulation program, needed occasional analgesic supplements to achieve 50% or more relief of the prestimulation pain. Pain secondary to arachnoiditis or perineural fibrosis following multiple intervertebral disc operations, when predominantly confined to one lower extremity, seemed to respond favorably to this treatment. Uniformly good results were also obtained in lower-extremity pain secondary to multiple sclerosis. Pain due to advanced peripheral vascular disease of the lower limbs was well controlled, and amputation below the knee was delayed for up to 2 years in some patients. Pain due to cauda equina injury, paraplegic pain, phantom-limb pain, pure midline back pain without radiculopathy, or pain due to primary bone or joint disease seemed to respond less well. Patients who responded to preliminary transcutaneous electrical nerve stimulation generally did well with electrode implants. Notable complications included wound infection, electrode displacement or fracturing, and fibrosis at the stimulating tip of the electrode. Three patients in this series died due to unrelated causes. Epidural spinal cord stimulation has proven to be an effective and safe means of controlling pain on a long-term basis in selected groups of patients. The mechanism of action of stimulation-produced analgesia remains unclear; further studies to elucidate it might allow spinal cord stimulation to be exploited more effectively in disorders that are currently refractory to this treatment modality. 
Cine magnetic resonance imaging for diagnosis of right coronary arterial-ventricular fistula. In two cases of coronary arterial-ventricular fistula, detailed morphologic evaluation of the affected coronary artery was performed by MRI. Cine-MRI enabled both identification of the fistula and evaluation of the direction of shunt blood flow. Thus, MRI is a valuable noninvasive procedure in the anatomic and physiologic diagnosis of coronary arterial fistula. 
Root of the superior mesenteric artery in pancreatitis and pancreatic carcinoma: evaluation with CT To determine if changes involving the root of the superior mesenteric artery are specific for neoplasm, the authors retrospectively reviewed 173 computed tomographic (CT) examinations of patients with proved pancreatitis (103 examinations) and pancreatic ductal adenocarcinoma (70 examinations). Streaky infiltration of the fat surrounding the root was seen in 27 of 56 examinations of acute pancreatitis, in four of 24 examinations of chronic pancreatitis, in 12 of 23 examinations of pancreatitis complicated by abscess, and in 25 of 70 examinations of pancreatic carcinoma. Periarterial lymph nodes were visible in 14 with acute pancreatitis, in three with chronic pancreatitis, in six with pancreatic abscess, and in 11 with pancreatic carcinoma. A focal mass extended to within 1 cm of the root in 10 with acute pancreatitis, in two with chronic pancreatitis, in four with pancreatic abscess, and in 24 with pancreatic carcinoma; the mass obliterated the periarterial fat in seven with acute pancreatitis, in one with pancreatic abscess, and in 18 with pancreatic carcinoma. Circumferential encasement occurred in one with chronic pancreatitis, in four with pancreatic abscess, in 14 with pancreatic carcinoma, and in none with acute pancreatitis; nearly all cases of encasement revealed loss of periarterial fat. Thus, these indicators are not specific for neoplasm. 
Study of belching ability in antireflux surgery patients and normal volunteers. The ability to belch was evaluated by a novel test, after gaseous stomach distension to standard volume, in 16 patients after antireflux surgery and nine healthy volunteers. A structured assessment of dyspeptic symptoms was also carried out in both groups. Repeat studies in volunteers showed acceptable reproducibility for the new test of belching capacity (within-subject coefficient of variance 4.5 per cent). After antireflux surgery, patients had lower volume individual belches (median(range) 27.5(0-104) ml in patients versus 76(15-165) ml in volunteers; P less than 0.02) and belched less gas within 1 h of the stimulus than volunteers (median(range) 205(0-1363) ml in patients versus 456(45-818) ml in volunteers; P less than 0.05). Belching frequency was similar in both groups. The incidence and severity of symptoms were unrelated to belched gas volumes. 
Platelet-free calcium and vascular calcium uptake in ethanol-induced hypertensive rats. This study examined the effect of moderate ethanol intake on systolic blood pressure, platelet cytosolic free calcium, aortic calcium, and rubidium-86 uptake in Wistar-Kyoto rats. Twelve Wistar-Kyoto rats, aged 6 weeks, were given 5% ethanol in drinking water the first week followed by 10% ethanol in drinking water for the next 6 weeks. Twelve control animals were given regular tap water. Systolic blood pressure in the ethanol-treated rats was significantly higher (p less than 0.05) than that in controls after 1 week and remained higher throughout the study. At 13 weeks of age, platelet cytosolic free calcium and calcium uptake by aortas were significantly higher (p less than 0.001) in ethanol-treated animals as compared with those in controls. Ethanol intake did not affect aortic ouabain-sensitive 86Rb uptake. The in vitro effect of ethanol on calcium-45 and 86Rb uptake was also investigated in aortas of untreated Wistar-Kyoto rats at 13 weeks of age. In vitro ethanol (2.5-20 mmols/l) did not significantly affect 45Ca and 86Rb uptake in rat aortas. The increases in systolic blood pressure, platelet cytosolic free calcium, and vascular calcium uptake suggest that increases in cytosolic free calcium and calcium uptake mechanisms are associated with ethanol-induced hypertension. 
Estimating the likelihood of severe coronary artery disease. PURPOSE: To determine which clinical characteristics obtained by a physician during an initial clinical examination are important for estimating the likelihood of severe coronary artery disease, and to determine whether estimates based on these characteristics remain valid when applied prospectively and in different patient groups. PATIENTS AND METHODS: We examined clinical characteristics predictive of severe disease in 6,435 consecutive symptomatic patients referred for suspected coronary artery disease between 1969 and 1983. RESULTS: Eleven of 23 characteristics were important for estimating the likelihood of severe coronary artery disease. A model using these characteristics accurately estimated the likelihood of severe disease in an independent sample of 2,342 patients referred since 1983. The model also accurately estimated the prevalence of severe disease in large series of patients reported in the literature. CONCLUSIONS: These findings suggest that the clinician's initial evaluation can identify patients at high or low risk of anatomically severe coronary artery disease. Cost-conscious quality care is encouraged by identifying patients at higher risk for severe coronary artery disease who are most likely to benefit from further evaluation. 
Cost and benefit of secondary prophylaxis for Pneumocystis carinii pneumonia. OBJECTIVE--To determine the relative cost and benefit of aerosolized pentamidine and the combination product of sulfamethoxazole and trimethoprim sulfate as secondary prophylaxis for Pneumocystis carinii pneumonia. DESIGN--A Markov-based cost-benefit analysis was performed. Drug efficacies, toxicities, and mortality rates were drawn from the current literature. SETTING--Hypothetical. PATIENT POPULATION--Patients infected with the human immunodeficiency virus who had had at least one episode of P carinii pneumonia. INTERVENTIONS--Regimen 1 required the use of aerosolized pentamidine as the sole first-line prophylactic agent in all patients. Regimen 2 required the use of sulfamethoxazole-trimethoprim in all patients who had no history of a toxic reaction to the drug; only patients with a history of toxic effects and those who developed toxic effects while receiving the drug would receive aerosolized pentamidine. Regimen 3 required that no secondary prophylaxis be given. MAIN OUTCOME MEASURES--Net cost, median patient survival, and 5-year survival for each regimen and for regimens 1 and 2 compared with regimen 3. MAIN RESULTS--Regimen 2 was dominant, with a net cost of $6332 per patient and a median survival of 2.050 years. Compared with no prophylaxis, regimen 2 resulted in a savings of $16,503 per patient and a 0.696-year increase in median survival. Compared with regimen 1, regimen 2 resulted in a savings of $2904 and a 0.067-year increase in median survival. CONCLUSIONS--Secondary prophylaxis for P carinii saves money and extends survival. Current data suggest that sulfamethoxazole-trimethoprim should be given whenever it can be tolerated. Use of aerosolized pentamidine as a first-line agent would result in a modest increase in cost and a decrease in life expectancy. 
Small bowel obstruction after colon resection for benign and malignant diseases. To determine the etiology and outcome of patients with small bowel obstruction after a colon resection for benign and malignant diseases, the medical records of 118 patients who underwent 120 laparotomies for small bowel obstruction were reviewed. Contrary to previous reports, benign adhesions were responsible for the obstruction in all patients with a history of benign colon disease, 82.6 percent of patients with a history of adenocarcinoma of the colon without known recurrence, and 30.1 percent of patients with known recurrent malignancy. The morbidity and mortality was more related to the etiology of the obstruction rather than the preoperative delay or operative procedure performed. Considering the high likelihood of adhesive obstruction in patients with a history of, or known, metastatic colorectal carcinoma, it is suggested that these not deter surgeons from aggressive early surgical intervention in these patients who develop small bowel obstruction. 
Epidemiological characteristics of subarachnoid hemorrhage in an urban population. Several risk factors for unfavorable outcome from subarachnoid hemorrhage (SAH) have been identified. The prevalence of such risk factors varies among ethnic groups and among men and women. The influence of ethnic background and gender as factors in the outcome after SAH has not been adequately studied and is the focus of the present investigation. Outcome in 145 consecutive patients was dichotomized as good and moderately disabled vs severely disabled, vegetative, and dead. A multiple logistic regression model was used to examine the factors of gender, ethnic group (white and non-white), age, admission neurological grade, pre-existing hypertension, and intravenous drug abuse. Our data reveal that hypertensive, white males, with a history of intravenous drug abuse, have a high risk of unfavorable outcome following SAH. These observations are important for the design and interpretation of future studies relating to SAH. 
Iodine-125 interstitial implants as salvage therapy for recurrent gynecologic malignancies. Twenty-one patients with the diagnosis of recurrent gynecologic pelvic malignancy from various primary sites were treated with iodine-125 (I-125) interstitial implants. Eighteen of these patients had been treated with a combination of surgery and radiation therapy for their primary malignancies and 90% had responded. Seventy-five percent had complete local responses. The overall survival time, volume-response relationship, and complications are discussed and the radioresponse of various histologic types is presented. 
Delayed presentation and treatment of popliteal artery embolism. In the course of reviewing a 10-year experience with popliteal artery embolism (PAE), two distinct patterns of clinical presentation were identified. In addition to those patients presenting with typical acute (symptom duration less than 7 days) arterial ischemia, a second group was identified who presented with more chronic symptoms. The present study was conducted to contrast the clinical factors and treatment of these two temporal patterns of presentation with PAE. Sixty PAEs in 58 patients were documented by the combination of angiography and/or exploration of the popliteal artery. Acute presentation (AP) was seen in 41 (68%) of these and delayed presentation (DP) was noted in 19 (32%) patients. Delayed presentation patients typically presented with a history of sudden onset of claudication or rest pain and a median symptom duration of 30 days. Eighty per cent of AP patients presented with immediately threatened limbs. Angiography was generally diagnostic of chronic popliteal embolism. In the acute group, 90% were treated with embolectomy alone, while 20% of the DP group required bypass grafting. However in two thirds of the DP group, embolectomy alone performed through a direct popliteal approach was possible. Current results with overall limb salvage (92%) and mortality (7%) represents a substantial improvement compared to the authors' previous experience with PAE. The current study suggests that as many as one third of patients with popliteal artery embolism may present in delayed fashion with chronic symptoms. Furthermore most of these patients can be treated with direct popliteal embolectomy alone with favorable results. 
Patterns of morbidity and mortality in typhoid fever dependent on age and gender: review of 552 hospitalized patients with diarrhea. Features of typhoid fever were correlated with age and gender through a review of the charts of 552 hospitalized culture-positive patients with diarrhea in Bangladesh. Seizures occurred more frequently in children from birth through 10 years of age (5%-11%) and pneumonia more frequently in children from birth through 5 years of age (8%-15%) than in older age groups (P less than .05), whereas intestinal perforation occurred more frequently in patients greater than or equal to 11 years of age (5%-25%) than in younger age groups (P less than .005). Compared with older age groups, children from birth through 10 years of age were more anemic, those from birth through 5 years of age had a higher mean white blood cell count, and those from birth through 1 year of age had a lower mean blood carbon dioxide content (all P less than .05). Female patients were more severely anemic than male patients (P less than .05). The case-fatality rate was 4.3% overall, with the highest rates for children from birth through 1 year of age (11%) and adults greater than or equal to 31 years of age (10%). Female patients had a higher case-fatality rate (6%) than male patients (3%), although the difference was not significant (P greater than .05). Death was independently associated with seizures, intestinal perforation, pneumonia, and delirium or coma. These results indicated that the patients with typhoid fever who were at highest risk of complications and death were children from birth through 1 year of age and adults greater than or equal to 31 years of age. 
Effect of nitroglycerin on coronary collateral function during exercise evaluated by quantitative analysis of thallium-201 single photon emission computed tomography. A noninfarcted, entirely collateral-dependent myocardial region provides an opportunity to assess the effect of nitroglycerin on coronary collateral function during exercise. Stress thallium-201 computed tomography was performed in seven patients with effort angina and no history of myocardial infarction, both before and after nitroglycerin (0.3 mg). All patients had single-vessel disease with total or subtotal (99% with delay) occlusion of proximal left anterior descending coronary artery and well-developed collaterals. The pressure-rate product, mean blood pressure, and heart rate at peak exercise did not differ before and after nitroglycerin. The size of the perfusion defect and the severity of ischemia during exercise estimated by quantitative analysis of thallium-201 single photon emission computed tomography were significantly less after nitroglycerin administration (extent score: 23 +/- 17 vs 7 +/- 9, p less than 0.01; severity score: 20 +/- 22 vs 3 +/- 4, p less than 0.05). The pressure-rate products at peak exercise did not differ before and after nitroglycerin, which suggested that the reduction in perfusion defect size was unlikely to be the result of decreased myocardial oxygen consumption. These results suggest that nitroglycerin improved coronary collateral function during exercise and thus prevented exercise-induced myocardial ischemia. 
Benign positional vertigo: incidence and prognosis in a population-based study in Olmsted County, Minnesota. A retrospective review of our population-based medical records linkage system for residents of Olmsted County, Minnesota, revealed 53 patients (34 women and 19 men; mean age, 51 years) with newly diagnosed benign positional vertigo in 1984. The age- and sex-adjusted incidence was 64 per 100,000 population per year (95% confidence interval, 46 to 81 per 100,000). The incidence of benign positional vertigo increased by 38% with each decade of life (95% confidence interval, 23 to 54%). One patient had an initial stroke during follow-up; thus, the relative risk for new stroke associated with benign positional vertigo was 1.62 (95% confidence interval, 0.04 to 8.98) in comparison with the expected occurrence based on incidence rates for an age- and sex-adjusted control population. The observed survival among the 53 Olmsted County residents with benign positional vertigo diagnosed in 1984 was not significantly different from that of an age- and sex-matched general population. Patients with benign positional vertigo seem to have a good prognosis. 
Value of regional wall motion abnormality in the emergency room diagnosis of acute myocardial infarction. A prospective study using two-dimensional echocardiography. Because regional wall motion abnormality (RWMA) is usually noted during ischemia, we hypothesized that the presence of this finding with two-dimensional echocardiography would be superior to conventional methods of diagnosing acute myocardial infarction (AMI) in the emergency room. We also hypothesized that because the absence of RWMA would probably not be associated with AMI, the use of two-dimensional echocardiography would significantly limit unnecessary hospital admissions. To test these hypotheses, we undertook a prospective study that used two-dimensional echocardiography in 180 patients presenting to the emergency room with symptoms suggestive of AMI. The emergency room physicians were not informed of the two-dimensional echocardiography findings, and their decision to admit or not admit to the hospital was based on conventional clinical and electrocardiographic criteria. Forty patients were not admitted to the hospital and 140 were admitted. Of the 30 patients with enzyme-confirmed AMI, nine had typical ST elevation on the ECG that was consistent with acute injury, three had normal ECGs, and eight had ECGs in the presence of which AMI could not have been diagnosed (left bundle branch block, paced rhythm, or repolarization changes); the rest had nonspecific ECG findings. Of the 29 AMI patients with technically adequate two-dimensional echocardiography studies, two did not demonstrate RWMA and 27 had RWMA, compared with nine with diagnostic ECG changes (p less than 0.001). Of the 13 patients with in-hospital complications only four had an initial ECG showing ST elevation, and all 13 had RWMA (p less than 0.001).(ABSTRACT TRUNCATED AT 400 WORDS). 
Autoimmunity after alpha-interferon therapy for malignant carcinoid tumors. OBJECTIVE: To determine the incidence of autoantibodies and autoimmune disease and their influence on therapeutic results during alpha-interferon treatment in patients with malignant midgut carcinoid tumors. DESIGN: Consecutive sample of patients. SETTING: University hospital. PATIENTS: One hundred thirty-five patients (70 women, 65 men; median age, 59 years) with biopsy-proven tumors, liver metastases, and no autoimmune disease. INTERVENTIONS: Leukocyte alpha-interferon (n = 88) or alpha-interferon 2b (n = 47) three times a week. MAIN OUTCOME MEASURES: Signs and symptoms of autoimmune disease or development of autoantibodies to thyroid antigens, nuclear antigens, or gastric parietal cells. Tumor responses were determined by reduced liver metastases or reduced urinary 5-hydroxyindole acetic acid excretion, or both. RESULTS: Twenty-five patients (19%) developed the following autoimmune disorders after a median of 9 months of therapy: thyroid disease (n = 18), systemic lupus erythematosus (n = 1), pernicious anemia (n = 4), and vasculitis (n = 2). Antibodies to microsomal thyroid antigen or thyroglobulin were detected in 16 patients before therapy and in another 11 patients during therapy. Antinuclear antibodies were detected in 16 patients before and in another 19 patients during therapy. Clinical thyroid disease developed in more than 60% of patients who had or developed thyroid antibodies but in only 7% of initially autoantibody-negative patients. Autoimmunity did not correlate with objective tumor response. CONCLUSION: Patients with malignant carcinoid tumors may develop autoimmune disease during alpha-interferon therapy, especially when autoantibodies are present. They should therefore be monitored for autoimmunity, which does not appear, however, to influence tumor responses. 
Chylous ascites and lymphocyst management by peritoneovenous shunt. Although lymphocyst (retroperitoneal lymphocele) is not an uncommon complication after retroperitoneal surgery, with a reported incidence ranging from 0.6% to 48%, the occurrence of chylous ascites is a rare phenomenon. Most reports are anecdotal, and hospital records list the incidence of diagnosis as 0.001% of admissions. Diagnosis of chylous ascites is usually not difficult, inasmuch as aspiration and chemical analysis of the fluid yield the answer. Visualization of retroperitoneal fluid collection by computerized tomography or ultrasonography, however, does always raise the possibility of recurrence of tumor in cases where the primary operation was for cancer. Treatment of smaller lesions can be expectant. Respiratory exercises causing an increase in negative intrathoracic pressure may aid in the movement of fluid through the lymphatics. For larger collections, elemental diets and total parenteral nutrition are also often enough, but surgery is sometimes required. Simple insertion of a peritoneovenous shunt, as in this patient, can be as effective as major operations such as identification and ligation of the offending lymphatic or marsupialization of the cyst. 
Subarachnoid hemorrhage in sickle-cell disease. The neurological complications of sickle-cell disease include cerebral intracerebral hemorrhage; subarachnoid hemorrhage (SAH) has been infrequently reported. Among 325 patients with sickle-cell disease followed at the University of Illinois between 1975 and 1989, 11 cases of SAH were identified. Aneurysms were found in 10 of these patients, three of whom had multiple aneurysms. All of the patients had some degree of anemia and nine underwent craniotomy without hematological or neurological complications. From this review it appears that SAH is not uncommon in sickle-cell disease patients and tends to occur at a younger age and with smaller aneurysm size than in the general population. With proper perioperative management, including exchange transfusions to reduce the proportion of hemoglobin S to less than 30%, these patients can undergo angiography and craniotomy without an increased incidence of complications. The techniques used in managing sickle-cell disease patients with SAH are discussed. 
Determinants of perinatal outcome in pregnancy-induced hypertension with absence of umbilical artery end-diastolic frequencies. Forty-three pregnancies that were complicated by pregnancy-induced hypertension and either absence of umbilical artery end-diastolic frequencies (n = 32) or reversal of umbilical artery end-diastolic frequencies (n = 11) were reviewed. The incidence of perinatal mortality and morbidity was similar for the two Doppler patterns. Perinatal survival was highly dependent on the gestational age when hypertension first appeared. Presentation at greater than or equal to 30 weeks' gestation was associated with a perinatal survival rate of 86%. Presentation at less than 30 weeks' gestation was associated with a perinatal survival rate of 38% (p less than 0.005). Pregnancy-induced hypertension that presented before 30 weeks was more often associated with a 5-minute Apgar score less than 7 (p less than 0.005) and a nonreactive nonstress test (p less than 0.05) compared with pregnancy-induced hypertension that presented at or beyond 30 weeks. For pregnancies that presented before 30 weeks, the only difference between perinatal survivors (n = 11) and perinatal deaths (n = 18) was a higher incidence of birth weight at or below the 10th percentile among deaths (p = 0.02). 
Comparison of ondansetron and ondansetron plus dexamethasone as antiemetic prophylaxis during cisplatin-containing chemotherapy. Ondansetron, a serotonin antagonist, is effective in controlling the emesis associated with cancer chemotherapy; however, emesis in patients receiving high-dose cisplatin is poorly controlled by ondansetron alone. Dexamethasone is an effective antiemetic with no known interaction with serotonin receptors and was thus chosen for study in combination with ondansetron. 31 patients (30 male, 1 female; median age 28.5 years, range 18-49) receiving a 4-day course of a chemotherapy regimen containing cisplatin (100-120 mg/m2) for metastatic germ-cell tumours were entered in a randomised, double-blind, cross-over trial comparing oral ondansetron plus placebo with oral ondansetron plus dexamethasone as antiemetic prophylaxis. Ondansetron (8 mg every 8 h) was given to all patients for 8 days from the start of chemotherapy. Patients were given 8 mg of dexamethasone or placebo every 8 h starting 2 h before cisplatin (on day 4) and continuing for six doses (ie, for 2 days only). A second course of chemotherapy began 14 days after the start of the first, during which patients crossed over to the alternative antiemetic regimen. Results were available from 27 patients. In the 24-48 h after cisplatin 78% of patients taking ondansetron plus dexamethasone reported complete or major control of emesis compared with 30% of those taking ondansetron plus placebo (p = 0.001). Cross-over analysis showed a significant advantage for ondansetron plus dexamethasone in the control of nausea (p = 0.013) and emesis (p less than 0.001) over the 8-day study. 24 of 26 patients expressed a preference for the combination therapy (p less than 0.001). Ondansetron plus dexamethasone is effective antiemetic prophylaxis for high-dose cisplatin chemotherapy, has few side effects, and is active when given orally. 
Gonadotropin-releasing hormone agonist (leuprolide acetate) induced ovarian hyperstimulation syndrome in a woman undergoing intermittent hemodialysis. Moderate ovarian hyperstimulation syndrome occurred after LA was administered to control menorrhagia in an anephric woman who required hemodialysis. We postulate that women who require dialysis may be at special risk for the development of this syndrome. 
Intrahepatic cholangiocarcinoma in hepatolithiasis: A frequently overlooked disease. Five cases of intrahepatic cholangiocarcinoma were found among 101 cases of hepatolithiasis. There was no definite sign of cholangiocarcinoma in ERCP and image studies of four cases. The possibility of the existence of occult cholangiocarcinoma should be kept in mind, especially when unusual presentations, such as body weight loss, anemia, palpable abdominal mass, and intractable pain, appear. An intraoperative frozen-section examination should be considered under the following circumstances: (1) whitish nodular mass over liver, (2) mucinous substance within bile duct, and (3) enlarged, firm lymph nodes clustered along the hepatic arteries and/or celiac arteries. 
Effect of theophylline and dipyridamole on the respiratory response to isocapnic hypoxia in normal human subjects. 1. Twelve healthy young men took part in this investigation of the effect of oral theophylline and dipyridamole (two drugs known to affect the pharmacological effects of the purine nucleoside adenosine) on the respiratory response to isocapnic hypoxia. 2. The subjects underwent hypoxic rebreathing manoeuvres after 3-day pretreatments with each of the drugs for 12 h and were at least 2 h postprandial. For each in-Minute ventilation, the maximum rate of isometric inspiratory pressure development at the mouth and the ratio of inspiratory duration to total breath duration were analysed breath-by-breath and regressions of these variables upon the haemoglobin oxygen saturation were performed. 3. The slopes and intercepts of the lines describing the relationships of minute ventilation and the maximum rate of isometric inspiratory pressure development at the mouth with haemoglobin oxygen saturation were unaffected by the study drugs, and no differences in the pattern of breathing were observed. 4. We conclude that oral administration of these drugs does not result in alteration of the response of the respiratory system to progressive isocapnic hypoxia. 5. This suggests that either adenosine has no physiological role in hypoxic respiratory control as measured, or that it has opposing peripheral chemoreceptor and central respiratory centre effects which could not be distinguished by the techniques used. 
An autopsy study of the peritoneal cavity from patients on continuous ambulatory peritoneal dialysis. Sixteen autopsies were performed on patients aged 56 +/- 15 (SD) years who were on continuous ambulatory peritoneal dialysis (CAPD) for 834 +/- 766 (SD) days. Lactate-buffered dialysate and povidone-iodine antiseptic were used in all cases. Multiple peritoneal sections were taken to evaluate peritoneal membrane thickening, inflammation, neovascularization, fibrosis, and adhesions. Peritoneal thickening, inflammation, or adhesions were not related to sex, race, or etiology of renal failure. Time on dialysis was also not a direct determinant of peritoneal adhesions or neovascularization. Peritonitis episodes correlated with chronic peritoneal serosal changes. This study supports the hypothesis that peritoneal alterations in patients on CAPD are related to episodes of peritonitis. 
Pneumocephalus associated with benign brain tumor: report of two cases. Two cases of spontaneous pneumocephalus, which developed after ventriculoperitoneal shunt procedures for severe hydrocephalus caused by benign brain tumors, are reported. In both cases there was no previous history of cerebrospinal fluid leakage. Operation revealed that both patients had many small defects of the dura mater and the bone in the middle cranial fossa, which were plugged by necrotic brain tissue. These defects were remote from the sites of the original tumors but may have been produced by long-standing raised intracranial pressure, and they presumably allowed air to enter after intracranial pressure was reduced by shunting. Repair of the defects prevented further intracranial air retention. 
Cardiovascular and metabolic characteristics of hypertension. Hypertension is now seen as a broader condition than high blood pressure alone. Large-scale epidemiologic studies have established that high blood pressure is associated with an increased risk of cardiovascular events, but clinical trials of antihypertensive therapy have shown an inconsistent reduction in major cardiovascular endpoints. Importantly, the incidence of coronary disease has been reduced to only a small extent, suggesting that factors beyond high blood pressure are important in the genesis of atherosclerotic disease in hypertensive patients. It is evident, for example, that patients with hypertension have an exaggerated vulnerability to the consequences of lipid abnormalities. Moreover, it has recently been established that hypertension is characterized by insulin resistance and altered glucose tolerance. As a result, high plasma concentrations of insulin produce proliferative effects on vascular smooth muscle and connective tissue, and they may adversely affect the lipid profile. The left ventricle is also involved in hypertension--independent of blood pressure. There is growing evidence that there are increases in the muscle mass of the left ventricle and changes in its diastolic filling characteristics at the very early stages of hypertension. The arterial circulation is similarly involved, for alterations in structure or function, reflected by diminished arterial compliance, can be demonstrated prior to the appearance of clinical hypertension. Treatment designed to protect hypertensive patients from cardiovascular events must not only be based on blood pressure, but must take into account all the components of the hypertension syndrome. 
Idioventricular rhythm: hypervagotonia associated with placebo. We report a case of hypervagotonia manifested by idioventricular rhythm in a healthy, athletic man who participated in a Phase I study of an investigational calcium-channel blocker. Upon breaking the study's double-blind study code, it was discovered that the subject had received placebo. We discuss this unusual finding and the implications of including athletic subjects in safety/tolerance studies. 
Characteristics of experimental Candida albicans infection of the central nervous system in rabbits. Different concentrations (10(7), 10(5), 10(3) cfu/ml) of Candida albicans were injected intracisternally in rabbits. The highest inoculum was fatal within 14 h in all animals. In recipients of 10(5) and 10(3) cfu/ml inocula, the mean +/- SD peak cerebrospinal fluid (CSF) tumor necrosis factor-alpha (TNF alpha) concentrations were 1.6 +/- 2.42 and 0.3 +/- 0.59 ng/ml, respectively, at 6 h; the mean +/- SD CSF leukocyte and protein concentrations were 6291 +/- 6515 and 453 +/- 674 cells/mm3 (at 24 h) and 118 +/- 90 and 109 +/- 122 mg/dl (at 12 and 24 h), respectively. At 6-10 days after inoculation, a second peak of TNF alpha activity was accompanied by increased CSF inflammation. Mortality in the 10(5) and 10(3) cfu/ml inoculum groups was 56% and 22%, respectively. Fatal infection was associated with higher second CSF peak TNF alpha and leukocyte concentrations and a larger proportion of culture-positive CSF samples. Histopathology revealed hyphal invasion, vasculitis, abscesses, and acute and chronic inflammatory infiltration of meninges and brain parenchyma. This model can be useful for evaluation of the pathogenesis and therapy of central nervous system fungal infections. 
Relationship of HBsAg subtypes with HBeAg/anti-HBe status and chronic liver disease. Part II: Evaluation of epidemiological factors and suspected risk factors of liver dysfunction. In this study, we examined a possibility that epidemiological factors or suspected risk factors of liver dysfunction could account for the different HBeAg/anti-HBe status or the different prevalence of liver dysfunction between the adr and adw carriers. A total of 428 HBsAg carriers were surveyed of their age, sex, racial background, socioeconomic status, place of residence, birthplace, alcohol consumption, smoking habit, and history of blood transfusion as epidemiological factors or suspected risk factors of liver dysfunction. Adjustment for those variables using multivariate analyses did not substantially affect the association of the HBsAg subtypes with either prevalence of liver dysfunction or HBeAg/anti-HBe status. HBsAg subtypes seem to directly affect HBeAg/anti-HBe status and consequently influence development of chronic liver disease. 
Innovative approach in the diagnosis of gliomatosis cerebri using carbon-11-L-methionine positron emission tomography. A case of gliomatosis cerebri was studied with positron emission tomography (PET). Carbon-11-L-methionine (11C-Met) accumulated in the diffusely infiltrative tumorous area more widely and accurately than the lesion detected by conventional x-ray computerized tomography (CT) or magnetic resonance (MR) imaging. Autopsy findings three months after the time of the PET study showed good anatomical correspondence between the extent of densely aggregated tumor cells and the region with high uptake of 11C-Met. PET may offer an innovative approach in the delineation of gliomatosis cerebri, which has not been clearly recognized by CT or MR. 
Transesophageal echocardiography: detection of an acquired left ventricular-right atrial shunt. Communication between the left ventricle and right atrium has a reported prevalence of less than 1%. Acquired left ventricular--right atrial shunt is caused by chest trauma or valvular surgery. A case of acquired left ventricular--right atrial shunt after aortic valve surgery is reported. The detection was possible by use of echo-Doppler, color flow imaging, and transesophageal echocardiography. Combined use of these modalities and multiple transducer positions when transthoracic echocardiography is used are recommended to make the diagnosis. 
Neurohumoral and metabolic effects of short-term dietary NaCl restriction in men. Relationship to salt-sensitivity status Published observations suggest that not everyone benefits from severe dietary NaCl restriction, since blood pressure responses appear heterogeneous and adverse metabolic effects may occur. We studied the cardiovascular, neurohumoral, and metabolic effects of 7 day periods of 20 v 200 mEq/day NaCl diets in 27 men. Twelve subjects were salt sensitive (SS), defined as mean intraarterial pressure (MAP, mm Hg) during high NaCl greater than or equal to 5% above MAP on low NaCl. Eleven subjects were salt resistant (SR), defined as MAP during the low NaCl phase greater than or equal to MAP during the high NaCl phase. The SR subset had a tendency to greater neurohumoral activity, assessed by changes in mean values for plasma norepinephrine (NE, P = .12) and plasma renin activity (PRA, P less than .001) on the low v high NaCl diet. In SR subjects the low v high NaCl diet also raised mean values for creatinine (P = .03), uric acid (P = .001), and low density cholesterol (LDL-C, P = .03), but not fasting insulin (P = .15). In SS subjects, the low v high NaCl diet did not raise NE (P = .35), although the PRA was greater (P = .002). Among SS subjects, mean values for uric acid (P = .005) and insulin (P = .02) were greater during the low v high NaCl phase, while creatinine (P = .15) and LDL-C (P = .67) were not different. The data suggest that severe, short-term NaCl restriction can be undesirable, especially in SR subjects, since potentially adverse neurohumoral and metabolic changes are not counterbalanced by the benefits of a lower MAP. 
Bilateral nephrectomy before transplantation: indications, surgical approach, morbidity and mortality. Forty patients with end-stage renal failure, who had undergone simultaneous bilateral native nephrectomy before a subsequent renal transplant operation, were reviewed with particular reference to the indications and surgical approach for bilateral nephrectomy and to the complications of the procedure. The main indications for bilateral nephrectomy are hypertension resistant to medical therapy, persistent symptomatic renal infection, severe renal protein loss and occasionally polycystic kidneys or bilateral renal tumours. In this consecutive series of 40 patients both kidneys were removed because of chronic pyelonephritis with reflux (n = 28), glomerulonephritis with reflux (n = 9) and uncontrolled hypertension (n = 3). Surgical morbidity was less in patients who had bilateral nephrectomy performed through bilateral vertical lumbotomy incisions. There was no surgical mortality. 
Tentorial subdural hemorrhage in term newborns: ultrasonographic diagnosis and clinical correlates. Tentorial subdural hemorrhage with its supratentorial and infratentorial extensions were diagnosed by cranial ultrasonography and computed tomography in 9 term newborns. Vacuum extraction or forceps delivery was used in 6 patients. Abnormal neurologic manifestations developed after a period of normality in 8 patients. Increased intracranial pressure was the most common presentation. All patients had hemorrhage at the falcotentorial junction near the incisura; 5 also had hemorrhage around the tentorial leaflet. Posterior fossa retrocerebellar subdural hemorrhage developed in 5 patients and posterior interhemispheric subdural hemorrhage developed in 4. All 6 patients who received conservative treatment had normal neurodevelopmental outcomes. Of the other 3 patients upon whom suboccipital craniotomies were performed, only 1 had a normal outcome. Although it localized the tentorial subdural hemorrhage either at the incisura area or at the tentorial leaflet, ultrasonography failed to identify all patients with retrocerebellar or posterior interhemispheric subdural hemorrhage. Parturitional tentorial subdural hemorrhage may not be uncommon. Ultrasonography and computed tomography are complementary in the diagnosis. Surgical decompression of the posterior fossa subdural hematoma is necessary only in the presence of acute hydrocephalus or signs of brainstem compression. 
Cardiac sources of embolism and cerebral infarction--clinical consequences and vascular concomitants: the Lausanne Stroke Registry. We studied clinical characteristics and coexisting causes of stroke in 305 patients admitted to a population-based primary care center with an initial ischemic stroke and a potential cardiac source of embolism (PCSE). Using systematic standardized cardiac, arterial, and cerebral investigations and the logistics of the prospective Lausanne Stroke Registry, we found that nonprogressive onset, hemianopia without hemiparesis or hemisensory disturbances, Wernicke's aphasia, ideomotor apraxia, involvement of specific territories (posterior division of middle cerebral artery, anterior cerebral artery, cerebellum, multiple territories), and a hemorrhagic component were associated with the presence of a PCSE, as compared with 1,006 initial ischemic stroke patients without PCSE. Although age and sex did not differ, the frequency of hypertension, diabetes, cigarette smoking, elevated blood cholesterol, and deep hemispheric or brainstem infarcts was higher in the patients without a PCSE. Nearly one-fourth of the patients with a PCSE had a coexisting potential arterial cause of stroke (large artery greater than or equal to 50% stenosis or small-vessel disease). In the majority of patients with a PCSE (76.7%), cardioembolism was the most likely cause of stroke, although a direct source of embolism was uncommon (4.3%) and intracranial embolic occlusions were present in less than one-half of the patients who were angiographed. 
Effect of daily etidronate on the osteolysis of multiple myeloma. Progressive bone disease in multiple myeloma frequently leads to osteolysis, bone resorption, pathologic fractures, vertebral compression, and hypercalcemia. We conducted a double-blind study in 173 newly diagnosed multiple myeloma patients of etidronate disodium (EHDP), a diphosphonate compound that reduces bone resorption by inhibiting osteoclastic activity. The patients were randomly assigned to receive oral EHDP 5 mg/kg/d or placebo until death or discontinuation due to intolerance or refusal. The extent of vertebral deformity was measured by a vertebral index as well as height. The frequency of pathologic fractures, hypercalcemia, and bone pain was regularly assessed, as well as size and number of osteolytic lesions. All patients received melphalan and prednisone daily for 4 days every 4 weeks as the primary chemotherapy for their disease. Although the repeated measures analysis showed a significant height loss, there was no difference between treatment arms (P = .98). There was no significant difference in bone pain, episodes of hypercalcemia, or development of pathologic fractures. Patients on EHDP showed less deterioration in their vertebral index, but this difference only approached statistical significance (P = .07). We conclude that EHDP therapy used in this dosage schedule does not have a clinically significant impact in multiple myeloma. 
Lung asbestos fiber content and mesothelioma cell type, site, and survival. All ascertainable cases of malignant mesothelioma in Australia were notified to a national surveillance program in the period January 1, 1980 to December 31, 1985. There were 854 cases obtained and 823 confirmed on clinical (77) or histologic (746) ground. Tumor site was known in 759 cases (685 pleural and 74 peritoneal). Lung fiber content analyses by light microscopy and analytic transmission electron microscopy with energy-dispersive x-ray analysis were done on 226 cases in which postmortem material was available, using the method of Rogers. Cell type was determined by a five-member expert panel of pathologists appointed by the Royal College of Pathologists of Australasia. There was a statistically significant trend between lung fiber content (fibers/g dry lung) and cell type from epithelial (low fiber content) through mixed to sarcomatous (high fiber content). This trend was most apparent for total uncoated fibers (chi-square = 6.8, df = 1, P less than 0.01) and crocidolite (chi-square = 6.7, df = 1, P less than 0.01). Lung fiber content also was associated with tumor site; higher lung fiber content being associated with peritoneal tumors. This relationship was significant for all fiber content measures except chrysotile and was independent of the fiber content-cell type relationship (log-linear analysis). Survival from time of provisional diagnosis was significantly longer for epithelial (mean, 13 months; standard deviation [SD], 12.8) and mixed (mean, 10.2 months; SD, 8.7) types than sarcomatous cell types (mean, 5.8 months; SD, 6.5; P less than 0.0001, by analysis of variance on log10 survival time). Survival time was significantly greater for pleural tumors (mean, 11.4 months; SD, 13.4) than peritoneal tumors (mean, 8.6 months; SD, 12.5) (P less than 0.005, by Student's t test on log10 survival time). 
Sclerotherapy of bleeding esophageal varices using a thrombogenic cocktail. The short- and long-term efficacy of a thrombogenic sclerosant (1% tetradecyl sulfate, thrombin, and cefazolin) was studied in 101 patients. The majority of patients had alcoholic cirrhosis with Child's C classification (84/101). Bleeding was controlled in 94 per cent of patients with the first sclerotherapy. In-hospital and early (within 6 weeks) mortality were 14 per cent and 19 per cent, respectively. There was a strong correlation with hospital mortality and the severity of hepatic disease. Long-term follow-up in 70 patients (mean of 16 months) showed that survival correlated with compliance to follow-up sclerotherapy and abstention from further alcohol intake. Mortality in patients compliant with follow-up was 5 per cent (1/19), as compared with 24 per cent (12/51) in patients who were not compliant with follow-up sclerotherapy. The mortality in alcoholic cirrhotic patients who abstained from further alcoholic intake was 6 per cent (1/17), as compared with 23 per cent (10/44) in those who continued to abuse alcohol. No systemic thrombotic or allergic events related to the use of bovine thrombin were noted during a total of 349 sclerotherapy sessions. 
Regression of coronary atherosclerosis: an achievable goal? Review of results from recent clinical trials. During the past decade, large, placebo-controlled, randomized trials have demonstrated that the incidence of coronary events can be reduced by treating hyperlipidemia. In studies with angiographic end points, marked lowering of total and low-density-lipoprotein cholesterol with comparable increases in high-density-lipoprotein cholesterol retards the progression of coronary atherosclerosis and favors regression. In the Cholesterol-Lowering Atherosclerosis Study (CLAS), such therapy also prevented the appearance and worsening of atherosclerotic lesions in coronary bypass grafts. In the recently reported Familial Atherosclerosis Treatment Study (FATS), in which coronary lesions were measured quantitatively, treatment induced clear regression of coronary atherosclerosis and also markedly decreased coronary events. The beneficial effect on coronary lesions in these studies appears to be proportional to the degree of lipid lowering. In addition, new evidence suggests that aspirin and calcium antagonists might prevent the development of early coronary lesions. The identification and aggressive treatment of patients with high serum cholesterol levels can have a major impact on the development and evolution of coronary atherosclerosis. 
Simplified limbal incision for extraocular rectus muscle surgery. We describe a limbal incision for extraocular muscle surgery which involves only one incision to the conjunctival-Tenon's layer instead of the three separate incisions required in the standard limbal approach. Based on the 316 extraocular muscle operations in which we have used this one-snip procedure, we conclude that it is simpler and faster than the standard limbal incision, and that it provides good surgical exposure and probably less tissue damage. 
Primary invasive vaginal carcinoma. A review of primary vaginal carcinoma treated at the Medical University of South Carolina from January 1970 through December 1989 included 76 squamous carcinomas, 12 adenocarcinomas, and 3 undifferentiated carcinomas. Staging was done according to the system of the International Federal of Gynecology and Obstetrics as modified by Perez et al. Stages I, II, III, and IV included 25, 39, 15, and 12 patients, respectively. Corrected 5-year survival rates were 73% for stage I, 39% for stage II, 38% for stage III, and 25% for stage IV. Sixteen percent of patients had received prior pelvic radiation. Invasive cervical cancer preceded vaginal cancer in 21% of patients. Detection of cancer was accomplished by routine cytologic testing in 17% of patients, palpation of an asymptomatic mass in 10% of patients, or palpation of a symptomatic mass in 72% of patients. Eighty-seven percent of patients were treated with radiation therapy. Survival curves of patients grouped by stage and other potential prognostic factors were compared. Lower stage (p less than 0.01), younger age (p less than 0.02), and no symptoms at detection (p less than 0.01) were statistically significant favorable prognostic factors. Histologic type, extent of vaginal involvement, vaginal location, prior radiation therapy, prior cervical cancer, and prior hysterectomy are factors that did not significantly affect survival. 
Solitary minute hepatocellular carcinoma. A study of 14 patients. Fourteen patients with clinical Stage I hepatocellular carcinoma (T1N0M0) were studied. All patients were asymptomatic, and their conditions were detected by alpha-fetoprotein (AFP) serosurvey and/or ultrasonography (US) either in the natural population in the early years of the study or in the high-risk population in the later years of the study. Cirrhosis was present in all patients. Radical resection was performed in all patients. There were no operative deaths or hospital deaths in this series. The 5-year survival rate after resection was 100%. There were seven long-term survivors in this series (14.2 years (alive), 11.3 years (alive), 8.8 years (alive), 8.8 years, 7.9 years, 7.6 years (alive), and 7.2 years after resection). The authors discuss aspects concerning early diagnosis, treatment, and prognosis of hepatocellular carcinoma (HCC). 
By how much does dietary salt reduction lower blood pressure? III--Analysis of data from trials of salt reduction [published erratum appears in BMJ 1991 Apr 20;302(6782):939] OBJECTIVE--To determine whether the reduction in blood pressure achieved in trials of dietary salt reduction is quantitatively consistent with estimates derived from blood pressure and sodium intake in different populations, and, if so, to estimate the impact of reducing dietary salt on mortality from stroke and ischaemic heart disease. DESIGN--Analysis of the results of 68 crossover trials and 10 randomised controlled trials of dietary salt reduction. MAIN OUTCOME MEASURE--Comparison of observed reductions in systolic blood pressure for each trial with predicted values calculated from between population analysis. RESULTS--In the 45 trials in which salt reduction lasted four weeks or less the observed reductions in blood pressure were less than those predicted, with the difference between observed and predicted reductions being greatest in the trials of shortest duration. In the 33 trials lasting five weeks or longer the predicted reductions in individual trials closely matched a wide range of observed reductions. This applied for all age groups and for people with both high and normal levels of blood pressure. In people aged 50-59 years a reduction in daily sodium intake of 50 mmol (about 3 g of salt), attainable by moderate dietary salt reduction would, after a few weeks, lower systolic blood pressure by an average of 5 mm Hg, and by 7 mm Hg in those with high blood pressure (170 mm Hg); diastolic blood pressure would be lowered by about half as much. It is estimated that such a reduction in salt intake by a whole Western population would reduce the incidence of stroke by 22% and of ischaemic heart disease by 16% [corrected]. CONCLUSIONS--The results from the trials support the estimates from the observational data in the accompanying two papers. The effect of universal moderate dietary salt reduction on mortality from stroke and ischaemic heart disease would be substantial--larger, indeed, than could be achieved by fully implementing recommended policy for treating high blood pressure with drugs. However, reduction also in the amount of salt added to processed foods would lower blood pressure by at least twice as much and prevent some 75,000 [corrected] deaths a year in Britain as well as much disability. 
Technetium-99m-d,1-hexamethylpropyleneamine oxime (HMPAO) uptake and glutathione content in brain tumors Technetium-d, HMPAO SPECT was performed in 70 patients suffering from intracerebral tumors of various histologic types (glioma n = 30, meningioma n = 19, metastases n = 10, angioma n = 3, neuroma n = 2, lymphoma n = 2, neurocytoma n = 1, epidermoid n = 1, gliosis n = 1, cholesteatoma n = 1). Tumor classification was histologically verified in all subjects except in two cases with inoperable angiomas. SPECT was performed under resting state conditions with a dual-head rotating camera (SIEMENS ZLC 37) following intravenous injection of 18-25 mCi 99mTc-d, 1-HMPAO. Regional tracer deposit was expressed in terms of a cerebellar index (CBI). Significantly higher regional HMPAO uptake was found in meningiomas when compared with gliomas of different malignancy (ANOVA p less than 0.05). Within gliomas, regional uptake increased with malignancy (n.s.). In 23 patients, a total of 32 tumor specimens were obtained for histochemical analysis of glutathione (GSH) content using high-pressure liquid chromatography. A significant correlation (least square method, p less than 0.001) between CBIs and GSH values was found, supporting the hypothesis that GSH is the predominant factor for the conversion of the lipophilic complex to hydrophilic derivates. 
Exercise but not methacholine differentiates asthma from chronic lung disease in children. Bronchial provocation challenges with exercise and methacholine were performed on the same day or within a short interval in 52 children with asthma, 22 with other types of chronic lung disease (including cystic fibrosis), and 19 control subjects with no evidence of chronic lung disease. There were no significant differences in the baseline lung function before the two types of challenge in the individual groups and differences between the patients with asthma and with chronic lung disease were minor. When the mean -2 SD of the methacholine response of the control group was taken as the lower limit of normal, 49/52 (94%) patients with asthma and 18/22 (82%) with chronic lung disease responded abnormally. In contrast, with the mean +2 SD of the exercise response of the control group as the upper limit of normal, 41/52 (79%) asthmatic patients responded but none of those with chronic lung disease. Thus the response to the two types of challenge helps to distinguish asthma from other types of chronic lung disease in children. 
The value of the tumor marker CA 15-3 in diagnosing and monitoring breast cancer. A comparative study with carcinoembryonic antigen. To estimate the utility of the tumor-associated antigen CA 15-3 in the diagnosis of patients with breast cancer, this tumor marker was measured preoperatively in 1342 patients. This group included 509 patients with malignant disease (134 breast cancer patients and 375 patients with other malignancies not involving the breast) and 833 patients with benign surgical diseases (95 patients with fibroadenoma of the breast and 738 patients with other benign diseases). The results were compared with those obtained for carcinoembryonic antigen (CEA) in the diagnosis of breast cancer. The CA 15-3 level was above normal (25 U/ml) in 31% of the patients with breast cancer, in 22% of patients with other malignancies, and in 9% of patients with benign diseases. The CEA level was elevated in 26% of patients with breast cancer (more than 3 ng/ml). There was a good correlation of CA 15-3 levels with the tumor stage of breast cancer. Both CA 15-3 and CEA also were determined in 671 patients who had received initial curative surgery of breast cancer and who regularly attended our follow-up clinic. The CA 15-3 was found to be more sensitive than CEA in detecting recurrences of breast cancer. In the postcare period, carcinoma recurred in 205 patients. Of these, 73% had CA 15-3 concentrations above 25 U/ml; only 50% had CEA values above 3 ng/ml (P less than 0.0001). Although neither CA 15-3 nor CEA were sensitive enough for the screening and diagnosis of early breast cancer, CA 15-3 was significantly better than CEA in the detection of breast cancer metastases. 
Human papillomavirus type 16 nucleoprotein E7 is a tumor rejection antigen. It has been speculated that immunological mechanisms play an important role in the control of carcinomas associated with human papillomavirus (HPV), such as cervical cancers. We have now demonstrated that immunization of C3H/HeN mice by syngeneic nontumorigenic fibroblast-like cells that contain the transfected HPV-16 E7 gene conferred protection against transplanted cells from a HPV-16 E7-positive syngeneic tumor. This protection was HPV-16 E7-specific and was mediated by CD8+ lymphocytes, which presumably were cytotoxic T lymphocytes. These results indicate that tumor cells containing HPV-16 E7, either as a result of transfection, as in our studies, or naturally, as occurs in many human carcinomas, can induce a tumor-specific rejection response and serve as targets for such a response. The system described here provides an animal model to further study immune responses to HPV-associated malignancies and to test the efficacy of anti-HPV vaccines toward the therapy and prevention of such tumors. 
Attenuation of IL-2-induced multisystem organ edema by phalloidin and antamanide. Interleukin 2 (IL-2) is a potent cytokine with diverse effects, including the ability to stimulate lymphocyte differentiation into cells capable of lysing tumor. Its therapeutic efficacy is limited because of side effects such as breakdown of the microvascular barrier and edema. Control of the microvascular barrier is in part regulated by endothelial cell cytoskeletal contractile proteins. This study tests whether the cyclopeptides that maintain actin filament organization and distribution and reduce macromolecular flux across the endothelial cell junction in vitro would similarly maintain barrier tightness and prevent early edema produced by IL-2 in vivo. Anesthetized rats were treated at 30-min periods with intravenous saline (0.5 ml, n = 41), phalloidin (20 micrograms in 0.5 ml, n = 21), or antamanide, (20 micrograms in 0.5 ml, n = 21), starting 30 min before the 1-h infusion of 10(6) U of recombinant human IL-2 or saline. Six hours after the start of IL-2, there was edema in the saline/IL-2 group, as measured by increased wet-to-dry ratios (W/D) in the lungs, heart, and kidney. With saline/IL-2, bronchoalveolar lavage (BAL) fluid contained an elevated protein concentration and higher plasma thromboxane levels compared with controls. The number of neutrophils sequestered in the lungs was more than twice that of saline controls. Phalloidin significantly attenuated edema in lung and reduced BAL protein leak. Antamanide treatment was as effective in limiting lung and heart edema, but, in contrast to phalloidin, antamanide prevented kidney edema and did not lead to an alteration in the liver W/D. Antamanide also prevented BAL fluid protein leak. 
Amenorrhoea in women with non-alcoholic chronic liver disease. Amenorrhoea is common in women with non-alcoholic chronic liver disease, but little is known about its causes or consequences. We investigated 12 young women with non-alcoholic chronic liver disease and amenorrhoea and compared them with 11 healthy age matched controls studied in the follicular phase of the menstrual cycle. None of the patients had raised serum concentrations of follicle stimulating hormone suggesting primary gonadal failure, but the variance in serum concentrations of testosterone, oestradiol, prolactin, and luteinising hormone were significantly greater in chronic liver disease patients than control subjects (p less than 0.01). Seven of the 12 chronic liver disease patients had low serum luteinising hormone concentrations, and compared with controls these patients also had significantly reduced median values of oestradiol (64 pmol/l), testosterone (1.1 nmol/l), and follicle stimulating hormone, and were significantly underweight as assessed by skinfold thickness measurements (all comparisons p less than 0.025). In the group with chronic liver disease skinfold thickness was significantly correlated with serum luteinising hormone (p less than 0.02). The five patients with normal serum luteinising hormone had higher median values of both oestradiol (237 pmol/l) and testosterone (3.0 nmol/l) than the control subjects (oestradiol: 113 pmol/l, testosterone: 1.9 nmol/l) but were not more obese or hirsute. Amenorrhoea was unrelated to the duration or severity of liver disease. The metacarpal cortical bone area (an index of bone density) was inversely related to the duration of amenorrhoea (p less than 0.02). We conclude that amenorrhoea in women with non-alcoholic chronic liver disease arises from hypothalamic-pituitary dysfunction and can occur at any stage. 
Postpericardiotomy and postmyocardial infarction syndrome presenting as noncardiac pulmonary edema. Three cases are reported that describe acute pulmonary edema as an early manifestation of a postpericardiotomy or postmyocardial infarction syndrome. Each of these cases occurred in the presence of good left ventricular function. The cases suggest this syndrome occurs in immunologically primed patients who have had prior cardiac injury resulting in readily available heart antibody. The first report followed an acute myocardial infarction that required a temporary pacemaker, and the two other cases occurred following coronary artery bypass surgery. Two of the patients had a history of distant myocardial or pericardial injury, and the third patient had an acute anteroseptal myocardial infarction two to three weeks before cardiac surgery. All three patients with pulmonary edema responded dramatically to corticosteroids, having been resistant to diuretic and pre-load and afterload reduction therapy, suggesting an autoimmune capillary injury process. Early recognition of such a syndrome is important since all three patients were successfully treated, and might otherwise have been confused with other causes of pulmonary edema. 
Cost-effectiveness of extracorporeal shock-wave lithotripsy versus cholecystectomy for symptomatic gallstones. To evaluate the cost-effectiveness of extracorporeal shock-wave lithotripsy vs. cholecystectomy for symptomatic gallstones, a model was constructed that projects charges and survival for both treatments. For a 45-year-old woman with one small stone, treatment with extracorporeal shock-wave lithotripsy rather than cholecystectomy is projected to result in an average gain of only 3 days of life and an average increase in direct medical charges of $1729 over 5 years of follow-up. The resulting marginal cost-effectiveness of extracorporeal shock-wave lithotripsy vs. cholecystectomy is $216,000 of extra charges per year of life gained with extracorporeal shock-wave lithotripsy. Extracorporeal shock-wave lithotripsy is projected to be much more cost-effective for elderly than for young patients (10-20-fold difference), but considerably less cost-effective for multiple stones than a single stone (2-4-fold difference), and less cost-effective for women than men (twofold difference). Adjusting for effects of morbidity on quality of life, extracorporeal shock-wave lithotripsy is projected to have slightly better quality-adjusted survival than cholecystectomy for the small subset of patients with one stone (by 8 to 43 days at 5 years) but not for young patients with multiple stones. It is concluded that decisions about appropriate use of extracorporeal shock-wave lithotripsy should consider the effects of patient characteristics on clinical and economic outcomes. 
Solitary extramedullary plasmacytoma of the maxillary antrum and orbit presenting as acute bacterial orbital cellulitis. Orbital involvement by plasma cell tumours is rare. Orbital tumours do not generally present as an acute orbital inflammatory disease in adults, though tumours such as rhabdomyosarcoma may cause clinical signs similar to an acute orbital cellulitis in children. We describe a patient with bacterial orbital cellulitis and sinusitis who was found to have an extra-medullary plasmacytoma of the maxillary antrum and orbit and coexisting testicular seminoma. 
Modified Rambo meatoplasty in translabyrinthine tumor removal. Spinal fluid otorrhea and otorhinorrhea are morbid complications that occur in up to 18% of patients after removal of translabyrinthine tumor. Both of these problems can be significantly reduced if, during the initial surgery, the posterior canal wall is taken down and the tympanic membrane and external auditory canal skin are removed for better exposure of the eustachian tube orifice. The external auditory meatus can then be sealed by a previously described modification of the Rambo procedure. This additional procedure adds about 20 minutes to the surgery and presents a small risk of retained squamous epithelium. Fifty consecutive patients were divided into two equal groups and studied retrospectively. In group I, the patients underwent a modified Rambo meatoplasty at the time of the removal of their translabyrinthine tumor, whereas patients in group II had the tympanic orifice of their eustachian tube obstructed through the facial recess. Review of the postoperative course of these fifty patients indicated that the addition of the modified Rambo meatoplasty was justified by the overall reduction in morbidity and expense it provided. 
Rapid resolution of ST elevation and prediction of clinical outcome in patients undergoing thrombolysis with alteplase (recombinant tissue-type plasminogen activator): results of the Israeli Study of Early Intervention in Myocardial Infarction. Alteplase (recombinant tissue-type plasminogen activator (rt-PA)) was infused within four hours of onset of symptoms in 286 patients with acute myocardial infarction. Delayed coronary angiography was performed 72 hours after admission with coronary angioplasty if indicated. Electrocardiographic monitoring was continuous during the first hour of treatment. The sum of the ST segment elevations (sigma ST) was calculated on electrocardiograms recorded at entry and an hour later. ST elevations resolved rapidly within one hour of treatment in 189 patients and persisted in 97 patients. Rapid resolution of ST elevation correlated with angiographic coronary patency as determined by coronary angiography 72 hours after admission. The patients with rapid resolution of sigma ST had significantly smaller infarcts and a better clinical outcome than the patients with persistent ST elevation. sigma ST values at entry and one hour after treatment had no additional independent predictive value. Rapid resolution of ST elevations in patients undergoing thrombolysis with alteplase was associated with a significantly smaller release of creatine kinase, better preservation of left ventricular function, lower morbidity, and less short and long term mortality. Rapid resolution of sigma ST elevation is an efficient indicator of clinical outcome in groups of patients with acute myocardial infarction undergoing thrombolysis with alteplase. 
Cirrhosis of the liver. A regenerative process. The ancient story of Prometheus, chained to a rock for defying Zeus by stealing fire from Mount Olympus and subjected to daily tearing at his liver by an eagle, attests to the early recognition of the extraordinary regenerative capacity of the human liver. This process had remained an intriguing mystery over the millennia. In the last 20 years, following the pioneering work of Bucher (1) and Moolten et al (2), there has been an explosion of research that has clarified some of the mechanisms underlying the process of hepatic regeneration. Regeneration implies proliferation and regeneration. After the fetal and postnatal growth of the liver is completed, hepatocytes no longer proliferate actively, but they can proliferate in response to cell death or loss (3). Hepatocyte growth responses are of particular research interest because they occur in vivo and involve cells that are normally quiescent. Hepatic regeneration constitutes a highly regulated process that is best shown by the arrest of liver growth following a partial hepatectomy precisely at the moment the hepatic mass reaches the mass of the original intact liver (3). This suggests that hepatic regeneration after a partial hepatectomy is a strictly regulated nonautonomous growth process that is controlled by the same factors that are responsible for the determination and maintenance of hepatic mass in a normal individual. In response to a partial hepatectomy, hepatocytes enter the cell cycle and progress to DNA synthesis and replication but only in numbers sufficient to restore the hepatic mass. The regeneration response is both synchronized and universal in that it affects all intrahepatic cell lines, including nonparenchymal cells. 
Respective timing of maximal color Doppler jet areas and of peak velocity of jets in left-sided valvular lesions: clinical implications. Time intervals between the R wave of the electrocardiogram and maximal dimension of jet areas of color Doppler and the R wave of the electrocardiogram and peak velocity of valvular jets of continuous-wave Doppler were compared by use of paired and correlative studies for a group of 55 patients with a total of 71 left-sided lesions. Mean values of both time intervals, mean difference, and its standard error were equal to zero for stenoses. Time intervals of 71% for mitral stenosis and 52% for aortic stenosis did not differ by more than 0.01 second; correlation coefficients were 0.96 for mitral stenosis and 0.85 for aortic stenosis. For regurgitations, differences in mean values and a mean difference with a standard error were found but remained unsignificant. However, the percentage of differences in time intervals below or equal to 0.01 second decreased to 35 for aortic regurgitation and 13 for mitral regurgitation, which showed the widest 95% range of differences. Correlation coefficients were 0.84 for the aortic regurgitation and 0.33 for mitral regurgitation. Thus the close relationship of time intervals suggests that standardized timing of area measurements at peak velocity is feasible for stenoses and remains under consideration for aortic regurgitation. Timing of measurements should remain empiric for mitral regurgitation. 
Shortcomings of current antihypertensive therapy. Effective antihypertensive agents have been available for the last four decades. Their use in the treatment of hypertension has resulted in a marked decline in hypertension-induced morbidity and mortality. There are, however, some notable shortcomings with the currently available antihypertensive therapies, including disappointing effects against coronary artery disease and the fact that, even with treatment, hypertensive patients still have considerably higher cardiovascular morbidity and mortality than matched normotensives. This may be due to insufficient lowering of the elevated arterial pressure in hypertensive patients. In theory, overtreatment may also constitute a risk, considering the J-curve phenomenon. Other factors which may play a role are the different pathophysiological mechanisms in stroke and myocardial infarction, the potentially negative metabolic effects induced by some antihypertensive drugs, the importance of cardiovascular hypertrophy (in particular, left ventricular hypertrophy), and the inability of some antihypertensive agents to reverse such changes. To rectify some of these shortcomings, a more effective antihypertensive therapy is required. Ideally, an antihypertensive agent should provide effective lowering of blood pressure, in most patients to normotensive levels, while being devoid of potentially negative metabolic effects. It should also induce reversal of the changes of cardiovascular hypertrophy and, if possible, limit tissue damage if and when a vascular complication occurs. 
Differential detection of plasma hydroperoxides in sepsis. OBJECTIVE: To determine whether plasma lipid hydroperoxides may be a useful marker for sepsis. DESIGN: Exploratory, open-label study. SETTING: Critical care unit at a university medical center. PATIENTS: Twelve patients with sepsis syndrome requiring hemodynamic monitoring with pulmonary artery catheters. Seven patients were diagnosed with pulmonary infections and five patients had intra-abdominal infections. INTERVENTIONS: Fatty acid hydroperoxide was measured in the fresh arterial plasma (radial artery) and mixed venous plasma (pulmonary artery) from each patient. Hydroperoxide was determined using a sensitive assay based on activating the cyclooxygenase reaction of prostaglandin H synthase. MEASUREMENTS AND MAIN RESULTS: The mean difference between the amount of fatty acid hydroperoxide measured in the plasma draining involved regions (arterial plasma for pulmonary sepsis, mixed venous plasma for intra-abdominal sepsis) compared with the paired, uninvolved regions was 0.45 +/- 0.14 microM (mean +/- SEM; p less than .005). CONCLUSIONS: Increased lipid hydroperoxides in blood-draining septic foci are markers of oxyradical release associated with severe infection, although they are not specific for infectious conditions, being released also from nonseptic regions of surgical trauma. Assays for hydroperoxides may be useful when relatively free of other tissue trauma. 
Early angioplasty in patients with acute myocardial infarction complicated by hypotension. Emergency percutaneous transluminal coronary angioplasty was performed in 62 patients with acute myocardial infarction complicated by hypotension. All patients were treated within 12 hours of the onset of chest pain. Angioplasty was completely successful (residual lesion less than or equal to 50%) in 48 patients, partially successful (patent vessel greater than 50% residual lesion) in four patients, and unsuccessful in 10 patients. Patients in whom angioplasty was successful had a hospital mortality rate of 19%; those in whom angioplasty was unsuccessful or only partially successful had hospital mortality rates of 60% and 50%, respectively, (p = 0.012). Patients with occlusion of the proximal left anterior descending vessel had the highest failure rate (42%) and the highest mortality rate (67%). Other univariate predictors of hospital mortality were older age and elevated end-diastolic pressure. Successful emergency angioplasty improves mortality in patients with acute infarction complicated by hypotension. 
HLA-DQA1 and -DQB1 alleles associated with genetic susceptibility to IDDM in a black population. Transracial analysis provides a method of distinguishing primary associations between insulin-dependent diabetes mellitus (IDDM) and HLA class II alleles from those secondary to linkage disequilibrium. Blacks show DR-DQ relationships that are different from other races and are a useful group in which to investigate HLA-D region associations with IDDM. In this study, the frequencies of HLA-DQA1 and -DQB1 alleles in Afro-Caribbean IDDM and control subjects were compared. Alleles were identified with sequence-specific oligonucleotide probing. The DQA1 allele A3 was positively associated with IDDM (relative risk [RR] = 25.3, corrected P [Pc] less than 7.0 x 10(-6). The DQB1 alleles DQw2 and DQw8 were also positively associated (RR = 4.7, Pc less than 6.5 x 10(-3) and RR = 12.3, Pc = 3.4 x 10(-3), respectively). The A1.2 and DQw6 alleles were negatively associated (RR = 0.16, Pc less than 3.5 x 10(-3) and RR = 0.15, Pc = 2.4 x 10(-2), respectively). These findings were compared to data from other races. The positive associations with A3 and DQw2 are consistent with all racial groups investigated. The negative association with DQw6 is present in all racial groups in which it is a common allele. These findings suggest that DQ alleles, and hence DQ molecules, may directly affect predisposition to IDDM. 
Automatic implantable cardioverter-defibrillator: is early implantation cost-effective? The evaluation of survivors of sudden cardiac death with serial electrophysiologic studies involves a lengthy and expensive hospitalization, especially when an automatic implantable cardioverter-defibrillator is ultimately necessary. The cost efficacy of this conventional approach was therefore compared with direct implantation of a cardioverter-defibrillator after the first electrophysiologic study. Thirty-two survivors of sudden death who had inducible ventricular tachycardia during their initial electrophysiologic study underwent serial drug trials. At discharge 12 (37%) were taking an antiarrhythmic drug found to prevent induction of ventricular tachycardia and 20 underwent cardioverter-defibrillator implantation after serial drug trials proved ineffective. The average length of hospitalization for this group that had undergone serial drug testing was 20.2 +/- 9.3 days at an average cost of $48,900 +/- $31,600. Seven survivors of sudden death had no inducible ventricular tachycardia during their initial electrophysiologic study and underwent direct cardioverter-defibrillator implantation. Their average length of hospitalization was 12.6 +/- 6.2 days at an average cost of $40,400 +/- $8,300. It is concluded that automatic implantable cardioverter-defibrillator implantation as an early intervention is not more costly and indeed may be cost-effective compared with therapy guided by serial electrophysiologic testing. As antitachycardia devices become more versatile, long lived and easier to implant, earlier implantation is likely to compare even more favorably with drug therapy. 
Use of parenteral medium-chain triglyceride emulsion for maintaining seizure control in a 5-year-old girl with intractable diarrhea. Medium-chain triglycerides (MCT) are an important component of an enteral ketogenic diet for seizure control. Previously, it was difficult to maintain ketosis when parenteral (iv) nutrition therapy was necessary. The use of iv MCT in a 5-year-old girl with Lennox-Gastaut syndrome who had diarrhea and dehydration is reported. Conventional 20% iv fat emulsion (long-chain triglycerides, LCT) and dextrose free hyperalimentation (HAL) in a 4:1 ketogenic ratio did not maintain adequate ketosis during bowel rest. Compassionate use of iv MCT (Clintec Nutrition) infused as a 70:30 MCT/LCT ratio plus HAL maintained moderate ketosis. Seizures were well controlled during the iv MCT regimen, which allowed normal daily functioning. Complications included abnormal liver function tests and severe iron deficiency anemia of unknown etiology. Serum triglyceride and cholesterol levels increased to 1717 mg/dl and 614 mg/dl, respectively, but decreased with a reduction of lipid infusion and use of an antihyperlipemic drug. Nutritional status was maintained. In this case, iv MCT proved to be a relatively safe and effective short-term method of continuing parenteral nutrition while maintaining ketosis for seizure control. 
Long-term effects of radiotherapy and bromocriptine treatment in patients with previous surgery for macroprolactinomas. The long-term effect of radiotherapy and bromocriptine treatment was retrospectively evaluated in 25 patients who had previously undergone transsphenoidal surgery for treatment of macroprolactinomas. Surgery had reduced the median serum prolactin (PRL) value from 613 micrograms/l, a reduction of 53%. Postoperative bromocriptine was administered to 21 of the 25 patients. In 14 of these patients, serum PRL values became normal or almost normal with medication. There were no radiological or ophthalmological signs of progressive tumor growth during bromocriptine treatment. Fourteen patients received postoperative radiotherapy. After withdrawal of bromocriptine in 13 of these patients an average of 7 years after radiotherapy, the median serum PRL value had further decreased by 95%. The PRL reduction was similar for all doses applied, 38 to 52 Gy. After withdrawal of bromocriptine in 8 patients not receiving radiotherapy an average of 7 years after operation, the median serum PRL level had further decreased by 75%. At follow-up, 18 additional instances of pituitary insufficiency had developed in the group receiving radiotherapy, compared with 8 cases of insufficiency in the group not receiving radiotherapy. Thus, because bromocriptine has a long-standing effect on prolactin secretion, and radiotherapy is associated with a notably high incidence of pituitary insufficiency, we propose that photon irradiation should be considered mainly for patients who are not candidates for surgical or medical treatment. 
Multiple, giant fibroadenoma. Multiple, giant fibroadenomas are histologic and clinical variants of "juvenile" or "giant" fibroadenomas. These tumors are rare and occur mainly in adolescent and young adult black females. The individual lesions are well encapsulated with a histologic pattern primarily of the "juvenile" type, although cases of the "adult" type have been reported. A high incidence of recurrence is noted upon local excision, although this may decrease as the patient becomes older. Management options include local excision with reconstruction, reduction mammoplasty, and simple mastectomy with reconstruction. A case is described of this condition with review of the literature. 
Developmental anterobasal temporal encephalocele and temporal lobe epilepsy. The authors describe the association between an antero-basal temporal lobe encephalocele and medically intractable temporal lobe epilepsy in three patients treated successfully by surgery. Two men and one woman, aged 26 to 37 years (mean 31 years), had onset of complex automatism and generalized seizures in their second and fourth decades (mean age 22.7 years). They had been epileptic for 6 to 14 years (mean 8.3 years) before surgery. Preoperative electroencephalograms localized ictal epileptic activity to the left mesial temporal lobe in all cases, and neuropsychological testing revealed dominant temporal lobe dysfunction. Magnetic resonance (MR) imaging demonstrated an anteromedial basal temporal encephalocele extending into the pterygopalatine fossa through a bone defect at the base of the greater sphenoid wing in the region of the foramen rotundum and pterygoid process, a discrete center of embryonal chondrification. At surgery, the encephaloceles were found in front of the uncus, and an area of gliosis extended from the encephalocele to the amygdalohippocampal region. All patients have been seizure-free following anterior temporal resection and amygdalohippocampectomy including the encephalocele. These three cases delineate a condition of disordered embryogenesis wherein a developmental anterobasal temporal encephalocele acts as the substrate for temporal lobe epilepsy. This lesion may be diagnosed preoperatively with MR imaging and should be considered in the differential diagnosis of late-onset temporal lobe epilepsy. 
Role of interferons in the therapy of melanoma. A range of potent immunoregulatory molecules termed cytokines has become available for the therapy of human melanoma. Among the cytokines, the interferons (IFN) have been examined in great depth for the therapy of melanoma. IFN are able to modulate host effector cell function, including the tumor cytolytic function of lymphocytes and monocytes. IFN also have the capacity to regulate the distribution of circulating immunoregulatory (T) lymphocytes and the expression of tumor cell surface antigens, as well as class I and II products of the major histocompatibility locus. These activities of the IFN have led to their early application for treatment of human melanoma. The empirical evidence that IFN alpha exerts clinically significant anti-tumor effects against melanoma is reviewed, and evolving status of adjuvant trials of IFN alpha and gamma is noted. New indirect host-mediated anti-tumor activities that may potentially be manifest by IFN have yet to be fully harnessed. The opportunity to obtain meaningful anti-tumor activity in advanced disease or adjuvant settings, at dose ranges below those which are toxic (conventional maximal tolerable), are at hand. The U.S. cooperative groups [Eastern Cooperative Oncology Group (ECOG), Cancer and Leukemia Group B (CALGB), and South West Oncology Group (SWOG)] are studying IFN gamma in pursuit of this goal in advanced and adjuvant settings for melanoma and other tumors. The determination of the clinical role of IFN as biologic response modifiers demands equal commitment to the clinical assessment of immunobiologic mechanisms and anti-tumor effects. The immunologic assessment of IFN and a number of other cytokines is a major focus of the Pittsburgh Cancer Institute. Regional delivery of cytokines such as interleukin-2 (IL-2) may be the most appropriate and least toxic approach, given their half-life. Regional therapy by the intralesional route has yielded enhanced activity for a range of biologics, including bacillus Calmette-Guerin (BCG), IL-2, and tumor necrosis factor (TNF). Intralymphatic therapy with methanol extraction residue of BCG (MER-BCG) has been tested, and trials are now in progress with IL-2 to assess the optimal dosage by this route. It is likely that the optimal role of IFN and other cytokines will be found in combination with one another, and with different biologic modalities such as monoclonal antibodies and vaccines, to allow expansion and heightened activity of the desired effector cell populations in the host. Enhanced host toxicities, as well as anti-tumor effects, may require that special attention be devoted to optimal sequence of administration to enhance the therapeutic index. 
Effectiveness of histopathological diagnoses in dysfunction of hepatic transplantation. Review of 146 histopathological studies from 53 transplants. In 47 patients who underwent 53 liver transplantations and immunosuppression with cyclosporine (cyclosporin A), methylprednisolone sodium succinate, and antithymocyte globulin, 146 histopathological studies were performed (138 biopsies, six hepatectomies, and two autopsies). The following microscopical diagnoses were made: 43 acute rejections (29.4%), six chronic rejections (4.1%), 18 liver blood perfusion changes (12.3%), 15 biliary changes (10.2%), 10 cases of functional cholestasis (6.8%), two drug reactions (1.3%), two hepatitis B virus recurrences (1.3%), 11 opportunistic viral infections (7.5%), 18 minimal changes (12.3%), two nonclassifiable changes (1.3%), and 19 plurietiological changes (13%). A histopathological diagnosis of acute rejection was made in 31 transplants (58.4%). In 22 (71%) of them, acute rejection was diagnosed with the protocol biopsy specimen that was obtained during the second posttransplant week. Leukocyte counts and serum bilirubin and enzyme levels were obtained on the same day that the hepatic biopsy specimens were taken. There was no significant statistical difference between the mean serum data that accompanied each histopathological diagnosis, allowing identification of a characteristic biochemical profile for the causes of graft dysfunction. We report a detailed description of the microscopical findings of each diagnosis and the following conclusions: (1) Acute rejection is the most frequent cause of hepatic dysfunction and has an early appearance during the posttransplant period. (2) Histopathological findings can identify the causes of the dysfunction. (3) There is no specific biochemical pattern to differentiate these causes. This may be due to the frequent combination of etiological factors in every dysfunction episode. 
Medical and surgical treatment of nonallergic asthma associated with gastroesophageal reflux Patients presenting to a chest clinic because of adult-onset wheezing with no history of allergy had a 90 percent prevalence of gastroesophageal reflux, even though reflux symptoms were mild or absent. Ninety patients were randomly assigned to receive cimetidine or an identical placebo or to undergo antireflux surgery. During a six-month period, all groups improved clinically; the cimetidine and surgical groups improved more than the placebo group. The intake of pulmonary medication decreased significantly in both cimetidine and surgical groups. Pulmonary function test results improved in the cimetidine- and surgically treated patients; improvement was not statistically significant. At long-term follow-up, the surgical group maintained clinical improvement and decreased pulmonary medication intake, whereas the placebo group worsened. We conclude that gastroesophageal reflux can play a significant role in some patients with nonallergic pulmonary disease and that its treatment can improve pulmonary symptoms and objective measurements of pulmonary function. 
Liver tumors in cirrhosis: experimental study with SPIO-enhanced MR imaging. The influence of cirrhosis on superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance (MR) imaging of the liver was studied in 31 rats. Experimental models included carbon tetrachloride-induced cirrhosis and liver engrafting of rhabdomyosarcoma S4T cells. Hepatic uptake of SPIO measured with relaxometry decreased dramatically with histologic grade, while splenic uptake increased; the same results were achieved by calculating K values. Imaging of 13 tumorous cirrhotic rats confirmed these results by showing a muted decrease in liver signal intensity on spin-echo images after injection of SPIO. Nevertheless, all intrahepatic tumors could be visualized, as confirmed by postmortem examination. On gradient-echo images, postinjection contrast between the tumor and the liver was not affected by cirrhosis. Thus, despite strong impairment of hepatic uptake in cirrhosis, the diagnostic efficacy of MR imaging with SPIO did not seem to be significantly affected. 
The prognostic value of postoperative seizures following epilepsy surgery. Among 55 patients undergoing temporal lobectomy for refractory epilepsy, patients with seizures in the week following surgery had a poor long-term, seizure-free outcome compared with patients without seizures. Outcome for patients with single seizures or seizures restricted to the first postoperative day seemed favorable compared with patients with multiple or later seizures. Seizure type and similarity to preoperative events did not predict outcome. 
Intracoronary recombinant tissue-type plasminogen activator in unstable angina: a pilot angiographic study. The effectiveness of intracoronary (IC) recombinant thromboplastin activator (rt-PA) was prospectively evaluated in seven patients with unstable angina and complex angiographic lesions or intracoronary filling defects (ICFD). There were four men and three women, with a mean age of 60 years. Three patients had multivessel disease and all patients had rest angina; none had evolving myocardial infarction. All patients were pretreated with aspirin and were given heparin. IC rt-PA was infused at the rate of 1 mg/min to a total of 50 mg, and angiographic changes were observed every 15 minutes. At 50 minutes, angiographic improvement was seen in two patients (28%), one of whom had complete and one of whom had partial resolution of ICFD. In two patients (28%) there was no change in the lesion, and three patients (42%) had worsening of the lesion appearance. In two of the latter, paradoxical closure was observed at the end of the infusion, and was treated successfully with ad hoc emergency angioplasty. This pilot study suggests that IC rt-PA at the dosage used may have variable effects on complex coronary lesions associated with unstable angina, and this may be of relevance in further trials evaluating IC thrombolysis in unstable coronary ischemic syndromes. 
Optimal dose of neuroleptic in acute schizophrenia. A controlled study of the neuroleptic threshold and higher haloperidol dose. After individual determination of neuroleptic threshold (NT) doses of haloperidol, 106 patients with schizophrenia or schizoaffective disorder (Research Diagnostic Criteria) were treated openly at such doses (mean, 3.7 +/- 2.3 mg/d) for 2 weeks. Ten responding patients were discharged and unavailable for follow-up or refused subsequent randomization, and one non-responding patient refused randomization. The remaining 95 responding or nonresponding patients were then randomly assigned, double-blind, to a dosage of haloperidol two to 10 times higher (mean, 11.6 +/- 4.7 mg/d) or to a continuing NT dosage (mean, 3.4 +/- 2.3 mg/d) for another 2 weeks. Of the 58 patients exposed only to NT dosages of haloperidol, 72% clinically recovered within the 5-week trial. Higher dosages given to 47 patients did not lead to greater improvement in measures of psychosis, but did produce slightly greater declines in measures of hostility. Higher dosages did regularly lead to significant increases in distressing extrapyramidal side effects. 
Oxygen-dependent lipid peroxidation during lung ischemia. The effect of alveolar oxygen tension on lung lipid peroxidation during lung ischemia was evaluated by using isolated rat lungs perfused with synthetic medium. After a 5-min equilibration period, global ischemia was produced by discontinuing perfusion while ventilation continued with gas mixtures containing 5% CO2 and a fixed oxygen concentration between 0 and 95%. Lipid peroxidation was assessed by measurement of tissue thiobarbituric acid-reactive products and conjugated dienes. Control studies (no ischemia) showed no change in parameters of lipid peroxidation during 1 h of perfusion and ventilation with 20% or 95% O2. With 60 min of ischemia, there was increased lipid peroxidation which varied with oxygen content of the ventilating gas and was markedly inhibited by ventilation with N2. Perfusion with 5-, 8-, 11-, 14-eicosatetraynoic acid indicated that generation of eicosanoids during ischemia accounted for approximately 40-50% of lung lipid peroxide production. Changes of CO2 content of the ventilating gas (to alter tissue pH) or of perfusate glucose concentration had no effect on lipid peroxidation during ischemia, but perfusion at 8% of the normal flow rate prevented lipid peroxidation. Lung dry/wet weight measured after 3 min of reperfusion showed good correlation between lung fluid accumulation and lipid peroxidation. These results indicate that reperfusion is not necessary for lipid peroxidation with ischemic insult of the lung and provide evidence that elevated PO2 during ischemia accelerates the rate of tissue injury. 
Surgical treatment of limbic epilepsy associated with extrahippocampal lesions: the problem of dual pathology. The authors present their review of 178 patients who underwent en bloc temporal lobectomies as surgical treatment for intractable epilepsy. Hippocampal cell density was quantitatively analyzed and the histology of the anterior temporal lobe was reviewed. Fifty-four patients (30.3%) had evidence of extrahippocampal lesions in addition to neuronal cell loss within the hippocampus (the dual pathology group). The pattern of cell loss was analyzed in the remaining 124 cases (69.7%) with no extrahippocampal pathology, and compared with that of the dual pathology group and a control group of four nonepileptic patients. Hippocampal cell loss was found in almost all epileptic patients compared to the control group. Severe cell loss greater than 30% of control values was found in 88.7% of patients without extrahippocampal lesions, but in only 51.8% of patients with dual pathology. The difference between these two groups was statistically significant (p less than 0.001). In the dual pathology group, lesions of different pathology had a significant relationship with the degree of hippocampal cell loss: all 12 patients with glioma had mild cell loss, whereas all 13 patients with heterotopia were associated with severe cell loss. Severity of hippocampal cell loss was also analyzed in relation to seizure history: a prior severe head injury was associated with severe cell loss. Other factors such as seizure duration, secondary generalization, or family history of seizures were not associated with hippocampal damage. Dual pathology may produce a combination of neocortical and temporolimbic epilepsies that warrants a precise definition of the true epileptogenic area prior to surgical treatment. 
Congenital cholesteatoma of the middle ear in children: a clinical and histopathological report. Forty-one children with congenital cholesteatoma of the middle ear seen from 1978 through 1989 are reviewed. The most common presentation was that of an asymptomatic white mass behind a normal intact tympanic membrane. Computed tomography (CT) scan was useful in documenting extension beyond the mesotympanum. Surgical removal was performed using an extended tympanotomy for lesions in the middle ear and tympanomastoidectomy for those that had extended into attic and mastoid air cells. Observation over an average 3.1-year period indicated that 80% of children were free of disease after initial surgery. Residual disease that required further surgery was present in 20%. The importance of early diagnosis of congenital cholesteatoma is strongly advocated. The prognosis is better when the cholesteatoma is confined to the anterosuperior quadrant of the middle ear. Seventeen patients in this study had such a lesion, and extended tympanotomy allowed removal of an encapsulated closed cholesteatoma with normal postoperative hearing and no residual cholesteatoma. The average age was 2.3 years. Temporal bone histopathological studies of three cases of congenital cholesteatoma demonstrate two distinct pathological types of congenital cholesteatoma. A "closed" keratotic cyst in the anterior mesotympanum, which is easily removed, and an "open" infiltrative type in which there is no containment of the keratotic debris and the cholesteatoma matrix is in direct continuity with middle ear mucosa. Surgical extirpation of the "open" type is difficult and more likely to be associated with residual disease. 
Sexually transmitted papilloma viral infection in the male. VII. Is cancer of penis sexually transmitted? Four cases are reported of squamous cell carcinoma of the genital tract in males. The close association of HPV 16/18 with in situ squamous carcinoma affecting the penis is demonstrated. The first documented case of a primary penile squamous cell carcinoma with metastatic deposits yielding positive HPV 16/18 isolates as shown by in situ DNA hybridization again demonstrates a close association of this virus to malignancy in humans. The clinical implications of these findings strongly suggest that squamous cell carcinoma of the penis is a sexually transmitted disease. A thorough examination of both sexual partners is necessary when Bowenoid papulosis or penile carcinoma is present, since the female partner is at high risk for cervical neoplasia. 
Hemi-Fontan operation in surgery for single ventricle: a preliminary report Mortality after Fontan operation is related to risk factors like ventricular hypertrophy, pulmonary artery deformity, and young age (infancy). Preliminary procedures may improve Fontan results. The hemi-Fontan operation includes atriopulmonary anastomosis and correction of all anatomical risk factors, but an atriopulmonary patch directs superior vena caval flow into both pulmonary arteries and inferior vena caval flow into the ventricle, thus maintaining cardiac output (modified Glenn physiology). We performed 17 hemi-Fontan procedures in 16 patients, 14 primarily (median age, 9 months) and 3 for takedown of a Fontan operation. The 14 primary operations were for hypoplastic left heart syndrome (5), pulmonary atresia with intact ventricular septum (4), and other (5). All patients had multiple risk factors. Extubation was at 18 hours (median), chest tube removal was at 3 days, and hospital discharge was at 8 days postoperatively. Important complications included subglottic stenosis, transient diaphragmatic paralysis, pulmonary artery stenosis and thrombosis requiring reoperation, and transient ventricular fibrillation. One patient required hemi-Fontan takedown, and this patient later (3 months postoperatively) became the only death. Fontan take-downs have had a high mortality rate. In 3 patients who tolerated Fontan operation poorly, converting Fontan to hemi-Fontan abruptly reversed the downhill course. For these patients, the operation was life-saving. Hemi-Fontan operation is safe and well-tolerated, even in infants, provides the advantages of modified Glenn physiology before Fontan operation, and may be especially useful for Fontan takedown after failed Fontan. 
A clinicopathological study of seven globes enucleated after primary radiation therapy for malignant melanoma of the choroid or ciliary body. Seven patients with malignant melanoma of the choroid or ciliary body were initially managed with radiation therapy, either teletherapy with proton or cobalt 60 external beam, or brachytherapy with the insertion of an episcleral plaque containing iodine 125, 60Co or gold 198. All seven globes subsequently were enucleated because of progressive growth of the tumours, total retinal detachment, persistent vitreous hemorrhage, or neovascular or angle-closure glaucoma. Six of the patients had severe visual loss at the time of enucleation. The effects of radiation therapy on the neoplasms and the mechanisms for the visual loss are discussed. 
Nerve cell loss in the thalamus in Alzheimer's disease and Parkinson's disease. Serial sections through the thalamus from the fixed right cerebral hemispheres of 15 cases (5 Parkinson's disease, 5 Alzheimer's disease (AD) and 5 controls) were used to obtain quantitative estimates of neuronal loss, neurofibrillary tangle formation and Lewy body inclusions within individual thalamic nuclei. Severe neuronal loss and tangle formation were evident in the anterodorsal nucleus from the AD cases. Nerve cell damage was also present in the centromedian nucleus but was not associated with tangle formation and occurred in all but 2 of the brains examined. It is likely that the anterodorsal neurons are damaged locally by the Alzheimer's disease process whereas the changes in the centromedian nucleus may be related to ageing. 
Effect of tumor necrosis factor-alpha on the proliferation of leukemic cells from children with B-cell precursor-acute lymphoblastic leukemia (BCP-ALL): studies of primary leukemic cells and BCP-ALL cell lines. The effect of recombinant tumor necrosis factor-alpha (rTNF-alpha) on the primary leukemic blasts and leukemic cell lines derived from children with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) was studied. The proliferation of leukemic cells from the bone marrow of 11 of 13 patients (seven at diagnosis, four in relapse) and from the 697 (BCP-ALL) cell line was significantly inhibited by rTNF-alpha at the lowest dose tested (0.1 ng/mL), as measured by 3H-TdR uptake. The degree of inhibition was variable, ranging from 17% to 78%. Furthermore, a dose-dependent inhibitory effect was observed, with approximately 70% mean inhibition of DNA synthesis detected when cells from 12 of 13 patients were incubated with 100 ng/mL of rTNF-alpha for 3 days. In contrast, rTNF-alpha did not inhibit another BCP-ALL cell line (EU-1/ALL) established recently in our laboratory. Studies indicated that the TNF-alpha gene was expressed by the primary leukemic blasts of one TNF-resistant case in his third relapse and by EU-1 cells. Also, TNF-alpha protein was detected by Western blot analysis and enzyme-linked immunoabsorbent assay in the supernatant of EU-1 cells; this is the first report of TNF production by a BCP-ALL cell lines. The production of TNF-alpha mRNA and protein was not detected in the 697 cell line and in the primary leukemic blasts from six patients (four at diagnosis, two in relapse) whose leukemic cells were inhibited by TNF. The partially purified TNF-alpha obtained from the EU-1 cell line also suppressed the proliferation of TNF-sensitive primary leukemic cells, and this inhibitory activity was abolished by an anti-TNF-alpha specific antibody. Our results demonstrate that TNF-alpha is an inhibitor of in vitro proliferation of BCP-ALL cells from most patients. The TNF-resistant leukemic cells from a few patients and the EU-1 cell line express TNF mRNA, suggesting that the induction of TNF gene expression is associated with the development of TNF resistance. 
Long-term results after balloon pulmonary valvuloplasty. BACKGROUND. The objective of this study was to determine the long-term outcome of patients after percutaneous balloon pulmonary valvuloplasty (BPV) treatment of congenital pulmonary valve stenosis. METHODS AND RESULTS. This study represents a case series with duration (mean +/- SD) of follow-up of 4.6 +/- 1.9 years. Forty-six patients with a median age of 4.6 years (range, 3 months to 56 years) had BPV at one academic institution between June 1981 and December 1986. Mean peak systolic pressure gradients from the right ventricle to the pulmonary artery were as follows: before BPV, 70 +/- 36 mm Hg; immediately after BPV, 23 +/- 14 mm Hg; at intermediate follow-up by cardiac catheterization or Doppler echocardiography at less than 2 years after BPV, 23 +/- 16 mm Hg (n = 33); and at long-term follow-up by Doppler at more than 2 years after BPV, 20 +/- 13 mm Hg (n = 42). BPV acutely reduced the gradient to less than 36 mm Hg for 41 of 46 (89%) patients. Available gradients at long-term follow-up were less than 36 mm Hg for 36 of 42 (86%) patients without additional procedures. A patient age of less than 2 years at the initial BPV was a significant risk factor for gradients over 36 mm Hg at follow-up. CONCLUSIONS. BPV provides long-term relief of pulmonary valvular obstruction in the majority of patients. Close follow-up of patients who require BPV at less than 2 years of age is warranted. 
Primary fibromyalgia and the irritable bowel syndrome: different expressions of a common pathogenetic process. Primary fibromyalgia (PFM) and the irritable bowel syndrome (IBS) are both common conditions which account for 30% or more of referrals to rheumatology and gastroenterology clinics. An association between symptoms in PFM and IBS has been suggested but the frequency with which they coexist has not been assessed. The aim of this study was to examine the prevalence of each condition in groups of patients with PFM and IBS compared to normal and disease control populations. We studied four patient groups, 20 patients in each group, with PFM, IBS, inflammatory arthritis, inflammatory bowel disease and also 20 normal controls. Using strict diagnostic criteria, each group was assessed by two investigators for symptoms and signs of PFM and IBS. Sigmoidoscopy was performed when indicated. Results indicate that 70% (14/20) of the PFM patients had IBS and 65% (13/20) of the IBS patients had PFM. This compared with the control groups where 12% (7/60) and 10% (6/60) had PFM and IBS respectively. In conclusion, these results indicate that PFM and IBS frequently coexist. A common pathogenetic mechanism for both conditions is therefore suggested. 
Diagnostic value of Lipiodol injection in focal nodular hyperplasia of the liver. We encountered a case of small focal nodular hyperplasia (FNH) of the liver. It was difficult to distinguish FNH from hepatocellular carcinoma by means of sonography, computed tomography (CT), and angiography. After the injection of Lipiodol, it accumulated densely on FNH, but was washed away after a short time, as observed on the follow-up CT. This progress was different from that in hepatocellular carcinoma. 
Tumor necrosis factor-beta in the serum of adult T-cell leukemia with hypercalcemia. Serum tumor necrosis factor-beta (TNF-beta) from patients with adult T-cell leukemia (ATL) was studied by a sandwich enzyme-linked immunosorbent assay (ELISA) developed in our laboratory using biotinylated monoclonal anti-TNF-beta and recombinant TNF-beta. Seven of eight patients with hypercalcemia showed elevation of serum TNF-beta. On the other hand, TNF-beta could not be detected by the ELISA in 28 patients without hypercalcemia. The lower detection limit in this assay was 100 pg/mL, corresponding to 500 pg/mL by the conventional method. In two patients serum TNF-beta level decreased after treatment in association with the level of serum calcium. Furthermore, immuno-staining using anti-TNF-beta and avidin-biotin complex showed the presence of cytoplasmic TNF-beta in not only human T-cell leukemia virus type I infected cell lines, but also freshly isolated cells from ATL patients with hypercalcemia. The actual biologic activity of TNF-beta in serum was confirmed by a conventional bioassay in a patient with hypercalcemia, and its cytotoxic activity was inhibited by the addition of anti-TNF-beta antibody in the assay. These results suggested that serum TNF-beta might be one of the factors contributing to the hypercalcemia, at least in patients with ATL. 
Warm ischemia induces alteration in lung immune cell functions. Warm ischemia is an important factor in early allograft dysfunction. To elucidate cellular events involved in such lung injury, we examined the effects of warm ischemia on the cytotoxic function of lymphocytes retrieved by bronchoalveolar lavage as compared with peripheral blood lymphocytes. Warm ischemia of the lung was induced in eight dogs by crossclamping left hilar structures for 1 hour. Bronchoalveolar cells from ischemia left and unaffected right lungs, as well as blood lymphocytes, were isolated before operation and 2 hours, 72 hours, and 7 days after operation. Lung and blood lymphocytes were assayed for natural killer and lectin-dependent cell-mediated cytotoxicity. Warm ischemia resulted in a significant impairment of natural killer activity within 2 hours of reperfusion (49% of preoperative control cytolysis, p less than 0.01). There was a significant increase in natural killer activity in bronchoalveolar lavage mononuclear cells 72 hours after reperfusion injury (178.4% of preoperative value, p less than 0.01). Interestingly, these functional alterations were not paralleled with changes seen in the peripheral blood lymphocytes or the opposite nonaffected lungs, where the natural killer activity appeared significantly depressed at 72 hours. Similarly, lectin-dependent cell-mediated cytotoxicity was noted to be increased in the bronchoalveolar lavage from the ischemic lung (179.5%, p less than 0.01) but decreased in the bronchoalveolar lavage from the nonaffected lung and peripheral blood lymphocytes at 72 hours after injury. We conclude that warm ischemia is associated with a functional alteration of the local lung immune cells. Such alteration is not observed in cells from the opposite lung or peripheral blood. The observed increase in nonspecific cytotoxicity of bronchoalveolar lymphocytes can be causative in the early damage seen in poorly preserved lung allografts. 
Is hypertension an insulin-resistant state? Metabolic changes associated with hypertension and antihypertensive therapy. In this review, the relationship between hypertension and abnormal carbohydrate metabolism is explored. A review of the current literature reveals that people with hypertension are also likely to suffer from insulin resistance, glucose intolerance, and hyperinsulinemia. Likewise, hypertension is prevalent in obese and diabetic patients. Deficiency of insulin at the cellular level may be a common mechanism in the development of hypertension in patients with type I or type II diabetes mellitus. Essential hypertension appears to be an insulin-resistant state. Insulin resistance may engender hypertension by increasing peripheral vascular resistance as well as by increasing salt retention at the level of the kidney. Therefore effective antihypertensive therapy should include agents that do not adversely affect carbohydrate metabolic abnormalities. Commonly used antihypertensive agents, such as thiazide, thiazide-like diuretics, and beta-blockers, are associated with glucose intolerance and increased insulin resistance. In contrast, angiotensin-converting enzyme inhibitors, calcium antagonists, and peripheral alpha-blockers (such as prazosin and terazosin) do not adversely affect glucose tolerance or insulin sensitivity. In addition, alpha-blockers have a positive effect on the serum lipid profile. The entire multifactorial cardiac risk profile must be considered when choosing therapeutic agents for conditions that have an impact on cardiovascular disease. 
The unstable ST segment early after thrombolysis for acute infarction and its usefulness as a marker of recurrent coronary occlusion. To investigate the incidence of early recurrent ST elevation after intravenous thrombolytic therapy for acute myocardial infarction, 12-lead electrocardiograms were continuously monitored for 571 +/- 326 minutes in 31 patients presenting within 4 hours of symptom onset. The study group comprised 9 women and 22 men (mean age +/- standard deviation 53 +/- 12 years), with ST elevation (anterior in 15, inferior in 16) on the initial electrocardiogram, who were given either tissue plasminogen activator (22 patients) or streptokinase (9 patients). Angiography was performed in 30 of 31 patients at 7 to 10 days. Early (less than 3 hours) resolution of ST elevation occurred in 19 patients (61%) at a median of 94 minutes (interquartile range 57 to 113) after thrombolysis, whereas 12 (39%) had no or late (greater than 6 hours) resolution. Eleven of the 19 with early resolution (58%) had either transient (5 patients) or sustained (6 patients) recurrences of ST elevation. Recurrent ST elevation was equal to or more than the initial peak elevation in 9 of 11 patients, and greater than 75% of initial peak in 2. A total of 25 episodes of recurrent ST elevation were observed in the 11 patients (19 transient and 6 sustained episodes), of which 8 (32%) were silent. The proportion of silent episodes was similar for transient (35%) and sustained (33%) recurrences. All patients with sustained recurrent ST elevation had at least 1 preceding transient recurrence. The median duration of transient recurrent ST elevation was 43 minutes (28 to 63). 
Management and long-term outcome of aortic dissection. All 163 patients admitted to one institution between 1975 and 1988 with aortic dissection were reviewed. Type I and type II patients received grafting of the ascending aorta, with an intraoperative mortality rate of 11%. For type III dissection, management was medical in 53 patients, while 19 required surgery for aortic rupture or expansion, with an intraoperative mortality rate of 11%. The 9- or 10-year survival rates were 29%, 46%, and 29% for types I, II, and III respectively. Of 135 patients with primary aortic dissection, 17 (13%) required subsequent aortic surgery. Cause of late death was other cardiovascular disease in 38%, rupture of another aortic segment in 18%, sudden death in 24%, and other medical conditions in 21%. Although operative therapy for types I and II dissections and reserving operation for selected type III dissections provides acceptable long-term survival, careful follow-up is necessary due to concurrent cardiovascular disease and residual aortic disease. 
Hemangiomas and vascular malformations. Vascular lesions in the neonate and infant are categorized as hemangiomas or malformations. Although their appearances may be similar, the pathobiology, natural history, and prognosis of these lesions are different. Selected important syndromes that are characterized as hemangiomas and vascular malformations are discussed, and an update on what is new in treatment, including laser therapy, is presented. 
"Angioglioma" and the arteriovenous malformation-glioma association. The term "angioglioma" denotes a highly vascular glioma, most of which are low-grade lesions associated with a favorable prognosis. The authors encountered an example of this pathology, a cystic oligodendroglioma associated with prominent vasculature which both clinically and histologically mimicked an occult arteriovenous malformation (AVM). This case and reports of the association of AVM and glioma prompted a histological review of 1034 surgically resected AVM's, both angiographically occult and visible, among which no oligodendroglial or astrocytic forms of "angioglioma" were found. Eight cases were observed, however, wherein oligodendroglial cells were increased in number within or about the malformation. Two basic histological patterns of oligodendroglial cell excess were seen; one appeared to be malformative in nature with abnormal disposition of oligodendroglial cells being an integral part of the AVM, whereas in the other an apparent increase in cellularity seemed the result of chronic ischemia with condensation of white matter. It appeared that the areas of increased oligodendrocyte content seen in association with AVM are non-neoplastic lesions that exhibit two rather distinct histological patterns of differing origin. In an effort to determine the frequency of "angioglioma," the authors examined Tissue Registry data for several glioma groups in which highly vascular examples are prone to occur. Tumors selected for study included 104 cerebellar-type (pilocytic) astrocytomas, 82 oligodendrogliomas, and 51 supratentorial pilocytic astrocytomas. Histological hypervascularity mimicking a vascular malformation (that is, an "angioglioma") was encountered in 5%, 4%, and 12% of the cases, respectively. Based upon clinical, radiological, and pathological reviews of these cases, as well as a careful review of the literature, it was concluded that 1) "angiogliomas" are neither rare nor represent a distinct clinicopathological entity; 2) in histological but not necessarily angiographic surgical terms, they represent simply highly vascular gliomas, usually of low grade; and 3) the clinicopathological and angiographic features as well as the prognosis of such lesions do not differ from those of similar gliomas without angioma-like vasculature. Finally, "angiogliomas" must not be confused with gliomas of high-grade malignancy which, due to neovascularity, may be highly vascular at angiography and at surgery. 
Differential gene expression in the recovery from ischemic renal injury. Recovery from renal ischemia requires regeneration of damaged tubular epithelium. Previous studies have examined the expression of proto-oncogenes and growth factors after ischemia, but the response of genes coding for structural and functional genes has not been scrutinized. Rats were subjected to 40 minutes of renal artery occlusion and 60 minutes to 96 hours of reperfusion. Total RNA was isolated and mRNA for the structural protein actin, the enzymes superoxide dismutase and renin, the proto-oncogene c-fos, the nuclear protein histone H2b, and the putative marker for cell injury TRPM-2 was quantitated by Northern hybridization. Expression of the proto-oncogene c-fos was seen early but for only short duration. Histone gene expression was not markedly increased until 24 hours after ischemia, but remained increased for several days. Renin mRNA was undetectable one hour after ischemia, but was present in normal amounts at 24 and 48 hours. In contrast, superoxide dismutase mRNA was present in decreased amounts 24, 48, and 96 hours after ischemia. TRPM-2 gene expression was greatly increased 24 to 72 hours after ischemia and began decreasing at 96 hours. This selective sequence of gene expression or repression after renal ischemia might maximize the proliferative repair process. This information will be useful for designing therapies to further enhance recovery from acute renal injury. 
Asymptomatic celiac and superior mesenteric artery stenoses are more prevalent among patients with unsuspected renal artery stenoses. The prevalence of unsuspected renal artery stenosis among patients with peripheral vascular disease has been reported to be as high as 40%, but the prevalence of asymptomatic celiac and superior mesenteric artery stenoses in these patients is not known. The biplane aortograms of 205 male patients who were military veterans and had aneurysms or occlusive disease were independently reviewed, and medical records were studied to determine associated coronary disease, risk factors, and patient outcome. Fifty-six patients (27%) had a 50% or greater stenosis in the celiac or superior mesenteric artery, and seven patients (3.4%) had significant stenoses in both mesenteric arteries. Patients with celiac or superior mesenteric artery stenoses were older (p = 0.002) and had a higher prevalence of hypertension (p = 0.029) than those without significant mesenteric stenoses. Fifty of the 205 patients had significant renal artery stenoses, and 20 had advanced (greater than 75% diameter loss) renal stenoses. Ten of the 20 patients (50%) with advanced renal stenoses had a concomitant celiac artery stenosis, compared to 40 of the 185 patients (22%) who did not have advanced renal stenoses (p = 0.011). In the present study asymptomatic celiac or superior mesenteric artery stenoses were common among male veterans evaluated for peripheral vascular disease, but the prevalence of significant stenoses in both the celiac and superior mesenteric arteries was low. The prevalence of significant celiac stenosis was higher in patients with advanced (greater than 75%) renal artery stenoses who might be considered for prophylactic renal revascularization. Lateral aortography with evaluation of the celiac artery is always appropriate in these patients. 
Dipyridamole thallium-201 scintigraphy as a preoperative screening test. A reexamination of its predictive potential. Study of Perioperative Ischemia Research Group BACKGROUND. We examined the value of dipyridamole thallium-201 (201Tl) scintigraphy as a preoperative screening test for perioperative myocardial ischemia and infarction. METHODS AND RESULTS. We prospectively studied 60 patients undergoing elective vascular surgery. We performed 201Tl scintigraphy preoperatively and blinded all treating physicians to the results. Historical, clinical, laboratory, and physiological data were gathered throughout hospitalization. Myocardial ischemia was assessed during the intraoperative period using continuous 12-lead electrocardiography (ECG) and transesophageal echocardiography (TEE) and during the postoperative period using continuous two-lead ambulatory ECG. Adverse cardiac outcomes (cardiac death, myocardial infarction, unstable angina, severe ischemia, or congestive heart failure) were assessed daily throughout hospitalization. Twenty-two patients (37%) had defects that improved or reversed on delayed scintigrams (redistribution defects), 18 (30%) had persistent defects, and 20 (33%) had no defects on 201Tl scintigraphy. There was no association between redistribution defects and adverse cardiac outcomes: 54% (seven of 13) of adverse outcomes occurred in patients without redistribution defects, and the risk of an adverse outcome was not significantly increased in patients with redistribution defects (relative risk 1.5, 95% confidence interval 0.6-3.9, p = 0.43). Consistent with these findings, there was also no association between redistribution defects and perioperative ischemia: 54% (19 of all 35) of perioperative ECG and TEE ischemic episodes and 58% (14 of 24) of severe ischemic episodes occurred in patients without redistribution defects. The sensitivity of 201Tl scintigraphy for perioperative ischemia and adverse outcomes ranged from 40% to 54%, specificity from 65% to 71%, positive predictive value from 27% to 47% and negative predictive value from 61% to 82%. CONCLUSIONS. These results differ from those of previous studies and suggest that the routine use of 201Tl scintigraphy for preoperative screening of patients undergoing vascular surgery may not be warranted. 
Frequency of the hypercalcemia-leukocytosis syndrome in oral malignancies. There have been a number of reports over the last 15 years of patients with cancer who develop both leukocytosis and hypercalcemia, particularly in patients with cancers of the oral cavity. In this study, the authors report the frequency of hypercalcemia and leukocytosis in 225 patients with oral malignancies. Ten patients (4.4%) had hypercalcemia, 11 patients (4.9%) had leukocytosis, and five (2.2%) had both hypercalcemia and leukocytosis. The occurrence of these two distinct paraneoplastic syndromes in the same patients was greater than could have been expected from chance alone (chi-square = 45.8, P less than 0.0001). This study demonstrates that although hypercalcemia and leukocytosis are relatively uncommon in oral cancers, when they do occur they are frequently associated. To the knowledge of the authors, this is the first report in which the frequency of the association hypercalcemia and leukocytosis is studied in detail in large numbers of patients with oral cancer. 
Patients who leave a public hospital emergency department without being seen by a physician. Causes and consequences OBJECTIVE: To determine whether patients who sought care at a public hospital emergency department and left without being seen by a physician needed immediate medical attention and whether they obtained care after leaving. DESIGN: Follow-up study of patients who left without being seen and of patients who waited to be seen by a physician. SETTING: A public hospital's emergency department in Torrance, Calif. PATIENTS: All patients who registered for care and left without being seen (n = 186) and a 20% random sample of patients who waited until they were seen (n = 211) in a 2-week period during spring 1990. MAIN OUTCOME MEASURES: At time of presentation: triage nurse urgency assessment, clinical acuity rating, and self-reported health status. At follow-up: hospitalization rates. RESULTS: Patients who left reported that they had waited 6.4 hours before leaving; those who stayed reported a 6.2-hour wait before being seen. There were no differences between those who left and those who stayed in chief complaint, triage nurse assessment, acuity ratings, or self-reported health status. Forty-six percent of those who left were judged to need immediate medical attention, and 29% needed care within 24 to 48 hours. Eleven percent of those who left were hospitalized within the next week, and three patients required emergency surgery. Nine percent of those who waited to be seen were hospitalized. Forty-nine percent of patients who left did not see a physician during the 1-week follow-up period. CONCLUSION: Overcrowding in this public hospital's emergency department restricts access to needed ambulatory medical care for the poor and uninsured. 
Immunogenicity of low-dose intradermal recombinant DNA hepatitis B vaccine. Low-dose intradermal vaccination with plasma-derived hepatitis B vaccine has been shown to give high rates of seroconversion at greatly reduced vaccine cost. We report a study comparing two groups given lower doses (1.0 or 1.5 microgram) of recombinant-derived vaccine intradermally with a control group given the standard intramuscular dose. Of the 132 randomized medical students and hospital employees, 95 completed the study. Rates of seroconversion and peak antibody titers were comparable, though antibody rose more slowly and fell somewhat faster in the intradermal groups. Increasing the intradermal dose did not improve response. Most intradermal vaccinees (80%) developed small (average 2 to 3 mm) areas of local induration, which faded slowly. Low-dose intradermal vaccination with recombinant hepatitis B vaccine results in high rates of seroconversion (greater than 90% in each protocol) at a cost that will allow individual practitioners and program with limited budgets to offer vaccination. 
Evaluation of right ventricular early diastolic filling by cine nuclear magnetic resonance imaging in patients with hypertrophic cardiomyopathy. Numerous studies have established abnormalities in systolic and diastolic function of the left ventricle in hypertrophic cardiomyopathy. A consistent feature of this disease is reduced diastolic function of the left ventricle, but little information is available regarding right ventricular function in this disease. Cine nuclear magnetic resonance (NMR) imaging has been found to be effective for measuring right ventricular volumes and therefore was used to assess early diastolic filling of the right ventricle in patients with hypertrophic cardiomyopathy. Right ventricular time-volume curves were obtained from cine NMR images in 10 patients with hypertrophic cardiomyopathy and 8 normal subjects. Right ventricular volume was calculated with use of Simpson's algorithm at approximately 18 phases of the cardiac cycle and, from the curve, peak filling rate and filling fraction during the first third of diastole were determined. In patients with hypertrophic cardiomyopathy, peak filling rate tended to be less (176 +/- 46 vs. 305 +/- 50 ml/s, p less than 0.01) and filling fraction decreased (39.5 +/- 13.8 vs. 74.5 +/- 13.3%, p less than 0.01) in comparison with values in normal subjects. Thus, analysis of right ventricular time-volume curves obtained by using cine NMR imaging demonstrated diastolic dysfunction of the right ventricle in hypertrophic cardiomyopathy. 
Parathyroid adenoma manifested as pancreatitis and polyuria. Although the data used to explain a relationship between hyperparathyroidism and pancreatitis remain incomplete, there does appear to be a relationship between the two. We believe our patient's clinical course strongly supports this. 
Diffuse large cell lymphoma occurring in a patient with Waldenstrom's macroglobulinemia. Evidence for the two different clones in Richter's syndrome. The authors report a 60-year-old man with Richter's syndrome, or diffuse large cell lymphoma (DLCL) occurring in a patient with either chronic lymphocytic leukemia (CLL) or Waldenstrom's macroglobulinemia (WM). Surface marker analysis revealed that the WM showed mu kappa surface immunoglobulin (Ig) chains, and that the DLCL showed mu lambda Ig chains. Flow cytometric DNA analysis demonstrated DNA content differences between WM and DLCL, the former diploid and the latter aneuploid. The current study suggests that Richter's syndrome derives from two independent B-cell malignancies. 
Pharmacokinetics of oral and intravenous omeprazole in patients with the Zollinger-Ellison syndrome. The pharmacokinetics and pharmacodynamics of oral and IV omeprazole after a single dose were studied in 9 patients with the Zollinger-Ellison syndrome to determine whether the increased dose required to control gastric acid hypersecretion could be explained on the basis of altered pharmacokinetics. Each patient was studied both after receiving a single IV bolus of omeprazole (40 mg) and after receiving a single oral dose of omeprazole (80 mg). Intravenous and oral omeprazole doses were administered 1 week apart. Gastric acid secretion and plasma concentrations of omeprazole after drug administration were determined in each patient. The area under the plasma concentration curve, clearance, and volume of distribution after IV omeprazole administration and the area under the plasma concentration curve, peak plasma concentration, and time required to reach the peak after oral omeprazole administration were not different from those reported previously for normal subjects and patients with peptic ulcer disease. Mean (+/- SEM) bioavailability of oral omeprazole for all patients was 68% +/- 16%, which was similar to the bioavailability reported previously for normal subjects. Three patients had a significantly lower bioavailability reported previously for normal subjects. Three patients had a significantly lower bioavailability (20% +/- 8%) than the others, and their basal acid outputs were significantly higher than those of the other 7 patients. For all patients there was an inverse correlation between bioavailability and basal acid output (r = 0.76; P less than 0.02). The mean (+/- SEM) elimination half-lives of IV and oral omeprazole were not different (2.3 +/- 0.4 vs. 2.4 +/- 0.5 hours) but were significantly longer than those reported previously for normal subjects (P less than 0.02). The duration of action correlated with the elimination half-life of the drug (r = 0.87; P less than 0.003) and area under the plasma concentration curve (r = 0.72; P less than 0.03). The mean durations of action of IV and oral omeprazole were not significantly different (34 +/- 7.2 vs. 35 +/- 6.2 hours). It was concluded that altered pharmacokinetics do not account for the increased drug requirement of omeprazole in patients with the Zollinger-Ellison syndrome. In contrast to a previous study, the oral and IV omeprazole had the same duration of action, suggesting that intermittent bolus administration of parenteral omeprazole will obviate the need for continuous infusion of histamine H2-receptor antagonists in patients requiring parenteral antisecretory drugs. Furthermore, an IV dose every 12 hours controlled acid secretion in all patients, suggesting this as the recommended dose interval in patients requiring parenteral drug therapy. 
Emphysema type in relation to silica dust exposure in South African gold miners. The relationship between silica dust exposure in gold mines and the type of emphysema was studied in a group of 1,553 white gold miners who had undergone autopsy examination between 1974 and 1987. Of particular interest was the contrast between centriacinar and panacinar emphysema as they relate to silica exposure and the presence of silicosis. Subjects with significant emphysema, that is, with an emphysema score of 30% or more, were classified as having predominantly panacinar or predominantly centriacinar emphysema, and compared to those without emphysema (emphysema score less than or equal to 10%). Of those who had significant emphysema (greater than or equal to 30%), 24% had predominantly panacinar, 43% predominantly centriacinar, and 33% were classified as mixed. The odds ratios (OR) for the association between each emphysema type and dust exposure (one unit of the cumulative dust index) were found to be statistically significant and of equal magnitude [1.019, with a 95% confidence interval (CI) of 1.005 to 1.033 for panacinar and 1.019 with a 95% CI of 1.007 to 1.031 for centriacinar emphysema]. In 163 nonsmokers insignificant panacinar emphysema was more common than centriacinar emphysema. The results indicate that a miner with 20 yr in high-dust occupations has a 3.5 (1.7;6.6) times higher odds of having a significant degree of emphysema at autopsy than a miner not in a dusty occupation. This is likely to be true of smoking miners only because there were only four nonsmokers with an emphysema score between 30 and 40%. 
Age-related differences in hepatic drug clearance in children: studies with lorazepam and antipyrine. The disposition of intravenous antipyrine and lorazepam, administered as model substrates for hepatic oxidative metabolism and conjugation, was evaluated in 50 children (mean age, 7.8 years; range, 2.3 to 17.8 years) with acute lymphocytic leukemia in complete remission and compared with a group of ten healthy adults. Antipyrine clearance normalized to body weight was significantly greater in children than in adults (0.91 versus 0.59 ml/min/kg; p = 0.012), but was not different when normalized to body surface area. In contrast, lorazepam total clearance (CL) and unbound clearance (CLu) normalized to body weight were not significantly different between children and adults but were smaller in children when normalized to body surface area (CL = 31.9 versus 40.6 ml/min/m2, p = 0.036; CLu = 352 versus 485 ml/min/m2, p = 0.010). The mean lorazepam fraction unbound in children was 0.087, which was not different from adult volunteers (0.084). This study has identified significant differences between children and adults in the disposition of these two compounds, with higher milliliter per minute per kilogram clearance for antipyrine but not lorazepam. 
Management of hypertension. Useful nonpharmacologic measures. Hypertension is a chronic problem commonly seen by primary care physicians. Inadequate treatment may result in significant morbidity and even death. Therefore, all patients with hypertension or at risk for hypertension should be educated about nonpharmacologic measures to control blood pressure. Weight reduction and sodium restriction are cornerstones of nonpharmacologic management of hypertension. Although studies of the effects of aerobic exercise on blood pressure are not well designed, data confirm the value of such exercise. Relaxation therapy has been shown to lower blood pressure, but effects may be transient. Potassium and calcium supplementation has lowered blood pressure, but because study results are contradictory, the exact clinical criteria for use of such supplements have not been determined. Vegetarians have lower blood pressure than nonvegetarians, but no specific dietary components (eg, fiber, fat) have been documented as the beneficial factors. Because of its significant pressor effect, alcohol should be avoided by hypertensives. A low-fat diet is recommended to decrease cardiovascular risk and assist in weight control. 
Pulmonary dysfunction in surgical conditions of the newborn infant. OBJECTIVE: To describe the pathophysiology of surgical conditions that are associated with respiratory insufficiency in the newborn infant. DESIGN: Survey. SETTING: Newborn ICU in a children's hospital. PATIENTS: Twenty-four newborn infants (1 to 28 days old) who required endotracheal intubation and mechanical ventilation for operative procedures or postoperative ventilatory support. INTERVENTIONS: Flow-volume curves obtained by manual inflation of the lungs, followed by forced deflation by negative pressure, and by passive expiration, under sedation and pharmacologic paralysis. MEASUREMENTS: Deflation flow-volume curves and passive expiratory curves were measured. Pulmonary function testing before and after bronchodilator administration (n = 11) began midway during the study period. Term and preterm groups served as controls. MAIN RESULTS: Forced vital capacity (FVC) was decreased in all groups with surgical disease as follows: abdominal wall defects and necrotizing enterocolitis groups to 48.3% and 62.1% that of preterm, respectively; pulmonary hypoplasia group to 55.5% that of term (p less than .05). Maximal expiratory flow at 25% of FVC decreased in all groups: abdominal wall defects and necrotizing enterocolitis group, to 36.8% and 37.9% that of preterm, respectively (p less than .05); pulmonary hypoplasia group, 20.0% that of term (p less than .05). The ratio of maximal expiratory flow at 25% of FVC divided by FVC was significantly decreased in necrotizing enterocolitis and pulmonary hypoplasia groups compared with that of preterm and term groups, respectively, but not in the abdominal wall defects group. Maximal expiratory flow at 25% of FVC, but not FVC, increased significantly (36%, p less than .05) after bronchodilator nebulization, indicating the presence of airway reactivity. Respiratory system compliance was decreased significantly (p less than .05) in all surgical disease groups compared with the term group. CONCLUSIONS: Bronchial reactivity contributes to decreased maximal expiratory flow at 25% of FVC, a feature also seen in premature infants with respiratory distress syndrome who later develop bronchopulmonary dysplasia. Babies who require chronic ventilatory support after operation and who have developed reactive airways may benefit from the administration of bronchodilators during postoperative ventilatory management. 
Acute appendicitis. A 5-year review. A startling 31 per cent rate of perforated appendicitis in 1984 prompted a 5-year review at the Guthrie Medical Center. An increase over previous rates of 13 per cent and 0 per cent in 1964 and 1944 was confirmed in this study. Perforation accompanied 44 of 240 cases of appendicitis (18.3%); diagnostic accuracy in 295 cases undergoing operation was 81.4 per cent. Groups at risk for perforation were patients in the first decade of life (34.3% with perforations) and those over 50 years of age (48% perforated). Perforation rates were generally inversely related to accuracy. Accuracy was poorest in women in the second to fourth decade or those in the mid-portion of the menstrual cycle. When the appendix was not perforated, complications occurred in 8.7 per cent of patients while 29.5 per cent with a perforation had a complication. The mean hospital stay was prolonged by 2.5 days if the appendix was perforated. An increased awareness of the risk by both the public and physicians is essential to reduce the number of perforations. 
Benign hemorrhagic adrenocortical macrocysts in Beckwith-Wiedemann syndrome. A new pseudotumorous lesion found in the adrenal cortex of six infants with Beckwith-Wiedemann syndrome is described. These cystic masses were discovered either prenatally by using sonography or early in the neonatal period as palpable flank masses. Imaging studies, including sonography and CT, could not confidently exclude malignancy. After the masses were removed surgically, histologic examination showed them all to be benign hemorrhagic macrocysts within the capsule or permanent cortex (in contrast to neonatal adrenal hemorrhage, which usually occurs more centrally in the fetal cortex). The cysts were as large as 8 cm in diameter, and in one case a solitary cyst was predominant. Hemihypertrophy was present in all cases. Four of the six lesions were right-sided, and there was a male-female ratio of 5:1. Benign hemorrhagic adrenocortical macrocysts are a cause of abdominal mass in the fetus and neonate with Beckwith-Wiedemann syndrome. 
Shoulder impingement syndrome. A critical review. Impingement syndrome is an ill-defined term for a variety of disorders of the shoulder that manifest as anterior shoulder pain, especially during overhead activities. These disorders each have a common pathologic course that includes rotator cuff tendinitis (RCT), and, if untreated, may proceed to cuff rupture. RCT has at least two distinct etiologies. Primary impingement of the supraspinatus tendon on the coracoacromial arch is responsible in the majority of nonathletic cases. Overhead movements in sports are prone to developing secondary mechanical impingement because of an instability pattern that is common in this population. Information from this review and clinical practice permits differentiation of the two distinct etiologies of RCT which is important in treatment planning. Much work still needs to be done in defining the microscopic pathology of RCT. 
Propranolol pretreatment reduces cardiorespiratory toxicity due to plain, but not epinephrine-containing, intravenous bupivacaine in rats. The purpose of this study was to evaluate the effects of pretreatment with propranolol on the cardio-respiratory toxicity of bupivacaine, either plain or with epinephrine 1:200,000 (5 micrograms.ml-1) added. Adult male Sprague Dawley rats, anaesthetized with intraperitoneal pentobarbital, were divided into four groups. Groups I and III were pretreated with iv propranolol 150 micrograms.kg-1, and Groups II and IV received iv NS as a placebo. Three minutes later, rats in Groups I and II received plain 0.5% bupivacaine, 4 mg.kg-1, and Groups III and IV received 4 mg.kg-1 of 0.5% bupivacaine with epinephrine, 5 micrograms.ml-1 iv. Five of eight rats pretreated with propranolol survived (Group I), compared with uniform fatality with NS pretreatment (Group II) (P less than 0.05). Addition of epinephrine to the bupivacaine eliminated the protective effect of propranolol. All rats pretreated with propranolol (Group III) or NS (Group IV) died when given bupivacaine with epinephrine. In conclusion, acute propranolol pretreatment reduced the fatal cardiotoxicity due to iv bupivacaine in male Sprague Dawley rats, but the addition of epinephrine 5 micrograms.ml-1 to bupivacaine eliminated the protective effect of propranolol. 
Quantification of valvular regurgitation by Doppler echocardiography. One of the widest uses of color Doppler echocardiography is for the quantification of valvular regurgitation. In this article we review the physics and instrumentation factors related to the most commonly applied method, that of planimetering areas of regurgitant jet spray within the receiving chamber, and relate features such as instrument gain, pulse repetition frequency, and important physical parameters such as receiving chamber compliance and driving pressure to the application of this method for precordial as well as transesophageal echocardiography. New approaches to the quantification of valvular insufficiency, such as measurement of the momentum of the jet and study of the acceleration flow in the proximal flow convergence region within the chamber of origin of an insufficiency jet and proximal to the orifice, are described and preliminary results given for a new method of quantification of volume flow across regurgitant orifices. 
Epidemiology of absence epilepsy: EEG findings and their predictive value. This population-based study of absence epilepsy comprised 97 children, ranging in age from newborns to 15 years. All had regular bilaterally synchronous and symmetric 2-4 Hz spike-and-slow wave discharges and absences with or without generalized tonic-clonic seizures (GTCS). Patients without GTCS tended to have long episodes of 2-4 Hz spike-and-slow wave discharges (greater than or equal to 10 sec), and simultaneous clinical correlates more frequently than those with GTCS. Posterior delta rhythm was found only in patients without GTCS. Focal abnormalities, albeit transient, were more frequent among patients with GTCS. The initial electroencephalogram was of some early predictive value in patients with only absences at the time of the initial registration. Brief episodes of 2-4 Hz spike-and-slow wave (less than 10 sec) without clinical correlates were associated with a slightly increased risk of future GTCS. 
Therapeutic adherence in the elderly: transdermal clonidine compared to oral verapamil for hypertension. This double-blind, double-dummy, randomized clinical trial, conducted in elderly patients with mild hypertension, compared adherence to treatment, efficacy, side effects, and quality of life during treatment with transdermal clonidine versus oral sustained-release verapamil (verapamil-SR). Blood pressure declined significantly--from 148/95 mm Hg at baseline to 139/84 after titration and 135/86 after maintenance--with transdermal clonidine (n = 29), and from 156/96 to 144/85 and 148/88, respectively, with verapamil-SR (n = 29). Adverse event rates and quality-of-life questionnaire responses were similar in the two treatment groups. Transdermal clonidine was worn as directed during more than 96% of patient-weeks of treatment. Compliance with the oral verapamil regimen was less consistent: Verapamil-SR was taken as directed during approximately 50% of patient-weeks of therapy, and individual compliance, assessed by tablet counts, varied from 50-120%. In all, 86% of subjects were satisfied or highly satisfied with the convenience of transdermal therapy; 87% reported that side effects were slightly or not bothersome; 65% indicated that transdermal patches were more convenient than oral therapy; and almost 60% preferred transdermal to oral therapy. In this study transdermal clonidine and oral verapamil were equally safe and effective. A substantial majority of patients preferred transdermal to oral therapy, and adherence to treatment was greater with transdermal therapy. 
Evaluation of the immune response in protection against experimental Streptococcus defectivus endocarditis. Immune protection from endocarditis caused by Streptococcus defectivus was examined by using a rabbit model. Previously we had demonstrated that immunization with nutritionally variant streptococci (NVS, now referred to as Streptococcus, species defectivus and adjacens) protected rabbits against endocarditis when they were challenged with the homologous strain. However, when high-titer immune globulin was transferred to nonimmunized rabbits, no protection was achieved. In the present study, immunosuppressive treatments were given to previously immunized rabbits, and alterations in the level of protection were determined by using the rabbit endocarditis model. Control-immunized rabbits as well as immunized rabbits receiving cyclosporin A or methylprednisolone treatments were protected from S. defectivus endocarditis at levels between 50% and 67%. Rabbits in each of these groups cleared S. defectivus organisms from the circulation by 3 hours after infection. Nitrogen mustard-treated rabbits (immunized or nonimmunized), however, were unable to clear S. defectivus organisms as efficiently (almost 100 times as many organisms in the blood when compared with other groups) by 3 hours, and all were susceptible to endocarditis. These data suggest that circulating phagocytes such as monocytes and granulocytes function to a certain extent in protection against S. defectivus endocarditis. Moreover, when neutrophils were transfused into granulocytopenic and monocytopenic rabbits, efficient clearance was prolonged, indicating that polymorphonuclear leukocytes were involved in the later (greater than 1 hour after infection) phase of protection. 
Fibrin glue sealing of pancreatic injuries, resections, and anastomoses. Fibrin glue made with highly concentrated human fibrinogen and clotting factors was evaluated as a means of preventing pancreatic fistulas in 15 patients operated on for traumatic and nontraumatic conditions. Fibrin glue was applied directly to penetrating pancreatic injuries, pancreatic suture and staple lines in patients treated by partial resection, and pancreaticointestinal anastomoses. Postoperatively, no patient developed pancreatic fistulas, pancreatic abscesses, or pseudocysts. Fibrin glue sealing of pancreatic injuries, resections, and anastomoses may aid in preventing fistulas after pancreatic surgery. Additional potential uses include the sealing of pancreatic biopsy sites and occlusion of the pancreatic duct in pancreatic transplantation. 
Improving survival in gastric cancer: review of operative mortality in English language publications from 1970. In this review of English language publications from 1970, operative mortality following surgery for gastric cancer has been analysed. Operative mortality has declined in series reporting operations in successive decades to 1970, 1980 and 1990. Series reporting patients having surgery for gastric cancer in the decade to 1990 show a mean operative mortality rate of 7.8 per cent (median 4.6 per cent). This improvement may have contributed to the declining mortality rates for gastric cancer in the face of unchanging surgical workload. Results of operations for gastric cancer should be reported in a standard manner. 
Chronic tuberculous empyema with bronchopleural fistula resulting in treatment failure and progressive drug resistance. We treated five patients with a past history of tuberculous pleural infection that led to chronic, quiescent, loculated empyema. Reactivation of TB was associated with formation of BPF and recovery of drug-susceptible Mycobacterium tuberculosis from sputum. All patients had recurrence of positive sputum cultures that yielded tubercle bacilli resistant to drugs they were receiving. The lungs demonstrated gross thickening with calcification of both visceral and parietal pleura. Two patients underwent retreatment chemotherapy followed by decortication-empyemectomy and lung resection surgery; both are now culture-negative for TB. One patient received retreatment chemotherapy but refused surgery; he remains clinically stable with negative sputum cultures. Two other patients' organisms became drug-resistant and they remain sputum-culture positive. We believe that thick, calcified pleural walls limit penetration of drugs into the infected empyema space, resulting in suboptimal drug concentrations and drug resistance. Intensified chemotherapy and surgical intervention should be considered in these cases. 
Prolonged QT interval and risk of sudden death in South-East Asian men. Sudden death in sleep occurs in substantial numbers among young men in South-East Asia. The frequencies of electrocardiographic abnormalities were measured in groups with varying risks of such sudden death. The mean heart-rate-corrected QT interval (QTc) was significantly (p less than 0.05) greater among 123 Laotian refugees in Thailand at high risk (405 [95% confidence interval 397-413] ms) than in 77 Laotian refugees in the United States at lower risk (364 [359-369] ms) and 199 non-Asian US residents at negligible risk (358 [354-362] ms). Among refugees in Thailand, prolonged QTc interval was associated with poor thiamine status and a history of seizure-like episodes in sleep. Thiamine deficiency may be a cause of prolonged QT interval and sudden death in this region. 
A variant of HLA-DR4 determines susceptibility to rheumatoid arthritis in a subset of Israeli Jews. HLA-DR4 is associated with risk for developing rheumatoid arthritis (RA) in most populations. In Israeli Jews, in whom the Dw10 subtype of DR4 predominates, no association of RA with DR4 has been found. The inability to detect an association could be due to the high frequency of DR4-Dw10. We used DNA typing with amplification by the polymerase chain reaction and dot-blotting with allele-specific oligonucleotides to determine DR4 variants in 131 Jewish RA patients living in Israel and 134 controls. In both Ashkenazi Jews and non-Ashkenazi Jews, the rare variant Dw15 (previously identified in Japanese populations and in Japanese patients with RA) was found to be the main allele associated with the risk of developing RA (relative risk = 9.2, corrected P less than 0.001). However, this low-frequency allele could be responsible for susceptibility in only 11.5% of the patients. Susceptibility for rheumatoid factor-positive RA was associated with Dw4 and Dw15; the risk for rheumatoid factor-negative RA was associated only with Dw14. The distribution of the HLA-DQ alleles associated with DR4 showed that more than half of the RA patients with Dw15 also had HLA-DQw2. The frequencies of DQw7 and DQw8 were not different in RA patients compared with controls. The results suggest that, as in other populations, susceptibility for the development of RA in Israeli Jews is associated with DRB1 locus alleles of the DR4 group. 
Fatigue and depression in brain-injured patients correlated with quadriceps strength and endurance. Many brain-injured (BI) patients complain of persistent fatigue that may alter their lifestyles. In order to assess muscular strength and endurance after brain injury, 22 BI men, greater than 9 months postinjury and aged 20 to 51 years, were separated into two groups based on a complaint of fatigue (fatigue n = 13, nonfatigue n = 9); each performed one maximal isometric knee extension at 60 degrees and 20 maximal isokinetic contractions at 20 rpm using a Cybex II dynamometer. A third group of age-matched, able-bodied men (n = 10) were used as controls. A battery of tests assessing the presence of fatigue (using a symptom checklist and two rating scales), depression, anxiety, and health status were given at the time of isokinetic/isometric testing. The mean fatigue rating, a subjective score, for the fatigue group of BI subjects was significantly worse than the other groups (p less than .01). There was a positive correlation between clinically significant Zung depression scores and fatigue rating (r = .46) and between Zung anxiety scores and fatigue rating. The depression scores for those who complained of fatigue were significantly higher than the other groups (p less than .005). Maximal isometric contractions were no different among the three groups. The mean maximal isokinetic torque during the 20 repetitions was greater in controls than in the BI groups, but did not reach statistical significance (p less than .25). There were no significant declines in isokinetic torque in the 20 repetitions for any of the groups, and the fatigue index was nearly equal for all three groups. 
Choledochal cysts: classification and cholangiographic appearance. A classification scheme for choledochal cysts is outlined and their appearance on cholangiograms is illustrated. Choledochal cysts are uncommon anomalies of the biliary system and are probably congenital in origin. They are manifested by cystic dilatation of the extra- or intrahepatic biliary tree or both. The classification system described here divides choledochal cysts into one of five main types. The most common, which is manifested by cystic or focal segmental dilatation of the common bile duct or fusiform choledochal dilatation, accounts for 80-90% of cases. 
Expression of a polymorphic epithelial mucin antigen defined by the monoclonal antibody BC2 in ovarian carcinoma. Use of the BC2 antibody for the detection of micrometastases. The BC2 monoclonal antibody, which binds to an epitope on the peptide backbone of polymorphic epithelial mucin, was tested immunohistochemically for reactivity with epithelial ovarian carcinoma. This epitope was expressed in 90 of 91 malignant ovarian tumors; in 88% of these, more than 50% of the tumor cells expressed the epitope. In 94% of the positive tumors, the epitope was expressed on the cell membrane; in 56%, cytoplasmic expression was evident; and in 39%, secreted extracellular antigen was detected. Differences were not clearly discernible between dissimilar histotypes with respect to the percentage of cells expressing antigen and antigen localization. Thirteen of 19 benign ovarian cystadenomas also expressed the epitope, but staining was weak and restricted to the luminal surface of the cell membrane. A blind retrospective immunohistochemical analysis of all second-look laparotomy biopsy specimens from 20 patients also was performed. All four patients in whom microscopic disease was detected by standard pathologic assessment had BC2-positive metastases. Of seven patients in whom recurrent disease subsequently developed despite negative pathologic findings, four had biopsy specimens containing BC2 antigen-positive adenocarcinoma-like cells. Of the nine patients with negative results on operation and no recurrence, one had biopsy specimens containing BC2 antigen-positive adenocarcinoma-like cells. Mesothelial cells, although typically negative, expressed the epitope in one biopsy specimen, necessitating caution in the interpretation of positive cells. The BC2 antibody is reactive with most epithelial ovarian carcinomas and appears to be a useful tool for the detection of micrometastases. 
Multivessel PTCA using the hugging balloon technique based on single guide catheter and dual balloon-on-a-wire systems. For percutaneous transluminal coronary angioplasty (PTCA) of oversized arteries, often-times a satisfactory dilatation cannot be achieved with conventional balloon systems due to the unavailability of adequately sized balloons. This fact has contributed to a higher restenosis rate for this group of patients. We were able to obtain a satisfactory dilatation result in an oversized right coronary artery with a shepherd's crook configuration and eccentric anatomy at the origin using two balloon-on-a-wire systems and an Amplatz type guiding catheter. Although such favorable dilatation of an oversized artery using this "hugging balloon technique" can be expected, issues do exist such as difficult maneuverability and estimation of the balloon size obtained through simultaneous dual balloon inflation wherein size does not simply equal the sum of the two balloon catheters. It is hoped that there will be further improvements of the technique and development of new systems. At this time, however, it is felt that this is the most effective and reasonable strategy to achieve a high chance of success in oversized vessel lesions. 
Comparison of the metabolic effects of continuous postoperative enteral feeding and feeding at night only. The effects of two different feeding patterns on oxygen consumption, nitrogen balance, blood biochemistry, and urinary catecholamine excretion were investigated over 5 d in patients after major head and neck surgery. Both groups of nine patients each were fed a regimen that provided 4.7 MJ on day 1 and 10 MJ on days 2-5 via a nasogastric tube by continuous infusion with an enteral feeding pump. One group was fed continuously for 24 h, the other was fed only at night, ie, from 1700 to 0900 the next morning. Oxygen consumption was significantly higher (P less than 0.01), nitrogen balance better (P less than 0.05), and urinary catecholamine excretion higher (P less than 0.05) in the 24-h-fed patients than in the night-fed patients. Postoperatively, feeding at night only is more energy efficient than is feeding continuously for 24 h, but is associated with poorer nitrogen balance. These differences may be mediated by sympathoadrenal mechanisms. 
Nonhealing leg ulcers: a manifestation of basal cell carcinoma. Seven patients with basal cell carcinomas presenting as nonhealing ulcers are reported. The importance of considering malignancy and taking biopsy specimens of leg ulcers that fail to respond to treatment is emphasized. 
Diagnostic value of transesophageal compared with transthoracic echocardiography in infective endocarditis. To compare the diagnostic value of transesophageal and transthoracic echocardiography in infective endocarditis, paired transesophageal and transthoracic echocardiograms were obtained prospectively for 66 episodes of suspected endocarditis in 62 patients. Echocardiographic results were compared with the presence or absence of endocarditis determined by pathologic or nonechocardiographic data from the subsequent clinical course. All echocardiograms were interpreted by an observer told only that the studies were from patients in whom the diagnosis of endocarditis was suspected. The diagnosis of endocarditis was eventually made in 16 of the 66 episodes of suspected endocarditis (14 by pathologic and 2 by clinical criteria). In 7 of 16 transthoracic and 15 of 16 transesophageal echocardiograms, endocarditis was diagnosed at a probability level of "almost certain," giving a sensitivity of 44% and 94%, respectively (p less than 0.01). For the remaining episodes, 49 of 50 transthoracic and all transesophageal studies yielded normal results, giving a specificity of 98% and 100%, respectively. This study suggests that transesophageal echocardiography is highly sensitive and specific for the diagnosis of infective endocarditis and significantly more sensitive than transthoracic echocardiography. Although echocardiography cannot rule out endocarditis, the high diagnostic sensitivity of transesophageal echocardiography results in a low probability of the disease when the study yields negative results in a patient with an intermediate likelihood of the disease. 
Uhthoff's symptom in optic neuritis: relationship to magnetic resonance imaging and development of multiple sclerosis. Eighty-one patients with a first attack of isolated optic neuritis, 40 with Uhthoff's symptom (Group 1) and 41 without (Group 2), were studied. All had a neurovisual examination, 74 of 81 patients had the pattern visual evoked potential recorded at rest, and 43 had magnetic resonance imaging brain scans. The pattern visual evoked potential P100 latency was prolonged, Group 1 with a mean of 136 +/- 19 msec. Group 2 with a mean of 131 +/- 19 msec (control subjects, 102 +/- 5 msec; n = 84), and the P100 amplitude was reduced, without significant difference between the groups. Abnormal magnetic resonance imaging scans were present in significantly more patients in Group 1 (p less than 0.025). Treatment of optic neuritis with corticosteroids had no effect on the evolution or duration of Uhthoff's symptom. Overall, 35 of 81 (43%) patients, followed for a mean of 3.5 years, developed multiple sclerosis. The incidence was significantly greater in Group 1 (p less than 0.01). Uhthoff's symptom also correlated with a higher incidence of recurrent optic neuritis. We conclude that Uhthoff's symptom is a prognostic indicator for the early development of multiple sclerosis. 
Prostatic abscess due to histoplasma capsulatum in the acquired immunodeficiency syndrome. We report a case of prostate abscess due to Histoplasma capsulatum in a patient with the acquired immunodeficiency syndrome. The diagnosis and management are discussed, and the literature is reviewed. 
Malignancy and chronic wounds: Marjolin's ulcer. Malignancy in chronic wounds is not uncommon and has been reported as occurring in chronic scars of diverse causes. We report an unusual case of bilateral thermal injuries of the lower extremities that 40 years later presented as very large, painful, fungating wounds of both lower legs. After histologic confirmation of squamous cell carcinoma, eradication of the disease required amputations of both the lower extremities and reconstructive procedures. In addition, we discuss current theories regarding the mechanism of malignant degeneration in chronic wounds and evaluate treatment on the basis of information currently available in the literature. 
Isolated atrial infarction in a patients with single vessel disease of the sinus node artery. Atrial infarction is found in approximately 17 percent of autopsy-proven cases of myocardial infarction, but is a frequently missed clinical diagnosis. The antemortem diagnosis of atrial infarction occurring in the absence of ventricular infarction has not been previously reported. We present a patient with ischemic chest discomfort associated with paroxysmal atrial fibrillation. Electrocardiographic and enzymatic changes were consistent with atrial infarction. Cardiac catheterization demonstrated single vessel critical stenosis at the origin of the sinus node artery. Combined atrial and ventricular infarction occurs frequently and should be considered in the setting of paroxysmal supraventricular arrhythmias occurring early in the course of ventricular myocardial infarction. Lone atrial infarction is a rare but distinct clinical entity. The tetrad of typical ischemic chest discomfort, paroxysmal supraventricular arrhythmia, P-Ta segment shifts, and elevated cardiac enzyme levels without evidence for ventricular infarction strongly suggests isolated atrial infarction. 
Dietary adjustments and nutritional therapy during treatment for oral-pharyngeal dysphagia. Dietary adjustments are an important part of the therapy for dysphagia. Once dysphagia is diagnosed, the patient must be nourished safely while being taught therapeutic and compensatory strategies for dealing with the swallowing disorder. The patient's nutritional status must be maintained despite any limitations on oral intake. Liquids may be thickened and the consistency of solid foods may be adjusted to ensure an adequate diet that is safe for the patient. When the patient cannot eat safely or take adequate amounts of food orally, an alternative feeding method should be instituted. 
Reproductive and menstrual factors and risk of peritoneal and ovarian endometriosis. OBJECTIVE: Between 1987 and 1989 data were collected to evaluate risk factors for pelvic endometriosis. DESIGN: A case-control study was conducted on 241 cases with laparoscopically or laparotomically confirmed peritoneal or ovarian endometriosis consecutively admitted to three teaching hospitals in Northern Italy. The control group consisted of 437 women admitted to hospitals for acute conditions covering similar catchment areas. RESULTS: Compared with nulliparous women, the risk of endometriosis decreased with increasing number of births: the point estimates were 0.4 and 0.3, respectively, for those with one and two or more births (X2(1) trend = 50.3, P less than 0.001). No relation emerged with age at first birth and spontaneous miscarriages. Relative to women whose menarche occurred at age 11 or younger, the risk of endometriosis was slightly lower in those who experienced later menarche, but the trend in risk was not significant. Women with irregular menstrual cycles showed a lower frequency of the disease (relative risk, 0.3; 95% confidence interval, 0.2 to 0.5). The role of various factors was largely similar for different disease locations (ovary, peritoneum, and both) and indication for diagnostic surgery (sterility, pelvic pain, and other reasons). CONCLUSIONS: This study found that parity and irregular/long menses lower the risk of endometriosis. These findings were similar in different subgroups of disease location and indication for surgery, giving strong evidence of the consistency of the general results. 
Benign arterial dissections of the posterior circulation. Four young adults with spontaneous dissection of the vertebrobasilar system are reported. Clinically, two patients presented with subarachnoid hemorrhage and two with brain-stem ischemia. In two cases of ruptured arterial dissection of the posterior cerebral artery, angiography demonstrated fusiform and "sausage-like" dilatation of the involved vessel. In two cases of occlusive dissection of the basilar artery, angiography revealed the typical "string sign." All four patients were treated conservatively: three survive in good clinical condition and one remains disabled. Follow-up angiograms showed spontaneous healing of the lesion with return to an almost normal arterial configuration in two cases; residual narrowing corresponding to the dissection was the most notable finding in the other two. It is recommended that, in a subset of neurologically stable patients, angiographic monitoring is undertaken to assess the tendency for spontaneous repair before surgical intervention is planned. 
Cystoscopic suction diathermy for the treatment of superficial bladder tumours. The treatment of superficial bladder tumours (Ta, T1) is a time-consuming exercise for urological surgeons and patients. A method of treating the tumours, whether primary or recurrent, by endoscopic suction diathermy has been developed. The technique significantly reduces the amount of tumour debris within the bladder during treatment as well as the amount of diathermy employed. By removing the free tumour cells in the irrigation fluid the risk of tumour cell implantation may be kept to a minimum. 
Right ventricular pacing and left ventricular filling pattern. An echo-Doppler study. The influence of right ventricular pacing on left ventricular filling has not been completely clarified. The aim of the study was to analyze the possible alteration in and effects on left ventricular filling resulting from right ventricular pacing. The study population consisted of two groups; group A was comprised of 12 patients with a spontaneous left bundle branch block, and group B had 12 patients without left bundle branch block. All the patients underwent an interrogation of the mitral valve inflow by Doppler echocardiography, in order to measure isovolumic relaxation time, early and late peak velocity (E and A wave), E/A ratio and deceleration time. The study was performed at spontaneous rhythm and after, inhibition of the pacemaker. In group A, there were no changes in the Doppler parameters when passing from a spontaneous to an 80/min electrically induced rhythm. Analysis of group B revealed a statistically significant lengthening of IVR and Dec t with electrical stimulation. No statistically significant differences were found when we compared the Doppler parameters of the two populations at the same pacing frequency. Right ventricular pacing causes interventricular asynchrony and abnormalities in diastolic filling times, which resulted in a lengthening of either IVR and Dec t, simulating a pattern of abnormal relaxation. 
Preoperative segmental localization of hepatic metastases: utility of three-dimensional CT during arterial portography. To evaluate the accuracy of a fast three-dimensional (3D) reconstruction technique in determining the segmental location of hepatic metastases, 14 patients (40 metastases) were prospectively investigated before surgery with dynamic two-dimensional (2D) computed tomography during sequential arterial portography (CTAP). All patients underwent subsequent hepatic tumor resection within 4 days. After computer-generated mapping of hepatic venous structures with high attenuation and metastases with low attenuation, 3D reconstruction was performed. Thirty-six of the 40 lesions (90%) were detected with 2D and 3D CTAP. The accuracy in determining the segmental location of hepatic metastases was 78% (28 of the 36 metastases) for 2D CTAP and 94% (34 of the 36 metastases) for 3D CTAP. The difference in localization rates between 2D CTAP and 3D CTAP was statistically significant. The 3D CTAP technique provides vital data unattainable with other imaging modalities that improve the preoperative assessment of the resectability of hepatic metastases and allows planning a safer surgical approach. 
Chorea-acanthocytosis: abnormal composition of covalently bound fatty acids of erythrocyte membrane proteins. Phospholipid class, peak profile of each phospholipid class, loosely bound fatty acids, covalently (tightly) bound fatty acids of the erythrocyte membranes, and plasma fatty acids were investigated using high-performance liquid chromatography in six patients with chorea-acanthocytosis and 14 age- and sex-matched normal control subjects. Additionally, six patients with Huntington's disease were included as disease control subjects in the study of covalently bound fatty acids. Study of covalently (tightly) bound fatty acids in erythrocyte membrane proteins after alkaline hydrolysis, hitherto undescribed in chorea-acanthocytosis, revealed that palmitic acid (C16:0) was significantly increased and stearic acid (C18:0) was decreased in the patients with chorea-acanthocytosis. Analyses for total covalently bound fatty acids disclosed that palmitic and docosahexaenoic (C22:6) acids were increased and stearic acid was decreased in chorea-acanthocytosis. Phospholipid class (phosphatidylcholine, phosphatidylethanolamine, sphingomyelin, and phosphatidylserine) and peak profile of each phospholipid class from the erythrocyte membranes did not differ between the patients with chorea-acanthocytosis and the control subjects. Of the loosely bound fatty acids, linoleic acid (C18:2) was significantly decreased in those with chorea-acanthocytosis, which seemed to be nonspecific. 
The anterior inferior cerebellar artery in the internal auditory canal. It has been proposed that compression of the auditory and vestibular nerve trunks by vascular loops might be the cause of otherwise unexplained hearing loss, tinnitus, and vertigo, as well as Meniere's disease. We studied the human temporal bone histological collection at the Massachusetts Eye and Ear Infirmary to determine whether audiovestibular symptoms could be correlated with the presence of the anterior inferior cerebellar artery within the internal auditory canal. Anterior inferior cerebellar artery loops were found within the internal auditory canals of 12.3% of 1327 temporal bones, about half the number found when preparations with intact brains are studied. This difference can be attributed to avulsion of the anterior inferior cerebellar artery during removal of the brain at autopsy. There were 5 cases of unexplained unilateral hearing loss with anterior inferior cerebellar artery loops: 3 in the opposite ear and 2 in both ears. There were 2 cases with unilateral unexplained tinnitus with anterior inferior cerebellar artery loops: 1 in the involved ear and 1 in the opposite ear. A case with bilateral tinnitus had an anterior inferior cerebellar artery loop in 1 ear. There were 29 cases of vertigo with no peripheral histopathological correlate or central nervous system disorder; anterior inferior cerebellar artery loops were found in the internal auditory canals of 7 (12.5%) of the 56 ears in this group, which is not significantly different from the 12.3% incidence recorded for the entire collection. In 23 cases of unilateral Meniere's disease, there were anterior inferior cerebellar artery loops in the hydropic ears in 3, the opposite ear in 1, and both ears in 1. We can find no correlation between unexplained hearing loss, tinnitus, vertigo, or Meniere's disease and the presence of the anterior inferior cerebellar artery in the internal auditory canal. 
The I-Abm12 mutation, which confers resistance to experimental myasthenia gravis, drastically affects the epitope repertoire of murine CD4+ cells sensitized to nicotinic acetylcholine receptor. Susceptibility to experimental autoimmune myasthenia gravis (EAMG), which is induced in mice by injection of purified Torpedo nicotinic acetylcholine receptor (TAChR), is influenced by the I-A locus products, which restrict presentation of AChR Th epitopes. The bm12 mutation of the I-Ab molecule in the C57BL/6 strain, which is highly susceptible to EAMG, yields the EAMG resistant mutant B6.C-H-2bm12 (bm12). We investigated here the consequences of the bm 12 mutation on the CD4+ response to the TAChR alpha subunit. Upon immunization with TAChR, CD4+ cells became sensitized to TAChR and anti-AChR antibodies were produced in both bm12 and C57BL/6 strains. Overlapping synthetic peptides, corresponding to the complete sequence of TAChR alpha subunit, were used to identify Th epitopes. CD4+ cells from C57BL/6 mice recognized peptides T alpha 150-169, T alpha 181-200, and T alpha 360-378. CD4+ cells from bm12 mice did not respond to any synthetic sequence. Upon injection of the three C57BL/6 Th epitope peptides, either individually or as a pool, CD4+ cells from C57BL/6 mice recognized each peptide and TAChR. Therefore they recognized epitopes similar or identical to those originated from TAChR processing. CD4+ cells from bm12 mice injected with the same peptides responded to T alpha 360-378 strongly, to a lesser extent to T alpha 181-200, never to peptide T alpha 150-169. Only CD4+ cells sensitized against the T epitope peptide T alpha 181-200 responded to TAChR. We tested if lack of response to T alpha 150-169, and the low response to T alpha 181-200, was due to inability of the I-Abm12 molecule to present the T epitope peptides. bm12 and C57BL/6 APC were used to present the T epitope peptides to specifically sensitized CD4+ cells from C57BL/6 mice. All T epitope peptides were presented by bm12 APC, although T alpha 150-169 was presented less efficiently than by C57BL/6 APC. Resistance to EAMG induced by the bm12 mutation may be due to the change in the epitope repertoire of AChR-specific Th cells, and lack of recognition of otherwise immunodominant Th epitopes. For at least one epitope this might be due to absence of potentially reactive, specific CD4+ clones. 
In vivo T-cell activation by staphylococcal enterotoxin B prevents outgrowth of a malignant tumor. Treatment of T cells with staphylococcal enterotoxins in vitro is known to activate T cells in a subset restricted manner based on beta-chain variable region (V beta) gene expression. In particular, staphylococcal enterotoxin B (SEB) activates T cells bearing V beta 7 or V beta 8. We examined the ability of SEB to activate T cells in vivo. Treatment of C3H mice with doses of SEB ranging from 5 to 250 micrograms resulted in a dose-dependent activation of V beta 8+ T cells as reflected by increased interleukin 2 receptor (IL-2R) expression, proliferation to exogenous IL-2 and allogeneic cells, and production of gamma interferon. SEB also caused proliferation of the CD8+ subset of V beta 8+ cells in vivo. Thus, T-cell activation by SEB in vivo appears to be specific since V beta 2+ cells (non-SEB reactive) did not show increases in IL-2R expression similar to those seen with V beta 8+ cells nor did they proliferate. We then studied the ability of these activated cells to potentiate the immune response to a malignant progressor tumor. Treatment of C3H mice with 50 micrograms of SEB at the time of inoculation with tumor fragments resulted in a statistically significant decrease in the frequency of tumor outgrowth. These data demonstrate that treatment of C3H mice with SEB results in specific activation of V beta 8+ cells in vivo and that these activated cells are capable of preventing the outgrowth of a malignant tumor. 
Value of follow-up procedures in patients with large-cell lymphoma who achieve a complete remission. Salvage therapy for relapsed large-cell lymphoma (LCL) is more effective in patients with minimal disease, suggesting that early detection of relapse might increase the chance of long-term survival. To determine whether current follow-up procedures are effective in identifying preclinical disease, we analyzed patterns of relapse in 139 LCL patients who achieved a complete remission (CR) with high/moderate-dose methotrexate with leucovorin, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone (M/m-BACOD). The timing and results of all posttreatment follow-up tests were examined in the 36 patients who relapsed from complete remission (CR) and 46 controls who remain in CR. Despite conscientious posttreatment follow-up, only two of the 36 relapses (6%) were detected before the development of symptoms. Sixty-seven percent of patients relapsed in new disease sites (42% in new and old sites, and 25% in new sites only). Consistent with this observation, the tests most sensitive to clinical relapse were those not targeted to specific sites of disease: gallium scan (sensitivity, 90%), physical examination (80%), and lactate dehydrogenase (LDH) (65%). Of screening tests performed, only LDH was successful in detecting preclinical relapse, with a sensitivity of 42% and specificity of 85% for impending symptomatic relapse. These results indicate that conventional screening was ineffective in detecting preclinical relapse in LCL patients. We recommend prospective evaluation of a strategy that (1) screens with a frequency appropriate to a patient's risk of relapse, (2) uses sensitive test(s) not targeted to specific sites, and (3) limits aggressive screening to those high-risk patients eligible for potentially curative salvage therapy. 
Acute monarticular arthritis. Sleuthing out the cause. The diagnosis of acute monarthritis depends heavily on a thorough history and physical examination. When these are combined with a few diagnostic tests, such as synovial fluid analysis, x-ray studies, complete blood cell count, and common blood chemical analyses, the majority of cases can be correctly diagnosed and properly treated. 
Occult breast masses: use of a mammographic localizing grid for US evaluation. To determine if there was a problem of misidentification of mammographically detected masses with freehand ultrasound (US), the authors examined 50 mammographically distinct masses in 47 patients who were scheduled to undergo needle localization. In only six cases were the masses to be localized in an area of the breast that contained other mammographic opacities that could have led to problems of identification. The patients were first studied with freehand US. Results were then compared with those subsequently obtained with a fenestrated mammographic compression grid to guide the US evaluation. Needle localization was then performed. In five of 50 cases, masses detected with freehand US and initially believed to correspond to the mammographically detected mass were subsequently found to represent different areas of the breast when US was used with the compression grid. These results suggest that the potential for misidentification of masses with freehand US is real and that a mammographic grid localization device can be used to overcome this problem. 
New trends in gallstone management. Many new therapies for the management of gallstone disease have been pioneered in the past decade. The object of this review is to equip the surgeon with the answers to all of the questions a patient will ask about gallstone therapy; the review is therefore didactic as well as comprehensive. 
Acute asthma. Admission chest radiography in hospitalized adult patients. The utility of admission chest radiography has been controversial in the management of adult patients admitted to the hospital with acute asthma. We reviewed the impact of admission chest radiography on in-hospital management of 54 adult patients with acute asthma. Each patient was admitted after a failed 12-h course of bronchodilator therapy in the emergency ward. Major radiographic abnormalities were found in 20 (34 percent) of 58 occasions. These abnormalities included focal parenchymal opacities, IIM, enlarged cardiac silhouette, pulmonary vascular congestion, new solitary pulmonary nodule and pneumothorax. Subsequent antibiotic use correlated with radiographic focal opacities or IIM, even in afebrile patients, but did not correlate with elevated blood leukocyte count. Based on the evidence of in-hospital alteration of management independent of elevated blood leukocyte count and body temperature, we recommend that chest radiographs be obtained for all adult patients admitted because of acute asthma. 
Identification of different laminin binding proteins in basolateral cell membranes of human colorectal carcinomas and normal colonic mucosa. The adhesive properties of tumour cells to laminin, the major glycoprotein of basement membranes, play a crucial part in the complex process of tumour invasion and metastasis. We therefore investigated the expression of laminin binding proteins in isolated basolateral cell membranes of human colorectal carcinomas and the adjacent normal colonic mucosa. Cell membrane binding assays and immunoblotting experiments showed appreciable quantitative and qualitative differences in the expression of these proteins in neoplastic and normal tissue. Epithelial basolateral cell membranes of colorectal carcinomas bound five to eight times more radioactive labelled laminin than basolateral cell membranes of the adjacent normal colonic epithelium. The expression of laminin binding proteins with Mr 66,000-69,000 daltons corresponding to the so called 'Mr 67,000 dalton laminin receptor' was three to four times higher in colorectal carcinomas than in normal colonic epithelium. In addition, laminin binding proteins with higher molecular weights, which may be related to the family of integrins, were also increased in colorectal carcinomas. In particular, laminin binding proteins with Mr 180,000 daltons were exclusively expressed on neoplastic epithelial cells of human colorectal carcinomas. Our data suggest that certain classes of laminin binding proteins may be selectively expressed on colonic tumour cells, leading to an increased capacity for migration, invasion, and metastasis. 
Hyperthermia deaths in Finland in 1970-86. All cases in which hyperthermia had been determined as the basic cause of death during the period 1970-86 were collected from the records of the Central Statistical Office of Finland. Of the total of 230 cases, 228 were included in the present study; the two remaining victims died abroad, and no autopsy was performed in Finland. Most of the hyperthermia deaths occurred while the decedent was taking a sauna bath; most decedents were men aged 42-62 years. An increase in the total number of hyperthermia deaths, and of male victims, was noted from the beginning of the 1970s onward; the number of female victims remained at a relatively steady level throughout, with the exception of a slight rise in 1986. Acute alcohol consumption was detected in most of the victims; in some cases there was also a reference to chronic alcoholism or recent long-term heavy drinking. The findings suggest that in addition to the acute hazardous effect of ethanol on thermoregulatory mechanisms, the long-term consumption of alcohol may have promoted fatal hyperthermia in these subjects. 
Socioeconomic status and morbidity and mortality in hypertensive blacks. Despite an overall limited range of social and economic opportunities in the recent past, blacks of lower socioeconomic status have experienced marked excesses in hypertension-related burdens compared with their more advantaged peers: the incidence, prevalence, and severity of hypertension and its end-organ sequelae increased with decreasing educational achievement and the 5-year mortality was two times higher for black hypertensives of lower than higher educational achievement under conditions of usual care in U.S. communities in the 1970s. The Stepped Care program of antihypertensive pharmacologic therapy of the HDFP reduced all-cause mortality by 19% for black hypertensive men and 28% for black women. The HDFP also eliminated the association of mortality with educational achievement; the favorable impact of the program was greatest in the group at highest risk, blacks of lowest socioeconomic status. 
Diagnostic usefulness of renal scanning after angiotensin converting enzyme inhibitors [editorial] Radioisotopic renal scanning after angiotensin converting enzyme inhibition (ACEI) has proven to be an exciting area for research. The biologic activity of markers such as DTPA and hippuran, when combined with the physiological effects of ACEI, may provide noninvasive methods of diagnosing both renal artery stenosis and renovascular hypertension. Recent investigators have demonstrated that the sensitivities and specificities of these tests may vary widely; these differences are probably due to variations in study design, patient population, diagnostic criteria, and outcome measurements. We have reviewed these studies and discuss these possible sources of variation and their impact on the clinical usefulness of these diagnostic tests, especially in relation to the prevalence of disease in the population. Current results suggest that the post-ACEI DTPA scan is relatively accurate in the diagnosis of renal artery stenosis, with sensitivity generally greater than 90% and specificity around 95%. However, the best results in predicting the response to angioplasty or surgery in patients with renal artery stenosis have been with the use of post-ACEI hippuran in combination with furosemide (sensitivity, 96%; specificity, 95%). With confirmation of these findings and continued investigation, it is expected that accurate noninvasive tests will be available for widespread clinical use in the near future. 
Prevention of cisplatin-induced emesis: a double-blind multicenter randomized crossover study comparing ondansetron and ondansetron plus dexamethasone. Ondansetron (OND) is a new 5-HT3 receptor antagonist that give complete protection from emesis/nausea in approximately 50% of cisplatin (CDDP)-treated patients. To evaluate if dexamethasone (DEX) added to OND increases antiemetic efficacy, we carried out a double-blind randomized crossover study to compare the antiemetic activity of OND with OND plus DEX. One hundred two chemotherapy-naive patients (44 women and 58 men) scheduled to receive CDDP chemotherapy at doses greater than or equal to 50 mg/m2 entered the study. Eighty-nine patients completed both cycles with the following results: complete protection from emesis/nausea was obtained in 57/59 patients (64.0%/66.3%) with OND and in 81/79 (91.0%/88.8%) with OND plus DEX (P = .0005/P = .0021). At the end of the study, 53% of the patients expressed a treatment preference, and of these, 74% chose OND plus DEX compared with 26% who preferred OND alone, a statistically significant difference (P less than .003). Side effects were very mild and not significantly different between the two treatments. We conclude that OND plus DEX is more efficacious than OND in protecting patients from CDDP-induced emesis and nausea. 
Autoimmune MRL-1 pr/1pr mice are an animal model for the secondary antiphospholipid syndrome. Patients with systemic lupus erythematosus often develop thrombosis, recurrent abortion, thrombocytopenia and neurological disease, in association with serum antibodies against phospholipids, termed the secondary antiphospholipid syndrome. In our search for an animal model for the human antiphospholipid syndrome, we examined the MRL-1pr/pr mouse, which develops a lupus-like illness. These mice were found to have significantly elevated levels of serum antiphospholipid antibodies (aPL) and thrombocytopenia compared to normal mice. By immunodiffusion, these antibodies are similar to human aPL. We observed histologic evidence of central nervous system thromboses as well as perivascular infiltrates of the choroid plexus. The high titers of serum aPL, thrombocytopenia, and thrombosis establish this strain as an animal model for the secondary antiphospholipid syndrome. 
Effects of splenectomy on pulmonary metastasis and growth of SC42 carcinoma transplanted into mouse liver. The carcinoma SC42 was transplanted into the liver of its syngeneic mice DS, and the immunological integrity of the spleen and the effects of splenectomy on the growth and pulmonary metastasis of the liver tumor were assessed. On day 7 after liver tumor transplantation, the natural killer (NK) activity of the splenocytes was significantly elevated; it subsequently decreased at a later stage of the tumor. The response of the splenocytes to PHA and Con-A decreased significantly from the early stage of the tumor. However, the mixed lymphocyte-tumor cell reaction increased significantly from day 14 to day 28. The survival rate of the mice, which had undergone simultaneous splenectomy and liver tumor transplantation, was significantly lower than that of sham-operated control mice. The number of pulmonary metastases in splenectomized mice was significantly greater than in the control mice. There was, however, no difference between the two groups in the weight of the liver tumor. By contrast, splenectomies performed 14 days before or 14 days after tumor transplantation had no significant influence on the survival of the mice. Splenectomies performed on day 0 and on day 3 after tumor transplantation significantly increased the number of pulmonary metastases. Furthermore, the intravenous injection of anti-asialo GM1 antisera on day 0 and day 3 significantly increased the number of pulmonary metastases, but injection of anti-Thy 1.2 antisera had no effect. These results suggest that splenic NK cells may play an important role in the suppression of pulmonary metastasis at early stages of the liver tumor. 
Serum endorphin levels in injured children. Plasma beta-endorphin levels (PBEL) are known to be elevated in acutely injured adults, but this has not been studied in pediatric patients with trauma. We measured PBEL in 46 children who sustained blunt injury. The mean acute PBEL was significantly elevated compared with the mean convalescent PBEL (40.5 +/- 29.0 versus 5.4 +/- 2.1 picomoles per liter, p less than 0.05). PBEL were highest in patients with multiple injuries (60.5 +/- 33.2 picomoles per liter, n = 16). PBEL were also elevated with isolated injuries of the head, face or limbs, and even with less severe injuries, namely multiple abrasions. PBEL were low in patients with abdominal (two patients) or spinal (two patients) injuries. Convalescent PBEL were consistently low. Severely injured patients (Injury Severity Score [ISS] of more than ten) had significantly elevated PBEL compared with patients with minor injuries (ISS less than 10), but some children with low ISS had elevated PBEL. The presence of head injury did not influence PBEL and there was no correlation between PBEL and systolic blood pressure. We have demonstrated that the PBEL is elevated in pediatric patients with trauma. 
Behavioral complications of drug treatment of Parkinson's disease. A variety of neuropharmacologic agents, including anticholinergic drugs, amantadine hydrochloride, levodopa, selegiline, bromocriptine, and pergolide, are now available for the treatment of Parkinson's disease. Of patients treated with dopaminergic agents, 30% develop visual hallucinations, 10% exhibit delusions, 10% have euphoria, 1% have mania, 10% to 15% experience increased anxiety, 15% have confusional periods, and a few exhibit altered sexual behavior. Anticholinergic drugs have a greater tendency to produce confusional states than dopaminergic compounds. Elderly patients and those with underlying dementia are most likely to have untoward side effects with anti-parkinsonism treatment. Dosage reduction is the optimum management strategy, although anti-psychotic agents may be necessary in patients with delusions, and lithium may help control drug-induced mania. Dopaminergic agents share the property of stimulation of D2 dopamine receptors, and this action may play an essential role in mediating their neuropsychiatric effects. 
Predicting radioresistance in early glottic squamous cell carcinoma by DNA content. Nuclear DNA content has been implicated as a prognostic factor in an increasing number of tumor types. Current data on the role of DNA content in head and neck carcinoma are conflicting and incomplete. To evaluate the role of DNA content in predicting radioresistance, 29 patients with T1N0M0 squamous cell carcinoma of the glottic larynx who had undergone uniform curative radiotherapy and whose clinical outcome was known had flow cytometric analysis for DNA content performed on their tumors with paraffin-embedded archival tissues. Five aneuploid lesions and 24 diploid lesions were identified. All aneuploid lesions occurred in radioresistant tumors. The probability of an aneuploid tumor failing radiotherapy was highly significant at p = .016. No DNA discordance was found in a sampling of half of the radioresistant lesions' pretreatment and recurrent specimens, for a 100% predictive value of moderate statistical power. On the basis of these findings, patients with aneuploid T1 glottic lesions should be referred for primary surgical therapy. 
Evaluation and management of patients with both peripheral vascular and coronary artery disease. The prevalence of serious angiographic coronary artery disease ranges from 37% to 78% in patients undergoing operation for peripheral vascular disease. Clinical studies have demonstrated that cardiac outcome after peripheral vascular surgery is not adequately predicted by the standard criteria of history, physical findings and rest electrocardiogram. An adequate exercise work load, left ventricular function and thallium redistribution have proved important in perioperative risk stratification. The choice of a perioperative functional cardiac test depends on patient-related factors and the nature of the peripheral vascular operation. Although procedures involving aortic cross-clamping exert a greater hemodynamic stress than do carotid endarterectomy and femoral popliteal surgery, late cardiac morbidity and mortality are significant in all patients with atherosclerotic disease. The decision to proceed with preoperative coronary angiography and myocardial revascularization should be based primarily on indications independent of the peripheral vascular procedure. However, peripheral vascular surgery may influence the timing of myocardial revascularization. Patients with high risk or unstable coronary artery disease may benefit from preoperative coronary revascularization, although this hypothesis remains unproved. In all patients, careful monitoring during and after operation is essential. All patients with peripheral vascular disease should be considered to be at lifelong risk for fatal and nonfatal cardiac events and should undergo appropriate clinical and laboratory evaluation and be treated accordingly. 
Vulvar squamous cell carcinoma and papillomaviruses: two separate entities? Vulvar squamous precancers (vulvar intraepithelial neoplasia) are associated with sexual factors, cigarette smoking, and human papillomaviruses. However, epidemiologic studies of invasive carcinoma of the vulva have produced conflicting evidence for these associations, in part because of a strong association with vulvar inflammatory disease (dystrophies) in older women. We analyzed a series of 42 vulvar invasive carcinomas for papillomavirus nucleic acids by deoxyribonucleic acid-deoxyribonucleic acid in situ hybridization and correlated their presence with age, smoking history, and morphologic type. The carcinomas were divided into well-differentiated, moderately and poorly differentiated, and intraepithelial-like growth patterns, the latter composed of nests of invasive neoplastic epithelium with preserved cell polarity, similar to intraepithelial disease. Of the lesions studied, 28% were human papillomavirus deoxyribonucleic acid-positive. Intraepithelial-like neoplasms segregated in women with a younger mean age (64 versus 73 years) than that of women with conventional squamous cell carcinoma and they more frequently had a history of cigarette smoking (88% versus 28%). Moreover, intraepithelial-like lesions contained human papillomavirus nucleic acids more frequently (67% versus 13%) when analyzed by in situ hybridization. These observations confirm the diverse nature of vulvar squamous cell carcinoma and may explain in part why conflicting results are obtained from studies investigating the role of sexual and viral factors in the genesis of vulvar cancer. They suggest that many invasive vulvar cancers may not be linked to papillomaviruses. 
Is there a premorbid personality typical for Parkinson's disease? For decades clinicians have postulated a characteristic preexisting personality in patients who develop Parkinson's disease (PD). They are described as moralistic, law-abiding, conscientious, and averse to risk-taking. The limited personality surveys tend to be confirmatory, but most of the literature is anecdotal or replete with unprovable psychodynamic postulates. In addition to an apparent stability of marriages and lack of alcoholism, patients with PD are less likely than controls to be smokers. It has been suggested that nicotine and its byproducts are not actually protective against PD, and it could be postulated that higher-than-average intrinsic dopamine may facilitate addiction. Smoking for the patient who is later to develop PD may be particularly unrewarding. In addition, the postulated personality for PD may predispose to hard work, perspiration, and increased exposure to putative trace elements in the water supply. 
Paralysis of the trapezius: a case report. A patient was referred to physical therapy for exercises to the right shoulder secondary to a peripheral nerve injury involving the spinal accessory nerve. A treatment program was designed to accommodate for lack of upward scapula rotation, which is necessary for elevation of the upper extremity above shoulder level. During the course of two and a half years of care, a variety of associated problems were encountered. There was no apparent nerve regeneration, and the patient was left with limited mobility of the affected upper extremity. 
Randomised, controlled trial of effectiveness of ampicillin in mild acute respiratory infections in Indonesian children. The recommended treatment for mild acute respiratory infections (ARI) in children is supportive care only, but many physicians, especially in developing countries, continue to prescribe antibiotic treatment because they believe it prevents progression to more severe ARI. To find out whether ampicillin treatment conferred any benefit over supportive care alone, a randomised, controlled trial was carried out among 889 children (under 5 years) with mild ARI in Indonesia. 447 were randomly allocated ampicillin (25-30 mg/kg body weight three times daily for 5 days) plus supportive care (continued breastfeeding, clearing of the nose, and paracetamol to control fever); 442 were allocated supportive care only. The treatment groups were almost identical after randomisation in terms of age, sex, level of parental education, history of measles immunisation, and fever. After 1 week the percentages cured were nearly identical (204 [46%] ampicillin; 209 [47%] control), as were the percentages of cases progressing to moderate ARI (56 [13%] vs 53 [12%]). The effect of treatment was not modified by age, sex, measles immunisation status, or the educational level of the parents. At the 2-week follow-up, the percentages cured were 62% (277) in the ampicillin group and 58% (256) in the control group; 14% of both groups had progressed to moderate ARI; and 24% (107) and 28% (123), respectively, still had mild ARI. None of the differences in outcome between the ampicillin and control groups was statistically significant. Thus, ampicillin plus supportive care offers no benefit over supportive care alone for treatment of mild ARI in young Indonesian children. 
Prevention of gram-positive infections after bone marrow transplantation by systemic vancomycin: a prospective, randomized trial. Gram-positive bacteria are the most commonly isolated organisms after bone marrow transplantation (BMT) and severe streptococcus septicemia has been reported. In order to evaluate the benefit of a gram-positive prophylaxis after BMT, we conducted a prospective, randomized trial of systemic vancomycin among 60 patients undergoing BMT for hematologic malignancies. Patients were randomized to receive (n = 30) or not receive (n = 30) prophylactic vancomycin 15 mg/kg every 12 hours from day -2 until resolution of neutropenia or until the first episode of fever. All patients were treated in laminar air-flow rooms, received sterile diet, total gut decontamination, and had central venous catheters placed surgically. Vancomycin was found to be highly effective in preventing gram-positive infections that occurred in 11 of 30 patients in the control group versus zero of 30 in the vancomycin group (P less than .002). All gram-positive infections occurring in the control group were symptomatic (nine septicemia and two local infections), and one patient with Streptococcus septicemia died with pneumonia. Thus, gram-positive prophylaxis was found to decrease infection morbidity after BMT. Moreover, the number of days with fever (P less than .001), and empiric antibiotic therapy (P less than .01) was reduced without added toxicity or cost. This study confirmed the high prevalence of gram-positive infections after BMT and emphasized the clinical benefits of an adapted prophylaxis. 
Aphthoid ulceration of the colon in strongyloidiasis. In humans, infestation with Strongyloides stercoralis most commonly involves the upper small intestine. We describe a 65-yr-old woman who presented with abdominal pain, weight loss, and hypoalbuminemia, and was found at colonoscopy to have patchy erythema with aphthoid ulcers scattered throughout the large intestine proximal to the splenic flexure. Biopsy of involved areas and examination of the colonic effluent revealed S. stercoralis larvae. Previous reports of colonic involvement with this nematode, and the differential diagnosis of aphthoid ulcers, a newly described lesion associated with S. stercoralis infestation, are discussed. 
Metastatic carcinoma in the neck: a clinical, radiological, scintigraphic and pathological study. This study was undertaken to compare clinical evaluation of the neck with 99mTc(v) DMSA planar scintigraphy and computerized tomography (CT) in patients with head and neck carcinoma. Twenty-six patients were studied and in all but one the neck was previously untreated. A total of 31 neck dissections were performed and the specimens examined histopathologically. CT was approximately as accurate (71%) as clinical examination (68%) and more accurate than 99mTc(v) DMSA planar scintigraphy (48%) in predicting which necks contained metastatic carcinoma. Overall, 13% of necks had their staging correctly changed by 99mTc(v) DMSA scintigraphy compared with 10% for CT. Although scintigraphy upstaged 13% of clinically N0 necks compared to 6% for CT, it was less sensitive and specific than either clinical examination or CT. 99mTc(v) DMSA planar scintigraphy has no role to play in the investigation of patients with metastatic carcinoma to include the clinically N0 neck. 
Coronary-subclavian steal corrected with percutaneous transluminal angioplasty. We describe a case of coronary-subclavian steal syndrome treated with percutaneous transluminal angioplasty. A 58-year-old female who had her first coronary bypass operation 6 years previously and a second operation 3 years previously involving the left internal mammary artery and right gastroepiploic artery, developed unusual angina on effort characterized by left precordial pain, pain in the left shoulder and arm, tinnitus and dizziness. Angiography revealed retrograde flow to the left subclavian artery via the left vertebral artery and left internal mammary artery. Severe stenosis of the left subclavian artery was demonstrated at its ostium. Restoration of antegrade flow to the vertebral artery and left internal mammary artery by transluminal angioplasty resulted in complete resolution of these symptoms. 
Effects of lower limb unloading on skeletal muscle mass and function in humans. A model to simulate effects of microgravity on skeletal muscle mass and function in humans has been developed. Unilateral lower limb unloading that allowed ankle, knee, and hip joint mobility was conducted in six healthy men by suspending one lower limb and having the subjects walk on crutches. They performed maximal unilateral concentric or eccentric quadriceps actions at different angular velocities before and after 4 wk of suspension and after 4 days and after 7 wk of uncontrolled recovery. Peak torque (PT) and angle-specific torque (AST) were measured. Muscle cross-sectional area (CSA) and radiological density (RD) of the thigh were assessed by means of computerized tomography. Concentric and eccentric PT and AST across speeds decreased (P less than 0.05) by 22 and 16%, respectively, in response to unloading. At 4 days of recovery PT (-11%) and AST (-7%) were still lower (P less than 0.05) than before. Muscle CSA and RD decreased (P less than 0.05) by 7 and 6%, respectively. After 7 wk of recovery PT, AST, CSA, and RD had returned to normal. The control limb showed no changes over the experimental period except for a 6% decrease (P less than 0.05) in RD. It is suggested that this human model of unloading could serve to simulate effects of microgravity on skeletal muscle mass and function because reductions in muscle mass and strength were of similar magnitude to those produced by bed rest. 
Serum antibodies against respiratory tract viruses in episodes of acute otitis media. Although the findings of epidemiological studies have suggested viral respiratory tract infection (RTI) to be crucially involved in the development of acute otitis media (AOM), the relationship between AOM and viral RTI remains unclear. Serum samples, obtained in the acute and convalescent phases of 57 AOM episodes (in 35 children during the first three years of life) were analysed for IgG antibodies against influenza A viruses, influenza B viruses, parainfluenza virus type 1, respiratory syncytial virus and adenoviruses. One third of the AOM episodes (18/57) could be related to viral RTI, as evidenced by significant increases in viral serum antibody activity. Treatment failure occurred in four AOM episodes where increases in serum viral antibody activity were noted. In three of these failures, antibiotic treatment was unsuccessful despite the bacterial strains not being resistant to the drug used. This suggests that concomitant viral infection may be a determinant of treatment outcome in some AOM episodes. 
Pelvic abscesses: CT-guided transrectal drainage. Percutaneous drainage of pelvic abscesses has been performed by using a number of approaches, including transabdominal, transgluteal, and transrectal. The authors present a technique for the drainage of pelvic abscesses by a transrectal route with use of computed tomographic (CT) guidance. Equipment for the technique included a plastic introducer tube, standard needle, angiographic guide wire, and pigtail catheters. The pelvic abscesses of 10 patients (six after appendectomy, three after colon resection, one secondary to diverticulitis) were successfully drained by using the new technique. No complications or recurrences were experienced. After initial catheter placement, patients were treated with use of gravity drainage and appropriate antibiotics. Success of drainage was determined with sequential CT scans. Compared with the transgluteal approach, the transrectal approach offered increased patient comfort and minimal risk of potential complications such as injury to the sciatic nerve or tracking of the abscess. Use of the plastic introducer tube promoted operator safety by protecting the guiding finger. On the basis of this initial series, CT-guided transrectal drainage appears to be an effective and well-tolerated method for the drainage of pelvic abscesses. 
Frequent hypoxemia and apnea after sedation with midazolam and fentanyl. More than 80 deaths have occurred after the use of midazolam (Versed), often in combination with opioids, to sedate patients undergoing various medical and surgical procedures. We investigated the respiratory effects of midazolam (0.05 mg.kg-1) and fentanyl (2.0 micrograms.kg-1) in volunteers. The incidence of hypoxemia (oxyhemoglobin saturation less than 90%) and apnea (no spontaneous respiratory effort for 15 s) and the ventilatory response to carbon dioxide were evaluated. Midazolam alone produced no significant respiratory effects. Fentanyl alone produced hypoxemia in half of the subjects and significant depression of the ventilatory response to CO2, but did not produce apnea. Midazolam and fentanyl in combination significantly increased the incidence of hypoxemia (11 of 12 subjects) and apnea (6 of 12 subjects), but did not depress the ventilatory response to CO2 more than did fentanyl alone. Adverse reactions linked to midazolam and reported to the Department of Health and Human Services highlight apnea- and hypoxia-related problems as among the most frequent adverse reactions. Seventy-eight per cent of the deaths associated with midazolam were respiratory in nature, and in 57% an opioid had also been administered. All but three of the deaths associated with the use of midazolam occurred in patients unattended by anesthesia personnel. We conclude that combining midazolam with fentanyl or other opioids produces a potent drug interaction that places patients at a high risk for hypoxemia and apnea. Adequate precautions, including monitoring of patient oxygenation with pulse oximetry, the administration of supplemental oxygen, and the availability of persons skilled in airway management are recommended when benzodiazepines are administered in combination with opioids. 
Induction of sustained patency after clot-selective coronary thrombolysis with Hybrid-B, a genetically engineered plasminogen activator with a prolonged biological half-life. BACKGROUND. Despite the utility of tissue-type plasminogen activator (t-PA) in eliciting coronary thrombolysis clinically, early reocclusion remains a problem, occurring despite anticoagulation in 5-30% of patients with initially successful recanalization. This study evaluated the utility of Hybrid-B, a molecular variant of t-PA with a prolonged half-life in the circulation, in eliciting coronary thrombolysis and maintaining patency in the presence of a continuing thrombogenic stimulus. METHODS AND RESULTS. In intact, anesthetized dogs, either 18 mg Hybrid-B over 30 minutes (n = 15) or 50 mg t-PA (Activase) over 60 minutes (n = 8) was administered starting 60 minutes after left anterior descending coronary artery occlusion was induced with a thrombogenic copper coil. Time to lysis averaged 54 +/- 26 (means +/- SD) minutes and 64 +/- 34 minutes with Hybrid-B and t-PA, respectively (p = NS). When Hybrid-B was administered as a bolus (20 mg over 1 minute) to induce a high initial concentration in blood, time to lysis was shortened markedly and averaged 15 +/- 5 minutes. Dogs given Hybrid-B by either infusion or bolus exhibited prolonged time to reocclusion (337 +/- 192 minutes compared with 192 +/- 125 minutes in dogs given t-PA, p less than 0.03), reflecting maintenance of a subthrombolytic but persistently active concentration of activator in blood. Despite the persistence of Hybrid-B in blood, concentrations of fibrinogen and alpha 2-antiplasmin were not depleted markedly and remained at 77 +/- 25 and 56 +/- 24%, respectively, of control values. CONCLUSIONS. Thus, Hybrid-B, a novel variant of t-PA with unique pharmacokinetic properties, elicits prompt, sustained, and clot-selective coronary thrombolysis. 
Recommendations for collection of laboratory specimens associated with outbreaks of gastroenteritis. Recent discoveries have implicated a number of "new" (i.e., previously unrecognized) infectious agents as important causes of outbreaks of gastroenteritis. Unfortunately, the ability to detect these agents in an outbreak can be limited by two factors: 1) the lack of appropriate assays-many of which are still in developmental stages and are not readily available to clinical laboratories, and 2) inadequately or improperly collected specimens. At CDC, many newly developed assays are being used for research and for outbreak investigations. The information in this report is especially intended for public health agencies that collaborate with CDC in investigating outbreaks of gastroenteritis. The report provides an update on guidelines and recommendations for the proper collection of specimens to be sent to CDC, gives general background information concerning some recently discovered pathogens, lists some of the tests available at CDC, and provides a list of CDC contacts. The guidelines and the general information provided on causes of outbreaks of gastroenteritis can be also used by public health workers for investigations when specific testing is available and appropriate. 
Root of the superior mesenteric artery in pancreatitis and pancreatic carcinoma: evaluation with CT To determine if changes involving the root of the superior mesenteric artery are specific for neoplasm, the authors retrospectively reviewed 173 computed tomographic (CT) examinations of patients with proved pancreatitis (103 examinations) and pancreatic ductal adenocarcinoma (70 examinations). Streaky infiltration of the fat surrounding the root was seen in 27 of 56 examinations of acute pancreatitis, in four of 24 examinations of chronic pancreatitis, in 12 of 23 examinations of pancreatitis complicated by abscess, and in 25 of 70 examinations of pancreatic carcinoma. Periarterial lymph nodes were visible in 14 with acute pancreatitis, in three with chronic pancreatitis, in six with pancreatic abscess, and in 11 with pancreatic carcinoma. A focal mass extended to within 1 cm of the root in 10 with acute pancreatitis, in two with chronic pancreatitis, in four with pancreatic abscess, and in 24 with pancreatic carcinoma; the mass obliterated the periarterial fat in seven with acute pancreatitis, in one with pancreatic abscess, and in 18 with pancreatic carcinoma. Circumferential encasement occurred in one with chronic pancreatitis, in four with pancreatic abscess, in 14 with pancreatic carcinoma, and in none with acute pancreatitis; nearly all cases of encasement revealed loss of periarterial fat. Thus, these indicators are not specific for neoplasm. 
The IgE and IgG subclass antibody response to foods in babies during the first year of life and their relationship to feeding regimen and the development of food allergy. This follow-up study of 191 babies investigated the development of food allergy in an unselected population and its relationship to total and antigen-specific IgE and IgG subclass levels. Sensitization to egg, as indicated by a positive skin test or RAST, was found in 5% of 1-year-old babies, but none of the babies in this series fulfilled the clinical criteria for immediate-type milk allergy. For both bovine casein (CAS) and egg albumin, the IgG response was largely restricted to IgG1 in contrast to the predominant IgG4 response to these antigens that is found in adults. The level of IgG4, but not IgG1, antibody to CAS and ovalbumin (OV) was lower in some of the babies compared with that of their mothers (N = 166; p less than 0.05, Student's paired t test). However, there was no difference in the total serum IgG subclass levels between mothers and babies. These results demonstrate that, in the population of babies studied, (1) type I hypersensitivity to egg occurred in 5% of 1-year-old babies, (2) the predominant IgG subclass of antibodies to CAS and OV in babies is IgG1, and (3) in the 22% of babies, there was substantially (greater than 1000-fold) less IgG4 antibody to CAS and OV than in their mothers, suggesting specific exclusion of some IgG4 antibodies. 
Comparison of coronary and myocardial morphologic findings in patients with and without thrombolytic therapy during fatal first acute myocardial infarction. The TIMI Investigators. The hearts of 61 patients (39 men aged 64 +/- 11 years) who died from 5 hours to 42 days (median 3 days) after a fatal first acute myocardial infarction without having undergone percutaneous transluminal coronary angioplasty or coronary bypass surgery were studied to compare clinical and cardiac morphologic features of patients receiving thrombolytic therapy with tissue-plasminogen activator (t-PA) to those not receiving thrombolytic therapy. Comparison of findings in the 23 patients who received t-PA intravenously 3 +/- 1 hours after onset of symptoms, with the 38 patients who did not, showed similar baseline characteristics with respect to: age, gender, history of hypertension; location of the infarct; heart weight; severity and numbers of coronary arteries narrowed; and frequencies of plaque rupture, plaque hemorrhage and coronary thrombi. Among the patients receiving t-PA, however, there was a greater frequency of platelet-rich (fibrin-poor) thrombi in the infarct-related coronary arteries (6 of 11 vs 4 of 25 thrombi; p = 0.02), more nonocclusive than occlusive thrombi (6 of 11 vs 4 of 25 thrombi; p = 0.02), and a lower frequency of myocardial rupture (left ventricular free wall or ventricular septum) (5 of 23 [22%] vs 18 of 38 [46%]; p = 0.045). 
Successful management of CMV pneumonia in a mechanically ventilated patient. We report a case of severe respiratory failure due to cytomegalovirus pneumonitis in a patient who underwent an allogeneic bone marrow transplant, who was successfully treated with the combination of ganciclovir and high-dose intravenous immune globulin. We also reviewed the rationale for the use of combination therapy with an antiviral agent and immunotherapy. Because of the bone marrow toxicity of ganciclovir, an aggressive diagnostic approach, including bronchoalveolar lavage and open lung biopsy, may be necessary to establish a definitive diagnosis prior to institution of therapy. 
Are concomitant surgical procedures acceptable in patients undergoing cervical exploration for primary hyperparathyroidism? Cervical exploration for primary hyperparathyroidism is an extremely safe procedure with essentially no operative mortality or morbidity and with success rates approaching 98%. These results have encouraged experienced surgeons to perform other surgical procedures concomitantly with cervical exploration with use of the same general anesthetic agent. This retrospective study was performed to assess the safety and efficacy of this practice. At our institution, 117 patients underwent cervical exploration for primary hyperparathyroidism in combination with an additional surgical procedure, including breast (25), biliary (21), gynecologic (19), intra-abdominal (18), and cardiothoracic (6) operations. The mean operative time was 155 minutes, and the mean duration of hospitalization was 7.6 days. Postoperatively, 115 patients (98%) were normocalcemic. Nine complications (mostly minor), which occurred in eight patients, related primarily to the concomitant surgical procedure. No operative mortality occurred. If performed by experienced surgeons in carefully selected patients, cervical exploration for primary hyperparathyroidism in combination with another elective operation is safe and cost-effective. 
Needle aspiration of extrathoracic metastases from bronchogenic carcinoma. Five patients with suspected metastatic bronchogenic carcinoma underwent needle aspiration of peripheral metastatic lesions instead of a diagnostic bronchoscopy. Aspirates were from the soft tissue of the proximal arm (three patients), an axillary mass (one patient), and a skin nodule (one patient). Two patients had non-small cell carcinoma, two had small cell carcinoma, and one patient had a nondiagnostic aspirate. The procedure had insignificant morbidity, was easy to perform, quickly established a diagnosis of metastatic disease, and obviated the need for a more invasive diagnostic procedure in four of the five patients. 
Reflex sympathetic dystrophy syndrome secondary to L5 radiculopathy. A 47-year-old woman developed radiating right lower extremity pain with weakness in the L5 myotomes. A CT scan, subsequent myelogram, and postmyelogram CT scan were reported as negative. Two months of bed rest diminished the radiating symptoms, but the weakness persisted. Three months post onset a severe burning dysesthesia developed in the right foot, and the patient became unable to bear weight on that extremity. Physical examination revealed 4-/5 weakness of the ankle dorsiflexors, foot evertors, toe extensors, and hip abductors. The entire right foot was swollen and had a red, mottled discoloration. An EMG was equivocal, and a three-phase bone scan was positive in the right foot in all three phases, which is characteristic of reflex sympathetic dystrophy. A repeat CT scan and review of the earlier scans revealed a high lateral disc fragment at the exit foramina of the L5 nerve root. Upon laminectomy, a free disc fragment at the exit foramina was removed, and the patient's symptoms resolved completely. Reflex sympathetic dystrophy syndrome is very rarely reported in association with lumbar radiculopathy. This case emphasizes the need to carefully evaluate the far lateral exit foramina on CT scan in patients with symptoms of radiculopathy. Myelogram is characteristically normal in these cases. 
Safety and efficacy of percutaneous transluminal coronary angioplasty in patients with left ventricular dysfunction. The risks and long-term outcome after 845 elective percutaneous transluminal coronary angioplasties (PTCA) in patients with left ventricular (LV) dysfunction (ejection fraction less than or equal to 40%) were examined. Procedural results were compared with 8,117 consecutive procedures in patients with ejection fractions greater than 40%. The patients with LV dysfunction were older (63 vs 60 years, p less than 0.01), had a greater incidence of prior myocardial infarction (84 vs 45%, p less than 0.001), prior bypass surgery (39 vs 21%, p less than 0.001), 3-vessel disease (62 vs 33%, p less than 0.001), and class IV angina (48 vs 41%, p less than 0.01) than the control group. Angiographic success was lower (93 vs 95%, p less than 0.01), and overall procedural mortality was increased ( 4 vs 1%, p less than 0.001) in the study group. Emergency surgery rates were identical (2%). No significant difference was found in rates of nonfatal Q-wave myocardial infarction (2 vs 1%). At mean follow-up of 33.5 months, 15% of the patients with LV dysfunction required late bypass surgery, 27% underwent repeat PTCA, and 59% were angina free. Actuarial survival at 1 and 4 years was 87 and 69%, respectively. Cox regression analysis identified 3-vessel disease, age greater than or equal to 70 years, class IV angina and incomplete revascularization as correlates of long-term mortality. These data suggest that PTCA may be an effective treatment for coronary artery disease in patients with LV dysfunction. 
Immunocytochemical localization of phospholipase C-gamma in rat embryo fibroblasts. Rat embryo fibroblasts (REF52) exhibit a distinctive, transformation-sensitive distribution of alpha-protein kinase C (alpha-PKC). Receptor-mediated activation of phospholipase C (PLC)-gamma generates diacylglycerol, the major cellular activator of PKC. Immunofluorescence techniques were used to investigate the subcellular localization of two PLC isozymes (PLC-gamma and PLC-delta) in normal and simian virus 40-transformed REF52 cells to determine (i) if PLC colocalizes with alpha-PKC and (ii) if PLC isozyme distribution is sensitive to transformation. PLC-delta was not detected in either cell type. In REF52 cells, PLC-gamma was associated with the actin cytoskeleton and was evenly distributed along the length of the actin microfilaments. PLC-gamma was coincident with alpha-PKC at the points where the filaments are anchored to the membrane (i.e., the focal contacts). Cytoskeletal association of PLC-gamma was not transformation sensitive, although the actin cytoskeleton was more disordered in simian virus 40-transformed cells. In REF52 cells, platelet-derived growth factor induced tyrosine phosphorylation of both soluble and cytoskeletal PLC-gamma. Tyrosine phosphorylation of PLC-gamma did not seem to be a determinant of its subcellular localization, but there was a detectable increase in cytoskeleton-associated PLC-gamma in response to platelet-derived growth factor treatment. 
Massive ossifying fibroma of the temporal bone. Ossifying fibromata are rare lesions of the temporal bone. Because the tumors tend to progress and can become clinically massive, early complete resection is advised whenever feasible to prevent clinically evident recurrences and potentially life-threatening complications. 
A simple technique for closure of a palatal fistula using a conchal cartilage graft. A simple technique for closure of a palatal fistula using a conchal cartilage graft as a substitute for nasal lining flaps is reported. This graft simplifies the repair of the palatal fistula and protects the suture line of the oral covering flaps from recurrence. 
Prospective evaluation of maternal serum human chorionic gonadotropin levels in 3428 pregnancies. As part of a multicenter prospective study, second-trimester human chorionic gonadotropin and alpha-fetoprotein concentrations were evaluated. Data included maternal age, human chorionic gonadotropin level, alpha-fetoprotein level, weight, race, and pregnancy outcome of 3428 pregnancies at between 15 and 20 weeks' gestation. The results of the study indicate that human chorionic gonadotropin levels decrease as maternal weight increases, that weight-adjusted human chorionic gonadotropin levels for Oriental and black women are higher than for white or Hispanic women, and that twin pregnancies have higher human chorionic gonadotropin levels than singleton pregnancies. Of 255 pregnancies that did not have normal outcomes, 54 (21.2%) had human chorionic gonadotropin levels greater than 2.0 multiples of the median and 26 (10.2%) had alpha-fetoprotein levels greater than 2.5 multiples of the median. Of 11 pregnancies with fetal aneuploidy, 6 (54.5%) had human chorionic gonadotropin levels greater than 2.0 multiples of the median. It is concluded that in human chorionic gonadotropin screening programs for fetal Down syndrome, weight and race adjustments are necessary for accurate risk assessment. 
Single motor end-plates in myasthenia gravis and LEMS at different firing rates. The jitter and frequency of blocking was studied at single motor end-plates in 10 patients with myasthenia gravis (MG) and in a patient with Lambert-Eaton myasthenic syndrome (LEMS), using single fiber EMG (SFEMG) with axonal microstimulation at rates varying from 0.5 Hz to 20 Hz. While some myasthenic motor end-plates showed lowest degrees of transmission disturbance at the lowest rates and most pronounced abnormality at the highest rates of stimulation, over one-half were most abnormal at intermediate rates and improved at higher rates. In 1 patient, all end-plates behaved in this way. On the other hand, all end-plates in the LEMS patient showed the expected improvement of the abnormal jitter and blocking on increasing the stimulation rate. It is argued that improvement of jitter and blocking at higher rates, unless dramatic, does not necessarily suggest a presynaptic abnormality. 
Fever: management and self-medication. Results from a Norwegian population study. A representative sample of the Norwegian population was interviewed in 1988 as part of a monthly national opinion poll to investigate lay management and self-medication of fever. Six hundred and nineteen women and 592 men over the age of 15 were interviewed in their homes. Approximately one-fifth reported inappropriate measuring of body temperature. A variety of management and self-medication was found. In cases of common cold or influenza with fever, 35% would use antipyretics. Forty per cent would start to use antipyretics at a temperature below 39.0 degrees C. Forty-four per cent did not know any antipyretic brand names at all. The results indicate a need for more definite and consistent information to make fever management and self-medication more rational. Such information should be discussed and given by general practitioners, nurses at child welfare centers and pharmacists. 
Microscopic hematuria and calculus-related ureteral obstruction. The evaluation of patients with ureteral calculi in the emergency department has historically included urinalysis (UA) and intravenous pyelograms (IVP). This retrospective study was done to determine if a statistically significant relationship existed between the degree of calculus-related ureteral obstruction, proven by IVP, and the presence or absence of microscopic hematuria. Urine red blood cells were recorded as less than 3 rbc/hpf (negative) or greater than or equal to 3 rbc/hpf (positive). IVPs were recorded as nonsevere or severe. IVP criteria were based on the presence or absence of extravasation, greater than 2-hour ureteral filling times, and a numerical scoring system of 1 to 4 for ureteral or calyceal dilatation and nephrogenic effect. Eighty-nine men (72%) had non-severe obstructions and 34 (28%) had severe obstructions. Twenty-five women (68%) had nonsevere obstructions and 12 (32%) had severe obstructions. Of the 28 patients with normal UAs, 11 had severe ureteral obstructions and 17 had nonsevere ureteral obstructions. There were no statistically significant differences between the presence or absence of significant microscopic hematuria and the presence or absence of severe ureteral obstruction. Microscopic hematuria is neither sensitive nor specific in determining the degree of calculus-related ureteral obstruction. 
Prolonged QT interval and risk of sudden death in South-East Asian men. Sudden death in sleep occurs in substantial numbers among young men in South-East Asia. The frequencies of electrocardiographic abnormalities were measured in groups with varying risks of such sudden death. The mean heart-rate-corrected QT interval (QTc) was significantly (p less than 0.05) greater among 123 Laotian refugees in Thailand at high risk (405 [95% confidence interval 397-413] ms) than in 77 Laotian refugees in the United States at lower risk (364 [359-369] ms) and 199 non-Asian US residents at negligible risk (358 [354-362] ms). Among refugees in Thailand, prolonged QTc interval was associated with poor thiamine status and a history of seizure-like episodes in sleep. Thiamine deficiency may be a cause of prolonged QT interval and sudden death in this region. 
Antepartum testing in the hypertensive patient: when to begin. Antepartum testing has been recommended for patients whose pregnancies are complicated by hypertension. Although this is considered accepted practice, there are little data available to help the clinician know when to start testing. To help answer this question in patients with chronic hypertension and nonproteinuric pregnancy-induced hypertension, we reviewed the results of all antepartum tests between 1976 and 1987 in patients with these diagnoses. The primary mode of surveillance in the majority of our patients was the contraction stress test. We determined when patients first had positive contraction stress test results and when intervention occurred because of an abnormal antepartum test result. There were a total of 917 patients tested with these diagnoses. Fifty-three (5.8%) of these patients had at least one positive contraction stress test result. Twenty-two patients were delivered of infants before 35 weeks' gestation because of abnormal antepartum test results. Those with early intervention (less than 35 weeks' gestation) could not be differentiated from those with later intervention (greater than or equal to 35 weeks' gestation) by maternal age, diastolic blood pressure, or systolic blood pressure at the time of testing. The majority of patients who were delivered of infants before 35 weeks' gestation had a concomitant diagnosis of systemic lupus erythematosus, intrauterine growth retardation, diabetes mellitus, or superimposed preeclampsia. On the basis of when compromise was evident, patients with these diagnoses may require testing to be started as early as the fetus is considered viable. However, in those without these diagnoses, the clinician may delay the beginning of testing until 33 weeks' gestation without significant risk of pregnancy loss before testing. 
Epithelial downgrowth following the removal of iris inclusion cysts. We present three patients in whom epithelial downgrowth occurred following the excision of iris inclusion cysts. The sheet-like downgrowth was aggressively treated and successfully eradicated in two of the three patients. Early identification and prompt therapy are essential. 
Clinical syndromes and differential diagnosis of spinal disorders. In this article an overview of the different clinical aspects of spinal syndromes is presented. The common disorders involving the spinal cord, the spine, and the intervertebral disc are emphasized. 
Rectosigmoid varices and other mucosal changes in patients with portal hypertension. A prospective study was performed to evaluate the prevalence of anorectal varices and their clinical significance as well as to study other proctosigmoidoscopic changes in 75 patients with portal hypertension of diverse etiology. Sixty-seven patients (89.3%) had lower gastrointestinal varices with no significant difference (p greater than 0.05) in prevalence between cirrhosis (92.1%), noncirrhotic portal fibrosis (87%), and extrahepatic portal venous obstruction (85.7%). The rectum was the most common site of lower gastrointestinal varices. External anal and sigmoid colonic varices almost always occurred in the presence of rectal and/or internal anal varices. There was no correlation between the presence of rectosigmoid varices and the severity of esophagogastric mucosal changes or portal hypertension. There was no suggestion that esophageal variceal sclerotherapy influenced the presence of anorectal varices. Seven patients (9.3%) had recent hematochezia, including three patients in whom it occurred in the absence of any upper gastrointestinal hemorrhage. Varices were the cause of bleeding in at least five patients. An abnormal mucosal vascular pattern in the form of telangiectasias or spiders was seen, irrespective of etiology of portal hypertension, in nine patients (12%). Hemorrhoids were present in 31 patients (41.3%) with an age-related difference (p less than 0.05) between patients with cirrhosis (55.3%) and extrahepatic portal venous obstruction (21.4%). 
Gonadal vein thrombosis in patients with acute gastrointestinal inflammation: diagnosis with CT. During a 31-month period, evidence of gonadal vein thrombosis (GVT) was demonstrated by computed tomography (CT) in seven patients who had a broad spectrum of acute gastrointestinal inflammatory lesions, including diverticulitis, ulcerative colitis, Crohn disease, appendicitis with abscess, and perforated appendix with pseudomembranous colitis. All patients had lower abdominal pain, tenderness, fever, and leukocytosis. CT demonstrated thrombus through the length of the gonadal vein in each patient; the entire lumen of the vein was filled. No symptoms relating to GVT were present. GVT may resolve with treatment of the underlying enteric disease alone, and anticoagulant therapy may not be necessary. 
Diagnosis and management of retroperitoneal soft-tissue sarcoma. Retroperitoneal soft-tissue sarcomas are locally invasive tumors that remain occult for long periods and grow quite large due to the abdominal cavity's remarkable ability to accommodate these slowly expanding masses with a paucity of attendant symptoms. An open biopsy is required to establish diagnosis definitively. Despite improved imaging techniques and preoperative and intraoperative patient management, resectability has not changed significantly in the past 20 years. Even with an aggressive operative approach, only one half the tumors can be resected completely, and of those, more than 90% recur locally and result in the death of the patient. The addition of adjuvant radiotherapy or chemotherapy has not altered this pattern of local failure, in contrast to promising results with extremity soft-tissue sarcoma. Because of the rarity of these tumors, there is an urgent need to establish a national retroperitoneal sarcoma registry and to form cooperative intergroup studies to evaluate, treat, and apply innovative multimodality combination therapies to these otherwise lethal tumors. 
Absence of autoantibodies in primary fibromyalgia. Sera from patients with primary fibromyalgia (223 sera, 210 women; 13 men) were analyzed, by immunofluorescence microscopy, for the presence of antibodies directed against cell nuclei (ANA), smooth muscle, mitochondria and other tissue antigens present in cryostat sections of rat organs (liver, kidney and stomach). Sera from blood donors (255 sera, 75 women; 180 men) served as a comparative group. The occurrence of serum autoantibodies in patients with fibromyalgia did not differ significantly from the reference group. Our results differ from those of others, who have suggested a relation between fibromyalgia and inflammatory rheumatic diseases. 
Can decision analysis help in the management of giant hemangioma of the liver? [editorial] We explore the trade-off between the risk and expected benefits from resection of giant liver hemangioma (GLH), one larger than 4 cm in diameter. We searched the English-language literature for studies of the postoperative mortality after resection of GLH and of the outcome of expectantly treated patients. The results of the data synthesis showed an operative mortality of 1.5% (90% confidence intervals, 0.1-3.0%) and an early surgical morbidity of up to 13%. Mortality among the 37 reported cases with ruptured GLH was 78%. There were no cases of spontaneous or traumatic rupture of unresected GLH during a follow-up of a total of 282 patient years. The main source of ambiguity regarding the management of GLH is the uncertain risk of its rupture. Rough estimates of this risk based on published data suggest that surgical resection is not justified in asymptomatic GLH. Yet, although rare, rupture of GLH does occur with disastrous consequences. Future research may attempt to define patient subsets whose GLHs are at higher risk of rupture, and in whom preventive resection may improve survival. 
Isolation of a yeast artificial chromosome spanning the 8;21 translocation breakpoint t(8;21)(q22;q22.3) in acute myelogenous leukemia. The 8;21 translocation is one of the most common specific rearrangements in acute myelogenous leukemia. We have identified markers (D21S65 and a Not I boundary clone, Not-42, referred to as probe B) flanking the chromosome 21 translocation breakpoint (21q22.3) that demonstrate physical linkage in normal genomic DNA, by using at least three restriction endonucleases (Not I, Sac II, and BssHII), and that are located not more than 250-280 kilobases apart. Pulsed-field gel analysis of DNA from somatic cell hybrids containing the 8;21 translocation chromosomes demonstrates rearrangement of these markers. A 470-kilobase yeast artificial chromosome, YAC-Not-42, has been isolated that contains both probes. Mapping of lambda subclones constructed from YAC-Not-42 suggests that greater than 95% (25/26 probes tested) of the yeast artificial chromosome DNA is located on the proximal (D21S65) side of the breakpoint. In situ hybridization studies using metaphase chromosomes from five acute myelogenous leukemia patients with the 8;21 translocation confirmed these results and demonstrated the translocation of probe B to the derivative chromosome 8. A chromosome walk of approximately 39 kilobases from probe B has allowed identification of the breakpoint in DNA from a somatic cell hybrid containing the derivative chromosome 8. Since probe B contains conserved DNA sequences and is in close proximity to the translocation breakpoint, it may represent a portion of the involved gene on chromosome 21. 
Poliomyelitis-like paralysis during recovery from acute bronchial asthma: possible etiology and risk factors. A poliomyelitis-like paralytic disease during recovery from an attack of bronchial asthma is described in two young children. They presented at the age of 13 and 22 months, respectively, with acute flaccid paralysis of one or both lower limbs and preserved sensation. Cerebrospinal fluid examinations revealed mild protein elevation in both and pleocytosis in the second infant. Enteroviruses were isolated in a nasal swab and stools of the second patient. Acute onset of flaccid paralysis with absent motor action potential and normal sensory responses, detected by electrophysiologic studies, are highly suggestive of motor anterior horn cell disease in these infants. A multifactorial setup of immune suppression, stress, and neurotoxic drugs during an acute bronchial asthma attack triggered by a viral disease may render the patient vulnerable to viral invasion of the anterior horn cell with enteroviruses other than poliovirus. The overall experience of 22 patients with this serious complication is reviewed. 
Pericardio-peritoneal window for malignant pericardial effusion. Pericardio-peritoneostomy for malignant and non-hemorrhagic pericardial effusion is effective. This method relieves the patients of their symptoms and enables them to be discharged within 24 hours. 
Healing assessment of osseous defects of periapical lesions associated with failed endodontically treated teeth with use of freeze-dried bone allograft. Freeze-dried bone allograft (FDBA) has been used extensively in periodontal surgery and in the treatment of pocket osseous defects resulting from inflammatory periodontal disease. No other endodontic investigation has used this type of graft material in the treatment of bony resorptive defects of the periapical lesions associated with failed endodontic therapy. Therefore this study was conducted with the use of FDBA, to assess healing ability of osseous defects after removal of periapical lesions associated with failed endodontically treated teeth. In all patients periapical lesions were surgically removed with retrograde amalgam seal and the graft material was then carefully packed without pressure into the bony defect. The lesions were fixed in 10% neutral buffered formalin and prepared for histologic examination. Long-term recall demonstrated bone regeneration and good tolerance of allograft material by the periapical tissues. The periapical lesions were either periapical granulomas or apical periodontal cysts. We conclude that FDBA is a biocompatible material of osteogenic potential and can be used effectively in treating osseous defects of periapical lesions associated with failed endodontically treated teeth. 
A selective loss of somatostatin in the hippocampus of patients with temporal lobe epilepsy. Although neuropeptides have been demonstrated to be hippocampal neuromodulators in laboratory animals, their role in human hippocampal physiology or pathophysiology remains to be defined. The concentrations of somatostatin, cholecystokinin octapeptide, vasoactive intestinal polypeptide, and dynorphin A 1-17 were determined in hippocampal tissue resected from patients with cryptogenic temporal lobe epilepsy, a common seizure disorder originating in or near the hippocampus. Control tissue was obtained from cadavera or epilepsy patients in whom the hippocampus was removed during the resection of temporal lobe tumors. Peptide determinations were performed on extracts of punch biopsy specimens taken from six different hippocampal regions. A significant decrease in immunoreactive somatostatin concentration was identified in the dentate gyrus and in region cornu ammonis 4 of cryptogenic temporal lobe epilepsy specimens. No significant changes were present in any other hippocampal region or in the levels of other peptides. In situ hybridization studies performed on cryostat sections from similar patients confirmed a marked loss of neurons expressing the somatostatin gene, which was restricted to the dentate hilus. The density of specific 125I-somatostatin binding to cryostat sections, as determined by semiquantitative in vitro autoradiography, was significantly increased in the dentate gyrus of the cryptogenic epilepsy patients, compared with tumor control specimens. We conclude that a loss of somatostatin-producing interneurons with an upregulation of dentate somatostatin receptors is a specific and characteristic element in the pathophysiology of human cryptogenic temporal lobe epilepsy. 
Altered load dependence of postischemic myocardium Intermittent myocardial ischemia can produce areas of postischemic ("stunned") myocardium in the heart of the human with coronary artery disease. These areas are no longer ischemic, but have diminished contractile performance. Although the effects of loading conditions on systolic contraction of normal, ischemic, and failing myocardium have been investigated in great detail, the way in which load affects contraction of postischemic myocardium is not known. The aim of this study was to determine in anesthetized dogs how loading conditions affect the systolic function of a region of myocardium after 10 min of ischemia and 1 h of reperfusion. Sets of piezoelectric crystals were implanted in a test zone and in a remote zone of myocardium. Measurements of systolic wall thickening were made during nine combinations of left atrial pressure (3, 6, and 9 cmH2O) and mean arterial pressure (70, 90, and 110 mmHg). One set of measurements was made under baseline conditions, and a second set was made after 10 min of coronary occlusion and 1 h of reperfusion. Ischemia and reperfusion reduced wall thickening in the test zone 36 +/- 3% and diminished the response to increases in preload. In contrast, the response of the test zone to changes in afterload was unchanged. An interaction between the test zone (in which depressed contraction was observed) and the surrounding myocardium (in which enhanced function was observed) produced the appearance of a regional wall motion abnormality as afterload increased. These results emphasize that the load dependence of postischemic myocardium differs from that of normal myocardium and must be taken into account in clinical studies in which regional contraction is used to monitor the heart for ischemia. 
Transesophageal electrocardiography using a temporary pacing balloon-tipped electrode in acute cardiac care. STUDY OBJECTIVE: The study was undertaken to determine the feasibility of obtaining esophageal ECGs using resterilized 3F temporary pacing balloon-inflated electrodes in place of the more expensive pill-electrode and its associated expensive preamplifier. SETTING: Tests were conducted in the emergency department and ICU. TYPE OF PARTICIPANTS: Subjects were 12 acutely ill patients for whom standard 12-lead surface ECGs were insufficient to afford accurate, immediate arrhythmia diagnosis. INTERVENTIONS: Reasonable quality esophageal ECGs were obtained by use of the electrodes, generally with minimal patient discomfort. The test never required more than ten minutes. Of the 12 patients who participated in this preliminary study, esophageal ECGs enabled definitive diagnoses to be made in ten cases. CONCLUSION: The use of resterilized temporary pacing balloon-inflated electrodes enables esophageal ECGs to be obtained in an acute care setting. 
Embolization with steel coils using a saline flush technique. A method using saline flush to push Gianturco steel coils through catheters is described, and has been successfully used in 45 patients. The saline flush technique requires no precise matching of coils and catheters, solves problems associated with the conventional method and simplifies the coil embolization procedure. 
Ascites and pleural effusions associated with endometriosis. We report a case of ascites and bilateral pleural effusions associated with an endometrioma in a 26-year-old woman of Chinese descent. She had a right salpingo-oophorectomy and partial omentectomy performed, and she received leuprolide acetate depot injections after the operation. We believe this is the first description of use of a GnRH agonist to treat this rare condition. 
Sodium-lithium countertransport and hypertension in Rochester, Minnesota. The objectives of the present study were to determine whether increased sodium-lithium countertransport is associated with essential hypertension in the general Caucasian population and to determine whether this association is independent of the effects of gender, age, body size, and plasma lipids. We studied 543 men and 589 women from the population of Rochester, Minnesota. Mean sodium-lithium countertransport was higher in hypertensive than in normotensive subjects in men (370 +/- 147 [mean +/- SD] versus 315 +/- 110 mumol/l red blood cells [RBC]/hr, p less than 0.001) and in women (339 +/- 114 versus 269 +/- 92 mumol/l RBC/hr, p less than 0.001). Interindividual differences in plasma triglycerides, body mass index (wt/[ht]2), and plasma total cholesterol explained 13.0% of sodium-lithium countertransport variation in men (p less than 0.001) and 20.2% in women (p less than 0.001). Age did not predict additional sodium-lithium countertransport variation in either gender. Slopes of the regressions of sodium-lithium countertransport on plasma triglycerides, body mass index, and plasma total cholesterol did not differ between diagnostic groups in men (p = 0.31) or in women (p = 0.29). After adjustment to remove sodium-lithium countertransport variation attributable to these covariates, mean sodium-lithium countertransport remained significantly higher in hypertensive than in normotensive subjects in men (354 +/- 139 versus 319 +/- 104 mumol/l RBC/hr, p less than 0.01) and in women (311 +/- 103 versus 278 +/- 83 mumol/l RBC/hr, p less than 0.01). 
Effects of enteral fat emulsion on fat absorption in obstructive jaundiced rats. The effects of fat emulsion given enterally on fat absorption were studied with obstructive jaundiced rats (J group) as compared with jaundice-free rats (C group). The J and C groups were subdivided into JE and CE groups using emulsified fat for the fat absorption test, and JU and CU groups using unemulsified fat. Rats in all groups were fed for 7 days with regular rat chow. After fasting for 12 hours, 14C-labeled fat emulsion was infused to the JE and CE, and 14C-labeled unemulsified fat to the JU and CU groups through a gastrostomy for the absorption test. The hourly and cumulative output of 14CO2 by respiration, absorption rate of 14C-labeled fat in the intestine, and metabolic oxidation rate of the absorbed fat were determined during an 8-hour period after the gastroenteral administration of emulsified or unemulsified fat. The peak of hourly output was seen after the first 2 hours in the CE, JE, and CU groups, following which a remarkable decline was seen in the CE and CU groups. However, a more gentle descent in the JE, and fluctuation at a low level in the JU group were observed. The cumulative output in the JE was 61% of that in the CE, while the output in the JU was 16% of that in the CU group. The absorption rate in the JE was 81% of that in the CE group, while the rate in the JU was 22% of that in the Cu group. 
Congenital cystic eye with multiple ocular and intracranial anomalies. We describe a newborn with congenital cystic eye, contralateral persistent hyperplastic primary vitreous, and cerebrocutaneous abnormalities. The cerebrocutaneous abnormalities consisted of agenesis of the corpus callosum, midbrain deformity, malformed sphenoid bone, right upper eyelid coloboma, and a left periocular hamartoma. The results of karyotype analysis of the patient and his parents were normal. The association of congenital cystic eye with contralateral persistent hyperplastic primary vitreous has not been previously reported, to our knowledge. Although no unifying diagnosis exists for the collection of anomalies demonstrated in this patient, the term cranial ectodermopathy broadly classifies most of the defects. 
Detection of talocalcaneal coalitions by magnification bone scintigraphy. Fibrocartilaginous talocalcaneal coalitions are very difficult to identify on plain radiography in symptomatic children and adolescents before gross ossification occurs. Computed tomography (CT) has been successful in identifying osseous and some fibro-osseous coalitions. In this series, magnification imaging of the tarsus on bone scintigraphy in the medial-lateral projection correctly identified talocalcaneal coalitions, seven of the nine bars were fibrous or fibro-osseous. Three of the fibrous lesions were equivocal or normal on conventional radiography and CT. Physiologic accumulations of activity in the growing hind foot are also presented from a control pediatric population. Magnification scintigraphy of the hind foot is offered as an adjunct to plain radiography and CT in the diagnosis of elusive nonosseous subtalar bars. 
Prognostic significance of basement membrane deposition in operable squamous cell carcinomas of the lung. Tumor histology, stage of disease, and performance status are the most important prognostic factors in squamous cell lung cancer (SqCLC). A potentially important descriptor is the pattern of tumor growth as reflected in the dissolution of preexisting or deposition of newly formed basement membrane (BM) around tumor cell nests. The possible correlation between the pattern of BM deposition and patient survival was investigated. Immunohistochemistry testing, using polyclonal antibodies to human type IV collagen, was done on tumor samples of 68 patients with operable Stages I or II SqCLC, and BM staining was scored semiquantitatively. More than 75% immunoreactivity was scored as extensive BM and less than 75% as moderate or limited BM. In six patients, no immunoreactivity could be detected. In 27 of 62 patients, extensive and, in 35 of 62 patients, moderate-limited BM deposition was found. This deposition had a significant effect on survival (P = 0.02). Cox regression analysis, including BM deposition and tumor stage, indicated that BM deposition might also have value as an additional independent prognostic indicator for survival (P = 0.02). Deposition of an appreciable amount of BM in the center of the SqCLC was a prognostically favorable sign, independent of tumor stage. 
Genes for epilepsy mapped in the mouse. The neurological mutant mouse strain E1 is a model for complex partial seizures in humans. The inheritance of epileptic seizures with seven conventional chromosomal markers and over 60 endogenous proviral markers was studied by means of back-crosses of E1 with two seizure-resistant strains, DBA/2J and ABP/LeJ. The major gene responsible for this epileptic phenotype (El-1) was localized to a region distal with respect to the centromere on chromosome 9. At least one other gene, El-2, linked to proviral markers on chromosome 2, also influences the seizure phenotype. In addition, a potential modifier of seizures was detected in the DBA/2J background. The location of El-1 on distal chromosome 9 may allow identification of an epilepsy candidate gene in humans on the basis of conserved synteny with human chromosome 3. 
Thymic carcinoid. Carcinoid of the thymus is a rare neoplasm. Differentiation from thymoma is important because they have entirely different prognosis. A patient in whom a 19 x 18 x 12 cm carcinoid tumor of the thymus was surgically removed is presented. The tumor metastasized to peritracheal and internal mammary nodes, and invaded the SVC, pleura, lung, and pericardium. This is apparently the largest reported tumor of its kind. Prior to induction of anesthesia cardiopulmonary bypass and rigid bronchoscopy were readily available. Awake intubation was utilized. Even though long-term prognosis is poor, an aggressive surgical approach and adjuvant radiotherapy may achieve extended survival with excellent quality of life. Central aspects of the disease as well as pivotal therapeutic points are discussed. 
Bacterial invasion of the biliary system by way of the portal-venous system. It has been suggested that bacteria in the intestine gain access into the biliary tract by entering the portal-venous blood. We have tested the hypothesis of hematogenous infection of the biliary system in cats. The animals were treated in three different groups: group A (no biliary obstruction), group B (acute biliary obstruction) and group C (chronic biliary obstruction). A mutant strain of Escherichia coli was infused into the splenic vein of cats at three different dosages (10(7), 10(5) and 10(3) with sham controls. In the unobstructed biliary system, the mutant E. coli was isolated from the bile 30 min and 90 min after the infusion of 10(7) and 10(5) E. coli, respectively. No bacteria were found in the bile with the infusion of 10(3) E. coli and in the control animals. Bile flow was significantly reduced with the infusion of bacteria. The biliary excretion of E. coli in group B was similar to that in group A. In group C, the bile output in the first hour was very high but declined rapidly. E. coli was excreted into the bile at all three dosages of infusion after 30 min. Histological sections of the liver showed that the infused bacteria entered the sinusoidal blood and that some were phagocytosed by Kupffer cells. The portal-venous blood was considered an important route of bacterial invasion into the biliary system, and the penetration of bacteria was facilitated in biliary obstruction. 
Medical treatment of peptic ulcer disease. Our understanding of PUD and its treatment has improved dramatically during the past 15 years. During this time, many new effective drugs have been approved by the FDA, and possibly even more potent and effective therapies are now being evaluated. The H2-blockers, sucralfate, and antacids heal over 90% of duodenal ulcers in 6 to 8 weeks, and H2-blockers heal about 80% of gastric ulcers by 8 weeks and over 90% by 12 weeks. The new, more potent pump blockers (omeprazole) promise to be even more effective drugs, even for the healing of patients who are taking NSAIDS. However, the potential hazards of marked, long-term acid suppression must still be evaluated. Maintenance therapy with H2-blockers or sucralfate, ideally used for patients who would otherwise have frequent symptomatic recurrences of duodenal ulcer disease or who have had complications, reduces the relapses, especially symptomatic relapses. Maintenance therapy with H2-blockers also seems to reduce the recurrences of GUD, but this use has not yet received FDA approval. Elimination of H. pylori infection with antibiotics may prove to reduce recurrent ulcer disease and negate the need for maintenance therapy. Colloidal bismuth subcitrate alone, which suppresses but does not eradicate H. pylori infection, seems to be an effective ulcer drug and may even reduce the rate of early recurrences. Effective ulcer therapy, especially if it prevents recurrent disease, may reduce the complications of PUD, but this expectation has yet to be established. The use of prophylactic cytoprotective prostaglandins (misoprostol) reduces the incidence of NSAID-induced GUD. 
Sinusoidal portal hypertension in hepatic amyloidosis. Hepatic venous catheterisation and transvenous liver biopsy were performed in five patients with hepatic amyloidosis. In three patients, hepatic venous pressures were normal and histological examination of the liver biopsy specimen showed discrete and sparse perisinusoidal amyloid deposits. In the other two, however, the gradient between wedged and free hepatic venous pressures was increased (12 and 16 mmHg; normal 1-4 mmHg) and amyloid deposits were abundant and diffuse in the Disse's space. This study shows that portal hypertension in patients with hepatic amyloidosis is of the sinusoidal type and is related to the reduction of vascular space of hepatic sinusoids by massive perisinusoidal amyloid deposits. Furthermore, portal hypertension is associated with a poor prognosis in patients with hepatic amyloidosis. 
Helicobacter pylori infection and the risk of gastric carcinoma BACKGROUND. Infection with Helicobacter pylori has been linked with chronic atrophic gastritis, an inflammatory precursor of gastric adenocarcinoma. In a nested case-control study, we explored whether H. pylori infection increases the risk of gastric carcinoma. METHODS. From a cohort of 128,992 persons followed since the mid-1960s at a health maintenance organization, 186 patients with gastric carcinoma were selected as case patients and were matched according to age, sex, and race with 186 control subjects without gastric carcinoma. Stored serum samples collected during the 1960s were tested for IgG antibodies to H. pylori by enzyme-linked immunosorbent assay. Data on cigarette use, blood group, ulcer disease, and gastric surgery were obtained from questionnaires administered at enrollment. Tissue sections and pathology reports were reviewed to confirm the histologic results. RESULTS. The mean time between serum collection and the diagnosis of gastric carcinoma was 14.2 years. Of the 109 patients with confirmed gastric adenocarcinoma (excluding tumors of the gastroesophageal junction), 84 percent had been infected previously with H. pylori, as compared with 61 percent of the matched control subjects (odds ratio, 3.6; 95 percent confidence interval, 1.8 to 7.3). Tumors of the gastroesophageal junction were not linked to H. pylori infection, nor were tumors in the gastric cardia. H. pylori was a particularly strong risk factor for stomach cancer in women (odds ratio, 18) and blacks (odds ratio, 9). A history of gastric surgery was independently associated with the development of cancer (odds ratio, 17; P = 0.03), but a history of peptic ulcer disease was negatively associated with subsequent gastric carcinoma (odds ratio, 0.2; P = 0.02). Neither blood group nor smoking history affected risk. CONCLUSIONS. Infection with H. pylori is associated with an increased risk of gastric adenocarcinoma and may be a cofactor in the pathogenesis of this malignant condition. 
Ischemic complications of abdominal aortic surgery. From 1982 through 1988, 634 consecutive patients underwent abdominal aortic reconstruction for occlusive (37%) or aneurysmal (63%) disease. We studied the ischemic problems affecting the branches of the aorta, excluding the coeliac and superior mesenteric arteries. Ischemic colitis (0.6%), spinal cord ischemia (0.16%), renal insufficiency (17%), and lower limbs ischemia (6.5%) were the major problems encountered. We identified the most significant factors associated with these complications such as hypotension, emergency, hypovolemia, preoperative renal function, suprarenal clamping, the quality of the preoperative investigation, and have suggested some specific preventive measures. 
The role of bupivacaine in post-tonsillectomy pain. The peritonsillar tissues on one side of 45 consecutive patients undergoing tonsillectomy were infiltrated with bupivacaine and adrenaline, the opposite side serving as a control. Although a significant difference was noted between the two sides this was not a substantial difference in terms of pain relief. 
Sonography of abnormal lymph nodes in vitro: correlation of sonographic and histologic findings. The sonographic evaluation of lymph nodes is based primarily on evaluation of their shape and size. Recently, however, the availability of high-frequency transducers has made consideration of internal structure possible. An important objective is to determine whether node enlargement is due to inflammatory or neoplastic processes. To determine the accuracy of sonography for this purpose, we obtained in vitro sonograms of 53 enlarged lymph nodes excised from 41 patients during surgery for neoplastic or nonneoplastic disease. The sonograms were obtained with 7.5- and 10-MHz transducers. They were interpreted by a radiologist who was unaware of the clinical diagnosis. The nodes were subsequently processed for anatomohistologic study; findings were compared side by side. In 26 of the 53 nodes, sonograms showed an identifiable central echogenic line, which on histologic specimen corresponded to the internal part of the medulla where the lymphatic sinuses converge. All these nodes were benign. Two other nodes had an echogenic internal structure not resembling the normal hilum; in one case this was caused by metastatic disease and in the other by fibrosis. Sonograms of the remaining 25 nodes showed no detectable hilar structure; 21 were involved by a tumor and four had diffuse fatty replacement. Our results suggest that the sonographic finding of a central echogenic line is a valid criterion of benignity. Absence of this finding may be due to factors other than neoplastic disease, such as fatty replacement. 
A generalized description of Wenckebach behavior with analysis of determinants of ventricular cycle-length variation during ambulatory electrocardiography. Although variation in ventricular cycle length during Wenckebach-type second-degree atrioventricular block traditionally has been explained by the direction of incremental change in PR lengthening preceding the blocked complex, changing PP intervals can also affect Wenckebach periodicity. A generalized algebraic solution was derived to define changing ventricular cycle length as a function of both changing PP and changing incremental PR interval behavior in Wenckebach block. Based on this solution, the determinants of cycle-length variation were examined for 65 episodes of Wenckebach block detected by ambulatory electrocardiography in 51 patients. As previously demonstrated, only 20% (13 of 65) of Wenckebach episodes were characterized by the "classic" shortening of RR intervals; in contrast, ventricular cycle length increased in 57% (37 of 65) and remained constant in 23% (15 of 65) of cases. Algebraic analysis of these episodes revealed that the direction of ventricular cycle-length change preceding the blocked complex was primarily determined by the direction of change of incremental PR intervals in only 35% (23 of 65) of Wenckebach episodes; RR change was governed by the direction of change of preceding PP intervals in 34% (22 of 65) and by equal change of PP and incremental PR intervals in 31% (20 of 65) of these episodes. Both inverse and concordant relationships between changing RP and PR intervals were primarily determined by the direction of PP variation during in vivo Wenckebach block. These data confirm that classic Wenckebach block is less common than "atypical" Wenckebach periodicity and demonstrate that RR variation in Wenckebach block is governed by the changing PP interval as often as by the changing incremental PR interval. 
Ventilatory responses to chemoreceptor stimulation after hypoxic acclimatization in awake goats. Our objective was to test the hypothesis that exposure to prolonged hypoxia results in altered responsiveness to chemoreceptor stimulation. Acclimatization to hypoxia occurs rapidly in the awake goat relative to other species. We tested the sensitivity of the central and peripheral chemoreceptors to chemical stimuli before and after 4 h of either isocapnic or poikilocapnic hypoxia (arterial PO2 40 Torr). We confirmed that arterial PCO2 decreased progressively, reaching a stable value after 4 h of hypoxic exposure (poikilocapnic group). In the isocapnic group, inspired minute ventilation increased over the same time course. Thus, acclimatization occurred in both groups. In goats, isocapnic hypoxia did not result in hyperventilation on return to normoxia, whereas poikilocapnic hypoxia did cause hyperventilation, indicating a different mechanism for acclimatization and the persistent hyperventilation on return to normoxia. Goats exposed to isocapnic hypoxia exhibited an increased slope of the CO2 response curve. Goats exposed to poikilocapnic hypoxia had no increase in slope but did exhibit a parallel leftward shift of the CO2 response curve. Neither group exhibited a significant change in response to bolus NaCN injections or dopamine infusions after prolonged hypoxia. However, both groups demonstrated a similar significant increase in the ventilatory response to subsequent acute exposure to isocapnic hypoxia. The increase in hypoxic ventilatory sensitivity, which was not dependent on the modality of hypoxic exposure (isocapnic vs. poikilocapnic), reinforces the key role of the carotid chemoreceptors in ventilatory acclimatization to hypoxia. 
Shower versus sink bath: evaluation of heart rate, blood pressure, and subjective response of the patient with myocardial infarction. The purpose of this study was to compare the effects of a sitting shower versus a sitting sink bath in low-risk patients with myocardial infarction (MI). Heart rate, blood pressure (mean blood pressure and rate-pressure-product), ratings of perceived exertion, and occurrence of symptoms during the baths and between resting, bathing, and recovery periods were evaluated. Thirty patients with MI were tested during their first and second self-bath on 2 consecutive days between 2 and 9 days after MI. The bathing methods produced significant increases from the resting values in all the variables (p less than or equal to 0.05). No significant differences between the resting and recovery values existed (p greater than 0.05). Ten subjects experienced atypical responses to bathing as indicated by heart rate and blood pressures. Fatigue was the most frequently encountered symptom at rest and during the bathing activities. The findings suggest that low-risk patients with MI can choose between a sitting sink bath or a sitting shower as their first self-bath after MI, based on preferences. However, because the bathing activity (and not the bathing method) did produce some atypical responses in one third of the subjects, readiness to engage in bathing activities should be individually assessed by objective and subjective criteria. 
Acute leukemia after a primary myelodysplastic syndrome: immunophenotypic, genotypic, and clinical characteristics. We studied the nature of blast cells in 41 patients with acute leukemia following a previous primary myelodysplastic syndrome (MDS) by a combined multiparameter analysis including morphologic, immunophenotypic, and molecular genetic (Igs, T-cell receptor (TCR)-beta, -gamma, and -delta and the major breakpoint cluster region [M-bcr]) investigations. In addition, the clinical and hematologic characteristics according to the immunophenotype of blast cells were analyzed. Our results show that, although the granulocytic and/or monocytic lineages are those most commonly involved in these acute leukemias, other cell components, including the megakaryocytic and lymphoid, may be present (12% and 15% of the cases, respectively). Moreover, both morphologic and phenotypic studies show the frequent coexistence of two or three cell populations. Interestingly, in all cases the lymphoblastic component constantly displayed an early B phenotype (CD19+, CD10-, TdT+). Upon analyzing whether the type of MDS conditioned any differences in the immunophenotype of blast cells, we observed that, although the lymphoid lineage may be involved in all MDS subgroups, some differences emerge within the myeloid leukemic transformations. Thus, the refractory anemias with excess of blasts (RAEB) and RAEB in transformation displayed a significantly higher incidence of myeloblastic and megakaryoblastic transformations, while in the RA, RA with ring sideroblasts and chronic myelomonocytic leukemia, the granulo-monocytic phenotype predominated. In addition, our results show that the clinical and hematologic characteristics of these patients may be partially related to the immunophenotype of the blast cells. Ig heavy chain gene rearrangements were found in two of 19 patients analyzed (11%), one with a hybrid leukemia (lymphoid-myeloid) and the other with a granulo-monocytic phenotype. Two other hybrid transformations analyzed were in germline configuration. Gamma and delta gene rearrangements were found in 21% and 37% of these acute transformation, respectively. The TCR-beta and M-bcr were in germline configuration in all 19 cases studied. In summary, immunophenotype and molecular studies point to a pluripotent stem cell with preferential myeloid commitment as the target cell of leukemias following a primary MDS. 
Low power laser biostimulation of chronic oro-facial pain. A double-blind placebo controlled cross-over study in 40 patients. The efficacy of low power laser stimulation in the treatment of chronic oro-facial pain conditions was investigated in a double-blind placebo controlled modified cross-over study in 40 patients. The laser was an invisible infrared (IR) diode laser with an emission at 904 nanometer (nm). Treatment effect was evaluated by means of VAS-scales and global assessment of pain. Outcome of treatment was correlated to changes in urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA). The clinical impression was that placebo was superior to laser stimulation. No statistically significant difference between the analgesic effect of the laser and placebo irradiation was found on VAS-scales. A significant (P = 0.05) increase in 5-HIAA excretion was found in the placebo group. It is concluded that the possibility of a substantial placebo response should be taken into consideration using 904 nm (IR) lasers for pain treatment in patients with this type of chronic oro-facial pain. 
A randomized trial of carboplatin versus iproplatin in untreated advanced ovarian cancer. Between August 1984 and October 1987, 120 patients with stage IC to IV epithelial ovarian cancer were randomly assigned to receive carboplatin (400 mg/m2) or iproplatin (300 mg/m2) every 4 weeks as initial treatment. Stratification was made according to International Federation of Gynecology and Obstetrics (FIGO) stage and according to size of residual disease after surgery. Response was evaluated after six courses when patients were restaged, with laparoscopy or laparotomy in clinical complete responders or those with no assessable disease. Treatment was then stopped in surgically proven complete responders. Patients with partial (PR) or minor response (MR) received a further six courses of their original drug at a reduced dose (carboplatin 300 mg/m2, iproplatin 225 mg/m2). Patients with stable (SD), progressive (PD), or recurrent disease were treated with cyclophosphamide (1 g/m2). The response rates were 63% (95% confidence interval [CI], 50% to 74%) for carboplatin and 38% (95% CI, 26% to 51%) for iproplatin. Fifteen patients were not assessable for response. The median survival was 114 weeks (95% CI, 82 to 233 weeks) for carboplatin patients and 68 weeks (95% CI, 48 to 82 weeks) for iproplatin patients (P = .008). The amount of residual disease after initial laparotomy was a prognostic factor for survival. Myelosuppression was the main toxicity and was greater with iproplatin. This study shows carboplatin to be more active than iproplatin in the treatment of ovarian cancer and less toxic. Few responses to cyclophosphamide occurred following either drug, implying resistance to the alkylating agent. 
Determinants of late stage diagnosis of breast and cervical cancer: the impact of age, race, social class, and hospital type [published erratum appears in Am J Public Health 1991 Aug;81(8):980] Previous studies of the relationship between cancer stage, age, and race have not controlled for social class and health care setting. Logistic regression analyses, using information from the New York State Tumor Registry and area-level social class indicators, demonstrated that, in New York City, older Black, lower class women in public hospitals were 3.75 and 2.54 times more likely to have late stage breast or cervical cancer, respectively, than were younger White, high social class women in non-public hospitals. 
Breast conservation therapy. Severe breast fibrosis after radiation therapy in patients with collagen vascular disease. Two patients with collagen vascular disease (rheumatoid arthritis and scleroderma) had extremely poor cosmetic results after breast radiation therapy (RT). The patient with rheumatoid arthritis received 5251 cGy at 210 cGy per day, followed by a 1600 cGy iridium-192 implant boost. Between 8 and 11 months post-RT she had severe breast fibrosis, retraction, and pain that required a mastectomy for relief. The patient with scleroderma received 5040 cGy at 180 cGy per day without a boost. Between 1 and 4 months post-RT the systemic symptoms of scleroderma progressed and the breast became hard and retracted. Both rheumatoid arthritis and scleroderma are chronic systemic diseases characterized by severe inflammation and an autoimmune component. The presence of scleroderma at or before treatment should be considered a contraindication to breast RT, whereas the presence of active rheumatoid arthritis should be considered a relative contraindication. An autoimmune mechanism will be presented to explain both the fibrosis and the systemic progression of collagen vascular disease that was observed. 
Antiinflammatory and antiarthritic properties of a substituted quinoline carboxylic acid: CL 306,293. CL 306,293, a substituted quinoline carboxylic acid at a daily oral dose between 1.5 and 3.0 mg/kg suppressed the inflammation and joint destruction (radiological criteria) associated with both developing and established adjuvant arthritis. When a weekly oral dosing regimen was used, joint destruction was attenuated when this agent was administered at a dose of 50 to 200 mg/kg. Inflammation associated with a delayed type hypersensitivity reaction in dogs was suppressed at a daily dose of 0.25 mg/kg or a weekly dose of 1 mg/kg. At efficacious doses, CL 306,293 had no effects on cyclooxygenase or lipoxygenase activities nor did it have an effect on carrageenin induced paw edema. In acute tests, the compound was not ulcerogenic. The above observations indicate that the antiinflammatory effects of CL 306,293 are distinct from those observed with nonsteroidal antiinflammatory agents. Mechanistic studies conducted and to be published indicate that CL 306,293 down regulates T cell function and this mechanism may account, at least in part, for the antiinflammatory and antiarthritic properties observed in animal models of inflammation and joint destruction. 
Vascular complications of lumbar decompression laminectomy and foraminotomy. A unique case and review of the literature. The possibility of vascular injury should always be kept in mind during lumbar laminectomy. Patients with pre-existing vascular disease are predisposed to injury. Unexplained hypotension is highly suggestive of a vascular catastrophe and is an indication for more detailed examination, sometimes laparotomy. If the patient's clinical condition is stable, consider arteriography. The development of high-output cardiac failure in a patient who has recently undergone lumbar laminectomy is almost diagnostic of traumatic arteriovenous fistula. The best prognosis for recovery of acute vascular interruption occurs with immediate treatment within 24-48 hours. Continued awareness of the possible occurrence of these injuries and familiarity with their various manifestations will facilitate early diagnosis, prompt operative repair, and improved mortality. 
Fulminant hepatic failure after repeated exposure to isoflurane anesthesia: a case report. A previously healthy but obese 26-yr-old woman was diagnosed as having hepatic dysfunction 17 days after the third of three consecutive exposures to isoflurane anesthesia for paranasal sinus surgery. Serum laboratory findings included elevated aminotransferases and bilirubin. Radiographical evaluations showed no evidence of extrahepatic disease. Serological studies were negative for acute viral infections, and serum copper was normal. The patient's condition deteriorated over the ensuing 17 days, with hyperreflexia, hypoglycemia and a rapid fall in serum aminotransferases with a concomitant rise in bilirubin level and prothrombin time despite maximal medical support. The liver volume as shown by computed tomography fell from 1,290 cm3 to 680 cm3 over 6 days. The patient underwent successful orthotopic liver transplantation 25 days after onset of symptoms. Histopathological examination of the resected liver showed submassive and massive necrosis, with a few foci of microvesicular steatosis and ultrastructural evidence of mitochondrial abnormalities. Although we found insufficient evidence to prove that this case was caused by isoflurane anesthesia, the clinical course and histopathological findings are similar to those in hepatic injury caused by halothane anesthesia. Therefore we report this as a possible case of fulminant hepatic failure resulting from isoflurane anesthesia. 
Endoscopy as an adjuvant to biliary radiologic intervention. Twenty-two patients underwent 24 percutaneous biliary procedures guided with choledochoscopy, an adjunctive percutaneous biliary technique. All but four procedures were performed through established percutaneous tracts; the others, through tracts less than 4 weeks old. The procedures were done for the following reasons: removal of calculi (n = 15), electrohydraulic lithotripsy (n = 1), biliary duct biopsies (n = 8), cauterization of a bleeding tract (n = 1), and evaluation of biliary-enteric anastomoses (n = 11). The only complication was one case of severe nausea after choledochoscopy. This patient required overnight hospitalization and medical treatment. All procedures were technically successful, except one case in which the tract was undersized. All patients received intravenously administered antibiotics before and after the procedure. It is concluded that choledochoscopy is a safe, atraumatic, and well-tolerated method of evaluating and treating biliary disease and that it markedly reduces radiation exposure. It can be performed rapidly with minimal sedation on an in- or outpatient basis. 
Implantation of human fetal ventral mesencephalon to the right caudate nucleus in advanced Parkinson's disease. Disaggregated ventral mesencephalic tissue from single aborted human fetuses of 11 to 18 weeks' gestation was implanted stereotaxically into a consistent striatal site in 12 patients with advanced Parkinson's disease. All were receiving optimum levodopa therapy and were examined preoperatively and at 3,6,9, and 12 months postoperatively. Immunosuppression was not used. There were significant sustained improvements at 12 months in three patients; motor fluctuations were absent in two. There were modest group improvements up to 6 months, with increased quality of "on" and "off" phases, quantity of on times, and specific improvements in contralateral upper limb bradykinesia. Preoperative levodopa requirements were reduced to a mean of 64% at 6 months and 61% at 12 months. Deterioration below baseline ratings occurred in three of nine patients who had consistent follow-up to 12 months. Grafting of midgestational human fetal tissue can lead to improvement in Parkinson's disease. Individual disease severity may be critical, and further trials are needed to identify host factors influencing outcome. 
Laparoscopic nephrectomy: initial case report. A tumor-bearing right kidney was completely excised from an 85-year-old woman using a laparoscopic approach. A newly devised method for intra-abdominal organ entrapment and a recently developed laparoscopic tissue morcellator made it possible to deliver the 190 gm. kidney through an 11 mm. incision. 
The assessment of visuo-spatial neglect after acute stroke. Forty four consecutive patients with acute hemispheric stroke and forty seven elderly controls with no neurological disease were assessed for visuo-spatial neglect, using a modified neglect test battery. Neglect was found to be equally common in patients with right hemisphere and left hemisphere stroke three days after stroke (72% versus 62%). It was more severe in those with a right hemisphere stroke and resolved more frequently in those with a left hemisphere stroke. The battery was validated against an occupational therapist's assessment of neglect on self-care tasks. The inter-observer reliability was good and it was possible to monitor changes over time with the battery. 
Second-trimester maternal serum alpha-fetoprotein levels and the risk of subsequent fetal death BACKGROUND. The finding of an elevated level of maternal serum alpha-fetoprotein during the second trimester of pregnancy may indicate that the fetus has died or is about to die. It is uncertain, however, whether the finding is associated with an increased risk of fetal death later in gestation independent of known causes of elevation, such as the presence of neural-tube defects or multiple gestation. METHODS. To address this question, we performed a case-control study of 612 women whose pregnancies ended in fetal death and 2501 women who gave birth to live infants, using reports from California vital statistics for 1987. All the women had signleton pregnancies and alpha-fetoprotein screening in the second trimester. RESULTS. Women with elevated levels of serum alpha-fetoprotein in the second trimester of pregnancy had an increased risk of fetal death, and the risk was increased until term. Women with the highest levels of serum alpha-fetoprotein--greater than or equal to 3.0 times the median value--had a very high risk of fetal death (odds ratio, 10.4; 95 percent confidence interval, 4.9 to 22.0) as compared with women who had normal levels of alpha-fetoprotein. Maternal serum alpha-fetoprotein levels that were 2.0 to 2.9 times the median were also associated with an elevated risk of fetal death (odds ratio, 2.4; 95 percent confidence interval, 1.7 to 3.4). Elevated levels of alpha-fetoprotein were especially likely to be associated with fetal death in cases in which maternal hypertension or placental infarction was also present. CONCLUSIONs. An unexplained elevated level of maternal serum alpha-fetoprotein in the second trimester of pregnancy is associated with an increased risk of subsequent fetal death, up to four to five months after alpha-fetoprotein screening. 
Identification and characterization of a cis-acting element that interferes with glucocorticoid-inducible activation of the mouse mammary tumor virus promoter. The rat hepatoma cell line M1.19 is stably infected by the mouse mammary tumor virus (MMTV), and the expression of the virus is induced by glucocorticoid treatment. However, in the 6.10.2 variant of M1.19, an increase in MMTV transcription is hardly detectable upon exposure to hormone. The mechanism of hormone-unresponsiveness in these cells has been unclear. In this study, we show that nuclear extract from 6.10.2 cells contains a specific DNA-binding activity that recognizes a sequence motif extending from positions -163 to -147 on the MMTV promoter. An oligonucleotide probe spanning this region binds a nuclear factor distinct from the glucocorticoid receptor. In vivo competition experiments, where increased amounts of a plasmid containing this element were transfected into 6.10.2 cells, showed a dose-dependent increase in hormonal inducibility of MMTV expression. Together, these results indicate that this sequence motif negatively modulates glucocorticoid-inducible activation of the MMTV promoter. Moreover, we have characterized a nuclear factor that preferentially binds to the coding strand of this element. 
An alternative for nasal tip reconstruction: the bilateral rotation flap. A large percentage of the skin tumors that dermatologic surgeons treat are located on the nose. Of these, a significant percentage are located on the nasal tip. The nasal tip is notoriously difficult to reconstruct and we present a bilateral rotation flap that may be useful in some instances for reconstruction of this area. 
Simultaneous potentiation and fatigue in quadriceps after a 60-second maximal voluntary isometric contraction. Potential mechanisms of fatigue (metabolic factors) and potentiation (phosphate incorporation by myosin phosphorylatable light chains) were investigated during recovery from a 60-s maximal voluntary isometric contraction (MVC) in the quadriceps muscle of 12 subjects. On separate days before and for 2 h after the 60-s MVC, either a 1-s MVC or electrically stimulated contractions were used as indexes to test muscle performance. Torque at the end of the 60-s MVC was 57% of the initial level, whereas torques from a 1-s MVC and 50-Hz stimulation were most depressed in the immediate recovery period. At this time, muscle biopsy analyses revealed significant decreases in ATP and phosphocreatine and a 19-fold increase in muscle lactate. Conversely, isometric twitch torque and torque from a 10-Hz stimulus were the least depressed of six contractile indexes and demonstrated potentiation of 25 and 34%, respectively, by 4 min of recovery (P less than 0.05). At this time, muscle lactate concentration was still 16 times greater than at rest. An increased phosphate content of the myosin phosphorylatable light chains (P less than 0.05) was also evident both immediately and 4 min after the 60-s MVC. We conclude that the 60-s MVC produced marked force decreases likely due to metabolic displacement, while the limited decline in the twitch and 10-Hz torques and their significant potentiation suggested that myosin phosphorylation may provide a mechanism to enhance contractile force under conditions of submaximal activation during fatigue. 
Blunt cervical spine Brown-Sequard injury. A report of three cases. Cervical spinal cord Brown-Sequard syndrome was diagnosed in three recent victims of blunt injury at the authors' Level II Trauma Center. While anatomic hemisection of the cord, resulting in ipsilateral motor and proprioception loss and contralateral pain and temperature deficit, is a fully understandable concept, in the context of the acute trauma evaluation, these findings may be confusing because they are unexpected. Penetrating trauma is far more likely to cause this uncommon syndrome than vehicular crash, fall, or crushing injury. Pediatric victims frequently have no fracture. Early neurosurgical consultation, computed tomography (CT), and magnetic resonance imaging (MRI) if plain film radiography is uninformative, and consideration for rapid decompression if the deficit and pathologic anatomy warrant, are the recommended approaches. Motor function recovery from blunt injury may be expected within six months, a better prognosis than for penetrating injury causing the syndrome. 
Serum iron and transferrin in acute neuroleptic induced akathisia. Thirty acute psychiatric patients were examined prospectively at the beginning of neuroleptic treatment for acute psychotic symptoms and on average 16 days later. Two alternative hypotheses were examined: 1) neuroleptic treatment affects the levels of serum iron and transferrin; 2) acute akathisia developing during the initial few weeks of treatment is associated with low levels of serum iron and transferrin, either initially or at follow up or both. Serum iron levels did not change on repeat measurement, while there was a small, but significant decrease of serum transferrin. There was a significantly greater decrease in iron and transferrin levels in patients with akathisia on follow up compared with non-akathisics. In addition, akathisia ratings were highly correlated with serum transferrin levels on follow up. 
Perineal excision of the rectum for prolapse in the elderly. A perineal operation is described for the treatment of rectal prolapse. The surgery improves functional outcome by correcting the anatomical anomalies associated with the condition. In 17 elderly women, there was one perioperative death and one recurrence. At a median follow-up of 24 months, 13 patients were able to control solid stool and three were profoundly incontinent. The operation may be an alternative to the more invasive abdominal procedures for the treatment of the majority of patients with prolapse. 
Reactive occipital epileptiform activity: is it benign? Occipital epileptiform activity that is almost continuous and reactive to eye opening has been associated with a childhood epilepsy syndrome and basilar migraine with seizures. An association of these syndromes with a benign course had been disputed. In this study, a retrospective investigation of reactive occipital epileptiform activity (ROEA) was performed to determine the prognostic value of this distinctive EGG pattern. The EEG and hospital record of patients with ROEA were reviewed with an observation period of 6 months to 8 years. The patients were divided into good and poor outcome groups based on response to treatment. Of 33 patients, 12 (36.4%) had complete seizure control; 21 (63.6%) continued to have poorly controlled seizures. Only 3 (9.1%) patients were able to discontinue antiepileptic drugs (AEDs) without seizure recurrence. Analysis of clinical and EEG variables showed that a history of perinatal difficulties, abnormal neurologic findings, and abnormal EEG background activities occur significantly more frequently in the poor outcome group. This study suggests that ROEA is not uniformly associated with a benign course and that other factors are involved in determining prognosis of the epilepsy. 
Stroke following oral trauma in children. Stroke after oral trauma in children is a rare but catastrophic event. We describe two cases of stroke in children after each child fell with a writing instrument in the mouth. Both children had a latent period prior to the onset of neurologic symptoms. Ischemic infarction in the distribution of the middle cerebral artery was present in both cases. Both children were left with permanent hemiparesis. The case reports are reviewed and diagnosis and therapy are discussed. Emergency physicians should be aware of the risk of neurologic complications following apparently asymptomatic oral trauma. 
The effect of ERCP on circulating pancreatic enzymes and pancreatic protease inhibitors. The pathogenesis of endoscopic retrograde cholangiopancreatography (ERCP)-induced pancreatitis is poorly understood. To elucidate a role for pancreatic enzymes in ERCP-induced pancreatitis, we measured serum amylase, lipase, trypsin, and elastase in 25 patients undergoing ERCP. Serum alpha 1-antitrypsin and alpha 2-macroglobulin, two major pancreatic protease inhibitors, also were measured. All pancreatic enzymes measured rose significantly after ERCP. Pancreatic duct cannulation was associated with a greater elevation in serum amylase and lipase. Circulating alpha 2-macroglobulin was reduced by 7% (p = 0.04) 6 h after ERCP, whereas circulating alpha 1-antitrypsin increased over the same time period. Papillotomy, stent placement, or underlying disease did not influence changes any further. Three patients developed ERCP-induced pancreatitis. All three patients had circulating alpha 2-macroglobulin levels below 243 mg/dl (p = 0.03). The ERCP-induced alterations in circulating pancreatic enzymes and their inhibitors are similar to changes seen in clinical pancreatitis. Low circulating alpha 2-macroglobulin levels may predispose to ERCP-induced pancreatitis. 
Is routine CT scanning necessary in the preoperative evaluation of patients undergoing carotid endarterectomy? To evaluate the usefulness of CT scanning before carotid endarterectomy, a prospective study was performed on 469 consecutive patients considered for carotid endarterectomy during a 5-year period. All patients underwent carotid duplex scanning and CT scanning before carotid arteriography. Two hundred thirty-seven patients (51%) had transient ischemic attacks, 109 (23%) had a prior stroke, and 122 (26%) were asymptomatic. Results of the CT scan were abnormal in 68 (62%) of the 109 patients with stroke. Fifty-one of the 360 patients (14%) without a clinical history of stroke had an abnormal CT scan outcome. Of patients with a stroke documented by CT scanning, 27 had lacunar infarcts, and 92 had cortical infarcts; these findings did not change surgical management in any patient. CT scanning did not reveal any unsuspected infarcts or tumors. Two hundred thirty carotid endarterectomies were performed on 206 patients. Forty-seven patients (23%) in the operative group had abnormal CT scan findings, but the scan did not influence operative decisions or timing in any case. Seventy-two patients (27%) in the nonoperative group had abnormal CT scan results, but CT scan findings did not exclude any patient from arteriography or surgery. Three perioperative strokes (1.3%) occurred. CT scan findings did not correlate with postoperative neurologic complications. Cost of CT scanning was one-half million dollars in our study alone. Routine CT scanning is unnecessary before carotid endarterectomy and is not cost-effective. 
Peptide selection by MHC class I molecules. Synthetic peptides have been used to sensitize target cells and thereby screen for epitopes recognized by T cells. Most epitopes of cytotoxic T lymphocytes can be mimicked by synthetic peptides of 12-15 amino acids. Although in specific cases, truncations of peptides improves sensitization of target cells, no optimum length for binding to major histocompatibility complex (MHC) class I molecules has been defined. We have now analysed synthetic peptide captured by empty MHC class I molecules of the mutant cell line RMA-S. We found that class I molecules preferentially bound short peptides (nine amino acids) and selectively bound these peptides even when they were a minor component in a mixture of longer peptides. These results may help to explain the difference in size restriction of T-cell epitopes between experiments with synthetic peptides and those with naturally processed peptides. 
No causal relationship between transdermal scopolamine and seizures: methodologic lessons for pharmacoepidemiology. Because of case reports suggesting that use of transdermal scopolamine might be associated with the subsequent development of seizures, a retrospective cohort study was performed with computerized Medicaid claims data. Patients receiving transdermal scopolamine were compared with patients receiving diphenhydramine, meclizine, prochlorperazine, and promethazine. A four-fold increased risk of seizures after transdermal scopolamine use was observed in the claims data. However, this was not supported by the primary medical records. All patients who had seizures after using transdermal scopolamine either had seizures before receiving the drug as well or did not really suffer from seizures. The original finding appeared to be the result of the use of transdermal scopolamine for "dizziness, rule out seizures"; the ICD-9-CM coding system does not include "rule out" diagnoses. Thus these data do not confirm the existence of an association between seizures and the use of transdermal scopolamine. In addition, this study demonstrates the usefulness of pharmacoepidemiology studies in documenting drug safety and the importance of obtaining primary medical records when performing pharmacoepidemiologic studies with claims data. 
A longitudinal study of respiratory symptoms in aluminum potroom workers. The influence of occupational work exposure and host factors on the incidence of dyspnea and wheezing as reported in questionnaires was examined in 1,301 new employees in aluminum electrolytic potrooms. The incidence appeared to decrease after 2 yr of exposure, and the estimated probability of development of symptoms was nearly 20% after 4 yr. A total of 105 subjects developed dyspnea and wheezing. Of 78 symptomatic subjects who were interviewed, 76% experienced improvement or absence of symptoms when off work. In 523 subjects who were assigned to specific levels of exposure at the end of follow-up, a dose-response gradient was found between the development of symptoms and fluoride exposure. Increased risk with increasing amounts of tobacco was also observed, but childhood allergy and a family history of asthma were not significantly related to the outcome variable. We conclude that both total fluoride exposure and smoking are related to asthmatic symptoms in potroom workers, and the suggestion of a dose-response gradient was found for both variables. However, a causal relationship between fluorides and symptoms should be investigated further by specific bronchial provocation testing and by research for specific antibodies and other immunologic markers. 
Preclinical detection in studies of the etiology, natural history, and treatment of Parkinson's disease. The development of reliable preclinical detection procedures for idiopathic Parkinson's disease may be the fundamental advance required for the establishment of the cause, the natural history, and ultimately, the prevention of this neurodegenerative disorder. The usefulness of these preclinical markers in efforts to better understand the etiology and development of this disorder will relate to whether they are direct measures of dopamine production or indirect measures such as metabolic changes or comorbidity, whether they can be used in the first or later decades of life, whether they are invasive, and whether they are expensive and sophisticated or simple and cheap. An overview of the criteria for evaluation of the utility of specific markers, as well as an assessment of the importance of early markers in future research, is presented. 
Opportunities to improve the cost-effectiveness of treatment for hypertension. The cost-effectiveness of treatment for hypertension depends on the pretreatment level of blood pressure, age and sex of the patient, presence of other cardiovascular risk factors, long-term control of blood pressure, and the annual costs of treatment. Treatment of very mild hypertension (diastolic blood pressure, 90-94 mm Hg), even if the benefits do exceed the risks, does not appear to be particularly cost-effective. Opportunities to improve the cost-effectiveness of hypertension management lie in 1) avoidance of patient mislabeling by careful documentation of blood pressures on multiple occasions in the office and during usual activities outside the office before the diagnosis is made and treatment is begun; 2) efforts to increase adherence to scheduled visits and medication regimens; 3) attempts to step-down dosages or discontinue medications after periods of good blood pressure control; 4) explicit consideration of costs, as well as benefits, in decisions on the needed frequency of office visits, choice of medications, and use of laboratory tests; and 5) efforts to improve practice efficiency. Future practice guidelines for hypertension management should take these factors into account and should make trade-offs between benefits, risks, and costs explicit for specific types of patients. 
Prevalence and clinical spectrum of skin diseases in kidney transplant recipients. Cutaneous lesions can be a significant problem in kidney transplant recipients. Factors such as climate and skin types have been implicated as modifiers of these clinical manifestations. With the purpose of determining the prevalence and clinical spectrum of skin diseases in a group of Hispanic kidney transplant recipients in a tropical climate, 82 serial unselected patients were examined. Seventy-eight were found to have some type of skin disease. Infections of the skin were the most common, followed by drug-induced changes and malignant or premalignant cutaneous tumors. Except for the preponderance of superficial mycotic infections, the overall results in our population are in agreement with other series. 
Helicobacter pylori infection induces antibodies cross-reacting with human gastric mucosa. The authors' previous observation that many of the monoclonal antibodies against Helicobacter pylori cross-react with the cells of the human gastric mucosa prompted them to investigate the possibility that gastric self-antigens cross-reacting with H. pylori could be involved in the immune response against this organism. It was found that three antibodies against H. pylori, CB-4, CB-10, and CB-14, that cross-react with the human gastric mucosa also intensely cross-reacted with murine gastric epithelial cells. A strong reaction against autologous mucosa was also evident in the sera of mice immunized with H. pylori but not with other bacteria. A serological study performed in a group of 82 patients undergoing gastroscopy showed that the presence of seropositivity against H. pylori was strongly correlated with the presence of autoantibodies against human antral gastric mucosa. This activity was neutralized after absorption of the sera with H. pylori but not with other gram-negative bacteria. The antibodies in the mouse and in the human did not react with other segments of the gastrointestinal tract or with most of the other organs. Mice bearing hybridomas secreting a cross-reacting antibody (CB-4) had histopathologic abnormalities in their stomachs. These lesions were absent in the stomachs of mice bearing hybridomas secreting a non-cross-reacting antibody (CB-26). It was concluded that H. pylori infection can stimulate antibodies cross-reacting with gastric autoantigens and that this immunologic mechanism may represent a pathogenic link between H. pylori and gastritis. 
Intraoperative identification of cardiac patients at risk to develop postoperative atrial fibrillation. Postoperative atrial fibrillation (AF) is a complication occurring in 11% to 36% of patients after cardiac operations, which results in increased morbidity and hospital costs. A new electrophysiologic screening test was developed to identify those patients at risk for development of postoperative AF. The test was validated in 50 patients (43 men and 7 women) with a mean age of 59.6 +/- 1.3 years who underwent coronary artery bypass grafting with or without other cardiac surgical procedures. After aortic and venous cannulation, but before initiation of bypass, the mid-right atrium was stimulated with a bipolar probe at 25 microA for 3 seconds. Alternating current was increased by 25 microA until AF was induced or up to a maximum of 200 microA. Postoperative AF occurred in 18 patients (36%), 17 of whom had inducible AF (sensitivity = 0.94). Of the remaining 32 AF-free patients, 13 had negative tests (specificity = 0.41). Age and sex were not factors affecting inducibility, although patients who developed AF were older than those who were AF free (63.6 versus 57.3 years, p = 0.02). Length of stay in the intensive care unit was longer for those with postoperative AF than for AF-free patients (3.6 versus 1.9 days, p = 0.02). The negative predictive value of the test was 0.93, and the positive value was 0.47. These data show that this new intraoperative technique may be used to identify patients at risk for postoperative AF. Prophylactic therapy can therefore be directed to only those patients at risk for postoperative AF. 
Comparison of morbidity and function after colectomy with ileorectal anastomosis or restorative proctocolectomy for familial adenomatous polyposis. Restorative proctocolectomy with an ileal reservoir (RPC) should prevent colorectal cancer in patients with familial adenomatous polyposis. Until this is confirmed its role compared with total colectomy and ileorectal anastomosis (IRA) will depend on the relative morbidity and postoperative bowel function after the two procedures. This was analysed in 99 patients (37 RPC, 62 IRA) operated on between 1977 and 1989. Morbidity was greater after RPC with subsequent ileostomy closure (median hospital stay, 24 versus 11 days; complications, 60 versus 21 per cent; reoperation, 29 versus 3 per cent; return to normal activity; 31 versus 14 weeks). There was little difference in bowel function; after IRA median frequency was 3/24 h and urgency (unable to wait 15 min) occurred in 50 per cent, compared with 4.5/24h and 17 per cent after RPC. Night evacuation occurred in 10 and 43 per cent respectively. IRA was performed in younger patients (median 19 versus 31 years) who had fewer bowel motions before operation (2 versus 5/24 h). The greater morbidity of RPC suggests that it should be restricted to patients at higher risk of developing later rectal cancer, including those unavailable for follow-up and those with large or confluent rectal polyps or with curable colon cancer at the initial colectomy. 
Anaphylactic reactions during general anesthesia among pediatric patients--United States, January 1990-January 1991. From March 1990 through January 1991, nine patients at one children's hospital in Wisconsin (hospital A) had onset of anaphylactic reactions (ARs) within 30 minutes following the start of general anesthesia; no patient had had a surgical incision at the time of their reaction. Eight of these patients required admission to the intensive care unit for supportive care. To determine the extent and potential source of the problem, an epidemiologic investigation was conducted at hospital A. 
Identification of a missense mutation in one allele of a patient with Pompe disease, and use of endonuclease digestion of PCR-amplified RNA to demonstrate lack of mRNA expression from the second allele. Infantile-onset glycogen storage disease type II, or Pompe disease, results from a genetic deficiency of the lysosomal enzyme acid alpha glucosidase (GAA). Sequencing of the cDNA from a cell line (GM 244) derived from a patient with Pompe disease demonstrated a T953-to-C transition that predicted a methionine-to-threonine substitution at codon 318. The basepair substitution resulted in loss of restriction-endonuclease sites for NcoI and StyI. Analysis of genomic DNA revealed both a normal and an abnormal NcoI fragment, indicating that the patient was a genetic compound. NcoI and StyI digestion of cDNA, amplified by PCR from reverse-transcribed RNA, demonstrated that greater than 95% of the GAA mRNA in GM 244 was derived from the allele carrying the missense mutation. The missense mutation was uncommon, since it was not detected in 37 additional GAA-deficient chromosomes, as determined by digestion of genomic DNA with NcoI and hybridization. The amino acid substitution predicts a new potential site for N-linked glycosylation, as well as major changes in secondary structure of the protein. We could confirm that the mutation was responsible for the enzyme deficiency by demonstrating that a hybrid minigene containing the mutation did not express GAA enzyme activity after transient gene expression. We have therefore now provided the first identification of a single-basepair missense mutation in a patient with Pompe disease and furthermore have demonstrated that the patient is a genetic compound with the second allele barely expressing mRNA. 
Inflammatory bowel disease. Part I: Nature and pathogenesis. Once regarded as medical curiosities, ulcerative colitis and Crohn's disease have achieved a remarkable change in status recently and today are among the more compelling of all human illnesses. The cause(s) of inflammatory bowel disease (IBD) are not known. Genetic, environmental, microbial, and immunologic factors are involved, but the precise mechanisms are obscure. The incidence of ulcerative colitis is relatively stable, while Crohn's disease continues to increase in frequency. In 10% to 15% of patients, it is hard to differentiate between ulcerative colitis and Crohn's colitis; however, problems with diagnosis usually resolve with time and repeated examinations. In part I of his two-part monograph on IBD, Dr. Kirsner addresses the nature and pathogenesis of the disease. Increased study of ulcerative colitis and Crohn's disease in recent years has generated new knowledge regarding their etiology. Part I focuses on microbial, immunologic, and genetic mechanisms and the inflammatory processes involved in the disease. In part II, which will be presented in next month's issue of Disease-a-Month, Dr. Kirsner deals with the clinical features, course, and management of IBD, based on the author's 55 years of experience with these problems and supplemented by critical examination of the recent (1988-1990) literature. Particular attention is directed to the symptoms and physical findings of ulcerative colitis and Crohn's disease, the laboratory, radiologic, endoscopic, and pathologic features, and the many systemic complications. The IBDs are mimicked by several enterocolonic infections and other conditions, making differential diagnosis necessary. Inflammatory bowel disease in children and the elderly conforms to conventional clinical patterns modified by the health circumstances of the respective age groups. Because the cause of IBD has not been established, current medical therapy is facilitative and supportive rather than curative. The principles of medical treatment are approximately the same for ulcerative colitis and Crohn's disease. Treatment emphasizes a program rather than a drug and also considers the individuality of the therapeutic response. A clearer understanding of dietary and nutritional needs, including hyperalimentation and electrolyte and fluid balance, aids treatment. Antidiarrheal and antispasmodic preparations and sedatives are prescribed for symptom relief. The bowel inflammation is controlled with sulfasalazine or the newer 5-amino salicylic acid (5-ASA) compounds, antibacterial drugs for complications of Crohn's disease and IBD, adrenocortical steroids, and the immunosuppressive compounds 6-mercaptopurine (6-MP), azathioprine, and cyclosporine, as determined in each patient. The surgical procedures available for treatment of ulcerative colitis include total proctocolectomy and ileostomy or ileoanal anastomosis.(ABSTRACT TRUNCATED AT 400 WORDS). 
Cerebrovascular CO2 reactivity in migraine: assessment by transcranial Doppler ultrasound. Cerebrovascular reactivity to CO2 inhalation was studied by transcranial Doppler sonography in 30 patients with classic or common migraine and 39 healthy controls without clinical or ultrasonic signs of arteriosclerosis. Systolic and diastolic Doppler frequencies of the middle cerebral artery were plotted against end-tidal CO2 partial pressure; the reactivity index (I x R) was defined as relative frequency change during a PCO2 increase of 5 mmHg. In the normal subjects, I x R was 20.0 +/- 6.3 for systolic velocities, and 26.0 +/- 8.2 for diastolic values. Migraineurs during their headache-free interval had significantly higher I x R values on the affected side (mean: 41.6 systolic, 61.2 diastolic), compared with either controls (P less than 0.01) or the contralateral side (mean: 28.3 systolic, 30.8 diastolic; P less than 0.01). During the headache attack, CO2 reactivity was significantly lower than normal only for systolic velocities (mean: 8.3; P less than 0.05). Increased CO2 reactivity is thought to be one phenomenon of migraine. Transcranial Doppler CO2 testing of cerebrovascular reactivity is a reliable method that may be of interest for the diagnostic evaluation and management of migraine patients. 
Methotrexate, vinblastine, doxorubicin, and cisplatin in metastatic breast cancer. A phase II trial of the Hoosier Oncology Group. Forty-six eligible patients with metastatic breast cancer (MBC) were treated with a combination of methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) as first-line chemotherapy. Of 44 patients evaluable for response, 28 (64%) had an objective response, including seven (16%) who had a complete response. The median duration of response was 4 months (range, 0 to 38 months), and the median survival from the time of entry was 14 months (range, less than 1 to greater than 45 months). Myelosuppression was the most common dose-limiting toxicity, with 54% of patients experiencing Grade 3 or 4 leukopenia (including 28% with granulocytopenic fever and one septic death), and cumulative Grade 3 anemia occurred in 28% of patients. Grades 3 to 4 stomatitis was observed in 18% of patients. An active, although highly toxic regimen when used as first-line therapy in MBC, M-VAC has a response rate and survival duration similar to existing, less toxic combination regimens. As such, M-VAC cannot be recommended in preference to other combination chemotherapy regimens in this clinical setting. 
Urodynamic evaluation of the patient with an imperforate anus: a prospective study. Prospective urodynamic evaluation of 14 patients with an imperforate anus revealed detrusor-sphincter dyssynergia in 4. Subsequent contrast voiding cystourethrograms demonstrated radiographic changes in all 4 cases, consisting of bladder trabeculation, new onset of vesicoureteral reflux or hydroureteronephrosis. Of the 4 patients 3 had a high (supralevator) imperforate anus, while 1 had a low (infralevator) lesion. Two patients had bony vertebral abnormalities and 2 had normal plain radiographs and magnetic resonance imaging of the spine. Therefore, early urodynamic study is recommended for all patients with an imperforate anus and it should complement neonatal uroradiographic evaluation. The finding of detrusor-sphincter dyssynergia should alert the urologist to the need for adjunctive management. 
Central arteriovenous malformations of the maxillofacial skeleton: case report. Central arteriovenous malformation of the maxillofacial skeleton, though rare, is a well-documented entity. Past treatments have usually included some form of surgical intervention. Surgical resection as an attempt to cure has been effective but costly, ie, in relationship to patient morbidity and hospital expenditures. A case of vascular malformation is presented in which selective angiography and embolization as a primary treatment were used rather than ablative surgery. The patient tolerated the procedures well, with complete resolution of bleeding. 
Comparison of the results of electrophysiologic testing after short-term and long-term treatment with amiodarone in patients with ventricular tachycardia. The results of electrophysiologic testing after short-term and long-term treatment with amiodarone were compared in 71 patients with ventricular tachycardia. Electrophysiologic testing was performed in the baseline state after 11 +/- 3 days of treatment with 1.2 to 2.4 gm/day of amiodarone, and after 13 +/- 4 weeks of therapy with a daily amiodarone dose of 400 mg. After short-term therapy, 62% of the patients had an adequate response to amiodarone. In 27 patients who were hemodynamically unstable, ventricular tachycardia was induced and became noninducible or hemodynamically stable after combination therapy with a class I agent. Among 18 patients who did not have inducible ventricular tachycardia after short-term therapy, eight (44%) had inducible, hemodynamically unstable ventricular tachycardia after long-term treatment with amiodarone. On the other hand, six of the 27 patients who had hemodynamically unstable ventricular tachycardia after short-term therapy had an adequate response after long-term treatment with amiodarone. Therefore an adequate electrophysiologic response after short-term therapy does not guarantee a similar response after long-term treatment, and an inadequate response after short-term therapy does not always predict a similar response after long-term therapy. 
Stress analgesia: the opioid analgesia of long swims suppresses the non-opioid analgesia induced by short swims in mice. In mice, room temperature swimming for as short a period as 15 sec has been found to induce a non-opioid analgesia with a time course of 10-12 min. As the duration of the swim is increased, an opioid analgesia develops with a longer persistence (25-30 min); the development of the opioid analgesia appears to suppress the expression of the non-opioid analgesia so that none of the latter is evident after 3 min swims. The characteristics of the tail-flick nociceptive test are also described. 
Health inequalities among British civil servants: the Whitehall II study The Whitehall study of British civil servants begun in 1967, showed a steep inverse association between social class, as assessed by grade of employment, and mortality from a wide range of diseases. Between 1985 and 1988 we investigated the degree and causes of the social gradient in morbidity in a new cohort of 10,314 civil servants (6900 men, 3414 women) aged 35-55 (the Whitehall II study). Participants were asked to answer a self-administered questionnaire and attend a screening examination. In the 20 years separating the two studies there has been no diminution in social class difference in morbidity: we found an inverse association between employment grade and prevalence of angina, electrocardiogram evidence of ischaemia, and symptoms of chronic bronchitis. Self-perceived health status and symptoms were worse in subjects in lower status jobs. There were clear employment-grade differences in health-risk behaviours including smoking, diet, and exercise, in economic circumstances, in possible effects of early-life environment as reflected by height, in social circumstances at work (eg, monotonous work characterised by low control and low satisfaction), and in social supports. Healthy behaviours should be encouraged across the whole of society; more attention should be paid to the social environments, job design, and the consequences of income inequality. 
Magnesium sulfate reverses experimental delayed cerebral vasospasm after subarachnoid hemorrhage in rats. We induced experimental delayed cerebral vasospasm by the intracisternal injection of greater than 0.5 ml blood in 30 rats. Seventy-two hours later the basilar artery was exposed via the transclival approach and photographed at high-power magnification through an operating microscope. We then evaluated the effect of topical (n = 30) and intravenous (n = 20) magnesium sulfate on the spastic artery by computerized image analysis. A greater than 50% reduction in baseline diameter of the basilar artery was observed in the rats subjected to subarachnoid hemorrhage compared with the 10 controls (p less than 0.0001). Intravenous magnesium sulfate dilated the spastic artery to approximately 75% of the baseline diameter in control rats (p less than 0.0001). Topical magnesium sulfate caused dramatic dilation of the basilar artery in both the control and the subarachnoid hemorrhage groups to near 150% of the baseline diameter in the controls (p less than 0.001). All rats receiving intravenous magnesium sulfate reached therapeutic plasma levels of the ion. Hemodynamic effects were mild and immediately reversible upon cessation of magnesium sulfate administration. We suggest that magnesium has a role in the treatment of subarachnoid hemorrhage-induced vasospasm in humans. 
Comparison of the predictive characteristics of heart rate variability index and left ventricular ejection fraction for all-cause mortality, arrhythmic events and sudden death after acute myocardial infarction. Heart rate (HR) variability index and left ventricular ejection fraction (EF) were compared for the prediction of all-cause mortality, arrhythmic events and sudden death in 385 survivors of acute myocardial infarction. For arrhythmic events, where, for a sensitivity of 75%, HR variability index had a specificity of 76%, EF had a specificity of only 45%. An EF of less than or equal to 40% had a sensitivity of 42% and a specificity of 75% for arrhythmic events; for the same sensitivity an HR variability index of 20 U had a specificity of 92%. An EF less than or equal to 40% had a sensitivity of 40% and a specificity of 73% for sudden death; HR variability index had a specificity of 83% for the same sensitivity. For all cause mortality, where, for a sensitivity of 75%, HR variability index had a specificity of 52%, EF had a specificity of 40%. It is concluded that HR variability index appears a better predictor of important postinfarction arrhythmic complications than left ventricular EF, but both indexes perform equally well in predicting all-cause mortality. 
Iodine-125 seed implantation as an adjunct to surgery in advanced recurrent squamous cell cancer of the head and neck. Survival for extensive recurrent squamous cell carcinomas of the head and neck remains poor, with the major cause of death being local recurrence. Surgical implantation of iodine-125 interstitial seeds allows tumoricidal doses of radiation to be delivered to residual tumor while minimizing radiation doses to the surrounding tissues. From 1978 to 1988, 39 implantations were performed on 35 patients for extensive recurrent squamous cell carcinoma of the head and neck. The decision for implantation was based on positive margins or close to resection margins from frozen sections after salvage resection. The determinate 5-year disease-free survival was 41%, with both the overall and no evidence of disease 5-year survivals being 29%. Significant complications occurred in 36% of all cases. This figure increased to 56% when flap reconstruction was required. Possible reasons for this seemingly high complication rate are discussed. Considering the advanced nature of these recurrent carcinomas, surgical resection with iodine-125 seed implantation appears to be an effective method of managing disease that might otherwise be judged unresectable and treated for palliation only. 
Cycling and the older athlete. Cycling provides a dynamic form of aerobic and anaerobic fitness to more than 86 million Americans. It provides a freedom that is attractive to individuals of any age, either sex, and any body type. It does not require specialized experience or coordination. In the older athlete, injuries result primarily from overuse or abuse, and are most common in the upper extremity. Such injuries are most often compressive and inflammatory syndromes. These injuries are in marked contrast to those seen in the younger cyclist. Both groups have a low and similar incidence of accident. Overuse injuries can be treated effectively by altering training technique, correcting rider malposition, and decreasing excessive stress, in conjunction with appropriate medical management. Prevention of injury (particularly overuse) is the key to avoiding recurrence. Appropriate frame size, rider position, personalized training techniques, and clothing are essential in the older athlete in whom change is poorly tolerated. Fitness is preserved by regular cycling, possibly by the slowing of the degenerative process, while relieving mental stress and providing "fun sport.". 
The first epidemic of dengue hemorrhagic fever in the People's Republic of China. The first epidemic of dengue in China associated with significant severe and fatal hemorrhagic disease which met the World Health Organization case definition occurred on Hainan Island in 1985-1986. The epidemic began in Zhan County in September 1985, spread throughout the coastal areas, and ultimately involved 13 counties and cities of the island in 1986. The mosquito vector was Aedes aegypti. The morbidity associated with dengue infection on Hainan Island was 1,913 per 100,000 residents, with a case fatality rate of 0.25%. Severe disease was more prevalent in the 10-29-year-old age group. Principal clinical features in laboratory-confirmed cases were fever, osteoarthralgia, hemorrhage and/or shock, and thrombocytopenia. Complications such as acute intravascular hemolysis, diffuse intravascular coagulation, hemoconcentration, pleural effusion, altered mentality, and pneumonia were also observed. One hundred twenty-five isolates of dengue 2 virus were recovered from acute-phase serum samples from 278 patients, and 5 strains of this same virus serotype were isolated from 5 pools of adult Ae. aegypti. 
Neglected topics in the treatment of chronic pain patients--relapse, noncompliance, and adherence enhancement. Although published treatment outcome studies for chronic pain have provided favorable support for the efficacy of many pain clinics and the use of specific modalities such as biofeedback and relaxation, there are several factors that mitigate against euphoria. Two related factors that influence interpretation of these reported outcomes are discussed, namely, noncompliance with therapeutic recommendations during treatment and subsequent to treatment termination, and relapse. Conceptual and methodological problems for establishing the prevalence of noncompliance and relapse are reviewed. Several factors that contribute to noncompliance (individual differences, nature of disease or injury, characteristics of the prescribed treatment regimen, health-care provider-patient relationship, and contextual) are discussed. The literature reveals that noncompliance with treatment regimens is quite prevalent across diverse treatment modalities and pain syndromes. The incidence of relapse following initially successful treatment of persistent pain also appears to be high, ranging from 30% to 60%. Studies on arthritis and heterogeneous pain clinic populations suggest that noncompliance and relapse are related; however, this association is less well established for headache patients. Strategies for assessing compliance (i.e., self-report, behavioral, biochemical, and clinical outcome) and the perspectives' of patients and health-care providers on the application of self-care recommendations are discussed. Strategic planning and adherence enhancement tactics to facilitate maintenance of post-treatment gains are described. 
Ocular findings in Turcot syndrome (glioma-polyposis). Turcot syndrome is a hereditary condition characterized by multiple, adenomatous gastrointestinal polyps associated with neuroepithelial tumors of the central nervous system. The authors examined a patient with Turcot syndrome who had multiple regions of congenital hypertrophy of the retinal pigment epithelium (CHRPE) with areas of surrounding hypopigmentation in the fundi of both eyes. Multiple, bilateral patches of CHRPE have been reported in patients with familial adenomatous polyposis and Gardner syndrome. This finding is thought to be a sensitive and specific clinical marker for these conditions and useful for predicting the presence and development of colorectal polyposis. Our findings provide further evidence that familial adenomatous polyposis, Gardner syndrome, and Turcot syndrome may be related conditions representing the variable phenotypic expression of a single, autosomal dominant genetic disorder. Children and young adults with multiple patches of CHRPE and a family history of adenomatous polyposis may be at increased risk for the development of central nervous system tumors as well as gastrointestinal polyps. 
High risk of squamous cell carcinoma of the cervix for women with HLA-DQw3. Many immune responses are controlled by genes of the major histocompatibility complex (MHC). In man these include the loci encoding the HLA-A, -B, -C, -DR, -DQ and -DP antigens, and many diseases have been linked with these. But attempts to identify HLA genes in man that might explain why an immune response against malignant tumours should be ineffective have so far been disappointing, apart from the association reported between the HLA-DR1 antigen and a susceptibility to a rare carcinoma of the thyroid gland. Here we describe another strong connection between a common malignant tumour and an HLA antigen, namely between HLA-DQw3 and squamous cell carcinoma of the cervix: from the 1988 United States tumour registry, 1 in every 63 newborn girls will develop this invasive cancer. We found that 88% of 66 patients had the leukocyte antigen HLA-DQw3 when it would normally be expected in only 50% of individuals. In animals the immune system and the MHC act in defence against virally induced tumours, but until now there has been no evidence that they do so in humans: as squamous cell carcinoma is probably virally induced, our discovery of its association with an HLA antigen will be important to the understanding of the immunogenetic basis of a susceptibility to this tumour. 
Aerosol pentamidine for secondary prophylaxis of AIDS-related Pneumocystis carinii pneumonia. A randomized, placebo-controlled study. OBJECTIVE: To assess the safety and efficacy of aerosol pentamidine for secondary prophylaxis of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome (AIDS). PARTICIPANTS: Patients recovering from a first confirmed episode of AIDS-related P. carinii pneumonia who had no evidence of either another active AIDS-defining opportunistic infection or another pulmonary abnormality were considered eligible for the study but were included only if they had received no immunomodulators or antiretroviral agents other than zidovudine within 30 days of entry. One hundred sixty-two patients were randomized and started on the study drug. INTERVENTION: Patients were randomly assigned to receive aerosol pentamidine, 60 mg per dose, or placebo, delivered using a hand-held, patient-triggered, ultrasonic nebulizer. The induction phase of treatment consisted of 5 doses over 14 days, followed by a maintenance phase beginning on day 21 and consisting of one dose every 2 weeks. RESULTS: Thirty-two cases of P. carinii pneumonia were diagnosed before the termination of the trial; 27 cases occurred among 78 patients receiving placebo and 5 occurred among 84 patients receiving aerosol pentamidine. Estimates of the cumulative relapse rate of P. carinii pneumonia by 24 weeks were 50% and 9% for the placebo and pentamidine groups, respectively (P less than 0.001). Adverse reactions attributed to the study drug occurred in 15 of 78 patients receiving placebo and in 28 of 84 patients receiving pentamidine (P = 0.04). These were all mild or moderate in severity and did not preclude continued administration of the study drug. CONCLUSION: Intermittent therapy with aerosol pentamidine is highly effective and well tolerated as secondary prophylaxis for AIDS-related P. carinii pneumonia. 
CT of the gastrointestinal tract: principles and interpretation. The experience accumulated in daily abdominal CT scanning and CT evaluation of gastrointestinal lesions has generated helpful technical guidelines and some reliable principles of interpretation. These general principles are briefly discussed in this review, and the importance of performing a CT examination that is adequate for the detection and evaluation of gastrointestinal lesions is stressed. CT features useful in differentiating benign from malignant lesions, limitations and pitfalls in CT interpretation, overlap in the CT appearance, and classical CT features leading to specific diagnoses are described and illustrated. Although CT is established as one of the most important techniques for imaging the gastrointestinal tract, it should be used selectively and only in the context of appropriate clinical and conventional radiologic examination. CT should not be regarded as competing with, but as complementing, barium examination of the gastrointestinal tract. 
Impairment of left ventricular function during coronary angioplastic occlusion evaluated with a nonimaging scintillation probe. Impairment of left ventricular function during controlled myocardial ischemia induced by coronary angioplasty has been reported from angiographic and echocardiographic studies. Ejection fraction, peak ejection, peak filling rates, and end-systolic and end-diastolic volumes were investigated before, during and after coronary occlusion on-line with a nonimaging scintillation probe. The study consisted of 18 patients (mean age 59 +/- 10 years) with coronary artery stenosis of greater than 70%. During balloon inflation of 60 seconds' duration, coronary occlusion pressure was 31.6 +/- 12 mm Hg. There was no significant change in heart rate. Delay between first and second dilatation was 109 +/- 63 seconds. Ejection fraction decreased from 53 +/- 16 to 40 +/- 12% (first dilatation, p less than 0.01) and to 39 +/- 14% (second dilatation, p less than 0.01) and recovered to 51 +/- 16% 5 minutes after the second dilatation. Peak ejection rate was significantly reduced during the first and second balloon inflations. Peak filling rate decreased from 2.5 +/- 0.8 to 2.0 +/- 0.7 end-diastolic volume.s-1 (first dilatation, p less than 0.01) and to 1.8 +/- 0.7 end-diastolic volume.s-1 (second dilatation, p less than 0.01) and remained reduced at 2.2 +/- 0.7 end-diastolic volume.s-1 (p = not significant) at 5 minutes after the second dilatation. End-systolic and end-diastolic volumes increased significantly during the first and second dilatations and returned to normal after dilatation. It is concluded that short, controlled myocardial ischemia during coronary angioplasty leads to a decrease in systolic and diastolic left ventricular function. Sequential dilatations do not further decrease function if a sufficient interval is kept. 
Severe hypertension with segmental renal infarction following surgical removal of a retroperitoneal malignant hemangiopericytoma: a case report. Severe hypertension developed in a fifty-five year-old woman after surgical removal of a retroperitoneal tumor, when the renal artery was injured. Renal arteriography after the surgery demonstrated a segmental infarction of the right kidney. A close relationship between activation of the renin-angiotensin system and the development of severe hypertension was observed. Satisfactory control of blood pressure concomitant with reduction of plasma renin activity was achieved by a combination of an angiotensin-converting anzyme inhibitor, beta-blocking agent, and calcium-entry blocker. The mechanism of activation of the renin-angiotensin system in renal infarction is discussed. 
Delayed time to peak serum myoglobin level as an indicator of cardiac dysfunction following open heart surgery. Postoperative changes in serum myoglobin levels have been studied in 47 patients undergoing open heart surgery. The patients were retrospectively divided into two groups according to the time to peak myoglobin level during reperfusion. In 38 patients, myoglobin levels increased rapidly to a peak within 3 hours after reperfusion, after which it was cleared from the blood (group 1). Contrarily, a rise in myoglobin levels was persistent for 24 hours and its time to peak was greater than 3 hours after reperfusion in nine patients (group 2). There were no differences in preoperative and early reperfusion (within 1 hour of reperfusion) values of myoglobin between the two groups. At 3, 6, and 12 hours of reperfusion, myoglobin levels were significantly greater in group 2: 448 +/- 196 vs 1,149 +/- 900 ng/ml, 359 +/- 172 vs 2,653 +/- 3,179 ng/ml, 184 +/- 95 vs 1,896 +/- 1,387 ng/ml, respectively, p less than 0.0001 in each. The maximum activities of both myoglobin and CK-MB were significantly higher in group 2 (myoglobin-max: 771 +/- 257 vs 3,221 +/- 3,024 ng/ml, p less than 0.0001; CK-MBmax: 107 +/- 60 vs 227 +/- 219 IU/L, p less than 0.005). Five of nine patients in group 2 required post-operative assistance with intra-aortic balloon pumping (p less than 0.0005 compared with one of 38 in group 1) and perioperative myocardial infarction developed in three patients (33.3 percent) in this group (p less than 0.005 compared with 0 percent in group 1). Thus, patients with a delayed peak of serum myoglobin level exhibited detrimental cardiac failure postoperatively. These findings suggest that myocardial injury accelerated by reperfusion following ischemia might progress in these patients. 
Prior poliomyelitis-reduced capillary supply and metabolic enzyme content in hypertrophic slow-twitch (type I) muscle fibres. Capillary supply and oxidative and glycolytic enzyme activities were determined in muscle biopsies from the tibialis anterior muscle in six prior polio patients and a control group. The polio patients, who had paresis and atrophy, but were able to walk normally by making maximal use of all remaining anterior tibial motor units, showed type I (slow-twitch) muscle fibre predominance with a mean (SD) of 98 (2%) type I fibres versus 81 (8)% in the controls (p less than 0.01) and muscle fibre hypertrophy, the average type I fibre cross-sectional area being 108% (p less than 0.005) larger than in the controls. The number of capillaries per muscle fibre was not significantly different from that in the control group, but with the increased muscle fibre area in the polio patients, the capillary density was significantly lower. The number of capillaries in contact with type I fibres relative to fibre area was 40% lower in the patients than in the controls (p less than 0.005). The levels of citrate synthase and phosphofructokinase were significantly lower (38% and 33%, respectively, p less than 0.05) in the patients than in the controls, indicating decreased oxidative and glycolytic potentials in the muscle fibres of the polio patients. It is proposed that the abnormal high-frequency activation of all remaining motor units during each step cycle recorded in these patients constitutes a stimulus for type I muscle fibre predominance and hypertrophy but that the overall low muscle usage results in a decreased stimulation of capillary proliferation and mitochondrial enzyme synthesis. 
Increased circulating levels of bromocriptine after vaginal compared with oral administration. OBJECTIVE: To compare the circulating levels of bromocriptine after oral and vaginal administration of the drug. DESIGN: Experimental PARTICIPANTS: Seven ovulatory female volunteers and one hyperprolactinemic patient. INTERVENTIONS: Ovulatory volunteers were randomized to receive either oral or vaginal bromocriptine (2.5 mg). In a second session, the subjects were crossed-over to bromocriptine by the alternate route. An additional hyperprolactinemic patient received vaginal bromocriptine only. MAIN OUTCOME MEASURE: Serum bromocriptine and prolactin (PRL) levels were measured hourly for 12 hours in the normal volunteers and for 10 hours in the hyperprolactinemic patient. RESULTS: Circulating bromocriptine levels were significantly higher after vaginal bromocriptine after the 7th hour (P less than 0.05). The reduction in serum PRL was significantly greater after oral administration between 2 and 6 hours. CONCLUSIONS: Vaginally administered bromocriptine may result in a reduction in the overall dose required, thereby improving compliance without compromising therapeutic efficacy. 
Left neglect for near but not far space in man. It has been suggested that, among the many visual areas of the human brain, there might be one set of spatial maps specialized for 'near' (peripersonal) and another for 'far' (extrapersonal) space. A distinction between 'grasping distance' and 'walking distance', or between a 'reaching field' and a pointing or throwing field has commonly been made. Evidence for such a division has been found in monkeys. Unilateral ablation of the frontal eye field (area 8) produces a more prominent inattention (or 'neglect') for objects in contralesional far space than in near space; by contrast, unilateral ablation of frontal area 6, which receives direct projections from area 7b (the rostral part of the inferior parietal lobules) results in inattention to visual stimuli limited to contralesional near space. Despite predictions that comparable dissociations should be found in man, there has been no convincing evidence. We report here such evidence in a patient with a unilateral right hemisphere stroke. Within peripersonal space, he showed severe left visuo-spatial neglect on conventional tests, including the highly sensitive task of line bisection. When line bisection was performed in extrapersonal space, neglect was abolished or attenuated. 
Perinatal outcome of fetal complete atrioventricular block: a multicenter experience. The clinical course and outcome of 55 fetuses with complete atrioventricular (AV) block detected prenatally were studied to identify factors that affect the natural history of this lesion. In 29 fetuses (53%) complete AV block was associated with complex structural heart defects, usually left atrial isomerism (n = 17) or discordant AV connection (n = 7). The other 26 fetuses had normal cardiac anatomy; in 19 cases the mother had connective tissue disease or tested positive for antinuclear antibodies. Six fetuses showed progression from sinus rhythm or second degree block to complete AV block. Of the 55 pregnancies, 5 were terminated and 24 fetuses or neonates died; at the end of the neonatal period 26 fetuses were still alive. Fetal or neonatal death correlated significantly with the presence of structural heart defects (4 of 29 surviving, p less than 0.001), hydrops (0 of 22 surviving, p less than 0.001), an atrial rate less than or equal to 120 beats/min (1 of 12 surviving, p less than 0.005) or a ventricular rate less than or equal to 55 beats/min (3 of 21 surviving, p less than 0.001). Mean atrial and ventricular rates were higher in surviving than in nonsurviving fetuses (142 +/- 8 vs. 127 +/- 21 beats/min, p less than 0.002; 64 +/- 8 vs. 52 +/- 8 beats/min, p less than 0.001, respectively). A slow atrial rate, however, was frequently associated with left atrial isomerism. 
Intrapericardial OK-432 instillation for the management of malignant pericardial effusion. Ten patients with malignant pericardial effusion were treated with intrapericardial injection of OK-432 (penicillin-treated and heat-treated lyophilized powder of the substrain of Streptococcus pyogenes A3). After intrapericardial insertion of a catheter, a maximal volume of pericardial fluid was withdrawn with cytologic confirmation of malignancy. Five or 10 Klinische Einheit (KE) (KE is a unit used to express the strength of a preparation) of OK-432 diluted in 20 ml of saline was injected into the pericardial space in seven and three patients, respectively. It was repeated in case of reaccumulation. Seven patients were treated only once and the remaining three required a second treatment. Complete control of pericardial effusion was achieved in all patients for an average of 329 days (range, 54 to 790 days). Fever and chest pain were experienced in six and five patients, respectively, but were controlled with antipyretics. Two of three patients who received 10 KE of OK-432 experienced hypotension that was successfully controlled with vasopressor drugs with or without reaspiration of pericardial fluid. Rapid reactive reaccumulation of the pericardial fluid was thought to be a cause of hypotension. A follow-up computed tomography (CT) scan was performed in seven patients and a thickened pericardium was noticed in five; no patients had constrictive pericarditis. These results suggest that intrapericardial administration of 5 KE of OK-432 is an effective and safe treatment for malignant pericardial effusion. 
Digitally-directed transrectal biopsy using Biopty gun versus transrectal needle aspiration: comparison of diagnostic yield and comfort. A technique for digitally-directed core biopsy using the Biopty device and prospective comparison of accuracy and comfort, using this technique simultaneously with transrectal needle aspiration, are presented. To better estimate the true prevalence of carcinoma in the study population, a repeat combined procedure was performed on all subjects who did not have carcinoma confirmed on the initial core biopsies. All procedures were done by one investigator and all pathology reviewed by one senior pathologist. A total of 180 combined procedures were performed on 100 consecutive patients with palpably abnormal prostates; 30 carcinomas were detected. Digitally-directed Biopty biopsy yielded a sensitivity rate of 87 percent compared with 57 percent for needle aspiration (p less than 0.05). Using a numerical comfort scale, the Biopty device was also rated less painful than needle aspiration (p = 0.0001). The morbidity of the combined procedure was minimal, with a minor complication rate of 2.2 percent. No infections occurred. 
Epidemiologic correlates of sporadic amyotrophic lateral sclerosis. We evaluated 74 selected patients with amyotrophic lateral sclerosis (ALS) and 201 matched controls for risk factors for ALS by a case-control design and a sequential questionnaire/interview technique to quantitate biographic data. We analyzed occupational and recreational data only for 47 male patients and 47 corresponding patient controls; data for women were insufficient. We used nonparametric analyses to evaluate five primary comparisons of ALS patients with controls: (1) more hard physical labor, p not significant (NS); (2) greater frequency of neurodegenerative disease in family members, p NS; (3) greater exposure to lead, p less than 0.05; (4) more years lived in a rural community, p NS; and (5) more trauma or major surgery, p NS. Men with ALS had worked more frequently at blue-collar jobs (although not a statistically significant difference, p = 0.10) and at welding or soldering (p less than 0.01). These results suggest that there may be an association between ALS in men and exposure to lead vapor. The limited nature of the association favors a multifactorial etiologic mechanism of ALS. 
Proportionate mortality trends: 1950 through 1986 Mortality trends in the United States from 1950 through 1986 were analyzed for the conditions that are or have recently been among the six leading causes of death. The age-adjusted mortality rate for all causes has decreased from 841.5 to 541.7 per 100,000 population. Cause-specific, age-adjusted mortality rates have declined from 1950 through 1986 for cerebrovascular disease, injuries, perinatal conditions, heart disease, and influenza and pneumonia. Time trends in the proportion of persons dying of each of these diseases, however, have varied; the proportion dying of cerebrovascular disease, injuries, and perinatal conditions has decreased, and the proportion of persons dying of heart disease and influenza and pneumonia has remained fairly stable from 1950 through 1986. During this same time, age-adjusted death rates have increased for chronic obstructive pulmonary disease and have remained fairly stable for malignant neoplasms, while the proportions of persons dying of chronic obstructive pulmonary disease and malignant neoplasms have increased dramatically. For people aged 35 to 64 years, malignant neoplasms have now overtaken heart disease as the leading cause of death. For those aged 65 years and older, heart disease remains the leading cause of death, accounting for almost 50% of all deaths in persons 85 years and older. 
Delayed time to peak serum myoglobin level as an indicator of cardiac dysfunction following open heart surgery. Postoperative changes in serum myoglobin levels have been studied in 47 patients undergoing open heart surgery. The patients were retrospectively divided into two groups according to the time to peak myoglobin level during reperfusion. In 38 patients, myoglobin levels increased rapidly to a peak within 3 hours after reperfusion, after which it was cleared from the blood (group 1). Contrarily, a rise in myoglobin levels was persistent for 24 hours and its time to peak was greater than 3 hours after reperfusion in nine patients (group 2). There were no differences in preoperative and early reperfusion (within 1 hour of reperfusion) values of myoglobin between the two groups. At 3, 6, and 12 hours of reperfusion, myoglobin levels were significantly greater in group 2: 448 +/- 196 vs 1,149 +/- 900 ng/ml, 359 +/- 172 vs 2,653 +/- 3,179 ng/ml, 184 +/- 95 vs 1,896 +/- 1,387 ng/ml, respectively, p less than 0.0001 in each. The maximum activities of both myoglobin and CK-MB were significantly higher in group 2 (myoglobin-max: 771 +/- 257 vs 3,221 +/- 3,024 ng/ml, p less than 0.0001; CK-MBmax: 107 +/- 60 vs 227 +/- 219 IU/L, p less than 0.005). Five of nine patients in group 2 required post-operative assistance with intra-aortic balloon pumping (p less than 0.0005 compared with one of 38 in group 1) and perioperative myocardial infarction developed in three patients (33.3 percent) in this group (p less than 0.005 compared with 0 percent in group 1). Thus, patients with a delayed peak of serum myoglobin level exhibited detrimental cardiac failure postoperatively. These findings suggest that myocardial injury accelerated by reperfusion following ischemia might progress in these patients. 
Altered corticospinal projections to lower limb motoneurons in subjects with cerebral palsy. The projections of cortical neurons activated by transcranial magnetic stimulation to the motoneurons of lower limb muscles were examined in 22 normal subjects and 14 subjects with cerebral palsy (CP). In normal subjects, magnetic stimulation produced strong facilitation of tibialis anterior (TA) motoneurons, but little or no facilitation of soleus (SOL) motoneurons. This differential facilitation of TA and SOL motoneurons was observed at all stimulus sites on the scalp and all stimulus intensities at which responses could be elicited. In subjects with CP, magnetic stimulation produced almost equal facilitation of TA and SOL motoneurons. This could not be explained by differences in the excitability of the respective motoneuron pools. It is postulated that the projections from the motor cortex to spinal motoneurons are altered in CP. These abnormal projections may contribute to the impairment of voluntary movements experienced by these subjects. 
HLA-DR antigen expression on peripheral blood monocytes correlates with surgical infection. Monocyte human leukocyte antigen-DR (HLA-DR) expression has correlated closely with clinical outcome in severely injured patients at high risk for infection. Monocytes from 77 asymptomatic volunteers expressed HLA-DR antigen with minimal variability in respect to age, gender, race, time of day or year, or serum alcohol level. Patients who developed infection after elective laparotomy had a significantly lower mean percentage of monocytes expressing HLA-DR antigen and a lower mean fluorescent intensity than uninfected patients (p less than 0.05). Severely infected nonsurgical patients had significantly lower values than normal volunteers (p less than 0.01), and the mean fluorescent intensity of those who died from infection was significantly lower than that of those who survived (p less than 0.05). Patients on immunosuppressive regimens after renal transplantation had levels of HLA-DR expression similar to those of the volunteers. Monocyte HLA-DR expression was found to be a reliable marker of clinical infection and showed remarkable reproducibility within the normal uninfected study population. 
The natural history of multiple endocrine neoplasia type 1. Highly uncommon or highly unrecognized? Among 2000 descendants of an English immigrant to Tasmania, Australia, the diagnosis of multiple endocrine neoplasia type 1 was found to be very highly probable or highly probable in 130 and moderately probable in 22. Another 242 children and siblings were 50% likely to have inherited this dominant gene. In all age groups, especially the elderly, the majority of affected members had symptoms of only one endocrine disorder or were asymptomatic. In teenagers, the most common presentation was pituitary lesions and the second most common presentation was insulinomas. Frequently, pituitary lesions or insulinomas developed before any parathyroid lesions could be detected. Elevation of gastrin levels, usually associated with hypercalcemia, was rarely seen in patients younger than 25 years. The classic presentation with symptoms of multiple endocrinopathy may represent only a small fraction of these patients in the community. 
Identification of perilymph proteins by two-dimensional gel electrophoresis. Perilymph has a total protein component that is quantitatively distinct from serum and cerebrospinal fluid (CSF). The goal of this research was to determine if perilymph contains any qualitatively unique protein constituents that will distinguish it from serum or CSF. To test this hypothesis, matched sets of perilymph, serum, and CSF were obtained from 18 guinea pigs and seven human subjects. The purity of each sample was assured by measurement of the protein concentration of each sample and comparison of this parameter to known normal values for perilymph, serum, and CSF. Each sample was then subjected to two-dimensional gel electrophoresis, separating proteins by isoelectric point in the horizontal dimension and by relative molecular weight in the vertical dimension. All gels were processed under precisely identical physical conditions by use of a diamine silver stain. A small number of perilymph proteins not found in plasma were identified in both the guinea pig and the human specimens. The finding of unique perilymph proteins may permit the development of a sensitive marker that will aid in the diagnosis of perilymph fistula. 
Association of supraglottic and gingival idiopathic plasmacytosis. Three cases of gingival plasmacytosis in which laryngeal symptoms eventually developed are reported. Two of the three patients underwent endoscopic biopsy of supraglottic lesions, which proved to be similar to those in the oral cavity. The third patient had supraglottic erythema only and was not subjected to biopsy. Known etiologic factors associated with plasma cell gingivitis were excluded. Treatment with oral and topical steroids resulted in good control of the lesions. 
Prognostic significance of acute epilepsia partialis continua. We present 3 patients in whom epilepsia partialis continua was the presenting sign of an acute, rapidly evolving and catastrophic neurologic illness. Initial seizures were partial simple (i.e., eye deviation in one, finger twitching in one) which progressed to multifocal partial seizures. The course of the epilepsia partialis continua was 36-41 days. Prognosis was uniformly poor (i.e., death in 2, vegetative state in 1); therefore, epilepsia partialis continua in the context of an acute neurologic illness may herald a grim outcome. 
Effects of electrophysiologic testing of the automatic implantable cardioverter-defibrillator on left ventricular systolic function and diastolic filling. We investigated the effects of electrophysiologic testing of the automatic implantable cardioverter-defibrillator (AICD) on left ventricular systolic function and diastolic filling in 12 patients. Ventricular tachycardia or ventricular fibrillation was induced by programmed electrical stimulation and alternating-current, respectively. Patients were studied before and immediately after, 10 minutes after, and 1 hour after defibrillation by the AICD using M-mode, two-dimensional, and pulsed Doppler echocardiography. Immediately after defibrillation, increases were found in the peak early filling velocity (70 +/- 10 cm/sec to 84 +/- 24 cm/sec, p less than 0.01), peak early-to-atrial filling velocity ratio (1.05 +/- 0.21 to 1.29 +/- 0.26, p less than 0.005), and maximum rate of diastolic chamber enlargement (82 +/- 26 mm/sec to 102 +/- 44 mm/sec, p less than 0.05). These changes were not evident at 10 minutes and 1 hour. Cardiac output and ejection fraction were unchanged after defibrillation. Heart rate and diastolic filling time were unchanged. We conclude that electrophysiologic testing of the AICD does not impair left ventricular function in the immediate to 1-hour period after defibrillation. Left ventricular systolic function is unchanged and diastolic filling is enhanced. 
Association between plasma viscosity and blood pressure. Results from the MONICA-project Augsburg. The relationship between determinants of blood viscosity and blood pressure (BP) variables was studied in a large sample of a population aged 25 to 64 years. Plasma viscosity, hemoglobin, and total serum protein were examined. Systolic and diastolic BP and the prevalence of hypertension showed a crude positive association with plasma viscosity levels in both sexes. Age, body mass index, and total serum protein appeared to have a confounding effect on this relationship, whereas hemoglobin, smoking behavior, and alcohol consumption did not. A crude positive association was also found between total serum protein levels and the prevalence of hypertension in men and women; however, since total serum protein was treated as a covariable, no further analyses were carried out. In contrast to findings reported in the literature, hemoglobin levels were not correlated with BP variables in either sex. After adjusting for all confounders, a significant main effect of plasma viscosity still was found. However, the magnitude of the effect was not as large as for body mass index, a well-established risk variable for hypertension. These results indicate that BP is positively associated with plasma viscosity. Whether increased plasma viscosity in hypertension constitutes a primary or a secondary phenomenon remains to be answered. Since plasma viscosity is significantly associated with hypertension but any BP variable, increased levels of plasma proteins (particularly fibrinogen as the main determinant of plasma viscosity) may represent the cause for elevated plasma viscosity. This might contribute to persistently increased resistance to blood flow on the microcirculatory level in arterial hypertension. 
Fibroblast stimulation in schistosomiasis. XI. Purification to apparent homogeneity of fibroblast-stimulating factor-1, an acidic heparin-binding growth factor produced by schistosomal egg granulomas. Liver fibrosis is the most serious complication of infection with Schistosoma mansoni and Schistosoma japonicum and is responsible for severe morbidity and mortality in hundreds of thousands of patients in many Third World nations. The pathogenesis of this condition remains to be elucidated. We proposed that certain cytokines produced by cells that comprise the chronic granulomas that surround the helminth eggs within the liver initiate hepatic fibrogenesis. We now report our successful purification to apparent homogeneity of the egg granuloma-derived fibroblast mitogen. The high affinity of this factor for heparin (elutes from heparin-Sepharose with 1.5 M NaCl) facilitates its purification by a two-step procedure, and identifies the cytokine as a heparin-binding growth factor (HBGF). Furthermore, because it has an isoelectric point approximately equal to 6.2, it has one of the characteristics of a class 1 (acidic) HBGF. We immunized rabbits with the purified factor and observed that the resulting antibodies (IgG) detected the factor but not acidic fibroblast growth factor (the prototypic class 1 HBGF) either by dot-blot ELISA or neutralization of biologic activity. The granuloma product and fibroblast growth factor also differ in target-cell specificity and amino acid composition. On the basis of these distinctions, we have designated the granuloma-derived mitogen fibroblast-stimulating factor-1. With the availability of purified fibroblast-stimulating factor-1 and the future analysis of its amino acid sequence, its structural relationship to other mesenchymal growth factors can be determined. 
Mixed venous oxygen saturation as a guide to tissue oxygenation and prognosis in patients with acute myocardial infarction. The relation of mixed venous oxygen saturation and the cardiac index to tissue oxygenation and prognosis was investigated in 119 patients with acute myocardial infarction. There was a positive correlation between mixed venous oxygen saturation and the cardiac index in 97 survivors and 22 nonsurvivors, but a significantly lower mixed venous oxygen saturation level at the same level of cardiac index was observed in nonsurvivors compared with survivors. Results of multivariate analysis with mixed venous oxygen saturation and the cardiac index indicated that only mixed venous oxygen saturation was significantly related to survival and to hyperlactacidemia. Oxygen delivery to tissues declined significantly in nonsurvivors because of a lower cardiac index and a lower hemoglobin concentration in these patients than in survivors. However, at the same level of oxygen delivery to tissues, nonsurvivors had a significantly higher rate of oxygen consumption leading to a correspondingly greater decrease in mixed venous oxygen saturation, suggesting that a greater increase in oxygen demand was also observed in nonsurvivors than in survivors. Thus mixed venous oxygen saturation after acute myocardial infarction is a better predictor of hyperlactacidemia and survival than the cardiac index, and this may be associated with an increased oxygen demand and an impaired oxygen transport system in seriously ill patients. 
Isolated muscle hypertrophy as a sign of radicular or peripheral nerve injury. Two patients with isolated neurogenic hypertrophy of the trapezius muscle due to accessory nerve injury and a patient with neurogenic hypertrophy of the anterior tibial muscle due to chronic radicular lesion L4 are described. Electromyography of the affected muscles showed dense continuing spontaneous discharges of complex potentials. Muscle biopsy performed in two patients showed abundant hypertrophic muscle fibres, identified in one case by ATP-ase reaction as being of predominantly type I. In the majority of previously reported patients with neurogenic muscle hypertrophy confined to the calf muscle, a passive stretch mechanism was suggested as a cause of the hypertrophy. It is assumed that the excessive spontaneous muscle activity gave rise to the hypertrophy in these patients. This may also be true in previously reported patients with neurogenic hypertrophy and similar spontaneous activity in electromyography. 
Heterotopic ossification and peripheral nerve entrapment: early diagnosis and excision. Heterotopic ossification can occur in neurologic disorders, burns, musculoskeletal trauma, and metabolic disorders. In addition to producing the complications of contracture, skin breakdown, and pain, it can cause peripheral nerve entrapment. Nerve entrapment due to heterotopic ossification may be misdiagnosed, and it is difficult to evaluate and treat without recurrence. Computed tomography is especially useful in localization before surgical release of the entrapped nerve. Resection of heterotopic ossification can be successful using disodium etidronate to decrease the risk of recurrence, and resection can improve range of motion and nerve function. Two case studies of nerve entrapment due to heterotopic ossification are presented with the results of computed tomography localization, successful resection, and long-term follow-up. Clinicians should be aware of this complication and the potential for rapid nerve injury. If heterotopic ossification is causing clinically significant peripheral nerve entrapment, early surgical treatment may be indicated, and may be successful. 
Primary fibromyalgia and the irritable bowel syndrome: different expressions of a common pathogenetic process. Primary fibromyalgia (PFM) and the irritable bowel syndrome (IBS) are both common conditions which account for 30% or more of referrals to rheumatology and gastroenterology clinics. An association between symptoms in PFM and IBS has been suggested but the frequency with which they coexist has not been assessed. The aim of this study was to examine the prevalence of each condition in groups of patients with PFM and IBS compared to normal and disease control populations. We studied four patient groups, 20 patients in each group, with PFM, IBS, inflammatory arthritis, inflammatory bowel disease and also 20 normal controls. Using strict diagnostic criteria, each group was assessed by two investigators for symptoms and signs of PFM and IBS. Sigmoidoscopy was performed when indicated. Results indicate that 70% (14/20) of the PFM patients had IBS and 65% (13/20) of the IBS patients had PFM. This compared with the control groups where 12% (7/60) and 10% (6/60) had PFM and IBS respectively. In conclusion, these results indicate that PFM and IBS frequently coexist. A common pathogenetic mechanism for both conditions is therefore suggested. 
Effects of sympathectomy in a model of causalgiform pain produced by partial sciatic nerve injury in rats. In a previous report we presented a novel behavioral model of neuropathic pain disorders, produced in rat by a unilateral ligation of about half of the sciatic nerve. The model is characterized by rapid onset of behaviors suggesting spontaneous pain and disordered responses to non-noxious and noxious stimuli. These include reduced withdrawal thresholds to repetitive touch in the partially deafferented skin ('touched-evoked hyperesthesia'), touch-evoked allodynia, reduced withdrawal thresholds to noxious thermal stimuli and exaggerated responses to noxious heat and mechanical stimuli ('thermal hyperalgesia'). Some of these disorders are seen at mirror image sites on the hind limb opposite the lesion. These disorder start within hours after partial nerve injury, last many months and are very similar to causalgia in humans following partial nerve injury. Since sympathetic efferent activity is known to aggravate causalgia in humans and sympathectomy is known to relieve it, we studied the effect of changing sympathetic outflow in the rat model. Reversible sympathectomy was carried out using guanethidine injected intraperitoneally in 3 experiments, each at a different time in relation to the partial nerve injury. We found that: (1) sympathectomy performed several months postoperatively alleviated the sensory disorders bilaterally; (2) sympathectomy prior to nerve injury partially prevented the appearance of thermal hyperalgesia but did not affect hyperesthesia to repetitive touch; and (3) sympathectomy at the time of nerve injury aggravated the sensory disorders during the first few days. As maintenance and production of the sensory disorders in this animal model depended on sympathetic nervous outflow, we conclude that the rats were suffering from a syndrome analogous to sympathetically maintained causalgia in man. 
Gastric antral vascular ectasia associated with gastric carcinoma. Gastric antral vascular ectasia (GAVE), or watermelon stomach, is an uncommon cause of chronic gastrointestinal blood loss and iron deficiency anemia. Although GAVE has not previously been reported in association with gastric cancer, it is often associated with atrophic gastritis and pernicious anemia, which are known risk factors for gastric malignancy. We report a 72-yr-old woman with pernicious anemia who was found to have GAVE associated with adenosquamous carcinoma of the gastric cardia and adenocarcinoma in situ of the pylorus. In view of recent reports of the use of endoscopic modalities rather than surgical resection to treat GAVE, our case alerts endoscopists to the possibility of coexisting carcinoma. 
Life-threatening cervico-mediastinal haematoma after carotid sinus massage. Retropharyngeal and cervico-mediastinal haematomas are rare but potentially fatal entities. The potential for airway compression necessitates rapid assessment and treatment. A cervico-mediastinal haematoma following carotid sinus massage which required cervical drainage is presented. This is a life-threatening event demanding a high index of suspicion. A review of the literature and indications for treatment are discussed. 
Ultrasound diagnosis of an obstructive cardiac rhabdomyoma with severe hydrops and hypoplastic lungs. A case report. Cardiac rhabdomyomas of the fetus and neonate are benign cardiac muscle hamartomas with an incidence of 0.027% in pediatric autopsies. This is the third reported case of prenatally diagnosed cardiac rhabdomyoma, the second with severe hydrops and the only one associated with aortic valve hypoplasia and hypoplastic lungs. 
Nausea and vomiting with use of a patient-controlled analgesia system. The incidence of nausea and vomiting following patient controlled analgesia and intramuscular morphine injections on demand was compared in a double-blind randomised study of 32 healthy patients undergoing elective cholecystectomy. There were no significant differences between the two groups in mean 24 hour postoperative morphine consumption, subjective experience of pain, nausea and sedation assessed by visual linear analogue scoring, and the postoperative requirements for antiemetic therapy. 
Potential availability of cadaver organs for transplantation OBJECTIVE--To determine the potential number of cadaver kidney donors by applying defined donor criteria to people dying in hospital. DESIGN--Prospective study of all deaths occurring in 21 hospitals from 1 September 1988 to 31 August 1989. Questionnaires were administered to medical and nursing staff and families of potential donors aged 1-69. SETTING--Acute care hospitals in Gwent, South Glamorgan, Mid Glamorgan, West Glamorgan, Pembrokeshire, and East Dyfed health authorities, serving a population of 2.2 million. MAIN OUTCOME MEASURES--Cause of death, age, ventilation at time of death, diagnosis of brain death, and consideration of consent. RESULTS--Adequate data were available for 9840 of 10,095 hospital deaths (97.5% coverage). 188 patients aged 0-69 were identified as potential organ donors (widest definition), and of these 108 died without being ventilated at the time of death. Tests of brain stem death were formally completed in 57 cases, and organ donation was considered by the families of 47 of these potential donors. 26 patients became organ donors. Patients aged 50-69 with stroke were less likely to be ventilated than those aged less than or equal to 49 (21/96 v 24/34). Families of potential donors aged 20-39 were least likely to give permission. CONCLUSIONS--The supply of donor organs (specifically kidneys) could be increased by altering the management of patients aged 50-69 dying of severe cerebrovascular disease in general medical wards, in particular by increasing the proportion ventilated. The ethics of elective ventilation for the purposes of organ donation require discussion. 
Recurrent condylomata acuminata treated with recombinant interferon alfa-2a. A multicenter double-blind placebo-controlled clinical trial. Condylomata International Collaborative Study Group. Systemic interferon has been advocated as an effective therapy for recurrent genital warts. A double-blind, placebo-controlled, multicenter international trial involving 172 patients with recurrent condylomata was conducted using systemic interferon alfa-2a in doses of 3 or 9 MIU three times per week for 4 weeks. The treatment period was followed by a treatment-free follow-up period of 2 months. Complete responders at month 3 were followed up to 9 months or until they had a recurrence, whichever occurred first. The combined rates of complete response (total disappearance of all lesions without appearance of new ones) and major incomplete response (at least a 75% reduction in total lesion area) at 3 months after the commencement of therapy were 34%, 25%, and 30%, respectively, in 166 patients receiving 3 and 9 MIU of interferon alfa-2a and placebo. The recurrence rates at the end of 9 months were 9% in the placebo and 3-MIU groups and 36% in the 9-MIU group. We conclude that systemic interferon alfa-2a administered three times weekly for 4 weeks at doses of 3 and 9 MIU is not effective as monotherapy for genital warts that have recurred after standard ablative therapy. 
An evaluation of pulse oximetry in prehospital care. STUDY OBJECTIVES: We performed this study to evaluate the accuracy of pulse oximetry oxygen saturation (SpO2) against direct measurements of arterial oxygen saturation (SaO2) in the field. DESIGN: Prospective, cross-sectional, paired measurements of SpO2 against SaO2. SETTING: This evaluation was done in the prehospital setting. INTERVENTIONS: A pulse oximeter with digital probe was used to measure SpO2 in 30 patients. Arterial blood gases were drawn in the field while the pulse oximeter was in use, and oxygen saturation (HbO2) was measured by CO-oximetry. MAIN RESULTS: There was no significant difference between SpO2 (94.6 +/- 5.4%) and HbO2 (94.9 +/- 5.1%) (P = .495, beta less than .2). There was a strong correlation between SpO2 and HbO2 (r = .898). The bias between SpO2 and HbO2 was -0.3, with a precision of 2.4. When SpO2 was 88% or more, HbO2 was 90% or more in every case. Mean carboxyhemoglobin was 1.3 +/- 0.9%, and mean methemoglobin was 0.9 +/- 0.3%. There was no significant difference between the pulse oximeter heart rate and the ECG heart rate (P = .223, beta less than .2). CONCLUSION: We conclude that pulse oximetry is sufficiently accurate to be useful in the field when SpO2 is more than 88%. It is potentially useful in patients with clinical signs of acute hypoxemia and in patients receiving interventions that may produce acute hypoxemia. Further work is needed to evaluate the accuracy of pulse oximetry in the settings of elevated carboxyhemoglobin, methemoglobin, and very low saturations. 
Magnetic resonance imaging of spinal trauma. A retrospective series of 118 magnetic resonance examinations of 110 patients who had sustained previous spinal trauma is reported. Examinations performed within 3 weeks of trauma showed extraspinal soft tissue (including ligamentous) injury in 48% and intraspinal lesions in 61% (mostly consisting of extradural haematoma and spinal cord contusion). In examinations performed more than 3 weeks after injury intraspinal abnormalities were shown in 51% and these represented spinal cord compression, atrophy, myelomalacia and syringohydromyelia. Magnetic resonance imaging has the unique capability of displaying non-invasively the late sequelae of spinal trauma permitting simultaneous evaluation of the extra-spinal soft tissues, vertebral column and spinal cord. It is therefore recommended as the technique of choice in the investigation of patients who have sustained previous spinal injury, particularly those with neurological deficit. In the acute phase potentially remediable causes of neurological impairment such as disc herniation or extradural haematoma can be identified. Signal changes in the cord may allow the prognosis for neurological recovery to be established. In the later stages sequelae such as cord atrophy, myelomalacia and syringohydromyelia are accurately identified and surgical therapy may be guided, where appropriate. 
Effect of surgery on the systemic inflammatory response to intermittent claudication The hypothesis that intermittent claudication initiates a systemic inflammatory response was investigated by studying the effect of exercise on markers of neutrophil activation and vascular permeability in 25 claudicants and 10 controls. Urinary albumin excretion, previously demonstrated to reflect vascular permeability, increased significantly after exercise in claudicants and was associated with decreased neutrophil filterability and increased serum lysozyme activity. No similar exercise-induced changes were seen in controls or in claudicants after successful arterial bypass surgery. These results suggest that intermittent claudication is associated with potentially deleterious systemic manifestations that are surgically reversible. 
Treatment of chronic mastoiditis by grafting of mastoid cavities with autologous epithelial layers generated by in vitro culture of buccal epithelium. Autologous cultured epithelial layers were established from biopsies from the mucosa of the cheek, a non-keratinizing region of the oral cavity. These were grafted to the unepithelialized mastoid cavities of nine patients with chronic mastoiditis and severe otorrhoea varying from two to 30 years' duration. All procedures were performed on an out-patient basis, with no anaesthesia except for topical anaesthesia for the mucosal biopsy. In seven of the patients the grafts took well, with complete resolution of the otorrhoea for a minimum follow-up period of eight months. In one patient there was a partial take of the graft with substantial improvement in the rate of discharge. The mastoid cavities of two patients were biopsied five months after grafting, and demonstrated a stratified squamous epithelium, with keratinization of the epithelium clearly evident. 
Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial. BACKGROUND AND METHODS. In the Cardiac Arrhythmia Suppression Trial, designed to test the hypothesis that suppression of ventricular ectopy after a myocardial infarction reduces the incidence of sudden death, patients in whom ventricular ectopy could be suppressed with encainide, flecainide, or moricizine were randomly assigned to receive either active drug or placebo. The use of encainide and flecainide was discontinued because of excess mortality. We examined the mortality and morbidity after randomization to encainide or flecainide or their respective placebo. RESULTS. Of 1498 patients, 857 were assigned to receive encainide or its placebo (432 to active drug and 425 to placebo) and 641 were assigned to receive flecainide or its placebo (323 to active drug and 318 to placebo). After a mean follow-up of 10 months, 89 patients had died: 59 of arrhythmia (43 receiving drug vs. 16 receiving placebo; P = 0.0004), 22 of nonarrhythmic cardiac causes (17 receiving drug vs. 5 receiving placebo; P = 0.01), and 8 of noncardiac causes (3 receiving drug vs. 5 receiving placebo). Almost all cardiac deaths not due to arrhythmia were attributed to acute myocardial infarction with shock (11 patients receiving drug and 3 receiving placebo) or to chronic congestive heart failure (4 receiving drug and 2 receiving placebo). There were no differences between the patients receiving active drug and those receiving placebo in the incidence of nonlethal disqualifying ventricular tachycardia, proarrhythmia, syncope, need for a permanent pacemaker, congestive heart failure, recurrent myocardial infarction, angina, or need for coronary-artery bypass grafting or angioplasty. CONCLUSIONS. There was an excess of deaths due to arrhythmia and deaths due to shock after acute recurrent myocardial infarction in patients treated with encainide or flecainide. Nonlethal events, however, were equally distributed between the active-drug and placebo groups. The mechanisms underlying the excess mortality during treatment with encainide or flecainide remain unknown. 
Reflex bradycardia during TMJ arthroscopy: case report. A case of bradycardia occurring during TMJ arthroscopy is presented. A similar case of the TVR has not previously been reported. This reflex must be recognized by oral and maxillofacial surgeons who perform arthroscopy. 
Progression and survival studies in early chronic lymphocytic leukemia. To investigate the natural history of stage A chronic lymphocytic leukemia (CLL) we reviewed 84 such patients. Among 74 cases evaluable for disease progression, 22 (29.6%) progressed to more advanced clinical stages (9 to stage B, 13 to stage C); the actuarial estimation of such an event at 4 years was 30% (95% CI: 26.3% to 33.6%). Despite a linear trend toward an increasing risk (r = .92), the hazard function analysis showed a constant pattern of progression, suggesting a lack of correlation of such an event with time (r = .04). Furthermore, disease progression when analyzed as a time-dependent variable had a clear-cut impact on survival (P less than .001). With the aim of identifying a subgroup of patients with low probability of disease progression and death, we applied to our set of patients four different proposals for subclassifying stage A. All methods were similar in terms of sample size, 5-year survival rate, and disease progression risk, suggesting that the choice between different proposals is somewhat arbitrary. Whatever the criteria are for defining "smoldering" CLL, such patients (accounting in the present study for 20.5% of overall series and 46.7% of stage A patients) should not be treated until progression occurs. 
Spinal mediation of thermally induced sweating. The sweat responses of nine patients with physiologically complete lesions of the spinal cord (six cervical and three thoracic) were recorded by two different techniques while the patients were exposed to elevated environmental temperatures. Oral temperatures, heart rate and respiration were monitored throughout the observational periods. Oral temperature invariably rose during exposure to heat and both heart rate and respiration tended to increase. Sweating was detected on all of the test areas by both the iodine-starch-paper technique and the quinizarin technique, but it was of widely varying intensity in different portions of the body. In the patients with cervical lesions sweating was generally profuse on the head and neck and occurred in progressively decreasing intensity down to the level of the umbilicus. It was invariably present, but only in very low intensity, on the lower extremity. Sweating was frequently present as a result of manipulation of the patient during the initial preparations, but this generally declined or stopped before the heat was turned on. With application of heat, sweating was recruited on previously dry areas or increased in intensity on those areas in which it was previously present. After oral temperature had increased moderately, the heat was turned off and the doors of the chamber opened widely so that the heat stimulus was suddenly removed. Despite a continued rise in oral temperature, sweating stopped or decreased dramatically. These results are interpreted to indicate the direct mediation by the isolated spinal cord of reflex sweating responses to a heat stimulus applied to the skin. 
The motor response to sequential apomorphine in parkinsonian fluctuations. Fifteen patients with Parkinson's disease and levodopa-induced motor fluctuations, were studied with repeated injections of apomorphine using two protocols to explore possible changes in the duration of motor response. One involved different interdose intervals; in the other, doses were given when the motor effects induced by the previous dose had just worn off. No significant change in the duration of motor response to sequential subcutaneous apomorphine with either protocol was found. The results suggest that rapid changes in receptor sensitivity during repeated intermittent dopaminergic stimulation do not contribute to the pathogenesis of Parkinsonian motor fluctuations. 
Afferent loop syndrome: sonographic findings in seven cases. We studied the sonographic findings in seven patients in whom afferent loop obstruction was first detected by sonography. All seven subsequently were proved at surgery to have afferent loop syndrome. The causes of the obstruction included internal hernia (n = 3), cancer recurrence (n = 2), marginal ulcer (n = 1), and development of cancer at the anastomosis site (n = 1). In all cases, the dilated afferent loop was seen on sonography as a tubular structure in the upper abdomen crossing transversely over the midline. The distal end of the afferent loop could be traced toward the anastomosis. The probable cause of the syndrome was predicted on the basis of sonography in two of three patients with cancer at the anastomosis. Our experience suggests that afferent loop syndrome can be diagnosed sonographically on the basis of the detection, location, and shape of the dilated afferent loop. 
Intraoral salivary gland neoplasms: a retrospective study of seventy cases in an African population. Intraoral salivary gland neoplasms diagnosed in the Department of Oral Pathology, Medical University of Southern Africa, Medunsa, were reassessed and revised with regard to histologic diagnosis. New entities and subclassifications that have been described in recent years were taken into account. Seventy cases were diagnosed during an 8-year period, and the sample consisted of black patients only. Benign mixed tumor was the most common entity and accounted for 48% of all tumors. Polymorphous low-grade adenocarcinoma comprised 15.7% of the sample and was the most frequent malignant tumor. The mean age of patients with benign and malignant tumors were 36.5 and 49.8 years, respectively (p less than 0.05), and the palate was the most common site involved. Geographic differences do exist in the pattern and pathology of intraoral salivary gland neoplasms when compared with findings in other studies. 
Detection of ACTH-producing bronchial carcinoid tumors: MR imaging vs CT. Adrenocorticotrophic hormone (ACTH)-producing bronchial carcinoid tumors tend to occur in the middle third of the lung adjacent to pulmonary vessels. Because they cause signs and symptoms when quite small (by virtue of their ACTH production), they may not be detected by CT. MR imaging was performed in 10 consecutive patients with surgically proved ACTH-producing bronchial carcinoid tumors in order to test the ability of MR to clarify equivocal or indeterminate findings on CT examinations. All bronchial carcinoid tumors had high signal intensity on T2-weighted and short-inversion-time inversion-recovery images, facilitating their distinction from pulmonary vasculature. In eight patients, the CT and MR images were equivalent in the detection of bronchial carcinoid tumors. In two patients, MR showed tumors in the middle third of the lung that were equivocal on CT. MR imaging may distinguish small bronchial carcinoid tumors from adjacent pulmonary vessels in the central third of the lung at a time when the CT study is nondiagnostic or equivocal. 
Prediction of outcome after mitral valve replacement in patients with symptomatic chronic mitral regurgitation. The importance of left atrial size. BACKGROUND. The ability to predict outcome after mitral valve replacement remains limited in patients with symptomatic chronic mitral regurgitation. The aims of this study were to determine the preoperative predictors of postoperative cardiac-related mortality and to assess the additive prognostic value of tests performed in such patients. METHODS AND RESULTS. Accordingly, 176 patients (mean age, 57 +/- 14 years) who underwent mitral valve replacement were followed up for 3.8 +/- 0.5 years. Four categories of variables were analyzed to predict postoperative cardiac-related mortality: clinical, laboratory, two-dimensional echocardiographic (2DE), and cardiac catheterization. There were 39 cardiac-related deaths (29 due to congestive heart failure and 10 sudden). When the four categories were analyzed separately, two clinical, one laboratory, two 2DE, and one catheterization variable best predicted postoperative death. When these six variables were examined simultaneously, only three (one clinical and two 2DE) remained significant predictors of cardiac-related mortality: presence of pulmonary rales, left atrial size, and the ratio of left ventricular wall thickness to left ventricular cavity dimension in end systole. A model based on these three variables may predict cardiac-related death with considerable accuracy. Laboratory data did not add to clinical information for predicting death. 2DE variables provided significant additional information in this regard (p less than 0.001). Further addition of catheterization variables was not useful. Prognostic value did not change significantly when 50 patients with prior mitral valve surgery or 49 patients undergoing concomitant aortic valve replacement or coronary artery bypass surgery were excluded from analysis. CONCLUSIONS. We conclude that 1) measures of both left ventricular systolic function and left atrial size are equally important in predicting postoperative cardiac-related mortality in patients with symptomatic chronic mitral regurgitation undergoing mitral valve replacement; 2) left atrial size may be important because it reflects the "history" (severity and duration) of mitral regurgitation; 3) 2DE assessment of left atrial size and left ventricular function provides prognostic information that is significantly greater than that obtained from clinical and laboratory parameters alone; the addition of catheterization variables does not increase the prognostic value of the clinical and 2DE data. 
Clobazam in treatment of refractory epilepsy: the Canadian experience. A retrospective study. Canadian Clobazam Cooperative Group. During the past 7 years in Canada, more than 1,300 refractory epileptic patients have been treated with clobazam (CLB) by 104 adult and pediatric neurologists. Using a standard case report, 32 neurologists, who had each treated greater than or equal to 10 patients, provided retrospective data for 877 patients. The population had the following characteristics; the percentages of children and adults were 51 and 49%, respectively; 38% of the patients were mentally retarded; the percentages for single and multiple seizure type diseases were 46 and 54%, respectively; and adults had more complex partial seizures, whereas children had more atypical absence and myoclonic types. Before clobazam, patients received an average of 2 other antiepileptic drugs (AEDs) (range 0-5 AEDs). Average dose of CLB in children was 0.87 mg/kg per day (range 0.05-3.8 mg/kg per day) and in adults 30 mg/day (range 2.5-150 mg/day). Duration of CLB therapy ranged from a few days to greater than 4 years, with 40% being treated greater than 1 year. Using Kaplan-Meier curves, we found that 4 years after starting, 40-50% of patients continued CLB. More than 40% of patients with single seizure type had at least a 50% reduction in seizure frequency (improved). At least 60% of patients with multiple seizure type had improvement in one or more seizure types, and nearly 40% of the patients had all their seizure types improved. The seizure frequency for each seizure type, except tonic, was reduced greater than 50% in 40-50% of patients and by 100% in 10-30% of patients. Twenty percent stopped CLB for poor efficacy, 4% stopped for safety-related reasons including drug interactions, and 8% stopped for both reasons. Possible side effects (predominantly somnolence) were reported by 32%; however, in only 11% were the side effects sufficiently severe to cause discontinuation of medication. "Tolerance," leading to discontinuation of CLB, was reported for 9%. Patients treated with CLB for at least 1 year were generally maintained with CLB greater than 1 year. Thus, CLB is useful in refractory epilepsy of all types, suggesting that a monotherapy trial in less severe epilepsy is now desirable. 
Correlation of quantitative angiographic parameters with changes in left ventricular diastolic function after angioplasty of the left anterior descending coronary artery. This study evaluates the changes in left ventricular (LV) diastolic filling after percutaneous transluminal coronary angioplasty and the relation of such changes to quantitative angiographic measurements of the severity of coronary narrowings. Pulsed Doppler echocardiographic measurements were performed in 40 patients with single left anterior descending artery narrowing before, and 10 and 30 days after angioplasty. Minimal luminal diameter and percent diameter stenosis of coronary lesions were measured by computer-assisted quantitation. The ratio of early to late diastolic flow velocities (E/A ratio), time velocity integral of early diastolic filling period (Ei) and the ratio of early and late diastolic filling periods (Ei/Ai ratio) increased gradually after angioplasty. Minimal luminal diameter correlated significantly with the percent changes in E/A ratio (r = 0.59 at 10 days, r = 0.57 at 30 days), Ei (r = 0.53 at 10 days, r = 0.55 at 30 days) and Ei/Ai ratio (r = 0.41 at 10 days, r = 0.49 at 30 days). Percent diameter stenosis showed overall weaker correlations than minimal diameter with the percent changes in E/A ratio (r = 0.39 at 10 days, r = 0.32 at 30 days) and Ei (r = 0.38 at 10 days, r = 0.31 at 30 days). Thus, LV diastolic filling improves serially after coronary angioplasty in patients with 1-vessel disease. The magnitude of improvement in diastolic filling correlates better with minimal luminal diameter than percent diameter stenosis. Therefore, minimal luminal diameter is a better predictor of changes in Doppler transmitral flow parameters after angioplasty than percent diameter stenosis. 
Survival after resection of carcinoma of the splenic flexure. Nine hundred ten patients undergoing colectomy for colon cancer were studied retrospectively. Seventy-four cancers (8 percent) were located at the splenic flexure. The stage at presentation was no different between splenic flexure cancers and colon carcinomas at other sites. Although splenic flexure cancers had twice the incidence of obstruction as did other colon cancers and obstruction in the overall series adversely affected survival, there was no difference in survival between splenic flexure cancer patients and patients with other colon cancers. 
Reduction in injection pain using buffered lidocaine as a local anesthetic before cardiac catheterization. Previous reports have suggested that pain associated with the injection of lidocaine is related to the acidic pH of the solution. To determine if the addition of a buffering solution to adjust the pH of lidocaine into the physiologic range would reduce pain during injection, we performed a blinded randomized study in patients undergoing cardiac catheterization. Twenty patients were asked to quantify the severity of pain after receiving standard lidocaine in one femoral area and buffered lidocaine in the opposite femoral area. The mean pain score for buffered lidocaine was significantly lower than the mean score for standard lidocaine (2.7 +/- 1.9 vs. 3.8 +/- 2.2, P = 0.03). The pH adjustment of standard lidocaine can be accomplished easily in the catheterization laboratory before injection and results in a reduction of the pain occurring during the infiltration of tissues. 
Electrophysiologic analysis of early Parkinson's disease. We have been interested in the application of quantitative measures of motor performance as a possible means of early detection of Parkinson's disease. To assess motor function, we have measured movement time (the physiologic correlate of bradykinesia) and reaction time (simple and directional choice) with an upper limb motor task, and tremor with accelerometry and electromyographic recordings. In this report we describe preliminary data from a Parkinson's disease patient group with symptoms of fewer than 2 years' average duration (compared with an age- and gender-matched normal control group) which indicate that precise, quantitative tests of motor function can detect the slight deviations from normal that are present in early Parkinson's disease. It appears that tests of bradykinesia are most sensitive, and detection of rest tremor is most specific. These tests may be applicable in screening individuals who are suspected of having or are "at risk for" Parkinson's disease and other related disorders. 
Malignancy supervening on an intramedullary nail. A primary, malignant, fibrous histiocytoma of bone occurring in association with a Hansen Street intramedullary nail occurred in a 39-year-old man. The physical and chemical characteristics of materials, in relation to the generation of secondary neoplasia are reviewed, but the problem of coincidence is difficult to exclude. 
Prolongation of repolarization time by electric field stimulation with monophasic and biphasic shocks in open-chest dogs. Recent studies suggest that 1) electrically induced fibrillation and defibrillation involve prolongation of refractoriness by the shock in addition to stimulation and 2) biphasic waveforms are more efficient for defibrillation than are comparable monophasic waveforms. The purpose of this study was to compare prolongation of action potential duration at 50% repolarization by monophasic and biphasic shocks during paced rhythm. A floating glass microelectrode was used to record intracellularly from the anterior right ventricular epicardium in seven open-chest dogs. After 10 S1 beats paced at an interval of 350 msec, 5-msec and 2.5-msec monophasic shocks and biphasic shocks, with each phase of 2.5 msec, were given via mesh electrodes on either side of the microelectrode. The shock strength was adjusted so that the shock field, measured from eight extracellular electrodes encircling the microelectrode, was about 5 V/cm. Monophasic and biphasic S2 shocks were given starting with an S1-S2 interval of 120 msec, which was increased in 5-msec steps until an action potential was produced by the S2 shock. Both monophasic and biphasic 5 V/cm shock fields caused significant prolongation of action potential duration. The prolongation of action potential duration increased as the S1-S2 interval increased. This prolongation occurred at shorter S1-S2 intervals for 5-msec monophasic shocks than for biphasic shocks. 
Emergency department treatment of alcohol withdrawal seizures with phenytoin. STUDY OBJECTIVE: Prevention of recurrent alcohol withdrawal seizures is a common emergency department problem. A prospective, randomized, placebo-controlled, double-blind study of adequate size was designed to assess the efficacy of phenytoin in preventing recurrence of alcohol withdrawal seizures. METHODS: Fifty-five patients who had seized from alcohol withdrawal were randomly assigned to treatment with IV phenytoin or placebo. Patients with known seizure disorders and those receiving any anticonvulsant were excluded. The study was terminated after seizure recurrence or passage of a six-hour, high-risk seizure interval. RESULTS: Six of 28 phenytoin-treated patients (21%) had recurrent seizures compared with five of 27 placebo-treated patients (19%). The 95% confidence interval for the difference in response probabilities was +16% to -20%. There was no statistically significant difference between the response rates for the two treatments (P greater than .05). CONCLUSION: Phenytoin does not show significant benefit over placebo in preventing recurrence of alcohol withdrawal seizures. 
Psychological distress and diagnostic subgroups of temporomandibular disorder patients. This study examined the nature and extent of psychological differences among diagnostic subgroups of temporomandibular disorder (TMD) patients. Three subgroups were identified and labeled as: (1) primary myalgia, (2) primary temporomandibular joint (TMJ) problems, or (3) combination myalgia and TMJ problems. Patients' (n = 112) levels of pain and distress were measured using a VAS pain scale, the McGill Pain Questionnaire, the Beck Depression Inventory, the State-Trait Anxiety Scale and the MMPI. Patients with primary myalgia had the highest scores on the pain and distress measures while patients in the combination group scored between the myalgia and TMJ problem subgroups. When differences in pain levels were controlled, the differences among groups on measures of anxiety and depression were attenuated while the differences on measures of somatic overconcern remained significant. Discriminant function analysis using psychological variables to predict diagnostic grouping produced correct identification of 74% of the structural patients and 46% of the myalgia patients. Implications for different etiological factors among the 3 groups are discussed. 
Effects of drive train stimulus intensity on ventricular refractoriness in humans. BACKGROUND. The strength-interval relation between the intensity of premature stimulus and the ventricular effective refractory period (VERP) has been well characterized. The effects of variation in the intensity of the basic drive train stimuli (S1) on VERP are not as well defined. This relation was studied in 44 patients undergoing clinically indicated electrophysiological study. METHODS AND RESULTS. The outputs of two stimulus isolation units were connected in parallel, allowing the intensity of S1 to be varied independently of intensity of the extrastimulus (S2). To prevent confounding effects from cycle length change, continuous overdrive pacing was performed for 3 minutes before each measurement of VERP. The effect of S1 intensity on VERP was assessed in 24 patients with S2 intensity kept constant at twice threshold. VERP shortened from 232 +/- 19 msec at an S1 intensity of 1.5 times threshold to 219 +/- 20 msec at 5 mA and 211 +/- 19 msec at 10 mA (p less than 0.0001 for baseline versus 5 mA and for 5 mA versus 10 mA). Autonomic blockade with atropine and propranolol blunted but did not completely eliminate this effect. To assess whether the effect of S1 intensity on VERP was independent of S2 intensity, S2 strength-interval curves were generated in 10 patients at low (1.5 times threshold) and high (10 mA) S1 intensities. All portions of the strength-interval curve were shifted to the left by an increase in S1 intensity. The time course of change in VERP after an abrupt increase in S1 intensity was assessed in an additional 10 patients. VERP changed slowly, requiring 18 +/- 28 seconds to shorten by 2 msec and 64 +/- 46 seconds to decrease by 10 msec after a change in S1 intensity from 1.5 times threshold to 10 mA. In a final group of 10 patients, VERP was measured using an eight-beat drive train and a 4-second intertrain interval. With this more conventional protocol, VERP shortened by 14 +/- 8 msec with an increase in S1 intensity from 1.5 times threshold to 10 mA. CONCLUSIONS. Increasing S1 intensity results in clinically significant, progressive shortening of VERP in man. This effect is independent of S2 intensity. The prolonged time course of the change in VERP after an increase in S1 intensity and the attenuation of this effect by autonomic blockade are consistent with stimulation of sympathetic nerve terminals and catecholamine release as a result of intense stimulation. 
Detection of human papillomavirus DNA by in situ DNA hybridization and polymerase chain reaction in premalignant and malignant oral lesions. The sensitivity of detection of human papillomavirus (HPV) DNA in premalignant and malignant oral lesions by in situ hybridization (ISH) and polymerase chain reaction (PCR) were compared. With both methods HPV DNA was found in 4 of 24 cases of epithelial dysplasia, 4 of 14 cases of verrucous hyperplasia, and 1 of 10 cases of squamous cell carcinoma. The 10 cases of smokeless tobacco keratoses and 3 cases of verrucous carcinoma that we examined were all negative for HPV DNA. The PCR for the E6 open reading frame of HPV-16 correctly identified all cases that were positive by ISH. Only a single case that was positive by PCR was negative by ISH for HPV DNA. However, the PCR demonstrated the presence of HPV-16 infection in one case, which had hybridized most intensely with the probe for types 31/33/35 in the ISH. This discrepancy probably is due to the high degree of cross-hybridization in the ISH assay. PCR appears to be an effective technique for identifying HPV-16 DNA sequences in biopsy material from premalignant and malignant oral lesions. 
Predictive testing for Wilson's disease using tightly linked and flanking DNA markers. We studied DNA polymorphisms for five new chromosome 13 markers in 52 Wilson's disease (WD) families from Europe, North America, and the Middle East. There was significant evidence for linkage between the Wilson's disease locus (WND) and all the marker loci. Multilocus linkage analysis, using a genetic linkage map established from reference pedigrees, suggested that WND is most likely between D13S31 and D13S59, at distances of 0.4 and 1.2 centimorgans, respectively. Our results suggest that the chromosomal location of the Wilson's disease gene is the same in all families from the populations studied. This evidence and the availability of many close, flanking, and polymorphic DNA markers make possible accurate and informative testing of potential carriers and WD homozygotes in families with at least one previously affected child. An advantage of a genetic linkage test over other laboratory methods for prediction of genotype in WD is that a reliable diagnosis can be made at a much earlier stage in life, including prenatally. In addition, DNA testing can be used in place of an invasive liver biopsy procedure to confirm a diagnosis in patients with borderline serum ceruloplasmin levels. Presymptomatic identification will also allow therapeutic intervention to prevent symptoms before irreparable liver or neurologic damage occurs. We describe the implementation of prenatal and preclinical diagnosis for two families with WD. 
Endocrine manifestations of human immunodeficiency virus (HIV) infection. Endocrine manifestations of HIV infection include both pathological changes and disturbances in function. Mechanisms include direct infection of glands by HIV or opportunistic organisms, infiltration by neoplasms, side effects of drugs, and production of humoral factors that may alter metabolism. The adrenal gland is most often affected, but virtually every endocrine system may be involved. Dysfunction is often subtle, with symptoms overlapping those of the HIV infection itself. Endocrine manifestations may be found at any time in the course of the disease, from the asymptomatic HIV-positive stage through full-blown AIDS. Optimal management of these patients may include a careful search for, and appropriate treatment of, associated endocrine abnormalities. 
Disease progression and viral genome variants in experimental feline leukemia virus-induced immunodeficiency syndrome [published erratum appears in J Acquir Immune Defic Syndr 1991;4(9):925] A fatal immunodeficiency syndrome with clinical and pathologic features similar to human AIDS is inducible in cats by experimental inoculation with a specific strain of feline leukemia virus (FeLV) called FeLV-FAIDS. The course of the feline disease is characterized by an age-dependent prodromal period during which a non-disease-specific, common form of proviral DNA is detected in bone marrow. Preceding clinical onset of immunodeficiency is production of high levels of specific, pathogenic variant genomes, primarily as unintegrated viral DNA, in bone marrow. Acute immunodeficiency syndrome (survival period approximately 3 months) is associated with a short prodromal period and appearance of a characteristic variant genome (variant A) that persists at high copy number as integrated and full-length unintegrated viral DNA in bone marrow. Chronic immunodeficiency syndrome (survival greater than 1 year) is marked by a longer prodromal period, a more gradual onset of severe clinical immunosuppression, and a predominance of other variant genomes that often contain substantial internal deletions. In both forms of the disease, tissue-specific replication of certain variant viruses is noted in the bone marrow, intestine, and lymph nodes. Evidence from in vitro and in vivo virus transmission studies indicates that the appearance of FeLV-FAIDS variant viruses reflects differential replication of viral genomes pre-existing in the inoculum rather than rapid de novo evolution of new variants within each animal. These results demonstrate that retrovirus-induced immunodeficiency disease in cats can be associated with and prefigured by the amplified replication of specific viral variants in target tissues. 
Treatment of gram-negative peritonitis with aztreonam in patients undergoing continuous ambulatory peritoneal dialysis. In a multicenter open study, intraperitoneal aztreonam was used together with vancomycin, cloxacillin, or flucloxacillin for initial empiric treatment of peritonitis associated with continuous ambulatory peritoneal dialysis (CAPD). Monotherapy with aztreonam was continued in 34 episodes of gram-negative peritonitis in 28 patients. The microorganisms isolated included Escherichia coli, Acinetobacter species, Pseudomonas species, and Klebsiella species. In three episodes, two organisms were cultured. Microbiologic assessment revealed cure in 27 episodes, cure with relapse in two, cure with superinfection in one, and treatment failure in four (with resistance to aztreonam in three). As assessed by clinical criteria, 27 episodes were cured, five failed to respond, and two responded partially. No adverse reactions to aztreonam were observed. Comparison of these 34 episodes with 35 episodes in historical controls (treated mainly with aminoglycosides and/or trimethoprim-sulfamethoxazole) showed significantly higher rates of cure (84% vs. 51%) and of survival (97% vs. 86%) as well as lower rates of catheter removal (65% vs. 87%) with aztreonam. Thus aztreonam is a safe and efficient agent for the treatment of peritonitis caused by gram-negative organisms in patients undergoing CAPD. 
Quantitative magnetic resonance imaging in cervical carcinoma: a report on 30 cases. T1 and T2 relaxation times were calculated, before radiation therapy, in 30 patients with cervical carcinoma. Eight healthy young women were submitted to magnetic resonance imaging (MRI) to determine T1 and T2 times of the normal cervix. Magnetic resonance imaging was repeated, in 22 patients, during radiation therapy and at follow-up. During treatment and follow-up, patients with complete tumour response showed a significant T1 reduction compared with the pre-treatment values. With persistence of palpable or visible tumour, T1 times showed a small decrease during therapy, and a marked increase at subsequent examinations. The results suggest that the modifications of T1 times, during radiation therapy and follow-up, could be considered as a useful discriminant between patients with differing tumour response. 
Prostaglandin F2 alpha and indomethacin in hepatogenic pulmonary angiodysplasia. Effects on pulmonary hemodynamics and gas exchange. We treated a 68-year-old man with cirrhosis of the liver associated with moderate hypoxemia. Contrast-enhanced echocardiography revealed late opacification of the left ventricle, and pulmonary perfusion imaging with 99mTc macroaggregated albumin showed evidence of a significant uptake in both lungs and in the liver, spleen, and kidneys. Right cardiac catheterization revealed pulmonary hypotension, low pulmonary vascular resistance, and high cardiac output. We administered prostaglandin F2 alpha intravenously (0.2 microgram/kg/min for 30 minutes) and indomethacin orally (75 mg/day for three days). There was some degree of resolution of the hypoxemia and increases in both pulmonary arterial pressure and pulmonary vascular resistance. These findings suggest that the pathophysiology of hepatogenic pulmonary angiodysplasia is a reversible intrapulmonary vascular dilatation. These conditions can to some extent be modulated by vasoactive substances such as prostaglandins or other eicosanoids. 
Effect of dietary nucleotides on intestinal repair in rats with experimental chronic diarrhea. Nucleic acid synthesis in tissues of rapid growth is preferentially done using dietary purines and pyrimidines via the salvage pathway. In the case of a low protein intake, dietary nucleotides may be semiessential for cell replication of gut, lymphocytes, and bone marrow, and especially in those intestinal diseases in which the mucosa is altered, dietary nucleotides may have a role in intestinal development. The effect of dietary nucleotides on intestinal weight and length, gut mucosal weight, intestinal protein and DNA contents, and lactase, maltase, and intestinal mucosal activities was assessed in a controlled way. Weanling (21-day-old) rats were separated into two groups of 36, each receiving blindly a basal diet containing glucose polymers (C) or a basal diet with lactose as the main carbohydrate (L) for 15 days. Those fed with L developed a syndrome of chronic diarrhea and malnutrition. Ten rats of each group were sacrificed at that time. The rest of the animals of each group were separated into two subgroups. The first was fed with the C diet and the second with the C diet supplemented with 50 mg/100 g of each of the following nucleotides: AMP, GMP, CMP, UMP, and IMP (CN). Thus the subgroups CC, CN, LC, and LN were formed. Rats were sacrificed after 4 weeks and gut separated into three segments corresponding to duodenum, jejunum, and ileum. Analysis of variance was used to compare the effect of diet or segments. DNA and lactase, maltase, and sucrase activities increased in the LN group with respect to LC especially in jejunum and ileum but there were not any differences between CC and CN. 
Hereditary coproporphyria: an imitator of multiple sclerosis. Hereditary coproporphyria can cause both peripheral neuropathy and central nervous system abnormalities. There are several similarities between multiple sclerosis and hereditary coproporphyria that are probably due to the central nervous system dysfunction present in both. This report describes a 62-year-old man with a five-year history of progressive paraparesis initially diagnosed as multiple sclerosis. Supporting evidence for the diagnosis of a demyelinating disease included three oligoclonal bands in the patient's cerebral spinal fluid, a prolonged visual evoked response bilaterally, abnormal sensory evoked potentials, and an area of increased signal in the posterior cervical cord suggestive of demyelination that was demonstrated on magnetic resonance imaging (MRI). Features atypical for multiple sclerosis were hypoactive deep-tendon reflexes, electromyographic evidence of peripheral neuropathy, and severe constipation. Elevated urine porphyrins and decreased levels of coproporphyrinogen oxidase confirmed the correct diagnosis of hereditary coproporphyria. The patient improved after being placed on a high-carbohydrate diet. Although central demyelination is known to occur in patients with porphyria, delayed evoked potentials and MRI abnormalities have not been previously reported. 
Early postoperative basal serum GH level and the GH response to TRH in relation to the long-term outcome of surgical treatment for acromegaly: a report on 39 patients. During a 10-year period 39 patients with acromegaly, aged 23-73 years, underwent selective adenomectomy via a trans-sphenoidal or transfrontal (one case) approach. Six to 12 months after the operation, the serum level of growth hormone (GH) was reduced to less than 5 micrograms l-1 in 28 patients (74%) in at least two of three random samples and/or suppressed to less than 3 micrograms l-1 during an oral glucose load, thus fulfilling the commonly used criteria for a successful operation. In 10 patients these criteria for adequate GH reduction were not fulfilled, but their median S-GH level was reduced from 38 to 11 micrograms l-1 (P less than 0.01) after the operation. Surgery was successful in 11 of 13 (85%) patients with a microadenoma (less than 10 mm in diameter), in 10 of 14 (71%) patients with an adenoma of diameter greater than 10 mm but still enclosed in the sella, and in seven of 11 (64%) patients with locally invasive tumours. Impaired pituitary function was observed in 23% of the patients after surgery, independent of tumour size. In one patient the postoperative period was complicated by a lethal intracranial infection. During follow-up for 1-10 years, four patients relapsed, after 1, 1.5, 6 and 9 years, respectively. Patients for whom surgery appeared to have been ineffective at the evaluation 6-12 months postoperatively, or who later relapsed were identified by early (within 7 d) postoperative serum GH with a sensitivity of 90%. The accuracy for identification of a satisfactory outcome of surgery was 85%, and the predictive value was 90%. The corresponding values for the GH response to TRH measured 6-12 months postoperatively were 47, 40 and 54%, respectively. It is concluded that the basal level of serum GH measured 1-7 d postoperatively has higher sensitivity and specificity than the GH response to TRH 6-12 months postoperatively for evaluation of the effect of surgery on GH overproduction, and that it has a higher predictive power with regard to the long-term outcome of surgery for acromegaly. 
Psychiatric aspects of chest pain in the emergency department. We estimate that a third of the patients who present to the ED with chest pain have a current psychiatric disorder and that psychiatric disorders among chest pain patients are associated with a high rate of ED utilization for chest pain evaluations. Physicians in the ED recognize only a small fraction of the psychiatric disorders, so appropriate treatment or referral may be infrequent. The proportion of chest pain patients with CAD who also have a psychiatric disorder may be in the range of 20% to 30%, justifying careful assessment of psychiatric disorders in CAD patients. We conclude that the psychiatric aspects of chest pain are sufficiently prevalent, clinically significant, and a contributor to unnecessarily high utilization of medical services. We call for clinical research to address these questions by outlining three areas of study that will advance our knowledge and care of the patient with chest pain. 
Alpha 2 macroglobulin state in acute pancreatitis. Raised values of alpha 2 macroglobulin-protease complexes in severe and mild attacks. Plasma values of C reactive protein, alpha 1 proteinase inhibitor, alpha 2 macroglobulin, and complexed alpha 2 macroglobulin have been determined in serial samples from 27 patients with acute pancreatitis. Complexed alpha 2 macroglobulin was measured by a novel enzyme linked immunosorbent assay with a monoclonal antibody specific for the complexed form. Patients with severe illness had lower concentrations of total alpha 2 macroglobulin and higher concentrations of complexed alpha 2 macroglobulin than those with mild illness, and in the majority of severe attacks the abnormal amounts of complexed alpha 2 macroglobulin were present throughout the eight days of the study. The proportion of total alpha 2 macroglobulin in the uncomplexed form, however, was generally greater than 90%, and in 26% of the mild cases completely normal concentrations of uncomplexed alpha 2 macroglobulin (greater than 99% of total) were found throughout the eight days of the study. This suggests that exhaustion of alpha 2 macroglobulin in plasma is unlikely to be a major factor in the pathogenesis of acute pancreatitis. 
Right ventricular hypertrophy detected by echocardiography in patients with newly diagnosed obstructive sleep apnea. We used polysomnography, echocardiography and ventilatory measurements to study 50 patients suspected of having OSA to determine a link to RVH. Twenty-eight patients (56 percent) had OSA and 20 (71 percent) of those had isolated RVH. We evaluated patients with RVH and divided them into two groups, those with apnea and those without apnea. The patients with sleep apnea were younger, weighed more, had greater BSA and had lower average oxygen saturations during the sleep study period. We divided the group with apnea into those with RVH and those without it. Those patients with RVH had a higher AI, longer average apnea time, a greater duration of longest apnea and a lower average oxygen saturation for the period of the sleep study. In addition, those with RVH had a lower average oxygen saturation during each apneic episode with a p value equaling 0.09. 
Carcinoid tumor of the common bile duct: evidence for its origin in metaplastic endocrine cells. Carcinoid tumors of the extrahepatic bile ducts are extremely rare neoplasms. The authors report the case of a 36-yr-old male patient with a carcinoid tumor that arose in the common hepatic bile duct. The non-neoplastic mucosa showed areas of gastric and intestinal metaplasia that included scattered argyrophil endocrine cells. Since the normal mucosa of the bile ducts lacks the latter type of cells, this case provides evidence for the first time that carcinoid tumors of this anatomic site probably originate from metaplastic endocrine cells. 
Emergency laryngectomy. From 1974 to 1990, 31 patients underwent emergency laryngectomy for airway obstruction due to laryngeal carcinoma, in an effort to avoid the complication of stomal recurrence. This group of patients had a greater proportion of multiregional tumours (35 per cent vs 13 per cent) than a comparison group of elective laryngectomies. In other respects the two groups were similar. Early post-operative mortality (6.5 per cent vs 3 per cent), stomal recurrence rates (4.2 per cent vs 4.8 per cent) and survival (53 per cent vs 55 per cent) were not significantly different between the emergency laryngectomy group and the comparison group undergoing elective laryngectomy. 
An autopsy case of I-cell disease. Ultrastructural and biochemical analyses. An autopsy case of I-cell disease in a 4-year-old Japanese girl is presented. In this report, the authors analyze the relationship between morphologic (including electron microscopic) and biochemical findings. Lymph node, spleen, and kidney, which were stained with Hale's colloidal iron method, contained large amounts of hexosamine. These substances had accumulated in lymphocytes of B-cell lineage. 
Late potentials are unaltered by ventricular filling pressure reduction in heart failure. Exacerbation of heart failure may increase susceptibility to arrhythmias. Therefore tests to assess the risk of arrhythmia, performed after hemodynamic improvement, may be of limited value. To determine whether hemodynamic improvement alters ventricular late potentials detected by signal-averaged ECG, we studied 27 consecutive patients with dilated heart failure (left ventricular ejection fraction 0.20 +/- 0.06, 15 with coronary artery disease) before and 3 +/- 2 days after tailored vasodilator and diuretic therapy reduced ventricular filling pressures. QRS duration, terminal QRS amplitude (root mean square [RMS]), and low-amplitude (less than 40 microV) signal (LAS) duration were determined by an automated algorithm from the vector magnitude of the QRS high-pass filtered at 25 Hz and at 40 Hz. Despite marked decreases in pulmonary capillary wedge (27 +/- 7 to 16 +/- 5 mm Hg, p less than 0.001) and right atrial (13 +/- 7 to 7 +/- 4 mm Hg, p less than 0.001) pressures and a 20% increase in cardiac output, there was not a significant change in QRS duration, RMS, or LAS. Before and after therapy late potentials, defined as abnormal QRS duration RMS, or LAS, were present in 14 (52%) patients with filtering at 25 Hz and in 22 (81%) patients with filtering at 40 Hz. The signal-averaged ECG after hemodynamic improvement predicted the results during exacerbation of heart failure in all patients. Thus in patients with advanced heart failure the signal-averaged ECG obtained after hemodynamic improvement reflects the findings during exacerbation of heart failure. 
The pediatrician's involvement in prevention and treatment of oral disease in medically compromised children. Significant oral health problems are associated with medical, physical, or mental disorders that occur in children. The pediatrician has the opportunity through early intervention to set the tone for a health care practice that will improve the quality of life for many disadvantaged children. When the pediatrician and pediatric dentist work hand in hand, the children can often expect a happy, healthy future. 
The physiologic basis of diuretic synergism: its role in treating diuretic resistance. Diuretic drugs usually improve edema when used judiciously. Some patients, however, become resistant to their effects. Diuretic resistance may result from dietary indiscretion, poor compliance, impaired bioavailability, imparied diuretic secretion into the lumen of the renal tubule, or because other drugs interfere with diuretic activity. When easily treatable causes of diuretic resistance have been excluded, resistance often reflects the intensity of the stimuli to sodium retention. Recent experimental work has indicated ways in which the kidney adapts to chronic diuretic treatment and has indicated how these adaptations may limit diuretic effectiveness. First, nephron segments downstream from the site of diuretic action increase sodium-chloride (NaCl) reabsorption because the delivered NaCl load increases. Second, diuretic-induced contraction of the extracellular fluid volume stimulates kidney tubules to retain NaCl until the next dose of diuretic is administered. Third, kidney tubules themselves may become hypertrophic because they are chronically stimulated by diuretic-induced increases in NaCl delivery. These adaptations all increase the rate of NaCl reabsorption and blunt the effectiveness of diuretic therapy. When diuretic resistance is present, using a second diuretic drug that acts in a different nephron segment is often effective. Recent experimental results suggest that a second class of drug may act synergistically with the first by blocking the adaptive processes that limit diuretic effectiveness. On the basis of an understanding of the mechanisms of diuretic adaptation and resistance, treatment regimens can be designed to block specific adaptive mechanisms and to improve diuretic therapy. 
Substance abuse: the designer drugs. Designer drugs, chemically altered compounds derived from federally controlled substances, have become a major cause of addiction and overdose deaths. These drugs include mescaline analogs, synthetic opioids, arylhexylamines, methaqualone derivatives and crack, a new form of cocaine. Sudden changes in mood, weight loss, depression, disturbed sleep patterns, deteriorating school or work performance, marital problems, and loss of interest in friends and social activities may be signs of drug addiction. Life-threatening complications of acute intoxication, such as hyperthermia, seizures, combative and psychotic behavior, and cardiorespiratory collapse, require prompt diagnosis and supportive intervention. 
Differential expression of CD25 (interleukin-2 receptor) on lamina propria T cells and macrophages in the intestinal lesions in Crohn's disease and ulcerative colitis Many interleukin-2 receptor (CD25) bearing cells can be identified by alkaline phosphatase immunohistochemistry in the diseased intestinal lamina propria of children with Crohn's disease or ulcerative colitis, but rarely in normal intestine. In both diseases, the CD25+ cells are present as aggregates in the lamina propria below the epithelium, and constitute a large proportion of the lamina propria mononuclear cells. In Crohn's disease, but not ulcerative colitis, CD25+ cells are abundant in the submucosa. The CD25+ cells in Crohn's disease are 58-88% CD3+, CD4+, CD8-, indicating that they are T cells, whereas in ulcerative colitis the CD25+ cells are greater than 80% CD3-, CD4+, HLA-DR+, indicating that they are macrophages. Thus, differential expression of CD25 on T cells and macrophages serves to distinguish the immunologic lesions in ulcerative colitis and Crohn's disease. 
Myonecrosis and myofibrosis as complications of sickle cell anemia. Painful crises in sickle cell anemia are associated with infarction and subsequent fibrosis of many different organs. Myonecrosis secondary to muscle infarction during a crisis and subsequent fibrosis are often not recognized as complications of sickle cell anemia. We describe four patients, all of whom had recurrent episodes of symmetric proximal muscle pain and swelling as prominent features of their crises. Muscle biopsies showed acute myonecrosis with a minimal inflammatory reaction as well as myofibrosis with abundant collagen deposition. Chronic sequelae consisted of muscle induration, atrophy, and contractures. 
Suppression of eicosanoid biosynthesis during coronary angioplasty by fish oil and aspirin. BACKGROUND. Percutaneous transluminal coronary angioplasty (PTCA) is an acute, localized stimulus to platelet and vascular function. Periprocedural cardiovascular complications are reduced by moderate-dose aspirin (ASA), presumably due to inhibition of thromboxane (TX) A2. METHODS AND RESULTS. Excretion of TXA2 and prostacyclin (PGI2) metabolites in urine increased during PTCA. Pretreatment for 3 days with either moderate- (325 mg/day) or low-dose (80 mg/day) ASA inhibited the increase in both eicosanoids. Pretreatment for 3 weeks with fish oil (10 g/day) only partially suppressed TXA2. Formation of trienoic eicosanoids and accumulation of omega-3 fatty acids in platelet membranes confirmed fish oil ingestion. Although basal PGI2 was not inhibited, the PTCA-related increment was suppressed. CONCLUSIONS. PTCA results in an acute, transient alteration of eicosanoid biosynthesis consistent with accelerated platelet-vascular interactions. Pretreatment for 3 days with moderate or low doses of ASA suppresses TXA to a similar extent during PTCA, and their effects on acute cardiovascular complications of this procedure are likely to be comparable. It is unlikely that even prolonged pretreatment with fish oil can substitute for the platelet inhibitory action of ASA during PTCA. Suppression of PGI2 may contribute to the residual acute periprocedural complication rate in patients taking ASA. 
Etidronate for hypercalcemia of malignancy and osteoporosis. The biphosphonates are becoming well established as effective agents for the treatment of metabolic bone diseases. Etidronate disodium is the only biphosphonate approved by the U.S. Food and Drug Administration. Accepted indications for etidronate therapy are symptomatic Paget's disease, heterotopic ossification and hypercalcemia of malignancy. An unapproved, but apparently successful use is treatment of postmenopausal osteoporosis. Both oral and intravenous preparations are available. Newer biphosphonates, which may be more efficacious and less toxic than etidronate, are being studied. 
Comparative angiographic quantitative analysis of the immediate efficacy of coronary atherectomy with balloon angioplasty, stenting, and rotational ablation. Interventional cardiology has branched in two directions: devices that primarily dilate coronary stenoses and those that debulk coronary tissue. Presently the optimum coronary intervention has not been found. While patients are awaiting randomized trials, a comparison based on matched quantitative coronary analysis may be useful to evaluate results of new interventional techniques. Therefore we compared 51 patients undergoing atherectomy with individually matched patients who were undergoing balloon angioplasty and stenting. The lesions were matched according to location of stenosis and reference diameter. Atherectomy and stenting resulted in larger gains in minimal luminal diameter compared with conventional balloon angioplasty. The minimal luminal diameter was increased from 1.2 +/- 0.4 mm to 2.6 +/- 0.4 mm in the atherectomy group and from 1.2 +/- 0.3 mm to 1.9 +/- 0.4 mm in the angioplasty group (p less than 0.00001). Atherectomy and stenting resulted in similar gains in minimum luminal diameter (1.4 mm vs 1.3 mm, p = NS). In addition, atherectomy and stenting appear to be more effective in resisting elastic recoil because of tissue removal and an intrinsic dilating effect, respectively. In matched populations directional atherectomy and stenting appear to be more effective intracoronary interventional devices than balloon angioplasty based on the immediate results. However, atherectomy is limited in smaller coronary vessels because of its larger size. 
Adaptive changes in the periphery and their therapeutic consequences. Systemic vasoconstriction in chronic heart failure is due to several compensatory mechanisms with different time courses. Peripheral vasoconstriction mediated by increased sympathetic tone and activation of the plasma renin-angiotensin system may act primarily for short-term control. The effects of the vascular renin-angiotensin system, impaired flow-dependent, endothelium-mediated dilation (resulting from chronically reduced flow) and structural alterations of the vessel wall slowly emerge with time. In addition, fluid retention may contribute to increased vascular stiffness in chronic heart failure. Improved cardiac output with acute administration of vasodilators and inotropes is not immediately translated into increased blood flow to skeletal muscle, because (1) the reversal of the peripheral alterations described develops slowly over time (in fact, vasodilators and inotropes given acutely may cause redistribution of blood flow in skeletal muscle without improving oxygen availability); and (2) intrinsic abnormalities of skeletal muscle exist in chronic heart failure (e.g., due to chronic deconditioning, resulting in reduced oxidative capacity of skeletal muscle, as suggested by ultrastructural analysis and nuclear magnetic resonance spectroscopy). Drugs that interfere with the underlying compensatory mechanisms (e.g., renin-angiotensin system) without development of tolerance during long-term therapy exert beneficial effects after long-term treatment (e.g., the beneficial effects of angiotensin-converting enzyme inhibitors are, in part, due to peripheral mechanisms--the inability of the peripheral vessels to dilate--and to improvement of peripheral oxygen extraction). 
Extracorporeal lithotripsy. An important adjunct in the nonoperative management of retained or recurrent bile duct stones. Retained or recurrent bile duct stones can be successfully removed in up to 80% to 85% of patients with the use of percutaneous or endoscopic techniques. However, problems related to difficult biliary access, large stones, and biliary strictures may decrease the success rate of this approach. We evaluated the safety and efficacy of extracorporeal shock-wave lithotripsy (ESWL) in 16 patients with complicated biliary stones treated prospectively over a 24-month period. Successful stone fragmentation was achieved in 15 patients (94%) using a Dornier HM3 lithotripter (average of 2290 shocks at 22 kV). Three patients (19%) required a second ESWL treatment. Biliary clearance of stone fragments was spontaneous in seven (43%) of the patients and required additional treatment in eight (57%) of the patients. Complications from ESWL were minor and included transient hematuria and ecchymoses at the skin entry site. Extracorporeal shock-wave lithotripsy failed in one patient (6%) with a biliary stricture and surgery was required. At hospital discharge, all patients were asymptomatic and stone free. Treatment with ESWL appears to be a safe and effective adjunct for selected patients with complex biliary stone disease. 
The orthostatic tachycardia syndrome: evaluation of autonomic function and treatment with octreotide and ergot alkaloids. Orthostatic tachycardia is a poorly understood syndrome in which patients develop dizziness, diaphoresis, or palpitations upon shifting from the supine to the upright posture. The present study was performed to determine whether autonomic neuropathy might be present in these patients, and whether the abnormal hemodynamic response to standing might be the result of failure of reflex vasoconstriction. We measured autonomic function in 9 patients with idiopathic orthostatic tachycardia and 2 patients with orthostatic tachycardia and insulin-dependent diabetes mellitus and compared them to 33 age-matched controls. Although most patients with orthostatic tachycardia had normal vasomotor reflexes and normal surface potential amplitudes, the latency of the autonomic response, a measure of sympathetic nerve conduction velocity, was prolonged in the soles (2.44 +/- 0.08 s in patients with idiopathic orthostatic tachycardia vs. 2.12 +/- 0.04 s in controls; P less than 0.005). In 6 of 9 patients, however, the latencies were within the normal range. Autonomic surface potentials were absent in 1 diabetic patient with orthostatic tachycardia; the latency of the response in the feet was greatly prolonged (2.95 s) in the second patient. We also assessed the response of orthostatic tachycardia patients to octreotide and dihydroergotamine, which are known to have a pressor effect in patients with recognized forms of autonomic neuropathy. These agents, in combination, suppressed orthostatic tachycardia (from 116 +/- 7 to 89 +/- 6 beats/min; P less than 0.001) in patients with this syndrome. In summary, our data indicate that evidence of autonomic dysfunction is present in only a minority of patients with orthostatic tachycardia. Nevertheless, administration of the vasoconstrictor drugs dihydroergotamine and octreotide can prevent the abnormal hemodynamic response to the upright posture shown by patients with this syndrome. 
Crohn disease in the pediatric patient: CT evaluation. Computed tomographic (CT) scans and medical records of 25 children (age range, 10-18 years) with pathologically proved Crohn disease were reviewed to better define the role of CT in the management of pediatric patients with Crohn disease. CT findings included small bowel thickening (range, 5-10 mm) (n = 20), colonic wall thickening (range, 6-15 mm) (n = 15), and small bowel dilation (n = 5). Mesenteric abnormalities such as adenopathy and focal fatty proliferation were seen in 11 to 18 patients, respectively. Extraluminal complications were easily identified with CT. Abscesses were noted in seven patients, inflammatory masses in four, and perirectal or perineal inflammation in 10. Fistulas were detected in four patients. The authors conclude that CT should be the initial imaging study performed in children with known Crohn disease and a changing pattern of clinical symptoms. 
Effect of bisoprolol on blood pressure and arterial hemodynamics in systemic hypertension. Blood pressure, heart rate, common carotid and brachial arterial hemodynamics using pulsed Doppler flowmetry and pulse wave velocity determinations were evaluated using a double-blind crossover design versus placebo in 14 patients with sustained essential hypertension treated by the selective beta 1 blocking agent bisoprolol. Blood pressure and heart rate significantly decreased after bisoprolol, whereas no significant change occurred in the diameter, the blood flow and in the vascular resistance of the carotid and brachial circulations. Pulse wave velocity significantly decreased in the brachioradial and the carotid femoral areas. The decrease in the latter was -1.6 +/- 0.8 m/s with bisoprolol and -0.06 +/- 0.80 m/s with placebo (p = 0.001). Brachial artery compliance significantly increased from 117 +/- 49 to 205 +/- 84 cm4 x dynes-1 x 10(9) (p = 0.001), indicating that the antihypertensive effect of beta 1 blockade is associated with an improvement in the viscoelastic properties of the brachial artery wall. 
J. Maxwell Chamberlain Memorial Paper. Role of staging in prognosis and management of thymoma. Eighty-five patients operated on for thymoma from 1972 to 1989 were evaluated, 32 with myasthenia gravis and 53 without. Masaoka staging revealed stage I disease in 45 (53%), stage II in 23 (27%), stage III in 14 (16%), and stage IVa in 3 (4%). There was no operative mortality. Actuarial survival at 10 years was 63.7% for all patients: 78.3% for those in stage I, 74.7% for those in stage II, and 20.8% for those in stage III. There was no recurrence in patients in stage I. Mediastinal recurrence developed in 4 patients in stage II considered to have noninvasive disease by the surgeon. It is recommended that all patients be followed up for a minimum of 10 years and that all patients in stages II and III receive postoperative radiotherapy. The presence of myasthenia gravis is no longer considered as an adverse factor in survival. 
Rhabdomyolysis following total hip arthroplasty. We report six cases of contralateral limb involvement during total hip arthroplasty including swelling of the gluteal muscle compartments, rhabdomyolysis, myoglobinuria, and sciatic nerve palsy. The risk factors for such complications include obesity, prolonged operative time, and positioning in the lateral decubitus position. The laboratory and clinical findings are consistent with a gluteal muscle crush-injury with consequent compartment syndrome. The patients should be treated conservatively as symptoms can be expected to resolve. 
Usefulness of the corticotropin-releasing hormone test during bilateral inferior petrosal sinus sampling for the diagnosis of Cushing's disease. Inferior petrosal sinus blood sampling for ACTH measurement (IPSS) is used for the differential diagnosis of ACTH-dependent Cushing's syndrome and for the preoperative location of pituitary microadenomas. Intermittent ACTH secretion from pituitary adenomas may result in insignificant differences between petrosal and peripheral ACTH levels at the time of sampling. Thus, pituitary stimulation during IPSS may improve the procedure. The aim of the study was to evaluate the usefulness of CRH injection in combination with IPSS. Twenty-two patients with Cushing's disease (CD; 5 macroadenomas, 16 microadenomas, and 1 corticotroph hyperplasia) and 5 patients with ectopic ACTH syndrome were studied. Bilateral IPSS was successfully carried out on 25 patients. Patients with ectopic ACTH syndrome had, before and after CRH injection, central to peripheral ACTH gradients below 1.7. Four patients with CD had basal gradients below 1.4. After CRH administration all patients with CD had gradients above 3.2. Despite correct location of central catheters, the predicted location of pituitary microadenomas was erroneous in 41% of the cases. It was not improved after CRH injection. In conclusion, the combination of CRH injection with IPSS was useful for the differential diagnosis of ACTH-dependent Cushing's syndrome, as it increased the discrimination of the procedure. On the contrary, it was useless for the preoperative location of pituitary microadenomas, which was poorly predicted by IPSS. 
Enhancement of ischaemic rabbit skin flap survival with the antioxidant and free-radical scavenger N-acetylcysteine. 1. The burst of damaging oxygen free-radicals at the time of reperfusion is one of the crucial factors affecting skin flap survival after an ischaemic interval. In these experiments the efficacy of the antioxidant and free-radical scavenger N-acetylcysteine in improving the survival of ischaemic rabbit epigastric skin flaps was tested. 2. At the time of reperfusion flaps were given: (1) balanced salt solution by intravenous whole-body administration, (2) N-acetylcysteine (200 mg/kg) by intravenous whole-body administration, (3) balanced salt solution by intra-arterial infusion into the flap, (4) N-acetylcysteine (20 mg/kg) by intra-arterial infusion into the flap, or (5) N-acetylcysteine (200 mg/kg) by intra-arterial infusion into the flap. Flap survival at 1 week, and tissue levels of parameters related to free-radical production, blood levels of thromboxane B2 and peripheral resistance during reperfusion were determined. 3. Compared with controls (groups 1 and 3) which had flap survival rates (expressed as percentage surface area surviving) of 27.1% and 31.6%, respectively. N-acetylcysteine treatment in group 2 (55.2%) and group 4 (51.9%) resulted in significant (P less than 0.05) improvements in flap survival. The survival rate in group 5 (37.7%) was not significantly better than that of the controls. 4. N-Acetylcysteine significantly reduced parameters related to free-radical production in the skin flap after 30 min of reperfusion, determined as tissue levels of malonyldialdehyde and protein oxidation products. There was also a significant decrease in peripheral resistance when low-dose N-acetylcysteine (group 4) was infused intra-arterially into the flap. 
Comparison of neuroendocrine activation in patients with left ventricular dysfunction with and without congestive heart failure. A substudy of the Studies of Left Ventricular Dysfunction (SOLVD). Neuroendocrine activation is known to occur in patients with congestive heart failure, but there is uncertainty as to whether this occurs before or after the presence of overt symptoms. In the Studies of Left Ventricular Dysfunction (SOLVD), a multicenter study of patients with ejection fractions of 35% or less, we compared baseline plasma norepinephrine, plasma renin activity, plasma atrial natriuretic factor, and plasma arginine vasopressin in 56 control subjects, 151 patients with left ventricular dysfunction (no overt heart failure), and 81 patients with overt heart failure before randomization. Median values for plasma norepinephrine (p = 0.0001), plasma atrial natriuretic factor (p less than 0.0001), plasma arginine vasopressin (p = 0.006), and plasma renin activity (p = 0.03) were significantly higher in patients with left ventricular dysfunction than in normal control subjects. Neuroendocrine values were highest in patients with overt heart failure. Plasma renin activity was normal in patients with left ventricular dysfunction without heart failure who were not receiving diuretics and was significantly increased (p less than 0.05) in patients on diuretic therapy. We conclude that neuroendocrine activation occurs in patients with left ventricular dysfunction and no heart failure. Neuroendocrine activation is further increased as overt heart failure ensues and diuretics are added to therapy. 
Use of azathioprine or 6-mercaptopurine in the treatment of Crohn's disease. The efficacy and safety of therapy with azathioprine/6-mercaptopurine was studied in 78 patients with Crohn's disease. Mean duration of therapy was 1.6 years; 52 patients were treated greater than or equal to 6 months. All patients were also on other antiinflammatory medications. Evaluations included self-assessment and physician's assessment of well-being, functional capacity, general clinical response, clinical activities indices (National Foundation for Ileitis and Colitis/International Organization for the Study of Inflammatory Bowel Disease and Harvey-Bradshaw), and achievement of specific therapeutic goals. General clinical condition improved in 70% of the patients. Median response time was 3 months. The average Harvey-Bradshaw score decreased 37% with therapy, and a decrease of greater than or equal to 30% occurred in 66% of the subjects. An overall 72% achievement rate for specified therapeutic goals included controlling refractory disease, 73%; corticosteroid "sparing," 76%; and lessening fistulization, 63%. Nine patients got worse despite therapy. Adverse effects requiring discontinuation of therapy occurred in 10%, whereas dosages were briefly lowered for mild side effects in another 10%. This study demonstrates the effectiveness and safety of azathioprine/6-mercaptopurine in the majority of selected patients with chronic, unremitting, or steroid-requiring Crohn's disease. 
Clinical, biochemical, and morphological correlates in patients bearing growth hormone-secreting pituitary tumors with or without constitutively active adenylyl cyclase. Somatic mutations in the alpha-chain (alpha s) of the stimulatory regulatory protein of adenylyl cyclase (Gs) causing constitutive activation of the enzyme have been identified in a subset of human GH-secreting pituitary adenomas. This study reports on the differences between acromegalic patients bearing tumors without (group 1; n = 51) or with (group 2; n = 29) this alteration. No difference in age, sex, clinical features, duration of the disease, or cure rate was observed between the two groups. By contrast, group 2 patients had higher basal GH levels than group 1. Moreover, a significant difference in sellar morphology was found; group 2 patients more frequently showed sellas of normal size (grade I) than group 1. Hypersecretory activity of group 2 tumors was also apparent at electron microscopy; contrary to those of group 1, cells of group 2 tumors were densely granulated and showed prominent rough endoplasmic reticulum and Golgi complex. With respect to group 1, group 2 patients were less responsive to GH-releasing hormone, while they were more sensitive to somatostatin- and dopamine-induced GH inhibition. These results suggest that patients with constitutively active adenylyl cyclase have hyperactive tumors; the sensitivity of these tumors to inhibitory agents (somatostatin and dopamine), possibly counteracting the expression of activating mutations, might explain the low rate of tumor growth. 
Hearing improvement after acoustic tumor removal. Hearing improvement after removal of an acoustic tumor is an uncommon occurrence. Hearing improvement was observed in 8.5% of acoustic tumor removals performed using the middle fossa approach in an attempt to preserve hearing. Improvement in speech discrimination occurred most frequently and was of greatest magnitude compared with changes in the speech reception threshold or pure-tone average. No preoperative factors were predictive of postoperative hearing improvement. Findings support the conclusion that candidates for hearing preservation surgery should be chosen on the merits of their existing preoperative hearing and not on the basis of anticipated improvement. 
Diabetes Intervention Study. Multi-intervention trial in newly diagnosed NIDDM. OBJECTIVE: In a randomized 5-yr multi-intervention trial, we tested the efficacy of intensified health education (IHE) in improving metabolic control and reducing the level of coronary risk factors and incidence of ischemic heart disease (IHD). RESEARCH DESIGN AND METHODS: Within the intervention group, the benefit of clofibric acid was evaluated in a double-blind study. One thousand one hundred thirty-nine newly diagnosed middle-aged (30- to 55-yr-old) patients with non-insulin-dependent diabetes mellitus (NIDDM) entered the study. They were classified as diet controlled after a 6-wk screening phase with conventional dietary treatment. During the follow-up, the control group (n = 378) was cared for at different diabetes outpatient clinics with a standardized surveillance. The intervention group (n = 761) had a structured IHE that included dietary advice, antismoking and antialcohol education, and ways to enhance physical activity. RESULTS: Randomly, 379 of the IHE patients received 1.6 g clofibric acid/day, and the others received placebo. IHE resulted in improved glucose control (adjusted fasting blood glucose) levels after 5 yr (control subjects 9.27 mM, IHE group 8.71 mM, and IHE plus clofibric acid group 8.60 mM, P less than 0.01). The better glycemic control was achieved with fewer antidiabetic drugs. After 5 yr, antidiabetic drugs were prescribed to 47% of the control subjects, 28% of the IHE group, and 34% of the IHE plus clofibric acid group (cutoff limit for drug application was postprandial blood glucose of greater than or equal to 13.87 mM). The ratio of polyunsaturated to saturated fatty acids (0.26 vs. 0.40, P less than 0.01) and physical activity (174 vs. 327 scores, P less than 0.01) were increased, and blood pressure, tobacco, and alcohol consumption were significantly reduced by IHE. However, IHE had no effect on calorie intake, percentage of fat in the diet (45%), and body weight. The most important finding was the significant increase of blood cholesterol in all three groups (+0.47, +0.36, and +0.34 mM, respectively). Clofibric acid only prevented the increase of triglyceride levels (+0.56, +0.24, and +0.05 mM, respectively). The incidence rate per 1000 for myocardial infarction was 30.3 for control subjects, 53.6 for the IHE group, and 55.6 for the IHE plus clofibric acid group. The corresponding rates for IHD incidence were 90.9, 97.8, and 98.8, respectively. Men suffered more frequently from myocardial infarction, whereas women developed ECG criteria for IHD more frequently. Among the 35 cases of death, besides cardiovascular diseases, liver cirrhosis and neoplasia were the predominant causes. The death rate per 1000 in control subjects was 46.2, 30.6 in the IHE group, and 27 among patients with IHE plus clofibric acid. CONCLUSIONS: IHE was of substantial benefit for the control of glycemia, significantly diminished the need for antidiabetic drugs, and reduced a cluster of risk factors but had no effect on the control of blood lipids. This could be one major reason for the failure of IHE, effective lowering of blood pressure, and clofibric acid to prevent cardiovascular complications. Clofibric acid was only effective in reducing triglycerides. 
Epidemiology of colonic symptoms and the irritable bowel syndrome. Functional gastrointestinal disease is believed to be very common, but reports of its prevalence have not usually evaluated random community samples, and validated questionnaires have not been used to elicit symptoms. The prevalence of specific colonic symptoms and the irritable bowel syndrome among representative middle-aged whites was determined from a defined population, and the impact of these symptoms on presentation for medical care was measured. An age- and sex-stratified random sample of 1021 residents of Olmsted County, Minnesota, aged 30-64 years, was obtained. All subjects were mailed a valid self-report questionnaire that identified gastrointestinal symptoms and functional gastrointestinal disorders. The response rate was 82% (n = 835). The age- and sex-adjusted prevalence of abdominal pain (more than six times in the prior year) was 26.2 per 100 (95% confidence interval, 23.1-29.2). The prevalence of chronic constipation (hard stools and straining and/or less than 3 stools per week greater than 25% of the time) was 17.4 (95% confidence interval, 14.8-20.0), whereas the prevalence of chronic diarrhea (loose watery stools, and/or greater than 3 stools per day greater than 25% of the time) was 17.9 (95% confidence interval, 15.3-20.5). The prevalence of abdominal pain and disturbed defecation was similar in women and men, except that infrequent defecation and straining at stool were more common in women. Using the Manning symptom criteria to identify irritable bowel syndrome (greater than or equal to 2 of 6 symptoms in those with abdominal pain more than six times in the prior year), the prevalence of irritable bowel syndrome was 17.0 per 100 (95% confidence interval, 14.4-19.6). Overall, 71 persons (9%) reported visiting a physician for abdominal pain or disturbed defecation in the prior year; a subset of variables related to pain severity were the best predictors of health care seeking after adjustment for age and gender. However, these accounted for only 22% of the log likelihood. In conclusion, more than one third of an unselected middle-aged population reported chronic abdominal pain or disturbed defecation, and more than one in six had symptoms compatible with the irritable bowel syndrome. Only a minority had presented for medical evaluation; moreover, the characteristics of the abdominal complaints did not explain the seeking of health care in most cases. 
The development of penicillin-resistant oral streptococci after repeated penicillin prophylaxis. Oral streptococci may cause infective endocarditis in patients with susceptible cardiac disease after dental treatment. Multiple dental visits, each preceded by penicillin prophylaxis, may result in the unwanted development of resistant oral streptococci. This study was undertaken to determine whether resistant oral streptococci would develop after the repeated use of penicillin prophylaxis in healthy adults. Plaque samples were collected from 20 subjects on each Monday for 5 successive weeks. Each subject was administered 2 gm penicillin V followed by 1 gm 6 hours later (standard prophylaxis regimen of the American Heart Association), on three successive Mondays (weeks 2, 3, and 4). The total cultivable oral streptococci and penicillin-resistant oral streptococci were determined for each plaque sample, and representative colonies of resistant streptococci were speciated. During the study, there was a significant increase in the number of subjects who harbored penicillin-resistant oral streptococci. However, with the exception of one subject who had resistant streptococci throughout the study, the number of resistant strains represented only 0.0003% to 0.41% of the total cultivable oral streptococci. 
Snoring and the risk of ischemic brain infarction. To determine if a history of snoring is a risk factor for brain infarction, I conducted a case-control study of risk factors for ischemic stroke using 177 consecutive male patients aged 16-60 (mean 49) years with acute brain infarction. For each patient I chose an age-matched (+/- 6 years) male control. Arterial hypertension, coronary heart disease, snoring (habitually or often), and heavy drinking (greater than 300 g/wk) were risk factors in the stepwise multiple logistic regression analysis. The odds ratio of snoring for brain infarction was 2.13. By McNemar's test this association increased strongly if a history of sleep apnea, excessive daytime sleepiness, and obesity were all present with snoring (odds ratio 8.00). My study indicates that snoring may be a risk factor for ischemic stroke, possibly because of the higher prevalence of an obstructive sleep apnea syndrome among snorers than nonsnorers. 
Kinetic modeling of in vivo--nuclear magnetic resonance spectroscopy data: 5-fluorouracil in liver and liver tumors. Kinetic modeling has been applied to the time course of the nuclear magnetic resonance signal intensities of 5-fluorouracil and the sum of its catabolites, alpha-fluoro-beta-ureido propanoic acid and alpha-fluoro-beta-alanine, as monitored in liver tumors of seven patients with cancer after brief intraarterial infusion of 5-fluorouracil. Because these data represent only relative tissue concentrations, only ratios of clearance and volume parameters can be estimated (e.g., clearance/central volume of distribution or central volume of distribution/steady-state volume of distribution). On the other hand, parameters that do not refer to volumes, such as half-lives or maximal velocity of metabolic conversion of a nonlinear model, can be estimated in absolute terms. A nonlinear three-compartment model gave satisfactory fits with all of the individual data sets. Kinetics of 5-fluorouracil and catabolites were similar in five patients with metastases of colorectal adenocarcinomas but differed from those of two patients with cholangiocarcinoma and metastases of an anaplastic carcinoma of unknown origin, respectively. 
Percutaneous cooling of ischemic myocardium by hypothermic retroperfusion of autologous arterial blood: effects on regional myocardial temperature distribution and infarct size. The effects of synchronized coronary venous retroperfusion of cooled autologous arterial blood on regional myocardial temperature distribution and infarct size were studied in open chest dogs with 3.5 h of left anterior descending coronary artery occlusion. After 30 min of occlusion, the dogs were randomly assigned to one of three groups: 1) untreated control group (n = 5), 2) normothermic retroperfusion group (infusion temperature 32 degrees C) (n = 7), and 3) hypothermic retroperfusion group (infusion temperature 15 degrees C) (n = 7). Regional myocardial temperatures were measured by using needle-tipped thermistors stabbed in the 1) anterior wall distal to the occlusion site, 2) anterior wall proximal to the occlusion site, 3) left lateral wall, 4) posterior wall, and 5) right ventricular free wall. Rectal and pulmonary artery temperatures were also measured. In the hypothermic retroperfusion group, the anterior wall temperature decreased rapidly by 5 degrees C at 15 min of retroperfusion (p less than 0.05 vs. normothermic retroperfusion or untreated control groups), whereas the temperature at other sites decreased with a linear trend over time. Myocardial temperatures in the ischemic area (distal anterior wall) were generally lower than those in the other sites during the first 60 min of hypothermic retroperfusion and the largest intramyocardial temperature difference (3.6 degrees C) was found at 15 min after retroperfusion. Infarct size expressed as a percent of the risk area was significantly smaller in the hypothermic retroperfusion group (6.2 +/- 3.3%) than in the control (64.9 +/- 14%) or normothermic retroperfusion groups (24.1 +/- 6.7%). 
Comprehensive evaluation and treatment of 75 men referred to chronic prostatitis clinic. We investigated the role of genitourinary tract infections, structural and psychologic abnormalities in 75 men referred to a "chronic prostatitis" clinic. Patients had had symptoms for an average of eighty-three months and had received an average of ten weeks of antimicrobial treatment during the three months prior to evaluation. Specific infectious diseases, structural or functional causes were identified in 34 (45%) of the 75 patients. Genitourinary tract pathogens were isolated from 26 patients and inflammation was documented in urethral or prostatic secretions of 24 patients. Structural or functional abnormalities that merited treatment were identified in 8 cases. In addition, major criteria for depression were documented in 9 of 17 patients who agreed to this evaluation. Overall, a comprehensive approach to diagnosis led to specific treatment for 37 (49%) of the 75 men with chronic prostatitis, despite longstanding symptoms and failure of multiple prior courses of therapy. 
A new anticancer drug delivery system for the management of carcinomatous peritonitis. To develop a new drug delivery system for the treatment of carcinomatous peritonitis, we constructed 5-fluorouracil poly L-microcapsules (5Fu-mc) by the organic phase separation technique and examined their drug-releasing capacities and anticancer effects. The microcapsules consisted of in vitro dissolvable polymolecular poly L-lactic acid and 5-fluorouracil (5Fu). The 5Fu-mc was about 200 microns in diameter and had a 5Fu content of about 40% (weight/weight). 5Fu-release time from the microcapsules was about 50 hours in vitro and about 48 hours in vivo. After the release of the 5Fu, the poly L-lactic acid was metabolized very slowly in the peritoneal cavity. The 5Fu-mc caused fewer side effects than the equivalent dose of a 5Fu solution. In addition, macroscopic and microscopic examinations of various abdominal organs revealed no toxic effects from the microcapsules. After administration of 5Fu-mc into the abdominal cavity of rats with AH-130 carcinomatous peritonitis, the 5Fu concentration remained at a high level for an extended period in the ascites but fell rapidly to low levels in the plasma. In conclusion, the present studies indicated that the 5Fu-mc were much more effective in prolonging the life of tumor-bearing hosts while producing less systemic side effects than a 5Fu solution. 
Acyclovir therapy in neonates. STUDY OBJECTIVE: To determine the pharmacokinetic parameters of acyclovir disposition in neonates with renal dysfunction. DESIGN: Prospective sequential open enrollment of neonates with presumed herpes group virus infections. SETTING: Neonatal intensive care units in the greater Minneapolis-St. Paul metropolitan area. PATIENTS: Sixteen neonates with gestational ages between 27 and 40 weeks (median 38 weeks) were given acyclovir between days 1 and 56 of life to treat presumed herpes virus infections. Six infants were critically ill with multisystem disease, five infants had hepatic failure and underwent blood exchange transfusion, and five infants had renal failure. A mean of four (range 1 to 19) serum acyclovir concentrations per patient were measured by radioimmunoassay. Pharmacokinetic parameters were calculated from acyclovir concentrations in 46 samples from 16 patients. MEASUREMENTS AND MAIN RESULTS: The pharmacokinetic disposition of acyclovir was described as a two-compartment model. Although the ranges for acyclovir clearance and terminal elimination (t 1/2 beta) were wide, a statistically significant relationship was demonstrated between clearance and beta versus serum creatinine concentration. The average t 1/2 beta for infants with serum creatinine level less than 1 mg/dl (88 mumol/L) was 5.0 hours, and 15.6 hours for those with serum creatinine level greater than 1 mg/dl. CONCLUSIONS: Neonates with hepatic or renal dysfunction or young premature infants accumulate acyclovir when dosed without adjustment for organ dysfunction. Measurement of serum creatinine or creatinine clearance can be useful in the dosing of acyclovir in neonates. 
Blood loss after total knee replacement. Effects of tourniquet release and continuous passive motion. We prospectively studied the cases of 121 patients who were being operated on for insertion of a unilateral total knee prosthesis with cement, and we placed them randomly in four groups. In Group I, the tourniquet was inflated throughout the operative procedure, and we released it postoperatively after a compressive dressing had been applied; a splint was used postoperatively for three days. In Group II, the tourniquet remained inflated throughout the operation, but no splint was applied postoperatively, and continuous passive motion was started immediately in the recovery room. In Group III, the tourniquet was released intraoperatively, and hemostasis was achieved by cauterization; postoperatively, a compressive dressing was applied, and a splint was used for three days. In Group IV, the tourniquet was released intraoperatively, hemostasis was established, and then the tourniquet was reinflated; a compressive dressing was applied, and continuous passive motion was started immediately in the recovery room. Hemoglobin and hematocrit values were monitored in all patients. Blood loss in suction drainage was recorded, and the total blood loss was calculated. The results show that total knee arthroplasty is associated with major loss of blood (mean, 1518 milliliters). The calculated blood loss for Groups I, II, and III averaged 1443 milliliters, while that for Group IV averaged 1793 milliliters. Loss in suction drainage correlated with total estimated blood loss and averaged 511 milliliters. The magnitude of blood loss after total knee arthroplasty should be appreciated, and special attention should be paid to the availability of adequate fluid and blood products, preferably blood donated by the patient preoperatively. 
Pregnancy outcome in patients with high titer anti-RNP antibodies. A retrospective study of 40 pregnancies. In a retrospective study the outcome of 40 pregnancies in 20 women with a high titer of anti-RNP antibodies was evaluated. In the 18 pregnancies that occurred after disease onset, transient proteinuria was noted in 3 and transient thrombocytopenia in 2. Deep venous thrombosis was observed in one patient. Preeclampsia in another woman necessitated cesarean sections in 2 pregnancies with successful outcome. The observed complications may all be seen in normal pregnancies. There was no evidence of exacerbation of maternal disease during pregnancy or in the postpartum period. Our study indicates that in women with high anti-RNP titer the risk of fetal loss or maternal worsening of disease seems slight. 
Effusion cytology. Cytologic evaluation is the best way to detect the presence of malignancy in body cavity fluids. Although a positive diagnosis is highly reliable, a negative result does not rule out a malignant cause. Adenocarcinomas, well-differentiated squamous carcinomas, small-cell carcinomas, malignant melanomas, large-cell lymphomas, and acute leukemias are accurately classified when present in effusions. The definitive diagnosis of malignant mesothelioma, small-cell lymphomas, and chronic leukemias, and subclassification of sarcomas and poorly differentiated neoplasms are difficult and may require additional diagnostic techniques. With a few exceptions, the exact causes of benign effusions cannot be determined by cytologic methods. 
Safety of simultaneous aortic reconstruction and renal transplantation. Patients with aortic disease and end-stage renal failure who require both aortic reconstruction and renal transplantation (simultaneously or staged) pose a formidable clinical challenge. Traditionally, the performance of either one of these procedures has been viewed as a relative contraindication to the performance of the other. From 1978 to 1989, eight patients were referred to us with the combination of aortic disease and end-stage renal failure. Seven had aneurysmal disease and one had aorto-iliac occlusive disease. Five patients presented with their diseases sequentially and had two sequential operations, with a mean interval of 4 years between procedures. Three patients presented with their diseases simultaneously and underwent simultaneous aortic reconstruction and living related renal transplantation. All patients were followed up for a mean interval of 4.5 years. By life-table analysis, the 5-year renal graft survival was 100%, the primary aortic graft patency was 82%, and the secondary aortic graft patency was 100%. The only death in this series occurred 11 years after aortic reconstruction and 4 months after a renal transplantation and was due to overwhelming cytomegalovirus sepsis. There were no significant differences between the simultaneous and staged groups in terms of operative mortality, postoperative complications, transplant function, or aortic graft patency. From this experience, we conclude that: (1) patients who present simultaneously with aortic disease and end-stage renal failure can safely undergo simultaneous aortic reconstruction and renal transplantation; (2) patients who present with these two diseases sequentially can undergo a second reconstructive procedure with very low operative morbidity and mortality rates; (3) when these two procedures have been performed sequentially, the second procedure has not significantly altered the 30-day or 5-year results of the first procedure; and (4) the 30-day and 5-year results of each procedure have been excellent regardless of the temporal sequence in which they were performed. 
Biomagnetic localization of ventricular arrhythmias. The magnetic fields caused by electrical activity of the human heart can be coherently measured with a highly sensitive, multichannel, superconducting quantum interference-device system and can enable noninvasive localization of the underlying electrical activity. The magnetocardiograms (MCGs) of 10 patients with spontaneous premature ventricular complexes (PVCs), three patients with ventricular tachycardia (VT), and four healthy subjects with induced paced beats were recorded for 2-15 minutes. After correction for superimposed repolarization activity, the site of origin of the arrhythmias was localized from the magnetic field distribution at the onset of the ectopic beats. The localization results of paced beats showed an error of a few millimeters in relation to the position of the catheter tip. The results of spontaneous PVC and VT were confirmed with endocardial mapping or associated with ischemic lesions. The authors conclude that multichannel magnetocardiographic studies enable the completely noninvasive localization of ventricular arrhythmias. 
Primary tumors of the facial (extracranial) nerve. Nearly 25% of all primary neurogenous tumors arise from peripheral nerves in the head and neck. The extracranial parts of the facial nerve, however, rank low as potential sites. Their tumors nonetheless pose diagnostic and management problems. In the intraparotid location the neurogenous tumors most often present as mass lesions, accompanied, in one third of patients, by various degrees of facial weakness. With the exception of a peculiar predilection of childhood plexiform neurofibromas to afflict the facial nerve, the majority of the tumors are neurilemomas. Recurrences are unusual after surgical removal of either neurilemomas or neurofibromas. The rare facial nerve sarcoma is a high-grade malignancy. 
Giant axonal neuropathy and leukodystrophy. An 11-year-old Persian boy, born to consanguineous parents, manifested a progressive gait abnormality beginning at 5 years of age. A severe cerebellar disorder developed with associated dysfunction of the peripheral nervous system, but no sign of mental impairment. The sensory and motor nerve conduction velocities were greatly reduced, especially in the lower extremities. Cerebrospinal fluid protein was normal. Computed tomography and magnetic resonance imaging revealed leukoencephalopathy, especially in the cerebellum, but also in periventricular areas. The diagnosis of giant axonal neuropathy was established by biopsy of the sural nerve. The few previous histologic examinations have documented hyperplasia of the microfibrils which accumulate in the axons as well as in neurilemma, endothelial, and perineural cells. This is the first report of involvement of supraspinal portions of the central nervous system documented by postmortem examination after in vivo imaging methods corroborated the morphologic concomitants of the clinical symptoms. 
Efficacy of intraarterial heparin in maintaining microvascular patency: an experimental model. Human-grade sodium heparin was studied to determine thrombosis model patency rates between an intraarterial infusion versus an intravenous method of delivery in a rabbit model. Specific differences in patency and partial thromboplastin times were studied in each group and compared with a saline-perfused group. Three animal groups (New Zealand white rabbits) were established (total = 35 animals). Standardized femoral arterial 5-mm inversion grafts (AIG) were done in each animal in each group. The animals in the control group received intravenous saline infusion, while the two treatment groups received intravenous heparin (12 animals) or intraarterial heparin (12 animals minus 1 anesthesia death). The route of instillation of the infusate was selected at random after completing the inversion grafts. A proximal epigastric branch was utilized for access in those animals randomized to the intraarterial group. Intravenous delivery was accomplished by means of a femoral venous catheter in the vena cava. A 72-hour period of infusion was used in all animals. A dose of 45 units per hour of heparin following a 500-unit bolus was used in the intravenous group. After an identical bolus dose, 25 units per hour of heparin was administered in the intraarterial group. The control (saline group) was given 1 cc saline (in a volume equal to the heparin-dosed groups) daily for 3 days. Arterial inversion graft patency rates were assessed by direct inspection at day 5. Systemic and regional (i.e., distal to the inversion graft) partial thromboplastin times (PTT) were measured in representative control, IV, and intraarterial heparin-treated groups. Complications were recorded. 
Attaching and effacing enteropathogenic Escherichia coli as a cause of infantile diarrhea in Bangkok. To identify Escherichia coli that cause infantile diarrhea in Bangkok, Thailand, E. coli isolated in a year-long study of infantile diarrhea were examined for O and H serotypes and virulence determinants. Classic enteropathogenic E. coli (EPEC) were isolated from 28 of 509 infants with diarrhea (cases) and 11 of 509 age-matched controls (P = .009; odds ratio [OR], 2.64). Most of this difference was attributable to EPEC adherence factor (EAF)-positive EPEC that produced an attachment and effacement lesion, as identified in the fluorescence actin staining assay, isolated from 13 cases and 1 control (P = .003; OR, 13.3). EAF-EPEC was isolated from 15 cases and 10 controls (P = .418; OR, 1.52) and EAF+ non-EPEC from 17 cases and 10 controls (P = .242; OR, 1.72). EAF+EPEC that caused an attachment and effacement lesion was found in 3% of children less than 6 months old with diarrhea who were studied in an outpatient clinic in Bangkok in 1988. 
Inflammatory pseudotumor of the spleen. Report of two cases with a review of the literature. This study reports two cases of inflammatory pseudotumor of the spleen. The first case was a 57-year-old woman in whom the splenic mass was an incidental finding during evaluation for an acute abdomen due to a perforated, lithiasic gallbladder. The mass in the spleen measured 12.7 cm in greatest dimension. The second case was of a 46-year-old woman with a palpable, left upper quadrant mass. A computed tomography scan revealed a splenic mass and the spleen was removed. The mass measured 12 cm in greatest dimension. In a review of the literature, 13 examples of splenic inflammatory pseudotumor were reported. The age range was 19 to 75 years, with a median age of 50 years. The splenic lesions were either discovered incidentally or manifested by left upper quadrant discomfort and/or mass. Inflammatory pseudotumor of the spleen, although rare, is being increasingly recognized and should be considered in the differential diagnosis of mass lesions of the spleen. 
Sixteenth Daniel C. Baker, Jr, memorial lecture. Surgical management of supraglottic cancer and its lymph node metastases in a conservative perspective. Supraglottic laryngectomy combined with functional elective or curative neck dissection is a priceless contribution toward treatment of supraglottic cancer and its lymph node metastases. The history and background of this conservative approach is reviewed. Results related to staging are presented. Irradiation as a combined or alternative therapy is considered. 
Role of hepatitis delta virus infection in hepatocellular carcinoma. Hepatitis B virus (HBV) DNA integrates into the host DNA and shows a series of potentially oncogenetic properties, but HBV is not an acutely transforming virus, because HCC develops decades after infection. Other factors, namely cirrhosis, inflammation, alcohol intake, and viral superinfections, could promote the oncogenetic process induced by HBV-DNA integration. We studied the impact of HDV infection in the pathogenesis of HCC in 62 consecutive patients. Their mean age was 59 years (range 25-75 years), 54 were male and eight female; 58 had cirrhosis. The findings suggest that HBsAg-positive patients with HDV superinfection developed cirrhosis and HCC at an earlier age than HBsAg carriers without HDV infection. HDV appears to represent a "promotion" factor for HCC in subjects with an oncogenic risk induced by HBV. A long-lasting necroinflammatory lesion of the liver substained by productive HBV and HDV infections may be a major pathogenetic mechanism. 
Chronic dermal ulcer healing enhanced with monophasic pulsed electrical stimulation. The purposes of this randomized, double-blind, multicenter study were to compare healing of chronic dermal ulcers treated with pulsed electrical stimulation with healing of similar wounds treated with sham electrical stimulation and to evaluate patient tolerance to the therapeutic protocol. Forty-seven patients, aged 29 to 91 years, with 50 stage II, III, and IV ulcers were randomly assigned to either a treatment group (n = 26) or a control (sham treatment) group (n = 24). Treated wounds received 30 minutes of pulsed cathodal electrical stimulation twice daily at a pulse frequency of 128 pulses per second (pps) and a peak amplitude of 29.2 mA if the wound contained necrotic tissue or any drainage that was not serosanguinous. A saline-moistened nontreatment electrode was applied 30.5 cm (12 in) cephalad from the wound. This protocol was continued for 3 days after the wound was debrided or exhibited serosanguinous drainage. Thereafter, the polarity of the treatment electrode on the wound was changed every 3 days until the wound progressed to a stage II classification. The pulse frequency was then reduced to 64 pps, and the treatment electrode polarity was changed daily until the wound was healed. Patients in the control group were treated with the same protocol, except they received sham electrical stimulation. After 4 weeks, wounds in the treatment and control groups were 44% and 67% of their initial size, respectively. The healing rates per week for the treatment and control groups were 14% and 8.25%, respectively. The results of this study indicate that pulsed electrical stimulation has a beneficial effect on healing stage II, III, and IV chronic dermal ulcers. 
Levamisole for corticosteroid-dependent nephrotic syndrome in childhood. British Association for Paediatric Nephrology. In children with corticosteroid-responsive nephrotic syndrome who are dependent on high-dose prednisolone, alkylating therapy often fails to maintain a remission, and long-term immunosuppression may be hazardous. An alternative approach to treatment is to use an immunostimulant such as levamisole. 61 children with frequently relapsing corticosteroid sensitive and dependent nephrotic syndrome were randomly allocated to receive levamisole, 2.5 mg/kg on alternate days (31 patients) or placebo (30 patients) for a maximum of 112 days. After entry to the trial, prednisolone was progressively reduced and was stopped by 56 days. The two groups were well matched for age and sex distribution, indices of corticosteroid toxicity, and previous alkylating therapy. 14 patients in the levamisole group and 4 in the placebo group remained in remission at 112 days (log rank analysis p less than 0.01). No significant adverse events were recorded. Levamisole is effective in maintaining a steroid-free remission in this condition and has few side-effects. 
Lack of efficacy of high-dose leucovorin and fluorouracil in patients with advanced pancreatic adenocarcinoma. Leucovorin potentiates the cytotoxicity of fluorouracil (5-FU) in experimental tumor systems and appears to enhance the effectiveness of 5-FU in patients with colon cancer. Twenty-two eligible patients (18 previously untreated) with advanced pancreatic adenocarcinoma were treated in a phase II trial of leucovorin 500 mg/m2/d for 6 days by continuous intravenous infusion with 5-FU 370 mg/m2/d by rapid intravenous injection on 5 consecutive days, beginning 24 hours after initiation of leucovorin infusion. Among the 20 assessable patients, there were no complete or partial regressions, although there was one minor response lasting 4 months. Three patients had stable disease for 5, 20, and 21 months, respectively. Median survival was 10 weeks. Toxicity was predominantly mucosal; stomatitis grade 2 or worse was seen in five patients, and diarrhea grade 2 or worse was seen in four. Hospitalization for toxicity was necessary in four previously untreated patients and three previously treated patients. The median WBC nadir was 4.6 (range, 1.4 to 9.6) x 10(3)/microL, and the median platelet nadir was 147.0 (range, 69.0 to 240.0) x 10(3)/microL. This combination of leucovorin and 5-FU did not demonstrate meaningful therapeutic activity in patients with adenocarcinoma of the pancreas and was associated with moderate to severe toxicity. It should not be considered a standard treatment for patients with this disease. 
Percutaneous placement of Hickman catheters: comparison of sonographically guided and blind techniques. We studied the value of sonographically guided puncture of the subclavian vein for placement of indwelling right atrial and permanent subcutaneously tunneled catheters (Hickman) for long-term venous access. The commonly used blind puncture is associated with complications such as pneumothorax, arterial puncture, and hemothorax. The results and complications of 40 sonographically guided punctures and fluoroscopically controlled catheterizations of the subclavian vein (group 1, 31 patients) performed in the radiology department were compared with those of 40 blind percutaneous punctures and fluoroscopically controlled catheterizations (group 2, 29 patients) performed in the operating room. The patients were selected consecutively. The groups were comparable in age, sex, and indication for catheter placement; administration of chemotherapy for hematologic malignancies was the major indication (group 1, 84%; group 2, 83%). All punctures in group 1 were successful; group 2 had two failures (5%). Puncture-related complications occurred significantly more in group 2 (10%) than in group 1 (0%) (p less than .05). These complications were pneumothorax in three cases and hemothorax in one. Complications not related to the puncture technique were prolonged bleeding at the entrance site (groups 1 and 2, two cases each), local infection (group 1, one case), thrombosis (group 1, three cases; group 2, two), catheter sepsis (group 1, 10 cases; group 2, 14), catheter occlusion (group 2, three cases), and catheter migration (groups 1 and 2, two cases each). We conclude that sonographically guided puncture increases the success rate and significantly decreases the puncture-related complications of percutaneous placement of Hickman catheters. 
Operative laparoscopy with the Nd:YAG laser in the treatment of endometriosis and pelvic adhesions. A multicenter, prospective trial was initiated to test the effectiveness and safety of the Nd:YAG laser equipped with artificial sapphire contact tips for the laparoscopic treatment of pelvic pain. Ninety-three women were enrolled in the study, 37 with endometriosis alone, 47 with endometriosis complicated by pelvic adhesions, and 9 women with adhesions alone. In over 90% of adhesions and 96% of endometriotic implants the Nd:YAG laser could be delivered to the site and be used to restore normal anatomy. The exception was deep bowel involvement with endometriosis, which was not treated. The majority of women had marked reduction or resolution of their symptoms for up to 12 months postoperatively. We conclude that the use of the Nd:YAG laser is an appropriate method to laparoscopically treat pelvic pain resulting from endometriosis or pelvic adhesions. 
Adult lipophagic atrophic panniculitis. We report two patients with chronic, recurrent, nodular panniculitis lesions that later developed areas of lipoatrophy. Histologically, there was a consistent lobular lipophagic replacement of fat cells with lipophagic giant cells. The clinical appearance was that of tender, erythematous, superficial or subcutaneous, symmetrical nodules and plaques of 1-2 weeks' duration. The lesions could occur with episodes of fever. One patient had hepatomegaly and the other had an increased sedimentation rate and leucocytosis. The histology and the clinical pattern of the panniculitus syndrome resembled those of lipophagic lipoatrophy of childhood. This is a panniculitis of unknown cause in which the principal inflammatory cell response in the subcutaneous tissue is the macrophage. 
Flow cytometric analysis of peripheral blood lymphocytes in ulcerative colitis and Crohn's disease. Using two colour immunofluorescence with fluorescein isothiocyanate and phycoerythrin labelled monoclonal antibodies, multi-parameter flow cytometry was used to examine the antigenic characteristics of peripheral blood lymphocytes in whole blood of patients with ulcerative colitis and Crohn's disease who were not taking immunosuppressive drugs. The numbers of CD4+ and CD8+ lymphocytes in patients with ulcerative colitis and Crohn's disease remained unchanged so that the CD4/CD8 ratio was the same as that of normal control subjects. In Crohn's disease there were many activated T cells (CD3+, CD25+). Although natural killer cells in active Crohn's disease were lower than in normal control subjects, cytotoxic T lymphocytes, as defined by CD3+, CD16+, did not differ in patients with inflammatory bowel disease compared with normal control subjects. For B cell subsets, there were differences in Leu-1+ B cells, Leu-8+ B cells, Fc epsilon R+B cells (Leu-16+, Leu-20+), and activated B cells (Leu-12+, Leu-21+) between patients with inflammatory bowel disease and normal control subjects. These differences are compatible with local activation of B cells in the inflamed colon. 
Carcinoma of the rectum: a 10-year experience. A consecutive series of 303 patients with carcinoma of the rectum and distal sigmoid colon treated by a single surgeon over a 10-year period are reported. Of these, 202 underwent an anterior resection, 85 an abdominoperineal excision of the rectum and 16 a coloanal anastomosis. Surgery was considered palliative in 52 patients undergoing anterior resection and 24 undergoing abdominoperineal resection. The 30-day hospital mortality rate was six patients (3 per cent) for anterior resection and two patients (2 per cent) for abdominoperineal resection. Peroperative anastomotic testing demonstrated leakage in five stapled anastomoses; these were rectified and no clinical sequelae occurred. Two patients (1 per cent) developed a clinical anastomotic leak, one of which proved fatal; in each case the intraoperative test was negative. The overall 5-year survival rate was 64 per cent after anterior resection and 52 per cent after abdominoperineal resection; the median follow-up was 64 months. The incidence of local pelvic recurrence was 6.4 per cent after anterior resection and 14 per cent after abdominoperineal (not significant). These results confirm the success of sphincter-saving anterior resection combined with total mesorectal excision, routine full mobilization of the splenic flexure and cancercidal lavage of the distal rectum in the treatment of low rectal carcinomas; morbidity, local recurrence and survival are not compromised. 
Internal mammary artery to lung parenchyma fistula after aortocoronary bypass grafting. Two unusual cases of internal mammary artery fistulization to lung parenchyma after coronary revascularization are reported. They were incidentally discovered during coronary angiography, and one of them was successfully closed with a percutaneous transvenous coil-spring occluder. The cause is thought to be the direct contact between the dissected mammary artery pedicle and the lung parenchyma. 
Diffuse neonatal hemangiomatosis: a new constellation of findings. Diffuse neonatal hemangiomatosis is a rare, frequently fatal disease characterized by multiple cutaneous and visceral hemangiomas. The skin, liver, lungs, intestines, and central nervous system are the most commonly affected organs. Death can result from high-output cardiac failure as a result of arteriovenous shunting. In this report we present a new constellation of findings in a patient with diffuse neonatal hemangiomatosis, namely, an absent corpus callosum, ectopia cordis (sternal agenesis) with median abdominal raphe, and tricuspid atresia. 
Laparotomy closure reinforced with buried polyglyconate retention sutures. A method of laparotomy closure using continuous no. 0 polyglycolic acid suture for accurate fascial approximation and buried retention sutures of no. 1 polyglyconate for prolonged wound strength is described. Both security and anatomical precision in fascial closure are achieved without the use of nonabsorbable suture material. This method of laparotomy closure is suitable for patients at high risk for fascial dehiscence. 
Adjuvant radiation therapy in patients with detectable prostate specific antigen following radical prostatectomy. Adjuvant radiation therapy following radical prostatectomy for adenocarcinoma of the prostate was given to 25 patients. Of these patients 8 had microscopic lymph node metastasis, 8 had seminal vesicle invasion without positive lymph nodes, 6 had positive surgical margins and 3 had only capsule penetration. Their only evidence of residual disease was detectable serum prostate specific antigen (PSA) by the Yang assay. A total of 15 patients (60%) had a subsequent decrease in PSA to less than 0.3 ng./ml. and an additional 5 (20%) had a decrease in PSA by more than 50%. Currently 8 patients have no detectable PSA after a median followup of 18 months (17 to 38 months) since initiating radiation therapy. Only 1 of 12 patients with detectable PSA immediately after radical prostatectomy has had a durable response to adjuvant radiation therapy. In contrast 7 of 13 patients with a delayed increase in PSA had a durable response. The ability of adjuvant radiation therapy to eliminate serum PSA in patients with a delayed increase in PSA after radical prostatectomy is encouraging. However, longer followup, including the use of nonradiated control subjects, is needed to assess the ability of adjuvant radiation therapy to control local disease and prolong patient survival. 
Combined portal vein and liver resection for carcinoma of the biliary tract. Twenty-nine patients with advanced carcinoma of the bile duct or gallbladder underwent combined portal vein and liver resection. Segmental excision of the portal vein was performed in 16 cases and wedge resection of the vessel wall in 13. The operative mortality rate was 17 per cent. The median survival for the 24 patients who left hospital was 19.8 months. Actuarial survival rates at 1, 3 and 5 years for all 29 patients were 48 per cent, 29 per cent, and 6 per cent respectively, whereas the median survival for 46 patients with unresectable carcinoma was 3 months and the 1 and 3-year actuarial survival rates were 13 per cent and zero respectively. This difference in survival times between patients undergoing hepatectomy with portal vein resection and those with unresectable carcinoma were statistically significant (P less than 0.01). Combined portal vein and liver resection is recommended as a reasonable surgical approach in selected patients with advanced carcinoma of the biliary tract. 
Soluble interleukin 2 receptor levels in serum and its relationship to T cell abnormality and clinical manifestations of the disease in patients with systemic lupus erythematosus. Systemic lupus erythematosus (SLE) is associated with alterations in immune regulation that results in T cell activation and release of the soluble interleukin 2 receptors (sIL-2R) in serum. SLE, a disease with varied clinical manifestations also has regulatory T cell subset abnormalities in blood. Levels of sIL-2R in serum of patients with active SLE were higher than in those with other common rheumatic diseases. Patients with active SLE and an increased percentage of CD4+ CDw29+ helper inducer (memory) and decreased percentage of CD4+ CD45R+ suppressor inducer (virgin) T cell subsets in blood demonstrated elevated levels of sIL-2R in serum. When compared with clinical manifestations of the disease, the sIL-2R levels in the sera of the patients with active SLE and thrombocytopenia were higher (mean 1710 units/ml) than those in active SLE with nephrotic syndrome (mean 1230 units/ml) or in active SLE with central nervous system disease (mean 1157 units/ml). However, patients with active SLE with humoral immunodeficiency (hypogammaglobulinemia) had highly elevated levels of sIL-2R in serum as compared to other patients with active SLE. The highly elevated levels of sIL-2R in serum may indicate that in vivo T cell activation plays an important role in this disease. 
Predictive value of ventricular arrhythmias for patency of the infarct-related coronary artery after thrombolytic therapy. In animal studies reperfusion of coronary arteries is commonly accompanied by ventricular arrhythmias. It is not certain, however, whether ventricular arrhythmias can be used as a reliable non-invasive marker of reperfusion in humans. Two-channel Holter recordings were obtained from the start of an intravenous infusion of streptokinase until coronary angiography (2.8 (2.7) hours (mean SD)) afterwards) in 57 patients with acute myocardial infarction of less than four hours who were generally not treated with antiarrhythmic drugs. Ventricular arrhythmias occurred in 21 (37%) of the 57 patients: accelerated idioventricular rhythm in 13 patients and non-sustained ventricular tachycardia in 15 patients. Seven patients had both accelerated idioventricular rhythm and non-sustained ventricular tachycardia. Coronary angiography showed a patent infarct-related vessel in 12 (92%) of the 13 patients with accelerated idioventricular rhythm (95% confidence interval 66 to 99%), in 22 (50%) of the 44 patients without accelerated idioventricular rhythm (95% CI 34 to 66%), in 11 (73%) of the 15 patients with non-sustained ventricular tachycardia (95% CI 45 to 92%), and in 23 (55%) (95% CI 39 to 71%) of the 42 patients who did not have non-sustained ventricular tachycardia. Seventeen (81%) of the 21 patients with accelerated idioventricular rhythm, or non-sustained ventricular tachycardia, or both, had a patent infarct-related vessel (95% CI 58 to 94%) as did 17 (47%) of the 36 patients with no ventricular arrhythmia (95% CI 29 to 65%). In patients with accelerated idioventricular rhythm after thrombolysis the infarct-related vessel is almost certain to be patent; but the infarct-related coronary artery can still be patent when no arrhythmia is seen. 
Clinical usefulness of amitriptyline in fibromyalgia: the results of 23 N-of-1 randomized controlled trials. Twenty-three double blind, randomized, multiple crossover trials (N-of-1 RCT) of amitriptyline were conducted in patients with fibromyalgia. The benefit of amitriptyline was assessed using a symptom questionnaire and count of tender points. To assess the usefulness of the method, the proportion of trials that provided a definite answer was examined. Completing the trial resulted in reaching a high degree of confidence in the final management decision in 74% of trials. In 35% of trials, results led to discontinuation of the drug which otherwise would have been continued indefinitely. The drug benefit, if present, was evident within first 2 weeks of therapy. We concluded that these results support the feasibility and usefulness of N-of-1 RCT in rheumatology practice. 
Fatal varicella-zoster virus meningoradiculitis without skin involvement. A 77-year-old man with T-cell lymphoma developed an acute fatal meningoradiculitis of cranial nerve roots and cauda equina, pathologically and virologically confirmed to be caused by varicella-zoster virus. This is the first report of fatal varicella-zoster virus-induced neurological disease in the absence of skin lesions. Varicella-zoster virus should be included in the differential diagnosis of acute radiculoneuropathy in the immunocompromised patient, particularly because antiviral treatment for varicella-zoster virus exists. 
Situational and psychophysiological factors in psychologically induced pain. To investigate pain that occurs in the absence of painful stimulation, normal subjects were connected to a sham stimulator and were told that a headache could occur as a result of the electrical current they would receive. Half of the subjects who received this suggestion reported pain. The frequency and intensity of pain reports in a group which was given prior pain experience as a reference point in reporting pain and in a group which was exposed to a manipulation designed to reduce intentional deception were not significantly different from the pain reports of a group not exposed to these manipulations. The frequency of pain reports in subjects not connected to the sham stimulator but still asked to report pain was 25% which was significantly less than the frequency for subjects who were told there would be stimulation to the head. Pain ratings increased as the settings of the sham stimulator were increased. Subjects who reported pain had significantly fewer electrodermal responses to tones signaling them to prepare for a reaction time task. The results suggest that pain can be produced in the absence of peripheral stimulation. The pain does not appear to be due to intentional deception or the lack of a standard for comparison, but is strongly influenced by environmental cues. Psychophysiologically, pain responders were less attentive to signal stimuli. 
Relationship of HBsAg subtypes with HBeAg/anti-HBe status and chronic liver disease. Part I: Analysis of 1744 HBsAg carriers. A total of 1744 HBsAg carriers were investigated to determine whether there are clinical differences among HBsAg subtypes or not. Although adr was more predominant than adw in 1078 asymptomatic carriers as well as in 666 carriers with liver dysfunction, the adr carriers had liver dysfunction more frequently than the adw carriers (p = 0.005). In addition, the adr carriers were more often positive for HBeAg and less often positive for anti-HBe than the adw carriers (p less than 0.001). Multivariate analyses indicated that the HBsAg subtypes were associated with liver dysfunction not directly but through the relationship between the HBsAg subtypes and HBeAg/anti-HBe status. HBeAg/anti-HBe status of each age bracket in the adr carriers and in the adw carriers suggested that adr carriers are seroconverted later than adw carriers. In conclusion, HBsAg subtypes may affect the development of chronic liver disease, through their association with HBeAg/anti-HBe status. 
Recurrent hepatocellular carcinoma after partial hepatectomy: value of treatment with transcatheter arterial chemoembolization. The usefulness of transcatheter arterial chemoembolization (TACE) of the hepatic artery was retrospectively evaluated in 66 patients who underwent the procedure for treatment of hepatocellular carcinoma that recurred after partial hepatectomy. The materials infused were Gelfoam sponge or Gelfoam sponge plus Lipiodol and an anticancer agent. A control group of 15 patients with recurrent tumor received oral anticancer agents alone. The cumulative survival rate for the TACE group was 88% for the first year, 57% for 2 years, 42% for 3 years, and 27% for 5 years, whereas that of the control group was 80% for the first year, 27% for 2 years, and 18% for 3 years. Thus, the prognosis of the TACE group was significantly better (p less than or equal to .01, log-rank test) than that of the control group. The survival rate was inversely correlated with the ratio of the volume of the recurrent tumor to the volume of the whole residual liver. These results suggest that TACE is more effective than oral chemotherapy for treatment of hepatocellular carcinoma that recurs after partial hepatectomy. 
Suppression of chronic myelogenous leukemia colony growth by interleukin-1 (IL-1) receptor antagonist and soluble IL-1 receptors: a novel application for inhibitors of IL-1 activity. In this study, we investigated the role of interleukin-1 beta (IL-1 beta) in the malignant evolution of chronic myelogenous leukemia (CML) and the functional activity of IL-1 inhibitors. Bone marrow (BM) and peripheral blood (PB) low-density cells from 38 CML patients were studied in the colony-forming unit-granulocyte, erythrocyte, monocyte, megakaryocyte colony culture assay. Samples from patients with early stage, interferon-alpha (IFN)-sensitive disease formed hematopoietic colonies in the presence of fetal calf serum (FCS), erythropoietin (Epo), and one of the following: granulocyte-macrophage colony-stimulating factor (10 ng/mL), IL-3 (15 ng/mL), both, or phytohemagglutinin-conditioned medium. The addition of IL-1 beta augmented IFN-sensitive CML colony growth in a dose-dependent manner at concentrations of 10 to 100 U/mL. In sharp contrast, addition of the above growth factors did not augment the colony growth-promoting effect of FCS and Epo in samples from IFN-resistant patients; further, adherent cell fractionation or T-lymphocyte depletion attenuated the "autonomous" colony growth. Lysates of 2.5 x 10(7) low-density cells from each of six IFN-resistant and six IFN-sensitive CML patients and three normal volunteers were tested for intrinsic IL-1 beta content in an enzyme-linked immunosorbent assay and yielded a mean of 610 pg, 54.6 pg, and 49.4 pg of IL-1 beta, respectively (P less than .045). Interestingly, both soluble IL-1 receptors (sIL-1R) and IL-1 receptor antagonist (IL-1RA) at concentrations of 5 to 100 ng/mL (sIL-1R) and 10 to 500 ng/mL (IL-1RA) inhibited CML colony growth in a dose-dependent fashion, with maximal inhibition of 64% and 65%, respectively. A similar effect was noted with the use of anti-IL-1 beta neutralizing antibodies. These data implicate IL-1 beta in CML disease progression and suggest that the inhibitory effects of molecules such as sIL-1R and IL-1RA could conceivably be the basis of a novel therapeutic strategy against this disorder. 
The incontinent myelodysplastic patient. Urinary incontinence is a socially devastating aspect of the lives of many myelodysplastic children. Incontinence results from abnormal bladder storage function, urethral sphincteric incompetence, or both. Unfortunately, the vesicourethral dysfunction in an individual patient cannot be discerned from the level of the vertebral defect or the coexisting neurologic deficits. Therefore, thorough urodynamic assessment is required to identify altered physiology precisely and to guide rational treatment. Our therapeutic armamentarium includes external devices, intermittent self-catheterization, pharmacologic therapy, prosthetics, electrical stimulation, biofeedback, and innovative surgical procedures. Comprehensive evaluation, thoughtful tailoring of therapy to the individual patient, and a commitment by the urologist to indefinite follow-up will enable most patients to attain social continence while preserving renal function. 
Effect of plasma from patients with essential hypertension on vascular resistance in the isolated perfused rat kidney. 1. Isolated perfused rat kidneys were used to study the effects of plasma fractions obtained by gel filtration from essential hypertensive patients (n = 40) and from normotensive subjects (n = 36) on resistance vessels. Perfusion pressure was recorded at a constant flow. 2. Plasma fractions were obtained by gel filtration and contained substances with a molecular mass in the range 1000-1500 Da. The plasma fractions from hypertensive patients used in this study had been shown to increase blood pressure after intravenous injection in rats. 3. In the isolated rat kidneys, the hypertensive fractions increased perfusion pressure by 20 +/- 17 mmHg (mean +/- SD, range 5-58 mmHg, n = 40). The analogous fractions from normotensive subjects did not change perfusion pressure significantly. 4. In Ca2(+)-free medium containing 2 mmol/l ethyleneglycol bis-(aminoethyl ether)tetra-acetate, the change in perfusion pressure induced by active plasma fractions was reduced by 95.2 +/- 6.3%. Addition of nifedipine to the perfusion medium reduced, but did not abolish, the pressure response of the kidneys. 5. In solutions containing phentolamine or saralasin, vasoconstriction was not reduced. 6. Thus in the active fractions from hypertensive plasma, a vasopressor agent with direct action on resistance vessels can be demonstrated. This substance probably acts by increasing Ca2+ influx in vascular smooth muscle cells. 
DNA diagnosis for hereditary cerebral hemorrhage with amyloidosis (Dutch type) Hereditary cerebral hemorrhage with amyloidosis of the Dutch type (HCHWA-D) is tightly linked to the Alzheimer amyloid precursor protein gene on chromosome 21, which codes for the amyloid beta-protein. A point mutation detected at position 1852 of the amyloid precursor protein gene in four HCHWA-D patients was hypothesized to be the basic defect. This study proves that 22 HCHWA-D patients from three pedigrees all carry this point mutation, whereas the mutation is absent in escapees from the HCHWA-D families as well as in randomly selected Dutch individuals. A mutation-specific oligonucleotide is now available for the confirmation of the HCHWA-D diagnosis. Therefore, presymptomatic testing and prenatal evaluation of individuals at risk in the HCHWA-D families is now feasible. 
Abdominal distension in female patients with irritable bowel syndrome: exploration of possible mechanisms. Abdominal distension is a common but little understood symptom of the irritable bowel syndrome. The authenticity of the symptom was confirmed by appreciable increases in girth measurement during the day in 20 patients with the irritable bowel syndrome compared with 20 control subjects. Objective corroboration of this finding was shown in the group with the irritable bowel syndrome by a highly significant increase in lateral abdominal 'profile' on computed tomography. Previously postulated mechanisms for distension--namely, retention of gas, depression of the diaphragm, and excess lumbar lordosis--were excluded by the radiological findings. Voluntary protrusion of the abdomen produced a completely different pattern on computed tomography to that observed in the irritable bowel syndrome. These observations suggest that abdominal distension may be related to changes in motility or tone of gastrointestinal smooth muscle. 
Buspirone: sedative or stimulant effect? OBJECTIVE: The primary objectives of this study were to evaluate the effects of initial and continued administration of buspirone on sleep induction and maintenance and sleep stage parameters, to determine the presence or absence of any drug-induced side effects, and to ascertain the presence or absence of sleep disturbances following abrupt withdrawal of the drug. METHOD: Six insomniac subjects who had chronic complaints of difficulty falling asleep and/or staying asleep and who were in good physical health, were not suffering from any major mental disorders, and had not used any medication for at least the last month participated in a 16-night sleep laboratory protocol. The protocol consisted of 4 placebo-baseline nights, 7 nights on which buspirone, 10 mg at bedtime, was administered, and 5 placebo-withdrawal nights. RESULTS: Wake time after sleep onset increased moderately during the first 3 nights of drug administration (there was a marked and significant increase on the first night) and increased by lesser degrees with continued drug administration. Overall, reports of side effects were infrequent. Following drug termination, there was a delayed and mild increase in sleep difficulty above baseline. CONCLUSIONS: These data not only confirm that buspirone lacks sedative effects but also suggest that the drug may have stimulant properties. Further, these findings suggest that buspirone has limited usefulness in anxious patients with concomitant sleep difficulties. 
Clustering of features of von Hippel-Lindau syndrome: evidence for a complex genetic locus von Hippel-Lindau syndrome (HLS), an autosomal-dominant inherited disease, was studied in 92 affected subjects from 29 kindreds. In an initial survey to identify HLS gene carriers, all patients treated at the University of Freiburg for angiomatosis retinae (22), haemangioblastoma of the central nervous system (CNS) (63), and phaeochromocytoma (54) were examined as potential HLS gene carriers. HLS was diagnosed in 86% of the patients with angiomatosis retinae, 19% of the patients with haemangioblastoma of the CNS, and 19% of the patients with phaeochromocytoma. Based on these and on an additional 49 newly diagnosed cases (24 by clinical examination and 25 by pedigree analysis), the calculated prevalence of the disease in the district of Freiburg, Germany, with a population of 1.909 million is 1/38 951. There was a striking tendency for familial clustering of HLS features in affected kindreds. Both angiomatosis retinae and haemangioblastoma of the CNS occurred in most families, whereas renal lesions and/or pancreatic cysts and phaeochromatocytoma were mutually exclusive. This finding suggests that HLS is caused by different mutations within a complex genetic locus, or additional genetic lesions, which cooperate with the HLS gene on chromosome 3p. The data point to a linear sequence of features as follows: phaeochromocytoma, angiomatosis retinae, haemangioblastoma of the CNS, renal lesions, pancreatic cysts, and epididymal cystadenoma. 
Improvement by acetylcysteine of hemodynamics and oxygen transport in fulminant hepatic failure. BACKGROUND. When administered early after an overdose of acetaminophen, intravenous acetylcysteine prevents hepatic necrosis by replenishing reduced stores of glutathione. How acetylcysteine improves the survival of patients with established liver damage induced by acetaminophen, however, is unknown. This study was undertaken to determine whether the beneficial effect of acetylcysteine under such circumstances could be due to enhancement of oxygen delivery and consumption. METHODS. We studied the effect of acetylcysteine on systemic hemodynamics and oxygen transport in 12 patients with acetaminophen-induced fulminant hepatic failure and 8 patients with acute liver failure from other causes. The acetylcysteine was given in a dose of 150 mg per kilogram of body weight in 250 ml of 5 percent dextrose over a period of 15 minutes and then in a dose of 50 mg per kilogram in 500 ml of 5 percent dextrose over a period of 4 hours; measurements were made before treatment began and after 30 minutes of the regimen. RESULTS. In the patients with acetaminophen-induced liver failure, the infusion of acetylcysteine resulted in an increase in mean oxygen delivery from 856 to 975 ml per minute per square meter of body-surface area (P = 0.0036), due to an increase in the cardiac index from 5.6 to 6.7 liters per minute per square meter (P = 0.0021). Mean arterial pressure rose from 88 to 95 mm Hg (P = 0.0054) despite a decrease in systemic vascular resistance from 1296 to 1113 dyn.sec.cm-5 per square meter (P = 0.027). There was an increase in oxygen consumption from 127 to 184 ml per minute per square meter (P = 0.0007) associated with an increase in the oxygen-extraction ratio from 16 to 21 percent (P = 0.022). The effects in the patients with acute liver failure from other causes were similar. CONCLUSIONS. The increase in oxygen delivery and consumption in response to acetylcysteine may account for its beneficial effect on survival in patients with fulminant hepatic failure induced by acetaminophen. 
A case of pheochromocytoma associated with meningioma. We have recently observed a rare case of pheochromocytoma associated with meningioma. To determine the mechanism of such a coexistence in this particular case, we compared the constitutional and pheochromocytoma genotypes of the patient using polymorphic four DNA markers, and we found a loss of heterozygosity at the D1S7 locus. A loss of heterozygosity at this locus has previously been reported by Mathew et al. in pheochromocytoma patients, and our results were in agreement with that study. Therefore the allelic deletion at the D1S7 locus may be an important step in the tumorigenesis of pheochromocytoma in this case. 
Midbrain vs. pontine medial longitudinal fasciculus lesions: the utilization of masseter and blink reflexes. Masseter (MR) and blink reflexes (BL) were investigated in 51 patients with internuclear ophthalmoplegia (INO) due to multiple sclerosis (28) and lacunar infarction (23). The MR was abnormal in 20 of 23 cases with bilateral INO and in 21 of 28 with unilateral INO. The R1 component of the BL (BL-R1) was abnormal in 7 of 23 patients with bilateral INO and 10 of 28 with unilateral INO. Combined MR and BL-R1 changes occurred in 8 of 28 cases with unilateral INO and 7 of 23 with bilateral INO. The findings provide evidence for a rostral/caudal localization of lesions within the medial longitudinal fasciculus causing INO on the basis of MR and BL-R1 abnormalities. An abnormality limited to MR suggests a midbrain location in 58.8% of patients while abnormal BL-R1 with or without an associated MR change suggests a rostral pontine location in 35.3%. 
False-positive immunostaining of normal epithelia and carcinomas with ascites fluid preparations of antimelanoma monoclonal antibody HMB45. HMB45 is a melanoma-specific monoclonal antibody that has found widespread use in diagnostic pathology. Recent reports, however, have suggested that this antibody may cross-react with a small number of carcinomas and other epithelial cells. The authors tested the hypothesis that these latter reports represent examples of false-positive immunostaining by comparing the immunostaining on breast, salivary gland, and lung tumors with the following: (1) a commercial ascites preparation of this monoclonal antibody; (2) a protein A-purified antibody preparation derived from ascites fluid; and (3) supernatant fluid obtained from the hybridoma cell line. The authors found that all examples of nonmelanoma immunostaining in the carcinomas tested were eliminated with the nonascites fluid preparations, whereas strong immunostaining of melanomas was retained. The authors conclude that contaminated commercial ascites fluid preparations of HMB45 may account for most, if not all, of the reports of nonmelanoma immunostaining with HMB45. 
Increased susceptibility to lung dysfunction in female smokers. The interaction between sex and smoking habits on pulmonary function was examined among 1,149 adults 25 to 59 yr of age in a rural community in Saskatchewan. Pulmonary function tests included FVC, FEV1, maximal midexpiratory flow rate (MMFR), the slope of phase III of the single-breath nitrogen test (delta N2/L), and closing volume as a percent of vital capacity (CV/VC). The data show that after fixing the effects of age, height, and weight by analysis of covariance, the adjusted means of delta N2/L in nonsmokers, ex-smokers, and current smokers were 0.92, 1.10, and 1.60% in women and 0.97, 1.05, and 1.23% in men, respectively. The difference in the adjusted means for delta N2/L between smokers and nonsmokers was larger in women than in men, 0.67% versus 0.26%, respectively. Multiple multivariate analyses show that the regression slopes for the residuals of FEV1, MMFR, and delta N2/L versus pack-years were significantly different between men and women. The regressions of FEV1 and MMFR decreased and the regression of delta N2/L increased with increasing pack-years more rapidly in women than in men. The combined effect of sex and pack-years on pulmonary function was not significant for ex-smokers. These data suggest that cigarette smoking may be more detrimental in its effects on lung function in women than in men. 
Devine exclusion for unresectable carcinoma of the stomach. Between July 1986 and July 1988, Devine exclusion was performed in 20 patients with unresectable carcinoma of the gastric antrum. All 20 patients presented with repeated vomiting. On endoscopy, 16 patients had complete gastric outlet obstruction while the remainder manifested significant gastric outlet stenosis. There was no hospital mortality. All except two patients could take an oral diet after surgery until their demise. Devine exclusion is safe and effective in relieving gastric outlet obstruction and is not associated with prolonged delay in return of gastric emptying. 
Descending thoracic aortofemoral bypass as an alternative for aortoiliac revascularization. We performed descending thoracic aorta to femoral bypass in six selected patients over the past four years. An alternative inflow source was selected because the standard transabdominal approach was contraindicated or considered hazardous. The inflow consisted of a single Dacron tube from the descending thoracic aorta to the left groin, and a femorofemoral bypass to the right groin. There was no operative mortality or major morbidity related to the surgical procedure. After an average follow-up of 17.1 months (range 6 to 23 months), all thoracofemoral grafts remained patent. One patient had repeated occlusions of the femorofemoral graft related to right lower extremity outflow disease, while the remaining five crossover grafts are patent. One patient died 22 months postoperatively from a myocardial infarct, with a patent bypass. Although this series represents a small group of patients, we feel that descending thoracic aortofemoral bypass offers excellent inflow and reliable patency, and is a good alternative when reoperation on the abdominal aorta is undesirable. This procedure may also be considered for conversion of an axillofemoral bypass that has failed repeatedly. 
Dopamine agonists prevent duodenal ulcer relapse. A comparative study with famotidine and cimetidine. The present study investigated both the healing rate (after four weeks) and the relapse rate (during six months) following treatment with the dopamine-like drugs bromocriptine (2.5 mg twice daily), amantadine (100 mg nocte), or with the H2 blockers cimetidine (800 mg nocte), and famotidine (40 mg nocte) in 124 patients with endoscopically proven duodenal ulcer (DU). The ulcer was completely healed in 27 (amantadine), 26 (bromocriptine), 23 (cimetidine), and in 24 (famotidine) patients. Relapse was noted in 34.7% (cimetidine) and 25% (famotidine) versus 11.7% (amantadine) and 7.7% (bromocriptine) DU patients. No significant difference was found in initial healing rates. However, the relapse rate in the cimetidine-treated group was significantly higher than in all the other test groups. Additional comparisons between all the treatment categories showed a significantly lower relapse rate with the dopamine-like agents. These important new results indicate that dopamine-like compounds are equally effective as H2 blockers in inducing DU healing and may offer a promising advantage over H2 blockers concerning their efficacy in preventing ulcer relapse in DU patients. 
Siriraj stroke score and validation study to distinguish supratentorial intracerebral haemorrhage from infarction. OBJECTIVES--To develop a simple, reliable, and safe diagnostic tool for acute stroke syndromes in a setting where computerised brain scanning was not readily available and to validate its accuracy with regard to pathological types of stroke. DESIGN--13 clinical variables that potentially might differentiate supratentorial cerebral haemorrhage from infarction were recorded and tested by multivariate analysis in a prospective study of 174 patients with acute stroke. In developing the Siriraj stroke score stepwise discriminant analysis of the variables was followed by a linear discriminant equation to differentiate between supratentorial haemorrhage and infarction. The score obtained was validated against scores in 206 other patients with stroke, computerised brain scans being used for definitive diagnosis. SETTING--Siriraj Hospital Medical School, Mahidol University, Bangkok. SUBJECTS--Prospective study: 174 consecutive patients with acute supratentorial stroke syndrome (not subarachnoid haemorrhage) admitted to Siriraj Hospital during 1984-5; validation study: 206 patients admitted to Siriraj Hospital or another hospital for supratentorial intracerebral haemorrhage or infarction. RESULTS--The Siriraj stroke score was developed and calculated as (2.5 x level of consciousness) + (2 x vomiting) + (2 x headache) + (0.1 x diastolic blood pressure) - (3 x atheroma markers) - 12. A score above 1 indicates supratentorial intracerebral haemorrhage, while a score below -1 indicates infarction. The score between 1 and -1 represents an equivocal result needing a computerised brain scan or probability curve to verify the diagnosis. In the validation study of the Siriraj stroke score the diagnostic sensitivities of the score for cerebral haemorrhage and cerebral infarction were 89.3% and 93.2% respectively, with an overall predictive accuracy of 90.3%. CONCLUSION--The Siriraj stroke score is widely accepted and applied in hospitals throughout Thailand as a simple and reliable bedside method for diagnosing acute stroke. 
Effect of heroin in decomposing tissues on the development rate of Boettcherisca peregrina (Diptera, Sarcophagidae) and implications of this effect on estimation of postmortem intervals using arthropod development patterns. Larvae of the flesh fly Boettcherisca peregrina (Robineau-Desvoidy) were reared on the tissues of rabbits to study the effects of heroin on the development rates of this species. The rabbits were given 6, 12, 18, and 24 mg of heroin by cardiac puncture. From Hours 18 to 96, larvae feeding on tissues containing heroin (as morphine) developed more rapidly than those feeding on tissues from the control. The time required for pupation was significantly greater for colonies fed on tissues from heroin-dosed rabbits than for the control colony. The differences observed in the rates of development were sufficient to alter postmortem interval estimates based on larval development by up to 29 h and estimates based on pupal development by 18 to 38 h. 
Recent trends in acute care hospital utilization in Ontario for diseases of the circulatory system. OBJECTIVE: To describe trends in the use of acute care hospital services for diseases of the circulatory system in Ontario. DESIGN: Observational study. DATA EXTRACTION: Information on diagnoses, procedures and demographic characteristics was obtained from routinely collected computerized abstracts of separations from all acute care hospitals in Ontario during 1979-80, 1983-84 and 1988-89. The data were combined with population estimates to calculate overall separation rates and rates specific for age, diagnosis and procedure. Resource intensity weights were used to estimate changes in resource use. MAIN RESULTS: The overall separation rate increased by 3% and the resource-intensity-weighted separation rate by 12% from 1979-80 to 1988-89. The overall medical separation rate increased by 2%, whereas the surgical rate increased by 12%. The surgical separation rate increased among patients 55 to 79 years of age but decreased in all the other adult age groups. The separation rates for coronary artery bypass surgery and cardiac valve surgery increased rapidly among patients 65 years of age or older. The medical separation rate decreased for patients of all ages except those less than 5 years and those 80 years or more. The medical separation rates decreased by less than 1% for diagnoses related to ischemic heart disease (IHD) and increased dramatically for coronary artery revascularization. CONCLUSIONS: The increasing elderly population has not resulted in large increases in acute care hospital utilization for diseases of the circulatory system. The impact of an aging population has been balanced by decreased utilization rates in the younger groups. The intensity of hospital care has risen primarily because of increases in surgical rates, especially in the elderly population. The large decrease in the rate of death from IHD over the past two decades has not been associated with similar decreases in acute care hospital utilization for this disorder. 
Somatostatin receptors in differentiated ovarian tumors. The presence of somatostatin receptors was investigated in 57 primary human ovarian tumors using in vitro receptor autoradiography with three different somatostatin radioligands, 125I-[Tyr11]-somatostatin-14, 125I-[Leu8, D-Trp22, Tyr25]-somatostatin-28, or 125I-[Tyr3]-SMS 201-995. Three cases, all belonging to epithelial tumors, were receptor positive; specifically 1 of 42 adenocarcinomas, 1 of 3 borderline malignancies, and 1 of 2 cystadenomas. Four other epithelial tumors (3 fibroadenomas, 1 Brenner tumor), 4 sex cord-stromal tumors (2 fibrothecomas, 2 granulosa cell tumors), and 2 germ cell tumors (1 dysgerminoma, 1 teratoma) were receptor negative. In the positive cases, the somatostatin receptors were localized on epithelial cells exclusively, were of high affinity (KD = 4.6 nmol/l [nanomolar]), and specific for somatostatin analogs. These receptors bound somatostatin-14 and somatostatin-28 radioligands with a higher affinity than the octapeptide [Tyr3]-SMS 201-995. Healthy ovarian tissue had no somatostatin receptors. A subpopulation of relatively well-differentiated ovarian tumors, therefore, was identified pathobiochemically on the basis of its somatostatin receptor content. This small group of somatostatin receptor-positive tumors may be a target for in vivo diagnostic imaging with somatostatin ligands. 
Natural history and effectiveness of aspirin in asymptomatic patient with cervical bruits. The Asymptomatic Cervical Bruit Study Group. We report a multicenter study in progress involving a prospective follow-up of asymptomatic patients with cervical bruits. The project consists of two components. All patients meeting clinical criteria for eligibility undergo duplex ultrasonography at the time of entry into the study. Those with a carotid stenosis of 50% or greater are enrolled in a randomized placebo-controlled trial of aspirin. All other patients are followed up in a natural history study, also involving biannual clinical and duplex ultrasonographic examinations. Both clinical and anatomic outcomes are assessed. The project consists of a 3-year accrual phase and a 3-year follow-up phase with completion planned for May 1994. Total anticipated enrollment is 588 patients. 
Pediatric heart transplantation at Stanford: results of a 15-year experience. The long-term results of pediatric heart transplantation were evaluated in 53 patients, aged 0.25 to 18.94 years, who received transplants at Stanford University Medical Center between 1974 and 1989. Indications for transplantation were idiopathic cardiomyopathy (68%), congenital heart disease (21%), endocardial fibroelastosis (8%), and doxorubicin cardiomyopathy (3%). Immunosuppression was achieved with combinations of cyclosporine, prednisone, and azathioprine. Thirty-seven of 42 recipients leaving the hospital after transplantation were alive and in New York Heart Association class I at study's end. Cumulative survival was 79% at 1 year, 76% at 3 years, and 69% at 5 years. Fourteen recipients have survived more than 5 years (5.1 to 12.4 years). Hospital readmission for illness has been infrequent, decreasing from 6.8 days to 0.9 days per year over 5 years. Eleven patients have required no rehospitalization. Posttransplant deaths were due to infection (19%), rejection (4%), pulmonary hypertension (4%), coronary artery disease (2%), and lymphoproliferative disease (2%). Retransplantation was required for intractable rejection in 4 patients and advanced coronary artery disease in 2. Hypertension and elevated blood urea nitrogen and creatinine levels were common in individuals receiving cyclosporine. Growth was often impaired in prepubertal children receiving daily prednisone. Based on this 15-year experience, it is concluded that heart transplantation represents a reasonable alternative for selected young patients with end-stage cardiac disease. 
Avoiding reoperation for indeterminate thyroid nodules identified as malignant after surgery. Thyroid nodules that are indeterminate as carcinoma by needle biopsy before surgery and by study of frozen sections at the time of surgery are occasionally identified to be malignant in later studies. If only a lobectomy has been performed, the advisability of reoperation to remove the remaining thyroid tissue to facilitate radioactive iodine therapy may cause concern. To obviate this difficulty as well as to reduce the occurrence of nodules later in a preserved contralateral thyroid lobe and to provide additional thyroid tissue for study, contralateral subtotal or near total lobectomy has been performed for indeterminate thyroid nodules. The small remnant of remaining thyroid tissue can later be ablated by radioactive iodine if desired. Of 37 patients with indeterminate thyroid nodules, none required reoperation, although the diagnosis of carcinoma was established after surgery for eight patients, three of whom were treated with radioactive iodine. 
Human hepatocyte growth factor in blood of patients with fulminant hepatic failure. Basic aspects. Human hepatocyte growth factor (hHGF) was purified from the plasma of six patients with fulminant hepatic failure due to hepatitis B in two and non-A, non-B hepatitis in four. The purified hHGF from each patient contained two major protein bands having molecular weights of 79,000 and 86,000 and several minor bands having molecular weights between 76,000 and 92,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis performed under nonreduced conditions. After reduction with 2-mercaptoethanol, three major bands having molecular weights of 58,000, 34,500, and 31,500 were evident. In addition, a band having a molecular weight of 21,000 was detected. hHGF activity was destroyed by its reduction. The hHGF purified from patients demonstrated a dose response in terms of an increase in DNA synthesis using cultured hepatocytes. The hHGF concentration in the plasma of the patients with grade III-IV hepatic coma was calculated to be in the range of 1.8-3.0 nM. Finally the heavy chain of hHGF was not recognized by an anti-human albumin antibody, indicating that hHGF is not biliprotein, an albumin-bilirubin complex, that has been reported to be a putative liver growth factor. 
Population-based study of surgery in juvenile onset Crohn's disease. A geographically based cohort of 68 children with Crohn's disease was derived by sampling from Scottish Hospital In-patient Statistics. Surgical histories were examined and analysed by actuarial methods, and the nature of major operations performed was compared with operations for Crohn's disease in the Lothians' Surgical Audit. Fifty-four of the 68 patients were treated surgically, with a total of 135 operations (71 major, 64 minor). Fifty per cent of the cohort had a major operation within 5 years of onset of symptoms; median time to a second operation was 4 years. The types of major operation performed in juvenile onset patients differed significantly from those recorded in the Lothians' audit, with a high rate of exploratory laparotomy in younger patients (12 cases). With a mean follow-up of 7 years, 12 patients (18 per cent) have a permanent stoma. There were five deaths, three postoperative. This study highlights the frequency of surgical intervention in young people with Crohn's disease. 
Endothelial modulation of vascular tone: relevance to coronary angioplasty and restenosis. The vascular endothelium importantly modulates many biochemical and physiologic properties of the vascular wall, including the release of potent vasoactive factors, maintenance of an anticoagulant state and modulation of vascular growth by the release of both proliferative and antiproliferative substances. Prominent among these endothelial roles is the production of a potent vasodilator or family of vasodilators termed the endothelium-derived relaxing factor, one of which has been identified to be nitric oxide or a closely related compound. Several diseases that commonly occur in patients undergoing coronary angioplasty alter many facets of endothelial function and may predispose to adverse clinical sequelae of angioplasty, including immediate thrombosis, restenosis and vascular spasm. Several features of the endothelium-derived relaxing factor, how it is altered by pathologic processes and how these considerations relate to the immediate and late postangioplasty periods are discussed. 
Evaluation of the traveler. An introduction to emporiatrics for the emergency physician. Travel medicine, or emporiatrics, presents an additional challenge to the practicing emergency physician. In this time of increased travel for business and pleasure, travel history should become a routine part of patient evaluation. While the emergency physician may not need to become facile with specific details concerning immunizations and prophylaxis, he or she should have a good working knowledge of these in order to provide the potential traveler with some basic information and to be able to adequately evaluate the returned traveler who becomes ill and seeks care. Air travel allows many travelers to arrive back in the United States before manifesting symptoms and signs of illness acquired abroad. Many of these illnesses are not usually found in the United States. Late diagnosis of certain illnesses, such as falciparum malaria, may increase the morbidity and mortality. As such, travel history should become a routine part of patient evaluation, and the physician should have a good working knowledge of illnesses that may be acquired abroad. 
Maximal sniff mouth pressure compared with maximal inspiratory pressure in acute respiratory failure. Inspiratory muscle strength most often is better reflected by sniff Pes than PImax against occlusion. Furthermore, sniff Pes can be estimated noninvasively by the measurement of sniff Pmo in normal subjects and in patients with respiratory muscle weakness. The aim of this study was to compare sniff Pmo and P.PImax to assess inspiratory muscle strength in patients with acute respiratory failure. The highest pressure was produced by P.PImax in 61 percent of measurements, and by sniff Pmo in 39 percent. Above 35 cm H2O P.PImax yielded the highest pressure in 55 percent of cases and the ratio sniff Pmo/P.PImax was 1.20 +/- 0.54. Below 35 cm H2O, P.PImax yielded the highest pressure in 75 percent of cases and the ratio sniff Pmo/P.PImax was 0.76 +/- 0.35 (p less than 0.02). Thus, measurements of sniff Pmo and P.PImax complement one another for assessing inspiratory muscle strength. However, sniff Pmo underestimates inspiratory muscle strength in patients with severe inspiratory muscle weakness. 
Clinical usefulness of serum squamous cell carcinoma antigen for early detection of squamous cell carcinoma arising in mature cystic teratoma of the ovary. Squamous cell carcinoma arising in mature cystic teratoma of the ovary is rarely diagnosed preoperatively. We measured the pre-treatment serum levels of squamous cell carcinoma antigen in three stage I patients in order to evaluate its usefulness as a tumor marker for early detection of the disease. The serum levels were elevated in each case, to 26.9, 5.1, and 3.2 ng/mL, respectively, and rapidly dropped to within the normal range after treatment. All patients are recovered and show no evidence of recurrence, and the levels of serum squamous cell carcinoma antigen have remained within normal limits. These results suggest that measurement of the serum squamous cell carcinoma antigen level may be useful in diagnosing an early-stage primary squamous cell carcinoma arising in a mature cystic teratoma of the ovary. An elevated preoperative serum level of squamous cell carcinoma antigen may indicate the need for a rapid pathologic examination of the tumor to look for malignant elements and may influence the surgical regimen. 
Macroreentry in the infarcted human heart: the mechanism of ventricular tachycardias with a "focal" activation pattern. Endocardial mapping of electrical activity was carried out in 150 patients to guide antiarrhythmic surgery for drug-resistant ventricular tachycardia in the chronic phase of myocardial infarction. In 20 of these patients, the activation pattern of 27 distinct tachycardias was focal and diastolic potentials were recorded at three or more sites. In 26 tachycardias, the sequence of diastolic potentials progressed from the area of latest activation of one cycle toward the "origin" of the next cycle. In two patients, the heart was stimulated during tachycardia, resulting in entrainment of the tachycardia in both. Late potentials were recorded during entrainment at sites where diastolic potentials occurred during tachycardia. In 11 of the 20 patients, endocardial mapping was performed during sinus rhythm. In four of these, late potentials were observed during sinus rhythm at sites where diastolic potentials were recorded during tachycardia. In two patients without late potentials during sinus rhythm, late potentials were observed during stimulation and induced ectopic beats. The results support the concept that the mechanism of several of these tachycardias is based on reentry in a macrocircuit comprising a tract of surviving tissue traversing the infarct and the remaining healthy tissue. They also indicate that the absence of late potentials during sinus rhythm does not guarantee the absence of arrhythmogenic pathways. 
Prehospital diagnosis and treatment of acute myocardial infarction: a north-south perspective. The Cincinnati Heart Project and the Nashville Prehospital TPA Trial. Intravenous thrombolytic therapy improves left ventricular function and reduces mortality in patients with acute myocardial infarction (AMI). In European and Middle Eastern trials, prehospital delivery of thrombolytic agents by physician-directed mobile intensive care units has been successful. This report describes two independently conceived and performed trials that used cellular telephone transmission of 12-lead ECGs to deliver recombinant tissue plasminogen activator (r-tPA) in the field to patients with AMI. In the Nashville Prehospital TPA Trial, 85 patients with chest pain were evaluated in the field for possible administration of r-tPA over a 6-month period. Three of 85 patients (3.5%) were found to be actual candidates for r-tPA treatment in the field. In phase II (dry-run phase) of the Cincinnati Heart Project, 374 patients were evaluated in the field with 14 documented cases of AMI (3.7%) before r-tPA was placed in ambulances for administration by paramedics. In phase III (active with r-TPA in ambulances), over a 1-year period 103 patients were evaluated with six (5.8%) documented cases of AMI. Three of five r-tPA field treatment decisions by emergency physicians using transmitted 12-lead ECGs were accurate (60%). When patients in phases II and III were combined, only 20 of 477 total patients (4.2%) were documented to have AMI. A decline in paramedic skills was noted because of the infrequent administration of the thrombolytic agent. Combining the Nashville and Cincinnati experiences, only 27 of 562 total patients with chest pain (4.8%) were candidates for prehospital thrombolysis. We conclude that few patients evaluated in the prehospital setting are actual candidates for thrombolytic therapy. Substantial allocation of financial and human resources for prehospital delivery of intravenous thrombolytic therapy does not appear warranted. 
Role of estrogens and epidermal growth factor in hepatocellular carcinoma (HCC). Estrogen (E) and epidermal growth factors (EGF) receptors were assayed in the liver of nine patients with hepatocellular carcinoma (HCC). Total E and nuclear E receptors were decreased significantly in neoplastic tissue as compared to the levels found in surrounding nonneoplastic tissue. The EGF receptor was decreased also in neoplastic tissue. On the basis of binding data, a decrease in the number but not in affinity of both the E and EGF receptors was found. 
Selective amplification of periportal transitional cells precedes formation of hepatocellular carcinoma in SV40 large tag transgenic mice. In a major urinary protein (MUP)-promoter/simian virus 40 (SV40)Tag transgenic mouse line (MT-D2) the liver-directed, androgen-regulated transgene expression leads to synchronized pathology resulting in a stepwise progression to multiple hepatocellular carcinomas. SV40Tag-activated replication gives rise to two different preneoplastic alterations in hepatocytes, which are characterized in detail: 1) dysplasia and finally cell death in the original hepatocyte population and 2) amplification of periportal transitional hepatocytes leading to multifocal hyperplasia and hepatocellular carcinoma. Multifocal hyperplasia, most probably the equivalent of SV40Tag-immortalization, grows confluent and leads to hepatomegaly. SV40Tag-independent, secondary events are necessary for the tumor development from confluent hyperplasia. This allows further investigation of the steps involved in malignant transformation and progression during hepatocarcinogenesis in vivo. 
Familial breast-ovarian cancer locus on chromosome 17q12-q23. Familial breast cancer has been linked to the D17S74 locus on chromosome 17q. To confirm this finding and to investigate whether ovarian cancer is also linked to this locus, five large families with a hereditary predisposition to cancer of the breast and ovary were investigated. Three families were positive for linkage. For the largest family the lod score was 2.72. These findings suggest that the chromosomal region 17q12-q23, previously shown to contain a gene for early-onset breast cancer, is also associated with a proportion of hereditary ovarian cancers. 
Pentoxifylline inhibits interleukin-2-induced leukocyte-endothelial adherence and reduces systemic toxicity. Interleukin-2 (IL-2) mediates the regression of metastatic cancer, but clinical application has been limited by the induction of dose-dependent toxicities in normal tissues. The most clinically significant toxicities occur secondary to a vascular leak syndrome and include acute respiratory failure and hemodynamic instability. Because previous studies suggested a role for pentoxifylline in attenuating the toxic effects of IL-2, we hypothesized that pentoxifylline would inhibit alterations in the microvasculature induced by IL-2 and would ultimately reduce IL-2-induced toxicity. To determine the validity of this hypothesis, we prepared four groups of rats for in vivo microvascular observation. In the first group, a bolus intravenous injection of IL-2 (1 x 10(6) units/kg) acutely induced hypotension, tachypnea, hypoxia, increased lung water, decreased microvascular blood flow, and increased leukocyte-endothelial adherence. No significant changes occurred in animals treated by pentoxifylline alone or the control IL-2 vehicle-alone group. However, pentoxifylline inhibited many of the IL-2-induced systemic and microvascular effects, such as hypotension, tachypnea, increased lung water, hypoxia, and increased leukocyte-endothelial adherence, but not tachycardia or increased microvascular protein leakage. These data support our hypothesis that systemic toxicities induced by IL-2 are associated with alterations in the microcirculation, which may be ameliorated by pentoxifylline. 
Dipyridamole thallium-201 scintigraphy as a preoperative screening test. A reexamination of its predictive potential. Study of Perioperative Ischemia Research Group BACKGROUND. We examined the value of dipyridamole thallium-201 (201Tl) scintigraphy as a preoperative screening test for perioperative myocardial ischemia and infarction. METHODS AND RESULTS. We prospectively studied 60 patients undergoing elective vascular surgery. We performed 201Tl scintigraphy preoperatively and blinded all treating physicians to the results. Historical, clinical, laboratory, and physiological data were gathered throughout hospitalization. Myocardial ischemia was assessed during the intraoperative period using continuous 12-lead electrocardiography (ECG) and transesophageal echocardiography (TEE) and during the postoperative period using continuous two-lead ambulatory ECG. Adverse cardiac outcomes (cardiac death, myocardial infarction, unstable angina, severe ischemia, or congestive heart failure) were assessed daily throughout hospitalization. Twenty-two patients (37%) had defects that improved or reversed on delayed scintigrams (redistribution defects), 18 (30%) had persistent defects, and 20 (33%) had no defects on 201Tl scintigraphy. There was no association between redistribution defects and adverse cardiac outcomes: 54% (seven of 13) of adverse outcomes occurred in patients without redistribution defects, and the risk of an adverse outcome was not significantly increased in patients with redistribution defects (relative risk 1.5, 95% confidence interval 0.6-3.9, p = 0.43). Consistent with these findings, there was also no association between redistribution defects and perioperative ischemia: 54% (19 of all 35) of perioperative ECG and TEE ischemic episodes and 58% (14 of 24) of severe ischemic episodes occurred in patients without redistribution defects. The sensitivity of 201Tl scintigraphy for perioperative ischemia and adverse outcomes ranged from 40% to 54%, specificity from 65% to 71%, positive predictive value from 27% to 47% and negative predictive value from 61% to 82%. CONCLUSIONS. These results differ from those of previous studies and suggest that the routine use of 201Tl scintigraphy for preoperative screening of patients undergoing vascular surgery may not be warranted. 
Genetic and environmental explanations for the distribution of sodium-lithium countertransport in pedigrees from Rochester, MN. An elevated level of erythrocyte sodium-lithium (Na-Li) countertransport has been suggested as a predictor of predisposition to essential hypertension. In order to evaluate whether a single genetic or environmental factor with large effects explains the mixture of distributions in Na-Li countertransport in the general population, complex segregation analyses were conducted by using 1,273 individuals more than age 20 years from 276 pedigrees selected without respect to disease risk factors or health status. Either a single genetic locus or a single environmental factor with large gender-specific effects explained the mixture of distributions for Na-Li countertransport in this sample equally well. In the subsample of pedigrees supporting a single-locus etiology, the single genetic locus explained 29.0% of the variability in adjusted Na-Li countertransport in males and 16.6% of that in females. In a subsample of pedigrees supporting an environmental factor etiology, the environmental factor explained 35.2% of the adjusted Na-Li countertransport in males and 20.5% of that in females. These results suggest that there are at least two different explanations for the mixture of distributions in Na-Li countertransport in the general population. Attempts to relate genetic variation in Na-Li countertransport to risk of essential hypertension must consider that the factor with large phenotypic effects on this trait is gender specific and may not be a single major locus in all pedigrees. 
Characterization of the decay-accelerating factor gene promoter region. Decay-accelerating factor (DAF) expression modulates susceptibility of cells to autologous complement attack. To characterize the regulatory region controlling DAF gene transcription, genomic DNA extending from 815 base pairs (bp) upstream to approximately 4 kilobases downstream of DAF's AUG codon (designated +1) was cloned and sequenced. The 5' flanking sequence showed 59-76% G + C content (-355 to +1), at least one GC box(es) (-135 to -131), and variable length sequences (from -629 to -285) conforming to the motifs TCCTCC and TCn. Nuclease S1 digestions and primer extensions localized a major transcriptional start site to -82/-81, 38 bp downstream of a possible TATA variant, (A)TTTAA. In COS cell transfections, the sequence encompassing -815 to -67 functioned 2.5% as efficiently as the Rous sarcoma virus 3' long terminal repeat, but following deletion upstream of -355 its activity increased approximately 4-fold. Two octanucleotides exhibiting partial homology to phorbol 12-myristate 13-acetate (PMA) and cAMP responsive elements (PREs and CREs, respectively) were detected, and the respective modulators enhanced transcriptional efficiency 2- and approximately 10-fold, respectively. Thus, the DAF gene promoter (i) exhibits sequences resembling both conventional and unconventional transcriptional control elements, (ii) possesses a region with negative regulatory activity, and (iii) responds to PMA and cAMP induction presumably via PRE- and CRE-like enhancer elements. 
Simple noninvasive method to test efficacy of drugs in the eradication of Helicobacter pylori infection: the example of combined bismuth subsalicylate and nitrofurantoin. Eradication of Helicobacter pylori infections has proved to be difficult. There is a need both for improved therapies and for ways to rapidly identify therapies that show sufficient promise to be worth pursuing. The objectives of this study were to evaluate the value of a therapeutic regimen of a bismuth salt plus nitrofurantoin for eradication of infection by H. pylori and to determine the validity/utility of the urea breath test in monitoring the progress of a clinical trial. We used an 80% eradication rule to define a promising therapeutic regimen, i.e., a regimen that eradicated the infection (no evidence of infection by H. pylori 4 wk after termination of therapy) in at least 80% of the individuals treated. Eighteen men (median age 38) with documented infection by H. pylori completed the study. At the end-of-study evaluation, H. pylori infection was eradicated (negative urea breath test, culture, and histology) in only one of 18 (5.5%) subjects; 15 were positive by the urea breath test, 16 by culture, 15 by Warthin-Starry stain, and 16 by the presence of acute-on-chronic inflammation. Using the 80% eradication rule, any one of these tests alone would have identified that the combination of antimicrobials tested was not effective in the eradication of the infection. We conclude that the urea breath test is a simple, noninvasive, cost-effective method to separate promising from unpromising candidate therapies and for the evaluation of new therapeutic concepts. 
Excimer laser-facilitated balloon angioplasty of a nondilatable lesion. Preliminary clinical experience with excimer laser coronary angioplasty shows that it is a safe and effective means of achieving nonsurgical coronary revascularization in selected patients but specific indications for its use are as yet undefined. In the present report a specific indication is proposed for the use of the excimer laser: to facilitate balloon inflation in a rigid stenosis that fails to dilate despite high balloon inflation pressures. 
Confirming the theoretical structure of the McGill Pain Questionnaire in acute clinical pain. Based upon a tripartite theoretical model of pain, the Pain Rating Index (PRI) of the McGill Pain Questionnaire (MPQ) continues to be one of the most frequently used instruments to measure clinical pain. Although a number of exploratory factor analytic studies have failed to consistently support the theoretical structure of the instrument, one previous confirmatory factor analytic study of chronic pain did statistically support the a priori model. Because it has been suggested that acute pain may not involve the same dimensions as chronic pain, this study provided a direct test of the theoretical structure of the MPQ through multi-sample confirmatory factor analysis (CFA) using data provided by women experiencing pain during labor (n = 185) and women experiencing acute postoperative pain (n = 192). Results of the LISREL CFA analysis indicated that the a priori, 3-factor, oblique model originally proposed by Melzack provided the most parsimonious representation of the data across the 2 samples of acute pain. 
Prophylactic sclerotherapy in high-risk cirrhotics selected by endoscopic criteria. A multicenter randomized controlled trial. Controlled trials of sclerotherapy for the prevention of the first variceal hemorrhage in cirrhotics have given conflicting results. In the present study, 106 cirrhotics were randomized to sclerotherapy (55 patients) or control group (51 patients). Admission criteria were no history of previous variceal bleeding and the presence of high-risk varices, i.e., a variceal score less than or equal to 0 according to Beppu et al. Sclerotherapy sessions were performed at time zero, 7 days, 30 days, and then monthly until eradication. Follow-up endoscopies were performed at 6-month intervals thereafter. Control patients underwent repeat endoscopy at 6-month intervals. Bleeding episodes were treated by sclerotherapy in both groups, whenever possible. Mean follow-up was 24 months. Analysis of the results was performed by the intention-to-treat method. Variceal bleeding occurred in 19 sclerotherapy patients (34.5%) and in 17 controls (35.4%, P = NS). Overall mortality was 34.5% in sclerotherapy patients and 50% in controls (P = NS). Seven of the 19 sclerotherapy patients (36.8%) and 11 of the 17 controls (64.7%) who bled died of hemorrhage (P less than 0.05, log-linear model). It is concluded that prophylactic sclerotherapy does not reduce the incidence of first variceal bleeding in cirrhotics. However, there seems to be a trend toward a lower bleeding-related mortality in sclerotherapy patients than in controls. 
Electrophysiologic effects of isoproterenol in patients with atrioventricular reentrant tachycardia treated with flecainide. The electrophysiologic effects of isoproterenol in patients treated with flecainide for atrioventricular (AV) reentrant tachycardia were studied to evaluate the mechanism of tachycardia inducibility after isoproterenol and the value of isoproterenol challenge as a predictor of spontaneous arrhythmia recurrence. Seventeen patients underwent electrophysiologic study before and after oral flecainide administration and after the addition of isoproterenol to flecainide. No patient had inducible sustained supraventricular tachycardia after flecainide alone. Two patients had inducible sustained and six had inducible nonsustained tachycardia after isoproterenol was added to flecainide. The patients were then followed up on the same flecainide dose they received at the time of the electrophysiologic study. Findings: 1) Flecainide treatment prolonged HV and VA intervals, and the addition of isoproterenol did not affect these variables. 2) Isoproterenol shortened anterograde and retrograde block cycle length and the refractory period of the accessory pathway and the AV node. It also decreased the tachycardia cycle length, an effect that was due solely to shortening of AV node conduction time. 3) Flecainide treatment prevented tachycardia induction by affecting retrograde conduction over the accessory pathway. Isoproterenol allowed for tachycardia induction and for more sustained episodes of tachycardia by reversing the effect of flecainide on retrograde accessory pathway conduction. 4) Tachycardia recurred during follow-up in all three patients in whom tachycardia of greater than or equal to 10 s duration was induced after isoproterenol but in no patient who had no or shorter episodes of induced tachycardia (and who did not have a change in medical regimen). Conclusions: 1) Isoproterenol reverses flecainide-induced prolongation of block cycle length and refractory periods of the accessory pathway and AV node. 2) Isoproterenol reverses flecainide-induced prevention of tachycardia induction through reversal of the effects of flecainide on the retrograde accessory pathway. 3) The addition of isoproterenol during flecainide restudy is valuable in predicting long-term drug efficacy. 
Screening for colon malignancy with colonoscopy. Screening of asymptomatic individuals for colon malignancy has been advocated for the past 20 yr in the hopes of reducing colon cancer mortality. Although sigmoidoscopy is an important element of current screening recommendations, the sensitivity of this test in asymptomatic subjects has never been studied. The purpose of this study was to determine the prevalence and location of polyps and cancers in an asymptomatic population by performing full colonoscopy. We wished to assess the sensitivity of screening flexible sigmoidoscopy to 60 cm by determining how many patients with adenomas or cancer had "index" adenomatous polyps in the distal 60 cm. One hundred five healthy male outpatients, over 50 yr old, with negative examinations for occult blood in stools and no prior history of colon pathology, had full colonoscopy. Careful examination of the distal 60 cm was performed, followed by a full colon examination to the cecum. Forty-three patients (41%) had adenomatous polyps, and only 19 of these patients had an index adenomatous polyp in the distal 60 cm. Therefore, the sensitivity of sigmoidoscopy was 44%. The prevalence of adenomas increased with age. Patients were assigned to one of three groups based on the findings in the distal 60 cm. Group 1 (n = 65) had no polyps in the distal 60 cm, but 18 of these patients (28%) had adenomatous polyps in the proximal colon. Among 21 patients with only hyperplastic polyps in the distal 60 cm (group 2), six patients (29%) had proximal adenomas. In group 3, eight of 19 patients (42%) with adenomas in the distal 60 cm also had proximal adenomatous polyps. We conclude that adenomatous polyps are common in asymptomatic men who have negative tests for fecal occult blood. Sigmoidoscopy to 60 cm had a sensitivity of only 44% in this patient population, suggesting that this is an insensitive test for the detection of patients with adenomatous polyps. 
Natural anticoagulants in systemic lupus erythematosus. Deficiency of protein S bound to C4bp associates with recent history of venous thromboses, antiphospholipid antibodies, and the antiphospholipid syndrome. The association of thrombosis with antiphospholipid antibodies (aPL) in patients with systemic lupus erythematosus (SLE) could be due to their interference with natural phospholipid dependent anticoagulant mechanisms. We studied antigenic protein C (APC), functional protein C (FPC), free protein S (FPS), protein S bound to C4 binding protein (C4bp-S), antithrombin III (ATIII), as well as IgG and IgM anticardiolipin antibodies (aCL) in 38 patients with SLE with a history of thromboses and 70 patients with SLE without such history. We found a high frequency of deficiencies of natural anticoagulants in both groups of patients with SLE but, because of patient selection, we could not determine the actual prevalence of these defects. Patients having had a venous thrombosis in the previous year had low C4bp-S more frequently than patients with older or no thromboses. When we divided our patients with SLE into those who had a definite, probable, questionable or no antiphospholipid syndrome (aPS) we found the frequency of C4bp-S deficiency to be significantly higher in those with definite aPS than in those without aPS. Intermediate proportions were found in patients with probable and questionable aPS. The levels of C4bp-S decreased as the levels of aCL, particularly IgG, increased. Stepwise discriminant analysis of natural anticoagulants selected deficiencies of C4bp-S and FPC with increased ATIII as a set of variables with highest predictive power for classification of patients with and without aPS. Thus, deficiencies of natural anticoagulants may occur frequently in patients with SLE. 
Psychiatric aspects of headache. Psychological factors, such as psychological stressors, personality style, conditioning, and psychodynamic issues, play a role in the etiology of chronic migraine and muscle contraction headaches. Psychiatric disorders, such as depression, anxiety, personality disorders, conversion, and hypochondriasis, may accompany and complicate headache. Psychiatric diagnosis and treatment add a useful and important dimension to the medical care of the patient. This article presented a useful conceptual model for discriminating between different kinds of psychological influencing factors and guidelines for selecting the appropriate form of psychiatric treatment. 
Regulation of phospholipase D and primary granule secretion by P2-purinergic- and chemotactic peptide-receptor agonists is induced during granulocytic differentiation of HL-60 cells. We have compared the abilities of extracellular ATP (acting via P2-purinergic receptors) and formylated peptides (FMLP) to stimulate both phospholipase D (PLD)-based signal transduction and primary granule (azurophilic) secretion in HL-60 cells induced to differentiate along the granulocytic pathway. In undifferentiated HL-60 cells, neither ATP nor FMLP elicited significant PLD activation or increased secretion despite the previously documented ability of ATP to stimulate large increases in polyphosphoinositide hydrolysis and Ca2+ mobilization. Conversely, within 1 d after induction of granulocytic differentiation by dibutyryl cAMP, both ATP and FMLP induced large increases in azurophilic secretion and corresponding increases in PLD activity. ATP-activated PLD activity was near-maximal within 1 d after dibutyryl cAMP treatment, while the FMLP-induced activity increased continuously over 4 d, with a maximal level twice that stimulated by ATP. Additional experiments characterized the activation of PLD by receptor-independent pathways at different stages of differentiation; these included studies of phorbol ester action in intact cells and GTP gamma S action in electropermeabilized cells. An apparent role for guanine nucleotide-binding regulatory proteins in PLD regulation was also indicated by the significant reduction in FMLP- and ATP-stimulated PLD activity observed in cells pretreated with pertussis toxin. At all stages of differentiation, there was good correlation between the relative efficacies of ATP versus FMLP in stimulating both secretion and PLD activity. These data indicate: (a) that the receptor-regulated phospholipase D signaling pathway is induced during differentiation of myeloid progenitor cells; and (b) that differential activation of this signaling system by various Ca(2+)-mobilizing receptor agonists may underlie the differential regulation of secretion and other phagocyte functions by such agents. 
Helicobacter pylori-associated exaggerated gastrin release in duodenal ulcer patients. The effect of bombesin infusion and urea ingestion. Recent studies have shown that the exaggerated meal-stimulated gastrin release in patients with duodenal ulcer abates after eradication of Helicobacter pylori infection. Bombesin-stimulated gastrin release was compared in 11 H. pylori-infected patients with chronic duodenal ulcer and 8 uninfected healthy volunteers both before and after therapy to eradicate H. pylori. Bombesin infusion significantly increased the gastrin release both in control subjects and in patients with duodenal ulcer. Antimicrobial therapy (bismuth, tetracycline, and metronidazole) to eradicate the H. pylori infection was associated with a significant reduction in bombesin-stimulated gastrin release in patients with duodenal ulcer (from 116.9 +/- 19 pg/mL to 69.5 +/- 7 pg/mL following 50 pmol.kg-1.h-1 bombesin; and from 158 +/- 29 to 83.4 +/- 10 following 200 pmol.kg-1.h-1 bombesin: P = 0.01 for each). Antimicrobial therapy had no effect on gastrin release in uninfected volunteers, thus excluding a nonspecific effect of antimicrobial therapy on antral G-cell function. Serum gastrin was also not increased by feeding 500 mg of urea to 5 H. pylori-infected volunteers. This suggests that access of hydrogen ion to the pH-sensitive sites governing gastrin release by mucosal ammonia produced by H. pylori urease is not a critical factor. These data suggest that exaggerated gastrin release present in patients with duodenal ulcer disease is secondary to H. pylori infection. 
Interleukin-1 mRNA-expressing macrophages in human chronically inflamed gingival tissues. Interleukin-1 (IL-1)-producing cells in inflamed gingival tissues obtained from patients with periodontitis were examined by combined immunohistochemistry and in situ hybridization. Macrophages, T cells, B cells, and endothelial cells were visualized in the lesions by the immunoperoxidase method using specific antibodies to each cell type. Subsequent in situ hybridization using 35S-labeled synthetic oligonucleotide probes complementary to human IL-1 alpha and IL-1 beta mRNA showed IL-1 transcripts in macrophages predominantly but not in T cells or B cells. Neither fibroblasts nor keratinocytes contained the IL-1 message to any significant extent. Endothelial cells also were essentially negative for IL-1 messages. These findings indicate that IL-1 is produced principally by macrophages in inflamed gingival tissues of humans. 
Current management, local management, and survival statistics of high-grade osteosarcoma. Experience in Japan. To report the current management of high-grade osteosarcoma in Japan, the authors studied the results of 55 cases treated in the authors' institutions and data provided by Osaka University (59 cases), Chiba Oncology Group (97), and Sapporo National Hospital (70). Twenty-five of the 55 cases in the authors' series were treated by limb-salvage surgery, 27 by amputation, and the remainder by chemotherapy. In all 226 cases from the three institutes, 106 were treated by amputation and 120 by limb-salvage surgery. Two local recurrences (4%) were found in the authors' series, three in the Osaka series, and eight in the Chiba series. Five-year accumulative survival rates in this study showed some differences, depending upon the institution or upon the protocol employed: in the authors' series it was 60% overall and 68% for a stronger chemotherapy group; in the Osaka series, it was 50% in a mild chemotherapy group and 72% in an intensive chemotherapy group; and in the Sapporo series, it was 36% and 73%, respectively. This study showed that local control of IIB osteosarcoma was successfully achieved by preoperative adjuvant chemotherapy and wide resection, and that an intensive chemotherapeutic combination of high-dose methotrexate, cisplatinum, and doxorubicin is promising. 
Nocardial meningitis: case reports and review. Twenty-eight episodes of nocardial central nervous system infection fulfilling criteria for meningitis were reviewed. In 21 cases Nocardia was cultured from cerebrospinal fluid (CSF). Associated predisposing conditions were present in 75% of cases. The typical presentation was subacute to chronic meningitis characterized by fever (68%), stiff neck (64%), and headache (55%). CSF studies revealed neutrophilic pleocytosis (83% of cases, greater than 500 white blood cells/mm3), hypoglycorrhachia (64%, less than 40 mg of glucose/dL), and elevated protein level (61%, greater than 100 mg/dL). In 43% of cases there was an associated brain abscess. Patients with brain abscess had more frequent and severe aberrations in mental status as well as higher initial white blood cell counts in CSF. Mortality was 52% for the 23 cases diagnosed antemortem and 57% overall. Compared with patients who died, survivors were younger, had lower initial CSF glucose levels, and were less likely to have brain abscess. Diagnosis was often delayed, and nocardial infection was rarely suspected before positive culture reports or autopsy findings became available. 
The influence of severity of spinal cord ischemia in the etiology of delayed-onset paraplegia. To clarify the cause of delayed-onset paraplegia, the authors evaluated the neurologic outcome after temporary (10 to 30 minutes) spinal cord ischemia in the awake rabbit. Loss of motor function occurred in less than 2 minutes in all animals. Restoration of flow within 16 minutes always resulted in full return of function, whereas with occlusion times of greater than 27 minutes all animals remained paralyzed. After temporary occlusion of 20 to 21 minutes, however, 71% of animals returned to normal neurologic function but developed delayed-onset paraplegia 14 to 48 hours later. This appears to be a reliable method for the creation of a model of delayed-onset paraplegia in the awake animal, and will facilitate more detailed studies of the pathophysiology of ischemia-induced paraplegia. 
Massive hemorrhage from a ruptured enteric varices of an augmented bladder. Intestinal varices are uncommon and usually occur secondary to portal hypertension. We report a case of variceal rupture in the intestinal segment of an augmentation colocystoplasty. The patient presented in shock from exsanguinating hemorrhage per urethram, and diagnosis was established at laparotomy. Although the bleeding was controlled with excision of the involved intestinal segment, the patient died of multiple organ failure. The diagnosis and treatment of this rare but fatal condition are discussed. 
Fatal aortic rupture during balloon dilatation of recoarctation. In an eight year old boy with a patch aortoplasty, the aorta ruptured during balloon angioplasty for recoarctation. At necropsy a 1.5 cm long, full thickness tear and a separate, smaller, intimal tear were found. Histological examination showed thinning of the elastic laminae of the aorta. Angioplasty for recoarctation may be dangerous in patients with a patch aortoplasty. 
Investigations on the biochemical characteristics of chronically underperfused muscle. During operation, biopsies from the gastrocnemius muscle and, in some cases, from the sartorius muscle were taken from 32 patients with peripheral arterial occlusive disease and from 5 subjects with normal peripheral circulation. In patients with inadequate circulation only during exercise, when compared with the control group, increased activities of enzymes involved in oxidative metabolism (malate dehydrogenase, nicotinamide adenine dinucleotide phosphate-dependent isocitrate dehydrogenase, cytochrome C oxidase, creatine kinase), in amino acid metabolism (asparate aminotransferase, alanine aminotransferase), and in anaerobic glycoysis (lactate dehydrogenase) were found. In patients with circulatory disturbances that manifested themselves already at rest, enzyme activities were, with the exception of LDH, lower than those of patients with exclusively exercise-related insufficiency. By means of intraindividual comparisons with the corresponding enzyme activities in the sartorius muscle, the author was able to show that the changes found were not simply the result of differences in training conditions. The diminished concentrations of energy-rich phosphate are an expression of the anaerobic metabolic state in patients with inadequate circulation at rest. It is concluded that chronic ischemia of muscle leads to changes in the energy metabolism of the cell. In the presence of more nearly adequate circulation at rest, the portion of oxidative potential of the total energy metabolism increases. In contrast, if there is an inadequate circulation at rest, the mainly anaerobic glycolysis becomes quantitatively predominant. 
Acute pulmonary embolism in pediatric patients awaiting heart transplantation. Acute pulmonary embolism with infarction can delay urgently needed heart transplantation and increase the postoperative pulmonary complications. Few data are available concerning pulmonary embolization in the pediatric patient with end-stage congestive heart failure. Sixty-two consecutive pediatric patients awaiting heart transplantation were monitored for evidence of acute pulmonary embolism. Acute pulmonary infarction was documented by ventilation-perfusion scan, pulmonary angiography or pathologic examination in six patients. The prevalence differed by diagnosis; 5 of 36 patients with dilated cardiomyopathy and 1 of 20 patients with congenital heart disease developed acute pulmonary embolism with infarction. No significant difference in age at the time of transplantation evaluation, duration of congestive heart failure, presence of cardiac arrhythmias or degree of cardiac dysfunction was seen between patients with and without pulmonary embolism. Two-dimensional echocardiography failed to detect the presence of an intracardiac thrombus in four of the six patients. Two patients who developed acute pulmonary infarction are alive after successful heart transplantation. The remaining four patients died within 6 weeks of initiation of anticoagulant therapy before transplantation could safely be performed. In summary, pediatric patients with end-stage congestive heart failure are at risk for acute pulmonary embolism. No specific clinical factor identified those patients who developed acute pulmonary infarction. Anticoagulant therapy is strongly recommended in the pediatric patient with poor ventricular function awaiting heart transplantation. 
Reliability of interviewer and subject assessments of nevus counts in a study of melanoma. Several types of data are presented concerning the reliability of counting or estimating the density of nevi (moles), a major risk factor for melanoma, using methods typically employed in epidemiologic studies. First, interviewer-derived counts of nevi on the arm produced estimates of inter-observer, inter-subject, temporal and random variability, and their interactions. Second, interviewer-derived arm counts and respondent self-reports of whole body nevus density were compared. Finally, we compared male and female cases and controls with respect to their reported rates of having a relative with a malignant mole. Overall, the intra-observer reliability ranged from 55 to 81%, and was better for observers with more experience. The correlation between the interviewer counts and respondents' self-reported estimates was 0.41. The data on malignant moles in relatives suggest higher reporting rates in male cases and lower reporting in male controls relative to their female counterparts, but there is little difference by sex in the reporting of one's own nevus density. 
The unstable ST segment early after thrombolysis for acute infarction and its usefulness as a marker of recurrent coronary occlusion. To investigate the incidence of early recurrent ST elevation after intravenous thrombolytic therapy for acute myocardial infarction, 12-lead electrocardiograms were continuously monitored for 571 +/- 326 minutes in 31 patients presenting within 4 hours of symptom onset. The study group comprised 9 women and 22 men (mean age +/- standard deviation 53 +/- 12 years), with ST elevation (anterior in 15, inferior in 16) on the initial electrocardiogram, who were given either tissue plasminogen activator (22 patients) or streptokinase (9 patients). Angiography was performed in 30 of 31 patients at 7 to 10 days. Early (less than 3 hours) resolution of ST elevation occurred in 19 patients (61%) at a median of 94 minutes (interquartile range 57 to 113) after thrombolysis, whereas 12 (39%) had no or late (greater than 6 hours) resolution. Eleven of the 19 with early resolution (58%) had either transient (5 patients) or sustained (6 patients) recurrences of ST elevation. Recurrent ST elevation was equal to or more than the initial peak elevation in 9 of 11 patients, and greater than 75% of initial peak in 2. A total of 25 episodes of recurrent ST elevation were observed in the 11 patients (19 transient and 6 sustained episodes), of which 8 (32%) were silent. The proportion of silent episodes was similar for transient (35%) and sustained (33%) recurrences. All patients with sustained recurrent ST elevation had at least 1 preceding transient recurrence. The median duration of transient recurrent ST elevation was 43 minutes (28 to 63). 
On lowering lipids in the post-infarction patient. In patients with coronary heart disease (CHD) elevated serum cholesterol levels, like other classical risk factors, remain predictive of further coronary events. The excess risk attributable to raised cholesterol levels is considerable, and greater than that in subjects without CHD. A recent meta-analysis of all eight qualifying trials of secondary prevention of CHD by cholesterol lowering is reviewed. There were significant reductions in recurrent non-fatal and fatal CHD, with a downward trend in total mortality. Mechanisms underlying the relationship between cholesterol lowering and secondary prevention are reviewed. The implication of this analysis of trials for clinical practice is that hypercholesterolaemia should be sought and effectively treated in patients with CHD, unless contraindications are present. 
Increasing use of soyfoods and their potential role in cancer prevention. The United States produces approximately half of the world's soybeans. Although most of what is produced is used as animal feed, soy-protein products (eg, soy-protein flour, concentrates, and isolates) are used extensively by the food industry, primarily for their functional characteristics, such as emulsification. During the past decade, however, there has been a marked increase in the use of both traditional soyfoods, such as tofu and soymilk, and second-generation soyfoods, products which generally simulate familiar American dishes. Recently, attention has focused on the possible role of soybean consumption in reducing cancer risk. Soybeans contain, in relatively high concentrations, several compounds with demonstrated anticarcinogenic activity. Two of these compounds--protease inhibitors and phytic acid--have traditionally been viewed as antinutrients. The scientific community has begun to appreciate the potential importance of nonnutritive dietary compounds (phytochemicals) in foods such as soybeans. Dietitians need to become more aware of the phytochemical content of foods and the possible effect of phytochemicals on health and disease. 
The low-affinity p75 nerve growth factor (NGF) receptor mediates NGF-induced tyrosine phosphorylation. Protein tyrosine phosphorylation is a potential mechanism for initial signaling in PC12 cells during differentiation in response to nerve growth factor (NGF). NGF-induced tyrosine phosphorylation has been found to be initiated by the trk protooncogene, which participates in the formation of high-affinity NGF binding sites. In contrast to transfection of wild-type low-affinity p75 NGF receptors, transfection of p75NGFR with mutations in the cytoplasmic domain resulted in an inability of NGF to elicit tyrosine phosphorylation of intracellular substrates, indicating that p75NGFR is involved in initiating phosphorylation events by NGF. Even though the p75NGFR receptor does not possess any inherent tyrosine kinase activity, these experiments demonstrate that the p75NGFR has a potential role in NGF-induced tyrosine phosphorylation. 
Renal calculi in lower pole calices: what is the best method of treatment? Percutaneous nephrolithotomy and extracorporeal shock wave lithotripsy (ESWL*) can be used in the treatment of lower pole caliceal calculi. In a retrospective analysis these 2 therapies were compared for treatment of solitary lower pole caliceal calculi to evaluate morbidity. During a 2-year period 23 patients treated with percutaneous nephrolithotomy and 24 who underwent ESWL with the Siemens Lithostar were analyzed in regard to the success rate, effectiveness quotient, complication rate, length of hospitalization and disability period. Followup consisted of ultrasound and/or a plain film of the kidneys, ureters and bladder 1 day and 1 to 3 months postoperatively. A nephrotomogram was included in the ESWL group. Complete removal of all stone fragments was achieved in 93.6% of the patients treated percutaneously without retreatment. In the ESWL group the success rate was 79.2% with a 41.6% retreatment rate. On the other hand, the ESWL group had a shorter hospitalization and an earlier return to normal physical activities. Among the patients who underwent a percutaneous operation 13% had complications compared to 4.1% in the ESWL group. The recurrence rate was higher in the former group (13% within a median of 18 months, compared to 8.3% within a median of 11 months in the ESWL group). The mean stone diameter was 1.42 cm. in the percutaneous group and 1.22 cm. in the ESWL group. Stone composition was similar in both groups. Since ESWL is an effective noninvasive procedure without the need for routine anesthesia and hospitalization, and with prompt return of the patient to a normal life it must be considered the method of choice for lower caliceal stones less than 2 cm. in diameter. However, percutaneous nephrolithotomy will continue to have a primary role in the management of larger stones. 
Biliary surgery after cardiac transplantation. Many patients have undergone successful cardiac transplantation. These patients are at risk of developing the same surgical diseases as the general population. The side effects of immunotherapy may mandate intervention at a different point in the natural history of these processes. From February 1984 through December 1989, 24 patients underwent an operative biliary tract procedure following cardiac transplantation. Seventeen patients underwent elective cholecystectomy with intraoperative cholangiography. The mean hospital stay was 5.4 days, and there was no morbidity or mortality. Seven patients underwent urgent procedures; four of them developed severe complications and three died as a result of their biliary tract disease. Two patients in the urgent group had previously exhibited symptoms of biliary tract disease, and five were previously asymptomatic. There was no significant difference in time from transplantation to biliary procedure between the elective group (mean, 17 months; range, 3 weeks to 47 months) and the urgent group (mean, 18 months; range, 3 weeks to 44 months). Patients who undergo cardiac transplantation should be screened for cholelithiasis. The presence of symptoms should not be required before recommending operative intervention. 
Postoperative infusional continuous regional analgesia. A technique for relief of postoperative pain following major extremity surgery. A new technique using postoperative infusional continuous regional analgesia (PICRA) for postoperative pain relief was investigated in 23 surgical patients treated by amputation (12 patients) or by limb-salvage resection operations (11 patients). Bupivacaine was delivered into peripheral nerve sheaths via catheters placed therein at the time of surgery. Only patients in whom the nerves were easily accessible were treated. Catheters were placed in the axillary sheath, the lumbosacral trunk, and the femoral nerve sheaths of patients treated with shoulder girdle and pelvic procedures (resections and amputations), and within the sciatic nerve sheath of those treated with lower extremity procedures. The anesthetic agent was delivered at controllable rates. Regional analgesia was obtained in the operative site with minimal motor or sensory decrease. To assess the efficacy of this technique, the results of this study group were compared with those of a matched group of 11 patients treated with similar surgical procedures but who received epidural morphine. Eleven of the 23 patients on PICRA required no supplemental narcotic agents. The mean level of the narcotic agents required by the remaining 13 PICRA patients was approximately one third of that required by the matched group of 11 patients receiving epidural morphine. Overall, the patients on PICRA had an 80% reduction of narcotic requirements when compared to the historical controls. The technique is reliable and can be performed by the surgeon, requiring about a ten-minute increase in operating time. It has potentially wide application in orthopedics in procedures in which the major nerves are easily accessible (e.g., pelvic fractures and revision hip surgery) and for patients with intractable pain of the extremities. 
Lambda-like and V pre-B genes expression: an early B-lineage marker of human leukemias. V pre-B and lambda-like genes are selectively expressed in human pre-B cells and encode polypeptide chains that associate in a mu-pseudolight chain complex that may regulate some crucial steps of early B-cell differentiation. We have followed by polymerase chain reaction and Northern blot analysis the expression of these "pre-B-specific" genes in correlation with the status (rearranged v germline) of Ig gene loci (H, kappa, lambda) in a panel of 32 leukemias pertaining mostly to the B lineage and including a number of ambiguously characterized samples. All cells that had rearranged the H locus only expressed V pre-B and lambda-like transcripts, in agreement with a pre-B status. In this group, some biphenotypic leukemias (mostly My/B) might, in fact, be already engaged in the B lineage. Rearrangement of V kappa or V lambda loci correlated with the disappearance of the pre-B gene products. In a pre-B acute lymphoblastic leukemia cell line that was induced to mature to the B-cell stage in culture upon kappa gene rearrangement, the mu-pseudolight chain complex was actually replaced by the classical mu-kappa molecule. Finally, V pre-B and lambda-like genes were found expressed in two leukemic cells that had retained all Ig loci in germline configuration. This finding raises the possibility of having an early pro-B progenitor in which V pre-B and lambda-like products associate with a H chain surrogate in a complex that would trigger an early event of B-cell differentiation such as the H locus rearrangements. 
Erythroderma, palmoplantar keratoderma and profound failure to thrive in an infant. The case is reported of a female infant, who at the age of 3 months developed severe erythroderma, marked hyperkeratosis of the palms and soles and subsequently extreme growth failure and intermittent diarrhoea. Her course was complicated by life-threatening infections but detailed investigation revealed no recognized underlying metabolic or immune abnormality. 
Role of interstitial therapy in the treatment of liver cancer. Conventional palliative management of inoperable focal hepatic tumours remains unsatisfactory. Interstitial techniques such as cryotherapy, alcohol injection, low power laser hyperthermia and interstitial radiotherapy offer alternative approaches. Cryotherapy is an effective and precise technique for inducing tumour necrosis. It can only be performed at laparotomy making it relatively invasive and retreatment impractical. Alcohol is cheap and can be injected percutaneously. However, inhomogeneous distribution produces imprecise and nonreproducible lesions. Low power laser hyperthermia produces precise and reproducible areas of necrosis that are roughly spherical in shape. At present, this technique is most effective for small tumours. Interstitial radiotherapy remains the least evaluated of all the interstitial techniques. Unlike cryotherapy and low power laser hyperthermia, the biological effect of ethanol injection and interstitial radiotherapy cannot be monitored in real time by ultrasound. With the exception of cryotherapy, all methods can be applied percutaneously with low morbidity and mortality. None of these techniques is established, but they may offer the prospect of cure in cases where all areas of tumour can be positively identified and fully treated. However, in most instances the intention is to control the growth of relatively small discrete volumes of tumour within the hepatic parenchyma. 
Middle ear fluid lysozyme source in experimental pneumococcal otitis media. Middle ear infection with Streptococcus pneumoniae is important in the pathogenesis of acute and chronic otitis media, and lysozyme in middle ear fluid (MEF) is an important inflammatory mediator in this disease. To determine the source of lysozyme during the early period of acute pneumococcal otitis media, chinchillas were irradiated to induce neutropenia, and their middle ears were inoculated with heat-killed, encapsulated pneumococci. The number of inflammatory cells and concentration of lysozyme were measured in MEF between 6 and 72 hours after inoculation. In pneumococcus-inoculated ears, the mean number of inflammatory cells but not lysozyme was significantly lower in MEF from irradiated animals than that from nonirradiated animals at 6 hours. Since lysozyme accumulated in MEF before the influx of inflammatory cells in irradiated animals, the initial release of this inflammatory mediator is most likely not from inflammatory cells; and mucosal epithelial cells, the only other known source of lysozyme in the middle ear environment, were the probable source induced by the direct stimulation of pneumococci. Inflammatory cells may contribute lysozyme later in the inflammatory response, since cellular and lysozyme concentrations in irradiated and nonirradiated animals were similar between 24 and 72 hours. These results suggest that future therapeutic interventions to limit middle ear inflammation in acute otitis media may need to recognize the direct action of pneumococcal cells or their envelope components on middle ear epithelium. 
Operative management of acoustic neuromas: the priority of neurologic function over complete resection. The objective of surgical management of acoustic tumors is to remove them entirely and preserve facial nerve function and hearing when possible. A dilemma arises when it is not possible to remove the entire tumor without incurring additional neurologic deficits. Twenty patients who underwent intentional incomplete surgical removal of an acoustic neuroma to avoid further neurologic deficit were retrospectively reviewed. They were divided into a subtotal group (resection of less than 95% of tumor) and a near-total group (resection of 95% or more of tumor) and were followed yearly with either computed tomography or magnetic resonance imaging. The subtotal group was planned and consisted of elderly patients (mean age, 68.5 years) with large tumors (mean, 3.1 cm). The near-total group consisted of younger patients (mean age, 45.8 years) and smaller tumors (mean, 2.3 cm). The mean length of followup for all patients was 5.0 years. Ninety percent of patients had House grade I or II facial function post-operatively. Radiologically detectable tumor regrowth occurred in only one patient, who was in the subtotal resection group. Near-total resection of acoustic tumor was not associated with radiologic evidence of regrowth of tumor for the period of observation. Within the limits of the follow-up period of this study, subtotal resection of acoustic neuroma in elderly patients was not associated with clinically significant recurrence in most patients and produced highly satisfactory rates of facial preservation with low surgical morbidity. 
The role of albumin in human physiology and pathophysiology, Part III: Albumin and disease states. The serum albumin level is one of several clinical parameters of the status of general health. There is a marked correlation between low albumin levels and the incidence of morbidity and mortality in hospitalized patients. Therefore, it is not surprising to find that hypoalbuminemia is a common finding among hospitalized patients. This results from alterations in the catabolic or anabolic rates, losses of albumin, or redistribution between the various fluid compartments of the body. Somewhat less well defined than the role of albumin as a prognostic indicator is its role in compounding pathophysiology. Hypoalbuminemia is known to be associated with delayed wound healing. The hypoalbuminemic state interferes with the normal functioning of the gastrointestinal tract. Qualitative changes in the albumin molecule which occur in renal disease may damage the nephron. Low serum albumin levels may adversely affect the coagulation system. Further investigation into the role of albumin in pathophysiology is warranted. 
Differentiation between renal allograft rejection and cyclosporine toxicity: a clinicopathological study. The differentiation between cyclosporine nephrotoxicity (CyN) and acute rejection (AR) still remains a matter of intensive research. In a retrospective study over the last 2 years, we assessed the clinical and histopathological data of 43 episodes of renal dysfunction in 39 renal transplant recipients immunosuppressed with cyclosporine (CyA). Ten episodes (23.2%) were identified as AR and 10 (23.2%) as acute CyN; in six cases (13.9%), signs of both AR and CyN were found. Fever (80%), oliguria (50%), and edema (50%) were prominent features in AR, but not in CyN. Renal blood flow was higher in the nephrotoxicity group and for corresponding degree of renal dysfunction. Significant hyperuricemia (greater than 8 mg/dL) was a prominent finding in CyN (80%) and to a lesser extent in AR (20%). The helper to suppressor cell ratio in the peripheral blood remained stable or slightly decreased in all cases with CyN, but increased in 70% of the cases with AR. CyN was associated with significantly higher whole blood CyA levels (P less than 0.005) and there was a positive correlation between plasma creatinine and CyA levels during the nephrotoxicity episodes (P less than 0.02). Diffuse mononuclear cell infiltrate was observed in 90% of the biopsies with AR and only in 20% with CyN (P less than 0.005). Concerning the extent of the tubular lesions, no significant differences were observed between the two groups. In contrast, vascular lesions such as arterial endothelial proliferation (P less than 0.05), hyalinosis (P less than 0.05), and glomerular capillary thrombi (P less than 0.05) were more commonly seen in nephrotoxicity biopsies. 
The paradox of 'chronic unstable angina' secondary to an organizing intracoronary thrombus [published erratum appears in South Med J 1991 Sep;84(9):1074, 1160] We have described a case in which coronary vasospasm and the resultant endothelial shear stresses most likely caused plaque rupture and transient coronary occlusion at the site of a minor atherosclerotic narrowing. Remodeling then led to a long, complex stenotic lesion that included ruptured and dissected endothelium and organized thrombus. This led to severe anginal symptoms over a 3-month period, or the paradox of "chronic unstable angina." Angioplasty was difficult but eventually successful after pulsed high-pressure balloon inflations and intracoronary thrombolytic therapy with streptokinase. This case demonstrates that the clinical course of a patient with minor or insignificant coronary disease may be a dynamic process that cannot be entirely predicted even by recent invasive cardiac studies. 
Lhermitte-Duclos disease and Cowden disease: a single phakomatosis. Two unrelated patients with macrocephaly, seizures, and mild cerebellar signs had a dysplastic gangliocytoma of the cerebellum (Lhermitte-Duclos disease). Both also had autosomal dominant Cowden disease as evidenced by facial, oral, and acral papules. In the two families, 9 sibs demonstrated the mucocutaneous lesions, thyroid disease, breast tumors, and ovarian tumors compatible with the diagnosis of Cowden disease. Some of the sibs also showed various degrees of neurological signs such as macrocephaly, mental retardation, seizures, tremor, and dysdiadochokinesia. Magnetic resonance imaging scans of sibs of one family demonstrated megalencephaly and other mild abnormalities. The occurrence of these two rare disorders in single patients is more than a coincidence, and the clinical findings in the combined condition establishes it as a new phakomatosis. 
Endothelin effects on renal function and tubuloglomerular feedback. Analysis of our data in conjunction with other recent literature allows the following conclusions regarding the role of endothelin in the tubuloglomerular feedback control mechanism and in the pathogenesis of acute ischemic renal failure: (1) Endothelin reduces nephron filtration rate in the nephrons with interrupted signal perception at the macula densa, in accord with preglomerular arteriolar constriction. Yet, the increase in filtration fraction in the whole kidney clearance study suggests a preferential postglomerular arteriolar constriction. Taken together, endothelin, which is a very potent renal vasoconstrictor, seems to constrict both preglomerular and postglomerular arterioles with a predominant constriction of the latter at the doses employed. (2) The endothelin-induced natriuresis is due to a fall in tubular reabsorption, reflecting a direct tubular action, possibly related to an elevation in blood pressure. (3) At the doses of endothelin used and under the present experimental conditions, changes in the magnitude of tubuloglomerular feedback (TGF) response or the feedback characteristic could not be detected. (4) No evidence was found for a participation of endothelin in the pathogenesis of acute postischemic renal failure, as evidenced by the absence of an improvement in glomerular filtration after treatment with endothelin antiserum. 
Idiopathic photoreceptor dysfunction causes unexplained visual acuity loss in later adulthood. Progressive visual loss, caused by initially unrecognized retinal photoreceptor dysfunction predominantly affecting cones, developed in six patients in late adulthood. Because of minimal ophthalmoscopic retinal abnormalities, the patients initially had been suspected of having optic neuropathy or psychogenic visual loss. The correct diagnosis was ultimately established by finding electroretinographic abnormalities and color discrimination losses out of proportion to visual acuity loss. In no case was a causative agent or a family history of photoreceptor disease identified. In many other respects, however, features of the patients' illness resemble those described previously under the headings of cone dysfunction syndrome, cone dystrophy, cone degeneration, and cone-rod dystrophy. 
Volvulus of the splenic flexure: radiographic features. Six cases of splenic flexure volvulus were studied over a 14-year period. The patients were aged 15-62 years. Five of the six patients were mentally retarded, lifelong residents of a long-term-care institution. Two patients had congenital absence of normal colonic attachments; the other four patients had elongated mesocolons, presumably from chronic constipation. All patients underwent abdominal radiography, followed by a barium enema study. In the appropriate clinical setting, radiographic diagnosis of a splenic flexure volvulus is suggested when the following are seen: (a) a markedly dilated, air-filled colon wtih an abrupt termination at the anatomic splenic flexure; (b) two widely separated air-fluid levels, one in the transverse colon and the other in the cecum; (c) an empty descending and sigmoid colon; and (d) a characteristic beak at the anatomic splenic flexure at a barium enema examination. 
Results of surgical therapy for biliary dyskinesia. One hundred eighty-seven patients who presented with symptoms consistent with biliary colic but had no ultrasonic evidence of cholelithiasis were observed in an effort to identify those with a functional gallbladder disorder that might benefit from surgical intervention. All patients underwent quantitative evaluation of gallbladder emptying using cholecystokinin biliary scanning, and ejection fractions less than 35% were considered abnormal. One hundred twenty-nine patients (69%) had abnormal ejection fractions, and 88 (68%) of these subsequently underwent cholecystectomy. Sixty of the surgical specimens revealed pathologic changes. Eighty-four percent of patients successfully contacted for follow-up experienced complete relief, and another 13% had partial relief of preoperative symptoms. Only two patients reported no change in symptom complex. Twenty-nine patients with abnormal ejection fractions elected not to undergo surgery. Fifty-nine percent of these patients continued to experience symptoms of biliary colic at a mean follow-up of 22 months. Of the 44 patients with normal ejection fractions, 35 (80%) reported resolution of symptoms during follow-up of medical treatment. Cholecystokinin biliary scanning can help identify patients with acalculous, functional gallbladder disease who may benefit from cholecystectomy. 
Impedance cardiography for repeated determination of stroke volume in elderly hypertensives: correlation with pulsed Doppler echocardiography. In this double-blind, crossover study the authors have validated stroke volume determination by impedance cardiography against the pulsed Doppler echocardiographic method in elderly hypertensives. They found a good correlation between the stroke volume values obtained by the two methods over a range of values from 30 to 130 mL. The coefficient of linear regression was about .95 at each visit. The mean of the differences was -0.73 mL with a standard deviation of 8.46. Given that individual differences are normally distributed, the values corresponding to 2 standard deviations of the mean define a range covering 95% of the observed differences. From the distribution of the data around the mean plot it appears that, in comparison with pulsed Doppler, impedance cardiography tends to slightly underestimate stroke volumes of greater than 90 mL and to overestimate values of less than 50 mL. The results of this study indicate that impedance cardiography may represent a reliable alternative to pulsed Doppler echocardiography for the noninvasive estimation of cardiac output at rest in elderly patients. 
Tricuspid annular motion. Triscupid annular motion is related to right ventricular systolic function in the same way mitral annulus motion is related to left ventricular function. Tricuspid annular excursion reflects the longitudinal motion of the right ventricle, and the systolic descent of the anulus correlates with systolic venous inflow to the right atrium. However, it has not been shown clearly how to reproducibly quantify this motion. Therefore we describe a method to measure triscuspid annular motion using two-dimensional oriented M-mode echocardiography from the apical view. We studied a group of 10 normal subjects (mean age, 28.7 years; range, 25 to 38 years) and a group of 29 patients (mean age, 57.2 years; range, 20 to 84 years) with disease of the left side of the heart but no evidence of involvement of the right side of the heart. In each subject, tricuspid and mitral annular motion were measured respectively at their lateral, septal or medial, anterior, and posterior margin points. The total tricuspid annular motion for normal subjects was, as follows: lateral, 24.9 +/- 3.5 mm; medial, 20.1 +/- 2.5 mm; anterior, 21.6 +/- 3.8 mm; and posterior, 22.3 +/- 2.3 mm. Interobserver and intraobserver variability was low, with a coefficient of variance for the different annular points ranging from 6.19% to 11.56% between observers and from 4.10% to 7.26% within observer. We conclude that it is possible to measure tricuspid annular motion with this method in a reproducible way and to use it as a diagnostic tool in evaluating function of the right side of the heart. 
Melanosis coli: a case report in a trauma patient and review of the literature. Melanosis Coli (MC) is a benign pigmentation disorder of the colon occasionally diagnosed at endoscopy. The authors report a case of M. coli in a patient with a gunshot to the abdomen, in whom the entity produced an interesting clinical picture, and a review of the literature on this condition. 
Asymptomatic myocardial ischemia during percutaneous transluminal coronary angioplasty and importance of prior Q-wave infarction and diabetes mellitus. Eighty-eight patients undergoing percutaneous transluminal coronary angioplasty (PTCA) of 100 stenoses were studied for the presence of factors deemed significant in the etiology of silent myocardial ischemia. Thirty-two patients were asymptomatic during balloon dilations of 36 arteries, and 56 patients had angina during PTCA of 64 arteries. There were no differences in age, sex, prior anginal history, antianginal regimen, extent of coronary artery disease and number or duration of inflations between the 2 study groups. Previous infarction (33 vs 12%, p less than 0.02), Q waves in the target area (31 vs 7%, p less than 0.005) and diabetes mellitus (36 vs 17%, p less than 0.05) were present more often in the asymptomatic group. Sixty-four% of all asymptomatic patients had either diabetes or previous infarction in the target territory. Collateral circulation was more frequent in asymptomatic patients, probably reflecting the ability of collateral arteries to ameliorate ischemia. During 2-vessel PTCA, patients without angina during dilation of only 1 of the 2 treated arteries (discordant responders) had previous infarction in that artery's territory (5 of 5, 100%), whereas patients without previous infarction were either symptomatic or asymptomatic (concordant responders) during PTCA of both arteries. This study shows that asymptomatic ischemia occurs frequently during PTCA in patients with symptomatic coronary disease. Prior Q-wave infarction and diabetes mellitus are important, independent factors associated with painless ischemia. It is suggested that infarction produces a localized dysfunction of afferent cardiac pain fibers, whereas diabetes can cause a global cardiac sensory neuropathy. 
Expanded clinical evaluation of lovastatin (EXCEL) study results: IV. Additional perspectives on the tolerability of lovastatin. This randomized, double-blind, multicenter, diet-and-placebo-controlled study was designed to clarify the dose-response relationship of lovastatin therapy to lipid-modifying efficacy and drug-related adverse events. Exclusion criteria were minimized so that study patients were representative of the majority of patients with moderate hypercholesterolemia seen in medical practice. After 6 weeks on the American Heart Association Step 1 Diet, a total of 8,245 patients were randomly assigned to 48 weeks of treatment with diet and placebo or lovastatin at dosages of 20 or 40 mg once a day or 20 or 40 mg twice a day. All adverse events were monitored, with particular attention to evaluation of liver and muscle. Liver transaminase elevations suggestive of possible hepatotoxicity, defined as successive elevations in either aspartate transaminase or alanine aminotransferase greater than 3 times the upper limit of normal, occurred in equal numbers of placebo and lovastatin 20 mg/day treated patients (0.1%). The frequencies were higher in lovastatin 40 mg/day and 80 mg/day patient groups (0.9 and 1.5%, respectively). No patient was diagnosed as having clinically symptomatic hepatic dysfunction. Creatinine kinase (CK) elevations above the upper limit of normal occurred frequently in placebo- (29%), as well as lovastatin-treated patients (29-35%), and muscle symptoms were reported with similar frequency in all groups (7-9%). The combination of muscle symptoms with marked CK elevations (greater than 10 times the upper limit of normal) was seen in only five patients: one in a 40 mg/day dose group and four in the 80 mg/day dose group. No patient developed rhabdomyolysis. The incidence of clinical and laboratory adverse events requiring discontinuation was 6% for the placebo group and from 7% (20 mg/day) to 9% (80 mg/day) for lovastatin treatment groups. No new types of adverse experiences related to lovastatin treatment were reported. Lovastatin, as an adjunct to diet for the reduction of elevated LDL cholesterol, was generally very well tolerated. 
Cis-platinum chemotherapy for ocular basal cell carcinoma. We have used intravenous cis-platinum chemotherapy in the treatment of three patients with basal cell carcinoma of the lid extending into the orbit. Cis-platinum chemotherapy caused a reduction in tumour size and thereby delayed surgery in all cases. It allowed for local resection in one case, appeared to delay a patient's exenteration in a second case, and was used prior to radiotherapy in a third case. While not curative, cis-platinum may be useful as an adjuvant to decrease tumour mass prior to local excision and for patients who refuse or must delay exenteration. 
Percutaneous radiofrequency catheter ablation for supraventricular arrhythmias in children. Nineteen procedures were performed in 17 children, aged 10 months to 17 years, using catheter radiofrequency applications for the management of malignant or drug-resistant supraventricular tachyarrhythmias. Diagnoses were junctional ectopic tachycardia in 1 patient, atrioventricular (AV) node reentrant tachycardia in 4 and accessory pathway-mediated tachycardia in 12. Accessory pathway locations were left lateral (n = 4), posteroseptal (n = 3), left posterior (n = 2), right posterolateral (n = 1), right posterior paraseptal (n = 1), right intermediate septal (n = 1) and right anterior (n = 1). Ablation of accessory pathways was performed using 20 to 40 W of energy. The catheter was passed retrograde to the left ventricle in patients with a left-sided pathway and anterograde to the right atrium in those with a right-sided or posteroseptal pathway. In the 12 patients with an accessory pathway, radiofrequency applications were successful in 11 pathways and failed in 2. There were no recurrences of accessory pathway-mediated tachycardia. Atrioventricular node reentrant tachycardia was treated by AV node modification using 15 W of energy applied until first degree AV block occurred. After radiofrequency catheter ablation, there was a prolonged AH interval, tachycardia was not inducible and tachycardia recurred in one patient. For the patient with junctional ectopic tachycardia, 15 to 18 W of energy was delivered at the site of the maximal His bundle electrogram until sinus rhythm and normal AV conduction appeared. After a recurrence, a second procedure abolished tachycardia and AV conduction. In summary, radiofrequency catheter ablation was initially successful in 17 of 19 procedures and ultimately curative in 14 (82%) of 17 patients with no serious complications. Radiofrequency catheter ablation appears to be a safe and effective method for the management of supraventricular tachyarrhythmias in children. 
The heterogeneity of human chorionic gonadotropin (hCG). I. Characterization of peptide heterogeneity in 13 individual preparations of hCG. Peptide variations in the alpha-subunit (molecules starting at alpha 3 and alpha 4) and beta-subunit (missing linkages at beta 44-45 and beta 47-48) of hCG have been reported by several investigators. Studies, however, have been limited to standard hCG preparations (purified from large pools of urine) and other hCG samples from mixed urines. In this study we used chromatographic procedures to purify the total hCG content of 13 individual urines, 6 from patients with pregnancy and 7 from those with trophoblast disease (no hCG-containing fractions were excluded). Then, we examined for the first time the peptide variability among individual samples of hCG. We report 1) that individual hCG preparations have nicks (missing linkages) in the beta-subunit, primarily between residue 47-48 (11 of 13 samples) and, less commonly, at the linkage 44-45 or 46-47 (3 of 13 samples); 2) the extent of nicking varies greatly between individual preparations (range, 0-100% of molecules); 3) varying alpha-subunit N-terminal heterogeneity (N-terminus starting at alpha 3 or alpha 4) was also present (range, 0-28% of molecules), but was confined to preparations from individuals with trophoblast disease (6 of 7 samples from trophoblast disease urine, 0 of 6 from pregnancy urine); 4) hCG missing the beta-subunit C-terminal region was also detected (2 of 13 hCG preparations); and 5) 1 of 13 preparations was nicked on the hCG alpha-subunit, between residues 70 and 71. Thus, 12 of 13 individual hCG samples demonstrated at least 1 of 4 different forms of peptide heterogeneity. We conclude that individual hCG samples vary widely in the type and extent of peptide heterogeneity, an observation that is not appreciated when pools of hCG are studied. 
Role of cardiac ATP-regulated potassium channels in differential responses of endocardial and epicardial cells to ischemia. Epicardial cells are more susceptible to the electrophysiological effects of ischemia than are endocardial cells. To explore the ionic basis for the differential electrophysiological responses to ischemia at the two sites, we used patch-clamp techniques to study the effects of ATP depletion on action potential duration and the ability of ATP-regulated K+ channels in single cells isolated from feline left ventricular endocardial and epicardial surfaces. During ATP depletion by treatment with 1 mM cyanide (CN-), shortening of action potential durations was significantly greater in epicardial cells than in endocardial cells. Thirty minutes after initiating exposure to 1 mM CN-, action potential duration at 90% repolarization was reduced to 0.70 +/- 0.12 of the control value for endocardial cells versus 0.39 +/- 0.18 for epicardial cells (p less than 0.01), and action potential duration at 20% repolarization was reduced to 0.72 +/- 0.13 for endocardial cells versus 0.12 +/- 0.09 for epicardial cells (p less than 0.01). In both endocardial and epicardial cells, the shortening of action potential by CN- treatment was partially reversed by 0.3 microM glibenclamide; the magnitude of reversal, however, was much greater in epicardial cells. After exposure to 1 mM CN-, the activity of ATP-regulated K+ channels in cell-attached membrane patches was significantly greater in epicardial cells than in endocardial cells. To study the dose-response relation between ATP concentration and open-state probability of the channels, intracellular surfaces of inside-out membrane patches containing ATP-regulated K+ channels were exposed to various concentrations of ATP (10-1,000 microM). The concentration of ATP that produced half-maximal inhibition of the channel was 23.6 +/- 21.9 microM in endocardial cells and 97.6 +/- 48.1 microM in epicardial cells (p less than 0.01). These data indicate that ATP-regulated K+ channels are activated by a smaller reduction in intracellular ATP in epicardial cells than in endocardial cells. The differential ATP sensitivity of ATP-regulated K+ channels in endocardial and epicardial cells may be responsible for the differential shortening in action potentials during ischemia at the two sites. 
Carcinoma of the esophagus: CT vs MR imaging in determining resectability. MR imaging and CT were performed prospectively in 35 patients with esophageal carcinoma to determine the resectability of the primary tumors, because at our institution patients with resectable tumors have surgery regardless of the presence of distant metastases. Tumors with evidence of aortic or tracheobronchial invasion on MR or CT were considered to be unresectable. Tracheobronchial invasion was diagnosed when the tumor extended into the lumen of the airway, and aortic invasion was diagnosed when the triangular fat space between the esophagus, aorta, and spine adjacent to the primary tumor was obliterated. Two patients were excluded because of suboptimal MR images produced by motion artifacts. Pathologic proof was obtained from either surgery or autopsy in 31 patients. Of these, six patients (19%) had proved unresectable tumors (three aortic invasion and three tracheobronchial invasion). In all six cases, these features were correctly detected with both MR and CT. One patient had false-positive findings on MR and CT. An indeterminate diagnosis was obtained with MR in three patients and with CT in four patients. These incorrect or indeterminate results were all related to the diagnosis of aortic invasion. No patient had a false-negative result. When indeterminate diagnoses were considered false-positive, sensitivity, specificity, and accuracy for resectability were 100%, 84%, and 87%, respectively, for MR and 100%, 80%, and 84%, respectively, for CT. We conclude that MR and CT have nearly the same accuracy in predicting resectability of tumors in patients with esophageal carcinoma. 
Diverticulitis of the duodenum: clinical and radiological manifestations of seven cases. Seven patients with duodenal diverticulitis were evaluated by computed tomography (CT) and various other abdominal imaging techniques. The series included four men and three women who ranged in age from 47 to 84 yr (mean: 65 yr). They had presented with epigastric or periumbilical pain, low-grade fever, leukocytosis, and loss of appetite and weight due to postprandial cramps or vomiting. In each instance, the abdominal CT examination proved crucial in the diagnosis of duodenal diverticulitis, with contained perforation or inflammatory changes involving the adjacent structures. Five patients underwent laparotomy while two others were treated conservatively with antibiotics and/or percutaneous drainage of peridiverticular abscess. The clinical and radiological features of this uncommon entity are herein described, along with a brief review of the medical literature regarding the current approach to its diagnosis and management. 
Cryotherapy for cutaneous Kaposi's sarcoma (KS) associated with acquired immune deficiency syndrome (AIDS): a phase II trial. To assess the response and toxicity of liquid nitrogen cryotherapy for cutaneous lesions of Kaposi's sarcoma (KS) associated with AIDS, we evaluated 20 subjects with biopsy-proven KS in a phase II clinical trial. Subjects had two to four cutaneous KS indicator lesions treated with liquid nitrogen cyrotherapy. Treatment was repeated at 3 week intervals, allowing adequate healing time. On average, subjects received three treatments per lesion with a mean follow-up time of 11 weeks (range of 6-25 weeks). One treatment consisted of two freeze-thaw cycles, with thaw times ranging from 11 to 60 s per cycle. A complete response was observed in 80% of treated KS lesions and lasted a minimum of 6 weeks following the completion of therapy. Greater than 50% cosmetic improvement of KS was observed. Histopathology of treated lesions correlated poorly with cosmetic improvement. Response was not predicted by tolerance to zidovudine therapy, CD4+ cell count, presence of B symptoms, or previous chemotherapy. Subjects without prior history of opportunistic infection (OI) were more likely to have a better response than those with a prior history of OI. Subjects tolerated cryotherapy well. Blistering occurred frequently, but local pain was limited and relieved by acetaminophen. Secondary infection did not occur. Based on this study, we recommend cryotherapy to subjects with cutaneous KS lesions. Liquid nitrogen cryotherapy is easily applied as a primary therapy, and may also have a role in the treatment of cutaneous KS lesions that respond slowly or show incomplete cosmetic improvement with systemic therapies. 
Clinical risk factors for Alzheimer's disease: a population-based case-control study. Using information on clinical risk factors provided through the medical record linkage system of the Rochester Epidemiology Project, we conducted a population-based case-control study of Alzheimer's disease (AD). During the period 1960 to 1974, we identified 415 newly diagnosed cases of AD among residents of Rochester, Minnesota, and matched one community control to each case based on age, sex, and duration of community medical record. We estimated odds ratios using conditional logistic regression for several potential clinical risk factors of AD. Among more than 20 clinical risk factors that were evaluated, the only statistically significant findings were for episodic depression, personality disorder, and hypertension. 
Increasing incidence of hypertrophic pyloric stenosis. The incidence of pyloric stenosis in the Mersey region rose from 1.54/1000 births in 1976-8 to 2.22/1000 births in 1986-8. Reliance on ultrasonography for diagnosis in the 1980s resulted in fewer 'tumours' being felt; diagnostic delay was not shortened overall but serial ultrasonography showed evolving lesions in six patients. Clinical examination and selective use of ultrasonography is advocated. 
Blunt abdominal trauma resulting in intestinal obstruction: when to operate? The overall approach to blunt abdominal trauma resulting in hematoma and intestinal obstruction has been variable and controversial. Recent reports recommend conservative nonoperative management. We reviewed six cases of duodenal and jejunal hematomas resulting from blunt trauma of which five resolved with nasogastric decompression and parenteral nutrition. The average hospital stay was 16 days (10-23 days), and total parenteral nutrition days were 9 days (4-16 days). Upper gastrointestinal series (UGI) demonstrated partial bowel obstruction in all five cases. In contrast, the sixth case was a restrained passenger who had evidence of complete bowel obstruction on UGI series, which failed to resolve after 18 days of conservative management. Laparotomy revealed jejunal and colonic strictures with fibrosis, which were successfully resected. We recommend that based on radiologic documentation of persistent high-grade obstruction, as well as the clinical course, patients whose obstructions do not resolve by 10 to 14 days ought to be further investigated and operative intervention considered. This approach may facilitate an earlier diagnosis of complications, reduce length of hospitalization and days on parenteral nutrition, as well as to expedite the proper management. 
Cold cerebroplegia. A new technique of cerebral protection during operations on the transverse aortic arch. Profound hypothermia associated with circulatory arrest is the commonest method of cerebral protection during operations on the aortic arch. This technique allows a limited time to perform the aortic repair, however. It also necessitates prolonged cardiopulmonary bypass to rewarm the patient. This may be the cause of coagulation disorders or infection. Selective perfusion of the carotid arteries can also be used. When the perfusion is derived from the main arterial line, however, the repair of the aorta requires that the vessel be crossclamped, and cannot be performed in an "open, bloodless" manner. To avoid the disadvantages of both techniques, we have developed a new technique of cerebral protection. After a regular cardiopulmonary bypass has been established, the carotid arteries are cannulated and perfused with blood cooled at 6 degrees to 12 degrees C, through a separate heat exchanger, while the core temperature is maintained at moderate hypothermia (25 degrees to 28 degrees C, rectal). To perform the "open" distal repair, the cardiopulmonary bypass is discontinued while the carotid perfusion is maintained (250 to 350 ml/min). When the distal repair is completed, cardiopulmonary bypass is resumed and the carotid perfusion is discontinued. Between 1984 and June 1989, 54 patients (mean age 55 years) were operated on with this method (45 elective operations, 9 emergency procedures). Mean duration of cardiopulmonary bypass was 121 minutes (65 to 248), and mean duration of circulatory arrest was 22 minutes (10 to 51). The electroencephalogram, routinely recorded, showed return of the cerebral activity after a mean time of 12 minutes and normal activity after a mean time of 66 minutes. There was no intraoperative death. Hospital mortality rate was 13% (7/54). One death was related to neurologic disorders. All patients but one awakened normally within 8 hours after operation. Two patients (4.3%) experienced a transient neurologic episode (lateral hemianopia) 9 and 11 days postoperatively. There was no hemorrhagic complication (24-hour average blood loss: 840 +/- 540 ml). In our experience the technique of "cold cerebroplegia" has been demonstrated to provide excellent cerebral protection. It requires no prolonged cardiopulmonary bypass and does not limit the time necessary to perform the aortic repair. It may be considered as a safe alternative to profound hypothermia associated with circulatory arrest. 
Lectin-reactive patterns of markedly elevated serum alpha-fetoprotein in patients with chronic active hepatitis. Four cases of chronic hepatitis associated with high serum levels of alpha-fetoprotein (AFP) without hepatocellular carcinoma are reported. All showed transient elevations of serum AFP, with peak levels of 13,500, 8,000, 4,450, and 3,000 ng/ml shortly after aggravation resulting from liver function tests. Liver biopsies revealed severe parenchymal damage in all the cases with piece-meal necrosis, bridging necrosis or bridging fibrosis. In two of four cases, there was a lobular distortion. AFP stain by an immunoperoxidase method showed a positive result in surviving hepatocytes. Lectin affinity electrophoresis of AFP in the four cases, together with an additional 12 patients with chronic hepatitis and cirrhosis and 44 patients with hepatocellular carcinoma, all having AFP levels above 1,000 ng/ml, revealed that the chronic hepatitis patients had a benign pattern of AFP bands, in contrast with the pattern of hepatocellular carcinoma with increased proportions of lentil lectin-reactive AFP-L3 and/or erythroagglutinating phytohemagglutinin-reactive AFP-P4, indicating that the analysis of lectin reactivity of AFP has a great value in differentiating the benign and malignant conditions with increased serum levels of AFP above 1,000 ng/ml. 
Effect of ST segment measurement point on performance of standard and heart rate-adjusted ST segment criteria for the identification of coronary artery disease BACKGROUND. Recent reports critical of the performance of heart rate-adjusted indexes of ST depression during exercise electrocardiography have used J-point rather than ST segment measurements. However, no standard exists for the optimal time after the J-point at which to measure ST segment deviation. METHODS AND RESULTS. To assess the effect of ST segment measurement position on performance of standard exercise electrocardiographic criteria, the delta ST segment/heart rate (delta ST/HR) index, and the ST segment/heart rate (ST/HR) slope for the detection of coronary artery disease, the exercise electrocardiograms of 50 clinically normal subjects and 80 patients with known or likely coronary disease were analyzed using ST depression measured at both the J-point and at 60 msec after the J-point (J + 60). A positive exercise electrocardiogram by standard criteria, defined as 0.1 mV or more of additional horizontal or downsloping ST depression at end exercise, had a specificity of 96% when ST depression was measured at either the J-point or J + 60. There was no difference in sensitivity of standard electrocardiographic criteria at J + 60 and J point (both 59%, p = NS). However, at matched specificity of 96%, the delta ST/HR index and ST/HR slope calculated using ST depression at J + 60 were significantly more sensitive (90% and 93%) than when calculated using J-point depression (64% and 61%, each p less than 0.001). Comparison of areas under respective receiver operating characteristic curves confirmed the superior performance of J + 60 as opposed to J-point measurements for both the delta ST/HR index (0.98 versus 0.89, p = 0.006) and the ST/HR slope (0.96 versus 0.87, p = 0.007) and also demonstrated modestly improved overall test performance for standard electrocardiographic criteria using J + 60 measurements (0.88 versus 0.82, p = 0.001). CONCLUSIONS. Use of J-point measurements significantly degrades performance of heart rate-adjusted indexes of ST depression but has less effect on standard criteria. 
Psychosis and physical aggression in probable Alzheimer's disease. OBJECTIVE: The purpose of this study was to determine the frequency and type of psychotic symptoms in patients with probable Alzheimer's disease and to test whether there is a relationship between specific psychotic symptoms and episodes of physical aggression. METHOD: From 209 patients with possible or probable Alzheimer's disease who had been assessed in a research clinic every 6 months for up to 4.5 years, 181 subjects with probable Alzheimer's disease were selected for study. On the basis of the summary note for each visit in the patients' charts, the presence of delusions, hallucinations, misidentifications, and episodes of physical aggression was determined. Data regarding psychotic symptoms and aggression were available for 170 and 169 subjects, respectively. RESULTS: Delusions had been reported for 74 (43.5%) of the patients and were the most frequent psychotic symptom; persecutory delusions were the most common type. Physical aggression had been noted for 50 (29.6%) of the patients. Delusions and misidentifications frequently preceded and were significantly associated with episodes of physical aggression. The presence of delusions was a significant predictor of physical aggression but accounted for only 3.5% of the variance. CONCLUSIONS: This study suggests that delusions are a risk factor for physical aggression in patients with probable Alzheimer's disease who have moderate to severe cognitive impairment. As delusions accounted for only a small percentage of the variance, further research is needed to identify other variables that may be significant predictors of physical aggression in this population. 
Management of complicated fractures involving the orbits and nasoethmoid complex in young children. This article presents some ideas and techniques for surgical reduction of complicated orbit and nasoethmoid complex fractures in young children. Operative techniques for surgical exposure and fracture reduction and fixation have evolved from standard facial incisions and wire fixation to complete exposure of the cranium and orbits via a bicoronal scalp flap, application of rigid plating techniques, and use of cranial bone grafts when necessary. This evolution of surgical techniques has been accompanied by an overall improvement in cosmetic and functional results. 
Postmenopausal estrogen therapy and cardiovascular disease. Ten-year follow-up from the nurses' health study BACKGROUND. The effect of postmenopausal estrogen therapy on the risk of cardiovascular disease remains controversial. Our 1985 report in the Journal, based on four years of follow-up, suggested that estrogen therapy reduced the risk of coronary heart disease, but a report published simultaneously from the Framingham Study suggested that the risk was increased. In addition, studies of the effect of estrogens on stroke have yielded conflicting results. METHODS. We followed 48,470 postmenopausal women, 30 to 63 years old, who were participants in the Nurses' Health Study, and who did not have a history of cancer or cardiovascular disease at base line. During up to 10 years of follow-up (337,854 person-years), we documented 224 strokes, 405 cases of major coronary disease (nonfatal myocardial infarctions or deaths from coronary causes), and 1263 deaths from all causes. RESULTS. After adjustment for age and other risk factors, the overall relative risk of major coronary disease in women currently taking estrogen was 0.56 (95 percent confidence interval, 0.40 to 0.80); the risk was significantly reduced among women with either natural or surgical menopause. We observed no effect of the duration of estrogen use independent of age. The findings were similar in analyses limited to women who had recently visited their physicians (relative risk, 0.45; 95 percent confidence interval, 0.31 to 0.66) and in a low-risk group that excluded women reporting current cigarette smoking, diabetes, hypertension, hypercholesterolemia, or a Quetelet index above the 90th percentile (relative risk, 0.53; 95 percent confidence interval, 0.31 to 0.91). The relative risk for current and former users of estrogen as compared with those who had never used it was 0.89 (95 percent confidence interval, 0.78 to 1.00) for total mortality and 0.72 (95 percent confidence interval, 0.55 to 0.95) for mortality from cardiovascular disease. The relative risk of stroke when current users were compared with those who had never used estrogen was 0.97 (95 percent confidence interval, 0.65 to 1.45), with no marked differences according to type of stroke. CONCLUSIONS. Current estrogen use is associated with a reduction in the incidence of coronary heart disease as well as in mortality from cardiovascular disease, but it is not associated with any change in the risk of stroke. 
The short test of mental status. Correlations with standardized psychometric testing. The Short Test of Mental Status can be administered to patients in inpatient and outpatient settings in approximately 5 minutes, and it contains items that test orientation, attention, immediate recall, arithmetic, abstraction, construction, information, and delayed (approximately 3 minutes) recall. The test was administered to a group of demented community patients and their age- and sex-matched control subjects. Using an age-adjusted approach, sensitivity of the test to identifying dementia is 86.4, with a specificity of 93.5. The test was compared with standardized tests of cognitive function such as the Wechsler Adult Intelligence Scale, Mattis Dementia Scale, and the Auditory Verbal Learning Test, and showed a high degree of correlation. Group means and standard deviations for subtest items and total score are presented for control subjects (n = 138), demented patients (n = 130), and patients with memory impairment only (n = 20). Percentile scores for subtest items in control subjects are also provided. 
Relationship of echocardiographic, shunt flow, and angiographic size to the stretched diameter of the atrial septal defect. Stretched diameter of the atrial septal defect (ASD), measured by balloon sizing, is generally used as a guide to the selection of the size of the device utilized for transcatheter closure of the ASD. Balloon sizing is a cumbersome procedure and sometimes requires the use of very large size balloon catheters. Several methods of assessment of ASD size, namely, echographic, pulmonary-to-systemic flow ratio (Qp:Qs), and angiographic measures, were undertaken in a group of 16 patients, aged 7 months to 45 years (median, 4.5 years), who were being evaluated for transcatheter closure of ASD; the results were compared with the stretched diameter. Although the echographic size of the ASD (9.9 +/- 4.1 mm, mean +/- SD) is similar (p greater than 0.1) to the angiographic size (7.9 +/- 2.5 mm), it is much smaller (p less than 0.01) than the stretched diameter (16.1 +/- 5.3 mm). When the relationship between various measures of ASD was examined, although the Qp:Qs ratio and angiographic size have a significant (p less than 0.05) correlation with the stretched diameter (r = 0.55 and 0.54, respectively), the echo diameter has the best correlation coefficient, r = 0.82, p less than 0.001. The stretched diameter can be estimated by the equation: 1.05 x echo + 5.49 mm. It is concluded that the echographic diameter is a useful adjunct in the estimation of the stretch ASD diameter, which in turn can be used in the selection of the size of the device for transcatheter occlusion of the ASD. 
Pattern of cell kinetics in colorectal mucosa of patients with different types of adenomatous polyps of the large bowel. It is generally accepted that adenomatous polyps represent the natural precursor of many colorectal malignancies. The sequence, however, which leads from a normally appearing mucosa to cancer is complex and involves many steps, including a hyperproliferative mucosa with an upward expansion of the replicative compartment. The current study evaluates cell replication in normal colorectal mucosa of patients with adenomatous polyps of various types and relates the observed findings to the main clinical and morphologic features of adenomas. Forty-four patients with polyps and 27 controls entered the study. Samples of colorectal mucosa were taken at endoscopy and cell replication was evaluated with a standard autoradiographic procedure. Cell replication was expressed as labeling index (LI), in the whole crypt and in each of the five longitudinal compartments in which the crypts were divided. Total LI and LI per crypt compartment were significantly higher (P less than 0.02 and P less than 0.01, respectively) than in controls. There was no appreciable difference of LI values between patients with single or multiple, tubular or tubulovillous, small or large adenomas, but in all of these subgroups LI was significantly higher than in controls. In conclusion, in normally appearing colorectal mucosa of patients with adenomatous polyps there was a significant increase of cell replication and a marked upward expansion of the proliferative zone; these changes were more evident in the left colon and in the rectum. Finally, cell replication did not seem to be related to the number of polyps, to the most common histotypes, or to the pattern of recurrence. 
A new manifestation and treatment alternative for heparin-induced thrombosis. We treated a coronary artery bypass patient whose postoperative course was complicated by heparin-induced thrombocytopenia and resultant pulmonary artery and saphenous vein graft thromboses. The pulmonary thromboemboli were found first, and pulmonary blood flow was restored with intravenously administered tissue plasminogen activator (tPA). A short time later, the vein grafts were found to be occluded, and we subsequently performed multivessel percutaneous transluminal coronary angioplasty (PTCA) using tPA as an adjuvant to oral warfarin sodium therapy with excellent results. We conclude that heparin-induced thromboses in the pulmonary arteries are amenable to thrombolytic therapy, including tPA, whereas this regimen appears to have little effect on saphenous vein grafts. We also found that a combination of warfarin and thrombolytic therapy is an alternative regimen for heparin-intolerant patients who require PTCA. 
Blood glucose control and albuminuria in type 1 diabetes mellitus. The relationship between long-term blood glucose control and albuminuria in type 1 diabetes was investigated in 42 male and 58 female patients who had had diabetes mellitus for more than 7 years. Their mean (+/- SD) age and diabetes duration were 18.6 +/- 3.6 and 12.1 +/- 3.5 years, respectively. For periods of observation ranging from 1 to 6 years (mean 4.4 +/- 1.5), hemoglobin A1c (HbA1c) was measured two to six times yearly (mean of 8.8 +/- 3.9 determinations per patient). Albumin excretion rate (AER) was measured in single-void urine samples two to four times in 93 patients and once in the other seven patients. The 52 patients with mean HbA1c no more than 9.0% had significantly lower mean AER than those whose HbA1c was greater than 9.0% (20.1 +/- 24.6 vs 265 +/- 1005 mg/gm Cr, p less than 0.001). Only five (9.6%) of these 52 patients had elevated AER values (greater than 40 mg/gm Cr), whereas 21 (43.7%) of 48 patients whose mean HbA1c was greater than 9.0% had elevated AER values (p less than 0.001). Six male but no female patients had mean AER values greater than 300 mg/gm Cr. The 74 patients with normal AER had significantly lower mean HbA1c values than the 26 with elevated AER (8.6 +/- 1.5 vs 10.1 +/- 1.6%, p less than 0.001). These results support the contention that maintenance of HbA1c levels at no more than 9% (one and one-half times the upper limit of normal) will significantly decrease the likelihood that diabetic nephropathy will develop. 
Massive cystic ureteral diverticula in infancy. We report 2 cases of massive abdominal distension due to a mid ureteral diverticulum. In a 1-year-old boy the mid ureteral diverticulum was associated with an atrophied chronically scarred kidney. In a female newborn the diverticulum was associated with an upper pole ureter of a completely duplicated system. To our knowledge this type of ureteral diverticulum has not been reported previously. 
Neuronal and glial properties of a murine transgenic retinoblastoma model. Antigenic properties of a murine transgenic model for hereditary retinoblastoma, induced by a chimeric gene coding for Simian virus 40 large T antigen, an oncogene that inactivates the retinoblastoma susceptibility gene product, were studied by immunohistochemistry. All transgenic mice develop bilateral intraocular retinal tumors in the inner nuclear layer with Homer Wright-like rosettes, and one quarter develop midbrain tumors resembling trilateral retinoblastoma. Cell lines TE-1 and TM-1 were established from intraocular and metastatic tumors, respectively. Intraocular tumors reacted with antibodies to neuron-specific enolase and synaptophysin, while vimentin, glial fibrillary acidic, and S-100 proteins were detected only in reactive glia derived from adjacent retina. The midbrain tumors showed weak reactivity to synaptophysin, and they blended with reactive astrocytes positive for glial markers. The tumors were negative for cytokeratins. Finally both derived cell lines expressed synaptophysin and individual neurofilament triplet proteins in immunofluorescence and Western blotting, supporting their essentially neuronal nature. The antigenic profile resembles human retinoblastoma, but differences in morphology and antigen distribution suggest a more close relationship to neurons of the inner nuclear layer than to photoreceptor cells. 
Quantitation of early myocardial ischemia using acridine orange fluorescence--an experimental study. It has been observed in the present investigation that ischemic myocardium consistently produces bright green fluorescence after Acridine Orange (AO) staining. The area of ischemia in the left ventricular myocardium at different time intervals after onset of experimental ischemia has been calculated by use of this AO fluorescence technique. Zonal distribution of ischemia in the epicardial, middle, and endocardial zones has also been evaluated quantitatively from ten minutes to six hours after ligation of the anterior descending branch of the left coronary artery in the Wistar strain of albino rats. No similar study was available for comparison from the literature reviewed. The total area of left ventricular ischemia showed an increase with the prolongation of duration of coronary ligation from 13.39 +/- 2.69 mm2 at ten to twenty-five minutes to 32.99 +/- 5.69 mm2 at six hours after ligation. Statistical analysis of the zonal area of ischemia has shown that ischemia in the middle and endocardial zones was greater than that in the epicardial zone at all time intervals recorded. Middle zone ischemia extended over a larger area than that over the endocardial zone at all intervals except at intervals II (30-45 min), IV (2-2 1/2 hrs) and V (3-4 hrs). The results of this experimental investigation are significant for these point to the value of Acridine Orange fluorescence in detecting early myocardial ischemia and in demarcating zonal differences in ischemia. The authors have successfully utilized the method in a few human cases of clinically suspected myocardial infarction and recommend the technique for routine use to detect early human myocardial ischemia. 
Cutaneous T-cell lymphoma associated with the acquired immunodeficiency syndrome Four cases of T-cell lymphoma occurring in the setting of the acquired immunodeficiency syndrome (AIDS) have been reported previously. We describe a 46-year-old man with AIDS in whom a cutaneous T-cell lymphoma with lymph node involvement developed. Immunohistochemical staining of the skin revealed the lymphoid infiltrate to be CD3+, CD4+, CD8+, and T-cell antigen receptor alpha/beta positive. Co-infection with human T-cell lymphotropic virus type I was not detected by polymerase chain reaction. Human immunodeficiency virus infection may have contributed to the development of this patient's lymphoma. This case represents the rare occurrence of cutaneous T-cell lymphoma and AIDS. 
The hemodynamic effects of intubation during nitroglycerin infusion in severe preeclampsia. The effectiveness of intravenous nitroglycerin infusion in lowering maternal blood pressure and in blunting the hemodynamic responses to endotracheal intubation was evaluated in six primigravid women with severe preeclampsia. Monitoring consisted of continuous electrocardiogram monitoring, arterial cannulation, and flow-directed pulmonary arterial catheterization in each patient. All patients underwent oxytocin induction of labor and crystalloid and/or colloid expansion to produce a pulmonary capillary wedge pressure of 10 to 15 mm Hg and a colloid osmotic pressure of greater than 17 mm Hg. Intravenous nitroglycerin was administered before induction of general anesthesia. The hemodynamic effects associated with endotracheal intubation revealed a change in the heart rate from 104 +/- 10 to 133 +/- 17 beats/min, an increase in mean arterial pressure from 134 +/- 12 to 164 +/- 32 mm Hg, and an increase in systemic vascular resistance from 1262 +/- 342 to 1351 +/- 259 dynes-sec-cm-5 that was accompanied by a small change in the cardiac index from 4.5 +/- 1.2 to 4.5 +/- 0.9 L.min-1.m-2. 
Malignant prolactinomas. Six cases of malignant prolactinoma have been reported; an additional two cases are presented here and the literature is reviewed. Diagnosis rests upon evidence of metastasis rather than histological criteria per se. Cases have arisen from known adenomas, particularly the invasive type. Bromocriptine is a useful palliative. The features and treatment of malignant prolactinoma are discussed. 
Evaluation of extracranial-to-intracranial bypass surgery using iodine 123 iodoamphetamine single-photon emission computed tomography. Eleven patients with occlusive cerebrovascular diseases were imaged with N-isopropyl-p-I-123 iodoamphetamine. Preoperative and postoperative single-photon emission computed tomography was performed in 10 patients undergoing extracranial-to-intracranial bypass procedures. New images were reconstructed from the two images obtained on the different days by superimposition and division in each pixel to get the ratio of cerebral perfusion change. All patients with bypass procedures had an increase in cerebral blood flow in the affected areas, and nine of 10 had an increase in cerebral blood flow in the contralateral cortex. There was no increase in cerebral blood flow in one case with no operation. Neither our procedure nor the results in this small series prove that recovery of function is due to an increase in blood flow, but we believe this is the case. 
Laser balloon angioplasty: clinical, angiographic and histologic results. Laser balloon angioplasty combines conventional coronary angioplasty with laser energy to transiently heat vascular tissue. Laser balloon angioplasty, was performed in 21 patients (aged 56 +/- 13 years), including 10 patients treated urgently after acute failure of conventional angioplasty and 11 patients treated with elective laser balloon angioplasty. Immediately after conventional angioplasty, laser doses (1 to 10 doses of 205 to 380 J each) were delivered during inflation of the laser balloon to a pressure of 4 atm. Seven (70%) of 10 patients with acute failure of conventional angioplasty were successfully treated with laser balloon angioplasty, but 3 (30%) were unsuccessfully treated with the laser procedure and required emergency coronary artery bypass surgery. In all three failures, the 3 mm laser balloon angioplasty catheter was not the optimal size for the vessel. In the 11 patients treated with elective laser balloon angioplasty (reference diameter 2.94 +/- 0.22 mm), the minimal luminal diameter increased from 0.45 +/- 0.25 to 1.85 +/- 0.46 mm after conventional angioplasty and to 2.44 +/- 0.29 mm after laser balloon angioplasty (p less than 0.001). This corresponded to a decrease in diameter stenosis from 84 +/- 9% before to 35 +/- 16% after conventional angioplasty and to 15 +/- 10% after laser balloon angioplasty (p less than 0.001). There were no instances of myocardial infarction, emergency coronary artery bypass surgery or death and no acute complications related to delivery of laser energy in this group. Follow-up coronary angiography was performed 5.5 +/- 1.1 months after laser balloon angioplasty in 18 patients discharged from the hospital after a successful procedure. Ten patients (56%) had angiographic restenosis, defined as recurrent diameter stenosis greater than 50%. Six patients were subsequently treated by directional coronary atherectomy, which revealed intimal proliferation indistinguishable from that in patients with restenosis after conventional angioplasty. In conclusion, laser balloon angioplasty may be effective in sealing severe coronary dissections and reversing abrupt closure associated with failed conventional angioplasty. After uncomplicated conventional angioplasty, laser balloon angioplasty improves immediate luminal dimensions, but restenosis appears to be mediated by intimal hyperplasia, similar to that seen after conventional angioplasty. 
Laser cordectomy for T1 glottic carcinoma: a 10-year experience and videostroboscopic findings. Fifty-three patients underwent laser cordectomy for T1 glottic squamous cell carcinoma between January 1980 and December 1989--sixteen after having undergone unsuccessful radiation and thirty-seven who had no previous treatment. There was a 51% five-year cure rate in the irradiated group vs. 62% in the nonirradiated group. Extension of tumor to the anterior commissure resulted in a higher failure rate. Patients experienced an overall 5-year cure rate of 98% after surgical or radiation salvage of unsuccessful laser cordectomies. Six patients had preoperative and postoperative videostrobolaryngoscopy. The most common postoperative problem with voice was a breathiness that did not resolve in any of the patients. All patients had absent or moderately reduced amplitude and mucosal wave patterns and imcomplete glottic closure proportional to the amount of cordal tissue removed. Despite it seemingly poor results in carefully selected patients, laser cordectomy is still indicated without compromising the ultimate oncologic results. Advantages over radiation therapy or conservation laryngeal surgery include a short treatment time, requiring only an outpatient surgical procedure at the time of the initial diagnostic and/or staging laryngoscopy, and the avoidance of potential radiation side effects or surgical complications. However, patients should be advised the possibility of persistent postoperative breathy dysphonia, in addition to the possibility of further treatment to effect a long-term cure. 
North American Symptomatic Carotid Endarterectomy Trial. Methods, patient characteristics, and progress. Fifty North American centers have combined to evaluate the benefit of carotid endarterectomy in randomized patients who have experienced symptoms related to arteriosclerotic stenosis of the carotid artery and who have received either best medical therapy alone or best medical therapy plus carotid endarterectomy. The outcome events are nonfatal and fatal stroke or death. A three-tier system identifies and adjudicates the type, severity, and location of each stroke and the cause of any death. Data about patients submitted to carotid endarterectomy outside the trial are compiled at the Nonrandomized Data Center at the Mayo Clinic. Between December 27, 1987, and October 1, 1990, 1,212 patients were randomized, 596 to medical therapy, 616 to carotid endarterectomy. Cross-over from the medical to the surgical arm has been low (4.2%). Patients eligible for the trial, but not randomized totaled 1,044; their characteristics were similar to those randomized so that, for the type of symptomatic patient in this study, our conclusions about the benefit of carotid endarterectomy can be generalized. Patients excluded by medical criteria totaled 679. Another 1,591 had carotid endarterectomy, but either lacked the disease under study, were asymptomatic, or received inadequate investigation to meet entry criteria. We set sample size at 1,900 patients, with continuing enrollment. The Monitoring Committee reviews at intervals the confidential analyses performed on the groups with moderate (30-69%) and severe (70-99%) stenosis. Stopping rules will be invoked for one or both groups if unequivocal benefit or harm is identified. 
Continuous automated monitoring of somatosensory evoked potentials in posttraumatic coma. Using a microcomputer system, 36 patients were continuously monitored with somatosensory evoked potentials (SSEPs) following closed head injury. The mean duration of monitoring was five days. The patients' GCS scores at the start of monitoring ranged from 3-10. Mortality was 44%. Of 14 patients who had initial absence of SSEP activity after the N20 wave or lost this activity during the period of monitoring, 12 died and two remained vegetative. Eighteen of 22 patients who had preservation or enhancement of this activity had a functional survival (3-month outcomes, p less than 0.001). The best outcomes were observed in the patients with the greatest number of peaks and highest amplitudes in the SSEPs, often in spite of increased intracranial pressure (ICP). The management of three patients was altered as a result of SSEP monitoring. We conclude that continuous monitoring of SSEPs is a useful adjunct in the management of comatose head-injured patients. 
Prostate specific antigen after irradiation for prostatic carcinoma. The clinical significance of serum prostate specific antigen after primary irradiation for adenocarcinoma of the prostate is uncertain. Between September 1986 and December 1987 serial prostate specific antigen values were determined in 43 patients before and after definitive radiation therapy. The study group included 6 patients with stage T0d, 10 with stage T1, 11 with stage T2 and 16 with stage T3 disease, with a mean pre-treatment prostate specific antigen level of 49.2 +/- 10.8. For all patients the first post-treatment prostate specific antigen level was less than the pre-treatment level. One patient failed locally with recurrent prostatic cancer that invaded the rectum. The 6 patients who failed with symptomatic metastases had an increasing prostate specific antigen level 2 to 7 months before detection of recurrence. Based on the absolute value and trend of the prostate specific antigen, patients were described as being at high, intermediate or low risk for distant metastases. Of 9 high, 6 intermediate and 28 low risk patients 4 (44%), 2 (33%) and 0 (0%) have experienced recurrent disease (p = 0.0025). We conclude that serial post-irradiation prostate specific antigen values may be useful in the early identification of patients at risk for treatment failure. 
Complications of infection and immunologic status after surgery for patients with esophageal cancer. Correlations between defective cell-mediated immunity (CMI) and infections following surgery for esophageal cancer were evaluated. Peripheral lymphocytes, T cells, B cells, PHA transformation, and PPD skin test were measured in 81 patients with esophageal cancer, 58 with gastric cancer, and 50 healthy controls. The depression of CMI was predominant to a similar extent in patients with esophageal cancer and in those with gastric cancer. The average level of PHA transformation immediately before surgery was significantly lower in the esophageal cancer patients with fatal septic complications than in those without such problems. Although preoperative radiation therapy markedly depressed the levels of the four parameters, this association was also noted in 28 patients not given radiation. It thus appears that PHA transformation may be valuable in the prediction of fatal septic complications after major surgery in patients with esophageal cancer. 
Evidence from cadavers suggestive of entrapment of fifth lumbar spinal nerves by lumbosacral ligaments. Lumbosacral spines from 51 geriatric-age cadavers (25 men and 26 women) were examined both grossly and under the dissecting microscope for evidence of compression of fifth lumbar spinal nerves by their respective lumbosacral ligaments. These ligaments were found to extend from the transverse process and body of L5 to the ala of the sacrum in 97% of the specimens, and from the transverse process and body of L5 to the promontory of the sacrum in 3% of the specimens. Anterior primary rami of the fifth lumbar spinal nerve were observed to be compressed in 11% (11 of 102) of the specimens examined grossly and under the dissecting microscope. Histologic evidence of chronic compression, as suggested by perineurial and endoneurial fibrosis, peripheral thinning of myelin sheaths, or subjective evidence of a shift in fiber diameter to a population of smaller size fibers was found, deep to the lumbosacral ligament, in three of the 11 nerves judged to be compressed. The information derived is of interest to the clinician whose patient presents with L5 root signs and a myelogram, discogram, and computed tomographic scan which do not show any abnormality. The possibility of extraforaminal compression must be considered as a possible source of the clinical signs. 
The use of transdermal scopolamine to control drooling. A case report. Drooling is a serious social handicap experienced by some neurologically impaired patients. No one method has been identified to control drooling for all patients, however, anticholinergic drugs recently have been utilized. In the case study described, transdermal scopolamine patches were found to be effective for controlling drooling in a traumatic brain-injured patient for whom more conservative methods failed. From a baseline saliva flow rate, saliva flow decreased an average of 30% with one-patch and 59% with two-patch dosing. No significant side effects were observed with treatment, and the decrease in drooling was maintained for a 4-month period. Although transdermal scopolamine may represent one acceptable facet of long-term treatment, it must be stressed that efficacy is variable across patient populations and that treatment approaches must be individualized. 
Gastric collision tumor (carcinoid and adenocarcinoma) with gastritis cystica profunda. We report a rare case of gastric collision tumor (carcinoid and adenocarcinoma) with gastritis cystica profunda that developed in a 49-year-old Japanese man. Early gastric cancer (moderately differentiated tubular adenocarcinoma) was present at the edge of an ulcer in the posterior wall of the upper gastric body. In addition, a carcinoid tumor was found adjacent to adenocarcinoma. This tumor displayed ribbonlike or trabecular patterns, and numerous constituent cells were positive for the argyrophil reaction with Grimelius' stain and serotonin. Electron microscopic features of this tumor confirmed typical carcinoid. There was no merged appearance between both tumors, suggesting collision-type tumor. 
Neopterin and interferon-gamma in serum and cerebrospinal fluid of patients with HIV-associated neurologic disease. We measured the levels of interferon-gamma (IFN-gamma) and neopterin in the serum and cerebrospinal fluid of 121 human immunodeficiency virus-seropositive (HIV+) and 62-seronegative (HIV-) individuals evaluated for neurologic disease. CSF levels of IFN-gamma and serum and CSF levels of neopterin were higher in HIV+ than in HIV- individuals. Patients with HIV- related meningitis and with opportunistic CNS infections had higher serum neopterin levels than HIV+ asymptomatic individuals. CSF levels of IFN-gamma were slightly higher in CSF of HIV+ individuals in all groups (0.31 +/- 0.03 U/ml) than in HIV- individuals (0.12 +/- 0.03). CSF levels of neopterin were similar in HIV+ asymptomatic individuals (6.9 +/- 0.7 nmol/l) and HIV- individuals (5.9 +/- 1.1), but were elevated in those HIV-infected individuals with neurologic disease, particularly patients with HIV-associated meningitis (72.1 +/- 13.3 nmol/l), opportunistic CNS infections (36 +/- 9.1), and inflammatory demyelinating polyneuropathies (32.4 +/- 17.2). Levels of neopterin correlated positively with levels of soluble interleukin 2 receptor and soluble CD8, 2 additional indicators of immune activation. In the absence of neurologic disease, levels of IFN-gamma and neopterin in both serum and CSF were stable for up to 4 years after seroconversion. These data suggest that increased CSF neopterin is associated with HIV-associated neurologic disease. 
Serum immunoglobulin G subclasses in children infected with human immunodeficiency virus type 1. We studied serum concentrations of IgG subclasses in 47 human immunodeficiency virus 1-infected (17 asymptomatic and 30 symptomatic) children. Thirty-nine of 47 (83%) had an abnormality of at least 1 subclass. Sixteen had only elevated IgG1, 6 had only elevated IgG3 and 12 had elevated IgG1 and IgG3 concentrations. IgG2, IgG4 and combined IgG2-IgG4 deficiency was found in 3, 4 and 4 patients, respectively. IgG2 concentrations did not differ between patients with (n = 23) or without (n = 24) bacterial infections. Additionally the number of bacterial infections was similar between the patients with normal or low IgG2 and/or low IgG4. These data indicate that IgG subclass abnormalities are found in most children with human immunodeficiency virus 1 infection, but quantitative deficiencies of specific subclasses do not appear to explain the high frequency of bacterial infections occurring in these patients. 
The bladder cooling test for urodynamic assessment: analysis of 400 examinations. The clinical significance of the bladder cooling test as one part of a standard urodynamic examination was studied in 375 consecutive patients and 25 controls. Inability to perceive cold sensation in the bladder was common in cases of neurogenic lesions and present in nearly half of the patients with outlet obstruction, some with no urodynamic abnormalities and some of the normal subjects. The bladder contractions provoked by the test were clearly associated with detrusor overactivity, as in those patients with upper motor neuron lesions of motor urgency, but 27% of such patients showed no response. In 7 cases the iced water provoked detrusor contractions when cystometry showed no overactivity. This clinical series confirms that the cold receptors found recently in animal experiments are also present in the human urinary bladder. The bladder cooling test is not an alternative to cystometry, but its inclusion as an integral part of the urodynamic examination seems to be useful, especially in cases where there is also a need to study the sensibility of the bladder at the same time. 
Choroideremia and deafness with stapes fixation: a contiguous gene deletion syndrome in Xq21. The study of contiguous gene deletion syndromes by using reverse genetic techniques provides a powerful tool for precisely defining the map location of the genes involved. We have made use of individuals with overlapping deletions producing choroideremia as part of a complex phenotype, to define the boundaries on the X chromosome for this gene, as well as for X-linked mixed deafness with perilymphatic gusher (DFN3). Two patients with deletions and choroideremia are affected by an X-linked mixed conductive/sensorineural deafness; one patient, XL-62, was confirmed at surgery to have DFN3, while the other patient, XL-45, is suspected clinically to have the same disorder. A third choroideremia deletion patient, MBU, has normal hearing. Patient XL-62 has a cytogenetically detectable deletion that was measured to be 7.7% of the X chromosome by dual laser flow cytometry; the other patient, XL-45, has a cytogenetically undetectable deletion that measures only 3.3% of the X chromosome. We have produced a physical map of the X-chromosome region containing choroideremia and DFN3 by using routine Southern blotting, chromosome walking and jumping techniques, and long-range restriction mapping to generate and link anonymous DNA sequences in this region. DXS232 and DXS233 are located within 450 kb of each other on the same SfiI and MluI fragments and share partial SalI fragments of 750 and greater than 1,000 kb but are separated by at least one SalI site. In addition, DXS232, which lies outside the MBU deletion, detects the proximal breakpoint of this deletion. We have isolated two new anonymous DNA sequences by chromosome jumping from DXS233; one of these detects a new SfiI fragment distal to DXS233 in the direction of the choroideremia gene, while the other jump clone is proximal to DXS233 and detects a new polymorphism. These data refine the map around the loci for choroideremia and for mixed deafness with stapes fixation and will provide points from which to isolate candidate gene sequences for these disorders. 
Mycobacterial infections after renal transplantation. Mycobacterial infections occurred in 11 of 633 (1.7 per cent) recipients of successful renal transplants. There were no cases of tuberculosis in patients receiving chemoprophylaxis, but amongst those who did not receive prophylaxis disease occurred in six of the 27 (22 per cent) high-risk patients. The major cause of morbidity during treatment was renal allograft rejection, largely due to reduction in immunosuppressive drug therapy. 
Facial reanimation after acoustic neuroma excision: the patient's perspective. Facial reanimation after acoustic neuroma excision is currently accomplished using a variety of surgical techniques. A multi-institutional survey of patient perceptions of facial reanimation success was accomplished by mailing a questionnaire to 809 randomly selected members of the Acoustic Neuroma Association. Four hundred sixty patients who underwent 296 reanimation procedures responded. Facial to hypoglossal nerve anastomosis, tarsorrhaphy, and upper eyelid implants were most frequently performed. The patient's estimations of initial deficit, spontaneous recovery, and overall satisfaction with the reanimation procedures are discussed. 
Successful shock-wave lithotripsy of bile duct stones using ultrasound guidance. Eighteen patients with 41 gallstones in the common bile duct, common hepatic, cystic, and intrahepatic ducts underwent shock-wave lithotripsy using the electrohydraulic Sonolith 3000 lithotripter. Lithotripsy was performed using ultrasound guidance alone under intravenous analgesia/sedation. All patients previously had failed stone extraction via retrograde endoscopy, T-tube, or cholecystostomy. Lithotripsy was performed according to an FDA-approved protocol allowing a maximum of two 2500 shock-wave treatments at a 48 hr interval. Following the final lithotripsy or cholangiographic evidence of stone fragmentation, residual fragments were removed via endoscopic or percutaneous route within 24-72 hr. Ultrasound localization of gallstones was aided by continuous infusion of the common bile duct with saline solution. In 15 of the 18 patients, complete fragmentation of the stones was accomplished, two had minimal fragmentation, and one with an encysted stone had no fracturing. No serious complications were encountered. Overall nonsurgical stone-free success rate was 17 of 18 patients, indicating biliary duct stones can be successfully treated using an ultrasound-guided lithotripter and intravenous sedation alone. 
Differentiation of F9 embryonal carcinoma cells induced by the c-jun and activated c-Ha-ras oncogenes. The activated c-Ha-ras oncogene induced AP1-site DNA-binding activity in F9 cells. This induction appeared to be due, at least in part, to the induction of c-jun transcription. Both activated c-Ha-ras and c-jun induced the differentiation of F9 cells to endoderm-like cells. Thus, AP1 appears to play a key role in the initial stage of F9 cell differentiation. 
Pseudolymphoma of the parapharyngeal space. A case report of pseudolymphoma of the parapharyngeal space is presented, together with a literature review of pseudolymphoma and management suggestions for such lesions when they occur in the head and neck. To the best of the authors' knowledge, this represents the first case report of pseudolymphoma presenting within the parapharyngeal space. The key to management of these lesions is based on accurate diagnosis, with differentiation of pseudolymphoma from lymphocytic lymphoma, the disease process which it mimics. 
Effect of level of patient acuity on clinical decision making of critical care nurses with varying levels of knowledge and experience. This study is an examination of the effect of patient acuity on the clinical decision making of critical care nurses (N = 68) completing two computerized clinical simulations. Ventricular tachycardia represented the high-acuity situation and atrial flutter the lower-acuity situation. Clinical decision making was measured by proficiency score, patient outcome (cure or die), and amount of data collected. Analyses of variance were conducted to examine proficiency score and the amount of data collected. Fisher's exact test and the McNemar test of homogeneity of proportions were used to examine patient outcome. In the atrial flutter simulation, proficiency scores were higher (p = 0.000), more dysrhythmias were cured (p less than 0.005), and more data were collected (p = 0.040). Experienced and inexperienced nurses did not differ on proficiency score; however, inexperienced nurses collected more data (p = 0.048) and cured fewer atrial flutter simulations (p = 0.040). Nurses certified in advanced cardiac life support had higher proficiency scores (p = 0.033) and collected fewer data (p = 0.048). 
Creutzfeldt-Jakob disease in a patient with a cadaveric dural graft. We report a 26-year-old woman with Creutzfeldt-Jakob disease (CJD) who had received cadaveric dural material 33 months before the onset of neurologic symptoms. This is the fourth case in which a dural graft was the putative source of the CJD agent. All four cases had the grafting before changes in the sterilization procedure adopted in 1987 to inactivate the CJD agent. 
Intraoperative death during lumbar discectomy. A patient suffered cardiovascular collapse and died during surgery for prolapsed intervertebral disc. At postmortem a tear was found in the abdominal aorta. 
Flexible sigmoidoscopy screening for asymptomatic colorectal disease in patients with and without inguinal hernia. Several studies have evaluated the diagnostic value of flexible sigmoidoscopy for screening asymptomatic patients before hernia repair. All have shown a 16% to 28% incidence of neoplastic (malignant or premalignant) lesions. None of these studies compared a similar group of asymptomatic patients without hernia to determine whether the incidence is increased in patients with hernias. We reviewed 87 consecutive cases of male surgical patients without hernia or any anorectal disease who had flexible sigmoidoscopy between June 1986 and December 1989 (group 1) and compared them with a group of hernia patients that we previously reported (group 2). Patients with stool positive for occult blood were excluded from this study. Examinations in both groups were done under the direct supervision of an attending surgeon (W.W., C.S.C., or J.K.). No significant difference was noted between group 1 and group 2 in mean age (mean 65.6 vs 59.7 years), rate of normal findings (68% vs 63%), and incidence of neoplastic lesions (14% vs 22%). All patients tolerated the procedure well, and there were no complications. 
The natural history of superficial femoral artery stenoses. Since the natural history of specific superficial femoral artery stenoses is not known, we examined progression rates of superficial femoral artery stenoses in 45 lower extremities found when arteriograms were obtained of 38 patients for symptomatic atherosclerotic disease in the opposite leg or abdomen. These initial superficial femoral artery arteriograms were compared with later arteriograms in 25 limbs, duplex scans in 27 limbs, and both modalities in 7 limbs. After a mean interval of 37 months, most superficial femoral artery stenoses (72%) did not progress. However, 12 superficial femoral artery stenoses progressed (28%; mean follow-up, 37 months, including 7 that occluded (17%). Superficial femoral artery stenoses progressed among patients who complained of symptom progression at a rate faster than that among asymptomatic patients (15.6%/year vs 3%/year; p = 0.006). Superficial femoral artery lesions also progressed more rapidly among patients whose contralateral superficial femoral artery was occluded (10%/year vs 1.6%/year; p = 0.04). By multivariate regression analysis, symptom progression and smoking history were predictive of superficial femoral artery stenosis progression. In the seven patients whose superficial femoral artery stenoses progressed to occlusion, the average rate of stenosis progression was 12%/year (maximum predicted rate, 30% per year by 95% confidence limit). These results indicate that superficial femoral artery stenoses usually progress with synchronous symptomatic deterioration. Other than symptom progression, only cumulative smoking history and contralateral superficial femoral artery occlusion could be associated with superficial femoral artery stenosis progression in this small series. 
Hyperglycemia and neurological outcome in patients with head injury. To examine the relationship between serum glucose and the outcome of patients suffering from head injury, the authors retrospectively reviewed the clinical course of 169 patients admitted for treatment to Harborview Medical Center (a regional trauma center). All patients underwent craniotomy for evacuation of intracranial hematoma and/or placement of a subarachnoid bolt for intracranial pressure monitoring under general anesthesia. Patients with a Glasgow Coma Scale (GCS) score of 8 or less had significantly higher serum glucose levels than patients with GCS scores of 12 to 15 (mean +/- standard error of the mean 192 +/- 7 mg/dl vs. 130 +/- 8 mg/dl or 10.7 +/- 0.4 mmol/liter vs. 7.2 +/- 0.4 mmol/liter) (p less than 0.0001). Patients who subsequently remained in a vegetative state or died had significantly higher glucose levels both on admission and postoperatively than patients who had good outcome or moderate disability (217 +/- 12 mg/dl vs. 167 +/- 6 mg/dl or 12.1 +/- 0.7 mmol/liter vs. 9.3 +/- 0.3 mmol/liter on admission, and 240 +/- 16 mg/dl vs. 156 +/- 5 mg/dl or 13.3 +/- 0.9 mmol/liter vs. 8.9 +/- 0.3 mmol/liter postoperatively) (p less than 0.0001). Among the more severely injured patients (GCS score less than or equal to 8), a serum glucose level greater than 200 mg/dl (11.1 mmol/liter) postoperatively is associated with a significantly worse outcome (p less than 0.01). The authors conclude that severely head-injured patients frequently develop hyperglycemia and the elevated serum glucose level may aggravate ischemic insults and worsen the neurological outcome in such patients. 
Human peripheral blood lymphocytes targeted with bispecific antibodies release cytokines that are essential for inhibiting tumor growth. We have compared the mechanisms by which human PBL targeted with bispecific antibodies either lyse tumor cells or block their growth in culture or in mice. We found that resting PBL were unable to mediate lysis, but were able to block tumor growth. Moreover, targeted PBL were unable to lyse bystander cells, whereas targeted PBL did block the growth of bystander tumor cells in culture and in nude mice. Supernatants from cultures of targeted PBL, or from PBL grown on anti-CD3-coated flasks, blocked the growth of tumor cells in the absence of added effector cells, and antibodies against TNF-alpha and IFN-gamma reversed the inhibition of tumor growth, but had no effect upon cytolysis mediated by targeted by PBL. Our results show that targeted human PBL mediate two different antitumor activities: lysis, which occurs rapidly and requires the direct attachment of the target cell to the cytotoxic cell, and tumor growth inhibition, which is mediated by cytokines released into the medium as a result of receptor cross-linking. The inhibition of bystander tumor growth in mice by targeted PBL suggests that factor release is sufficient to block tumor growth in vivo. Targeted factor release therefore provides a mechanism by which targeted PBL could block the growth of tumor cells in vivo that were not bound by the effector cells, but which were located in the vicinity of tumor cells that were bound. 
Digital artery embolization as a result of fibromuscular dysplasia of the brachial artery. A 74-year-old woman was admitted to the hospital with sudden onset of a blue, painful right index finger, and the condition progressed to digital ulceration. The ulcer gradually healed over a period of 2 months. Peripheral pulses, Doppler-derived brachial and radial systolic pressures, and results of an echocardiogram were normal. Digital pulse volume recordings showed obstructive waveforms in all digits of the right hand. Arteriography showed a normal arch and normal innominate, subclavian, and axillary arteries. The midbrachial artery was markedly abnormal and had alternating areas of stenosis and aneurysm formation. Multiple occlusions involved the palmar arch and proper digital arteries. The abnormal brachial artery segment was excised and replaced with an autogenous reversed saphenous-vein conduit. Histologic examination confirmed the lesion to be medial fibromuscular dysplasia. Fibromuscular dysplasia that involves upper extremity arteries is extremely uncommon and rarely presents with digital artery embolization. This case emphasizes the importance of exclusion of proximal reconstructible arterial occlusive disease by means of complete arteriographic examination of patients who were admitted with unilateral finger or hand ischemia. 
Intracranial hemorrhage and hemophilia: case report and management guidelines. Hemophiliacs, as a result of low coagulation factor levels, may suffer spontaneous intracranial hemorrhage. A case of intracranial hemorrhage in a hemophiliac patient with a history of intravenous drug abuse and HIV infection is reported. Factor replacement, airway management, and risks of HIV exposure to emergency department personnel are discussed. 
Cerebral sparganosis: case report and review. Sparganosis is a rare infection caused by a tapeworm larva from the genus Spirometra. A 21-year-old Indian man presented with an 18-month history of episodic confusion followed by a grand mal seizure. Computed tomography and magnetic resonance imaging of the brain confirmed the presence of a lesion of the left occipital lobe. Subsequent stereotactic biopsy revealed a plerocercoid larva or sparganum. Surgical resection resulted in cure. This case prompted a review of the literature on central nervous system sparganosis. Altogether, 17 other cases of primary cerebral sparganosis have been reported previously. Seizures, headache, and focal neurologic signs are common at presentation. Neuroradiologic imaging is sensitive but not specific for the identification of lesions. Enzyme-linked immunosorbent assay of cerebrospinal fluid or serum may be diagnostically helpful. However, the diagnosis is generally made after surgical resection, which is usually curative. 
An unusual complication of high dose infusion computerized tomography in a patient with a continent diversion. We describe a myelodysplastic woman with a Kock continent ileal reservoir who suffered parastomal herniation of the pouch following high dose infusion computerized tomography. Prophylactic indwelling catheterization in patients with continent diversion undergoing procedures that induce significant diuresis or involve prolonged distension of the reservoir is probably indicated. 
Analysis of invasive squamous cell carcinoma of the vulva and vulvar intraepithelial neoplasia for the presence of human papillomavirus DNA. We have analyzed a number of invasive squamous cell carcinomas for the presence of human papillomavirus (HPV) DNA using dot blot and Southern blot analysis. Seven of 31 samples (23%) were positive by dot blot and/or Southern blot analysis. In contrast, six of 11 (55%) of vulvar intraepithelial neoplasias contained HPV DNA by dot blot and/or Southern blot hybridization. Less than 50% of the invasive vulvar carcinomas contained detectable HPV DNA. The average age at onset of vulvar carcinoma is higher than that for cervical carcinoma (in which HPV DNA is detected in over 80% of cases). Therefore, the role of HPV in the genesis of vulvar carcinoma may be different from the role of HPV in the genesis of cervical carcinoma. 
Familial nemaline myopathy: case reports. Two siblings of two generations in the same family with nemaline myopathy are described. The disease affects all skeletal muscles, especially the facial muscles, producing a typical facial appearance. The diagnosis was made by light microscopy of histologically stained sections of muscle biopsy. The disease in our patients seems to be transmitted in an autosomal dominant manner. The purpose of this article is to emphasize the importance of recognition of the facial appearance by maxillofacial surgeons and the appropriate referral of patients for further neurologic examination. 
Failure of motor evoked potentials to predict neurologic outcome in experimental thoracic aortic occlusion. Motor evoked potential monitoring was tested as an alternative to somatosensory evoked potential monitoring in evaluating spinal cord function during thoracic aortic occlusion in dogs. Twenty-seven animals underwent 60 minutes of cross-clamping of the proximal descending thoracic aorta with (n = 18) or without (n = 9) cerebrospinal fluid drainage. Spinal cord blood flow was measured with microspheres, and neurologic outcome was evaluated at 24 hours with Tarlov's scoring system. Cerebrospinal fluid drainage improved neurologic outcome (p less than 0.05). Motor evoked potentials recorded over the lumbar spinal cord were lost in 9 of 20 dogs with ischemic cord injury and were not lost in any of the 7 dogs that were neurologically normal. Somatosensory evoked potential were lost in 19 of 20 paraplegic/paraparetic dogs and lost in 3 of 7 normal dogs (p less than 0.01). After reperfusion, motor evoked potentials returned in all nine neurologically injured dogs that lost the potentials and were still present at 24 hours. Changes in amplitude, latency, or time until loss or return of motor evoked potentials or somatosensory evoked potentials did not predict neurologic injury. Loss of somatosensory evoked potentials had a high sensitivity (95%) but had low specificity (67%) because of peripheral nerve ischemia. Loss of motor evoked potentials recorded from the spinal cord had high specificity (100%) but a low sensitivity (46%) and was therefore not a reliable predictor of neurologic injury. Return of motor evoked potentials during reperfusion did not correlate with functional recovery. Motor evoked potentials stimulated in the cortex and recorded from the spinal cord had low overall accuracy (59%). 
Snoring and the risk of ischemic brain infarction. To determine if a history of snoring is a risk factor for brain infarction, I conducted a case-control study of risk factors for ischemic stroke using 177 consecutive male patients aged 16-60 (mean 49) years with acute brain infarction. For each patient I chose an age-matched (+/- 6 years) male control. Arterial hypertension, coronary heart disease, snoring (habitually or often), and heavy drinking (greater than 300 g/wk) were risk factors in the stepwise multiple logistic regression analysis. The odds ratio of snoring for brain infarction was 2.13. By McNemar's test this association increased strongly if a history of sleep apnea, excessive daytime sleepiness, and obesity were all present with snoring (odds ratio 8.00). My study indicates that snoring may be a risk factor for ischemic stroke, possibly because of the higher prevalence of an obstructive sleep apnea syndrome among snorers than nonsnorers. 
Mechanisms of disruption of the articular cartilage surface in inflammation. Neutrophil elastase increases availability of collagen type II epitopes for binding with antibody on the surface of articular cartilage. We recently observed that specific antibodies to type II collagen do not bind in appreciable amounts to the intact surface of articular cartilage, whereas antibodies to the minor collagen types V, VI, and IX do. These results suggest that the outermost cartilage surface layer prevented interaction of the antibodies with the major collagen type in articular cartilage. The present studies were designed to investigate the pathogenic mechanisms involved in the disruption of the cartilage surface layer in inflammatory arthritis. Articular cartilage obtained from rabbits undergoing acute antigen-induced arthritis of 72 h duration showed a significant increase in binding of anti-type II antibody to cartilage surfaces compared with normal control cartilage (P less than 0.01). Augmentation of anti-type II binding was also observed upon in vitro incubation of bovine articular slices or intact rabbit patellar cartilage for 1 h with human polymorphonuclear neutrophils (PMN), PMN lysates, or purified human PMN elastase. This increase was not inhibited by sodium azide, nor was it enhanced by incubation of cartilage with the strong oxidant hypochlorous acid. Chondrocyte-mediated matrix proteoglycan degradation in cartilage explants cultured in the presence of cytokines failed to increase antibody binding appreciably. The augmentation in antibody binding seen with PMN lysates was inhibited by the nonspecific serine-esterase inhibitor PMSF, but not by the divalent metal chelator EDTA. The elastase-specific inhibitor AAPVCMK also inhibited most of the PMN-induced increase in antibody binding, whereas the cathepsin G-specific inhibitor GLPCMK was much less effective. Incubation of intact cartilage with purified human PMN elastase indicated that this serine esterase could account for the increase in anti-type II collagen antibody binding to intact cartilage surfaces. These studies suggest that in an inflammatory response, PMN-derived elastase degrades the outer layer of articular cartilage, exposing epitopes on type II collagen. They also help clarify the pathogenic mechanisms involved in early articular cartilage damage in inflammatory joint diseases. 
Duplex sonography in splenomegaly. The aetiology of splenomegaly is seldom clear from either clinical or imaging assessment of the spleen. In the majority of cases sonographic assessment of the spleen produces a homogeneous enlargement of variable echodensity, but with very poor correlation with pathology. A study has been undertaken to assess the Doppler characteristics of the splenic artery in splenomegaly, excluding cases of portal hypertension in an attempt to provide further diagnostic information. Duplex assessment of 18 normal subjects and 10 patients with splenomegaly due to five different causes was undertaken. Analysis of waveform, peak frequency and pulsatility index were compared and failed to demonstrate any significant change. In the normal subject there is a broad systolic spectrum related to the tortuosity of the splenic artery, with persistence of forward flow throughout diastole, a reflection of the low peripheral resistance of the spleen. In splenomegaly the broad systolic spectrum is unchanged, since vessel tortuosity persists. Pathological and physiological assessment of the spleen in splenomegaly shows that a low resistance circulation persists, explaining maintenance of the diastolic flow pattern in splenomegaly. Increased blood flow to the spleen in splenomegaly occurs either as a result of an increase in vessel diameter or an increase in flow velocity, or a variable combination of the two which does not seem to be governed by specific pathology. An increase in peak frequency in some cases reflected some increase in flow velocity but provided no useful correlation. Analysis of the pulsatility index supported the above findings without adding further information. 
Reflex anal dilatation: effect of parting the buttocks on anal function in normal subjects and patients with anorectal and spinal disease. Anal dilatation in response to gentle parting of the buttocks has been advocated as a sign of sexual abuse in children, but nothing is known of the physiology of this response or its existence in normal subjects, in patients with spinal disease, and in patients with a weak sphincter and whether it can be elicited after training. To answer these questions we investigated the effect of parting the buttocks on anal function. Combined anal manometry and electromyography was conducted in six normal subjects (five men, one woman, aged 19-53 years), in 18 patients with faecal incontinence (three men, 15 women, aged 30-80 years), and in seven paraplegic patients (six men, one woman, aged 25-36 years), in four of whom the posterior sacral roots had been cut. Parting the buttocks in normal subjects reduced the pressure in the anal canal from 102 (20) to 14 (3) cm H2O (mean (SEM), p less than 0.00001), but did not cause the anus to gape. This drop in pressure was associated with increased electrical activity in the external anal sphincter. Normal subjects could consciously relax the external anal sphincter and reduce the anal pressure but not so as to result in anal gaping during traction on the buttocks, even after anal dilatation. Stimulation of the anal lining by moving a probe in and out of the anal canal increased the activity of the external anal sphincter, raising anal pressures. Paraplegic patients who had lost conscious control of their external sphincters showed anal gaping when the buttocks were parted. 
Maple syrup urine disease in Mennonites. Evidence that the Y393N mutation in E1 alpha impedes assembly of the E1 component of branched-chain alpha-keto acid dehydrogenase complex. Maple Syrup Urine Disease (MSUD) in Mennonites is associated with homozygosity for a T to A transversion in the E1 alpha gene of the branched-chain alpha-keto acid dehydrogenase complex. This causes a tyrosine to asparagine substitution at position 393 (Y393N). To assess the functional significance of this missense mutation, we have carried out transfection studies using E1 alpha-deficient MSUD lymphoblasts (Lo) as a host. The level of E1 beta subunit is also greatly reduced in Lo cells. Efficient episomal expression in lymphoblasts was achieved using the EBO vector. The inserts employed were chimeric bovine-human cDNAs which encode mitochondrial import competent E1 alpha subunit precursors. Transfection with normal E1 alpha cDNA into Lo cells restored decarboxylation activity of intact cells. Western blotting showed that both E1 alpha and E1 beta subunits were markedly increased. Introduction of Y393N mutant E1 alpha cDNA failed to produce any measurable decarboxylation activity. Mutant E1 alpha subunit was expressed at a normal level, however, the E1 beta subunit was undetectable. These results provide the first evidence that Y393N mutation is the cause of MSUD. Moreover, this mutation impedes the assembly of E1 alpha with E1 beta into a stable alpha 2 beta 2 structure, resulting in the degradation of the free E1 beta subunit. 
In vivo regulation of virulence in Pseudomonas aeruginosa associated with genetic rearrangement. A chronic pulmonary infection model was used to induce conversion to the mucoid phenotype by Pseudomonas aeruginosa PAO. At 6 months after initial inoculation, organisms isolated from infected lungs demonstrated the mucoid phenotype. Significant decreases (P less than .01) were seen in the levels of exotoxin A, exoenzyme S, phospholipase C, and pyochelin produced by the mucoid P. aeruginosa PAO rat lung isolates that returned to parental levels after reversion to the nonmucoid phenotype. In addition, lipopolysaccharide of the mucoid PAO lung isolates failed to react with serotype B-specific antibody in contrast to the original PAO and the revertant PAO organisms. Digestion of chromosomal DNA and hybridization with P. aeruginosa virulence factor-specific probes demonstrated that conversion to the mucoid phenotype was associated with rearrangement of chromosomal DNA upstream of the exotoxin A gene. Analysis of DNA from revertant organisms revealed hybridization patterns identical to the original PAO organism. 
Delay to invasive investigation and revascularisation for coronary heart disease in south west Thames region: a two tier system? OBJECTIVES--To assess the accessibility of invasive investigation and revascularisation procedures in the management of coronary heart disease in a defined population in the South West Thames region over 10 years, and to audit the performance of both the NHS and the private sector. DESIGN--Analysis of all patient referrals to the regional cardiothoracic centres for coronary heart disease during 1979-88. SETTING--North West Surrey District Health Authority, which had a mean catchment population of 205,000 during the study period. The health district is one of the 13 in the South West Thames region. PATIENTS--823 patients aged 34-80 years with suspected coronary heart disease, 204 of whom were referred for private investigation and 619 were referred within the NHS. The NHS referrals were mainly to St Thomas's Hospital during 1979-83 and to St George's Hospital during 1984-8. MAIN OUTCOME MEASURES--Difference in time to investigation and intervention between the NHS and the private patients. RESULTS--After some variation in earlier years the mean (SD, range) waiting times from referral to cardiac catheterisation and then revascularisation increased progressively in NHS patients, to 115.8 (126.5, 22-482) days and 305.9 (164.4, 22-620) days respectively in 1988. There was no significant change over the 10 years in waiting times within the private sector, with a mean of 17.2 (18.2, 1-62) days to angiography and 22.8 (14.5, 2-152) days to surgery. Fifteen people on the NHS waiting list died of probable cardiac causes. No people on the private waiting list died. CONCLUSIONS--The performance of the NHS system in South West Thames region in response to emergency referral is adequate. The waiting time to routine investigation and revascularisation is prolonged and seems to be worsening despite increased investigative and surgical activity by the regional centre. The delays may subject NHS patients to unnecessary risk, which is not shared by private patients. 
Prevention of retrovirus infection after injury with contaminated instruments: an experimental study. Owing to similarities between human immunodeficiency virus and feline retroviruses, the feline model was chosen for the study to investigate the efficacy of timely topical treatment of accidental human immunodeficiency virus infection in the operating room. Cats were subcutaneously inoculated with either feline leukemia virus or feline immunodeficiency virus. An effort was made to neutralize the virus in loco either by infiltration of the inoculation site with povidone-iodine or with monoclonal antibodies, or by cauterization and excision. The animals were periodically monitored for feline leukemia virus antigens or for feline immunodeficiency virus antibodies. The results indicated that in the feline model, the development of generalized virus infection may be prevented by local measures if applied immediately. 
Nuclear exercise testing and the management of coronary artery disease. Three hundred seventy-eight patients referred for nuclear exercise testing were classified using demographics and symptoms into low, intermediate, and high coronary disease likelihood categories. These likelihood groups constituted 15%, 41%, and 15% of referrals, respectively. Patients with prior infarction or disease at angiography (proven disease) made up the remaining 29% of patients. Only 2% of low likelihood patients had typical angina, but physicians diagnosed coronary disease in 64%, prescribed antianginal therapy in 50%, and were considering catheterization in 28% of these patients, all as frequently as for patients with intermediate or high likelihoods for disease. Patients with proven disease were treated differently in that 79% were receiving antianginal therapy and 56% were considered for catheterization (p less than 0.001). Nuclear exercise test results reduced the perceived need for catheterization in all groups, on average by 49%. Nuclear exercise tests are a standard by which patients are managed, sometimes substituting for the traditional role of the history in physician decision making. 
Arteriovenous malformation in meningothelial meningioma: case report. An unusual association of a meningioma and an arteriovenous malformation is reported. A 68-year-old man developed left homonymous hemianopsia, left hemiparesis, and gaze palsy. Magnetic resonance imaging showed a right occipital mass lesion containing multiple signal-void areas with tubular and honeycomb appearance, suggesting a marked vascular component. An angiogram showed abnormal vasculature in the mass supplied by the posterior cerebral artery and a dural arteriovenous malformation on the tentorium. Neuropathological examination after total removal of the mass revealed a meningothelial meningioma including major portions of an arteriovenous malformation that extended from the dura and leptomeninges, through the meningioma, and into the occipital lobe, where the tumor was located. 
Role of vasopressin in salt-induced hypertension in baroreceptor-denervated uninephrectomized rabbits. To elucidate the contributions of renal, humoral, and arterial baroreceptor reflex components to salt-induced hypertension, we administered 10% NaCl intravenously for 10 days to sinoaortic-denervated rabbits with unilateral nephrectomy (n = 7), sinoaortic-denervated rabbits with intact kidneys (n = 7), and sham-operated sinoaortic-denervated rabbits with unilateral nephrectomy (n = 7). Serial changes in mean arterial pressure (MAP), heart rate, and blood pressure variability were recorded. In sinoaortic-denervated rabbits with unilateral nephrectomy, MAP increased significantly from 109 +/- 2 to 124 +/- 3 mm Hg (day 4) and remained elevated for the rest of the experiment. This elevation of MAP was accompanied by a reduction in the standard deviation of MAP, with significant elevations in plasma vasopressin, norepinephrine, and atrial natriuretic peptide concentrations and in sodium retention. In the other groups, there were no significant changes in these vasoactive hormones. In the sham-operated sinoaortic-denervated rabbits with unilateral nephrectomy, sodium retention was similar to that of sinoaortic-denervated rabbits with unilateral nephrectomy. Continuous infusion (1 microgram/kg/hr) of a V1 antagonist prevented the elevation of blood pressure and plasma norepinephrine, the accumulation of sodium, and the reduction of blood pressure lability, whereas a bolus injection (10 micrograms/kg) on day 4 reduced blood pressure from 128 +/- 3 to 115 +/- 2 mm Hg (p less than 0.005). These results imply that vasopressin plays a crucial role in the expression of salt-induced hypertension in rabbits with compromised baroreceptor and renal function. 
Giant adult malignant sacrococcygeal teratoma. Successful treatment by combined abdominosacral resection. This report describes the successful removal of the largest adult sacrococcygeal teratoma (18.75 kg) the authors could find on record. The patient was 58 years of age. The tumor had been present at birth and had been biopsied at the time of her cesarean section 34 years earlier without further treatment. Special planning was necessary for moving and positioning the patient for operation to prevent injury due to the size and weight of the tumor. A combined abdominosacral resection with preliminary ligation of the internal iliac arteries and a diversionary colostomy were performed without difficulty or undue blood loss. The defect was closed primarily and drained. The tumor proved to be malignant on pathologic examination. 
Ultrasonic decalcification of the aortic annulus during aortic valve replacement. Aortic valve replacement for calcifica aortic stenosis requires meticulous debridement of the aortic annulus to effect optimal valve seating. Since 1987, we have used ultrasonic energy to debride the aortic annulus during aortic valve replacement in 56 patients. In our experience, ultrasonic debridement of the annulus is superior to traditional methods of debridement, affords improved seating of the valve, and may allow placement of a larger valve. Our follow-up ranges from 2 to 32 months (mean follow-up, 13 +/- 9 months) with 0% incidence of paravalvular leak or valve failure. We advocate the use of ultrasonic debridement as an adjunctive tool in aortic valve replacement. 
Unilateral lumbar fusion. Unilateral fusion of the lumbar spine is rarely necessary or indicated. However, in patients with a "far-out syndrome" requiring decompression or in cases where unilateral posterior element resection is necessary for any reason, it may be both necessary and indicated. This unilateral destabilization effectively removes one leg of the tripod, rendering that intervertebral joint potentially unstable. The charts and radiographs of 13 patients (seven men, six women) with an average age of 60 years (range, 25 to 76) who underwent unilateral fusion were retrospectively reviewed. Follow-up time ranged from 12 1/2 to 2 years with a median follow-up of 8 years. Eleven of the fusions were at one level, and two were at two levels. Seven patients had a far-out syndrome secondary to degenerative scoliosis; four were secondary to spondylolisthesis. Two patients had an osteoid osteoma involving a pedicle. A paraspinal approach was used in the majority of patients. Autologous bone graft was used in all patients. Unilateral pedicle screw fixation was used in the last patient in the series. The fusion rate was 85% (11/13). Three patients were smokers, two of whom developed pseudarthrosis. Disc space height did not appear to affect fusion rate. There was no progression of slip noted in any of the patients. One complication was noted in this group: a moderate postoperative infection, which cleared spontaneously. 
Double compartment hydrocephalus in an adult. A case of double-compartment hydrocephalus in an adult is presented. Although this entity is infrequently noted in children, it is diagnosed even more rarely in the adult population. A discussion of the spectrum of abnormal cerebrospinal fluid dynamics of the 4th ventricle and treatment options are presented. 
Neurophysiologic assessment of the anal sphincters. One hundred twenty consecutive patients with either fecal incontinence (60 patients), chronic constipation (41 patients), or idiopathic intractable pelvic pain (19 patients) were prospectively assessed. Patients underwent concentric needle electromyography (EMG), bilateral pudendal nerve terminal motor latency evaluation, anorectal manometry, and cinedefecography. The most common EMG finding in patients with fecal incontinence was decreased recruitment of motor units with squeezing and polyphasic motor unit potentials; these are consistent with an injury pattern. The most common EMG finding in the constipated patients was paradoxical puborectalis contraction. This latter abnormality was also a frequent finding in patients with rectal pain, as was prolongation of pudendal nerve latency. Paradoxical puborectalis contraction was diagnosed more frequently with EMG than with cinedefecography. Inter-examination correlation was best in the incontinent group between EMG and manometry. Cinedefecography had poor correlation with EMG in all patient groups but was valuable in the detection of additional pathology such as rectoanal intussusception and anterior rectocele. Electromyography including pudendal nerve terminal motor latency assessment is a valuable adjunct in the evaluation of disorders of evacuation. The information it yields is complementary to that offered by more routine physiologic examinations. 
Carpal tunnel syndrome: surgical treatment using the Paine retinaculatome. The operative technique for the relief of carpal tunnel syndrome has remained controversial. This report presents the results of 445 patients or 577 hands operated on using a transverse technique that varies little from that described by Paine and Polyzoidis. The patients were followed for 9 months to 3 years. In addition to the data received from follow-up visits, a questionnaire was sent to each patient for evaluation of their results. All surgery was performed under local anesthesia, sometimes with intravenous supplement. Of the 445 patients, 313 had unilateral operations and 132 had bilateral operations at one sitting. Postoperatively, normal hand function was achieved in 59.4% of patients in 1 week or less. Of the 577 hands operated on, 535 (92.7%) exhibited satisfactory results from surgery. No patient required postoperative physical therapy or splinting. There were no injuries to the median nerve or any of its branches. 
Motor responses after transcranial electrical stimulation of cerebral hemispheres with a degenerated pyramidal tract. Motor responses were evoked in the thenar muscles by transcranial electrical cortex stimulation in 5 stroke patients with an isolated lacuna in the internal capsule, in whom wallerian degeneration of the pyramidal tract was demonstrated in vivo. Suprathreshold stimulation of the affected hemisphere elicited bilateral motor responses; whereas, stimulation at identical intensities of the undamaged hemisphere yielded strictly unilateral responses in the contralateral hand, like the responses of all normal control subjects. Focused magnetic brain stimulation was performed in 1 patient and gave identical results. Because muscular excitability to cortical stimulation is preserved in spite of pyramidal tract disruption, other pathways must bypass the lesion. Because of the bilaterality of responses, we suggest polysynaptic corticoreticulospinal connections. 
Treatment of constitutional growth delay in prepubertal boys with a prolonged course of low dose oxandrolone. Forty six prepubertal boys who had constitutional growth delay were treated with oxandrolone. Mean age at the onset of treatment was 11.9 years (range 9.0-14.0) and bone age delay was 1.9 'years'. The dose of oxandrolone used was a mean of 0.05 mg/kg (range 0.03-0.18) for a mean of 0.9 years (range 0.2-3.6). Height velocity increased from a mean (SD) before treatment of 4.0 (1.0) to 7.5 (1.2) cm/year with oxandrolone. Growth rate was sustained at 7.6 (2.2) cm/year in the period after treatment. Those boys who attained a testicular volume of 4 ml or greater at the end of the treatment period had the most pronounced sustained growth acceleration. Height for bone age SD score did not alter significantly from a mean of -1.0 before treatment to -1.2 after treatment. Oxandrolone is a safe and effective treatment for prepubertal boys with constitutional growth delay. 
Use of duplex scanning in the diagnosis of arteria profunda femoris stenosis. To evaluate the accuracy of duplex scanning in diagnosing arteria profunda femoris stenoses in patients with concomitant superficial femoral artery occlusions, 123 femoral artery bifurcations were examined in 103 patients. Peak systolic and time-averaged maximal flow velocity parameters were measured in the arteria profunda femoris and compared with independently performed angiography. For detecting stenoses greater than 30% diameter reduction (50% by area) of the arteria profunda femoris, duplex scanning had a sensitivity of 91% and 96%, a specificity of 85% and 98%, a positive predictive value of 86% and 98%, and a negative predictive value of 91% and 96%, for a peak systolic velocity of 180 cm/sec and more, and for a time-averaged maximal velocity of 50 cm/sec and more in the arteria profunda femoris, respectively. The day-to-day variability for peak systolic and time-averaged maximal velocity parameters was low with correlation coefficients between velocity measurements on both days of 0.96 and 0.98 (n = 20), respectively. In 10 patients with arteria profunda femoris stenoses and superficial femoral artery occlusions, undergoing percutaneous transluminal angioplasty of arteria profunda femoris stenosis, the duplex scan revealed a reduction in stenotic peak systolic velocity from 330 +/- 84 to 163 +/- 50 cm/sec and a decrease in stenotic time-averaged maximal velocity from 156 +/- 47 to 54 +/- 17 cm/sec after the interventional procedure. These results show that peak systolic and time-averaged maximal velocities are accurate parameters to detect significant arteria profunda femoris stenosis in patients with superficial femoral artery occlusions. 
Hemobilia due to vasculitis of the gall bladder in a patient with mixed connective tissue disease. A 30-year-old woman with mixed connective tissue disease presented with acute abdominal pain and signs of blood loss. At cholecystectomy she appeared to have lost a considerable amount of blood into the biliary tract due to bleeding of the gall bladder. Microscopic examination showed vasculitis of the gall bladder wall. Hemobilia has not been described before as a complication in mixed connective tissue disease. 
Southern blot analysis in a case of Richter's syndrome. Evidence for a postrearrangement heavy chain gene deletion associated with the altered phenotype. Richter's syndrome (RS) can be defined as the emergence of an aggressive lymphoma in patients suffering from chronic lymphocytic leukemia (CLL). The authors performed immunophenotypic and Southern blot analysis of the peripheral blood and tissue specimen of a patient with RS. Using immunoperoxidase and immunogold-silver staining techniques and a panel of monoclonal antibodies, the authors found that the large cells characteristic of RS showed an altered immunophenotype as compared with the CLL cells and did not express mu heavy chain. Southern blot analysis revealed identical kappa light chain rearrangements in both tumoral cell populations consistent with a common clonal origin. Using the JH probe and several restriction enzymes, the authors also found evidence for a postrearrangement deletion of the heavy chain mu gene. These findings suggest that in this case of RS, a deletion of the heavy chain mu gene resulted in loss of mu expression by the larger cells that were characteristic of RS and was associated with their altered phenotype. 
Arterial insufficiency in hemodialysis access procedures: correction by "banding" technique. Arterial insufficiency distal to an antecubital access is fortunately an infrequent but disturbing and often debilitating complication resulting in suboptimal access. During an 8 1/2-year period, 335 vascular access procedures were performed, 108 of which were antecubital brachiocephalic Gore-Tex conduits. Of these Gore-Tex conduits, 1.8% (2/108) had developed symptoms of vascular insufficiency 2 to 3 1/2 months after such access surgery. As previously published, arterial steal after the creation of an AV fistula could be corrected by the placement of an interposition Gore-Tex loop that would cure the problem and save the access. We have presented a procedure to correct a steal syndrome once a Gore-Tex conduit is already in place. Proximal banding and distal ligation with division of the cephalic vein below an end-to-side Gore-Tex loop is a simple surgical solution. It is not only curative but the procedure also maintains the existing Gore-Tex graft as a sustained avenue for access. 
Clinical significance of the V-shaped space in the subluxed shoulder of hemiplegics. Recently, it has been proposed that shoulder subluxation in hemiplegia is accompanied by 1) the appearance of a V-shaped articular configuration occurring between the humeral head and glenoid fossa and 2) the presence of chronic pain. The main purpose of this study was to investigate the validity of these statements. We evaluated 40 hemiplegic subjects over 3 months. Radiographs of the affected and nonaffected shoulders were taken at both a frontal plane (0 degree) and a 45 degree incidence. From these patients, subluxed (n = 19) and nonsubluxed (n = 21) groups were formed. Pain was evaluated using the Present Pain Intensity index of the McGill Pain Questionnaire. On these x-ray films, measurements were taken of the V-shaped space, abduction of the arm, and rotation of the scapula. The statistical analysis (analysis of variance for repeated measures) contrasted the results obtained from the nonaffected side with those from the affected side over the 3 months studied. At the 45 degree angle, which better exposes the articular configuration of the shoulder, the difference in the V angle between the affected and nonaffected shoulders was significant for the subluxed group (p less than 0.01), indicating that such a V-shaped space can be identified. The measures taken also indicate that a downward subluxation of the humeral head occurs relative to the scapula without any systematic abduction of the humerus or downward rotation of the scapula. None of the results obtained from the frontal plane x-ray films was significant. Finally, no significant relation was found between subluxation and shoulder pain. 
Telangiectatic osteogenic sarcoma of the extremities. Results in 17 patients treated with neoadjuvant chemotherapy. Seventeen patients with telangiectatic osteogenic sarcoma (TOS) of the extremities were treated with neoadjuvant chemotherapy, according to two different protocols. Preoperatively, the patients received high-dose methotrexate (HD-MTX) and cisplatinum (CPD) (HD-MTX/CPD) and doxorubicin. CPD was delivered intraarterially, the other drugs intravenously. Limb-salvage surgery was performed in 12 instances, and five patients were treated with amputation. Postoperative chemotherapy was tailored according to the grade of chemotherapy-induced necrosis. In 13 cases (86%), the resultant grade of necrosis was greater than 90% (good responders). The mean follow-up interval was 3.5 years with a range of 18 to 78 months. Fourteen patients (82%) remained continuously disease-free, while three patients developed lung metastases. Two of these died because of uncontrolled disease, whereas the third patient is alive and disease-free after metastasectomy. No local recurrences were observed. These results are better than those observed in 215 contemporary cases of conventional osteosarcoma treated with the same protocols. This study confirms that TOS is not a uniformly lethal tumor as suggested by prior reports. By employing neoadjuvant chemotherapy, a high percentage of patients with TOS can be cured, and in most of them, a limb-sparing surgery is possible and safe. 
High-dose medroxyprogesterone acetate versus estramustine in therapy-resistant prostatic cancer: a randomised study. A series of 105 patients with metastatic prostatic cancer, having progressed on first-line hormonal treatment, were randomised to high-dose medroxyprogesterone acetate (MPA) 1000 mg i.m. daily for 15 days, followed by 1000 mg weekly (53 patients), or to estramustine 280 mg per os twice daily (52 patients). The treatment was discontinued because of side effects in 3 of 51 evaluable MPA-treated patients and in 8 of 51 evaluable estramustine-treated patients. Progression-free survival was short in both groups and no statistically significant difference between them was observed. After 1 year, 70% of the patients had died and there was no statistically significant difference between the 2 treatments in the cumulative observed survival rates. According to modified SPCG criteria, remissions lasting from 12 to 56 weeks were noted in 13 MPA-treated patients and in 4 estramustine-treated patients. This difference was statistically significant. After cross-over, 6 of 33 patients in the MPA group had a remission compared with 1 of 24 in the estramustine group. It was concluded that the response rate, considering both subjective and objective response criteria, was better with MPA and the side effects were fewer. 
Evidence for alpha 1-adrenoreceptor hyperresponsiveness in hypotensive cirrhotic patients with ascites. Cirrhosis with ascites is often characterized by arterial hypotension associated with increased plasma norepinephrine levels. Clinical evidence suggests a decreased sensitivity to norepinephrine in this clinical setting, indicating a potential derangement of alpha 1 adrenoreceptors. The aim of the present study was to evaluate the reactivity of the alpha 1-adrenoreceptor, using phenylephrine, a selective alpha 1 receptor agonist. First, we evaluated the pupillar response to the intraconjunctival administration of the agonist. Hypotensive cirrhotic patients showed a trend to a more marked and prolonged response, compared with age-matched healthy controls. Second, we studied the response of alpha 1-adrenoreceptors in the peripheral vasculature by administering iv phenylephrine to a similar group of patients. A significantly greater and longer lasting pressor response was observed in hypotensive cirrhotic patients (p less than 0.0001 vs. healthy controls). Our results indicate that in this group of patients, there is a rather peculiar situation, characterized by alpha 1-adrenoreceptor hyperresponsiveness in the presence of high levels of circulating norepinephrine. This finding could be related to biochemical abnormalities within the peripheral sympathetic nervous system endings. 
Hepatitis C virus infection and chronic liver disease in children with leukemia in long-term remission. Antibody to the recently identified hepatitis C virus (HCV) was investigated in sera of 50 leukemic children who had chronic liver disease (CLD), observed for 1 to 12.6 years after therapy withdrawal. All patients were tested for anti-HCV at regular intervals: Ortho-enzyme-linked immunosorbent assay (ELISA) test was performed in all cases. Reactive sera were also tested by recombinant immunoblotting assay to define the specificity of the results obtained by ELISA. Twelve cases (24%) were persistently positive (group A), 11 (22%) were transiently anti-HCV+ positive (group B), and 27 (54%) were negative. Mean SGPT peak during follow-up was significantly higher in group A (P = .014, A v B and P less than .00001, A v C). SGPT normalized off-therapy in 1 of 12 cases (group A), 10 of 11 (group B), and 19 of 27 (group C) (P = .0004, A v B and P = .012, A v C). Accordingly, liver histology, available in 37 patients, showed signs of chronic hepatitis in all patients in group A while most patients in group B and C had less severe liver lesions. These results indicate that HCV plays a significant role in the etiology of chronic hepatitis in leukemic patients and that persistent anti-HCV activity correlates with a more severe CLD, which could jeopardize the final prognosis of children cured of leukemia. 
Superselective embolization of superior gluteal artery pseudoaneurysms following intramuscular injection: case report. Two bleeding superior gluteal artery pseudoaneurysms occurred in a patient with advanced malignant disease following an intramuscular injection. This was diagnosed by angiography and successfully managed by superselective embolization. This avoided further surgery and no additional complication from the pseudoaneurysm occurred up to the time of the patient's demise. 
Sternal wound infections and use of internal mammary artery grafts. Previous studies have provided conflicting evidence as to whether an increased risk of mediastinitis is associated with use of the internal mammary artery as a coronary bypass graft. In this study the effects of internal mammary artery grafts on wound complications were analyzed in a prospective, nonrandomized fashion. At New York University Medical Center from January 1985 through May 1988, 2356 patients underwent isolated coronary revascularization. Among these patients 1394 received one or more internal mammary artery grafts (group I) and 962 had vein grafts only (group II). Group I had a mean age of 59.5 years versus 67.7 years in group II; diabetes was equally present in both groups (22.7% versus 24.7%). Operative mortality rate was 1.3% in group I and 5.6% in group II. Sternal infection was significantly more prevalent in group I (2.2%, 31/1394) than in group II (0.8%, 8/962). Multivariate analysis revealed that aortic crossclamp time, use of a single internal mammary artery graft, use of a double mammary graft, and diabetes were associated with increased risk of sternal infection. The use of bilateral internal mammary artery grafting doubled the odds ratio of the risk compared with use of a single mammary graft, and the combination of diabetes and double internal mammary artery grafts increased the odds ratio 13.9-fold. Patients with an internal mammary artery graft who had sternal infection had a longer period of hospitalization than patients without a mammary artery graft who had sternal infection. We conclude that the risk of sternal infection is increased by the use of an internal mammary artery graft, especially use of double mammary grafts in the presence of diabetes. 
Socioeconomic status and cancer survival. Survival data from eight Cancer and Leukemia Group B (CALGB) protocols were examined for patients with lung cancer (N = 961), multiple myeloma (N = 577), gastric cancer (N = 231), pancreatic cancer (N = 174), breast cancer (N = 87), and Hodgkin's disease (N = 58). After accounting for differences in survival rate attributable to type of cancer, initial performance status, age, and 14 other protocol-specific prognostic indicators, the additional predictive value of socioeconomic status (SES) was evaluated. Race (white v non-white) was not a significant predictor of survival time, but income and education were. People with lower annual incomes (below $5,000 per year in the years 1977 to 1981) and those with lower educational level (grade school only) showed survival times significantly shorter than those with higher income or education, respectively. These survival differences were associated with, but could not be fully explained by, severity of disease at initial presentation. SES continued to exert a small but significant impact on cancer survival, even after controlling for all known prognostic variables. Economically and educationally disadvantaged cancer patients may require treatment programs that include education about treatment and compliance, even after an initial diagnosis is made and treatment is initiated. Because SES is related to survival independent of all known prognostic variables, it should be included in the data bases of clinical trial groups to provide a more accurate test of the effectiveness of new therapies. 
Extracapsular spread of squamous cell carcinoma in neck lymph nodes: prognostic factor of laryngeal cancer. Fifty-two patients with laryngeal cancer who underwent radical neck dissections were studied to provide further information on the prognosis of various clinical and histopathological parameters. Extracapsular spread (ECS) was found in 31% of patients with N1 nodes, and in 60% of patients with histopathologically positive nodes. The 5-year survival rate of histopathological findings was as follows: patients with no pathological evidence of neck metastasis (81%), patients with neck metastasis confined to the lymph node (no ECS) (76%), and patients with ECS (17%). The difference in survival rate between patients with no ECS and patients with ECS was statistically significant (P = .001). Staging classification, T-stage classification, the number of malignant nodes, the diameter of malignant nodes, and combined therapy had no prognostic importance. The most significant factor was the presence of extracapsular spread. 
Terazosin: pharmacokinetics and the effect of age and dose on the incidence of adverse events. Terazosin is a new, long-acting, selective, postsynaptic alpha 1-adrenergic receptor antagonist with a chemical structure similar to that of prazosin. In this article the pharmacokinetics of terazosin are reviewed, and the incidence of adverse events in a dose-response study and a meta-analysis of 20 placebo-controlled trials involving a total of 1814 patients is presented. Peak plasma concentrations of terazosin are achieved 1 to 2 hours after oral administration. The relatively long half-life of terazosin (12 hours) enables it to be administered in a once-a-day regimen. Dose and plasma levels of terazosin show a linear relationship. Terazosin is rapidly and completely absorbed after oral administration. The pharmacokinetics of terazosin are not significantly affected by food, age, hypertension, or renal impairment. Adverse events after the administration of terazosin are usually minor and not age related. The incidence of syncope after therapeutic dosages of terazosin is minimal. Terazosin's effectiveness, combined with its pharmacokinetics, safety profile, and potentially favorable lipid effect, makes it a highly appropriate choice for antihypertensive therapy. 
Positron emission tomography suggests that the rate of progression of idiopathic parkinsonism is slow. We performed sequential positron emission tomography scans with 6-[18F]fluoro-L-dopa in 9 patients with idiopathic parkinsonism and 7 age-matched normal control subjects to compare changes in the nigrostriatal dopaminergic pathway over time. The mean interval between the scans was 3.3 years for the group with idiopathic parkinsonism and 3.9 years for the control subjects. The scans were analyzed by calculating the ratio of striatal to background radioactivity. Both groups showed statistically significant reductions of striatal uptake over the interval. The rate of decrease was almost identical in each group (p = 0.6). We infer that the usual rate of loss of integrity of the dopaminergic nigrostriatal pathway in patients with idiopathic parkinsonism is slow and the rate of change between the two groups was comparable. 
Aggressive peripheral T-cell lymphomas containing Epstein-Barr viral DNA: a clinicopathologic and molecular analysis. The Epstein-Barr virus (EBV) has been shown to be associated with posttransplant lymphoma, Hodgkin's disease, and T-cell lymphoma, in addition to African Burkitt's lymphoma. In a retrospective study of 56 consecutive cases of T-cell lymphoma, EBV DNA was found by Southern blot and in situ DNA hybridization in 10 (20%) of 50 peripheral T-cell lymphomas, but in none of six cases of T-lymphoblastic lymphoma. Peripheral T-cell lymphomas containing EBV DNA could be subclassified into three categories according to histology and immunophenotypic studies: (1) T-cell lymphoma of the helper phenotype, five cases. Two cases had histologic features resembling angioimmunoblastic lymphadenopathy (AILD). (2) T-cell lymphoma of the cytotoxic/suppressor phenotype, four cases. AILD-like features could also be recognized in two cases. Reed-Sternberg-like giant cells were identified in three cases designated Hodgkin-like T-cell lymphoma. (3) Angiocentric T-cell lymphoma or lymphomatoid granulomatosis in one case, initially affecting the skin and nose; no T-cell subset could be defined. Six of the eight EBV DNA-positive patients tested for serum EBV antibodies had elevated titers of IgG antiviral capsid antigen (greater than 640) and/or early antigen (greater than 10). From combined studies of Southern blot hybridization by using EBV termini fragment probe and in situ DNA hybridization, the EBV genomes appeared to be clonotypically proliferated in the neoplastic T cells. The patients in all three groups usually had prolonged fever preceding the diagnosis, hepatosplenomegaly, an aggressive clinical course, and poor response to chemotherapy; nine died with a median survival of only 8 months. We propose that these EBV-associated aggressive T-cell lymphomas, like human T-cell leukemia/lymphoma virus-positive T-cell lymphoma, have characteristic clinicopathologic features and should be treated as a separate disease entity. 
Seizures in series: similarities between seizures of the west and Lennox-Gastaut syndromes. We observed seizures resembling infantile spasms in patients with Lennox-Gastaut syndrome (LGS). Infantile spasms, the type of seizures that occurs in patients who have West syndrome, have been well characterized by video-EEG studies and typically occur as a series of sudden generalized flexor or extensor jerks. The seizure types that occur in LGS have not been as clearly delineated. Some patients with West syndrome (WS) in early infancy later develop LGS. Using intensive video-EEG monitoring, we evaluated 14 LGS patients who had seizures that occurred in series. Clinically, the seizures greatly resembled infantile spasms, and the ictal EEG changes were identical to those that occur with infantile spasms. These findings expand the number of features known to be shared by these two syndromes and strengthen the hypothesis that the two syndromes represent age-related manifestations of similar epileptogenic processes. 
Genetic susceptibility to Parkinson's disease. Genetic factors clearly cause Lewy-body Parkinson's disease (PD) in a subset of autosomal-dominant families. However, most cases of PD are sporadic. The two most likely models of four discussed for sporadic PD are the reduced penetrance model and the multifactorial model. Sporadic PD is likely to be caused by the combined effect of environmental precipitating factors and genetic susceptibility factors. Because the number of major genetic factors is likely to be small, these hypotheses can be tested and genetic factors located using linkage mapping techniques. The affected pair analysis methods are especially suited to PD. Finding the genetic susceptibility factors for PD is important because this may be the fastest way to identify the environmental precipitating factors and because it may lead to prevention of PD. Because of the usefulness of identifying genetic susceptibility factors for PD, we are carrying out linkage studies in a group of 16 large autosomal-dominant families with PD and more than 300 living affected PD pairs. 
Natural course of clinically localized prostate adenocarcinoma in men less than 70 years old. A total of 61 patients, less than 70 years old at diagnosis, with clinical stage T1-2, NX, M0, cytologically well or moderately differentiated prostate adenocarcinoma was prospectively included in a surveillance study. Median patient age was 63 years (range 38 to 69 years). Mean followup was 96 +/- 24 months. The probability of local progression to stage T3 disease after 5 and 10 years was 49 and 72%, respectively. The probability of metastases developing after 5 and 10 years was 8 and 23%, respectively. The probability of dying of prostate adenocarcinoma was 2 and 8%, respectively. Moderately differentiated cancer progressed locally significantly faster than well differentiated disease. The relative number of patients who had metastases or died of prostate adenocarcinoma found in our study was comparable to the relative numbers reported after radical prostatectomy and radiation therapy. Therefore, deferred therapy may be an alternative to active therapy in patients with clinically localized prostate adenocarcinoma and with a life expectancy of less than 10 years. 
Carcinoid tumors: the relationship between clinical presentation and the extent of disease. In this study the relationship between the initial clinical presentation and the extent of tumor progression was determined in a group of 31 patients with carcinoid tumors. The proportion of patients with symptomatic tumors was similar to those patients with carcinoid tumors that were incidentally found (55% versus 45%; SE = 0.089). Symptoms were caused by metastatic tumor in nine (30%) of the patients and by local effects of the primary tumor in eight (26%) of the patients. The patients with symptoms had a significantly increased frequency of metastatic disease, even when the symptoms were due to the primary tumor, compared to patients with no symptoms (76% versus 7%; p less than 0.001). Tumor size was related to the presence of symptoms and metastases. Symptoms were most common when the size of the primary tumor was greater than 1.0 cm (p less than 0.005), although the rate of metastases increased when primary tumors were 2.0 cm and larger (p less than 0.01). These results indicate that the presence of symptoms or a primary tumor 2.0 cm or larger are associated with an increased risk of metastatic disease in patients with carcinoid tumors. These patients should be treated with wide resection of the primary tumor and its lymphatic drainage. 
Colonic volvulus. The Army Medical Center experience 1983-1987. Colonic volvulus was first described in 1836 by von Rokitansky. The condition has been a formidable one, fraught with innumerable complications responsible for many deaths. Even with advances in surgical technology, mortalities have remained high. Often the diagnosis is delayed for hours or even days after presentation, and serious concomitant systemic diseases are often present. Treatment has been controversial, particularly the role of elective resection following successful nonoperative reduction. The Army Medical Center experience with colonic volvulus from 1983 through 1987 is reviewed. Fifty-four patients at the eight medical centers carried this diagnosis. Their presenting signs and symptoms are discussed. The Army patients are compared and contrasted with reviews presented in the surgical literature, and conclusions are made to give guidelines for diagnosis and treatment. 
Neuroanatomy and pathophysiology of pain related to spinal disorders. Sensation is achieved through the integration of many neural elements: receptors, afferent and efferent neurons, the spinal cord with its subdivisions, and the higher brain centers. One of the many sensations perceived by the human body is that of pain or nociception. To understand the concept of "back pain" associated with various spinal pathologies, some basic knowledge of the anatomy and physiology of sensation, and more specifically nociception, is necessary. This knowledge is presented herein. 
Development of a "Steps Questionnaire". Thousands of men and women have begun their recovery from alcoholism through the support of Alcoholics Anonymous (AA) and its well-known "12-Step" program. The purpose of the present study was to develop a scale to measure alcoholics' levels of agreement with the first three of AA's 12 Steps and to test the relationship between sobriety and belief in these three steps. Using both factor analysis and Rasch analysis, two versions of a "Steps Questionnaire" were developed. A 96-member subset of the original subject pool was assessed quarterly for 1 year following inpatient treatment to determine the predictive validity of the questionnaire. The results of this study suggested that agreement with AA's first three steps can be measured and that agreement with AA's first step correlates with number of sober days posttreatment. The dichotomization of Steps Questionnaire scores into total agreement versus partial agreement with Step 1, and from this the reduction of uncertainty in the prediction of abstention over a lengthy follow-up period, provides support for AA's contention that total surrender to one's powerlessness over alcohol is part of the process of achieving abstention. 
Retrospective postmortem dementia assessment. Validation of a new clinical interview to assist neuropathologic study. Neuropathologic studies of dementia and normal aging suffer from a lack of individuals examined for the presence and severity of dementia before death. To increase clinical information in such cases, a retrospective collateral interview was developed. Thirty-nine individuals were studied; 27 had autopsies. In all cases, the autopsy confirmed the Retrospective Collateral Dementia Interview (RCDI) diagnosis of the presence or absence of dementia; the RCDI had a sensitivity of 88% and a specificity of 80% for specifically detecting probable Alzheimer's disease. Agreement between the RCDI and premortem diagnosis was 96%; between RCDI and medical records, 100%. Agreement between RCDI staging of dementia severity and the last assessment of the living subject was 70%; between the RCDI and a brief staging at death, 86%. This validation confirms the value of postmortem interviews with close informants to assess dementia presence and severity. 
Retrolabyrinthine vestibular nerve section: efficacy in disorders other than Meniere's disease. The retrolabyrinthine vestibular nerve section has evolved as an effective treatment for intractable vertigo of peripheral vestibular origin when hearing preservation is desired. This report studies the efficacy of retrolabyrinthine vestibular nerve section for control of vertigo due to causes other than Meniere's disease. This report details our experience with 42 patients with a wide variety of diagnoses. The reduced success rate of retrolabyrinthine vestibular nerve section in these patients is difficult to evaluate, as very few patients have been analyzed with respect to their specific diagnoses. Of patients who underwent retrolabyrinthine vestibular nerve section for control of vertigo, 23 patients had uncompensated vestibular neuritis and 19 others had a wide range of other diagnoses. For patients with uncompensated vestibular neuritis (n = 23), the physician record noted that 39% of patients were cured and 30% improved. This compares to our series of patients with Meniere's disease (n = 48), where 94% were cured and 2% improved. The true vestibular abnormality may be less reliably identified in patients with uncompensated vestibular neuritis, contributing to the less effective results. Since the development of a vestibular rehabilitation program, retrolabyrinthine vestibular nerve section for uncompensated vestibular neuritis has been all but abandoned. Retrolabyrinthine vestibular nerve section appears to achieve a high cure rate in patients with sensorineural hearing loss associated with their vestibular abnormalities. While retrolabyrinthine vestibular nerve section is helpful for control of vertigo in some diagnoses, a substantial incidence of persistent postoperative dysequilibrium was noted. 
Determinants of increase in plasma concentration of beta-carotene after chronic oral supplementation. The Skin Cancer Prevention Study Group. We studied the relationship between eight variables, including age, sex, baseline plasma beta-carotene (BC) concentration, and smoking status and the increase in plasma BC in 582 subjects receiving oral supplementation with 50 mg BC/d. Median plasma BC concentrations after 1 y of supplementation increased from 335 nmol/L at entry to 3163 nmol/L. Changes in plasma BC concentrations ranged widely from -313 to 16,090 nmol/L (median 2721 nmol/L). Multivariate analysis revealed that the subject's plasma BC concentration before supplementation was the most important indicator of the amount of increase after supplementation. Nonsmokers, women, and leaner subjects all had larger increases in plasma concentrations although the statistical model could account for relatively little of the variability in subjects' plasma response to BC supplementation (R2 = 0.14). We conclude that between-subject variability in response to daily supplementation with oral BC is very large and that the best predictor of this response is the initial plasma BC concentration. 
Ibuprofen provides longer lasting analgesia than fentanyl after laparoscopic surgery. The authors compared the analgesic efficacy of one dose of oral ibuprofen with that of intravenously administered fentanyl for relief of pain after outpatient laparoscopic surgery. Thirty healthy female patients received either 800 mg of oral ibuprofen preoperatively or 75 micrograms of intravenous fentanyl intraoperatively plus respective intravenous or oral placebos in a randomized, double-blind manner. Patients recorded their degree of pain and nausea in the recovery room, in the same-day surgery stepdown unit, during the ride home, and upon arrival at home. The postanesthesia care nurse recorded the amount of fentanyl and droperidol needed to treat pain and nausea in the recovery room. Patients who received ibuprofen were more comfortable in the stepdown unit (P less than 0.05) and after arrival home (P less than 0.05) than those in the fentanyl group. Additionally, patients who received ibuprofen had lower nausea scores in the step-down unit (P less than 0.05); this may have been related to the lower total fentanyl dose in these patients. The authors conclude that ibuprofen may be a useful alternative to fentanyl for providing postoperative analgesia for outpatient surgery. 
Leiomyosarcoma of the buttock. A 56-year-old man had a deeply invasive leiomyosarcoma of the right buttock. Leiomyosarcomas of the skin and subcutaneous tissues are rare, and most occur on the extremities. Wide local excision is the therapy of choice. 
Crohn's disease in a patient with multiple sclerosis. We report the occurrence of Crohn's disease in a patient with well-established multiple sclerosis. A relationship between inflammatory bowel disease and multiple sclerosis is supported by a higher than expected coexistence of these disease among families and individuals, as well as similar accepted and proposed mechanisms of pathogenesis and therapy. 
Class I and class II major histocompatibility complex antigens on hepatocytes: importance of the method of detection and expression in histologically normal and diseased livers. Methodological differences in major histocompatibility complex (MHC) antigen detection were investigated on isolated, viable hepatocytes and cryostat hepatic sections from 27 children with liver disorders, six of whom had normal histology. Class I antigens were constantly found on sections using a three step immunoperoxidase technique after acetone/chloroform fixation, other techniques being less sensitive, or on isolated hepatocytes by indirect immunofluorescence alone. With mechanical isolation the percentage of positivity ranged from 85 to 100%, while with collagenase isolation it ranged from 22 to 49% on immediate testing, and from 53 to 80% after 24 hour incubation. Class II antigens were only detected in one patient with autoimmune chronic active hepatitis and two with primary sclerosing cholangitis. Flow cytofluorimetric analysis in 11 cases confirmed class II or class I positivity, or both, on isolated hepatocytes, allowing MHC antigen expression on hepatocytes to be measured. Class I and II antigen detection on hepatocytes is influenced by the technique used. Although class I antigens are invariably expressed on hepatocytes, class II antigens are only found on hepatocytes from patients with immune mediated liver disorders. 
Stress echocardiography for detection of coronary artery disease. Stress echocardiography is a relatively new technique that combines cardiovascular stress with echocardiographic imaging for the diagnosis of coronary artery disease. It is based on the hypothesis that stress-induced ischemia will result in regional wall motion abnormalities that can be detected by two-dimensional echocardiography or abnormalities of global function that can be detected with Doppler ultrasound. Its accuracy for detecting coronary artery disease is high enough to allow for clinical use. In such a role it has added value to the analysis of the routine electrocardiogram and symptoms during exercise. In the patient unable to exercise, pharmacological stress with the use of dobutamine or dipyridamole are realistic alternatives. In addition to the diagnosis of coronary disease, stress echocardiography can be used to demonstrate recovery of function after interventions and to assess prognosis after myocardial infarction. 
Premedication: an audit. A prospective study of routine premedication management was carried out at a large teaching hospital. Many patients received their premedication at times inappropriate for it to be effective. Several patients receiving regular medication had this suddenly stopped pre-operatively. Prolonged fasting occurred in both elective and emergency groups of patients. Benzodiazepines and opioids were prescribed most frequently and drying agents were used widely. Antacids, H2-blockers and agents to promote gastric emptying were used very little despite the potential of aspiration in many groups of patients. This audit of activity has revealed several areas of practice that can either be improved immediately or warrant detailed investigation. 
Comparison of the findings on preoperative dipyridamole perfusion scintigraphy and intraoperative transesophageal echocardiography: implications regarding the identification of myocardium at ischemic risk. The evidence of myocardium at potential ischemic risk on preoperative dipyridamole perfusion scintigraphy was compared with that of manifest ischemia on intraoperative transesophageal echocardiography in 26 patients at high risk of a coronary event undergoing noncardiac surgery. The clinical outcome was also assessed. Induced intraoperative wall motion abnormalities were more common in patients and myocardial segments with, than in those without, a preoperative reversible perfusion defect (both p less than 0.05). Conversely, a preoperative reversible perfusion defect was more common in patients and segments with, than in those without, a new intraoperative wall motion abnormality (both p less than 0.05). Six patients, five with a reversible scintigraphic defect but only three with a new wall motion abnormality, had a hard perioperative ischemic event. Events occurred more often among patients with, than in those without, a reversible perioperative scintigraphic defect (5 [33%] of 15 vs. 1 [9%] of 11) but this difference did not reach significance (p = 0.14), probably owing to the sample size. Intraoperative wall motion abnormalities were all reversible and did not differentiate between risk groups; these findings were possibly influenced by treatment. These preliminary data support the known relation between reversible scintigraphic defects and perioperative events and identify another manifestation of ischemic risk in the relation between reversible scintigraphic defects and induced intraoperative wall motion abnormalities. The value of intraoperative echocardiography in identifying ischemia and guiding therapy in patients with a reversible scintigraphic abnormality should be further assessed. 
Stress gastritis revisited. In current ICU populations, overt bleeding from stress gastritis occurs in 10% to 20% of patients. Bleeding rates may be reduced to about 3% in patients receiving prophylactic therapy. Although patients with bleeding have higher mortality rates than other critically ill patients, it is not clear that the mortality rate is improved with prophylactic therapy, as most patients die from their underlying disease. As new complications of prophylactic therapy are identified, better definitions of the population at risk to develop complications of stress gastritis will be necessary to select those patients who will benefit most from prophylactic therapy. 
Extra-anatomic bypass of failed traumatic arterial repairs. Arterial injuries are best treated by primary repair or anatomically placed interposition grafts. Occasionally, these repairs fail due to adverse local factors, such as soft-tissue infection or enteric contamination. In these instances, limb salvage may require extra-anatomic arterial reconstruction. Between 1979 and 1989, 13 extra-anatomic bypasses were performed in ten male patients following nine failed primary repairs and one ligation of a traumatic arterial injury. The sites of arterial injury were: aorta (two), iliac (five), femoral (two), popliteal (one). Enteric contamination was present at initial operation in six patients; the remaining four had sustained massive soft-tissue injury. Reoperation was required for hemorrhage (seven), pseudoaneurysm (two), and arteriovenous fistula (one). All patients had developed local wound problems that militated against another anatomic repair. Extra-anatomic bypasses performed were: axillo-femoral (three), femoro-femoral (four), obturator (one), and two extra-anatomic femoral to popliteal saphenous vein grafts routed around an infected field. A second extra-anatomic reconstruction was performed for recurrent hemorrhage in three patients, (axillo-femoral--two, obturator--one). One patient with a neuropathic extremity and a functioning graft underwent amputation at 2 months following the initial injury. Two patients died of systemic sepsis. Seven patients (70%) have functional extremities with intact pulses at 2 to 24 months post bypass (mean, 7 months). Limb salvage after secondary disruption of secondarily infected arterial repairs can be achieved by appropriate extra-anatomic arterial reconstruction. In such cases, limb loss is due to soft-tissue sepsis or neuro-skeletal injuries and not vascular insufficiency. 
The clinical significance and pathophysiology of stress-related gastric mucosal hemorrhage. Critically ill patients admitted to intensive care units (ICUs) develop a spectrum of gastroduodenal mucosal lesions that may result in mucosal hemorrhage and subsequent morbidity and mortality. Although stress-related mucosal lesions may be detected endoscopically in most critically ill patients, the incidence of clinically significant bleeding from these lesions is difficult to establish because of the heterogeneity in patient populations, the definitions of bleeding, and the methods of monitoring in various studies. Bleeding occurs overall in approximately 16% of patients not receiving prophylaxis, but the incidence of life-threatening hemorrhage appears to be much lower (less than 6%). In light of the increasing use of pharmacologic prophylaxis in ICUs, the clinical impact of stress-related bleeding and its prophylaxis is discussed in terms of bleeding incidence, morbidity and mortality, cost, and potential side effects. The pathophysiology of stress-related mucosal ulceration involves the complex interaction of gastric luminal factors, alterations in blood flow and intramucosal pH, and alterations in numerous factors that are normally responsible for maintaining an intact mucosa. The pathophysiology of stress ulceration is discussed, with an emphasis on cause-and-effect relationships, evolving areas of investigation, and implications for prophylaxis and treatment. 
Microbiological analysis of sepsis complicating non-surgical biliary drainage in malignant obstruction. Cholangitis with sepsis is a common complication of non-surgical biliary drainage and represents a difficult management problem. Microbiological data for 18 septic episodes in 15 patients following endoscopic biliary drainage (EBD) and 14 septic episodes in 14 patients following percutaneous transhepatic drainage (PTD) were reviewed. In the EBD group, all 18 patient episodes of sepsis had blood cultures and 10 had bile cultures obtained. In total, 17 gram-negative isolates and 5 gram-positive isolates were grown in the EBD sepsis group. All of the 14 PTD patients had bile cultures and 13 had blood cultures. In total, 23 gram-negative isolates and 26 gram-positive isolates were grown in the PTD sepsis group. When PTD cultures were compared with EBD cultures, there were significantly more gram-positive cultures (26 vs. 5) associated with PTD sepsis than EBD sepsis (p less than 0.0005). Analysis of the antibiotic sensitivities revealed that a combination of ticarcillin clavulanate with gentamicin covered 20 of the 22 (91%) EBD organisms and 38 of the 49 (78%) PTD organisms. Based on this data, ticarcillin clavulanate with gentamicin is the therapy of choice for EBD and PTD sepsis at our institution. 
Anaesthetic-induced ventricular tachyarrhythmia in Jervell and Lange-Nielsen syndrome. A four-year-old deaf girl with a history of convulsions developed polymorphous ventricular tachycardia during induction of anaesthesia. The arrhythmia reverted to sinus rhythm spontaneously. Post-anaesthetic ECG showed marked prolongation of the QTc interval (570-690 msec). Deafness and prolonged QTc interval in association with microcytic-hypochromic anaemia confirmed the diagnosis of the Jervell and Lange-Nielsen syndrome. This case report highlights the potentially lethal complication of halothane anaesthesia in patients with long QTc interval syndrome. 
Reduction of myocardial infarction after emergency coronary artery bypass grafting for failed coronary angioplasty with use of a normothermic reperfusion cardioplegia protocol. Emergency coronary artery bypass grafting is necessary in 2.7% to 13.5% of patients undergoing elective percutaneous transluminal coronary angioplasty. Myocardial infarction develops in 11% to 49% of these patients, with 18% to 46% of infarcts resulting in new Q waves. Since February 1987 a revised protocol for myocardial preservation has been used in 19 patients undergoing emergency bypass grafting for failed angioplasty. Cardioplegia is induced with a normothermic blood cardioplegic solution. Multiple maintenance doses of cold (4 degrees C) blood cardioplegic solution are then delivered through the aortic root and vein grafts. Before the aortic crossclamp is removed, normothermic reperfusion cardioplegic solution is delivered through the aortic root and vein grafts. This group was compared with all patients undergoing emergency bypass grafting for failed angioplasty before February 1987. These 45 patients received cold induction of cardioplegic solution, multiple maintenance doses of cold cardioplegic solution, and no reperfusion cardioplegic solution. The prevalence of myocardial infarction in the group receiving cold cardioplegic solution was 65% versus 26% in the group receiving normothermic cardioplegic solution (p less than 0.007). Multivariate analysis identified the use of the normothermic cardioplegia protocol (p less than 0.005), nontotal occlusion of the angioplasty vessel (p less than 0.03), and presence of collateral flow to the angioplasty vessel (p less than 0.04) as being independently associated with absence of myocardial infarction. 
The lower trapezius island musculocutaneous flap revisited. Report of 45 cases and a unifying concept of the vascular supply. The lower trapezius island musculocutaneous flap is valuable in head and neck reconstruction. It offers thin, pliable tissue and a long arc of rotation to reach virtually any defect in the head and neck. Recent reports have shown unacceptably high rates of failure and have questioned the reliability of the vascularity. We report our experience with 45 reconstructions using the lower trapezius island musculocutaneous flap. The literature is reviewed and the vascular anatomy is described in detail. The concept of angiosomes is applied to the trapezius muscle to help explain the reasons for flap failure and to provide guidelines for flap design and harvest. 
Perioperative chemotherapy in oral cancer. This is an interim report of a study of perioperative adjuvant chemotherapy following radical surgery for oral cancer, based on the hypothesis of Goldie and Coleman. 135 patients of alveolobuccal carcinoma, clinically stage III and IV, were entered on the protocol. After a curative resection, they were randomized. The test arm received methotrexate 50 mg/m2 on the 3rd, 10th, and 17th postoperative days. The control arm was only observed. This analysis at 12 months showed a disease free survival of 71% in the test arm vs. 45% in the control arm, which is statistically highly significant (P less than 0.01). Analysis of recurrence pattern showed that recurrence at the primary site was dramatically reduced during the first 6 postoperative months (P less than 0.01). Our study provided further clinical evidence in support of the concepts of Goldie and Coleman that the timing of chemotherapeutic drugs is very critical for a successful end result. 
Comparative evaluation of acid- and bile-induced damage to pedicled jejunal or colonic segments in the rat. The choice of the esophageal substitute after surgical resection for peptic stricture lies between the colon and jejunum. The current study was designed to compare long-term resistance of the colonic and jejunal mucosa to gastric or mixed duodenogastric secretions. The following preparations were performed in Wistar rats: transposition of a colonic or jejunal patch (a) to the gastric body, with or without truncal vagotomy, or (b) to the gastric antrum and proximal duodenum, with or without truncal vagotomy. Jejunal and colonic patches were removed 4, 8, and 12 months after surgery. The only damage to the transposed mucosae was the alteration of microvilli. The alteration was more severe in colonic than in jejunal patches and was prevented by truncal vagotomy. Long-term resistance of the transposed mucosae to the environmental challenge may depend on their adaptation potentiality, involving both specific and nonspecific mechanisms. Nonspecific mechanisms include the increased production of mucus and the gastric-like transformation of the superficial epithelial layer. Specific mechanisms include the reduction of the mucosal surface size for jejunal segments and the shifting in mucin secretion patterns for colonic segments. 
Are history and physical examination a good screening test for sleep apnea? OBJECTIVE: To determine whether presenting clinical history, pharyngeal examination, and the overall subjective impression of the clinician could serve as a sensitive screening test for sleep apnea. DESIGN: Blinded comparison of history and physical examination with results of nocturnal polysomnography. SETTING: Sleep clinic of a tertiary referral center. PATIENTS: A total of 410 patients referred for suspected sleep apnea syndrome. Most patients reported snoring. MEASUREMENTS: All patients were asked standard questions and given an examination relevant to the diagnosis of the sleep apnea syndrome, and all had full nocturnal polysomnography. Patients with more than ten episodes of apnea or hypopnea per hour of sleep were classified as having sleep apnea. Stepwise linear logistic regression was used to develop two predictive models of sleep apnea: one based on the presence of characteristic clinical features, age, sex, and body mass index; and one based on subjective clinical impression. RESULTS: The prevalence of sleep apnea in our patients was 46%. Only age, body mass index, male sex, and snoring were found to be predictors of sleep apnea. The logistic rule discriminated between patients with and without sleep apnea (receiver operating characteristic [ROC] area, 0.77 [95% Cl, 0.73 to 0.82]). For patients with a predicted probability of apnea of less than 20%, the clinical model had 94% sensitivity and 28% specificity. Subjective impression alone identified correctly only 52% of patients with sleep apnea and had a specificity of 70%. CONCLUSIONS: In patients with a high predicted probability of the sleep apnea syndrome, subjective impression alone or any combination of clinical features cannot serve as a reliable screening test. However, in patients with a low predicted probability of sleep apnea, the model based on clinical data was sufficiently sensitive to permit about a 30% reduction in the number of unnecessary sleep studies. 
Serum tumor necrosis factor-alpha concentrations in children hospitalized for acute lower respiratory tract infection. Tumor necrosis factor-alpha (TNF alpha) concentrations were measured by radioimmunoassay in sera of 118 children (median age, 1.7 years; range, 2 months-15 years) hospitalized for acute lower respiratory tract infection (ALRI). Both viral and bacterial ALRI were associated with elevated concentrations of TNF alpha. Concentrations greater than 40 ng/l were seen in children with bacterial or mixed ALRI in 64% and with viral ALRI in 50% of cases. Elevated concentrations were associated with longer duration of fever before admission (P less than .05) and with a higher serum C-reactive protein concentration (P less than .05). There were no significant differences in TNF alpha concentrations between gram-positive and gram-negative infections, nor was there an association with clinical severity of ALRI. TNF alpha concentrations decreased in most patients to normal within 5 days of hospitalization, irrespective of the etiology of the infection. 
Exercise testing and left main coronary artery stenosis. Can patients with left main disease be identified? Exercise testing is commonly used to evaluate patients with coronary artery disease who have serious anatomic characteristics. To study the characteristic exercise test variables in patients with left main coronary artery disease, the computerized data base of the Hungarian Institute of Cardiology Exercise Test Laboratory was used. Among 2,378 patients who had undergone a supine bicycle exercise test and who had abnormal coronary angiographic results, 65 patients with significant (greater than 50 percent diameter narrowing) stenosis of the left main coronary artery were found. The 65 patients were subgrouped according to their previous history and other vessel involvement. Nine patients had isolated left main coronary artery disease and no myocardial infarction (group 1); 28 patients had left main coronary artery stenosis and another diseased vessel but no prior myocardial infarction (MI) (group 2); and 28 patients had left main coronary artery disease, another diseased vessel, and a prior MI (group 3). For comparison, the 27 patients selected to be the control group (group C) had no history of MI but had significant stenosis of both the left anterior descending and the left circumflex arteries. Exercise time, calculated oxygen consumption, maximal work load, time to ST depression, prevalence of ST segment depression, and maximal ST depression were similar in the groups. Maximal heart rate and double product were higher in group 1, but we could find no single variable or group of variables characteristic of left main coronary artery disease. 
Cause of death in patients attending multiple sclerosis clinics. Between 1972 and 1988, 145 deaths occurred among 3,126 patients attending the Multiple Sclerosis (MS) Clinics in Vancouver, British Columbia (N = 1,583), and London, Ontario (N = 1,543). We could determine the exact cause of death in 82.1% of cases (119 of 145). Of the 119 patients for whom the cause of death was known, 56 deaths (47.1%) were directly attributed to complications of MS. Of the remaining 63 deaths, 18 (28.6%) were suicides, 19 (30.2%) were due to malignancy, 13 (20.6%) to an acute myocardial infarction, seven (11.1%) to stroke, and the remainder (9.5%) to miscellaneous causes, of which two may have been suicides. The proportion of suicides among MS deaths was 7.5 times that for the age-matched general population, and the proportion of MS deaths from malignancy was 0.67 times that for the age-matched general population. The proportion of deaths due to malignancy and stroke was the same for the MS patients and the age-matched general population. 
A phase I study of high-dose ifosfamide and escalating doses of carboplatin with autologous bone marrow support. The dose-limiting toxicity in two separate phase I trials of the high-dose single agents ifosfamide and carboplatin was renal insufficiency at 18 g/m2 and hepatic and ototoxicity at 2,400 mg/m2, respectively. In this phase I study, 16 adults were treated with ifosfamide at 75% of the single-agent maximum-tolerated dose (MTD) (12 g/m2) and escalating doses of carboplatin (400 to 1,600 mg/m2) to determine the nonhematologic dose-limiting toxicity and the maximum-tolerated dose of the combination. Both drugs as well as mesna for uroprotection were given by continuous infusion over 4 days with an additional day of mesna (total dose per course, 15 g/m2). Autologous bone marrow support was stipulated for subsequent dose levels once granulocytes remained less than 500/microL for more than 14 days in two of three to five patients entered at a given dose level. Autologous bone marrow support was used at doses above the 400 mg/m2 carboplatin dose level. At the maximum-tolerated dose level of 1,600 mg/m2 of carboplatin, renal toxicity precluded further dose escalation. Of the five patients entered at this dose level, reversible creatinine elevation greater than 2 mg/dL (median peak, 2.6 mg/dL) was observed in three patients, and irreversible renal failure occurred in an additional patient (peak creatinine, 6.9 mg/dL. Transient gross hematuria appeared more common with the combination than with ifosfamide alone. Two patients developed severe somnolence and confusion associated with a rising creatinine. There were two complete (CRs) and four partial responses (PRs) in 14 heavily pretreated assessable patients (including four partial or complete responses in eight assessable patients with advanced refractory sarcoma, and one CR in two patients with germ cell carcinoma). Carboplatin and ifosfamide appear to have overlapping renal toxicity. Nevertheless, carboplatin and ifosfamide can be combined at 80% and 75% of the single-agent maximum-tolerated doses, respectively, with acceptable nonhematologic toxicity. Ifosfamide and carboplatin are an attractive core combination for further studies in the treatment of sarcoma, germ cell, ovarian, and lung carcinomas. 
A randomized, controlled study of behavioral intervention for chemotherapy distress in children with cancer. Fifty-four pediatric cancer patients were studied to determine the relative efficacy of two forms of behavioral intervention for reducing chemotherapy-related distress. Following baseline assessment, subjects were randomly assigned to receive either hypnosis, non-hypnotic distraction/relaxation, or attention placebo (control) during the subsequent identical chemotherapy course. Observational and interview measures of anticipatory and postchemotherapy nausea, vomiting, distress, and functional disruption served as outcome data. Results indicated that treatment condition was the single best predictor of change from baseline to intervention, with children in the hypnosis group reporting the greatest reduction of both anticipatory and postchemotherapy symptoms. The cognitive distraction/relaxation intervention appeared to have a maintenance effect in which symptoms did not get much worse or much better, while children in the control group had symptoms that consistently became worse over time. Emetic potential of the chemotherapy and the prophylactic use of antiemetics each appeared to contribute to the overall severity of symptoms. While the efficacy of hypnosis in the management of chemotherapy distress is supported, the complexities of interacting biologic and psychologic factors are highlighted. 
Fatal puerperal cerebral vasospasm and stroke in a young woman. A woman who experienced postpartum cerebral infarction, brain edema, and death is described. Angiography implicated cerebral vasospasm as the primary etiology. 
First-line management of sinusitis: a national problem? Overview. Traditional concepts of sinus disease as primarily involving the maxillary sinuses are giving way to understanding of the primary involvement of the ostiomeatal complex. Recognition of predisposing factors is also improving, as is localization of disease in the ethmoid, maxillary, frontal, and sphenoid sinuses. Because of the interdependence of the sinuses, acute sinusitis is rarely limited to one sinus. The diagnosis of acute disease is relatively easy compared with that of chronic sinusitis, which mimics many other conditions. Antibiotics and decongestants typically constitute initial therapy for acute sinusitis, and surgery is reserved for patients with threatened complications. The principal goal of this symposium is to outline the most rational approach to treatment of sinus disease on the basis of currently available diagnostic and therapeutic techniques. Emphasis will be placed on first-line management, on therapeutic response, and on objective evaluation of therapeutic efficiency. 
Paroxysmal nocturnal hemoglobinuria with onset in childhood and adolescence. BACKGROUND. Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematologic disorder characterized by hemoglobinuria, thrombosis, infection, and a tendency toward bone marrow aplasia. Onset usually occurs in adulthood. Few children and adolescents with PNH have been described, and data on diagnosis, clinical course, and survival in young patients are unavailable. METHODS. We retrospectively reviewed clinical and laboratory data on all patients 21 years old or younger in whom PNH had been diagnosed at Duke University Medical Center from 1966 to 1991. RESULTS. Medical records and clinical follow-up data were available for 26 young patients. Although 50 percent of adult patients present with hemoglobinuria, only four of our patients (15 percent) presented with this feature. In contrast, 15 of our patients (58 percent) had moderate or severe bone marrow failure at presentation, as compared with about 25 percent of adults in cases from the literature; all 26 patients eventually had evidence of bone marrow dysfunction. Eight patients (31 percent) have died, with a median survival of 13.5 years since their initial symptoms. CONCLUSIONS. Children and adolescents with PNH have a greater prevalence of bone marrow failure than do adults with this disorder, and their morbidity and mortality are high. Bone marrow transplantation should be considered for selected young patients with PNH. 
Malignant blue nevus. To elucidate the histologic features and biologic behavior of malignant blue nevus (MBN), 12 cases were analyzed in which the tumor showed no junctional activity and arose in a blue nevus background. Seven patients were men and five were women; their mean age was 48.8 years. Eight lesions were on the scalp, and no patient had a family history of melanoma. The histologic appearance of most lesions was a nodule or nodules of malignant cells in a blue nevus. Mitoses were present in all lesions with atypical forms in eight; however the mitotic rate exceeded two per ten high-power fields in only one lesion. Four lesions had necrosis, and four had a heavily pigmented malignant component. Four patients had recurrences; ten patients had metastases, and eight died of their disease. Therefore MBN is an aggressive neoplasm. 
Assessment of value of routine bone scans in patients with newly diagnosed prostate cancer. The value of routine bone scans as a staging procedure was assessed in patients with newly diagnosed prostate cancer. Records from 277 patients were reviewed retrospectively to determine the serum acid and alkaline phosphatases, the presence or absence of bone pain, and the results of bone scans and other radiographic studies at the time of initial diagnosis. We determined the sensitivity and specificity of an abnormal acid phosphatase, an abnormal alkaline phosphatase, and the presence of bone pain used in combination for assessing bone metastases. If at least one of these three parameters was present, the sensitivity was 97 percent, whereas if all three tests were normal, the specificity was 78 percent. The negative predictive value for all three tests combined is 99 percent. These results suggest that a routine bone scan to stage patients with newly diagnosed prostate cancer who have no bone pain and normal acid and alkaline phosphatases may not be warranted in all cases. 
Hypertensive heart disease in blacks. Although blacks may differ from whites in the response of hypertension to therapy, present data do not suggest that potential racial differences in cardiac structural adaptation to hypertension by themselves mandate a difference in therapeutic strategy. The results of large racially mixed trials of therapy that monitor LV mass regression, such as the VA Cooperative Monotherapy Trial, will be of interest in this regard. 
Association of Chlamydia pneumoniae (strain TWAR) infection with wheezing, asthmatic bronchitis, and adult-onset asthma OBJECTIVE--To study the clinical characteristics of respiratory tract illness caused by Chlamydia pneumoniae. DESIGN.-Prospective clinical, bacteriologic, and serologic study. Secondarily, a matched comparison of patients with and without evidence of C pneumoniae infection (serologic titers greater than or equal to 1:64 and less than 1:16, respectively). SETTING.--Four primary care (family practice) clinics in Madison, Wis, and nearby towns. PATIENTS.--The study included 365 white males and females (mean age, 34.2 years). MAIN OUTCOME MEASURES.--Association of acute C pneumoniae infection with signs and symptoms of respiratory illness and the relationship of C pneumoniae antibody titer with wheezing at the time of enrollment in the study, and with the diagnosis of asthmatic bronchitis. RESULTS.--Nine (47%) of 19 patients with acute C pneumoniae infection had bronchospasm during respiratory illness, and there was a strong quantitative association of C pneumoniae titer with wheezing at the time of enrollment in the study (P = .01). In the matched study, C pneumoniae antibody was significantly associated with asthmatic bronchitis after, but not before, respiratory illness (odds ratio, 7.2; 95% confidence interval, 2.2 to 23.4). Four infected patients had newly diagnosed asthma after illness, and four others had exacerbation of previously diagnosed asthma. There was no serologic evidence of coexisting Mycoplasma pneumoniae, Chlamydia trachomatis, or respiratory viral infection in 96% of patients with asthmatic bronchitis and asthma. CONCLUSIONS.--Some C pneumoniae antibody titers, although not diagnostic of chlamydial infection by present criteria, probably represent acute reinfection or ongoing chronic infection. Repeated or prolonged exposure to C pneumoniae may have a causal association with wheezing, asthmatic bronchitis, and asthma. 
Pigmented postacne osteoma cutis in a patient treated with minocycline: report and review of the literature. Postacne osteoma cutis is a rare complication of acne vulgaris. If it occurs during a course of tetracycline or minocycline therapy, pigmented osteomas can occur as a result of tetracycline or minocycline bone complexes. We report a case of pigmented postacne osteoma cutis that developed after extensive acne surgery and a 2- to 3-month course of minocycline. Previously reported cases have been treated surgically, but our patient responded to 0.05% tretinoin cream, with transepidermal elimination of some osteomas. 
Correlation of motor units with strength and spectral characteristics in polio survivors and controls. The purpose of this study was to determine whether quantitative motor unit analysis in postpolio individuals correlates with muscle strength, endurance, work capacity, or power spectral characteristics of surface EMG and to determine whether power spectrum differentiates postpolio from control subjects. This study was designed to compare these variables in 34 symptomatic postpolio, 16 asymptomatic postpolio, and 41 control subjects. Quantitative motor unit analysis of the quadriceps femoris muscle was performed using a concentric needle electrode. Isometric knee extension peak torque, endurance (time to exhaustion) at 40% of maximal torque, work capacity (tension time index), and recovery of force through 10 minutes post-exhaustion were determined. Median frequency of the surface power spectrum was determined during the above testing. Power spectrum histograms were compared at the onset and termination of endurance exercise. Motor unit action potential variables did not correlate with isometric peak torque, tension time index, endurance time, recovery of strength, or with median frequency. Surface power spectrum did not differentiate postpolio from control subjects. 
Diverticulitis of the duodenum: clinical and radiological manifestations of seven cases. Seven patients with duodenal diverticulitis were evaluated by computed tomography (CT) and various other abdominal imaging techniques. The series included four men and three women who ranged in age from 47 to 84 yr (mean: 65 yr). They had presented with epigastric or periumbilical pain, low-grade fever, leukocytosis, and loss of appetite and weight due to postprandial cramps or vomiting. In each instance, the abdominal CT examination proved crucial in the diagnosis of duodenal diverticulitis, with contained perforation or inflammatory changes involving the adjacent structures. Five patients underwent laparotomy while two others were treated conservatively with antibiotics and/or percutaneous drainage of peridiverticular abscess. The clinical and radiological features of this uncommon entity are herein described, along with a brief review of the medical literature regarding the current approach to its diagnosis and management. 
Arrhythmogenic effects of graded coronary blood flow reductions superimposed on prior myocardial infarction in dogs. BACKGROUND. We studied arrhythmogenesis and its underlying pathophysiology during graded reductions of coronary blood flow, superimposed on prior myocardial infarction to test the hypothesis that spontaneous ventricular fibrillation and induced ventricular tachycardia are dependent on different patterns of coronary flow reduction in hearts with prior myocardial infarction. METHODS AND RESULTS. In 10 sham-operated dogs (control group) and 24 dogs with 3-week-old experimental apical myocardial infarction, the left circumflex coronary artery was constricted to produce four grades of flow reduction: 25%, 50%, 75%, and 100%. Among the sham-operated control animals, only one of 10 (10%) developed spontaneous ventricular fibrillation and only two of nine (22%) were inducible into sustained ventricular tachycardia during 100% circumflex coronary artery flow reduction. No spontaneous ventricular fibrillation or inducible ventricular tachycardia occurred with lesser grades (25%, 50%, or 75%) of flow reduction among the control animals. In the myocardial infarction group, five of 24 dogs (21%) were inducible before flow reduction. However, 50% flow reduction in the myocardial infarction group resulted in inducibility of ventricular tachycardia in 12 of 24 dogs (50%); nine of 16 (56%) during 75% flow reduction; and six of 11 (55%) with 100% flow reduction. In addition, none of the dogs in the myocardial infarction group developed spontaneous ventricular fibrillation during 25% or 50% flow reduction, whereas six of 22 (27%) developed ventricular fibrillation during 75% flow reduction and 10 of 21 (48%) during 100% flow reduction. In dogs with spontaneous ventricular fibrillation during flow reduction, the total myocardial mass of the ischemic "risk" zone and infarcted zone was significantly greater than in those without spontaneous ventricular fibrillation (68 +/- 5% versus 56 +/- 6% [p less than 0.01]). There was no difference in the total myocardial mass of the ischemic risk zone and infarcted zone between dogs with and without inducible ventricular tachycardia during flow reduction. CONCLUSIONS. In canine model of subacute myocardial infarction, superimposed ischemia increased the likelihood of inducible sustained ventricular tachycardia with lesser grades of coronary flow reduction compared with that necessary to allow spontaneous ventricular fibrillation. The underlying pathophysiology appears to differ between spontaneous ventricular fibrillation and electrically induced sustained ventricular tachycardia. 
Diagnosis and cure of the Wolff-Parkinson-White syndrome or paroxysmal supraventricular tachycardias during a single electrophysiologic test BACKGROUND. We conducted this study to determine the feasibility of an abbreviated therapeutic approach to the Wolff-Parkinson-White syndrome or paroxysmal supraventricular tachycardia, in which the diagnosis is established and radiofrequency ablation carried out during a single electrophysiologic test. METHODS. One hundred six consecutive patients were referred for the management of documented, symptomatic paroxysmal supraventricular tachycardias (66 patients) or the Wolff-Parkinson-White syndrome (40 patients). All agreed to undergo a diagnostic electrophysiologic test and catheter ablation with radiofrequency current. No patient had had such a test previously. RESULTS. Among the 66 patients with paroxysmal supraventricular tachycardias, the mechanism was found to be atrioventricular nodal reentry in 46 (70 percent) (typical in 44 and atypical in 2), atrioventricular reciprocating tachycardia involving a concealed accessory pathway in 16 (24 percent), atrial tachycardia in 2 (3 percent), and noninducible paroxysmal supraventricular tachycardia in 2 (3 percent). A successful long-term outcome was achieved in 57 of 62 patients (92 percent) with paroxysmal supraventricular tachycardia in whom ablation was attempted and in 37 of 40 patients (93 percent) with the Wolff-Parkinson-White syndrome. The only complications were one instance of occlusion of the left circumflex coronary artery, leading to acute myocardial infarction, and one instance of complete atrioventricular block. The mean (+/- SD) duration of the electrophysiologic procedures was 114 +/- 55 minutes. CONCLUSIONS. The diagnosis and cure of paroxysmal supraventricular tachycardia or the Wolff-Parkinson-White syndrome during a single electrophysiologic test are feasible and practical and have a favorable risk-benefit ratio. This abbreviated therapeutic approach may eliminate the need for serial electropharmacologic testing, long-term drug therapy, antitachycardia pacemakers, and surgical ablation. 
Liposarcoma of the thyroid gland. Fine-needle aspiration cytology, immunohistology, and ultrastructure. A 56-year-old woman presented with a rapidly growing tumoral mass of the thyroid. In fine-needle aspirates, neoplastic cells were interpreted as undifferentiated (anaplastic) carcinoma. In contrast, histologic examination of tissue samples revealed a tumor with features suggestive of myxoid liposarcoma. The non-epithelial nature was confirmed by immunohistochemical and electron microscopic evaluation. Immunostains for vimentin and S-100 protein were positive, whereas no reactivity was obtained for epithelial markers. Ultrastructurally, the tumor consisted of poorly differentiated mesenchymal cells and lipoblastic elements in various stages of differentiation. Review of the literature reveals only one previous report of thyroid liposarcoma, the diagnosis of which was based on conventional light microscopic studies. 
Potent cytodifferentiating agents related to hexamethylenebisacetamide. Bishydroxamic acids are effective inducers of differentiation in murine erythroleukemia cells. Flexible analogs of suberic acid bisdimethylamide are approximately 100 times as active as the parent compound or hexamethylenebisacetamide. They also induce differentiation of human promyelocytic leukemia cells (HL-60) and a subclone of human colon carcinoma cells (HT-29-U4). Some rigid bishydroxamic acids with benzene rings in the spacers are even more active toward murine erythroleukemia cells but show curious biological differences. In contrast to the flexible molecules, those with benzene spacers show poor activity toward HL-60 cells; they also have different geometric requirements, and they are not additive with hexamethylenebisacetamide in their effect. It is likely that rigid bishydroxamic acids, with a benzene ring spacer, induce differentiation by a different mechanism in spite of their chemical resemblance to the flexible bisamide and bishydroxamic acid inducers. 
Percutaneous excimer laser coronary angioplasty of lesions not ideal for balloon angioplasty BACKGROUND. Excimer laser coronary angioplasty is a new, investigational technique for treating coronary artery stenoses. Initial reports have demonstrated acute efficacy and relative safety of this procedure, but have not addressed the effect of lesion type on acute success and complication rates. METHODS AND RESULTS. In the first 100 patients undergoing percutaneous excimer laser coronary angioplasty at our institution, acute laser success was obtained in 84% and procedural success was obtained in 94%. There were six acute closures during laser angioplasty and one myocardial infarction. Two patients required emergency coronary bypass surgery. Sixty-five percent of patients had lesions not ideal for balloon angioplasty because of lesion morphology (tubular, diffuse, or chronic total occlusion) or ostial location. There were 10 tubular stenoses, 29 diffuse lesions, 18 chronic total occlusions, and eight ostial lesions, including five aorto-ostial lesions. In this nonideal subgroup, the acute success rate with laser was 86% (72% of chronic total occlusions and 91% of non-totally occluded lesions), and the procedural success rate was 94%. There were three acute occlusions during laser angioplasty but no myocardial infarctions, emergency bypass surgeries, or deaths. One coronary artery perforation occurred without clinical sequelae. Laser angioplasty was successful in four of six lesions (67%) in which balloon angioplasty had failed. Laser success was obtained in 10 of 11 (91%) moderately or heavily calcified stenoses. Eight eccentric lesions and two lesions on bends were successfully treated without dissection or perforation. No side branch occlusions occurred in the 15 patients in whom one or more major branches originated within the lesion treated. Adjunctive balloon angioplasty was performed in 47% of cases, usually to obtain a larger final luminal diameter. Need for adjunctive balloon angioplasty decreased to 36% after a larger (2.0 mm) laser catheter became available. Twenty-eight percent of the 105 lesions treated were American College of Cardiology/American Heart Association classification type A, 47% were type B, and 25% were type C. Laser and procedural successes were obtained in 83% and 97% of type A, 88% and 96% of type B, and 85% and 88% of type C lesions, respectively. CONCLUSIONS. In our initial experience, excimer laser angioplasty was found to be acutely effective and safe therapy for lesions identified as not ideal for balloon angioplasty. This technique may provide a useful adjunct or alternative to balloon angioplasty in selected patients. 
Management of bleeding liver tumours in Hong Kong. A retrospective study was undertaken of 41 patients diagnosed as having suffered spontaneous liver rupture over a 4-year period to identify the clinical features, treatment and outcome of this complication in an area in which hepatocellular carcinoma is endemic. Two patients were excluded with a revised diagnosis of haemorrhagic malignant ascites. Of the remaining 39 patients, 37 bled from ruptured hepatocellular carcinoma, one from peliosis hepatis and multiple liver cell adenomas, and one from a malignant hepatic epithelioid haemangioendothelioma. Analysis showed that 59 per cent of patients were in shock on admission and that all but two of the 37 patients with ruptured hepatocellular carcinoma were men with cirrhosis. The association with cirrhosis was significantly higher than in a series of 45 patients with hepatocellular carcinoma undergoing elective resection during the same period (P less than 0.05). Treatment consisted of supportive care only in two patients, angiographic embolization in four, emergency liver resection in 11 of whom six died, hepatic artery ligation in 12 of whom eight died, and suture and/or packing in eight of whom six died. One patient died at laparotomy and in another patient bleeding was successfully arrested by intratumoural injection of absolute alcohol. Because of the high operative mortality of emergency surgery in these poor risk patients, prospective evaluation of emergency angiographic embolization is required. 
Where there is no anaesthetist.... In an unselected series of 254 operations representing a wide range of surgical, obstetric and gynaecological procedures carried out on the small Pacific island of Tuvalu, the majority (85 per cent) involved the lower half of the body. In all cases but one anaesthesia was administered by a non-specialist. In operations below the level of the diaphragm epidural anaesthesia was usually used with a success rate of 96 per cent. In the upper half of the body ketamine was used where local or regional block was insufficient. Only one operation was performed under general inhalation anaesthesia. The overall postoperative mortality rate was 0.4 per cent and the morbidity rate was 13 per cent. Only two minor complications were attributed to the anaesthetic method used. In situations where anaesthetists are not available, epidural and ketamine anaesthesia in the hands of non-specialists are safe and practical options to general inhalation anaesthesia and are appropriate for most surgical procedures. 
Lupus anticoagulant inhibition of in vitro prostacyclin release is associated with a thrombosis-prone subset of patients. PURPOSE: The effect of lupus anticoagulant-containing sera on endothelial prostacyclin generation (both basal and after thrombin stimulation) was determined. Subsets of patients who had experienced arterial, venous, or no thrombosis were compared with respect to the quantitation of antiphospholipid antibody and effects on prostacyclin production. PATIENTS AND METHODS: Serum antiphospholipid antibodies were detected in 26 patients by immunologic (enzyme-linked immunosorbent assay) and kinetic (anticoagulant) assays. Cultured human endothelial cells were exposed to patient or normal serum, and the release of prostacyclin was determined by radioimmunoassay of supernatants. Release was determined in the absence and presence of the secretagogue, thrombin (1 U/mL), corrected for interassay variation, and correlated with other clinical and laboratory variables. RESULTS: The normal prostacyclin response was a 2.5-fold increase after thrombin (1 U/mL) compared to basal production. Patients with a history of arterial thrombosis (Group 1, n = 10) had the highest IgG anticardiolipin antibody titers (449 +/- 115 [OD x 1,000]), most prolonged kaolin clotting times (140 +/- 15 seconds), and the least prostacyclin response to thrombin (1.36-fold). Patients with venous thrombosis (Group 2, n = 6) had lower titers (329 +/- 120), intermediate clotting times (125 +/- 19 seconds), and slightly impaired prostacyclin responses (2.18-fold). Patients with no history of thrombosis (Group 3, n = 10) had low antibody titers (220 +/- 20), mildly prolonged clotting times (108 +/- 6 seconds), and normal prostacyclin responses (2.33-fold). Patient serum did not alter basal or arachidonate-induced prostacyclin production. Group 1 had significantly lower platelet counts (99 +/- 19) compared to Group 2 (167 +/- 35) or Group 3 (167 +/- 34), but were similar in age and associated diagnoses. CONCLUSIONS: Inhibition of prostacyclin responses is commonly found in serum from patients with lupus anticoagulants, and is likely to be present in patients with high IgG anticardiolipin antibodies, strong lupus anticoagulants, low platelet counts, and a recent arterial thrombosis. 
Interrelationship between activation of dopaminergic pathways and cerebrospinal fluid concentration of dopamine tetrahydroisoquinoline metabolite salsolinol in humans: preliminary findings. The main objective of this study was to determine whether the activation of dopaminergic pathways, through adrenal-caudate transplantation, stimulated the production of dopamine and salsolinol in cerebrospinal fluid (CSF) of patients with Parkinson's disease. Dopamine sulfate and salsolinol sulfate in CSF specimens were measured by radioenzymatic technique. The results of this study demonstrated that the replacement of degenerative nigrostriatal neurons with new dopamine-producing cells by adrenal brain transplants in patients with Parkinson's disease resulted in significant increase (p less than 0.05) in CSF levels of free dopamine, dopamine sulfate, free salsolinol, and salsolinol sulfate as compared with preoperative levels. Moreover, the oral administration of L-dopa to these transplanted patients caused substantial (p less than 0.001) elevation in CSF levels of free dopamine (before L-dopa, 146 +/- 57 pg/ml; after L-dopa, 575 +/- 207 pg/ml), dopamine sulfate (before L-dopa, 1966 +/- 945 pg/ml; after L-dopa, 41679 +/- 29326 pg/ml), free salsolinol (before L-dopa, 43 +/- 29 pg/ml; after L-dopa, 186 +/- 90 pg/ml), and salsolinol sulfate (before L-dopa, 405 +/- 477 pg/ml; after L-dopa, 2908 +/- 2572 pg/ml), respectively. 
Use of mammography in screening for breast cancer. Recognizing the enormous impact that quality breast screening mammography can have on reducing breast cancer deaths, we need to determine when women's and physician's perceived restrictions for mammography examination impede the progress of its use for early cancer detection. A uniform system should emphasize valid communication and education between women and their physicians. Women seek to have a voice in their medical treatment. Yet that responsibility has an emotional price. Physicians and patients must decide together on the most appropriate strategies to enhance communication and adopt specific guidelines they will adhere to, to detect and cure early breast cancer. Women must be educated about breast screening mammography, and physicians must increase their efforts to proclaim its importance. Women need be assured the trend is toward using the most modern mammographic techniques. Quality medical care is medicine's purpose and in women's best interest. At present, no other diagnostic method is equivalent to mammography and capable of providing an equivalent impact on improving the detection and cure rate of breast cancer. Despite medical activities designed to reduce uncertainty in medicine, scientific evidence has not provided systematic answers as to the "best" way to approach issues of quality, cost, accessibility, or communication for breast screening mammography. No particular expert opinion or preference prevails for breast screening protocols. What is needed is adoption of a multidisciplinary approach, educating and motivating women and physicians to participate in breast screening activities. With trends directed toward high-volume breast screening operations, low-cost, quality mammography must be available and be impeccably performed. Some activities are natural subjects for financial quantification. It is objectionable to assume, however, that we can accurately place and agree on dollar amounts alone to represent the costs and benefits of screening mammography. The gaps between practices and attitudes about the benefits, risks, and costs of screening mammography suggest that people are not satisfied with the way physicians, women, influential groups, or regulatory agencies are balancing all of the elements. Better communication must exist between physicians and their peer groups involved in performing responsible mammography. Better communication must be achieved between physicians and women to take advantage of the usefulness of quality breast screening mammography. High-quality screening programs must be linked to third-party reimbursement and to legislation, if we are to make a difference. Screening mammography deserves our medical, economic, social, and political attention and action. 
Delayed sternal closure for life-threatening complications in cardiac operations: an update. Over a 7-year-period, 25 patients had delayed sternal closure after open heart operations out of 34 patients whose sternum was not closed. The indications were extreme cardiac dilatation and uncontrollable mediastinal hemorrhage. This represented a 1.79% incidence in the overall open heart surgical experience at our unit. Sternal closure was performed at a mean of 2.64 days after the initial operation. Eighteen patients (52.9%) left the hospital alive and well, representing a 72% survival rate among patients undergoing delayed sternal closure. No mediastinal or fatal infection developed and only 1 patient had late superficial wound infection after delayed sternal closure. We conclude that delayed sternal closure is an effective method to treat severe complications after cardiac operations. 
Cerebellorubral degeneration after resection of cerebellar dentate nucleus neoplasms: evaluation with MR imaging. The authors describe the magnetic resonance (MR) findings in seven patients who developed severe cerebellar symptoms and atrophy of the contralateral red nucleus following removal of unilateral neoplasms in the deep nuclei of the cerebellum. For most patients, pre- and postoperative spin-echo MR images were obtained with long repetition times (TRs) at 1.5 T. The long TR images obtained before surgery demonstrated unilateral masses involving the dentate nucleus. Long TR images obtained after surgical resection of the dentate nucleus showed increased signal intensity in all of seven contralateral red nuclei, three of seven ipsilateral superior cerebellar peduncles, and two of seven contralateral inferior olivary nuclei. Three other patients who underwent surgery for cerebellar neoplasms without resection of the dentate nuclei showed no postoperative brain stem changes on MR images. The authors speculate that the changes in the contralateral red nuclei are due to cerebellorubral degeneration (since well-described neural tracts interconnect the dentate nucleus and the contralateral red nucleus). Injury of the dentate nucleus may result in degeneration of distant neural connections. 
N-terminal pro atrial natriuretic peptide in human plasma. N-Terminal pro ANP (atrial natriuretic peptide) in human plasma has been measured by radioimmunoassay after extraction on Sep-Pak cartridges. Immunoreactive N-terminal pro ANP circulates in human plasma at higher levels than alpha-hANP (approximately 20-fold higher in normal subjects) and was elevated in patients with essential hypertension, cardiac transplantation and patients with chronic renal failure. In chronic renal failure patients undergoing hemodialysis, C-terminal ANP (ANP 99-126), but not N-terminal ANP, declined significantly after dialysis. Gel filtration experiments demonstrated a single peak of N-terminal ANP immunoreactivity, eluting in parallel with synthetic human pro ANP 1-67, indicating a similar molecular size and the absence of low molecular weight N-terminal fragments. 
Activity of intrapleural recombinant gamma-interferon in malignant mesothelioma. Twenty-two consecutive patients with malignant diffuse pleural mesothelioma were treated with recombinant gamma-interferon by the intrapleural route. Diagnosis was made by thoracoscopic examination and all cases were confirmed by the French Mesothelioma Panel of Pathologist. Patients were staged based on thoracoscopic examination and computed tomography (CT) scan: 12 patients were classified as Stage I and 10 were Stage II. A solution of gamma-interferon (40 X 106 U) was infused twice a week over 2 months. Every patient experienced fever. One patient had a Grade 2 leukopenia and one patient suffered from pleural empyema. Response evaluation was based on the following: (1) CT scan performed 2 weeks after treatment ended, and (2) repeat thoracoscopic examination with histopathologic verification in nine patients who had demonstrated a stabilization or a regression of the disease on CT scan. From the original group, 19 patients could be evaluated. Four complete thoracoscopic histopathologic responses and one partial response were observed in Stage I patients (56%). One partial response was observed in Stage II patients. 
Hyperreninemic hypoaldosteronism due to hepatocellular carcinoma metastatic to the adrenal gland. Metastases to the adrenal glands are common in patients with cancer, but among those affected, hyperreninemic hypoaldosteronism is noted very rarely. A case of hyperreninemic hypoaldosteronism secondary to metastatic hepatocellular carcinoma is reported. Laboratory data revealed selective aldosterone deficiency with hyperreninemia. Biopsy documented replacement of the adrenal glands with metastatic hepatocellular carcinoma. A review of the literature disclosed that the present case was an extremely rare one of its kind. 
Controlling gastric pH: the impact of newer agents on the critically ill patient. The critically ill patient is at increased risk for developing erosive injury of the stomach, duodenum, and esophagus. To date, the most effective way to prevent and treat this problem is by assuring excellent intensive care support and by reducing gastric acid secretion. The histamine H2-receptor antagonists (H2RAs) are effective in both prevention and treatment of such gastric mucosal injury. Newer agents are available that have potential for use in this setting, although none have been studied as extensively in critically ill patients as have the H2RAs. These new agents include proglumide, pirenzepine, misoprostol, omeprazole, and somatostatin. To date, only the latter has been extensively studied in critically ill patients. Omeprazole, which suppresses acid very effectively, may be problematic in the critically ill, limited by its oral dosage form, acid-labile properties, and potential drug interactions. 
Beta-adrenergic-antagonist drugs in the prevention of gastrointestinal bleeding in patients with cirrhosis and esophageal varices. An analysis of data and prognostic factors in 589 patients from four randomized clinical trials. Franco-Italian Multicenter Study Group. BACKGROUND. The value of beta-adrenergic-antagonist drug therapy for the prevention of initial episodes of gastrointestinal bleeding in patients with cirrhosis and esophageal varices is uncertain, both positive and negative study results having been reported. METHODS. In this study, we analyzed data on individual patients from four randomized, controlled trials to assess the efficacy of this treatment. Of the 589 patients studied, 286 received a beta-adrenergic-antagonist drug (propranolol in 203 and nadolol in 83) and 303 received placebo. RESULTS. After two years, the mean (+/- SE) percentage of patients who had had no upper gastrointestinal bleeding was 78 +/- 3 percent in the beta-adrenergic-antagonist treatment group and 65 +/- 3 percent in the control group (P = 0.002). The percentage of patients without fatal bleeding was 90 +/- 2 percent in the treatment group and 82 +/- 3 percent in the control group (P = 0.01). The percentage of patients surviving after two years was 71 +/- 3 percent in the treatment group and 68 +/- 3 percent in the control group (P = 0.34). After age and severity of cirrhosis were taken into account, the survival rate was better in the treatment group (P = 0.09). The percentage of surviving patients who had had no bleeding after two years was 62 +/- 3 percent in the treatment group and 53 +/- 3 percent in the control group (P = 0.04). Both propranolol and nadolol prevented a first episode of bleeding. Severe cirrhosis and especially the presence of ascites were associated with bleeding (P less than 0.001) and death (P less than 0.001) in both groups. The efficacy of beta-adrenergic-antagonist therapy in the prevention of bleeding (P less than 0.001) and of fatal bleeding (P = 0.004) and in the prevention of bleeding or death (P = 0.005) was the same after adjustment for cause and severity of cirrhosis, ascites, and size of varices. CONCLUSIONS. Propranolol and nadolol are effective in preventing first bleeding and reducing the mortality rate associated with gastrointestinal bleeding in patients with cirrhosis, regardless of severity. 
Effect of irreversible dermal necrosis on phagocytic activity of reticuloendothelial system. A model of full-thickness dermal necrosis was produced in rats by the application of liquid nitrogen to a 20% total body surface area of the dorsal skin surface. In this model there was an alteration of reticuloendothelial system phagocytic activity of the lung and spleen as measured by the uptake of technetium 99m-labeled sulfur colloid in vivo. The present results suggest that marked alterations in reticuloendothelial system phagocytic activity can be produced by full-thickness dermal necrosis in the absence of heat. 
Iodine 131 metaiodobenzylguanidine scintigraphy of medullary carcinoma of the thyroid [published erratum appears in South Med J 1991 Jul;84(7):816, 937] We have presented a case of sporadic medullary carcinoma of the thyroid with documentation of localization of tracer 131I-MIBG within the primary neoplasm. A review of the nuclear medicine literature of localization techniques for MCT demonstrates that 131I-MIBG, while an excellent choice for diagnosis of pheochromocytoma and neuroblastoma, produces low yield and unpredictable concentration in other neural crest apudomas, including MCT. A low incidence of true-positive results with 131I-MIBG uptake and a high incidence of false-negative results make this radiopharmaceutical a suboptimal choice for diagnostic studies, but a potentially promising one as a therapeutic agent. 
Treatment of idiopathic nephrotic syndrome with cyclosporin A in children. Cyclosporin A (CyA, Sandimmun) was given to 71 children with idiopathic nephrotic syndrome, 45 of whom were steroid-dependent with signs of steroid toxicity, and 23 who were steroid-resistant. Cyclosporin A was effective in 80% of the steroid-dependent patients, allowing cessation of corticosteroid treatment. However, most of these patients relapsed when CyA was tapered or withdrawn. In these patients, CyA may be required for long periods of time. Conversely, CyA was less effective in steroid-resistant patients; only 7% achieved remission with CyA alone. Cyclosporin A in association with prednisone may be an effective alternative as 8 out of 14 patients entered remission with this treatment combination. Serial renal biopsies were performed in 43 patients to evaluate the potential nephrotoxicity of the treatment. Eighteen patients developed significant tubulointerstitial lesions which were attributable to CyA nephrotoxicity. The risk of developing chronic nephrotoxicity appears to be higher in steroid-resistant patients, and was not related to the duration of treatment. Cyclosporin A nephrotoxicity can develop in patients with normal renal function. 
Calcium metabolism in hypertension and allied metabolic disorders. Data suggest a critical role for Ca metabolism in the pathophysiology of hypertensive disease. Intracellularly, all hypertension displays elevated cytosolic free-Ca2+ and suppressed free-Mg2+ levels. Extracellularly, however, heterogeneous defects in Ca and Mg metabolism are observed. This apparent divergence may be explained by considering all hypertension as the expression, in varying degrees, of two underlying Ca-related mechanisms: one (salt sensitive, low renin, Ca(2+)-antagonist sensitive) dependent on inappropriate cellular Ca2+ uptake from the extracellular space and the other (salt insensitive, renin dependent, Ca(2+)-antagonist insensitive) dependent on increased cellular Ca2+ release from intracellular sites. Recent work highlights the role of 1,25-dihydroxyvitamin D3 and the newly described parathyroid hypertensive factor in volume-dependent low-renin forms of hypertension. Altered cellular ion handling may also explain metabolic and clinical correlates of hypertension, e.g., peripheral insulin resistance, hyperinsulinemia, obesity, and non-insulin-dependent diabetes mellitus (NIDDM). Thus, all subjects with NIDDM, whether hypertensive or not, display the same elevated cytosolic free-Ca2+ and suppressed free-Mg2+ levels observed in hypertension. Furthermore, adiposity, the level of blood pressure, and fasting and postglucose hyperinsulinemia are all closely and quantitatively related to intracellular free-Ca2+, free-Mg2+, and pH levels. This suggests a broader hypothesis, in which hypertension, obesity, insulin resistance, and NIDDM, each usually considered a distinct clinical entity, represent different clinical expressions of a common defect in cellular ion handling, hence explaining their frequent clinical coexistence in the general population. 
Model for studying virus attachment. II. Binding of biotinylated human T cell leukemia virus type I to human blood mononuclear cells potential targets for human T cell leukemia virus type I infection. Purified human T cell leukemia virus type I (HTLV-I) was biotinylated and used to study its attachment to human PBMC. The use of biotinylated HTLV-I (biot-HTLV-I) in conjunction with mouse mAb specific for selected cell-surface molecules and flow cytometric analysis allowed us to positively identify virus-binding cells among a heterogeneous blood mononuclear cell population. Biot-HTLV-I efficiently bound not only to T cells, but also to B cells and monocytes. Preincubation of monocytes with excess of unlabeled HTLV-I significantly reduced the attachment of biot-HTLV-I. HTLV-I not only bound to, but also infected, B cells, as suggested by: i) in situ hybridization of a 35S-labeled full length HTLV-I DNA probe with EBV-transformed B cells, previously cocultured with HTLV-I-producing (G11MJ) T cells, and ii) hybridization of the same nick-translated 32P-labeled DNA probe with blotted DNA from similar HTLV-I-infected EBV-transformed B cells. HTLV-I infection did not affect the ability of B cells to secrete IgG. These findings suggest that HTLV-I cannot only infect cells of the T lineage, but can also infect B cells. 
In vivo thrombus formation on a guidewire during intravascular ultrasound imaging: evidence for inadequate heparinization. We present a case in which thrombus formation on a guidewire was visualized during intravascular ultrasound imaging despite the administration of 10,000 units of heparin sulfate prior to the procedure. Gross thrombus formation was confirmed upon removal of the guidewire. The activated clotting time was found to be 191 s, suggesting heparin resistance. This report graphically illustrates the potential thrombogenicity associated with intravascular guidewire manipulation during procedures such as intravascular ultrasound imaging and percutaneous transluminal coronary angioplasty. Moreover, this case suggests that adequate heparinization should be routinely verified by measuring the activated clotting time prior to introducing a guidewire into the arterial system. 
Infections with Chryseomonas luteola (CDC group Ve-1) and Flavimonas oryzihabitans (CDC group Ve-2) in neurosurgical patients. During a 20-month period at Temple University Hospital, three cases of infection with bacteria of the Ve group--Chryseomonas luteola (CDC group Ve-1) and Flavimonas oryzihabitans (CDC group Ve-2)--were seen in neurosurgical patients. Two of the patients, including one with what is thought to be the first reported case of meningitis due to C. luteola, had complications caused by prosthetic material. A review of the literature revealed 14 well-described cases of infection with C. luteola or F. oryzihabitans, the majority of which were cases of bacteremia or peritonitis in patients undergoing dialysis. The presence of foreign material and the use of corticosteroids may predispose to and influence the course of disease. As prosthetic material becomes even more widely used, the incidence of infection with bacteria of the Ve group will likely increase and the manifestations of the infections will probably become more varied. 
The use of absorbable sutures in laser-assisted microvascular anastomoses. The efficacy of the laser in performing microvascular anastomoses has been well established in the laboratory using a number of wavelengths. These studies have concluded that laser-assisted microvascular anastomoses are at least comparable to, if not superior to, ordinary suture techniques. The advantages have been the diminished foreign body reaction that occurs as a consequence of using only a few stay sutures to hold the vessels in approximation while the laser bonding is performed, as well as the rapidity of the surgery. We have already shown that absorbable sutures (polyglactin 910) are as efficacious as standard nonabsorbable sutures (nylon) in both arterial and venous microanastomoses. The current study was undertaken to see if the foreign body reaction could be diminished even further by the use of absorbable 10.0 sutures and compare these findings to laser-assisted microvascular anastomoses performed with nonabsorbable sutures. The carbon dioxide milliwatt laser was used to perform laser-assisted microvascular anastomoses in rat femoral arteries and veins. Patency rates and histological response were compared at intervals of 3 days and 1, 2, 4, 8, and 12 weeks postoperatively. Both arterial and venous patency rates were comparable (overall absorbable, 91.2%-52/57; overall nonabsorbable, 87.7%-50/57), as was the degree of inflammation and fibrosis. We conclude that absorbable sutures can be used for laser-assisted microvascular anastomoses and have the potential of allowing healing to occur without any foreign material within the surgical site. 
Immunomodulation of the induction phase of lymphokine-activated killer activity by acute phase proteins. Effective treatment of head and neck cancer with biologic response modifiers may be benefitted by an understanding of in vivo factors capable of modulating the lymphokine-activated killer (LAK) cell phenomenon. Eighteen patients with squamous cell carcinoma of the head and neck were studied. Killer cells from each patient, activated by recombinant interleukin-2 (10 U/ml), were induced in either complete medium alone or complete medium plus 10% autologous serum solution and analyzed. Cytotoxicity against both K562 and squamous cell carcinoma (MDA686-Ln) cell lines was determined by use of standard chromium-release assays. The immunomodulatory capacity of serum was correlated with levels of various acute phase proteins. Autologous serum significantly inhibited the induction phase of the LAK phenomenon in 61% of patients and stimulated it in 22%. No patients with early stage I or II disease had significant inhibition of induction. No direct correlation between inhibition and serum acute phase protein levels were seen. An inverse relationship was seen between the C3 component of complement and induction inhibition (r = -0.6). These findings suggest that advances of in vivo immunomodulatory therapy will require elucidation of mechanisms of serologic inhibition of the induction phase of the LAK phenomenon. Such studies may lead to serologic modification to enhance treatment efficacy of biologic response modifiers. 
Diffuse esophageal spasm. A rare motility disorder not characterized by high-amplitude contractions. Diffuse esophageal spasm (DES) has frequently been described as a motility disorder characterized by simultaneous, high-amplitude contractions. We reviewed the results of esophageal manometry testing on a total of 1480 patients referred to our lab over 36 months. Lower esophageal sphincter (LES) pressure was determined by a mean of four station pull-through. Esophageal body motility was assessed following 10 wet swallows. In our lab a diagnosis of DES is made when greater than 10% but less than 100% of contractions are simultaneous. Manometric findings of DES were rare, with an overall prevalence of 4% (56/1480). Of the 56 patients with a manometric diagnosis of DES, high-amplitude (mean greater than or equal to 180 mm Hg) peristaltic contractions were found in only two (4%). No simultaneous contractions with amplitude greater than or equal to 180 mm Hg were seen. Pressures of simultaneous contractions were consistently lower than peristaltic contractions. A hypertensive LES pressure (greater than or equal to 45 mm Hg) was present in 5/56 DES patients (9%). Poor LES relaxation was found in 7/56 DES patients (13%). We conclude that DES is a rare manometric finding, regardless of the reason for referral, and that the occurrence of high-amplitude contractions in DES is equally rare. 
Proteins of the complement system and acute phase reactants in sera of patients with spinal cord injury. Complement activity was studied in patients with spinal cord transection. In some sera acute phase reactants: haptoglobin, C-reactive proteins, ceruloplasmin, as well as fibrinogen and fibrin degradation products, and immune complexes were monitored. Complement and acute phase reactants are increased in a majority of patients. Continuing inflammation and release of inflammatory mediators could be responsible for poor healing that commonly occurs in spinal cord injury. Urinary tract and other infections are associated with some but not all of the protein abnormalities. These proinflammatory proteins may contribute to the lack of healing of spinal transection. 
The influence of severity of spinal cord ischemia in the etiology of delayed-onset paraplegia. To clarify the cause of delayed-onset paraplegia, the authors evaluated the neurologic outcome after temporary (10 to 30 minutes) spinal cord ischemia in the awake rabbit. Loss of motor function occurred in less than 2 minutes in all animals. Restoration of flow within 16 minutes always resulted in full return of function, whereas with occlusion times of greater than 27 minutes all animals remained paralyzed. After temporary occlusion of 20 to 21 minutes, however, 71% of animals returned to normal neurologic function but developed delayed-onset paraplegia 14 to 48 hours later. This appears to be a reliable method for the creation of a model of delayed-onset paraplegia in the awake animal, and will facilitate more detailed studies of the pathophysiology of ischemia-induced paraplegia. 
Trauma history in diagnostic groups of temporomandibular disorders. Trauma history was studied for association with disease among six diagnostic subgroups of 230 patients with temporomandibular disorder (TMD) from a private practice setting with (1) disk displacement (DD) with reduction, (2) DD without reduction, (3) osteoarthrosis (OA) with prior derangement history, (4) primary OA, (5) myalgia only, and (6) subluxation only. Except for subluxation (29%), trauma history typified TMD patient groups 1 to 5 (63%, 79%, 44%, 53%, 54%) (p less than 0.001) compared with 13% and 18% of asymptomatic (n = 61) and symptomatic (n = 161) student control subjects, and 11% of general dental patients (n = 150). TMD groups 2 and 3 differed significantly (p less than 0.05). The high prevalence of trauma in the myalgia-only group complicates the concept of myofascial pain-dysfunction syndrome as solely a stress or centrally mediated disorder. DD without reduction (43%) and with reduction (38%) had the highest prevalences of motor vehicle accident trauma, myalgia and OA groups had less, and subluxation-only cases had none. On the other hand, patients with DD without reduction were also the only group to report multiple trauma (29%), suggesting that although specific traumatic events may seem to precipitate clinical symptoms, they may not always have initiated the problem. Trauma may be both an important cumulative and precipitating event in TMDs. 
Limitations of balloon angioplasty for vein graft stenosis. Vein graft stenosis remains an important contributing factor to the failure of infrainguinal arterial reconstruction. Repair of these lesions before graft occlusion provides sustained patency, yet the optimal method of repair has not been established. Percutaneous transluminal balloon angioplasty of these vein graft lesions has been repeatedly advocated as an alternative to surgical revision. Balloon angioplasty was used in 30 patients with 54 stenotic lesions occurring in autogenous vein grafts after infrainguinal reconstruction. The primary 5-year cumulative patency rate was 18% overall, with no significant differences observed among patency rates based on initial indication, length of stenotic lesion, or requirement for preliminary thrombolytic therapy. The 3-year patency rate associated with vein graft lesions requiring only a single angioplasty proved significantly higher (59%) than those requiring repetitive dilations (6%). It is our conclusion that balloon angioplasty for vein graft stenosis has significant limitations in providing sustained secondary patency. 
Safety and tolerance of oral dextromethorphan in patients at risk for brain ischemia. Experimental ischemia models have shown the antitussive dextromethorphan to be an N-methyl-D-aspartate antagonist with neuroprotective properties. We treated 10 patients with a history of recent stroke or transient ischemic attack with oral dextromethorphan (60 mg q.i.d.) for 3 weeks in a placebo-controlled, double-blind, crossover tolerance study. We documented no clinical evidence of toxicity attributable to dextromethorphan in this preliminary study. 
Imaging of cocaine-induced global and regional myocardial ischemia. Severe and often fatal cardiac complications have been reported in cocaine users with narrowed coronary arteries caused by atherosclerosis as well as in young adults with normal coronaries. We have found that in normal dogs cocaine induces severe temporary hypoperfusion of the left ventricle as indicated by a significantly lower 201Tl concentration compared to the baseline state. The most significant decrease in uptake occurred 5 min after injection and was more pronounced in the septal and apical segments. Following intravenous administration of cocaine, instead of gradual disappearance of 201Tl from the left ventricle, there was continuous increase in 201Tl concentration in the left ventricle. These imaging experiments indicate that the deleterious effects of cocaine on the heart are probably due to spasm of the coronaries and decreased myocardial perfusion. Since spasm of the large subpericardial vessels does not seem to explain the magnitude of the increased coronary resistance and decreased coronary flow after cocaine as described in the literature, it is suggested that microvascular spasm of smaller vessels plays a major role in the temporary decrease in perfusion. The data may also suggest that severe temporary myocardial ischemia is probably the initiating factor for the cardiac complications induced by cocaine. 
Fulminant childhood hemophagocytic syndrome mimicking histiocytic medullary reticulosis. An atypical form of Epstein-Barr virus infection. Ten cases of pediatric fulminant hemophagocytic syndrome, encountered between 1986 and 1989, are described. They occurred in the summer, and the patients presented with fever, jaundice, hepatosplenomegaly, pancytopenia, coagulopathy, and abnormal liver function. Bone marrow studies revealed infiltration by atypical T-lymphoid cells, rare B immunoblasts, and mature histiocytes with hemophagocytosis. Initially, histiocytic medullary reticulosis was suspected in six cases. The clinical course was characterized by rapid deterioration, with a mean period of 16 days from onset of fever to death. The main causes of death were coagulopathy with multiple organ failure and opportunistic infection. In seven of eight cases studied by serologic assay and Southern blot hybridization, acute or active Epstein-Barr virus (EBV) infection was documented. It is suggested that an atypical or fulminant form of primary EBV infection distinct from classic infectious mononucleosis was prevalent in previously healthy children in Taiwan. Younger age involvement and seasonal clustering were characteristic of the disorder described. 
Mechanisms of visual spatial neglect. Absence of directional hypokinesia in spatial exploration. This study examines whether visuospatial neglect derives from failure in directing hand movements to the left (directional hypokinesia), or from loss of mental representation of the left side of space. Forty right brain-lesioned patients, 28 of whom revealed mild, moderate, or severe neglect in clock drawing and cancellation tasks, were asked to search for concealed targets on a stimulus display board, by either (1) moving a covering panel with a small window until the target appeared, or (2) moving the stimulus display board beneath a stationary covering panel until the target became visible through the window. In the second procedure, the direction of physical space exploration and hand movement is reversed, so that in order to bring a target from the right side of the stimulus into view (under the window) the entire display board had to be moved to the left. This pair of procedures was supplemented by an analogous pair of visual tasks in which the entire display board was visible during the search. As expected, response times were generally longer for targets located on the left side of the display board; however, the direction of required hand movement (left vs right) did not have a significant effect on response times, irrespective of the degree of clinically assessed neglect. 
Chimeric NGF-EGF receptors define domains responsible for neuronal differentiation. To determine the domains of the low-affinity nerve growth factor (NGF) receptor required for appropriate signal transduction, a series of hybrid receptors were constructed that consisted of the extracellular ligand-binding domain of the human epidermal growth factor (EGF) receptor (EGFR) fused to the transmembrane and cytoplasmic domains of the human low-affinity NGF receptor (NGFR). Transfection of these chimeric receptors into rat pheochromocytoma PC12 cells resulted in appropriate cell surface expression. Biological activity mediated by the EGF-NGF chimeric receptor was assayed by the induction of neurite outgrowth in response to EGF in stably transfected cells. Furthermore, the chimeric receptor mediated nuclear signaling, as evidenced by the specific induction of transin messenger RNA, an NGF-responsive gene. Neurite outgrowth was not observed with chimeric receptors that contained the transmembrane domain from the EGFR, suggesting that the membrane-spanning region and cytoplasmic domain of the low-affinity NGFR are necessary for signal transduction. 
Effects of percutaneous transvenous mitral commissurotomy on levels of plasma atrial natriuretic peptide during exercise. To clarify the factors that influenced the secretion of human atrial natriuretic peptide (ANP) during exercise, we studied the relations between the changes in ANP, transmitral pressure gradient, heart rate and blood pressure at exercise in 16 patients with mitral stenosis before and after percutaneous transvenous mitral commissurotomy (PTMC). Before PTMC, ANP levels increased from 107 +/- 70 to 183 +/- 96 pg/ml during exercise testing (p less than 0.01), concomitant with the increment in mean transmitral pressure gradient, heart rate and systolic blood pressure. After PTMC, ANP levels also increased from 78 +/- 43 to 117 +/- 64 pg/ml, concomitant with the increment of those parameters. However, increments of ANP, mean transmitral pressure gradient and heart rate after PTMC were lower than those before PTMC. Because the most important factor influencing the secretion of ANP was unclear, the differences between these parameters were calculated at submaximal exercise before and after PTMC. There was a significant relation only between the change in ANP and mean transmitral pressure gradient (r = 0.70, p less than 0.01). These results suggest that the most important factor influencing the secretion of ANP during exercise is the change in transmitral pressure gradient in patients with mitral stenosis. 
Self-administered hyperventilation cardiopulmonary resuscitation for 100 s of cardiac arrest during Holter monitoring. An 80-year-old man remained conscious due to vigorous deep breathing during 100 s of ventricular arrest which was recorded on a Holter ECG. Arterial blood flow is considered to have been maintained by changes in intrathoracic pressure produced by deep respiratory movements. This case may represent a pure model of the "thoracic pump" mechanism. 
Natural history of vaginal intraepithelial neoplasia. The natural history of vaginal intraepithelial neoplasia (VAIN) was studied in 23 patients followed for at least 3 years with no treatment. The mean age of the patients was 41 years of age. A large proportion of the VAIN lesions (50%) were multifocal, and approximately one half of the lesions were associated with concomitant cervical or vulvar intraepithelial neoplasia. Progression to invasive vaginal carcinoma occurred in two (9%) cases, persistence of VAIN occurred in three (13%) cases, and regression of VAIN occurred in 18 (78%) cases. The risk for progression to invasive carcinoma emphasizes the significance of colposcopic examination of the vagina with directed biopsy specimens obtained from all lesions. 
Central retinal and posterior ciliary artery occlusion after particle embolization of the external carotid artery system. A 15-year-old boy underwent neuroradiologic embolization of the left internal maxillary artery with polyvinyl alcohol to stop traumatic epistaxis after failure of surgical clipping and nasal packing. Selective catheterization of the external carotid artery before embolization showed a faint choroidal blush. Although the procedure provided hemostasis, embolization to the central retinal artery and ciliary arteries resulted in loss of vision. The route of the emboli to the eye was via the anastomotic network of the lacrimal artery supplied by the external carotid artery system. Neuroradiologic embolization of the external carotid artery is an effective mode of therapy for dural-cavernous fistulas when fed by the external carotid artery system. Because the blood flow to the brain and eye is predominantly supplied by the internal carotid artery, embolization of the external carotid artery is considered relatively safe. The authors document the importance of recognition of the choroidal blush during selective external carotid artery angiography as a sign of collateral blood flow to the eye. Physicians and patients need to be aware of the risk of blindness as a complication of external carotid artery embolization when this sign is present. 
Functional domains of the poliovirus receptor. A number of mutant cDNAs of the human poliovirus receptor were constructed to identify essential regions of the molecule as the receptor. All mutant cDNAs carrying the sequence coding for the entire N-terminal immunoglobulin-like domain (domain I) confer permissiveness for poliovirus to mouse L cells, but a mutant cDNA lacking the sequence for domain I does not. The transformants permissive for poliovirus were able to bind the virus and were also recognized by monoclonal antibody D171, which competes with poliovirus for the cellular receptor. These results strongly suggest that the poliovirus binding site resides in domain I of the receptor. Mutant cDNAs for the sequence encoding the intracellular peptide were also constructed and expressed in mouse L cells. Susceptibility of these cells to poliovirus revealed that the entire putative cytoplasmic domain is not essential for virus infection. Thus, the cytoplasmic domain of the molecule appears not to play a role in the penetration of poliovirus. 
Resting energy expenditure in patients with pancreatitis. OBJECTIVE: To assess the resting energy expenditure of hospitalized patients with pancreatitis. DESIGN: Prospective, case-referent study. SETTING: Nutrition support service in a university tertiary care hospital. PATIENTS: Patients referred to the Nutrition Support Service with the diagnosis of pancreatitis. Excluded from study entry included those with cancer, obesity (greater than 150% ideal body weight), those measured within 3 postoperative days, or patients requiring ventilator support with an FIO2 of greater than 0.5. Forty-eight patients with either acute pancreatitis (n = 13), chronic pancreatitis (n = 24), acute pancreatitis with sepsis (n = 7), or chronic pancreatitis with sepsis (n = 7) were studied. The two septic groups were combined into a single pancreatitis-with-sepsis group, since no significant differences among measured variables were observed between individual septic groups. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Resting energy expenditure was measured by indirect calorimetry and compared with the predicted energy expenditure, as determined by the Harris-Benedict equations. Resting energy expenditure (percent of predicted energy expenditure) was significantly (p less than .02) greater for patients with pancreatitis complicated by sepsis (120 +/- 11%) compared with the nonseptic chronic pancreatitis group (105 +/- 14%). Resting energy expenditure for the nonseptic acute pancreatitis patients (112 +/- 17%) was not significantly different from the other groups. The septic pancreatitis group had the largest percentage (82%) of hypermetabolic (resting energy expenditure greater than 110% of predicted energy expenditure) patients, whereas 61% and 33% of the acute and chronic pancreatitis groups were hypermetabolic, respectively (p less than .02). CONCLUSIONS: Resting energy expenditure is variable in patients with pancreatitis (77% to 139% of predicted energy expenditure). The Harris-Benedict equations are an unreliable estimate of caloric expenditure. Septic complications are associated with hypermetabolism and may be the most important factor influencing resting energy expenditure in pancreatitis patients. 
MRC European Carotid Surgery Trial: interim results for symptomatic patients with severe (70-99%) or with mild (0-29%) carotid stenosis. European Carotid Surgery Trialists' Collaborative Group The European Carotid Surgery Trial is a multicentre trial of carotid endarterectomy for patients who, after a carotid territory non-disabling ischaemic stroke, transient ischaemic attack, or retinal infarct, are found to have a stenotic lesion in the relevant (ipsilateral) carotid artery. Over the past 10 years 2518 patients have been randomised, and the mean follow-up is now almost 3 years among the 2200 thus far available for analysis of the incidence of strokes that lasted more than 7 days. For the patients with "moderate" (30-69%) stenosis on their prerandomisation angiogram the balance of surgical risk and eventual benefit remains uncertain, and full recruitment continues. For 374 patients with only "mild" (0-29%) stenosis there was little 3-year risk of ipsilateral ischaemic stroke, even in the absence of surgery, so any 3-year benefits of surgery were small, and were outweighed by its early risks. For 778 patients with "severe" (70-99%) stenosis, however, the risks of surgery were significantly outweighed by the later benefits: although 7.5% had a stroke (or died) within 30 days of surgery, during the next 3 years the risks of ipsilateral ischaemic stroke were (by life-table analysis) an extra 2.8% for surgery-allocated and 16.8% for control patients (a sixfold reduction, p less than 0.0001). There was also a small reduction in other strokes, and at 3 years the total risk of surgical death, surgical stroke, ipsilateral ischaemic stroke, or any other stroke was 12.3% for surgery and 21.9% for control (difference 9.6% SD 3.3, 2p less than 0.01). The main concern was to avoid disabling or fatal events, and, among severe stenosis patients, 3.7% had a disabling stroke (or died) within 30 days of surgery, an extra 1.1% surgery versus 8.4% control (p less than 0.0001) had a disabling or fatal ipsilateral ischaemic stroke by 3 years, and the total 3-year risk of any disabling or fatal stroke (or surgical death) was 6.0% surgery versus 11.0% control (overall difference 5.0% SD 2.3, 2p less than 0.05); but, for disabling or fatal stroke the control risks seemed to diminish after the first year, so delay of surgery by just a few months after clinical presentation might make this overall difference non-significant. 
Relapsing transverse myelitis. Acute transverse myelitis is a monophasic disorder, the recurrence of which raises the question of multiple sclerosis (MS) or other multifocal CNS disease. We now report three patients with a previously undescribed syndrome of relapsing isolated acute transverse myelitis. Each had two to five attacks over periods of 3 to 8 years, characterized by ascending paresthesias, urinary retention, sensory loss with a thoracic or cervical level, paraparesis, hyperreflexia, and bilateral Babinski signs. MRI demonstrated areas of increased signal intensity on T2- and proton density-weighted scans and decreased signal intensity on T1-weighed scans of the cervical or thoracic spinal cord consistent with an inflammatory or demyelinating process. All patients had normal complete myelograms, oligoclonal IgG bands were consistently absent from the cerebrospinal fluid, cranial MRIs were normal, and there was no other clinical or laboratory evidence of MS, collagen-vascular disease, or active viral infection. They were treated with high doses of intravenous corticosteroids, stabilized between episodes, and had partial or complete recovery. The recognition of these three patients at a single medical center in a 1-year period suggests that relapses of acute transverse myelitis may not be rare. 
Clarification of the identity of the major M2 autoantigen in primary biliary cirrhosis. 1. In primary biliary cirrhosis, the major M2 autoantigen, reacting with antimitochondrial antibodies in sera from greater than 90% of patients, has been identified as the E2 component of the pyruvate dehydrogenase complex. However, two recent reports suggest that alternative polypeptides may be major autoantigens. 2. The evidence that a 75 kDa subunit of complex I of the respiratory chain is a major autoantigen (Frostell, Mendel-Hartvig, Nelson, Totterman, Bjorkland & Ragan, Scand. J. Immunol. 1988; 28, 157-65) is refuted. The findings of Frostell et al. can be explained by contamination of complex I with the pyruvate dehydrogenase complex, evidence for which is presented here. 3. Inspection of the partial amino acid sequence of an unidentified mitochondrial autoantigen (Muno, Kominami, Ishii, Usui, Saituku, Sakakibara & Namihisa, Hepatology 1990; 11, 16-23) shows that it is the E1 beta-subunit of the pyruvate dehydrogenase complex, previously identified as a major autoantigen, and not a 'new' alternative major autoantigen. 4. These findings substantiate previous work showing that the mitochondrial M2 autoantigens identified so far in primary biliary cirrhosis are all polypeptide components of the pyruvate dehydrogenase complex or the other related 2-oxo acid dehydrogenase complexes. 
A randomized comparative study of laser photocoagulation, heater probe, and bipolar electrocoagulation in the treatment of actively bleeding ulcers. A randomized study was performed to compare the efficacy of Nd:YAG laser, heater probe, and bipolar electrocoagulation in the treatment of active bleeding from peptic ulcers. Nine hundred and forty-eight consecutive patients with upper gastrointestinal bleeding underwent endoscopy and 91 patients with active bleeding from peptic ulcer were randomized to receive laser (N = 30), heater probe (N = 31), and bipolar electrocoagulation (N = 30). The angulation of the probe to the ulcer base was assessed at endoscopy. The three treatment groups were comparable in their clinical and endoscopic characteristics. There was no significant difference among patients treated with laser, heater probe, and bipolar electrocoagulation in the rate of re-bleeding (10%, 19.4%, and 10%), duration of hospital stay (4, 4, and 5 days), and proportion requiring emergency surgery (7%, 13%, and 7%), but the cost per patient was higher with laser than heater probe and bipolar electrocoagulation. The angulation of the probe to the ulcer base did not affect the re-bleeding rate. No complication was reported. We conclude that the three modalities were equally effective and safe in endoscopic hemostasis but because bipolar electrocoagulation and heater probe were cheaper, they were recommended for use. 
Occlusive and reperfused myocardial infarcts: MR imaging differentiation with nonionic Gd-DTPA-BMA. To increase the time during which effective contrast exists between normal and infarcted myocardium, a high dose (0.6 mmol/kg) of the nonionic contrast medium gadolinium diethylenetriaminepentaacetic acid bismethylamide (Gd-DTPA-BMA) was used to distinguish between occlusive and reperfused myocardial infarctions in rats. After administration of Gd-DTPA-BMA, there was clear and persistent demarcation of both occlusive and reperfused infarcts on T1-weighted MR images. In occlusive infarcts, normal, infarcted, and periinfarcted myocardium could be identified. High signal intensity was evident for 60 minutes in a band straddling the border between infarcted and normal myocardium, namely, the periinfarction zone. In the reperfused infarct, normal and infarcted myocardium could be identified. The reperfused zone was immediately enhanced after injection of Gd-DTPA-BMA. A differential pattern of enhancement between occlusive and reperfused myocardial infarcts was evident for 1 hour. Thus, Gd-DTPA-BMA has the potential to allow (a) depiction of occlusive and reperfused acute myocardial infarcts, (b) documentation of reperfusion of myocardial infarction, and (c) distinction between occlusive and reperfused infarction. 
Update on thrombolytic therapy in acute myocardial infarction. There is a continuum of clinical research in thrombolytic therapy that will eventually evolve into the most effective regimen to chemically open a thrombosed artery. Numerous previous clinical trials, a number of ongoing trials, and planned future trials are shown in a list of acronyms and their translations as a convenience for identifying the trials. 
Discontinuation of phenytoin and carbamazepine in patients receiving felbamate. Five patients participated in a controlled discontinuation of phenytoin (PHT) and carbamazepine (CBZ) after a study in which all subjects had felbamate (FBM) added to both PHT and CBZ. Four subjects (three women and 1 man aged 23-36 years) completed the protocol. Mean total seizure frequency per day with PHT and CBZ was 1.33 +/- 0.93 (mean +/- SEM), decreasing to 0.87 +/- 0.71 with addition of FBM, and 0.82 +/- 0.78 after discontinuation of PHT. Only one subject tolerated discontinuation of CBZ; the other three had dosage reductions of 33, 54, and 63%. Toxicity attributable to FBM was not observed, and patients often described less severe seizures. Results from four refractory patients indicated that FBM was able to replace PHT and reduce the need for CBZ. In addition, as PHT dosages were reduced, FBM clearance decreased 21%. As the CBZ dosages were reduced. FBM clearance decreased an additional 16.5%. 
Immunocytological diagnosis of primary cerebral non-Hodgkin's lymphoma. Four men with primary cerebral non-Hodgkin's lymphoma diagnosed by immunocytological analysis of cerebrospinal fluid (CSF) presented with cranial nerve palsies. All had CSF lymphocytoses and low CSF glucose. The cell phenotypes were two T cell tumours, one B cell, and one null. A review of 13 previously recorded cases of immunocytologically diagnosed CNS non-Hodgkin's lymphoma showed that there were 10 B cell, two T cell, and one null tumour. Overall (17 cases) the cell phenotype distribution was 65% B cell, 24% T cell, and 11% null. High CSF lymphocyte counts were found in 94%, proteinosis in 85%, and low CSF glucose in 87%. In contrast to the B cell tumours, all of the T cell tumours were diagnosed by CSF cytology before being visualised radiologically. It is suggested that all CSF lymphocytes (greater than 5 x 10(6)/ml) should be immunohistochemically typed to permit earlier diagnosis of CNS non-Hodgkin's lymphoma. 
Surface appearance and instability of empty H-2 class I molecules under physiological conditions. Recent evidence suggests that endogenously produced antigenic peptides are required for assembly of major histocompatibility complex class I chains with beta 2-microglobulin and transport to the cell surface. The RMA-S mutant cells are thought to be defective in intracellular peptide loading to class I molecules and, therefore, devoid of class I surface expression. Here we report that at physiological temperature (37 degrees C) "empty" class I molecules appear at the cell surface of RMA-S cells where they can be trapped with H-2 antibodies. In the absence of the stabilizing ligand, the class I molecules rapidly alter their conformation but remain at the cell surface as demonstrated with a rabbit antiserum. Such denatured H-2 molecules can also be found on normal wild-type RMA cells. However, their amount is strongly reduced after culture of RMA cells with a class I binding peptide. These findings indicate that empty class I molecules appear at the surface not only on mutant but also on normal cells, suggesting that in normal cells the supply with peptides is limited. 
Temporal bone findings in a family with branchio-oto-renal syndrome (BOR). A family group with confirmed branchio-oto-renal (BOR) syndrome was investigated in this study. Computerized tomography of the temporal bones has demonstrated that the malformations of the inner ear consist of hypoplastic structural changes within the cochlea with reduced vertical diameters, and absent or hypoplastic semicircular canals and normal endolymphatic ducts. It is concluded that in the present cases, the Mondini malformation of the cochlea is not associated with the BOR syndrome. 
Melanoma tumor vaccine: five-year follow-up. For many years, various melanoma vaccines have been employed. This is a unique melanoma vaccine in that it is a subcellular tumor homogenate and no adjuvants have been added. This vaccine has been given to 129 stage I and 61 stage II melanoma patients. All were followed at least 5 years and had 87.5% and 63.9% 5-year survival rates, respectively. Sixty-four stage I males and 65 stage I females had 84% and 90% 5-year survival rates, respectively. We saw no difference between those with or without lymph node dissection. Thirty-six stage II males and 25 stage II females had 66.7% and 60% 5-year survival rates, respectively. Of stage II patients, 23 had only one positive node, 22 had two to four positive nodes, and 9 had five or more positive nodes with 69%, 63%, and 55% 5-year survival rates, respectively. Large published series were used as historical controls [6,27,28], and significant differences were noted when compared to our stage II patients (P = 0.001)--those with two to four positive nodes (P = 0.03), and those with five or more positive nodes (P = 0.04). We conclude that there is a significant increase in survival for these stage II patients, at high risk of recurrence, receiving a tumor homogenate vaccine. This vaccine warrants further analysis, development, and use in a phase III randomized clinical trial. 
Reoperative pulmonary resection in patients with metastatic soft tissue sarcoma Resection of pulmonary metastases from soft tissue sarcoma has been shown to be associated with a 3-year survival of 25% to 30%. The role of multiple resections for recurrent pulmonary metastases, however, has not been clearly defined. Since 1976, 43 patients have had two or more thoracic explorations for the purpose of resecting pulmonary metastases from adult soft tissue sarcoma at our institution. In 89 reexplorations, through either median sternotomy or lateral thoracotomy, the operative mortality was 0%, and 31 of the 43 patients (72%) could be rendered free of disease at the second thoracotomy. Median survival from the second thoracotomy for the patients with resectable disease was 25 months, whereas median survival of patients who had unresectable disease was 10 months. A disease-free interval between the first and second thoracotomies of greater than 18 months was associated with prolonged survival from the second thoracotomy. Owing to lack of other therapies with proven salvage efficacy and in the absence of randomized trials, repeated thoracotomies to render patients free of disease from pulmonary soft-tissue sarcoma metastases appear justified considering the potential survival benefit and low attendant risk. 
Intracellular calcium transients in myocardium from spontaneously hypertensive rats during the transition to heart failure. To investigate the mechanism of impaired myocardial function after long-term pressure overload, we studied cardiac muscle mechanical contraction and intracellular calcium transients using the bioluminescent indicator aequorin. Left ventricular papillary muscle preparations were examined from three groups of rats: 1) aging spontaneously hypertensive rats (SHR) with clinical and pathological evidence suggesting heart failure (SHR-F group), 2) age-matched SHRs with no evidence of heart failure (SHR-NF group), and 3) age-matched normotensive Wistar-Kyoto rats (WKY group). Isometric force development was depressed in both SHR groups relative to the WKY group. Resting [Ca2+]i was lower in the SHR-F group, and the time to peak [Ca2+]i was prolonged in this group. The relative increases in peak [Ca2+]i with the inotropic interventions of increased [Ca2+]o and the addition of isoproterenol were similar among groups. Although inotropy increased in all groups with increased [Ca2+]o, after isoproterenol, inotropy increased only in the WKY group. Thus, in SHR myocardium, [Ca2+]i increased after isoproterenol, but inotropy failed to increase. Myosin isozymes were shifted toward the V3 isoform in both SHR groups; the V3 isoform was virtually 100% in papillary muscles from the SHR-F group. These changes may reflect events directly contributing to the development of heart failure or represent adaptive changes to chronic pressure overload and heart failure. 
A video system for investigating breathing disorders during sleep. A system has been developed for investigating breathing during sleep that superimposes physiological signals on a video image of the patient, with the combined image plus sound recorded on video tape for later analysis. Signals normally displayed include oxygen saturation, airflow, chest wall motion, electroencephalogram, and electrooculogram; but others can be recorded if desired. The information is displayed on a timebase appropriate for the recognition and analysis of respiratory events during sleep. In addition, use is made of normally invisible video lines to record the analogue voltage waveforms so that on replay this information can be displayed on a fast timebase for analysing the more rapidly changing waveforms of electrophysiological signals. The system allows detailed polysomnography to be performed in the normal ward setting with the subject monitored overnight by the nursing staff. Subsequent analysis of the synchronised video, audio, and analogue signals allows measurement of the conventional indices obtained by polysomnography and aids their interpretation. 
Events in the Cardiac Arrhythmia Suppression Trial (CAST): mortality in patients surviving open label titration but not randomized to double-blind therapy. The patient characteristics and outcomes were studied in the 318 patients who survived open label drug titration in the Cardiac Arrhythmia Suppression Trial (CAST) and who were not randomized to double-blind therapy and in 942 patients, who were randomized to double-blind placebo therapy. The patients randomized to placebo therapy had a lower total mortality or resuscitated cardiac arrest rate (4% vs. 8.5%). However, at baseline, nonrandomized patients were dissimilar from patients randomized to placebo in the following ways: older; lower left ventricular ejection fraction; greater use of digitalis, diuretic drugs and antihypertensive agents; lesser use of beta-adrenoceptor blocking agents and more frequent prior cardiac problems, including runs of ventricular tachycardia and left bundle branch block. A matched comparison that took these inequities into account showed no significant differences in mortality or rate of resuscitation from cardiac arrest between nonrandomized patients and clinically equivalent patients randomized to placebo. Cox regression analysis indicated that two factors significantly increased the hazard ratio for arrhythmic death or resuscitated cardiac arrest in the nonrandomized patients: female gender (4.7, p less than 0.05) and electrocardiographic events (ventricular tachycardia, proarrhythmia, widened QRS complex, heart block, bradycardia) during open label titration (7.0, p less than 0.005). However, some potentially important differences between men and women were not included in the Cox regression model. Of the nonrandomized patients, approximately 70% were not randomized because of lack of suppression of ventricular premature depolarizations or adverse events, or both, and the remaining 30% because of patient or private physician request with no indication of another reason. 
Quantification of cell kinetic characteristics using flow cytometric measurements of deoxyribonucleic acid and bromodeoxyuridine for bladder cancer. A total of 56 human bladder tumors that were histologically proved to be transitional cell carcinoma was analyzed by simultaneous flow cytometric 2-color measurements of deoxyribonucleic acid (DNA) and bromodeoxyuridine. Bromodeoxyuridine in vitro labeling was performed by sample incubation with bromodeoxyuridine under high atmospheric pressure oxygen. Grade 1 tumors showed 33.3% aneuploidy with a mean bromodeoxyuridine positive stained ratio (labeling index) of 5.1 +/- 3.4%. Grade 2 tumors featured 51.7% aneuploidy with a mean labeling index of 8.9 +/- 7.7%. On the other hand, a markedly increased labeling index of 15.2 +/- 8.2% with aneuploidy was observed in all but 1 grade 3 tumors. When DNA ploidy and labeling indexes were compared according to the presence or absence of muscular invasion of tumors, all 16 muscle invasive tumors showed aneuploidy (mean labeling index 18.7 +/- 8.0%), while 17 of 40 nonmuscle invasive tumors showed aneuploidy (mean labeling index 8.6 +/- 5.4%). This labeling index difference was statistically significant (p less than 0.01). These results indicate that bromodeoxyuridine/DNA 2-color flow cytometry may provide an objective parameter for quantification of the malignant potential of bladder cancers. 
Development of a computer-aided surgery system: three-dimensional graphic reconstruction for treatment of liver cancer. Simulation of the needle puncture and volume estimation for the tumors in the liver were carried out with the three-dimensional image reconstruction system, which consists of a medical image acquisition system, a data processing system, and a graphic display. A set of sliced-image data from a computerized tomography and/or a magnetic resonance imaging was used to reconstruct the liver, the vessels, and the tumors of the patients with liver cancer. A good agreement of anatomic locations of both the intrahepatic vessels and the tumors between the reconstructed liver model and the echography done intraoperatively was observed. Surgical simulations with these graphic models clearly indicated safety areas for needle puncture in the laser coagulation therapy. In addition liver volumes were calculated within 3% of error in comparison to the measured values. These results indicate that the computer-aided surgery system is a highly promising method that avoids cumbersome stereoscopic recognition of the anatomical location of the diseased area and the vessels, before and after surgery. 
External annular prosthesis in repair of biliary tract stricture. A surgical technique for treatment of benign intrahepatic or extrahepatic biliary stenosis is described. It is based on the use of annular prostheses of Teflon placed around the outside of the anastomotic line using appropriate surgical instruments. This procedure leaves the blood supply to the bile duct intact, achieves hermetic apposition of epithelia, and prevents leakage of bile. It eliminates the use of intraductal splints, avoids retraction of scar tissue around the anastomotic zone, and increases or maintains the internal diameter of the biliary duct on the anastomotic line. The technique has been used in 33 patients with follow-up from 1 to 10 years. Excellent results were achieved in 32 patients, with 1 patient having a poor result. The average postoperative hospital stay was only 6 days. 
Adrenal rest carcinoma in hilum of kidney. Adrenocortical rests are uncommon in adults and infrequently undergo malignant changes. Most of the published cases are those of functional tumors allowing preoperative diagnosis on the basis of the resulting endocrinopathy. Most nonfunctioning tumors were found accidentally at operation or autopsy. A case is presented of a parapelvic nonfunctioning adrenocortical rest carcinoma situated in the renal hilus in a fifty-year-old woman. No such tumor has been described previously. 
A qualitative approach to primary care research: the long interview. Qualitative research methods offer useful complements to the traditional epidemiologic approaches most commonly used by primary care researchers. Narrative texts generated through open-ended interviews are one form of qualitative data that may provide useful insights into primary care issues that are otherwise overlooked by more structured designs. This paper presents a step-by-step process for conducting a long interview, a qualitative approach with distinct potential for primary care research. Advantages and limitations of the long interview and its relationship to other qualitative methods are also discussed. 
Evidence of a selective increase in cardiac sympathetic activity in patients with sustained ventricular arrhythmias BACKGROUND. Although enhanced efferent cardiac sympathetic nervous activity has been proposed as an important factor in the genesis of ventricular arrhythmias and sudden cardiac death, direct clinical evidence has been lacking. METHODS. We measured the rates of total and cardiac norepinephrine spillover into the plasma, which reflect respectively overall and cardiac sympathetic nervous activity, in 12 patients who had recovered from a spontaneous, sustained episode of ventricular tachycardia or ventricular fibrillation outside the hospital 4 to 48 days earlier. The results were compared with those from three age-matched reference groups without a history of ventricular arrhythmias: 12 patients with coronary artery disease, 6 patients with chest pain but normal coronary arteries, and 12 healthy, normal subjects. RESULTS. The patients who had had ventricular arrhythmias had reduced left ventricular ejection fractions, as compared with the patients with coronary artery disease or chest pain (mean [+/- SE], 46 +/- 3 percent vs. 58 +/- 4 percent and 69 +/- 5 percent, respectively; P less than 0.003). The rates of total norepinephrine spillover into the plasma were similar in the three reference groups, but 80 percent higher in the patients with ventricular arrhythmias (P less than 0.005). The rate of cardiac norepinephrine spillover was 450 percent higher in these patients (176 +/- 39 pmol per minute, as compared with 32 +/- 8 pmol per minute in the normal subjects; P less than 0.001), a disproportionate increase relative to the increase in total spillover, which indicated selective activation of the cardiac sympathetic outflow. This increase in cardiac norepinephrine spillover was probably caused by a reduction in left ventricular function. CONCLUSIONS. These results suggest that in some patients major ventricular arrhythmias are associated with and perhaps caused by sustained and selective cardiac sympathetic activation. We speculate that depressed ventricular function was present before the ventricular arrhythmia occurred, and that this resulted in reflex cardiac sympathetic activation, which in turn contributed to the genesis of the arrhythmia. 
Bezold-Jarisch reflex in postoperative pediatric cardiac surgical patients. The Bezold-Jarisch reflex is an inhibitory reflex that originates from the heart, is mediated by the vagus nerve, and is manifested by hypotension and bradycardia. We present 4 pediatric cardiac surgical patients, aged 1 day to 9 months, who exhibited cardiovascular collapse in their early postoperative course. In each patient, cardiovascular deterioration was marked by an insidious decrease in arterial blood pressure without an associated change in heart rate, central venous pressure, or airway pressure. Bradycardia followed the decrease in blood pressure. The Bezold-Jarisch reflex was suspected and atropine was administered, first as a bolus injection at 0.01 mg/kg, and later, as a continuous infusion at 0.01 mg.kg-1.h-1. Atropine prevented recurrent episodes of hypotension and bradycardia. We believe the Bezold-Jarisch reflex is more prevalent than previously suspected in postoperative pediatric cardiac surgical patients. 
Sonography in the diagnosis of acute appendicitis. Acute appendicitis can be a diagnostic dilemma. The classic triad of leukocytosis, pain at McBurney's point and a history compatible with appendicitis has a diagnostic accuracy rate of only 80 percent. Ultrasonography, combined with this triad, can improve the diagnostic accuracy, decreasing the negative laparotomy rate from 20 percent to less than 10 percent. 
Mycotic aneurysms of the carotid arteries--case report and review of the literature. Mycotic aneurysms of the extracranial carotid arteries are rare. We report a new case with a mycotic aneurysm of the carotid bifurcation associated with acute bacterial endocarditis of the aortic valve. A concomitant treatment of both lesions was performed. Twenty-six cases of mycotic aneurysms of the extracranial carotid arteries have been reported in the literature. We present a review of all these cases. 
Prevalence of proximal faecal stasis in active ulcerative colitis. Proximal faecal stasis may occur when faecal matter accumulates in the uninflamed colon above an area of active ulcerative colitis. This phenomenon is thought to be the cause of symptoms in some patients with distal disease. It is not known, however, how often patients with active distal colitis exhibit slow colonic transit. Fifty two consecutive patients with active ulcerative colitis each ingested 10 radio-opaque markers nightly for 14 days. Minimum colonic transit times were derived from counts of retained markers shown by plain abdominal radiography on the 15th day. The transit times for each patient were related to their disease extent and bowel frequency. Four patients had colonic transit times greater than one week and two others had evidence of relative stasis. The results indicate that approximately 10% of attacks of distal colitis are associated with faecal stasis. 
Adenocarcinoma of the pancreas: a multimodality approach--a single surgeon's experience (1979-1988). A retrospective review of a single surgeon's experience with adenocarcinoma of the pancreas was performed. One hundred-one patients were treated over a 10-year period from 1979 to 1988. Seven patients underwent potentially curative resections and 28 patients presented with metastatic (stage IV) disease. Sixty-four patients had locally advanced and unresectable primary lesions. A total of 51 patients received I-125 seed implantation. There was no statistically significant difference in morbidity (33% vs. 30%) or mortality (6% vs. 8%) between patients receiving I-125 implantation and those undergoing palliative surgical procedures without implantation. Operative mortality was highest in patients presenting with stage IV lesions (11%). In those patients with locally advanced and unresectable carcinomas, there was a nonsignificant increase in survival (12.8 mo vs. 10.7 mo) in those receiving intraoperative I-125 implants when compared to those who did not when both groups received postoperative adjuvant chemotherapy and external beam radiotherapy. Based on these encouraging results, it is concluded that I-125 implantation can be performed safely and shows a trend toward improving long-term survivorship in patients with locally advanced pancreatic carcinoma when used in conjunction with chemotherapy and external beam radiation. 
Head-up tilt for the evaluation of syncope of unknown origin in children. Fifteen patients aged 10 to 18 years with syncope of unknown origin, and 10 healthy control children aged 11 to 18 years, were evaluated by head-up tilt to 60 degrees for 60 minutes. Six patients (43%) reproduced symptoms of syncope during the examination. Four had a typical vasovagal reaction; two had marked hyperventilation. None of the children in the control group had syncope. The head-up tilt test offers a simple, noninvasive, high-yielding diagnostic tool for evaluation of syncope in children. 
Analysis and interpretation of treatment effects in subgroups of patients in randomized clinical trials. A key principle for interpretation of subgroup results is that quantitative interactions (differences in degree) are much more likely than qualitative interactions (differences in kind). Quantitative interactions are likely to be truly present whether or not they are apparent, whereas apparent qualitative interactions should generally be disbelieved as they have usually not been replicated consistently. Therefore, the overall trial result is usually a better guide to the direction of effect in subgroups than the apparent effect observed within a subgroup. Failure to specify prior hypotheses, to account for multiple comparisons, or to correct P values increases the chance of finding spurious subgroup effects. Conversely, inadequate sample size, classification of patients into the wrong subgroup, and low power of tests of interaction make finding true subgroup effects difficult. We recommend examining the architecture of the entire set of subgroups within a trial, analyzing similar subgroups across independent trials, and interpreting the evidence in the context of known biologic mechanisms and patient prognosis. 
Ventricular dysfunction does occur during liver transplantation. Ventricular dysfunction, then, does indeed occur during liver transplantation, particularly at the time of reperfusion. Pulmonary embolism contributes to right ventricular and right atrial encroachment on left-heart filling, and paradoxical embolism may occur. Pericardial effusions, tricuspid regurgitation, hypothermia, and the release of substances, particularly potassium from the donor liver, may further contribute to compromises in ventricular function. Proper monitoring and appropriate treatment, however, lead to successful operative outcomes in most cases. 
Impact of variability among surgeons on postoperative morbidity and mortality and ultimate survival. OBJECTIVE--To assess the differences among surgeons in postoperative complications, postoperative mortality, and survival in patients undergoing surgery for colorectal cancer. DESIGN--Prospective study of patients with colorectal cancer managed by one of 13 consultant surgeons, none of whom had a special interest in colorectal surgery. SETTING--Royal Infirmary, Glasgow. PATIENTS--645 sequential patients with colorectal cancer presenting over the six years from 1974 to 1979. MAIN OUTCOME MEASURES--Postoperative complications, postoperative mortality (within 30 days), and survival (up to 10 years); predictive factors for postoperative mortality and survival; and relative hazard rate ratios for individual surgeons. RESULTS--The proportion of patients undergoing apparently curative resection varied among surgeons from 40% to 76%; overall postoperative mortality varied from 8% to 30%. After curative resection postoperative mortality varied from 0% to 20%, local recurrence from 0% to 21%, and the rate of anastomotic leak from 0% to 25%. Survival at 10 years in patients who underwent curative resection varied from 20% to 63%, two year survival in those who underwent palliative resection varied from 7% to 32%, and median survival in those who underwent palliative diversion varied from one to eight months. The hazard rate ratios among individual surgeons, taking into account the identified risk factors, varied from 0.56 to 2.03, from 0.17 to 1.92, and from 0.57 to 1.50 for curative resection, palliative resection, and palliative diversion, respectively. CONCLUSION--There were significant variations in patient outcome among surgeons after surgery for colorectal cancer; such differences compromise survival. A considerable improvement in overall survival might be achieved if such surgery were undertaken by surgeons with a special interest in colorectal surgery or surgical oncology. 
Effects of alfentanil and fentanyl on induction of anaesthesia in patients with severe pregnancy-induced hypertension. Forty patients with severe pregnancy-induced hypertension presenting for Caesarean section under general anaesthesia were allocated randomly to receive either fentanyl 2.5 micrograms kg-1 or alfentanil 10 micrograms kg-1 as part of the anaesthetic induction sequence. In all patients, the cardiovascular response to tracheal intubation was measured. Both drugs attenuated the response equally but did not abolish it in all patients. Alfentanil 10 micrograms kg-1 is a suitable alternative to fentanyl 2.5 micrograms kg-1 for patients with pregnancy-induced hypertension. 
Hemangioma of the nasal vault: MR and CT features. Six patients with a history of epistaxis (five patients) or nasal obstruction (one patient) were found to have a capillary hemangioma of the nasal vault that involved one or more nasal turbinates. Four patients underwent computed tomographic (CT) examination; two of these also underwent magnetic resonance (MR) imaging. Four others underwent only MR imaging. At CT and MR, all of the lesions were well circumscribed and intensely enhancing, with contralateral deviation of the nasal septum. Remodeling of the surrounding bone was present in three patients. On T1-weighted MR images, the masses were intermediate in signal intensity. Varying degrees of T2 shortening were shown on T2-weighted MR images, with an appearance that suggested the presence of blood products surrounding an inner matrix of higher-signal-intensity tumor. Intense enhancement at CT and MR assisted differentiation of tumor from retained sinonasal secretions. In two patients, external carotid arteriography revealed small foci of pooling contrast material; in one of these patients, arteriovenous shunting was also present. Pathologic examination in all patients demonstrated capillary hemangiomas with varying degrees of fibrosis and hemosiderin deposition. 
Sarcomatous change in a teratoma after treatment of testicular carcinoma. Treatment can transform the metastases of nonseminomatous germ cell carcinoma into histologically mature teratoma. These lesions typically have a benign clinical course. The authors present a case of leiomyosarcoma occurring within such a lesion. It arose 18 years after therapy for metastatic embryonal carcinoma of the testis and appears to have been radiation induced. 
Ossicular chain reconstruction: a combined prosthesis with organic and synthetic material. The surgical techniques to restore the sound pressure transfer mechanism in surgery of chronic otitis media are still in an evolutionary stage. Ossicular interposition is effective and certainly is not controversial. The use of various organic prostheses has been criticized. The prosthesis with a shaft of Teflon and a homograft bone flange is an alternative method which has been successful in our hands. 
Polycystic ovaries: do these represent a specific endocrinopathy? Serum pituitary gonadotrophins, oestradiol, testosterone and insulin pulse patterns were examined at 15-min intervals for 6 h in 40 women with a previous diagnosis of polycystic ovarian disease (PCO) based on clinical, endocrinological and ultrasound data. Age, duration of symptoms, body mass index (BMI) and ovarian volume showed no correlation with the 6-h mean value of any hormone and testosterone blood levels did not correlate with those of insulin. Some patients had high and others low LH pulse pattern components, and few had an inverted LH:FSH ratio. Morphological polycystic ovarian changes may be a reflection of various rather than a single pattern of gonadotrophin secretion. 
Interferon-gamma inhibits arterial stenosis after injury. BACKGROUND. Arterial injury initiates a proliferative response among the smooth muscle cells of the artery. This leads to the formation of a thickened intima that may reduce the diameter of the arterial lumen. Such intimal lesions often develop after vascular surgery and angioplastic procedures. Previous cell culture studies have shown that the lymphokine, interferon-gamma (gIFN), inhibits smooth muscle cell proliferation. METHODS AND RESULTS. We therefore tested whether administration of exogenous gIFN could inhibit the development of intimal lesions. Rat carotid arteries were denuded with a balloon catheter, resulting in the formation of a standardized intimal lesion. The animals were then treated with recombinant rat gIFN at 200,000 units (approximately 400,000 units or 100 micrograms/kg body wt) administered parenterally once daily for 7 days. Autoradiographic analysis of 3H-thymidine incorporation revealed that gIFN reduced the early smooth muscle replication by approximately 75%. gIFN treatment for 1 week resulted in a 50% reduction of intimal cross-section area at 2 weeks after injury when compared to control rats injected with buffer alone. The difference in lesion development persisted in rats analyzed 10 weeks after injury, suggesting that proliferative events during the first week determine the long-term development of the intima. Inhibition of lesion development was accompanied by expression of the class II histocompatibility (Ia) gene, RT1B, suggesting that both were directly related to the administration of gIFN. CONCLUSIONS. These results show that gIFN is a potent inhibitor of the formation of arterial proliferative lesions in vivo. It is possible that gIFN could be useful in preventing arterial stenosis after surgery and angioplasty in man. 
Genetic susceptibility to Parkinson's disease. Genetic factors clearly cause Lewy-body Parkinson's disease (PD) in a subset of autosomal-dominant families. However, most cases of PD are sporadic. The two most likely models of four discussed for sporadic PD are the reduced penetrance model and the multifactorial model. Sporadic PD is likely to be caused by the combined effect of environmental precipitating factors and genetic susceptibility factors. Because the number of major genetic factors is likely to be small, these hypotheses can be tested and genetic factors located using linkage mapping techniques. The affected pair analysis methods are especially suited to PD. Finding the genetic susceptibility factors for PD is important because this may be the fastest way to identify the environmental precipitating factors and because it may lead to prevention of PD. Because of the usefulness of identifying genetic susceptibility factors for PD, we are carrying out linkage studies in a group of 16 large autosomal-dominant families with PD and more than 300 living affected PD pairs. 
Changes in neutrophil met-enkephalin containing peptides in episodic cluster headache. We have previously demonstrated an increase in plasma met-enkephalin levels during the pain attacks in episodic cluster headache. The present study was undertaken in order to clarify the source of the plasma met-enkephalin increase. Recent evidence has shown that peripheral blood polymorphonuclear cells contain peptides derived from the proenkephalin A system, which can be released by specific stimuli. We studied neutrophil met-enkephalin containing peptides (NMECP) in 27 episodic cluster headache patients: 24 in a cluster period (6 of them during a pain attack), and 3 in the remission period. Neutrophil met-enkephalin containing peptide levels (after sequential enzymatic digestion with trypsin and carboxypeptidase B) were determined by radioimmunoassay with specific antiserum. Neutrophil peptide concentration (pmol/mg prot) was lower (p less than 0.01) in patients during the pain attack (14.4 +/- 0.36) than after their pain had subsided (36.7 +/- 0.31) and lower than in the remission period patients (35.8 +/- 0.4). We conclude that neutrophil met-enkephalin containing peptides decrease during pain in episodic cluster headache, and that they may be involved in the concomitant plasma met-enkephalin increase. 
Early abdominal complications following heart and heart-lung transplantation. In the first 11 years of the heart and heart-lung transplantation programme at Papworth Hospital, Cambridge, 356 patients underwent heart transplantation, and 73 patients received both heart and lungs. Out of 429 patients 41 (9.5 per cent) developed abdominal complications within the first 30 days, and 20 of the 41 required surgery. The complications included pancreatitis (10), peptic ulceration (8), and pseudo-obstruction (8), in addition to colonic perforation and small bowel obstruction. When laparotomy was performed it was well tolerated. This paper supports the view that successful management of abdominal complications following transplantation requires prompt diagnosis and treatment. Where doubt exists in the presence of an acute abdomen, laparotomy is the appropriate way to establish a definitive diagnosis. 
Acute and chronic hemodynamic effects of xamoterol in mild to moderate congestive heart failure. Xamoterol, a new beta 1 partial agonist, has the potential to modulate cardiac response to variations in sympathetic tone in patients with heart failure. Its properties should result in beta-receptor stimulatory effects at low levels of sympathetic tone and beta-receptor protective effects at higher levels of sympathetic tone. The acute effects of intravenous (i.v.) xamoterol on hemodynamics at rest and during exercise were studied in 30 patients with mild to moderate heart failure (13 patients in New York Heart Association class II; 17 in class III) due to ischemic (n = 24) or cardiomyopathic (n = 6) heart disease. Cardiac index, stroke volume and stroke work index at rest were significantly improved after i.v. administration of xamoterol and consistent with net agonist effects. During exercise, heart rate and double product were significantly reduced (net antagonist effects), but with preservation of the expected increases in cardiac index and systolic blood pressure. These hemodynamic findings confirm the ability of xamoterol to modulate cardiac response to variations in sympathetic tone. Tachyphylaxis and arrhythmogenicity limit the chronic use of drugs with full beta-agonist properties as positive inotropes in heart failure. The patients were therefore entered into a 6-month double-blind, placebo-controlled, crossover study of chronic oral xamoterol therapy, 200 mg twice daily, and the hemodynamic responses to i.v. xamoterol were repeated at the end of the trial. No impairment in either resting or exercise effects was observed, indicative of a maintained response and absence of tachyphylaxis after chronic therapy. Furthermore, 24-hour ambulatory electrocardiographic monitoring showed no change in ventricular arrhythmias during oral treatment. 
Ewing's sarcoma in children: twenty-five years of experience at the Instituto Portuges de Oncologia de Francisco Gentil (I.P.O.F.G.). Fifty children with Ewing's sarcoma were consecutively treated from 1962 to 1987 and retrospectively analyzed at the I.P.O.F.G. of Lisbon. At first diagnosis, 10 cases had distant metastases. The remaining 40 patients had clinically localized disease, and different protocols were followed over the years. The best results were obtained with chemotherapy and radiotherapy with or without surgery; and for these children the two-year survival rate was 42.8% vs. 8.3% for the group of patients submitted to local treatment alone. Besides the treatment modality, other factors influenced the prognosis, such as inflammatory signs, sex, tumor volume, and tumor site as well as evidence of distant metastases. 
The role of epidermal growth factor in the pathogenesis of peptic ulcer disease. Duodenal biopsies obtained from seven normal subjects and six ulcerous patients were cultured in vitro for 30 min at 37 degrees C under various experimental conditions. Epidermal growth factor (EGF) and somatostatin released in the culture medium were determined by radioimmunoassay. Under basal conditions, EGF and somatostatin levels were significantly higher in normal subjects (11.49 +/- 3.07 ng/mg protein and 3.06 +/- 0.8 ng/mg protein, respectively) than in ulcerous patients (6.9 +/- 1.98 ng/mg protein and 1.75 +/- 1.23 ng/mg protein, respectively). However, when antibodies to somatostatin and vasoactive intestinal polypeptide (VIP) were added together to the culture media, in ulcerous patients, EGF levels also were lower as absolute values, but were higher as a percentage of variation than controls (p less than 0.05). The fall of EGF secretion from tissue cultures of ulcerous patients could be the consequence of endocrine cellular loss or damage, rather than the cause of ulceration. Moreover, the EGF-producing cells around the lesion in ulcerous patients seems to be hyperactive, and this hyperfunction of EGF-producing cells might contribute to the in vivo repair of tissue damage. 
Validation of hourly pain intensity profiles with chronic pain patients. This study examines how empirically derived pain intensity profiles relate to psychological adjustment in chronic pain patients. Hourly pain intensity ratings over the course of a day of 189 chronic pain patients were categorized into 6 groups using a hierarchical regression analysis technique. The profiles reflected linear, curvilinear, multilinear or "no profile" effects. Judges' ratings of pain intensity profiles were found to be less reliable than ratings based on empirical analysis. The majority of patients showed linear profiles while 26% of the patients showed no consistent relationship between hourly pain intensity and time of day. Patients who showed no consistent trend in their pain ratings reported having significantly higher ratings of emotional distress. They tended to have conflicts at home and showed more pain behavior than patients who had a distinct pain profile. Support is given for the potential clinical utility of pain rating profiles. 
Intrathoracic complications following allogeneic bone marrow transplantation: CT findings. The authors retrospectively reviewed computed tomographic (CT) scans of 18 patients who developed 21 episodes of intrathoracic complications after allogeneic bone marrow transplantation (BMT). Pathologic and/or microbiologic diagnoses were available for all patients. All patients were immunocompromised due to either graft-versus-host disease (GVHD), neutropenia, or recurrent malignancy after BMT. CT demonstrated diagnostically relevant findings that were not apparent at radiography in 12 of the 21 cases (57%). These included a ground-glass pattern in early pneumonia (n = 5); a peripheral distribution in GVHD, bronchiolitis obliterans organizing pneumonia, and eosinophilic drug reaction (n = 4); cavitating lesions in Pneumocystis carinii pneumonia (n = 1); hemorrhagic infarcts in aspergillosis (n = 1); and mediastinal adenopathy in recurrent Hodgkin disease (n = 1). The authors conclude that chest CT is superior to radiography in demonstrating the presence, distribution, and extent of intrathoracic complications developing in patients after allogeneic BMT. CT is useful in guiding procedures for tissue diagnosis. 
Resting energy expenditure in patients with newly detected gastric and colorectal cancers. Resting energy expenditure (REE) was measured in 104 patients with newly detected gastric or colorectal (GCR) cancer and was compared with two groups of control subjects without cancer: healthy subjects (H control subjects) and patients with nonmalignant diseases of the gastrointestinal tract (GI patients). REE in GCR-cancer patients was not significantly different from REE in GI patients or H control subjects. Comparison of measured REE with predicted REE obtained from prediction equations may erroneously suggest that increased REE is a contributing factor in the development of cancer cachexia. No significant differences in REE were found when patients with liver metastases were compared with patients without metastases. There were no differences in REE between gastric and colorectal cancer patients. The decrease in energy expenditure, which normally occurs during starvation and weight loss in healthy men and women, could not be demonstrated in weight-losing, GCR-cancer patients. In conclusion, elevation of REE contributes little to the pathogenesis of cancer cachexia in GCR-cancer patients. 
Caesarean section in undiagnosed Eisenmenger's syndrome. Report of a patient with a fatal outcome. An obstetric patient is described in whom the first sign of cardiac disease was unexplained hypoxaemia during emergency anaesthesia for antepartum haemorrhage, with an eventual fatal outcome. The case highlights the importance of patient information at the booking clinic, and the implications of a raised haemaglobin in early pregnancy. 
Acute airway obstruction, hypertension and kyphoscoliosis. An elderly woman developed acute respiratory obstruction after choking on a bolus of food. On rigid bronchoscopy no foreign body, or anatomical obstruction was seen, but airway obstruction recurred during emergence from general anaesthesia, and was thought to be functional in nature. A recurring airway obstruction followed, relieved by induction of anaesthesia and by sedation. This was subsequently demonstrated to be caused by a tortuous aorta which impinged intermittently on the anterior tracheal wall, as a result of kyphoscoliosis of the thoracic spine. We attribute the relief of airway obstruction by general anaesthesia to a reduction in arterial blood pressure. 
Serum immune response to Helicobacter pylori in children: epidemiologic and clinical applications. Antibody responses to Helicobacter pylori were measured by a solid-phase whole-cell enzyme-linked immunosorbent assay in 150 children and adolescents; in 47 consecutive children undergoing upper gastrointestinal endoscopy, including 17 with H. pylori infection before and after antimicrobial treatment; and in 46 family members of the infected children. Abnormal levels of either IgG or IgA were found in 6% of the 150 children. In the latter group the prevalence of H. pylori seropositivity increased with age. Parents and siblings of the infected children had 94% and 71% seropositivity, respectively, suggesting intrafamilial spread. Abnormal levels of IgG or IgA against H. pylori identified infected children with 95% sensitivity and 84% specificity. Eradication of the infection was accompanied by a significant decrease in IgG and IgA titers, with normalization in 10 cured patients in 12 months or less. We conclude that the method described for evaluation of H. pylori-specific IgG and IgA antibodies gives helpful information on the epidemiology of the infection and represents a useful adjunct to diagnosis and management of chronic gastritis in children. 
Endothelium-dependent responses of cerebral blood vessels during chronic hypertension. Acetylcholine produces less dilatation of pial arterioles in stroke-prone spontaneously hypertensive rats (SHRSP) than in normotensive (WKY) rats. Responses of cerebral vessels to acetylcholine and bradykinin appear to involve different mechanisms. Our first goal was to determine whether responses of pial arterioles to bradykinin are impaired in SHRSP. Diameter of pial arterioles (20-60 microns) was measured using intravital microscopy in WKY rats and SHRSP (9-12 months old). Superfusion of bradykinin (3 x 10(-7) M) dilated pial arterioles by 35 +/- 6% (mean +/- SEM) in WKY rats, but only 21 +/- 3% in SHRSP (p less than 0.05 versus WKY rats). Both nitric oxide (5 x 10(-7) M) and nitroglycerin (10(-5) M) produced similar vasodilatation in WKY rats and SHRSP. Our second goal was to determine whether alteration of postreceptor mechanisms contributes to impairment of endothelium-dependent cerebral vasodilatation in SHRSP. Calcium ionophore A23187 (10(-5) M) produced more vasodilatation in WKY rats than in SHRSP (32 +/- 8% versus 9 +/- 4%, p less than 0.05). Responses to A23187 (10(-5) M) were inhibited by indomethacin (46 +/- 13% versus 15 +/- 5%, p less than 0.05) in WKY rats, whereas responses to A23187 (10(-6) M) were potentiated modestly by indomethacin (-3 +/- 2% versus 4 +/- 2%, p less than 0.05) in SHRSP. 
Molecular epidemiology and the genetics of environmental cancer. Environmental, occupational, and recreational exposures to carcinogens contribute to cancer risk in humans. Cancer formation is a multistage process involving tumor initiation, promotion, conversion, and progression. Carcinogens can affect any of these stages through genetic and epigenetic mechanisms. The association of a suspected carcinogenic exposure and cancer risk can be studied in populations with classic epidemiologic techniques. However, these techniques are not applicable to the assessment of risk in individuals. Molecular epidemiology, in contrast, is a field that integrates molecular biology, in vitro and in vivo laboratory models, biochemistry, and epidemiology to infer individual cancer risk. Carcinogen-macromolecular adduct levels, and somatic cell mutations can be measured to determine the biologically effective dose of a carcinogen. Molecular epidemiology also explores host cancer susceptibilities, such as carcinogen metabolic activation, DNA repair, endogenous mutation rates, and inheritance of mutated tumor suppressor genes. Substantial interindividual variation for each of these biologic end points has been shown and, therefore, highlights the need for assessing cancer risk on an individual basis. Given the pace of the last decade, it is feasible that the next 10 years will allow molecular epidemiologists to develop a cancer-risk profile for an individual that includes assessment of a number of factors. This will help focus preventive strategies and strengthen quantitative risk assessments. 
Abnormal small bowel permeability and duodenitis in recurrent abdominal pain. Thirty nine children with recurrent abdominal pain aged between 5.5 and 12 years, underwent endoscopic duodenal biopsy to find out if there were any duodenal inflammatory changes, and if there was a relationship between duodenal inflammation and intestinal permeability to 51Cr-EDTA. Duodenal inflammation was graded by the duodenitis scale of Whitehead et al (grade 0, 1, 2, and 3). In 13 out of 39 patients (33%) definite signs of inflammation were found (grade 2 and 3). Intestinal permeability to 51Cr-EDTA in patients with duodenitis (grade 1, 2, and 3) was significantly higher (4.42 (1.73)%) than in patients with normal (grade 0) duodenal biopsy appearances (3.3 (0.9)%). A significant association was found between duodenal inflammation and abnormal intestinal permeability. Our results give further evidence that there is an intestinal origin of these patients' complaints. 
Clinical evaluation of closed-loop control of blood pressure in seriously ill patients. OBJECTIVE: To compare the effectiveness of a new method of closed-loop (automatic) control of BP with usual manual control. DESIGN: Within-subject crossover trial. SETTING: General and open heart ICUs in a university teaching hospital. PATIENTS: Convenience sample of 74 seriously ill patients aged 17 to 88 yr. Twenty had hypertension: postoperative (n = 7), neurologic damage (n = 6), miscellaneous (n = 7), and were prescribed nitroprusside (n = 11) or nitroglycerin (n = 9). Fifty-four had hypotension: septic (n = 33), other (n = 21), and were prescribed norepinephrine (n = 30), dopamine (n = 11), epinephrine (n = 8), or dobutamine (n = 5). An additional 21 trials were omitted from analysis because of technical (n = 7), clinical (n = 1), or drug-related problems (n = 13). INTERVENTION: Closed-loop and manual drug administrations 1-hr were studied during periods in each patient. The target and observed mean arterial pressure (MAP) and drug infusion rate were recorded electronically every 30 sec. MAIN OUTCOME MEASUREMENTS: Time taken to achieve initial control (min); fidelity of control (the integral of size and duration of error from target MAP +/- 10% in mm Hg.hr/hr); and average drug dose administered (microgram/min as % maximum possible per drug). RESULTS: Compared with manual control, closed-loop achieved faster initial control (log-rank chi 1 = 5.04, p less than .05) and greater fidelity (mean 1.37 vs. 2.36; F = 7.15, p less than .01). There was no difference in average drug dose administered. There was uniformity in the efficacy advantage of closed-loop drug administration across drugs and patient classifications. CONCLUSION: The new closed-loop system is more effective than the usual manual control in managing acute BP disturbances in the seriously ill patient. 
Hemodynamic and oxygen transport changes following endotracheal suctioning in trauma patients. Hemodynamic and oxygen transport responses to four preoxygenation techniques prior to endotracheal suctioning (ETS) were evaluated in 24 critically ill trauma patients with no preexisting lung disease. A within-subjects, repeated measures design was used. All patients had functional arterial and pulmonary artery catheters and were ventilated with a Puritan-Bennett 7200 which could immediately deliver a fraction of inspired oxygen (FIO2) of 1.0. Six breaths of maintenance FIO2 and hyperinflation without hyperoxygenation caused a fall in tissue oxygen delivery as measured by continuous transcutaneous oximetry (PtcO2). The largest increases in PtcO2 and arterial oxygen tension were seen with hyperoxygenation alone and a combination of hyperoxygenation and hyperinflation. No significant changes were found in hemodynamic (cardiac index, mean arterial pressure, mean pulmonary artery pressure, pulmonary capillary wedge pressure, systemic vascular resistance, pulmonary vascular resistance) or oxygen transport variables (oxygen delivery, oxygen extraction, oxygen consumption) 5 minutes postsuctioning. During both hyperinflation protocols, patients experienced dyspnea. It was concluded that three hyperoxygenation breaths before ETS, using a clinically feasible protocol, are adequate in preventing postsuction hypoxemia in young, hemodynamically stable trauma patients. Large volumes of hyperinflation, although found to increase PtcO2, are not advocated because of demonstrated patient discomfort and the possibility of barotrauma. 
1990 ARRS Executive Council Award. Intravascular sonography in the detection of arteriosclerosis and evaluation of vascular interventional procedures. The purpose of this study was to evaluate the use of intravascular sonography for the detection of arteriosclerosis and to determine the effects of vascular interventional procedures on the arterial wall. A catheter-based 20-MHz transducer was used. Forty patients were studied. Twelve had clinical evidence of peripheral vascular disease, 13 were healthy renal donors, and 15 underwent vascular interventional procedures. The aorta and the ipsilateral iliac artery were examined in real time under fluoroscopic guidance and the results were compared with angiography. Sonography in eight of the 13 renal donors showed arterial wall abnormalities in the absence of angiographic evidence of disease. Sonography of the 15 patients after angioplasty or atherectomy demonstrated plaque fractures, intramural dissections, or atherectomy grooves. Our experience suggests that intravascular sonography is of value in reducing the use of angiography to monitor progress or complications of vascular interventional procedures. 
Bilateral episodic mydriasis as a migraine equivalent in childhood: a case report. We report a 14-year-old girl who presented with yearly attacks of bilateral internal ophthalmoplegia, nausea and headache, since the age of nine. The episodic isolated bilateral mydriasis in this child is believed to be a migraine equivalent. 
Altered swallowing function in elderly patients without dysphagia: radiologic findings in 56 cases. Swallowing disorder is an increasing problem in our aging population. A majority of these patients have a functional abnormality of the oral, pharyngeal, and/or esophageal stage of swallowing. However, what constitutes normalcy is not well understood, and baseline swallowing in elderly persons without dysphagia has not been adequately described. We therefore evaluated 56 persons with a mean age of 83 years who had no symptoms of dysphagia or eating difficulty. Videofluoroscopy and radiographs with the subject erect and recumbent were obtained. Normal deglutition, as defined in young persons, was present in only 16%. Oral abnormalities (difficulty ingesting, controlling, and delivering bolus relative to swallowing initiation) were seen in 63%. Pharyngeal dysfunction (bolus retention and lingual propulsion or pharyngeal constrictor paresis) was seen in 25%. Pharyngoesophageal segment abnormalities were observed in 39% (mostly cricopharyngeal muscle dysfunction). Esophageal abnormalities (mostly motor in nature) were observed in 36%. What has been described as swallowing dysfunction in young persons may not be abnormal in very elderly persons. It is difficult to distinguish the effect of normal aging from the effects of specific diseases or gradual degenerative changes. 
Double intensive consolidation chemotherapy in adult acute myeloid leukemia. Of 115 adult patients with de novo acute myeloid leukemia (AML), 87 (75.5%) achieved complete remission (CR) after induction treatment with zorubicin and conventional doses of cytarabine (Ara-C). Patients under age 45 years with histocompatibility locus antigen-identical sibling underwent bone marrow transplantation (BMT). The others were treated with two courses of intensive consolidation chemotherapy (ICC): course 1 with 4 days of high-dose Ara-C and 3 days of amsacrine (m-AMSA); course 2 with carmustine (BCNU), Ara-C, cyclophosphamide, and etoposide. Forty-two patients received both planned courses, 15 received only the first, and 13 patients could only support conventional maintenance therapy. Four patients died during consolidation. With a median follow-up of 60 months, the disease-free survival (DFS) after ICC at 5 years is 40.3% (+/- 6.5%), with no statistically significant difference between patients receiving one or two courses. The DFS for the 17 transplanted patients is comparable (P = .72) and is lower for the 13 excluded patients (23% +/- 11.5%, P = .046). Age did not influence the probability of remaining in CR. In univariate analysis, three parameters had a negative impact on the 5-year DFS: a high initial WBC count (52% for patients with less than 30 x 10(9) WBC/L v 12% for patients with greater than 30 x 10(9) WBC/L, P = .01), a long delay between induction treatment and course 1 (+/- 60 days; 63% v 29%, P = .01), and a long delay between course 1 and course 2 (+/- 60 days, 61.5% v 28.5%, P = .05). In multivariate analysis (Cox model), only the WBC count remained significant. This study confirms the value of intensive postremission chemotherapy, which can be compared in AML with allogeneic or autologous BMT. It also demonstrates the prognostic value of the initial WBC count. The optimal modalities of ICC remain to be defined by further studies. 
Intravascular IL-8. Inhibitor of polymorphonuclear leukocyte accumulation at sites of acute inflammation. IL-8 has been characterized primarily as a polymorphonuclear leukocyte (PMN) chemoattractant and proinflammatory mediator. Recently, we have reported that [Ala-IL-8]77 is secreted by activated cultured human endothelial cells and can function as a potent inhibitor of PMN adhesion to these monolayers. The pathophysiologic relevance of this in vitro observation was examined by determining the effects of intravascular or extravascular administration of IL-8 on PMN emigration at sites of acute inflammation in the skin of NZW rabbits. An i.v. bolus of [Ala-IL-8]77 (12 micrograms/kg) produced a marked and selective reduction of circulating PMN within 3 min, which returned toward preinjection levels within 30 min, and subsequently exceeded this level. A similar response was observed for circulating radiolabeled PMN, and gamma-scintigraphy determined that the lungs were the primary site of leukosequestration. During the 30- to 150-min interval after i.v. infusion of [Ala-IL-8]77, PMN emigration into acute inflammatory sites, elicited by various chemoattractants or cytokines, was significantly reduced, as judged histologically and quantitated with 51Cr-labeled PMN and myeloperoxidase measurements. Intravenous administration of [Ser-IL-8]72 yielded similar results. This inhibitory effect of i.v. IL-8 was transient and reinducible and did not reflect a suppression of the responsiveness of circulating PMN to chemoattractants. Intradermal injections of [Ala-IL-8]77 or [Ser-IL-8]72 induced dose-dependent PMN accumulation, which also was significantly reduced by i.v. administration of either form of IL-8. These results indicate that i.v. IL-8 can function as a PMN-directed leukocyte adhesion inhibitor and suggest that local secretion of IL-8 by activated endothelium may differentially modulate leukocyte-endothelial interactions at sites of acute inflammation. 
Acute and chronic urticaria and angioedema. Urticaria and angioedema are clinical manifestations of various immunologic and inflammatory mechanisms, or they may be idiopathic. The respiratory and gastrointestinal tracts as well as the cardiovascular system may be involved in any combination. Patients with urticaria and/or angioedema can be classified based on pathophysiologic mechanisms into those with IgE-dependent or complement-mediated immunologic disorders, those with nonimmunologic disorders in which there is a direct effect on the mast cell or on arachidonic acid metabolism, and those whose condition is idiopathic. Evaluation of patients should focus on a thorough history. Laboratory tests provide minimal additional information. About one half of patients with urticaria alone and 25% with urticaria and angioedema or angioedema alone are free of lesions within 1 year. With urticaria, angioedema, or both, 20% of patients experience episodes for more than 20 years. 
Breathing during sleep in patients treated for obstructive sleep apnea. Nasal CPAP for only part of the night. To determine whether long-term NCPAP therapy influences severity of sleep disordered breathing during the second part of a night when NCPAP is applied for only the first four hours of sleep, we studied 21 patients with OSA receiving NCPAP therapy for 253 +/- 41.6 days. Results from polysomnography for the period after withdrawal from NCPAP (night B) were compared to the corresponding period of sleep prior to initiation of NCPAP therapy (night A). There was no significant change in RDI from night A (53.9 +/- 8.6) to night B (28.7 +/- 3.3), but maximal apnea length diminished from 55 +/- 2.9 s to 40 +/- 2.9 s (p less than 0.05). Whereas daytime Po2 and the amplitude of desaturations during sleep remained equal, overall oxygenation during sleep improved slightly (mean SaO2 night A = 90.6 +/- 0.9 percent; night B = 92.8 +/- 0.5 percent; p less than 0.05). Differences between nights A and B were more prominent the more severe sleep apnea had been prior to treatment and could not be explained by weight loss. There was strong correlation between improvements in oxygenation measurements and the daily time of NCPAP use. In conclusion, we found a subgroup of OSA patients receiving long-term NCPAP therapy with less disturbed ventilation during sleep following use of NCPAP for only the first part of the night, but in the majority of patients, sleep disordered breathing off NCPAP remained unchanged. 
Synchronous lung cancers defined by deoxyribonucleic acid flow cytometry. When two pulmonary tumors are seen simultaneously in patients with lung cancer, it always raises a question as to whether the lesions are synchronous lung cancers or lung cancer with intrapulmonary metastasis. To settle this issue, we used deoxyribonucleic acid flow cytometry. Deoxyribonucleic acid ploidy patterns of tumors were able to be analyzed in 14 patients with two simultaneous pulmonary tumors resected by operation. These two tumors, with completely different patterns of deoxyribonucleic acid ploidy, were defined as synchronous lung cancers. Tumors were defined as lung cancer with intrapulmonary metastasis when both tumors showed diploidy or when at least one deoxyribonucleic acid index of abnormal clones between two aneuploid tumors was the same or almost identical. Tumors of the five patients with stage I disease were classified as synchronous lung cancers according to the criteria involving deoxyribonucleic acid flow cytometry. Both tumors were adenocarcinomas in four patients and large-cell and squamous cell carcinomas in one. Both tumors in four patients were located in the same lobe but different segments. All but one patient with different histologic types are alive without recurrence from 24 to 100 months after operation. Tumors of the nine patients with stage III disease in whom intrapulmonary metastasis was clinically suspected were classified as lung cancer with intrapulmonary metastasis according to the criteria. These data suggest that deoxyribonucleic acid flow cytometry of tumors may have diagnostic value in determining synchronous lung cancers. 
Inferior vena caval involvement by renal cell carcinoma. Use of venovenous bypass as adjunct during resection. Venovenous bypass allows the safe conduct of operation during resection of renal cell carcinoma with inferior vena caval involvement by allowing venous return when the inferior vena cava is clamped, thus preventing hypotension. It obviates the heparin required for full cardiopulmonary bypass and therefore decreases postoperative bleeding. A blood retrieval system decreases the volume of banked blood required. A Moretz clip placed early on the intrapericardial inferior vena cava allows adequate venous return and prevents a massive pulmonary tumor embolism. 
Aortoesophageal fistula: a comprehensive review of the literature. Aortoesophageal fistula (AEF) is a relatively rare but life-threatening cause of upper gastro-intestinal bleeding. The clinical characteristics of AEF are so unique that a presumptive bedside diagnosis can be made at the time of presentation. In the past decade, surgical management has improved to the point that cure is now possible. For these reasons, we have reviewed the literature. We summarize our findings with respect to the etiology and clinical characteristics of AEF. Further, we discuss the diagnostic modalities that may be used to confirm the diagnosis, and the therapeutic modalities available to slow the hemorrhage, so as to allow time to correct the anatomic defect. 
Metastases of a gastric adenocarcinoma presenting as colonic polyposis. Report of a case. The authors report a case of multiple colonic metastases of a gastric signet ring cell adenocarcinoma, presenting as colonic polyposis revealed by diarrhea, iron deficiency anemia, and left supraclavicular lymph node. 
Placenta previa percreta involving the urinary bladder: a report of two cases and review of the literature. The incidences of both placenta previa and placenta accreta are increased in patients with scarred uteri, and patients with uterine scars and placenta previa are at increased risk for also having placenta accreta. Two cases are presented of placenta previa percreta with involvement of the urinary bladder necessitating cesarean hysterectomy, partial cystectomy, and, in one case, bilateral ureteral reimplantation. Both patients had two previous cesarean deliveries. Serious hemorrhage is common in patients with placenta percreta. The primary goal of surgical management must be to control bleeding, which usually requires resection of all tissue involved by the infiltrating placenta. After hemorrhage is controlled, the surgeon must reestablish the integrity of the urinary system and reconstruct the pelvis as necessary. 
Porencephalic cyst: a complication of fetal intravascular transfusion. A case of unilateral porencephalic cyst as a result of intravascular intrauterine transfusion is reported. Although other factors may have contributed, fetal bradycardia and relative hyperviscosity as a result of increased fetal hematocrit value were considered to be related to this event. Because some authors recommend direct intravascular transfusion to supraphysiologic hematocrits to prolong the interval between procedures, we would caution the use of this approach on the basis of theoretic considerations and the occurrence of this complication. 
Suppressive effect of sulfate on the development of hypertension in DOCA-salt hypertensive rats. The purpose of this study was to examine the effect of the sulfate ion on blood pressure in DOCA-salt hypertension, which involves increased sympathetic nervous activity. Male Wistar rats were divided into four groups, and received one of the following drinking solutions: distilled water [control], 171 mmol/L sodium chloride [NaCl group], 171 mmol/L sodium chloride plus 12 mmol/L magnesium sulfate [S(+) group], or 171 mmol/L sodium chloride plus 12 mmol/L magnesium chloride [S(-) group]. In the S(+) group, the elevation of systolic blood pressure (SBP; mm Hg) was significantly attenuated (168 +/- 17 v 213 +/- 26, P less than .005) and intraerythrocyte calcium concentration (R-Ca; mumol/L cells) was significantly lower (11.5 +/- 3.0 v 17.4 +/- 6.5, P less than .05) than in the S(-) group. The cardiac norepinephrine content (H-NE; ng/100 g tissue) of the S(+) group was significantly lower than that of the S(-) group. SBP was correlated negatively with H-NE (r = -0.70, P less than .001) and positively with R-Ca (r = 0.45, P less than .005). R-Ca was negatively correlated with H-NE (r = -0.36, P less than .05). These results suggest that the replacement of chloride with sulfate ion suppresses the development of hypertension in DOCA-salt rats at least in part by its inhibitory effect on sympathetic nervous activity through the decreased intracellular calcium concentration. 
Physiologic stress and cellular ischemia: relationship to immunosuppression and susceptibility to sepsis. Multiple organ system failure secondary to infection is the most frequent cause of late mortality after hemorrhage, burns, and trauma. Although multiple immunologic abnormalities have been identified following injury, blood loss, and tissue ischemia, the mechanisms that produce these alterations in T- and B-cell function have not been completely defined. Physiologic stress and ischemia result in increased release of neuroendocrine peptides and hormones, capable of affecting normal neuroendocrine-immunologic balance and producing immunosuppression. Tissue ischemia leads to increased expression of heat shock proteins by hypoperfused cells, which can alter T-cell function. Injury also is followed by the appearance of serum immunosuppressive factors, which have been shown to inhibit T- and B-cell function. Future therapies directed at these and other cellular and molecular abnormalities initiated by tissue hypoperfusion may reverse the immunosuppressed state in critically ill patients and lead to improved outcome in this setting. 
Metachronous occurrence of collagenous colitis and ulcerative colitis. Collagenous colitis and ulcerative colitis are distinct disorders. A 67 year old woman with clinical and histological evidence of collagenous colitis had an abrupt symptomatic exacerbation while taking anti-inflammatory treatment with sulphasalazine and prednisone. Repeat colorectal endoscopy showed active mucosal inflammation and colonic biopsy specimens were consistent with active ulcerative colitis. After bowel rest, total parenteral nutrition, intensification of the anti-inflammatory regimen, and withdrawal of non-steroidal anti-inflammatory drugs (which she had taken continuously for osteoarthritis) diarrhoea abated. Colorectal biopsy specimens obtained when the patient's symptoms had improved showed inactive ulcerative colitis with no evidence of collagenous colitis. This may be the first case to be reported of the metachronous association of collagenous and ulcerative colitis. 
The use of aspirin to prevent heterotopic ossification after total hip arthroplasty. A preliminary report. The reported incidence of heterotopic ossification (HO) after total hip arthroplasty (THA) ranges up to 50%. HO causes pain and restricted range of motion (ROM) in a significant number of these THA patients. From 1983 to 1988, 177 primary cemented THAs were performed in 131 consecutive patients. Six hundred fifty milligrams of buffered aspirin administered twice daily for two weeks was used as a prophylaxis for thromboembolic disease. There was an unusually low incidence of HO in this group of patients. Aspirin treatment was instituted the night before surgery and continued for two weeks, except in 13 patients (7%) who had to stop treatment because of gastrointestinal symptoms. All patients had at least one year of roentgenographic study postoperatively. According to the Brooker Classification of HO, there were 169 (96%) Grade I and Grade 0 hips, six (3%) Grade II, two (1%) Grade III, and no Grade IV. None of the patients had symptomatic restriction of ROM attributable to heterotopic bone. Aspirin is a safe and inexpensive agent for prevention of HO after THA. 
Salvage of thrombosed forearm polytetrafluoroethylene vascular access grafts by reversal of flow direction and venous bypass grafting. A technique is described for salvage of looped forearm polytetrafluoroethylene (PTFE) vascular access grafts that fail because of thrombosis due to cephalic vein outflow obstruction. It entails reversal of blood flow direction through the graft and construction of a new venous outflow in the medial upper arm. This procedure was performed in nine patients and, at the present time, has increased the graft life by an average of 6.2 months (range: 2 to 14 months) in eight. We conclude that this is a useful alternative to abandoning failed looped forearm PTFE grafts that have cephalic vein outflow obstruction. 
High rate of portal thrombosis after splenectomy in patients with esophageal varices and idiopathic portal hypertension. Data on 126 consecutive patients who were admitted to our clinics from January 1979 to May 1989 were scrutinized to assess changes in portal hemodynamics following splenectomy. Two groups were classified: (1) a group of 106 patients with cirrhosis of the liver and (2) a group of 20 patients with idiopathic portal hypertension (IPH). Portal thrombosis was present in five (25.0%) of the 20 patients with IPH and in two (1.8%) of the 106 patients with cirrhosis of the liver. As seen on celiac arteriography, the mean (+/- SD) diameter of the trunk of the splenic artery and vein was 8.99 +/- 1.55 and 16.2 +/- 3.6 mm, respectively, in patients with IPH, while it was 7.94 +/- 1.28 and 14.2 +/- 3.1 mm, respectively, in patients with cirrhosis of the liver. Changes in portal venous pressure were 78.4 +/- 59.4 mm H2O in patients with IPH and 43.5 +/- 38.7 mm H2O in patients with cirrhosis of the liver. There were no significant differences in the maximum level of thrombocytes in patients with IPH or in those patients with cirrhosis of the liver. These events suggest that portal thrombosis can occur with a significantly higher incidence in patients with IPH than in those patients with cirrhosis of the liver after splenectomy, and a decrease in blood flow in the portal vein may be closely linked to the formation of portal thrombosis after splenectomy in patients with IPH. Preoperative examination of portal hemodynamics must be thorough. 
The value of Doppler echocardiography in the management of patients with valvular heart disease: analysis of one year of clinical practice. Management recommendations based on Doppler echocardiographic examination and cardiac catheterization were compared in a prospective study in 100 consecutive patients who were admitted for evaluation and treatment of suspected valvular heart disease during 1988. Management recommendations were provided independently after both Doppler echocardiography and cardiac catheterization by different and blinded investigators. Criteria for severe (clinically significant) and moderate to mild (insignificant) valvular lesions and management recommendations were agreed on in advance. There was disagreement on the severity of aortic stenosis based on the aortic valve area and maximum instantaneous pressure gradient in 1 of 54 patients, which resulted in differing management recommendations. Mitral stenosis was severe (valve area less than or equal to 1 cm2) at Doppler echocardiography but not at cardiac catheterization in 5 of 14 patients. Because pulmonary artery pressure increase during exercise at cardiac catheterization also suggested severe obstruction, management recommendations were similar. There was a potentially significant disagreement on the severity of aortic regurgitation in 9 of 76 patients and of mitral regurgitation in 14 of 90 patients; however, this did not produce differing management recommendations because with most patients coexistent valvular lesions or an impaired ventricular function mainly determined the ultimate management decision. Although of good quality, Doppler echocardiographic examination was nonconclusive for clinical decision-making in 15% of the study population because of uncertainty about the severity of mitral regurgitation or aortic regurgitation or because of problems in assessing the degree of left ventricular dysfunction in patients with severe regurgitation. 
Sexual asphyxia in siblings. We present an accidental autoerotic asphyxiation of a 24-year-old man. Further investigation revealed that 18 years earlier, his brother, then 13, had been found dead, hanging in the family bathroom. Although that death had been ruled a suicide, reevaluation of the death scene indicates that this was also an autoerotic asphyxiation. This is the first reported case of sexual asphyxia involving siblings. 
Larynx preservation with combined chemotherapy and radiation therapy in advanced but resectable head and neck cancer. Forty patients with advanced, resectable squamous cell carcinoma of the larynx, oropharynx, or hypopharynx whose surgery would have required total laryngectomy (TL), were treated with one to three cycles of cisplatin-based chemotherapy before local therapy with the goal of larynx preservation. Clinical complete responses (CRs) or partial responses (PRs) to chemotherapy were seen in 26 of 40 patients (65%). Three patients with primary-site disease unresponsive to chemotherapy underwent resection of the primary lesion and neck dissection followed by radiation therapy (RT). Thirty-seven patients were referred after chemotherapy for RT +/- neck dissection. Thirty-one of 40 patient (78%) were rendered disease-free (no evidence of disease [NED]). With a median follow-up of 49 months (range, 31 to 76), the overall actuarial survival rate for the group was 58% at 2 years and 33% at 5 years. The failure-free survival rate was 42% and 33% at 2 and 5 years, respectively. Seven patients refused recommended TL throughout their course. This may have adversely affected survival results. A greater proportion of patients who achieved a CR or PR to chemotherapy remained disease-free compared with those who achieved less than a PR (P less than .001). Sixteen patients relapsed, 10 with locoregional disease. Six patients underwent TL, either for initial induction failure or at relapse, for an actual larynx-preservation rate of 34 of 40 patients (85%). If the seven patients who refused TL are included, the anticipated preservation rate is 27 of 40 patients (68%). Larynx preservation with combined chemotherapy and radiation is feasible and effective in patients with advanced, resectable squamous cell carcinoma of the head and neck (SCHN). This treatment approach requires a motivated patient, careful patient monitoring, and close interdisciplinary cooperation among oncologists. 
Development of a novel 1,25(OH)2-vitamin D3 analog with potent ability to induce HL-60 cell differentiation without modulating calcium metabolism. We describe several novel analogs of the seco-steroid 1,25(OH)2-vitamin D3[1,25(OH)2D3] and their effects on differentiation and proliferation of HL-60 human myeloid leukemic cells in vitro as well as their effects on calcium metabolism in vivo. The 1 alpha-25(OH)2-16ene-23yne-26,27F6-vitamin D3 is the most potent analog reported to date, having about 80-fold more activity than the reference 1,25(OH)2D3 for inhibition of proliferation and induction of differentiation of HL-60 cells. Also, this analog decreased RNA expression of MYC oncogene in HL-60 by 90% at 5 x 10(-10) mol/L. Intriguingly, intestinal calcium absorption and bone calcium mobilization mediated in vivo by 1 alpha-25(OH)2-16ene-23yne-26,27F6-D3 was found to be markedly (15-fold) less than that of 1,25(OH)2D3. In addition, 1 alpha-25(OH)2D3 bound to 1,25(OH)2D3 receptors of both HL-60 and intestine more avidly than did 1 alpha-25(OH)2-16ene-23yne-26,27F6-D3. This novel analog may open up new therapeutic strategies for several hematopoietic, skin, and bone abnormalities and may provide a new tool to understand how vitamin D3 seco-steroids induce cellular differentiation. 
Identification of the proximal neck of giant paraclinoidal aneurysms. Technical note. Introduction of a double-lumen Swan-Ganz balloon catheter into the parent artery facilitated precise identification of the proximal neck in two giant paraclinoidal aneurysms. Reduction of the flow rate as low as possible and positioning of the patient's head were the most important factors in this procedure. 
Glutethimide treatment of disabling action tremor in patients with multiple sclerosis and traumatic brain injury. Glutethimide has been used to control essential tremor. Its efficacy in the treatment of disabling cerebellar and rubral tremor was assessed in an open study of six patients with multiple sclerosis and two patients with traumatic brain injury. Functional and quantitative tremor severity was assessed before treatment and 7 to 14 days after a stable dose was achieved. Six of eight patients exhibited visible functional benefit from treatment with glutethimide; abstract testing results correlated well with functional status in most cases. Four patients chose to continue to receive medication. Controlled trials of glutethimide to compare its efficacy with that of other medications used in the treatment of action tremor are indicated. 
Short-course versus long-course antibiotic treatment of spontaneous bacterial peritonitis. A randomized controlled study of 100 patients. In an attempt to determine the optimal duration of therapy of spontaneous bacterial peritonitis, 100 patients with neutrocytic ascites and suspected spontaneous bacterial peritonitis were randomized to short-course vs. long-course treatment groups. Empiric therapy was initiated before the results of ascitic fluid culture were available. Of the 90 patients who met strict criteria for spontaneous bacterial peritonitis or culture-negative neutrocytic ascites, 43 were randomized to a group receiving 5 days and 47 to a group receiving 10 days of single-agent cefotaxime, 2 g IV every 8 hours. Infection-related mortality (0% vs. 4.3%), hospitalization mortality (32.6% vs. 42.5%), bacteriologic cure (93.1% vs. 91.2%), and recurrence of ascitic fluid infection (11.6% vs. 12.8%) were not significantly different between the 5- and 10-day treatment groups, respectively. Recurrence rates were comparable to the values reported in the literature. The cost of antibiotic and antibiotic administration were significantly lower in the short-course group. Short-course treatment of spontaneous bacterial peritonitis is as efficacious as long-course therapy and significantly less expensive. 
Acid secretion and suppression. Hydrochloric acid is involved in the causation of peptic ulcer, but the exact role has not been defined. Suppression of acid secretion is associated with ulcer healing. The acid secreting cell is the parietal cell, which possesses a proton pump in the secretory membrane; morphologic changes accompany and facilitate the active secretion of hydrochloric acid. Stimulation of acid secretion occurs by three major pathways, which utilize acetylcholine, histamine, and gastrin. The predominant effects of histamine are mediated by adenylate cyclase, whereas those of gastrin and acetylcholine involve cytosolic calcium. There is a complicated arrangement of receptors and pathways that culminate in the activation of the proton pump. The parietal cell is influenced by neurocrine, hormonal, and paracrine mechanisms. Peptides join the more familiar neurotransmitters in affecting the parietal cell. Somatostatin is present in the gut and acts to decrease acid secretion. The hormone gastrin is released, in a feedback fashion, when the antrum is alkalinized. Most stimuli of acid secretion are blocked by H2-antagonists. Inhibitory hormones are released when acid arrives in the intestine. Inhibition of acid secretion can be achieved by influencing the parietal cell at the level of histamine, gastrin, and muscarinic receptors. The proton pump itself can be blocked by drugs that inhibit the final phase of acid secretion. 
Platelet emboli in rat brain cross when the contralateral carotid artery is occluded. The pathogenesis of embolic events ipsilateral to an occluded carotid artery is uncertain. To examine this question we combined occlusion of the left common carotid artery with embolism from the right common carotid artery in rats. Following ligation of the left carotid artery in 20 experimental rats, we irradiated the right carotid artery with a laser (632 nm, 200 mW/cm2, 12-15 minutes) following the intravenous injection of 12.5 mg/kg of the photosensitizing agent Photofrin II. Controls had left carotid artery occlusion with (n = 13) or without (n = 6) Photofrin II. Fifteen of the 20 experimental rats survived to be perfused at 24 hours; cerebral infarcts were identified in 12 rats, with bilateral infarcts in 10. There were 112 infarcts (101 small [less than 2.5 mm] and 11 large [greater than 2.5 mm] on the right and 103 (93 small and 10 large) on the left. Emboli were seen in association with some infarcts and were evenly distributed in the two hemispheres (37 emboli on the right and 40 on the left, with the midline azygous artery occluded in four animals). Left carotid artery occlusion did not produce infarcts or emboli in the controls. We conclude that cerebral infarcts in the distribution of an occluded common carotid artery may be caused by emboli from the contralateral carotid artery in rats. 
Traditional first-line therapy. Overview of medical benefits and side effects. When diuretic-based stepped care was first advocated for the treatment of hypertension, there were fewer classes of antihypertensive medication than there are today. In 1984, the third Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC) for the first time suggested an alternative initial treatment with a beta-blocker in selected hypertensive patients, and the fourth JNC report has recommended the alternatives of calcium channel blockers or angiotensin converting enzyme inhibitors for step-one therapy as well. However, only the diuretic drugs and beta-blockers have been shown to reduce cardiovascular morbidity and mortality in prospective, long-term, controlled trials. Moreover, 30 years' experience with diuretic agents and 20 years' experience with beta-blockers have defined the advantages, disadvantages, and potential side effects of these drugs more precisely than is possible for newer agents. The diuretic drugs and beta-blockers remain excellent choices in the management of hypertension. 
Timing of invasive procedures in therapy for primary and secondary spontaneous pneumothorax. Timing of invasive procedures during chest tube therapy in spontaneous pneumothorax is undefined. Evaluation of 115 patients with primary and secondary spontaneous pneumothorax treated with tube thoracostomy revealed nearly maximal healing rates after 48 hours without a relevant increase if drainage was maintained for up to 10 days. In secondary spontaneous pneumothorax, a significantly lower healing rate was observed after 48 hours compared with primary spontaneous pneumothorax (60% vs 82%). Therapeutic success was not predictable by single clinical variables available at admission (eg, age, gender, and smoking habits) nor by their combinations. Recurrence rates were 30% in both primary and secondary spontaneous pneumothorax. Hospital stay averaged 6 days in primary and 15 days in secondary spontaneous pneumothorax. Considering their efficacy and the low incidence of complications, the early use of invasive procedures such as surgical pleurectomy, after 48 hours of persistent gas leaking, seems justified. Shorter in-patient care and lower recurrence rates may result. 
Focal high signal on MR scans of the midbrain caused by enlarged perivascular spaces: MR-pathologic correlation. Punctate and linear foci of abnormal signal were observed near the substantia nigra in the midbrains of 32 (20%) of 157 patients undergoing high-resolution MR imaging of the brainstem. The lesions were most easily seen on long TR/long TE images, where they were of high signal intensity. Their location was consistently in the lower mesencephalon near the junction of the substantia nigra and cerebral peduncle. Unilateral lesions were observed in 18 cases, while bilateral lesions were noted in 14. A review of anatomic specimens revealed the constant presence of penetrating branches of the collicular or accessory collicular arteries in this location. Enlarged perivascular spaces around these vessels were frequently seen in the specimens and probably account for punctate and linear foci observed on high-resolution MR images of the midbrain. 
Dietary calcium supplementation as a treatment for mild hypertension. The blood pressure responses of 19 mildly hypertensive (diastolic blood pressure 90-104 mmHg) individuals to treatment with either 1200 mg of elemental calcium supplementation or placebo were assessed weekly in a 6-month randomized, double-blind, placebo-controlled crossover study. Both groups showed a decrease in blood pressure (calcium treated: 6 +/- 12 mmHg systolic, 7 +/- 7 mmHg diastolic; and placebo controlled: 9 +/- 14 mmHg systolic, 9 +/- 8 mmHg diastolic). Differences between the two groups were not significant (P greater than 0.1). There were no adverse effects to either treatment. This study does not support the hypothesis that dietary calcium supplementation is more effective than placebo in reducing blood pressure in mildly hypertensive individuals. 
The contributions of interpersonal conflict to chronic pain in the presence or absence of organic pathology. This study investigated the influences of social support and interpersonal conflict on chronic pain in patients with arthritis or with myofascial disorders. Measures of social support, conflict, and pain were drawn from subscales of the McGill Pain Questionnaire, the Multidimensional Pain Inventory, the Family Environment Scale, and the Interpersonal Relationship Inventory. Patients with myofascial disorders reported significantly worse pain (sensory and affective), higher depression scores, more interpersonal conflict, and less support from others than patients with arthritis, but did not differ from them on personality traits. Also, the contributions of conflict to pain were found to depend on the nature of the chronic disorder and on the source of the conflict, i.e., significant other, family, or social network members. For patients with arthritis, less intense pain (sensory and affective) was associated with higher family conflict. Less intense sensory pain in arthritis was also associated with more punishing responses from the significant other to pain. For patients with myofascial disorders, more intense affective pain was associated with higher social network conflict. Social support did not significantly contribute to pain for either group. Thus, chronic painful disorders may differ on the influences that social relationships have on pain. The implications of these differences for treatment are discussed. 
cis-platinum ototoxicity in children. Cis-platinum is an ototoxic antineoplastic drug. Evaluation of auditory thresholds in 33 children receiving cis-platinum shows that a threshold shift at 6 and 8 kHz is first measurable after a cumulative dose of 201 to 300 mg/m2. A 35- to 40-dB high-frequency threshold shift is evident after a cumulative cis-platinum dose of 301 to 400 mg/m2. Increasing cumulative doses of cis-platinum are associated with a greater degree of hearing loss. Receiver-operator characteristic curves were used to find a criterion value that effectively identified threshold shifts that were due to cis-platinum ototoxicity. A 15-dB or greater shift in the 6- and 8-kHz threshold average identifies a high true-positive (50%) and low false-positive (0%) rate of cis-platinum-induced hearing loss. Using this criterion, cis-platinum ototoxicity affected 77% of children who received cis-platinum (median cumulative dose 360 mg/m2). 
Ultrastructural localization of interferon-producing cells in the livers of patients with chronic hepatitis B. Cells expressing alpha- and gamma-interferon were localized in the liver tissue of patients with chronic hepatitis B by means of light and electron microscopy using monoclonal antibodies. Interferon-positive cells were regularly seen in the infiltrating mononuclear cells, and the number showed a good correlation with the degree of the necroinflammatory activity of the disease. In chronic persistent hepatitis and in normal livers, they were infrequent or virtually absent. alpha-Interferon was shown to be positive in lymphocytes, polymorphonuclear leukocytes and fibroblasts, Kupffer cells and, weakly, in the cytoplasm of a few hepatocytes in cases of active hepatitis, whereas gamma-interferon was demonstrated only in lymphocytes. The expression of human leukocyte class I antigens on hepatocytes showed a close association with the number of interferon-producing cells, but not with the presence of virus particles and HBcAg in liver cells, when studied using electron microscopy and double-labeling. Interferon seems to be an important regulator of the local immune response in the liver in patients with chronic hepatitis B. Its functions may play a role in inducing the human leukocyte class I antigen expression on hepatocytes, thus enhancing the elimination of virus-containing hepatocytes by major histocompatibility complex-restricted cytotoxic lymphocytes. 
Factors affecting perioperative pulmonary function in acute respiratory failure. To determine the magnitude, duration, and associated factors of perioperative changes in pulmonary function, we retrospectively reviewed the medical records of 145 patients who required preoperative mechanical ventilation for acute respiratory failure before undergoing 200 surgical procedures. Patients were grouped into five pulmonary diagnostic categories: (1) adult respiratory distress syndrome (ARDS) (n = 49); (2) pneumonia (n = 20); (3) atelectasis (n = 65); (4) congestive heart failure (n = 11); and (5) acute ventilatory failure (n = 55). Sixty patients underwent intra-abdominal surgery, 135 patients required surgery on the periphery, and five patients had a thoracotomy. For all patients, PaO2/FIO2 declined significantly from 321 mm Hg (mean) preoperatively to 258 mm Hg intraoperatively, and shunt fraction (Qs/QT) increased from 0.16 to 0.23 without a significant change in PaCO2. The magnitude of the increase in Qs/QT did not differ among pulmonary diagnostic groups. Preoperatively, patients undergoing laparotomy had lower PaO2/FIO2 (278 vs 340) and higher Qs/QT (0.19 vs 0.14) than patients requiring surgery on the periphery. Intraoperatively, Qs/QT increased more during abdominal procedures than during peripheral procedures. Intraoperative hypoxemia (PaO2/FIO2 less than 80 mm Hg) occurred during 13 procedures. Hypoxemic patients had a mean increase in Qs/QT of 0.20 (0.25 preoperatively to 0.45 intraoperatively), and a significant increase in PaCO2 from 38 mm Hg to 45 mm Hg intraoperatively). In general, these patients had ARDS (n = 10), sepsis (n = 10), a laparotomy (n = 9), and intraoperative mechanical ventilation via the Ohio Anesthesia ventilator (n = 8), a commonly used operating room ventilator. Their preoperative peak airway pressure (54 cm H2O) and minute ventilation (20 L/min) requirements exceeded the capabilities of the Ohio Anesthesia ventilator and likely contributed to impaired gas exchange intraoperatively. Within the first several hours postoperatively, PaO2/FIO2 recovered to preoperative levels in all patients, even in those who had severe intraoperative hypoxemia develop and who underwent laparotomy. We conclude that most patients with acute respiratory failure receiving preoperative mechanical ventilation experienced mild-to-moderate deterioration in intraoperative pulmonary oxygen exchange that rapidly returned to preoperative levels after surgery. We recommend that necessary surgery not be postponed by concern that pulmonary function will be worsened by surgery and anesthesia. 
Spinal cord pial metastases: MR imaging with gadopentetate dimeglumine. The purpose of this investigation was to describe gadopentetate-dimeglumine-enhanced MR findings in metastatic disease to the pial lining of the spinal cord. Correlation was made with clinical data, other radiologic studies, and pathologic findings. Eighty-six patients with a known malignancy and unexplained neurologic signs or symptoms were studied with pre- and postcontrast T1-weighted images. In seven of these patients, abnormal enhancement of the pial lining of the cord was seen on the sagittal postcontrast T1-weighted images. This appeared as a thin rim of enhancement along the surface of the cord in six patients and as a focal, thick rim of enhancement in addition to the thin rim of enhancement in the seventh patient. Axial images confirmed the location along the pial lining in each case. Precontrast T1-weighted images in all seven cases and precontrast T2-weighted images in five cases failed to detect any focal abnormalities of the pial lining of the cord. Pathologic confirmation was available in five of the seven patients. Primary malignancies in these patients included breast carcinomas (two), lymphoma (one), leukemia (one), adenocarcinoma of the lung (one), prostate carcinoma (one), and malignant melanoma (one). Three of seven patients had metastatic disease evident only within the CNS, while four patients had widespread disease outside the CNS. We conclude that contrast-enhanced MR imaging is useful in the diagnosis of pial spread of metastatic disease in patients with a known primary malignancy and unexplained neurologic signs or symptoms. 
Cough, exertional, and other miscellaneous headaches. We have discussed several miscellaneous headache disorders not associated with structural brain disease. The first group included those headaches provoked by "exertional" triggers in various forms. These include benign cough headache, BEH, and headache associated with sexual activity. The IHS diagnostic criteria were discussed. Benign exertional headache and cough headache were discussed together because of their substantial similarities. In general, BEH is characterized by severe, short-lived pain after coughing, sneezing, lifting a burden, sexual activity, or other similar brief effort. Structural disease of the brain or skull was the most important differential diagnosis for these disorders, with posterior fossa mass lesions being identified as the most common organic etiology. Magnetic resonance imaging with special attention to the posterior fossa and foramen magnum is the preferred method for evaluating these patients. Indomethacin is the treatment of choice. The headache associated with sexual activity is dull in the early phases of sexual excitement and becomes intense at orgasm. This headache is unpredictable in occurrence. Like BEH, the headache associated with sexual activity can be a manifestation of structural disease. Subarachnoid hemorrhage must be excluded, by CT scanning and CSF examination, in patients with the sexual headache. Benign headache associated with sexual activity has been successfully treated with indomethacin and beta-blockers. The second miscellaneous group of headache disorders includes those provoked by eating something cold or food additives, and by environmental stimuli. Idiopathic stabbing headache does not have a known trigger and appears frequently in migraineurs. Its occurrence may also herald the termination of an attack of cluster headache. Indomethacin treatment provides significant relief. Three headaches triggered by substances that are eaten were reviewed: ingestion of a cold stimulus, nitrate/nitrite-induced headache, and MSG-induced headache. For the most part, avoidance of these stimuli can prevent the associated headache. Lastly, we reviewed headache provoked by high altitude and hypoxia. The headache is part of the syndrome of AMS during its early or benign stage and the later malignant stage of HACE. The pain can be exacerbated by exercise. The best treatment is prevention via slow ascent and avoidance of respiratory depressants. Acetazolamide and dexamethasone have proved useful in preventing this syndrome. 
Differentiation therapy of acute promyelocytic leukemia with tretinoin (all-trans-retinoic acid). BACKGROUND AND METHODS. Patients with acute promyelocytic leukemia have a characteristic (15;17) translocation, with a breakpoint on chromosome 17 in the region of the retinoic acid receptor-alpha (RAR-alpha). Since this receptor has been shown to be involved with growth and differentiation of myeloid cells in vitro, and since recent clinical studies have reported that tretinoin (all-trans-retinoic acid) induces complete remission in patients with acute promyelocytic leukemia we studied the effects of tretinoin on cellular maturation and molecular abnormalities in patients undergoing the induction of remission with this agent. RESULTS. Eleven patients with acute promyelocytic leukemia were treated with tretinoin administered orally at a dose of 45 mg per square meter of body-surface area per day. Nine of the 11 patients entered complete remission. In two patients, complete remission was preceded by striking leukocytosis that then resolved despite continued drug treatment. Serial studies of cellular morphologic features, cell-surface immunophenotypic analysis, and fluorescence in situ hybridization with a chromosome 17 probe revealed that clinical response was associated with maturation of the leukemic clone. All patients who responded to treatment who were tested by Northern blot analysis had expression of aberrant RAR-alpha. As patients entered complete remission, the expression of the abnormal RAR-alpha message decreased markedly; however, it was still detectable in several patients after complete morphologic and cytogenetic remission had been achieved. CONCLUSIONS. Tretinoin is a safe and highly effective agent for inducing complete remission in patients with acute promyelocytic leukemia. Clinical response to this agent is associated with leukemic-cell differentiation and is linked to the expression of an aberrant RAR-alpha nuclear receptor. Molecular detection of the aberrant receptor may serve as a useful marker for residual leukemia in patients with this disease. 
Canine myocardial creatine kinase isoenzymes after chronic coronary artery occlusion. BACKGROUND. Creatine kinase (CK) exists as three cytosolic isoenzymes, CK-MM, CK-MB, and CK-BB, and one mitochondrial isoenzyme. Animal and human observations suggest that the CK-MB content of myocardium is dynamic and may increase in response to ischemia, but the response of the myocardial CK system to chronic coronary artery occlusion is not well-defined. METHODS AND RESULTS. We measured serial changes in myocardial total CK, percent CK-MB, and percent CK-BB before and 3 weeks after coronary artery occlusion in 17 pentobarbital-anesthetized dogs. Tissue biopsies were obtained from the left anterior descending (LAD) coronary artery myocardium, the right coronary artery (RCA) myocardium, and the circumflex coronary artery myocardium at baseline and 3 weeks after LAD occlusion (n = 6), RCA occlusion (n = 5), and no coronary artery occlusion (n = 6). Tissue samples were assayed for total CK, percent CK-MB, and percent CK-BB. Samples were also examined by electron microscopy for evidence of ischemic myopathy. Total myocardial CK activity did not change over 3 weeks. Percent CK-MB increased significantly in the tissue supplied by the occluded artery (4.1-fold in dogs with LAD occlusion and 6.7-fold in dogs with RCA occlusion). Percent CK-BB did not change. Dogs with LAD occlusion had ultrastructural evidence of myopathic fibers interspersed with normal fibers in the LAD myocardium. Dogs with RCA occlusion had no ultrastructural evidence of myopathic fibers in the RCA myocardium. CONCLUSIONS. Chronic coronary artery occlusion causes a pronounced change in the canine myocardial CK system that is limited to the tissue supplied by the occluded coronary artery. These biochemical alterations do not correlate with any cellular ultrastructural changes. Myocardial CK-MB content is dynamic, varies geographically within the heart, and increases rapidly after coronary artery occlusion. 
Segmental neurofibromatosis. Two patients had localized multiple cutaneous neurofibromas; one had bilateral involvement of the scalp and the other had true segmental neurofibromatosis. Other signs of neurofibromatosis were absent. Segmental neurofibromatosis may not be related to the generalized types of neurofibromatosis but may be a cutaneous hamartoma. 
Mandible reconstruction with vascularized bone grafts. A histologic evaluation. To our knowledge, a histologic evaluation of bone healing after mandible reconstruction with vascularized human bone grafts has not been previously reported. Serial sections through both the decalcified graft and the junction between mandible and graft were evaluated in four patients who required surgical removal of their reconstructed mandibles. A failed scapular bone graft that had been wrapped within a pectoralis major myocutaneous flap for salvage following pedicle thrombosis showed markedly resorbed but viable bone with a fibrous union to the native mandible. Viable vascularized grafts without evidence of ongoing resorption characterized an iliac osteocutaneous bone graft and two scapula osteocutaneous grafts that healed with continuity of healthy bone between graft and mandible. Observations from the evaluation of these specimens are made regarding bone circulation, bone union, and bone graft survival as they occur clinically. Implications regarding the techniques of bone plating and indications for use of vascularized bone in mandible reconstruction are discussed. 
Conservative treatment and long term prophylactic thyroxine in the prevention of recurrence of multinodular goiter. It has not been universally agreed upon that there is an optimum treatment for multinodular goiter and that use of thyroxine postoperatively in preventing recurrence is effective. We have studied a group of 185 patients who underwent thyroid gland operations and who were observed for a mean period of 10.25 years. Of these, 171 patients received postoperative thyroxine in a dose of 100 micrograms per day and a small group (14 patients) received no medication. In the group receiving no thyroxine, there were six recurrences, and in the group that received postoperative prophylactic thyroxine, there were nine recurrences, which is statistically significant (p = 0.003 per cent). When recurrences did occur in the thyroxine treated group they were small and easily managed by increasing the dose of thyroxine. No patient who took thyroxine postoperatively continuously underwent a second thyroidectomy. We conclude that, in this series, our policy of resecting only macroscopically pathologic thyroid tissue and prescribing prophylactic postoperative thyroxine is successful in preventing recurrent nodular goiter. 
Immunohistochemical quantification of substance P in spinal dorsal horns of patients with multiple system atrophy. Using a computer-assisted image analyser, an immunohistochemical quantification method of substance P-like immunoreactivity (SPLI) in laminae I + II of spinal dorsal horn was established and applied to 13 patients with multiple system atrophy (MSA) with no disturbance of pain sensation, including olivo-ponto-cerebellar atrophy and striatonigral degeneration, and 13 neurologically normal controls. To investigate whether alteration of SPLI is related to an autonomic disorder, myelinated fibre counts of the fourth thoracic ventral roots were performed. Eleven of 13 MSA patients showed a significant decrease in small and large myelinated fibres, and were diagnosed with definite Shy-Drager syndrome (SDS), with the exception of two who had no apparent history of autonomic dysfunction. SPLIs in laminae I + II in 10 of these 11 patients, when adjusted for age, were significantly decreased at both levels of the fourth thoracic and third lumbar spinal segments. The results suggest the disorder of SP-containing synapses of primary afferent neurons and/or those of interneurons in SDS. 
Screening for renovascular hypertension. The most common curable cause of high blood pressure is renovascular hypertension. Although hypertension is common in the United States, only a minority, approximately 1%, of patients have a renovascular cause. Using clinical criteria, a subgroup of these patients can be selected in which the prevalence of renovascular hypertension will be approximately 15%. In these selected patients, it is appropriate to proceed to a radiographic screening modality to look for a significant renal artery stenosis. The choice of modality should reflect the strengths and expertise of each specific institution. Hypertensive urography is no longer recommended for screening. Excellent results have been reported with intravenous DSRA in institutions where a strong interest in this procedure exists. Furthermore, intravenous DSRA is easily coupled with the collection of renal vein samples for renin assay. Intravenous DSRA, however, has not maintained widespread use. Although the radionuclide renogram is no longer adequate as a radiographic screening tool, stimulation with an ACE inhibitor, such as captopril or enalaprilat, may produce excellent results. In many institutions, this is the most appropriate examination. Furthermore, it is relatively noninvasive. Merely detecting a significant renal artery stenosis does not, however, mean the patient has renovascular hypertension. Both hypertension and a renal artery stenosis may be present and not be causally related. Because renovascular hypertension is, at least initially, renin mediated, the demonstration of increased renin production by the ipsilateral kidney should confirm renovascular hypertension. Prospective application of these results to patients undergoing revascularization techniques, however, has been disappointing. This may be related to problems in patient preparation, sample collection, renin assay, or even the physiology of chronic hypertension, which is incompletely renin mediated. Thus, offering revascularization only to those patients with lateralizing renal vein renins is not appropriate. If radiographic screening is limited to those patient at greatest likelihood for a renovascular etiology, intra-arterial DSRA or conventional arteriography may be used. These techniques most reliably detect renal artery stenosis. Their main disadvantage lies in their relatively invasive nature, as an arterial puncture is required. The poor predictive value of selective RVRRs implies that revascularization may be attempted without awaiting those results. If percutaneous transluminal renal angioplasty can be performed with a satisfactorily low complication rate, both the diagnostic and the interventional procedure may be undertaken at the same setting. It is expected that further refinements in these diagnostic procedures, particularly with the use of stimulating drugs such as ACE inhibitors, will lead to further improvement in the diagnostic results.(ABSTRACT TRUNCATED AT 400 WORDS). 
Malignant colorectal polyps: venous invasion and successful treatment by endoscopic polypectomy. We reviewed the pathology of 81 malignant colorectal polyps in 80 patients treated by endoscopic polypectomy and assessed the importance of carcinomatous invasion of veins in the stalk (submucosa). All the patients were followed up for at least five years. Venous invasion was present in 30 of the polyps (37%). The histological features of lymphatic invasion were considered too subjective to be of value. Most of the tumours were well or moderately differentiated adenocarcinomas, one was poorly differentiated, and one was a signet ring cell carcinoma. Seventy one patients were treated by polypectomy alone, and 58 of these were alive and well five years later, with no evidence of recurrence. Nine died of unrelated causes within five years, but four died of carcinomatosis: one with recurrent tumour, one with a possible metachronous caecal cancer, and in two patients there was late development of malignancy of uncertain nature. The remaining nine patients underwent surgical resection after initial endoscopic polypectomy because of incompleteness of excision, poor differentiation of the tumour, or a decision by the surgeon. Tumour was not present in the resection specimens apart from a single lymph node deposit in the patient with signet ring cell carcinoma. These nine patients were alive and well without evidence of recurrence five years later. The results reemphasise the necessity of good cooperation between endoscopist and pathologist, meticulous laboratory technique, strict histopathological criteria including examination of resection margins and degree of differentiation of the tumour, and regular endoscopic follow up. 
Acute promyelocytic leukemia in Crohn's disease. Case report and review of the literature. A 19-year-old man with a documented 2-year history of Crohn's disease abruptly developed leukopenia and thrombocytopenia. A diagnosis of acute promyelocytic leukemia was established by bone marrow cytology. Chromosomal analysis of bone marrow aspirate revealed aberrations of no. 8 trisomy and translocation between no. 15 and no. 17 [46,XY,t(15q+,17q-)/47,XY,+8,t(15q+,17q-)]. Nine cases of Crohn's disease complicated by leukemia have been reported, including the present one; once again, a relationship between Crohn's disease and leukemia is suggested. 
Endocrine therapy for desmoid tumors. Two female patients with desmoid tumors (aggressive fibromatosis) showed tumor regression after endocrine therapy. In one patient, tumor response to tamoxifen has been maintained over several years of treatment. In the second patient, who had inoperable mesenteric fibromatosis, the tumor progressed on tamoxifen but regressed after treatment with Zoladex (goserelin acetate, ICI, Melbourne, Australia) and medroxyprogesterone acetate (MPA). To the authors' knowledge this is the first report of the use of Zoladex in the treatment of desmoid tumors. This review of the literature reveals that the biology of this disease is related to the endogenous hormonal environment and that estrogen receptors have been documented in desmoid tumors. Thirty-five cases are identified where endocrine agents have been employed, with a response rate of 51%. Furthermore, tumors may respond to second-line hormonal therapy after failing to respond to initial endocrine treatment. Endocrine treatments have also been used in other disorders of fibroblastic origin. The authors recommend that endocrine treatment be employed in inoperable desmoid tumors or where there has been postsurgical recurrence. In addition, the role for endocrine therapy in other soft tissue neoplasms should be determined. 
Risk factors for subarachnoid hemorrhage in a longitudinal population study. The known risk factors of atherosclerotic diseases may be involved in the development of a subarachnoid hemorrhage. We studied the morbidity and mortality due to subarachnoid hemorrhage among 42,862 men and women aged 20-69 years who had participated in a large health survey in Finland. During a mean follow-up of 12 years, 102 non-fatal and 85 fatal cases of subarachnoid hemorrhage were observed. The total incidence was 37 per 100,000 person-years. Smoking and hypertension were positively associated and body mass index was inversely associated with the risk of subarachnoid hemorrhage. These associations were not confounded by age or each other. No statistically significant association with risk was detected for serum cholesterol level, hematocrit content, known heart disease, or diabetes. The risk was especially elevated among lean hypertensive subjects and lean smoking subjects. The age-adjusted relative risks of subarachnoid hemorrhage for lean, hypertensive smokers were 18.3 (95% confidence interval (CI), 7.8-42.7) among women and 6.7 (95% CI, 2.3-19.7) among men as compared to the risk among subjects without these risk factors. We conclude that modifiable risk factors are predictive of subarachnoid hemorrhage, for which reason subarachnoid hemorrhage may in part be preventable. Leanness combined with arterial hypertension and/or smoking, in particular, poses a substantially elevated risk. 
On a possible protective effect of HLA-A11 against skin cancer and keratotic skin lesions in renal transplant recipients. Renal transplant recipients who have skin cancer potentially related to human papillomavirus were HLA typed with a special focus on HLA-A11, which in nonimmunosuppressed patients is negatively associated with the occurrence of virus-related carcinoma of the cervix. We found also a negative association between HLA-A11 and skin cancer; none of the 66 transplant recipients with skin cancer were positive for HLA-A11. As HLA-A11 seems to have a protective effect against skin cancer, we speculate that antigens induced by squamous cell carcinomas and possibly also by human papillomavirus may be efficiently presented through HLA-A11 to cytotoxic T cells. We also investigated a possible influence of other HLA alleles on the susceptibility of renal transplant recipients to skin cancer. The frequency of HLA-B27 was significantly higher in the transplant recipients with skin cancer, with a relative risk of 3.4 relative to healthy controls. No significant differences were found for other HLA class I or class II antigens. 
Acute promyelocytic leukemia in Crohn's disease. Case report and review of the literature. A 19-year-old man with a documented 2-year history of Crohn's disease abruptly developed leukopenia and thrombocytopenia. A diagnosis of acute promyelocytic leukemia was established by bone marrow cytology. Chromosomal analysis of bone marrow aspirate revealed aberrations of no. 8 trisomy and translocation between no. 15 and no. 17 [46,XY,t(15q+,17q-)/47,XY,+8,t(15q+,17q-)]. Nine cases of Crohn's disease complicated by leukemia have been reported, including the present one; once again, a relationship between Crohn's disease and leukemia is suggested. 
Glucagon and clonidine testing in the diagnosis of pheochromocytoma. We assessed the sensitivity and specificity of glucagon stimulation and clonidine suppression tests in the diagnosis of pheochromocytoma in 113 hypertensive patients, 39 with and 74 without the tumor. In the glucagon stimulation test, blood was sampled 2 minutes after intravenous injection of 0.28 mumol (1 mg) glucagon, and in the clonidine suppression test, blood was sampled 3 hours after administration of oral clonidine, 1.30 mumol (0.3 mg)/70 kg body wt. Baseline levels of catechols in antecubital venous blood were abnormal, with norepinephrine greater than 7.10 nmol/l (1,200 pg/m), epinephrine greater than 1.51 nmol/l (276 pg/ml), norepinephrine/dihydroxyphenylglycol (DHPG) ratio greater than 1.09, or dopa greater than 35.53 nmol/l (7,000 pg/ml), in 30 of 39 patients with pheochromocytoma (sensitivity 77%) and 1 of 74 patients without pheochromocytoma (specificity 99%). Results of the glucagon test were abnormal (norepinephrine greater than 11.83 nmol/l [2,000 pg/ml] or more than threefold increase from baseline) in 25 of 31 patients with pheochromocytoma (sensitivity 81%) and 0 of 72 patients without pheochromocytoma (specificity 100%). Results of the clonidine test were abnormal (after clonidine norepinephrine greater than 2.96 nmol/l [500 pg/ml] or less than 50% decrease from baseline) in 29 of 30 patients with pheochromocytoma (sensitivity 97%) and in 7 of 30 patients without pheochromocytoma (specificity 67%). Very high baseline levels of catechols therefore indicated the presence of pheochromocytoma, but there were several false-negative results when normal levels were obtained. The glucagon test alone was highly specific but not sensitive, and the clonidine test was highly sensitive but less specific. 
The relationship between locomotor disability, autonomic dysfunction, and the integrity of the striatal dopaminergic system in patients with multiple system atrophy, pure autonomic failure, and Parkinson's disease, studied with PET. 18F-dopa and S-11C-nomifensine (NMF) are positron emitting tracers whose caudate and putamen uptake reflects striatal dopamine storage capacity and the integrity of dopamine reuptake sites, respectively. Using these two tracers, the integrity of the presynaptic striatal dopaminergic system has been studied with positron emission tomography (PET) in 10 subjects with multiple system atrophy (MSA, Shy-Drager syndrome) who had an akinetic-rigid syndrome that was poorly responsive to L-dopa, autonomic failure, and cerebellar ataxia. PET findings for the 10 MSA patients were compared with those for 13 age-matched controls, 8 subjects with L-dopa responsive Parkinson's disease (PD), and 7 subjects with pure autonomic failure (PAF). Influx constants, Ki, reflecting specific 18F-dopa uptake into striatal tissue, were severely reduced in the putamen and caudate of the 10 MSA subjects (mean putamen Ki 0.005 min-1 MSA vs 0.013 min-1 controls; mean caudate Ki 0.007 min-1 MSA vs 0.013 min-1 controls). Reduction of putamen, but not caudate, 18F-dopa uptake correlated with severity and duration of locomotor disability. Eight patients with PD, and a similar degree and duration of locomotor disability to the patients with MSA, demonstrated equal impairment of mean putamen 18F-dopa uptake, but significant preservation of mean caudate function. The 7 PAF patients had normal mean levels of putamen and caudate 18F-dopa uptake, although 1 individual PAF patient had significantly impaired striatal function. The MSA and PD groups of subjects both showed significantly reduced levels of specific striatal S-11C-NMF binding, again caudate function being relatively preserved in PD. It is concluded that in both MSA and PD there is a parallel decline of striatal dopamine storage capacity and reuptake site integrity, probably reflecting a loss of nigrostriatal nerve terminals. Caudate function is relatively preserved in PD compared with MSA. The majority of PAF patients have an intact nigrostriatal dopaminergic system, suggesting that PAF is a condition distinct from PD and MSA in spite of some pathological similarities. PET is capable of detecting subclinical nigrostriatal involvement in PAF patients when this is present. 
Factors affecting decisions made by family members of patients with severe head injury. An exploratory descriptive study was conducted to determine factors affecting decisions made by families of patients with severe head injury during the first two stages of recovery. Nineteen family members of 11 patients participated in this study. Five interviews of each family member were conducted over a 1-month period after the injury. Sixty decisions were identified by family members. Six factors: personal functioning, relationships, information, uncertain outcomes, environment, and emotions, were found to affect these decisions. The six factors identified by family members have specific implications for nursing. 
Birth interval among breast-feeding women not using contraceptives. One hundred twelve Orthodox Jewish mothers were surveyed by means of questionnaire about birth interval in relationship to formula-feeding (n = 30) and breast-feeding (n = 236) experiences in the absence of birth control. Analyses indicate that mothers who breast-fed have longer birth intervals than those who did not. Moreover, data obtained from the same mothers show that birth intervals preceded by breast-feeding were longer than those preceded by formula-feeding of the previous infant. For those mothers who breast-fed, there was significant positive correlation between duration of breast-feeding and the length of lactational amenorrhea and total birth interval. The age at which night feeding was terminated had corresponding but less strong associations with lactational amenorrhea and total birth interval. 
Statistical modeling of prognostic indices for evaluation of critically ill patients. OBJECTIVE: To identify the most predictive association of variables from the usual indices of severity of illness by statistical objective analysis. DESIGN: Logistic regression analysis of the different variables of the most important indices. SETTING: A general critical care medicine group practice in a university hospital. PATIENTS: A total of 630 critical care patients age 12 to 87 yrs were evaluated. The most important indices of severity of illness and the corresponding variables were recorded and the patient's course was followed for 3 months after ICU admission. MEASUREMENTS AND MAIN RESULTS: One of our hypotheses was that the inclusion of an excessive number of variables to obtain the most common prognostic indices of mortality in critical care patients results in an underestimation of mortality and a redundancy of prognostic information. We performed a logistic regression analysis using the variables of the currently used indices of critical care prognosis: Acute Physiology Score, Simplified Acute Physiology Score, Acute Physiology Score-II, and Mortality Prediction Model. This mathematical approach resulted in a model of five variables: organ system failure, blood glucose, serum calcium, serum prothrombin activity, and serum osmolality. The score obtained from this model gave accurate prognostic criteria:sensitivity 91.2% and specificity 90%, using a cutoff point of 0.7; sensitivity 86% and, specificity 94%, using a cutoff point of 0.5. CONCLUSIONS: Our results show that suitable statistical management of the discriminant prognostic variables allows reduction of the number of variables of the severity indices currently used, obtaining five more predictive variables. 
Enhancement of tumor-associated glycoprotein-72 antigen expression in hormone-related ovarian serous borderline tumors. The immunoreactivity of monoclonal antibody (MoAb) B72.3 with ovarian serous tumors of borderline malignancy from 44 women who were pregnant, were on hormone medication containing a progestin, or were known to be in the secretory phase of the menstrual cycle, was compared with that of similar tumors of 32 patients who were not known to be in any of these three categories. All 76 borderline tumors expressed the tumor-associated glycoprotein (TAG-72) recognized by MoAb B72.3. Striking staining differences (P less than 0.0001) were observed between the hormone-related and the nonhormone-related tumors. Differences were also noticed between the staining of tumors from pregnant patients and that of previous, persistent, or recurrent tumors of the ipsilateral or contralateral ovaries when the same patients were not pregnant. Tumor MoAb B72.3 reactivity increased with progressive gestational age and fell to lower levels at term and during the postpartum period. Although it has been suggested by cell culture studies, enhanced TAG-72 expression in human tumors under hormonal stimulation has not been described before. 
Pilonidal disease: 25 cases treated by the Dufourmentel technique. Twenty-five patients with pilonidal disease were treated by the Dufourmentel technique between 1984 and 1989. In this series, 18 patients (72 percent) were women and 7 (28 percent) were men (mean age, 24 years); hospital stay averaged 4 days. There were no recurrences and no reports of surgical wound infection. Diagnosis was confirmed histologically in all cases. 
Bleeding complications following initiation of thrombolytic therapy for acute myocardial infarction: a comparison of helicopter-transported and nontransported patients. STUDY OBJECTIVE: To evaluate the effect of helicopter transport of acute myocardial infarction (AMI) patients after initiation of thrombolysis on bleeding complications through hospital discharge. DESIGN: Prospectively identified incidence (cohort) study. SETTING: Air medical service of tertiary-care teaching hospital. TYPES OF PARTICIPANTS: Ninety-five consecutive AMI patients transported within 12 hours of the initiation of thrombolysis with recombinant tissue-type plasminogen activator were compared with 119 nontransported AMI patients treated in a similar manner. RESULTS: The transported and nontransported populations were similar with regard to age, sex, and infarct location. Transport was well tolerated with no episodes of cardiac arrest or cardioversion occurring during transport. Hypotension requiring fluids or increased pressors occurred in 18 patients. Bleeding complications of all types occurred in 43.2% of the transported and 49.6% of the nontransported patients, respectively (relative risk, 0.87; 95% confidence interval, 0.65 to 1.17). CONCLUSION: Helicopter transport of AMI patients after initiation of thrombolysis appears to be safe acutely and without a clinically significant increase in risk of bleeding complications through hospital discharge when accomplished by a highly skilled team. 
Oral melanoma and other pigmented lesions of the oral cavity. This article presents a review of oral malignant melanoma and other oral cavity pigmented lesions. The dismal prognosis for patients with oral malignant melanoma is partly due to patients' delayed recognition of signs of early disease and delayed diagnosis by physicians. Pigmented macules and plaques in the oral cavity, representing the radial growth phase of tumors, often go unrecognized for months or years before tumor invasion. Therefore, if early detection of thin oral melanomas is to be achieved, all pigmented oral cavity lesions should be viewed with suspicion. Biopsies of such lesions are indicated when the clinical diagnosis is uncertain. Prompt aggressive surgical treatment is essential in reducing the morbidity and mortality from oral melanomas. The differential diagnosis of oral melanomas includes nevi, oral melanotic macules, amalgam tattoos, Kaposi's sarcoma, oral melanoacanthoma, and physiologic pigmentation. 
Social density, stressors, and depression: gender differences among the black elderly. This research examined gender differences with regard to the effects of social density and stressors upon depressive symptomatology among 600 Black elderly community residents (aged 55-85 years) of Nashville, Tennessee. The sample had more females than males and fewer married individuals. Approximately half of the males and females lived alone. Regression analyses show that poor ego and chronic medical problems were the common predictors of depression among both the males and females. Gender differences were found with regard to life events in that females tended to become more depressed as the number of events increased and as level of contact with relatives and friends decreased. Further, females with lower levels of social attachment, guidance, and reliability were more depressed. None of these social support dimensions related to depression among the males. These relationships tended to be stronger for those living alone than for those living with others. 
Maintenance treatment of duodenal ulceration: ranitidine 300 mg at night is better than 150 mg in cigarette smokers. Two hundred patients received either ranitidine 150 mg or 300 mg at night for 18 months to prevent duodenal ulcer relapse. Recurrence rates were lower in patients receiving the higher dose of ranitidine (3.1% v 9.7%, p = 0.78; 6.5% v 16.7%, p = 0.037; and 8.9% v 17.0%, p = 0.121 at six, 12, and 18 months respectively). In patients receiving ranitidine 150 mg, recurrences were significantly more common in smokers than non-smokers after 12 and 18 months, while in patients receiving ranitidine 300 mg recurrence rates were similar in smokers and non-smokers. Ranitidine 300 mg at night abolishes the adverse effect of smoking observed during maintenance treatment with ranitidine 150 mg at night and may therefore be an appropriate maintenance dose for smokers who relapse during standard dose maintenance treatment. 
Impact of dosage schedule on the efficacy of gentamicin, tobramycin, or amikacin in an experimental model of Serratia marcescens endocarditis: in vitro-in vivo correlation. Aminoglycosides are usually considered to be concentration-dependent antibiotics and to have similar pharmacodynamic and pharmacokinetic properties. To verify the equivalent activity of the aminoglycosides on a susceptible strain, we tested the killing rate of three aminoglycosides (gentamicin, tobramycin, and amikacin) on one strain of Serratia marcescens both in vitro and in vivo by using a rabbit model of left-ventricle endocarditis. Despite, similar MICs, the time-kill curve of gentamicin was consistently better than those of amikacin and tobramycin, whatever the concentration of each antibiotic used (1, 2, 4, 8, 16, or 32 mg/liter), after a 5-h incubation. The in vivo bacterial reduction in the vegetations was measured 24 h after administration of an intravenous 48-mg/kg bolus of each antibiotic or at the end of a 24-h continuous intravenous infusion of the same dose. Gentamicin was significantly more effective when administered as a bolus than when administered as a continuous infusion (2.8 +/- 0.2 versus 6.4 +/- 1.5 log10 CFU/g of vegetation, respectively; P less than 0.01), whereas amikacin was more effective as a continuous infusion than as a bolus injection (3.6 +/- 2.0 versus 7.5 +/- 1.3 log10 CFU/g of vegetation, respectively; P less than 0.01). Tobramycin was not very effective, whatever the dosage tested (approximately 6.5 to 7 log10 CFU/g). These results suggest that concentration-dependent bactericidal activities, both in vitro and in vivo, may vary greatly among aminoglycosides despite similar MICs. 
Morbidity and mortality from chronic hepatitis B virus infection in family members of patients with malignant and nonmalignant hepatitis B virus-related chronic liver diseases. Three-hundred forty-one HBsAg-positive family members of 152 patients with chronic hepatitis B virus infection (47 asymptomatic carriers, 59 with chronic hepatitis, 17 with cirrhosis and 29 with hepatocellular carcinoma) were prospectively studied to determine the morbidity and mortality from chronic hepatitis B virus infection in the family members of patients with malignant and nonmalignant hepatitis B virus-related chronic liver diseases. Most of the family members had no history of acute hepatitis, were asymptomatic and were unaware of their carrier status. However, 5.3% had stigmata of chronic liver disease, 6% had serum ALT levels that exceeded two times the upper limit of normal and 78% of those who had biopsies had chronic hepatitis with or without cirrhosis. During a follow-up period of 12 to 90 mo (median = 39 mo), 3% had symptoms of chronic liver disease; 24% had transient, recurrent or persistent elevation in serum ALT levels, 1.4% had cirrhosis and 1% had hepatocellular carcinoma. Neither hepatocellular carcinoma in the index patient nor a previous history of hepatocellular carcinoma in the family was associated with an increase in the morbidity and mortality from chronic hepatitis B virus infection in the HBsAg-positive family members. 
Transthoracic and transesophageal echocardiography in the diagnosis and surgical management of right atrial myxoma. An asymptomatic patient was discovered to have a large right atrial myxoma by transthoracic echocardiography. Preoperative considerations included the possibility of satellite lesions, left atrial origin, and a question of tricuspid valve involvement. Subsequent operative transesophageal echocardiography demonstrated single-stalk attachment in the right atrial septal wall and no satellite lesions. Doppler and color flow examination immediately following tumor removal aided in the decision not to perform tricuspid annuloplasty as there was no significant tricuspid regurgitation. The combined use of transthoracic and transesophageal echocardiography with Doppler and color flow imaging aids in the preoperative and intraoperative diagnosis and surgical management of right atrial tumors. 
Age differences in depressive symptom experiences. Age differences in depressive symptom experiences were investigated in a community sample of 368 women between the ages of 51 and 92 who were administered the SCL-90 Depression and Additional Symptoms Scales. Confirmatory factor analysis was used to assess and compare depressive symptom experiences in a younger (age 51-65) and older (age 66-92) age cohort. Findings show that two somewhat different depressive syndromes underlie symptom reporting patterns, one having higher levels in the older age cohort, the other having higher levels in the younger age cohort. In addition, three more delimited forms of distress -- feelings of enervation, dysphoria, and sleep disturbances -- show higher levels among the older cohort. Implications of these findings for future research on the relation between aging and depression are discussed. 
Experimental treatment of thrombotic vascular occlusion. The role of laser energy in the treatment of thrombotic vascular occlusion was evaluated in two sets of experiments. First, 10 polytetrafluoroethylene grafts were used to replace segments of the superficial femoral arteries in dogs and were thrombosed by distal ligation. Occlusion was maintained for one hour, or for 7, 14, 21, and 28 days in each of two grafts. Patency was restored in all 10 grafts without perforation or anastomotic disruption using a 2 mm hot tip probe powered by an Argon laser. However, increased organization of thrombus related to the duration of occlusion lead to decreased laser channel diameters, and 75% of the 28 day thrombus remained in the graft after recanalization. The second experiments tested the added benefit of thrombolytic infusion following laser recanalization. Bilateral external iliac artery thrombosis was induced in dogs by operative vessel isolation, de-endothelialization, and thrombin injection. At 7 days the efficacy of laser-assisted thrombolysis (LAT) versus enzymatic thrombolysis (ET) alone was compared. Eight vessels underwent ET by urokinase (4000 I.U./min.); 14 vessels were laser recanalized prior to thrombolytic infusion. LAT was performed from a carotid artery approach in 8 vessels (antegrade) and from a femoral artery in 6 vessels (retrograde). In contrast to studies using the hot tip alone, both ET and LAT accomplished complete thrombus removal. However, LAT lead to significant iliac arterial flow in 9 +/- 8 min. (antegrade) and 25 +/- 8 min. (retrograde) while ET required 109 +/- 47 min (p less than 0.01). 
Using anticoagulants safely. Guidelines for therapeutic and prophylactic regimens [published erratum appears in Postgrad Med 1991 Sep 1;90(3):48] Heparin and warfarin sodium (Coumadin, Panwarfin, Sofarin) are used most often to treat acute and recurrent venous thromboembolic disease, arterial disease, valvular heart disease, and atrial fibrillation. These agents along with dextran, pneumatic compression devices, and gradient stockings are also used to prevent deep venous thrombosis and pulmonary embolism in patients at high risk (eg, those with venous stasis, lower limb or spinal cord trauma, clotting abnormalities). Anticoagulation therapy is monitored by maintaining the activated partial thromboplastin time and the prothrombin time in the therapeutic range. 
Trends in preterm survival and incidence of cerebral haemorrhage 1980-9. The annual survival rates and incidence of cerebral haemorrhage in 2618 preterm infants of 34 weeks' gestation or less were examined in one referral centre over a 10 year period from January 1980 to December 1989. Survival was independently related to weight, gestation, sex, and inborn delivery. When these variables had been taken into account, survival was 56% greater at the end of the decade compared with 1980. The incidence of cerebral haemorrhage (diagnosed by cranial ultrasound scanning) was related to birth weight, gestation, sex, inborn delivery, and caesarean section, but there was no significant trend in the incidence with time. Rates of caesarean section in this group increased from 31% in 1980 to over 50% more recently. Haemorrhage affecting the brain parenchyma was related to gestation and inborn delivery, and showed a small but significant decline over time. The lack of association between changes in survival rates and rates of cerebral haemorrhage may indicate that factors associated with both neonatal mortality and the incidence of cerebral haemorrhage may not be causally related as previously assumed. 
Endoscopy as an adjuvant to biliary radiologic intervention. Twenty-two patients underwent 24 percutaneous biliary procedures guided with choledochoscopy, an adjunctive percutaneous biliary technique. All but four procedures were performed through established percutaneous tracts; the others, through tracts less than 4 weeks old. The procedures were done for the following reasons: removal of calculi (n = 15), electrohydraulic lithotripsy (n = 1), biliary duct biopsies (n = 8), cauterization of a bleeding tract (n = 1), and evaluation of biliary-enteric anastomoses (n = 11). The only complication was one case of severe nausea after choledochoscopy. This patient required overnight hospitalization and medical treatment. All procedures were technically successful, except one case in which the tract was undersized. All patients received intravenously administered antibiotics before and after the procedure. It is concluded that choledochoscopy is a safe, atraumatic, and well-tolerated method of evaluating and treating biliary disease and that it markedly reduces radiation exposure. It can be performed rapidly with minimal sedation on an in- or outpatient basis. 
Blood transfusion and laryngeal cancer. Evidence exists to suggest a detrimental effect of blood transfusion on survival after resection for malignant disease. Immune suppression due to transfusion has been implicated, though this remains unproven. We have conducted a retrospective study of 69 patients (38 transfused, 31 not transfused) with squamous carcinoma of the larynx to assess the effect of blood transfusion on survival after laryngectomy. Patients were compared for age, sex, smoking habit, tumour site and stage, grade of operating surgeon, preoperative haemoglobin, tumour nucleolar organizer region status, and operation time. The minimum follow-up was 5 years. In the transfused group 21/38 died as a result of their malignant disease and only 4/31 in the untransfused group. This difference was highly significant (P less than 0.001, chi-squared test) and using a multivariate analysis the only variable associated with a decreased survival time was whether a blood transfusion had been received. We conclude that peri-operative blood transfusion is associated with decreased survival after laryngectomy. However, whether this association is causal remains unproven. 
L-tryptophan supplementation does not affect postoperative pain intensity or consumption of analgesics. Aiming at optimizing serotonin levels in endogenous pain-modulating systems, L-tryptophan supplementation pre- and postoperatively (2 g/day for 7 days) did not affect pain development or analgesic consumption after third molar surgery. Biological effects related to an increase in mood were observed, however, indicating transport of L-tryptophan to the central nervous system. The findings are discussed in relation to earlier reports on favorable effects of L-tryptophan on experimental pain in healthy subjects and in chronic pain patients. 
A chemical score to evaluate the protein quality of commercial parenteral and enteral formulas: emphasis on formulas for patients with liver failure. Essential amino acids, found in abundance in high-quality dietary protein, are required daily by hospitalized patients and healthy persons to maintain the dynamic process of protein metabolism. One method for assessing dietary protein quality is by determining a diet's chemical score, ie, the ratio of a gram of the limiting amino acid in a test diet to the same amount of the corresponding amino acid in a reference diet (eg, whole-egg protein) multiplied by 100. This investigation used the chemical score to evaluate the protein quality of 9 parenteral and 17 enteral diets commonly used to feed hospitalized patients. Standard parenteral and enteral products (ie, formulas that had not been designed for patients with a specific disease state) had chemical scores that ranged from 46% to 70%. Limiting amino acids were either methionine (plus cysteine) or phenylalanine (plus tyrosine). Products designed for patients with renal failure had the highest scores, which ranged from 85% to 145%. Products that were enriched with branched-chain amino acids for trauma patients had scores that ranged from 38% to 73%. The only product available for patients with pulmonary compromise had a score of 50%. The lowest scores, which ranged from 5% to 13%, were found in products for patients with hepatic failure. All products, except those with chemical scores below 13%, may be fed in relatively small amounts of protein (7 to 33 g) to satisfy the minimum daily requirements of essential amino acids, although such levels would not meet minimal daily nitrogen requirements. We recommend that dietitians use the chemical score to assess the protein quality of parenteral and enteral diets. 
Cecal rupture after continent ileocecal urinary diversion during total pelvic exenteration. Continent ureteral diversion at the time of pelvic exenteration avoids an external appliance and allows patients to retain "bladder" reservoir function. The technical difficulty of this procedure requires meticulous attention to operative and perioperative care, particularly after pelvic irradiation. A patient with recurrent stage IIIB carcinoma of the cervix underwent total pelvic exenteration with reconstructive procedures including low rectal anastomosis, neovagina formation, and ileocecal (Indiana) continent diversion. Early catheterization of the reservoir began 2 weeks postoperatively. One week later cecal rupture occurred, not related to suture line (technical) failure. Because of the high wall tension and reduced compliance in the irradiated cecum, we do not recommend catheterization of the urinary reservoir before 4-6 weeks. In order for continent diversion to become the standard diversion in exenteration patients, the major complication rate must remain comparable to that of noncontinent diversion. 
Percutaneous transhepatic choledochoscopic electrohydraulic lithotripsy for common bile duct stones: experience in four high-risk patients. Choledochoscopic electrohydraulic lithotripsy was applied through a percutaneous transhepatic approach in four high-risk patients with common bile duct stones that were not extractable by duodenoscopic means. All stones were fragmented and removed from three patients, but one patient died from bronchopneumonia before ductal clearance could be achieved. The procedure was well tolerated, without any complication. The major disadvantage is the multiple maneuvers required and the prolonged hospital stay. Percutaneous transhepatic choledochoscopic electrohydraulic lithotripsy provides a safe and effective alternative for nonoperative treatment of common bile duct stones in high-risk patients when the duodenoscopic approach fails. 
Evaluation of the extracranial carotid arteries: correlation of magnetic resonance angiography, duplex ultrasonography, and conventional angiography. We compared duplex scanning, "bright blood" and "black blood" magnetic resonance angiography, and conventional angiography for evaluation of the extracranial carotid arteries. All three methods were applied to 39 vessels in 20 patients. Duplex scanning was inaccurate when compared to conventional angiography in six instances. In three instances the degree of stenosis was overgraded by the scanner, and in three cases the stenosis was undergraded. Magnetic resonance angiography was inaccurate when compared to conventional angiography in three instances. In all cases magnetic resonance angiography overgraded the degree of stenosis. By use of a greater than 70% stenosis as a positive study, the sensitivity of magnetic resonance angiography was 100% and the specificity 92%. With use of the same criteria, the sensitivity of duplex scanning was 86%, and specificity was 84%. In those evaluations where the results of the magnetic resonance angiography and duplex scanning were in agreement, the correlation with conventional angiography was 100%. We conclude that magnetic resonance angiography is an alternative means to duplex scanning for noninvasive carotid imaging. A combination of bright and black blood magnetic resonance angiography is precise in delineating lesions of the extracranial carotid artery and may ultimately eliminate the need for conventional angiography in the evaluation of carotid stenosis. 
Percutaneous balloon valvotomy for the treatment of isolated tricuspid stenosis. A 46-year-old woman with isolated tricuspid stenosis complained of increasing fatigue and dyspnea on exertion. Exercise Doppler echocardiography reproduced her symptoms and revealed a marked increase in trans-tricuspid gradient. Successful percutaneous balloon tricuspid valvotomy was performed, with resolution of her symptoms. 
Urticaria and angioedema: diagnosis and evaluation. Because urticaria clears spontaneously in most patients, an extensive workup is not advised during the early weeks of an urticarial eruption. Whether and when to perform a screening workup or a more extensive workup depend on the degree of suspicion that the patient is ill, the urgency with which the patient presses for an answer, and the presence or absence of signs or symptoms that might lead the physician to pursue a diagnosis other than chronic idiopathic urticaria. Angioedema may occur with urticaria, and when it does, the prognosis is worse. Whereas urticaria manifests as circumscribed edema involving the superficial dermis, angioedema involves primarily the deep dermis or subcutaneous or deeper layers. Individual urticarial lesions usually disappear within 2 to 4 hours, whereas those of angioedema can persist for 72 hours. The workup for patients with chronic angioedema can be similar to that for patients with urticaria. However, several additional diagnostic possibilities should be pursued in patients with angioedema, such as hereditary angioedema caused by C1-esterase inhibitor deficiency, because anabolic steroids are effective in the treatment of these conditions. 
Hemodynamic effects of octreotide in patients with autonomic neuropathy. BACKGROUND. The somatostatin analogue, ectrootide, is being used to treat postprandial hypotension in patients with autonomic neuropathy. Although the therapeutic effect of the drug is presumably secondary to a splanchnic vasoconstrictor action, its effect on splanchnic hemodynamics has never been characterized in patients with autonomic neuropathy. Moreover, it is unknown whether octreotide acts on other vascular beds in this group of patients or whether it affects cardiac output. We, therefore, measured splanchnic, forearm, and systemic vascular resistance and cardiac output before and after administering octreotide (0.4 microgram/kg s.c.) to patients with idiopathic autonomic neuropathy and diabetic autonomic neuropathy. METHODS AND RESULTS. Splanchnic blood flow was determined from the clearance of indocyanine green in seven patients. We observed that octreotide decreased splanchnic blood flow (from 850 +/- 77 to 664 +/- 48 ml/min, p less than 0.005), increased mean blood pressure (from 97 +/- 6 to 115 +/- 3 mm Hg, p less than 0.005), and increased splanchnic vascular resistance (from 0.118 +/- 0.012 to 0.18 +/- 0.018 mm Hg/ml/min, p less than 0.005). Forearm blood flow was measured by plethysmography in 13 patients. Octreotide increased forearm vascular resistance in patients with idiopathic autonomic neuropathy (n = 8) from 19.1 +/- 1.0 to 27.2 +/- 3.8 mm Hg/ml/min/100 ml forearm volume (p less than 0.01) and from 25.2 +/- 3.9 to 41.0 +/- 6.8 mm Hg/ml/min/100 ml (p less than 0.01) in patients with diabetic autonomic neuropathy (n = 5). Cardiac output was measured by two-dimensional echocardiography. Octreotide administration increased cardiac output in five of six patients with idiopathic autonomic neuropathy (from 4.4 +/- 0.4 to 5.0 +/- 0.5 l/min, p less than 0.02) and five of five patients with diabetic autonomic neuropathy (from 3.8 +/- 0.4 to 5.1 +/- 0.4 l/min, p less than 0.02). Systemic vascular resistance increased in patients with idiopathic autonomic neuropathy from 21.2 +/- 2 to 24.9 +/- 2.6 (p less than 0.05) but did not change in patients with diabetic autonomic neuropathy. CONCLUSION. The pressor effect of octreotide in patients with autonomic neuropathy is associated with increased splanchnic and forearm vascular resistance and with increased cardiac output. 
Persistence of hepatitis B viral DNA after serological recovery from hepatitis B virus infection. Chronic hepatitis B virus infection is a major medical problem worldwide. Apart from HBsAg carriers, hepatitis B virus has also been identified in some HBsAg-individuals with or without antibodies to viral antigens. The molecular mechanisms underlying hepatitis B virus persistence in HBsAg-individuals are unresolved, however. To identify a possible genetic basis for viral persistence, we cloned the viral genome from the liver of a patient serologically immune to hepatitis B virus infection. DNA sequence analysis of the complete viral genome identified numerous mutations in all viral genes. Analysis of the biological effects of these mutations revealed three major findings: a low level of HBsAg synthesis, absence of HBeAg production and a defect terminating viral replication. These data suggest that mutations accumulating during the natural course of hepatitis B virus infection may be a mechanism underlying viral persistence in HBsAg-individuals, presumably through escape from immune surveillance. 
Complete ophthalmoplegia as a complication of acute corticosteroid- and pancuronium-associated myopathy. We report acute complete external ophthalmoplegia and severe myopathy in a patient treated with high doses of IV methylprednisolone and pancuronium. Awareness of this rare syndrome in a common clinical setting can lead to prompt recognition and avoid confusion with other causes of acute weakness and ophthalmoparesis. 
Feasibility of universal screening mammography. Lessons from a community intervention. It is estimated that 44,500 American women will die of breast cancer in 1991. The breast cancer screening guidelines of the American Cancer Society and the National Cancer Institute calling for annual mammography for all women older than 50 years have been endorsed by numerous professional groups. Third-party reimbursement for screening mammography is becoming more prevalent, and payment for screening mammography is now a Medicare benefit. Our studies, conducted as part of a National Cancer Institute grant to increase the routine use of screening mammography and clinical breast examination in women 50 to 75 years of age, have uncovered a number of significant barriers to the implementation of screening guidelines among women, primary care physicians, and providers of mammography services. These barriers, as well as methods to assure the quality of mammography, need to be addressed before universal screening is feasible. 
The association of laryngoceles with squamous cell carcinoma of the larynx. The clinical diagnosis of laryngoceles simultaneously occurring with squamous cell carcinoma of the larynx is infrequent; however, when specimens from patients with laryngeal cancer have been examined closely, the two entities have been associated in 4.9% to 28.8% of cases. Despite this apparent relationship, the literature has failed to address the potential impact of a concurrent laryngocele on surgical decision making. Also, the wide variation in the reported rates of simultaneous occurrence of these two entities is unexplained. We performed whole-organ histopathologic analysis on a laryngeal specimen with bilateral external laryngoceles associated with squamous cell carcinoma and correlated this to computed tomography findings. Based on this information and other reports concerning the pattern of spread of carcinoma within laryngoceles, it appears that supraglottic laryngectomy is oncologically sound in the presence of a laryngocele as long as the usual criteria for this procedure are met. 
Esophageal motility disorders and chest pain. Motility abnormalities have long been recognized as a possible esophageal cause of chest pain; however, their exact role and prevalence remain largely unknown. Baseline manometry and the various provocative tests may suggest an esophageal origin, but their yield is low. The recent advent of prolonged ambulatory monitoring of intraesophageal pressure and the assessment of psychological factors are contributing to a clearer understanding of this complex problem. 
Absent left main coronary artery: angiographic findings in 83 patients with separate ostia of the left anterior descending and circumflex arteries at the left aortic sinus. Among 20,332 adult patients who underwent consecutive cardiac catheterization and coronary arteriography, 83 (0.4%) were angiographically identified as having an absent left main coronary artery. The angiographic characteristics of this coronary anomaly include: (1) the presence of two well-separated coronary ostia at the left aortic sinus resulting in separate origin of the left anterior descending and circumflex arteries; (2) an increased incidence of left coronary dominance; (3) a higher (6%) than usual (0.5% to 1.5%) incidence of myocardial bridging; (4) lack of a high incidence of congenital heart anomalies; and (5) an incidence of atherosclerotic coronary artery disease similar to that of patients whose left main artery is intact. In 39% of the patients difficulties in selectively cannulating the separate ostium of the circumflex artery and adequately opacifying this vessel resulted in a need to change the diagnostic catheter size. Recognition of this coronary anomaly is needed to ensure accurate angiographic interpretation and is important for patients undergoing cardiac surgery to selectively perfuse these separate vessels during cardiopulmonary bypass. 
Popliteal aneurysm with spontaneous arteriovenous fistula. This report documents a rare manifestation of aneurysmal disease of the popliteal artery. We describe a popliteal aneurysm presenting with acute venous hypertension due to a spontaneously occurring arteriovenous fistula. The fistula was defunctionalized by treating the aneurysm with a standard technique of exclusion and bypass with resolution of the symptoms of venous hypertension and maintenance of normal distal perfusion. 
Liver dysfunction associated with long-term total parenteral nutrition in patients with massive bowel resection. Sixteen patients with massive bowel resection receiving long-term home total parenteral nutrition (HTPN) for 31 to 145 months were reviewed for evidence of liver disease. Patients were divided into three groups: group 1 with duodenocolostomy (n = 3), group 2 with an estimated 15-43 cm residual small bowel (n = 7), and group 3 with an estimated 55-120 cm residual small bowel (n = 6). Two patients in group 1 developed liver cirrhosis; one was diabetic and died of sepsis and liver failure at the 88th month on HTPN; the other died of lung cancer at the 46th month on HTPN. The third patient, followed for 33 months, had transient severe liver function abnormalities associated with a blood transfusion. In groups 2 and 3, only one patient (with a history of probable liver disease before HTPN) developed biopsy-proven cirrhosis at the 60th month of HTPN. All four patients with clinically apparent liver disease developed persistent elevation of serum aspartate aminotransferase (AST) early in HTPN. Four other patients (all in group 3) with abnormal AST values in the early phase of HTPN normalized them later; they did not develop clinical liver disease over a mean follow-up time of 110 months (range, 39-152). None of the remaining eight patients (seven in group 2 and one in group 3) had significant liver function test abnormalities and none developed clinical liver disease over a mean follow-up period of 72 months (range, 39-120). 
Prenatal hepatitis B testing in a midsize southern city. Universal prenatal screening for hepatitis B in low-risk populations remains controversial. The purpose of this study was to characterize the obstetric population of the city/county hospital in a midsize southern city. A total of 2013 patients were screened for hepatitis B surface antigen and antibody between June 1988 and February 1990, with 1893 negative for both, 105 (5.2%) positive for surface antibody, and 15 (0.8%) positive for surface antigen. Only 25% of the patients with positive results of hepatitis B screening would have been identified by the 1984 Centers for Disease Control risk group criteria, and no other predictive features were identified. We conclude that universal prenatal screening for hepatitis B is indicated in low-risk populations because of the high prevalence and the lack of predictive features. 
Hypertension sustains plaque progression despite reduction of hypercholesterolemia. To assess the effect of hypertension on diet-induced coronary artery plaques after a return to a nonatherogenic diet, 10 cynomolgus monkeys were fed an induction regimen containing 2% cholesterol and 25% peanut oil for 6 months and then were subjected to midthoracic aortic coarctation to induce hypertension. The animals were then fed a nonatherogenic "prudent" ration for 6 additional months (hypertension-regression group). Twelve additional monkeys were fed the atherogenic diet for 6 months; six were killed (lesion-induction control group) and six were changed to the prudent diet for 6 additional months without coarctation (normotension-regression control group). At the end of the induction period, cholesterol levels averaged 744 +/- 178 mg/dl for the 22 animals and were similar for the three groups throughout the induction period. For the animals restored to the nonatherogenic diet (hypertension-regression and normotension-regression groups), serum cholesterol levels fell to 486 +/- 252 mg/dl at 1 month, to 341 +/- 162 mg/dl at 2 months, and to 234 +/- 78 mg/dl at 6 months. There was no significant difference between the hypertensive and normotensive animals. Six months after coarctation, blood pressure proximal to the coarctations for the hypertension-regression group ranged from 100/60 to 220/145 mm Hg with a mean of 166/103 +/- 36/28 mm Hg. Cross-sectional area of coronary plaques was somewhat lower for the normotension-regression control group compared with the lesion-induction control group, but the difference was not significant. Plaque area was, however, markedly greater in the hypertension-regression group than in either the lesion-induction or the normotension-regression groups (p less than 0.05 for each) despite progressive reduction in hyperlipidemia. 
Public health consequences of acute displacement of Iraqi citizens--March-May 1991. In late March 1991, following military and civil strife in Iraq, approximately 400,000 ethnic Kurds and other Iraqi minority groups sought refuge in rugged mountains on the border of Iraq and Turkey; an additional estimated 1.3 million Iraqi refugees fled to Iran. In contrast to groups affected in other recent refugee emergencies, a large proportion of this displaced population comprised educated urban dwellers. This report describes the major public health consequences of this population displacement and international relief efforts directed toward these problems. 
Serum interleukin-6 levels correlate with disease status in patients with epithelial ovarian cancer. Interleukin-6 is a pleiotropic cytokine with a wide range of effects, including induction of B-cell and cytotoxic T-cell differentiation, and induction of acute phase reactant production by hepatocytes. Interleukin-6 also can act as an autocrine growth factor in malignancy. Various cell types produce interleukin-6, including T and B cells, monocytes, fibroblasts, and some solid tumor cells. In previous work we detected the production of substantial amounts of interleukin-6 by human ovarian cancer cells, including the ovarian cancer cell lines CAOV-3, OVCAR-3, and SKOV-3, and several primary ovarian tumor cultures. In this study we retrospectively examined 90 separate serum specimens for interleukin-6 in 36 patients with epithelial ovarian cancer. The mean serum interleukin-6 concentration of those ovarian cancer patients with macroscopic disease (n = 57) was 0.26 +/- 0.04 U/ml (mean +/- SEM). Healthy adult donors have interleukin-6 serum levels of 0.12 +/- 0.03 U/ml. Sixteen of 21 ovarian cancer patients with macroscopic disease (76%) had elevated (greater than 0.20 U/ml) levels of serum interleukin-6, with levels approaching 1 U/ml in some patients (p less than 0.01). Of those nine patients with bulky tumor (residual greater than 2 cm), eight (89%) had an elevated interleukin-6 level (mean, 0.31 +/- 0.05), while eight of 12 (66%) with minimal residual disease (less than 2 cm) had elevated levels. Only two of 15 (13%) patients who were in clinical remission and who had microscopic disease had elevated values. Of the 36 patients, 22 were CA 125 negative (less than 35 U/ml), and of these, four had elevated interleukin-6 levels. Of the 14 patients with an elevated CA 125 level, 12 (86%) had elevated interleukin-6 levels. In those 16 patients in whom serial levels of interleukin-6 were measured, rising levels were found over a 3 to 4 month interval in nine (56%); this correlated with tumor progression. Furthermore, the subsequent survival of patients was shown to correlate with the level of interleukin-6, such that patients whose levels were elevated greater than 0.20 U/ml interleukin-6 survived a mean of 12.5 months, compared with 27.2 months for patients with normal levels (p less than 0.001). These data support the concept that interleukin-6 may be a useful tumor marker in some patients with epithelial ovarian cancer, as it correlates with the tumor burden, clinical disease status, and survival. 
The nature of congenital posterior cervical or cervicothoracic midline cutaneous mass lesions. Report of eight cases. Between 4% and 8% of cases of spina bifida cystica occur in a cervical or cervicothoracic location. Despite a large body of literature concerning spinal dysraphism, there has been little written specifically about patients afflicted with this disorder in a cervical location. Eight children who presented at birth with posterior cervical or cervicothoracic lumps, all of which represented a dysraphic state, are discussed. Two types of abnormalities were noted. Three patients had hydromyelia with an associated myelocystocele herniating posteriorly into a meningocele sac. In these three patients there was an associated Chiari II malformation and hydrocephalus. The other five children had a meningocele in which a band of tissue extended from the posterior aspect of the spinal cord through a defect in the bone and fascia to the posterior part of the meningocele sac itself. No patient had a lesion that could be described as a meningomyelocele. The investigation and surgical management of these conditions are discussed and the need for intradural exploration to untether the spinal cord in the cervical region is stressed. 
MSG and hydrolyzed vegetable protein induced headache: review and case studies. Monosodium glutamate (MSG), an established headache trigger, has become far more prevalent in canned, packaged and prepared foods over the past decade. The presence of MSG in food may be difficult to detect since the terms "natural flavor," "flavoring," or "hydrolyzed vegetable protein (HVP)," all may appear on food labels to refer to MSG, according to current FDA food labeling codes. HVP typically contains 10-30% MSG. Case studies are presented in which the elimination of all food sources of MSG resulted in decreased headache frequency. Information and food lists helpful in identifying dietary MSG and HVP are presented. When patients are put on an MSG-free trial diet, attention needs to be given to identification of the wide variety of foods containing MSG and HVP. 
Identification of false positive exercise tests with use of electrocardiographic criteria: a possible role for atrial repolarization waves Atrial repolarization waves are opposite in direction to P waves, may have a magnitude of 100 to 200 mu V and may extend into the ST segment and T wave. It was postulated that exaggerated atrial repolarization waves during exercise could produce ST segment depression mimicking myocardial ischemia. The P waves, PR segments and ST segments were studied in leads II, III, aVF and V4 to V6 in 69 patients whose exercise electrocardiogram (ECG) suggested ischemia (100 mu V horizontal or 150 mu V upsloping ST depression 80 ms after the J point). All had a normal ECG at rest. The exercise test in 25 patients (52% male, mean age 53 years) was deemed false positive because of normal coronary arteriograms and left ventricular function (5 patients) or normal stress single photon emission computed tomographic thallium or gated blood pool scans (16 patients), or both (4 patients). Forty-four patients with a similar age and gender distribution, anginal chest pain and at least one coronary stenosis greater than or equal to 80% served as a true positive control group. The false positive group was characterized by 1) markedly downsloping PR segments at peak exercise, 2) longer exercise time and more rapid peak exercise heart rate than those of the true positive group, and 3) absence of exercise-induced chest pain. The false positive group also displayed significantly greater absolute P wave amplitudes at peak exercise and greater augmentation of P wave amplitude by exercise in all six ECG leads than were observed in the true positive group. 
Supravalvar aortic stenosis: a 29-year review of surgical experience Between February 1960 and August 1989, 73 consecutive patients underwent surgical correction for supravalvar aortic stenosis (SVAS) at the Texas Heart Institute. There were 43 male (59%) and 30 female patients (41%) ranging in age from 5 days to 27 years (mean age, 12 years). Preoperatively, 8 patients were in New York Heart Association functional class I, 43 in class II, 18 in class III, and 4 in class IV. Of the 73 patients, 62 had localized SVAS and 11 (15%), diffuse SVAS. For all procedures, patients were placed on cardiopulmonary bypass. Those with localized SVAS were successfully treated with patch aortoplasty, whereas those with diffuse SVAS required either an apicoaortic conduit or extensive end-arterectomy with extended patch aortoplasty. There were eight early deaths (less than or equal to 30 days postoperatively) (11%) and four late deaths (greater than 30 days postoperatively) (6%) in a follow-up period ranging from 2 months to 28 years. Sixteen patients (25%) underwent one or more additional operations in the follow-up period. Postoperatively, there were 44 patients in New York Heart Association functional class I and 17 in class II. Preoperative functional class III and class IV (p less than 0.0005), diffuse SVAS (p = 0.05), and the presence of associated congenital defects (p less than 0.01) were important determinants of death. 
An innovative method for neuraxis radiotherapy using partial transmission block technique. Whole CNS (neuraxis) radiotherapy is an important part of therapy for certain CNS tumours which seed via the CSF. Many, if not the majority, of these predominantly young patients are cured but the neuropsychometric, neuroendocrine and growth morbidity of neuraxis radiotherapy on children by conventional methods may be considerable; patients receiving such therapy at an early age often are eventually in the educationally subnormal category. Recent radiobiological data support the concept that all aspects of CNS radiation tolerance are heavily dependent on daily fraction size. We describe a new radiotherapy technique that allows lower daily fraction sizes to be delivered to the neuraxis without prejudicing the total dose to the neuraxis or primary area and without prolonging the overall treatment time. Published radiobiological data support the concept that all the major morbidities attributed to conventional neuraxis radiotherapy will be reduced by the currently described technique without reducing tumour control rates. 
Mechanical obstruction to ventilation from an ovarian cyst during pregnancy. This report documents the danger of the gravid uterus fixing a large ovarian cyst in a position disadvantageous to diaphragmatic excursion and thereby obstructing ventilation. A 34-year-old pregnant patient presented at 18 weeks amenorrhoea with a large ovarian cyst. She gave a history of exertional dyspnoea and orthopnoea. Clinical examination revealed a grossly enlarged abdomen and a respiratory rate of 28 breaths.min-1. Intraoperatively, ventilation was markedly impaired resulting in cyanosis and bradycardia. This was relieved by drainage of the ovarian cyst. A left lateral tilt with manual traction on the tumour may have avoided this problem. Should the above measures be inadequate, immediate drainage of the cyst is essential. Severe respiratory distress may require ultrasound-guided, percutaneous, aspiration of the cyst preoperatively. However, as in this patient, the absence of gross signs of respiratory failure does not preclude acute ventilatory failure after induction of anaesthesia. 
Different lectin-binding patterns in primary breast cancers and their metastases. The expression of glycoconjugates in primary tumors and their metastases in 18 consecutive cases of metastasized breast cancer was studied by use of lectin histochemistry. Paraffin sections were stained with a panel of seven fluorochrome-labeled lectins with defined sugar specificities. The study revealed variation in the lectin binding patterns of individual cancers. In the primary tumors the lectin reactivity was diversified, whereas in their respective metastases it was rather homogeneous. This finding indicates that there is intratumoral heterogeneity in the primary cancers, whereas the selected subclones of malignant cells with restricted glycoconjugate expression seem to give rise to metastases. 
A report of familial carotid body tumors and multiple extra-adrenal pheochromocytomas. A case of familial carotid body tumors and multiple extra-adrenal pheochromocytomas is reported. The carotid body tumors, resected previously, were bilateral and associated with 4 intra-abdominal extra-adrenal pheochromocytomas. Magnetic resonance imaging was far superior to computerized tomography and 131iodine-metaiodobenzylguanidine in visualizing the intra-abdominal lesions, and may soon become the imaging technique of choice in the evaluation of patients with suspected pheochromocytoma. 
Prevention of alloimmunization in patients with acute leukemia by use of white cell-reduced blood components--a randomized trial. Platelet refractoriness arising from HLA alloimmunization is a serious complication of transfusion therapy. In a prospective randomized trial, white cell (WBC)-reduced blood components were compared to standard platelet and red cell concentrates with respect to alloimmunization, refractoriness, and platelet increments after transfusion. Sixteen of 31 adult acute leukemia patients received only WBC-reduced platelet concentrates (PCs) and red cells (RBCs), with fewer than 10(6) WBCs per unit. Fifteen control patients received standard blood components with a mean of 0.1 x 10(9) (PCs) and 1 x 10(9) (RBCs) WBCs per unit. Platelet loss during cotton-wool filtration averaged 14 percent (range, 3-32%) from fresh PCs and 24 percent (range, 9-62%) from stored PCs. Filtration did not change corrected increments (CI) measured after transfusion of fresh PCs. The Cl 1 hour after filtration of stored PCs diminished by 27 percent, but the difference was smaller after 18 hours, which suggests better survival of WBC-reduced platelets. The number of platelet units transfused did not differ in the two groups. No patient in the WBC-reduced group developed permanent platelet refractoriness; transient HLA antibodies of low titer developed in two patients. In the control group, one patient became refractory because of immunization and two developed transient HLA antibodies. It can be concluded that the reduction of WBCs in blood components can effectively prevent alloimmunization. 
Basophil-bound and serum immunoglobulin E directed against Helicobacter pylori in patients with chronic gastritis. The immunoglobulin (Ig) E immune response in patients with Helicobacter pylori-associated chronic gastritis has been evaluated. Of 26 patients with H. pylori infection, 22 (84%) tested positive for basophil-bound specific IgE (determined by the histamine release test) and 18 (69%) for serum specific IgE (determined by an enzyme-linked immunosorbent assay). In contrast, only 1 of 17 persons in whom the bacterium was not detected presented cell-bound and serum specific IgE. In the 4 histamine release test--positive but enzyme-linked immunosorbent assay--negative patients, removal of antibody from the basophil surface by acid elution showed that histamine release occurred through an IgE-dependent mechanism. When normal basophils, passively sensitized with serum from IgE-positive patients, were exposed to the H. pylori antigen, a significant release was observed, confirming the class specificity of the response. Inhibition experiments with bacteria other than H. pylori showed that the IgE antibody was specifically directed against this organism. The percentage of antigen-induced histamine release did not correlate with serum specific IgE level. However, the response of basophils to antigenic challenge was proportional to IgE-dependent cellular releasability. This finding suggests that target cell sensitivity may be the most important factor in determining the entity of biological response to the antigenic challenge. The ability of H. pylori to induce a specific IgE immune response could answer key questions regarding the mechanisms inducing gastric inflammation. 
Personality traits in the mechanisms of interferential therapy for osteoarthritic knee pain. The role of hypochondriacal, depressive, and hysterical personality traits in response to interferential therapy (IFT) was studied in 50 patients with chronic knee osteoarthrosis. Personality traits were assessed through the Minnesota Multiphasic Personality Inventory. Each patient received ten sessions of IFT during two weeks. Pain relief was assessed subjectively (with a numerical pain-relief scale) at the end of treatment and one week later in a single-blind method. Patients who experienced pain relief of 50% or more were considered responders (n = 22). Those who experienced pain relief of 25% or less were considered nonresponders (n = 24). No statistically significant difference was found between the two groups on any of the personality traits studied. These personality traits apparently have no effect on the response of osteoarthritic knee pain to IFT. 
Human gallbladder morphology after gallstone dissolution with methyl tert-butyl ether. The effects of methyl tert-butyl ether exposure on the human gallbladder in five patients who were treated for gallstones by contact dissolution is described. Two patients underwent cholecystectomy within 1 week of methyl tert-butyl ether treatment, one patient 2 weeks after, another 10 weeks after, and one 12 weeks after. Indications for cholecystectomy were bilirubinate stones (resistant to methyl tert-butyl ether), catheter dislodgement, bile leakage, and gallstone recurrence (2 patients). Gallstones were dissolved completely in three patients, there was approximately 50% stone reduction in one patient, and no dissolution occurred in the fifth patient. Each gallbladder was examined grossly and histologically. Electron microscopic evaluation was performed in one cases. Typical inflammatory findings of chronic cholecystitis were observed in each gallbladder and were most conspicuous in the submucosa; the mucosal and serosal surfaces were intact. Mild acute inflammatory changes were noted in the submucosa in the two patients with the shortest interval between methyl tert-butyl ether administration and cholecystectomy. There were no ulcerations in the mucosa and no unusual wall thickening or fibrosis in any patient. These observations support the safety of methyl tert-butyl ether perfusion in the human gallbladder; the mild acute changes may be a transient and reversible phenomenon. 
Extensive hepatic granulomas associated with peripheral T-cell lymphoma. A case of T-cell lymphoma presenting with marked hepatosplenomegaly and extensive hepatic granulomas is described. A 55-yr-old female experienced long-term liver damage showing histological triaditis with atypical lymphoid cell infiltration and erythrophagocytosis. The patient developed marked hepatosplenomegaly and eventually died of respiratory failure. Neither systemic lymphadenopathy nor hematological disorder was noted until her death. Autopsy revealed small atypical lymphoid cells positive for T-cell marker, as well as extensive infiltration of generalized organs, including the liver, spleen, and lungs. As a result of diffuse proliferation of atypical lymphoid cell admixed with variable reactive cells, mainly at the T-zone, the lymph nodes underwent effacement of normal architecture; however, the peripheral sinuses and the fibrous capsule remained relatively well preserved. These histological features were consistent with a diagnosis of peripheral T-cell lymphoma (PTL). It is interesting to note that there were numerous epithelioid granulomas admixed with a small number of atypical lymphoid cells within the hepatic parenchyma. The atypical lymphoid cells may be responsible for the granulomatous reaction in the liver. To our knowledge, there have been no other reported cases of PTL that presented with numerous epithelioid granulomas confined to the liver. 
Aggressive malignant hemangiopericytoma in the neck. Hemangiopericytomas are rare vascular tumors, one fourth of which occur in the head and neck. These lesions are characteristically slow growing and slow to metastasize. We describe an otherwise healthy patient with a hemangiopericytoma on the left side of his neck that metastasized to his chest wall within 3 months after the tumor was first observed. The metastasis occurred while the patient was receiving radiation therapy. The patient died soon afterward. This case illustrates the aggressive malignant potential of hemangiopericytomas. 
Immunization response varies with intensity of acute lymphoblastic leukemia therapy. Twenty-four children receiving maintenance chemotherapy for acute lymphoblastic leukemia were given booster doses of tetanus-diphtheria combined toxoids. One month later, 19 of the 24 children were given Haemophilus influenzae B oligosaccharide-cross-reacting material conjugate vaccine. Following immunization, all patients had protective antibody titers against tetanus, 92% had protective antidiphtheria titers, and 84% had protective titers against H influenzae. Preimmunization titers, postimmunization titers, and response to immunization varied according to the intensity of therapy. There was no correlation with duration of therapy or quantitative hematologic values in the peripheral blood. These observations support the recommendation that children treated for acute lymphoblastic leukemia should be immunized against H influenzae B. 
Anomalous insertion of papillary muscle directly into anterior mitral leaflet in hypertrophic cardiomyopathy. Significance in producing left ventricular outflow obstruction. BACKGROUND. Obstruction to left ventricular outflow in hypertrophic cardiomyopathy (HCM) is usually due to systolic anterior motion of the mitral valve. Occurrence of structural mitral valve abnormalities in HCM and their significance in producing outflow obstruction (even in the absence of typical systolic anterior motion) has not been fully appreciated. METHODS AND RESULTS. Analysis of 78 mitral valves excised from patients with obstructive HCM showed that 10 (13%) had anomalous insertion of one or both left ventricular papillary muscles directly into the anterior mitral leaflet. This malformation was identified by echocardiography, which demonstrated direct continuity between the hypertrophied papillary muscle and mitral leaflet, resulting in a long rigid area of midcavity narrowing that appeared to be solely or largely responsible for outflow obstruction. Basal subaortic pressure gradients were large (70-150 mm Hg). Mitral valve replacement reduced the outflow gradient substantially to 0-15 mm Hg in four patients with postoperative cardiac catheterization. However, two other patients who underwent septal myotomy/myectomy had persistent symptoms and incomplete relief of obstruction (gradients 60 and 70 mm Hg) because of continued midcavity apposition of papillary muscle and ventricular septum. CONCLUSIONS. Anomalous papillary muscle insertion into anterior mitral leaflet represents a mechanism of obstruction to left ventricular outflow in patients with HCM and differs considerably from typical dynamic obstruction caused by mitral valve systolic anterior motion that occurs in many other patients with HCM. Recognition of this malformation emphasizes the diverse morphological expression of HCM and also has important clinical implications for patients requiring operation because the gradient is likely to persist even after adequate myotomy/myectomy; consequently, mitral valve replacement would appear to be the operation of choice in most such patients. 
Coronary stenting with a new, radiopaque, balloon-expandable endoprosthesis in pigs. BACKGROUND. Intracoronary stents may be effective when used as "bail-out" devices for acute complications after percutaneous transluminal coronary angioplasty. Furthermore, preliminary reports have demonstrated some promising results with stents with regard to the reduction of restenosis. Several stent devices are available for preclinical and clinical evaluation. The use of these stainless-steel stents has been limited by poor visibility during fluoroscopy and thrombogenicity during the first days to weeks after implantation. We therefore investigated the immediate and short-term effects on arterial patency of a new, radiopaque, balloon-expandable coil stent in normal coronary arteries of pigs. METHODS AND RESULTS. In 10 animals, a stent was placed in two of the three epicardial coronary arteries. During the implantation procedure, the animals received heparin; after the procedure, no antithrombotic drugs were administered. After 1 week (five animals and 10 stents) or 4 weeks (five animals and 10 stents), repeat angiography was performed, followed by pressure-fixation of the coronary arteries for light and electron microscopic examination. Angiographic analysis revealed that all stented coronary segments were patent and without signs of intraluminal defects. Scanning electron microscopy showed complete endothelial covering of all stents within 7 days. Light microscopy showed a reduced tunica media locally under the stent wires, which resulted from exerted pressure. The neointima on top of the stent wires measured 56 microns (range, 42-88 microns) after 1 week and 139 microns (range, 84-250 microns) after 4 weeks. CONCLUSIONS. Results from this study show that this radiopaque endoprosthesis can be safely placed in normal coronary arteries of pigs. After 4 weeks, all stents were patent and there was no need for additional antithrombotic treatment, whereas neointimal proliferation was limited. 
Focal nodular hyperplasia of the liver: assessment with contrast-enhanced TurboFLASH MR imaging. Twenty-two patients with 25 cases of focal nodular hyperplasia (FNH) proved with pathologic study were imaged with a TurboFLASH (fast low angle shot) sequence combined with bolus administration of gadolinium tetraazacyclododecanetetraacetic acid (DOTA), spin-echo (SE) T2-weighted sequences, and postcontrast T1-weighted sequences. FNH-liver signal-difference-to-noise ratios were quantified; the features of the central scar were qualitatively analyzed. On SE T2-weighted images, all FNHs were hyperintense; in two cases the central scar exhibited a high signal intensity associated with hypointense areas corresponding to fibrous tissue within the branches of the scar. Unenhanced TurboFLASH images always demonstrated the FNHs as hypointense and always depicted the central scar as a hypointense area within the lesion. After bolus injection, arterial enhancement of FNH was clearly seen, and in 10 of 25 lesions, enhancement within the scar was seen 40-80 seconds after injection. Both unenhanced and enhanced TurboFLASH sequences produced the best signal-difference-to-noise ratios in comparison with T2-weighted images. 
Solitary extradural cavernous hemangiomas in the spinal canal. Report of five cases. Five cases of solitary extrathecal cavernous hemangioma in the spinal canal are reported. In one case, two coexistent massive cerebral venous medullary malformations were found. The symptomatology and prognosis of extrathecal spinal cavernous hemangiomas are discussed, as is the significance of various diagnostic measures. The patient material further permitted a rough calculation of the incidence of symptomatic extrathecal cavernous hemangiomas in the spinal canal. 
Adverse psychologic consequences of positive cytologic cervical screening. Cervical cancer is still widely prevalent in the female population. This study explores the relationship of cervical cancer screening, positive versus negative Papanicolaou's test results, and psychologic status among lower-income minority women. All patients were interviewed 3 months after they had received initial test results. One hundred six women with normal Papanicolaou's test results were compared with 118 women who were referred for colposcopic examination for follow-up of positive test results. Women with positive Papanicolaou's-test results showed statistically significant elevations in worries about cancer and impairments in mood, daily activities, sexual interest, and sleep patterns. More fine-grained analyses revealed that the effects of positive results were most pronounced among those women who did not comply with colposcopy (n = 53). These findings suggest that lack of compliance with follow-up may maintain high levels of uncertainty about disease and may interfere with successful psychologic adaptation. Health education targeted to psychologically vulnerable individuals may reduce psychologic distress and enhance compliance. 
Hypothyroidism resulting from generic levothyroxine failure. In today's cost-conscious health care system, generic preparations should be prescribed whenever possible provided that safety and efficacy are not compromised. Several reports, however, suggest that generic levothyroxine may not always be interchangeable with the proprietary preparations. Such interchangeability is critical because patients are likely to receive different brands of levothyroxine during the life of their treatment. We report a case of severe hypothyroidism that developed in a patient who had been well controlled before receiving a generic levothyroxine preparation. Analysis of the patient's tablet by high-pressure liquid chromatography showed that the levothyroxine content was approximately 30 percent less than its labeled content and outside current Food and Drug Administration (FDA) requirements. It is likely that poor tablet bioavailability was a contributory factor. Euthyroidism was achieved with the same dose of a more potent and possibly more bioavailable brand-name product. Until levothyroxine products become more uniform and the FDA confers therapeutic equivalence, product substitution with expense as the principal consideration should be avoided. 
Risk factors for pancreatic cellular injury after cardiopulmonary bypass BACKGROUND. Pancreatitis is a known complication of cardiac surgery with cardiopulmonary bypass. Although ischemia is believed to be a factor, the cause of pancreatitis after cardiopulmonary bypass remains unknown. METHODS. We prospectively studied 300 consecutive patients undergoing cardiac surgery with cardiopulmonary bypass. Serum amylase, pancreatic isoamylase, and serum lipase were measured on postoperative days 1,2,3,7, and 10. Pancreatic cellular injury was defined as the presence of hyperamylasemia (greater than 123 U per liter) with an increase in either the serum level of lipase (greater than 24 U per liter) or the peak level of pancreatic isoamylase. Trypsinogen-activation peptides, which indicate intrapancreatic enzyme activation, were measured in the urine of the last 101 patients studied. RESULTS. Evidence of pancreatic cellular injury was detected in 80 patients (27 percent), of whom 23 had associated abdominal signs or symptoms and 3 had severe pancreatitis (2 with pancreatic abscess and 1 with necrotizing hemorrhagic pancreatitis). Two of 19 postoperative deaths were secondary to pancreatitis. In multivariate analyses, the development of pancreatic cellular injury was significantly associated with preoperative renal insufficiency, valve surgery, postoperative hypotension, and perioperative administration of calcium chloride. The administration of more than 800 mg of calcium chloride per square meter of body-surface area was an independent predictor of pancreatic cellular injury, and the increase in risk was dose-related. No differences were found in the level of trypsinogen-activation peptides between patients who had pancreatic cellular injury and those who did not. CONCLUSIONS. Pancreatic cellular injury, as indicated by hyperamylasemia of pancreatic origin, is common after cardiac surgery. The administration of large doses of calcium chloride is an independent predictor of pancreatic cellular injury and may be a cause of it. 
The golden hours of the myocardial infarction: nonthrombolytic interventions. Emergency care of patients with acute myocardial infarction requires active decision making to use agents that may improve morbidity and mortality. Thrombolysis remains the primary tool to accomplish this goal. Other pharmacologic agents, including lidocaine, nitrates, calcium channel blockers, beta-blockers, and aspirin, have been used acutely in myocardial infarction in the hopes of preventing death and salvaging myocardium. The decision to select one or all of these agents requires a knowledge of the clinical evidence of their efficacy and risk-to-benefit ratios. The clinical studies of the use of these agents acutely in the management of myocardial infarction are reviewed. 
Lower limb problems in diabetic patients. What are the causes? What are the remedies? Peripheral neuropathy, infection, and peripheral vascular disease can produce serious problems in diabetic patients, particularly in the lower limbs. Ulceration of the foot may progress to gangrene and ultimately necessitate amputation. Distal symmetric polyneuropathy causes sensory loss. Such loss in patients with peripheral vascular disease creates a high risk for foot ulcers, which are vulnerable to infection. Treatment includes relief of neuropathic pain and antibiotic therapy for infection. Pentoxifylline (Trental) improves microvascular flow and appears to be effective against peripheral vascular disease. Aldose reductase inhibitors are being investigated as therapy for diabetic neuropathy. Prevention is the mainstay of management in these patients. Patient education is essential to help maintain health and prevent the potential adverse effects of diabetes. 
Assessment of 21-[18F]fluoro-16 alpha-ethyl-19-norprogesterone as a positron-emitting radiopharmaceutical for the detection of progestin receptors in human breast carcinomas. We have used 21-[18F]fluoro-16 alpha-ethyl-19-norprogesterone (FENP) for imaging progestin receptors by PET in patients with primary carcinoma of the breast. In vitro binding and in vivo tissue distribution studies in rats have shown that FENP has high specific activity, high affinity for progestin receptors, and receptor-mediated uptake in target tissues. Eight patients with primary breast carcinoma were studied. Breast carcinoma was identified correctly in 50% of the patients with progestin-receptor-positive tumors; however, the FENP uptake was not correlated with progestin-receptor levels. We noted a low target-to-background ratio in humans, with high relative activity in the spine, blood pool, and normal breast tissue. Our findings indicate that FENP is not a suitable agent for imaging progestin receptors in humans. 
Comparison of intravenous urokinase plus heparin versus heparin alone in acute myocardial infarction. Urochinasi per via Sistemica nell'Infarto Miocardico (USIM) Collaborative Group. In a randomized trial of the effects on in-hospital mortality of intravenous urokinase plus heparin versus heparin alone, 2,531 patients with acute myocardial infarction in 89 coronary care units were enrolled for greater than 30 months. Patients admitted within 4 hours of the onset of pain were randomized to receive either intravenous urokinase (a bolus dose of 1 million U repeated after 60 minutes) plus heparin (a bolus dose of 10,000 U followed by 1,000 IU/hour for 48 hours) or heparin alone (infused at the same rate). Complete data were obtained in 2,201 patients (1,128 taking urokinase and 1,073 taking heparin). At 16 days, overall hospital mortality was 8% in the urokinase and 8.3% in the heparin group (p = not significant). Among patients with anterior infarction, mortality was 10.3% in the urokinase and 13.9% in the heparin group (p = 0.09; relative risk = 0.73). The incidence of major bleeding (urokinase 0.44%, heparin 0.37%) as well as the overall incidence of stroke (urokinase 0.35%, heparin 0.20%) was similar in the 2 groups. The rates of major in-hospital cardiac complications (reinfarction, postinfarction angina) were also similar. 
A case report of malignant pleural mesothelioma with long-term disease control after chemotherapy. Long duration of responses to chemotherapy in patients with malignant pleural mesothelioma (MPM) is rare. The authors report a patient with inoperable MPM who achieved complete remission with combination chemotherapy of cyclophosphamide, doxorubicin, and cisplatin. 5-fluorouracil and mitomycin C (FM) induced another remission after recurrence of the tumor. Retreatment with FM after chemotherapy had been stopped for 20 months yielded another continuing response. The overall tumor-control time is more than 4 years. Literature reviews and the authors' results suggest that MPM may be a chemosensitive tumor in some patients. Additional evaluations of CAP, FM, and methotrexate combination regimens in this disease should be considered. 
Tonic pain perception in the mouse: differential modulation by three receptor-selective opioid agonists. The proposition that tonic nociception models are more analogous to clinical pain than traditional acute models prompted our previous development of a modified mouse paw formalin test. To discern possible modulatory roles and site(s) of action of endogenous opioid systems, the receptor-preferring agonists sufentanil (mu), U-50,488H (kappa) and [D-Pen2,5]enkephalin (DPDPE, delta) were evaluated for antinociceptive activity in the formalin paradigm by systemic (except DPDPE), spinal and supraspinal routes. All observations were done under blind conditions. Doses causing overt behaviors that indicated a breach of receptor specificity (during the observation period) were rejected. Higher doses of centrally administered DPDPE (greater than 0.3 micrograms/mouse, intrathecal; greater than 3 micrograms/mouse, intracerebroventricular) induced a behavioral syndrome traditionally associated with mu agonism, and thus were not considered for this study. A50 values from behaviorally acceptable dose ranges for mean percent analgesia (reduction of paw licking compared to controls) were: trans-(+/- )-3,4-dichloro-N-methyl-N-[U-50,488H 2-pyrrolidinyl)cyclohexyl]-benzeneacetamide methanesulfonate,U-50,488H--3200 nmol/kg, subcutaneous, 1100 nmol/kg, intrathecal and 314 nmol/kg, intracerebroventricular; sufentanil--11.1 nmol/kg, subcutaneous, 8.6 nmol/kg, intrathecal; and DPDPE--inactive. On the basis of our dose-response data, we suggest that, in mice, kappa and mu, but not delta, opioid receptors modulate tonic pain perception at both spinal and supraspinal loci. The results also support inclusion of the modified formalin test in preclinical evaluations of potential kappa agonists. 
Myocardial infarct size reduction by the synergistic effect of hyperbaric oxygen and recombinant tissue plasminogen activator. Fasting mongrel dogs underwent hyperbaric oxygen treatment (HBOT), recombinant tissue plasminogen activator (rt-PA) treatment, and simultaneous HBOT and rt-PA treatment following prior experimental left anterior descending coronary artery occlusion for 2 hours. Thrombosis in and around a copper coil was recorded angiographically at regular intervals, and immediately prior to treatment conclusion. Controls (n = 10) were untreated. Group two animals (n = 10) were treated additionally with 90 minutes of HBOT at 2 atm absolute. Group three animals (n = 8) were treated additionally with 50 mg rt-PA over 90 minutes. Group four animals (n = 10) were treated additionally with simultaneous HBOT and rt-PA over 90 minutes. Myocardial injury was determined by a combination of triphenyltetrazolium chloride histochemical staining and by formazan dye extraction. Damage was measured as a percent of left ventricular cross-sectional area studied. HBOT alone restored 35.9% of oxidative enzyme activity (p greater than 0.001). Treatment with rt-PA alone restored 48.9% of enzyme activity (p greater than 0.001). The combination of HBOT and simultaneous rt-PA resulted in 96.9% restoration of oxidative enzyme activity versus the control group (p greater than 0.001). 
Sequence variations in the 5' flanking and IVS-II regions of the G gamma- and A gamma-globin genes of beta S chromosomes with five different haplotypes. We have amplified and sequenced the 5' flanking and the second intervening sequence (IVS-II) regions of both the G gamma- and A gamma-globin genes of the beta S chromosomes from sickle cell anemia (SS) patients with homozygosities for five different haplotypes. The sequencing data, compared with previously published sequences for the normal chromosomes A and B, show many similarities to chromosome B for haplotypes 19, 20, and 17, while haplotypes 3 and 31 are remarkably similar to chromosome A and also similar to each other. Several unique mutations were found in the 5' flanking regions (G gamma and A gamma) of haplotypes 19 and 20 and in the IVS-II segments of the same genes of haplotypes 19, 20, and 17; the IVS-II of haplotypes 3 and 31 were identical to those of chromosome A. Dot-blot analyses of amplified DNA from additional SS patients with specific probes have confirmed that these mutations are unique for each haplotype. The two general patterns that have been observed among the five haplotypes have most probably arisen by gene conversion events between the A and B type chromosomes in the African population. These patterns correlate with high and low fetal hemoglobin expression, and it is speculated that these and other yet unknown gene conversions may contribute to the variations in hemoglobin F and G gamma levels observed among SS patients. In vitro expression experiments involving the approximately 1.3-kb 5' flanking regions of the G gamma- and A gamma-globin genes of the beta S chromosomes with the five different haplotypes failed to detect differences between the levels of expression, suggesting that the sequence variations observed between these segments of DNA are not the primary cause of the differences in hemoglobin F levels among the SS patients. 
Left ventricular regional wall motion assessment by radionuclide ventriculography: a comparison of cine display with Fourier imaging Radionuclide ventriculography and contrast ventriculography were performed in two comparable projections on 50 patients with suspected coronary artery disease. The efficacy of conventional cine display and Fourier image analysis of the radionuclide ventriculogram was compared using contrast ventriculography as the gold standard. Of seven different combinations of Fourier images, the combination of left anterior oblique amplitude and phase and left posterior oblique amplitude and phase provided the highest sensitivity (87%), specificity (83%), accuracy (86%), and kappa coefficient (0.64). To increase statistical power, segment data were collapsed to global data in which a heart was considered normal if all segments were normal and abnormal if one or more segments were abnormal. Fourier images had higher sensitivity (Fourier 87%, cine 47%); lower specificity (Fourier 83%, cine 92%), higher accuracy (Fourier 86%, cine 58%), and higher kappa coefficient (Fourier 0.64, cine 0.25), and these differences were statistically significant (p less than 0.01). 
Variable histotoxicity of histoacryl when used in a subcutaneous site: an experimental study. Histoacryl (butyl-2-cyanoacrylate) is one of the least histotoxic cyanoacrylate derivatives and is used as a tissue adhesive. Clinical applications primarily include skin closure (blepharoplasty incisions, etc.). In a recent study, we demonstrated that Histoacryl elicits minimal histotoxicity when used to glue bone grafts to rabbit-ear cartilage. Acute inflammation was limited to areas where Histoacryl escaped from between the bone graft and ear cartilage to contact well-vascularized soft tissue. In this study, Histoacryl was applied between bone graft and cartilage in one rabbit ear and adjacent to well-vascularized soft tissue with no graft in the opposite ear. Histologic analysis revealed minimal if any inflammation when small amounts of glue was used in the nonvascular region between bone graft and cartilage. However, subcutaneous implantation contacting well-vascularized soft tissue resulted in increased acute inflammation and prolonged foreign-body giant-cell response. Further studies are required to rule out any long-term problems associated with subcutaneous implantation of Histoacryl. 
Stroke and hypertension and its prevention. Systolic and diastolic hypertension in both men and women is a well-established risk factor for the development of ischemic and hemorrhagic stroke. Antihypertensive treatment decreases the risk, but questions remain as to the precise level of hypertension to be treated, whether the effects of antihypertensive treatment are blunted with increasing age, and the best type of antihypertensive drug or combination of drugs to be used. Further questions remain concerning the incidence of pseudohypertension and the potentially harmful effects of its treatment on the brain, and the possibility that fluctuations in blood pressure may be worse than elevation alone. A pragmatic approach would be to treat hypertension with vigor in the young, with caution in the mature, and with reluctance in the old. 
Management options in fulminant hepatic failure. The diagnosis of FHF carries with it a high mortality rate. Though the early results of OLT for FHF are encouraging, some have called for caution as these results are in a select population and may be similar to the optimistic early reports of now-discredited therapies. However, OLT differs fundamentally from all other interventions and, as such, it is ethically unjustified to withhold potentially life-saving therapy from patients with a predicted mortality in excess of 60%. Therefore, patients with FHF should be transferred at an early stage to an experienced liver unit where the option of liver transplantation can be considered. 
Predictors of relapse into major depressive disorder in a nonclinical population. OBJECTIVE: This study sought to describe, the natural history of major depressive disorder in a large group of nonclinical subjects. In particular, the analysis determined demographic and clinical risk factors for the recurrence of major depressive disorder. METHOD: Relatives, comparison subjects (matched to relatives for age and sex), and spouses of affectively ill probands underwent structured clinical assessments before and after a 6-year interval. RESULTS: Of 396 individuals who had had only major depressive disorder that ended before the initial evaluation, 33.8% (N = 134) developed a new episode during the 6-year follow-up period. Youth, but not sex, was an important demographic risk factor. The presence of minor depression at the time of initial evaluation and the number of symptoms recalled from the worst previous episode were additional clinical risk factors. At the initial evaluation, 200 other subjects had described a previous history of both major depressive disorder and a nonaffective mental disorder. When compared to the subjects who recalled only a history of major depressive disorder, these subjects were more likely to have been in an episode of chronic intermittent depression at the initial evaluation and to recall a greater number of episodes as well as a greater number of symptoms in the worst episode. A history of a nonaffective mental disorder significantly increased the risk of relapse into major depressive disorder. CONCLUSIONS: These findings agree well with a recent review of clinically based follow-up studies. Thus, youth and a history of nonaffective illness are important risk factors for the recurrence of major affective disorder in a broad variety of settings. 
Postoperative epidural morphine is safe on surgical wards. The use of epidural morphine for postoperative analgesia outside of intensive care units remains controversial. In this report our anesthesiology-based acute pain service documents experience with 1,106 consecutive postoperative patients treated with epidural morphine on regular surgical wards. This experience involved 4,343 total patient days of care and 11,089 individual epidural morphine injections. On a 0-10 verbal analog scale, patient-reported median pain scores at rest and with coughing or ambulation were 1 (inter-quartile range 3) and 4 (interquartile range 4), respectively. The incidence of side effects requiring medication were as follows: pruritus 24%, nausea 29%, and respiratory depression 0.2%. There were no deaths, neurologic injuries, or infections associated with the technique. Migration of epidural catheters into the subarachnoid space and into epidural veins each occurred twice. Overall, 1,051 of the 1,106 patients (95%) experienced none of the following problems: catheter obstruction, premature dislodgement, painful injections, catheter migration, infection, or respiratory depression. We conclude that postoperative pain can be safely and effectively treated with epidural morphine on surgical wards. 
Recombinant granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation for lymphoid cancer. BACKGROUND. The period of neutropenia after autologous bone marrow transplantation results in substantial morbidity and mortality. The results of previous phase I-II clinical trials suggest that recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) may accelerate neutrophil recovery and thereby reduce complications in patients after autologous bone marrow transplantation. METHODS. We conducted a randomized, double-blind, placebo-controlled trial at three institutions. The study design and treatment schedules were identical, and the results were pooled for analysis. One hundred twenty-eight patients were enrolled. Sixty-five patients received rhGM-CSF in a two-hour intravenous infusion daily for 21 days, starting within four hours of the marrow infusion, and 63 patients received placebo. RESULTS. No toxic effects specifically ascribed to rhGM-CSF were observed. The patients given rhGM-CSF had a recovery of the neutrophil count to 500 x 10(6) per liter 7 days earlier than the patients who received placebo (19 vs. 26 days, P less than 0.001), had fewer infections, required 3 fewer days of antibiotic administration (24 vs. 27 days, P = 0.009), and required 6 fewer days of initial hospitalization (median, 27 vs. 33 days; P = 0.01). There was no difference in the survival rate at day 100. CONCLUSIONS. In patients undergoing autologous bone marrow transplantation for lymphoid neoplasia, rhGM-CSF significantly lessens morbidity. Further studies will be required to establish its optimal dosage and schedule of administration. 
Frequency of deep venous thrombosis in asymptomatic patients with coronary artery bypass grafts. The frequency of deep vein thrombosis (DVT) in patients undergoing coronary artery bypass graft (CABG) surgery has not been established. Therefore to estimate the frequency of clinically silent DVT, we performed ultrasound examinations of the leg veins in 29 asymptomatic CABG patients before hospital discharge. We used high-resolution B-mode ultrasonography with color Doppler imaging. Fourteen (48.3%, 95% confidence interval 30.1 to 66.4%) had 20 documented leg vein thromboses, and all but one patient had DVT limited to the calf veins. Of the 20 thrombi 10 (50.0%) were present in the leg ipsilateral and 10 (50.0%) in the leg contralateral to the saphenous vein harvest site. None of the DVTs were suspected clinically. DVT was not associated with any local sign attributed to saphenous vein harvest such as pitting edema, incisional drainage, or local tenderness or with any putative risk factor for DVT such as cigarette use, distant history of malignancy, or varicose veins. Follow-up of these patients 5 to 11 months after CABG surgery showed no clinical evidence of DVT or pulmonary embolism. Our findings indicate that asymptomatic DVT of the calf occurs with surprisingly high frequency, 44.8% after CABG surgery. Future studies in patients undergoing CABG surgery should address the natural history of asymptomatic DVT, determine its clinical importance, and develop optimal strategies for prophylaxis and treatment. 
Expansion of immature thymic precursor cells in peripheral blood after acute marrow suppression. Leukemoid reactions occur in response to a number of infectious agents and sometimes may be associated with bone marrow suppression. After acute suppression of the bone marrow, a resurgent hyperplasia occurs that may appear as synchronous maturation of a single cell type. The authors describe the case of a 13-year-old child in whom a remarkable lymphocytosis developed during a period of pancytopenia associated with a febrile syndrome resembling Ehrlichiosis. Most of these lymphoid cells were morphologically similar to large granular lymphocytes (LGLs), but many appeared to be less mature. Immunophenotypic studies demonstrated most of these lymphoid cells to be immature T cells at an "intermediate" or "transitional" stage of thymocyte differentiation characterized by the CD1-CD3+CD4-CD8- phenotype, as well as positivity for nuclear terminal deoxynucleotidyl transferase. In T-cell ontogeny, this stage represents a transition between thymic precursors and mature thymocytes. Their presence in the peripheral blood of this child is thought to represent a lymphocytic leukemoid response to his infection. Cases such as this may be confused with malignancy. 
Preventing upper gastrointestinal bleeding in patients receiving nonsteroidal antiinflammatory drugs. Severe upper gastrointestinal (GI) bleeding is a serious adverse effect of nonsteroidal antiinflammatory drugs (NSAIDs) and the elderly are at increased risk of developing this complication. Bleeding episodes can be prevented. Replacing NSAIDs with acetaminophen may be appropriate when a simple analgesic is needed that eliminates the risk of GI bleeding. Using the lowest effective NSAID dose may decrease the incidence and severity of NSAID gastropathy. Histamine H2-receptor antagonists, sucralfate, and misoprostol have been studied for the prevention of NSAID gastropathy, but only misoprostol prevents mucosal injury in both the stomach and duodenum. Patients who have a history of peptic ulcer disease or gastric bleeding from NSAIDs are candidates for prophylactic measures. Although other patients are at risk, no one knows who should receive prophylactic therapy for NSAID gastropathy. Future studies should attempt to define patient populations that warrant prophylactic therapy. 
An analysis of ten-year trends in infections in adults on continuous ambulatory peritoneal dialysis (CAPD). Infectious complications are the Achilles heel of CAPD. To determine trends in these events, we analyzed the CAPD related infections of 303 adults on CAPD at a single university center between 1979 and 1989. During this decade the percentage of insulin-dependent diabetics increased from 14% to 39% (p less than 0.005). Peritonitis rates fell from 2.4 episodes/y in 1979 to 0.8 episodes/y in 1989. The proportion of patients with multiple episodes of peritonitis decreased (40% of the patients in 1979-1982 vs 15% in 1983-1989, p = 0.0001) while the proportion of patients with no episodes of peritonitis increased during the same periods (29% vs 49%, p = 0.005). The proportion of peritonitis episodes due to S. aureus rose over the 10-year period (p = 0.005), while those due to S. epidermidis decreased (p less than 0.10). The overall incidence of S. aureus peritonitis remained unchanged. Catheter infection rates initially increased and then fell during the decade; S. aureus remained the predominant cause. The proportion of peritonitis episodes associated with catheter infection rose (13% in 1982 vs 24% in 1989, p = 0.025), and in 1989, 80% of these episodes were caused by S. aureus. Catheter loss was also primarily due to S. aureus infections in 1989 (80%). Infections due to P. aeruginosa were a persistent problem. The proportion of patients transferring to hemodialysis each year paralleled catheter loss rates, which in turn appeared to be more related to catheter infection rates than to peritonitis rates. We conclude that control of S. aureus and P. aeruginosa will be the key to future reductions in the infectious complications of CAPD patients. 
The silence: the asbestos industry and early occupational cancer research--a case study. To gain insight into corporate activities regarding the identification of occupational carcinogens earlier in this century, the actions of one industry, the asbestos industry, were reviewed. This industry, in concert with many of its insurers, systematically developed and then suppressed information on the carcinogenicity of asbestos. The development of warnings for those exposed to the asbestos was delayed. As a result, millions of workers were exposed to the carcinogen and hundreds of thousands died. These events are placed into the context of similar activities in other industries during this time. 
Coronary artery bypass grafting in the octogenarian. We have performed coronary bypass grafting in 25 patients 80 years of age or more. The patients' preoperative conditions were characterized by recent myocardial infarction (16/25, or 64%), obesity (15/25, or 60%), hypertension (14/25, or 56%), and left ventricular dysfunction (21/25, or 84%). There were no deaths in the hospital or within 30 days of operation (0/25, or 0%). Postoperative complications occurred in five cases (20%). Complications were leg incision infection (2/25, or 8%), urinary tract infection (1/25, or 4%), stroke (1/25, or 4%), and transient neurologic deficit (1/25, or 4%). There were no instances of reoperation for bleeding, perioperative myocardial infarction, renal failure, pulmonary failure, intraaortic balloon pump use, or sternotomy infection in these patients. Eleven patients (44%) were hospitalized for fewer than 10 days after operation, and all but two (23/25, or 92%) were discharged within 20 days after operation. All patients were followed up, and survival and New York Heart Association functional class were determined. Cumulative survival rate was 94% at 1 year and 88% at 5 years. The cumulative percent survival rate with class I or II function was 92% at 1 year and 80% at 5 years. No patient had recurrent angina. 
Myocardial oedema and ventricular function after cardioplegia with added mannitol. Myocardial oedema may contribute to the impaired myocardial performance which commonly follows open heart surgery with cardioplegia-induced cardiac arrest. The rate of oedema formation during crystalloid cardioplegia and the relation of this to changes in ventricular compliance and ventricular function following reperfusion were studied using an isolated rabbit heart preparation. Myocardial tissue water content increased during cardioplegic arrest and the water content prior to reperfusion demonstrated an inverse correlation with ventricular function after reperfusion. In further studies the effect of adding mannitol to a standard crystalloid cardioplegic solution was investigated. The preparations were divided into two groups: nine were administered a standard cardioplegic solution (Plegisol*) (control group) and a further eight were administered the same solution mixed with mannitol to adjust the osmotic pressure to 360 mOsmol.L-3 (mannitol group). The mannitol group demonstrated less increase in RV water content and superior LV dP/dtmax following reperfusion. It is concluded that mannitol enhances protection of the myocardium during cardioplegic cardiac arrest. 
Sternohyoid muscle biopsy. A diagnostic technique in respiratory failure of neuromuscular origin. Patients with neuromuscular disease may develop respiratory failure requiring mechanical ventilation. We describe a sternohyoid muscle biopsy technique as a diagnostic aid in such patients undergoing tracheostomy for prolonged ventilatory support. The biopsy procedure is quick and without added discomfort or morbidity for the patient. Our preliminary observations in three patients suggest that the sternohyoid muscle biopsy may be a useful diagnostic tool in this selected group of patients. 
Mechanical complications associated with mentor inflatable penile prosthesis. The Mentor inflatable penile prosthesis was developed in an attempt to decrease the mechanical failure rate of the various prostheses' components. We herein report on the reliability of the device in 46 men implanted with the Mentor device from December 1982 to June 1987. Prior to manufacturer device modification in 1985, mechanical failure mainly attributable to input tubing cracks occurred in 10 of 30 implantations. Since device improvement in April 1985, the mechanical failure rate has decreased to 4 percent. The Mentor inflatable penile prosthesis has been a mechanically reliable device since design improvement in 1985. 
Pituitary hormone response to thyrotropin-releasing hormone in secondary amenorrheic women associated with simple weight loss. OBJECTIVE: To investigate endocrine dysfunction in simple weight loss amenorrhea. DESIGN: We studied pituitary hormone responses to thyrotropin-releasing hormone (TRH) in 10 women with simple weight loss amenorrhea. SETTING: Department of Obstetrics and Gynecology, University Hospital, University of Tokushima at Tokushima, Japan. PATIENTS, PARTICIPANTS: Secondary amenorrheic women associated with simple weight loss who did not have anorexia nervosa. INTERVENTIONS: Intravenous injection of 500 micrograms of synthetic TRH. MAIN OUTCOME MEASURE: Serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), thyrotropin, and prolactin were measured before and 15, 30, and 60 minutes after TRH injection. RESULTS: In normally menstruating women on day 7 of the cycle TRH did not affect serum LH and FSH levels. In women with simple weight loss amenorrhea, however, TRH raised serum LH and FSH levels significantly (P less than 0.01, respectively). Prolactin response to TRH was significantly (P less than 0.05) lower in women with simple weight loss amenorrhea than in normally menstruating women. CONCLUSIONS: These results indicate that TRH causes a significant rise in serum LH and FSH and the impaired prolactin response in women with simple weight loss amenorrhea. 
Risk factors in relation to postoperative complications and mortality after total gastrectomy in aged patients. To clarify the risk factors contributing to postoperative complications in elderly patients undergoing total gastrectomy, 84 patients with primary gastric cancer were evaluated. Twenty-seven patients were older than 65 years of age; they had much more preoperative cardiac (P = 0.00003), respiratory (P = 0.0008), and multiorgan impairment (P = 0.009) than did the control group (age less than 65 yrs). Although overall morbidities (44.4% vs. 19.2%; P = 0.01) and overall septic complication rates (33.3% vs. 12.2%; P = 0.02) were higher in aged patients, no significant differences between the two groups were found in the incidence of major surgical complications (18.5% in aged patients vs. 10.5% in control groups; P = NS), serious septic (sepsis score greater than 10) complications (18.5% vs. 7.0%; P = NS) and hospital mortalities (11.1% vs. 3.5%; P = NS). In older patients the occurrence of multiorgan impairment and malnutrition was significantly related to postoperative complication rates. These results suggest that the degree of organ impairment rather than age is predictive of postoperative difficulty and should be used in assessing preoperative risk. 
Interferon gamma response region in the promoter of the human DPA gene. The interferon gamma (IFN-gamma) response region of the human class II major histocompatibility complex gene, DPA, has been localized to a 52-base-pair (bp) DNA fragment in the proximal promotor at -107 to -55 bp after transfection into HeLa cells of a series of 5', 3', and gap deletion mutants linked to a reporter gene, human growth hormone, as well as of synthetic oligonucleotides fused to the heterologous promoter thymidine kinase. The 52-mer sequence contains the X and Y box elements conserved in all class II genes; their presence is indispensable for IFN-gamma inducibility. Furthermore, an additional 5 bp immediately 5' of the X box of the DPA gene are necessary and sufficient for IFN-gamma induction. This region may contain an IFN-gamma response element. A closely related sequence has also been found in the vicinity of the critical deletion sites of three other well-studied class II gene promoters, all of which require a much longer sequence 5' of the X box. A fourth element, the W element, located about 15 bp 5' of the X box in all class II genes, is clearly of little importance in IFN-gamma inducibility of the DPA gene. 
Microvascular permeability increases early in the course of acid-induced esophageal injury. To test the hypothesis that microvascular injury is involved in the pathophysiology of acid-induced esophagitis, the effect of acid perfusion on intraluminal plasma protein loss was studied in relation to histological changes. Four groups of opossums (n = 6 in each) were perfused with either normal saline control) or 10, 20, or 100 mmol/L isoosmolar hydrochloric acid at 2 mL/min for 90 minutes using a midesophageal catheter. The distal esophagus was cannulated via a gastrostomy, and the effluent was collected and measured for intraluminal loss of IV injected 125I-bovine serum albumin. Plasma protein loss in the control group was constant with a total loss of 3.40 +/- 0.69 mg/g dry wt. Perfusion of 10, 20, and 100 mmol/L hydrochloric acid increased total protein loss to 8.06 +/- 2.62, 13.94 +/- 2.72, and 27.34 +/- 4.34 mg/g dry wt, respectively. The protein loss was not associated with intraluminal blood loss, as measured by previously injected 51Cr-labeled autologous red blood cells. Histological changes, scored by a blinded observer, were significant only between control animals and those perfused with 100 mmol/L hydrochloric acid. Separate studies using the vascular tracer monastral blue B demonstrated an increase in labeling of lamina propria blood vessels that varied directly with the concentration of acid perfusate, thereby providing direct morphological evidence of microvascular injury. These studies suggest that increased microvascular permeability occurs early in the course of acid-induced esophageal injury. 
Patterns of gene expression that characterize the colonic mucosa in patients at genetic risk for colonic cancer. We have used a computer-driven scanning and image-processing system to identify a panel of 30 cDNA clones whose pattern of expression in individual biopsy specimens distinguishes the flat, normal-appearing colonic mucosa of patients in two genetic groups at high risk for development of colorectal cancer from that of normal colonic mucosa in low-risk individuals. The two high-risk groups, familial adenomatous polyposis and hereditary nonpolyposis colon cancer, are indistinguishable based on the pattern of expression of the 30 selected clones. This suggests that the extensive pleiotropic effects of the inherited loci, which may play an important role in the mechanism of increased risk and early onset of the disease, are similar in these populations. 
Molecular genetic considerations in osteosarcoma. Osteosarcoma tumorigenesis is consistent with a model by which tumorigenesis results if both alleles at the retinoblastoma susceptibility locus (RBI) are altered. Additional genetic evidence strongly suggests that another obligate event in osteosarcoma tumorigenesis is the homozygous alteration of another gene, p53. Both the RB1 gene and p53 have been proposed to act as tumor-suppressor genes, suggesting that, in this instance, tumorigenesis is the result of the loss of gene function of these two genes, rather than a gain of function. 
Ovarian cancer screening: potential effect on mortality. Serum tumor markers and ultrasonography are being investigated as possible ovarian cancer screening tests. Data from the United States on ovarian cancer incidence and survival were used to estimate the potential benefit on ovarian cancer mortality from screening tests of various sensitivities. A test with 80% sensitivity could reduce ovarian cancer mortality by 50% if all screening-detected cases were to experience current stage I survival rates; the benefit would be greatest among women aged 45 or older. For each cancer detected there would be at least 50 false-positive screening tests unless test specificity is greater than 98%. If our most optimistic assumptions about screening could be met, then universal periodic screening of women aged 45 to 74 would result in about 5000 additional 5-year survivors of ovarian cancer annually. Uptake of existing screening tests is far less than universal; thus we would expect the impact of any ovarian cancer screening program to fall short of these projections. 
Rare presentation of a parapharyngeal schwannoma. Schwannoma, or neurilemmoma, is included in the differential diagnosis of masses in the parapharyngeal space. Schwannomata do not usually cause acute inflammation, and therefore do not tend to present as emergencies as in this case, in which there was acute respiratory embarrassment. 
Intracellular free magnesium and high energy phosphates in the perfused normotensive and spontaneously hypertensive rat heart. A 31P NMR study. We have employed 31P nuclear magnetic resonance (NMR) spectroscopy to examine the relationship between cytosolic free Mg2+ ([Mg2+]in), intracellular pH, high energy phosphates, and genetic hypertension using the Wistar-Kyoto rat (WKY) as a control and the spontaneously hypertensive rat (SHR) as a model for essential hypertension. The mean systolic blood pressures (measured using the tail cuff method) of control and hypertensive rats (aged 7 to 12 weeks) were 113 +/- 4 mm Hg (mean +/- 2 SE, n = 14) and 162 +/- 5 mm Hg (mean +/- 2 SE, n = 17), respectively. Intracellular free Mg2+ levels were significantly depleted in the isolated Langendorff perfused hypertensive rat hearts (452 +/- 39 mumol/L, mean +/- 2 SE, n = 17) compared to control hearts (756 +/- 52 mumol/L, n = 14); however, intracellular pH did not differ in the SHR hearts (7.02 +/- 0.03, mean +/- 2 SE, n = 7) compared with controls (7.03 +/- 0.03, n = 7). Although we could not demonstrate a statistically significant difference in the levels of P-creatine or ATP, intracellular Pi was two-fold higher (5.71 +/- 2.28 mmol/L v 2.92 +/- 0.66 mmol/L, n = 4) and the phosphorylation potential, [MgATP]/[MgADP][Pi], was correspondingly lower (3.0 X 10(4) +/- 1.6 x 10(4) v 8.3 X 10(4) +/- 1.4 X 10(4) (mol/L)-1, n = 4) in SHR compared to WKY hearts. These data demonstrate free magnesium depletion in heart muscle and indicate an alteration in cardiac bioenergetics in essential hypertension. 
Direct derivation of conditionally immortal cell lines from an H-2Kb-tsA58 transgenic mouse. Studies on cell lines have greatly improved our understanding of many important biological questions. Generation of cell lines is facilitated by the introduction of immortalizing oncogenes into cell types of interest. One gene known to immortalize many different cell types in vitro encodes the simian virus 40 (SV40) large tumor (T) antigen (TAg). To circumvent the need for gene insertion in vitro to generate cell lines, we created transgenic mice harboring the SV40 TAg gene. Since previous studies have shown that TAg expression in transgenic mice is associated with tumorigenesis and aberrant development, we utilized a thermolabile TAg [from a SV40 strain, tsA58, temperature sensitive (ts) for transformation] to reduce the levels of functional TAg present in vivo. To direct expression to a broad range of tissues, we used the mouse major histocompatibility complex H-2Kb promoter, which is both widely active and can be further induced by interferons. tsA58 TAg mRNA was expressed in tissues of all animals harboring the hybrid construct. Development of all tissues was macroscopically normal except for thymus, which consistently showed hyperplasia. Fibroblast and cytokeratin+ thymic epithelial cultures from these mice were readily established without undergoing crisis and were conditionally immortal in their growth; the degree of conditionality was correlated with the levels of tsA58 TAg detected. One strain of H-2Kb-tsA58 mice has been bred through several generations to homozygosity and transmits a functional copy of the transgene. 
Concomitant medical disease and headache. The treatment of headache disorders in patients with concomitant medical illness constitutes one of the more challenging areas of headache therapy. As new agents are added to our pharmacologic armamentarium, it will become easier to tailor therapy to our patients. The physician who treats the headache patient with concomitant medical illness must be particularly aware of drug side effects and pharmacology in order to prevent a worsening of underlying medical conditions or an exacerbation of headaches. 
Utilizing lung sounds analysis for the evaluation of acute asthma in small children. One of the most difficult aspects of management of acute asthma in the small child is the clinician's inability to quantitate the response or lack of response to bronchodilator agents because of the inability of a child this age to perform objective lung measurements in the acute state. The present study was designed to evaluate bronchodilator responsiveness in children between 2 and 6 years of age with wheezing by means of a computerized lung sound analysis, computer digitized airway phonopneumonography. Children between ages 2 and 6 who were experiencing acute exacerbations of asthma were included in this study population. The 43 children were evaluated by physical examination, pulmonary function testing, if possible, by use of (spirometry or peak flow meter) and transmission of lung sounds to a computer using an electronic stethoscope to obtain a phonopneumograph with sound intensity level determinations during tidal breathing. A control group of 20 known asthmatic patients between the ages of 8 and 52 years who also presented to the office with acute asthma were evaluated similarly. In each of these individuals, a physical examination was followed by complete spirometry as well as computer digitized airway phonopneumonography recordings. Following initial measurements, all patients were treated with nebulized albuterol (0.25 mL in 2 mL of saline). Five minutes after completion of the nebulization all patients were reexamined and repeat pulmonary function tests were performed followed by CDAP recordings. In the study group of children, the mean pretreatment sound intensity level was 1,694 (range 557 to 4,950 SD +/- 745). 
Use of femoral venous catheters in critically ill adults: prospective study. OBJECTIVE: To determine the frequency of clinically important complications of femoral venous catheters. DESIGN: Prospective survey of major and minor complications. SETTING: A mixed medical/surgical ICU in a university hospital. PATIENTS: One hundred twenty-three patients admitted to the ICU who underwent femoral venous catheterization over a 2-yr period. MEASUREMENTS AND MAIN RESULTS: There were 150 catheters inserted in 123 patients for a mean duration of 6.4 days. There were no major complications including catheter-related sepsis. Minor complications consisted of arterial puncture (9.3%), local bleeding (10%), and local inflammation (4.7%). Critical care fellows had a significantly lower rate (6%) of insertion complications than interns or medical students (16%). We did not specifically look at the frequency of deep venous thrombosis. CONCLUSIONS: Femoral venous catheterization offers an alternative site of insertion to the subclavian and jugular veins for central venous access in the critically ill. The occurrence rate of clinically important complications is acceptably low. 
Prevalences of endoscopic and histological findings in subjects with and without dyspepsia OBJECTIVE--To examine the association between dyspeptic symptoms and endoscopic and histological diagnoses. DESIGN--Cross sectional study of people with dyspepsia and controls matched for age and sex identified by questionnaire survey of all inhabitants aged 20 to 69. Endoscopy and histological examination was performed with the examiner blind to whether or not the patient had dyspepsia. SETTING--Population based survey in Sorreisa, Norway. SUBJECTS--All people with dyspepsia and age and sex matched people without dyspepsia were offered endoscopy. A total of 309 people with dyspepsia and 310 without dyspepsia underwent endoscopy, giving 273 matched pairs. MAIN OUTCOME MEASURES--Prevalences of endoscopic and histological diagnoses made according to internationally accepted standards. RESULTS--In all, 1802 of 2027 (88.9%) people returned the questionnaire. Of the 163 subjects who refused endoscopy, 114 were controls. Of five endoscopic and four histological diagnoses only peptic ulcer disease, endoscopic duodenitis, and active chronic gastritis were diagnosed significantly more often in people with dyspepsia. In all, 30% to 50% of the diagnoses of mucosal inflammation and peptic ulcer disease were made among subjects without dyspepsia, and only 10% of both those with and those without dyspepsia had normal endoscopic findings. CONCLUSIONS--The diagnostic findings, with possible exceptions of peptic ulcer disease and endoscopic duodenitis, showed no association of clinical value with dyspeptic symptoms. The small number of "normal" endoscopic findings in both those with and those without dyspepsia challenge well accepted endoscopic and histological diagnostic criteria with relation to the upper gastrointestinal tract. 
Outpatient liver biopsy: one man's experience. As an academically based gastroenterologist, I performed 94 outpatient liver biopsies over a 42-month period, using the standard suction technique. Differential blood count and vital signs were monitored, with no statistically significant postbiopsy changes noted in the group at large. One patient required admission to the hospital for bleeding, and six patients required intramuscular analgesics for pain at the biopsy site. Four patients had bradycardia, and one of them required atropine for bradycardia and hypotension. Outpatient liver biopsy is a safe procedure with low morbidity and complication rate. It would appear that prolonged monitoring is not necessary. 
Vagally mediated acid hypersecretion and lesion formation in anesthetized rat under hypothermic conditions. The pathophysiological changes associated with hypothermia were investigated in the rat stomach under anesthetized conditions. The animal was placed in a styrene foam box and the core body temperature was kept between 24 and 36 degrees C using a heat lamp and refrigerant pack. Lowering of body temperature (less than 30 degrees C) produced acid hypersecretion and induced hemorrhagic lesions in the gastric mucosa; these responses reached the maximum at 28 degrees C, and a significant relationship was found between acid output and lesion score. Hypothermia (28 degrees C) also caused a marked increase of gastric contractile activity and mucosal blood flow (MBF), but the ratio of acid output to MBF became greater when compared to that obtained under normothermic conditions. These changes induced by hypothermia (28 degrees C) were completely blocked by vagotomy and were significantly inhibited by atropine, hexamethonium, clonidine, or TRH antiserum. However, lowering body temperature did not significantly affect acid secretory, motility, and ulcerogenic responses induced by carbachol in the vagotomized rat, excluding local mechanisms (suppression of the inhibitory nerves) in the hypothermia-induced changes. We conclude that hypothermia alone stimulates vagally dependent acid secretion and motility, resulting in damage in the gastric mucosa. These changes may be centrally mediated by TRH, which is released in association with the thermogenic response to hypothermia. 
Nonneoplastic enhancing lesions mimicking intracanalicular acoustic neuroma on gadolinium-enhanced MR images. The authors describe five patients with nonneoplastic lesions of the facial and/or vestibulocochlear nerves that demonstrated focal enhancement within the internal auditory canal on magnetic resonance (MR) images. MR and surgical findings for four patients with unilateral sensorineural hearing loss and one with Ramsay Hunt syndrome were reviewed. Three patients with hearing loss underwent surgical exploration and decompression of the internal auditory canal. The MR findings in all four patients with hearing loss were similar: Focal enhancement of the internal auditory canal was depicted on postcontrast T1-weighted images. Nonneoplastic lesions of the seventh and eighth cranial nerves may show focal enhancement on MR images, which mimics the appearance of a small intracanalicular neuroma. This potential for misdiagnosis may have important therapeutic implications. 
Supratentorial dermoid cysts. Supratentorial dermoid cysts are rare lesions. In eight cases presented here, the lack of recurrence after subtotal removal of the capsule and the good long-term prognosis are emphasized. This finding is in agreement with the literature. The frequent relationship of these lesions with the cavernous sinus suggests a vascular genesis in the development of intracranial dermoid cysts. 
Plasma concentration of atrial natriuretic peptide in spontaneous atrioventricular re-entrant tachycardias of childhood. Plasma atrial natriuretic peptide was measured in 13 children between the ages of 1 week and 2 years 9 months during atrioventricular re-entrant tachycardia and 15 minutes after the restoration of sinus rhythm. There was a significant decline in atrial natriuretic peptide during sinus rhythm. Plasma concentrations of the peptide were significantly higher during tachycardia in seven infants under 1 year than in the six older children. The heart rates and the duration of tachycardia were not significantly different in the two age groups. Cardiac failure was present in five of seven children under 18 weeks of age during tachycardia but in none of the older children. The plasma concentration of atrial natriuretic peptide did not significantly correlate with duration of tachycardia or heart rate. If tachycardia occurs in young infants the low functional reserve capacity of the developing heart leads to cardiac failure more frequently and it is likely that this was the cause of the significantly higher plasma concentration of atrial natriuretic peptide in the younger children. 
Sexual transmission of hepatitis C virus and its relation with hepatitis B virus and HIV OBJECTIVE--To determine the extent of transmission of hepatitis C virus in sexual partners of intravenous drug misusers and to examine the relation between the prevalences of HIV, hepatitis B virus, and hepatitis C virus infections in homosexual men and intravenous drug misusers and their sexual partners. DESIGN--Serum samples collected between 1984 and 1988 were tested for hepatitis B virus markers and antibodies against hepatitis C virus by enzyme linked immunosorbent assay (ELISA) and for HIV antibody by enzyme immune analysis and western blotting. SETTING--Large referral university hospital with an external AIDS clinic in the metropolitan area of Barcelona, Spain. SUBJECTS--243 Intravenous drug misusers, 143 of their regular heterosexual partners, and 105 homosexual men. MAIN OUTCOME MEASURES--Prevalences of hepatitis C virus, hepatitis B virus, and HIV infections. RESULTS--In all, 178 of the 243 (73%) intravenous drug misusers, 16 out of 143 (11%) of their partners, and 17 of the 105 (16%) homosexual men had antibodies against hepatitis C virus. The presence of hepatitis C virus infection was unrelated to sex, age, the presence of HIV or hepatitis B virus infections, or the Centers for Disease Control stage of HIV. In sexual partners of intravenous drug misusers there were strong correlations between the presence of hepatitis C virus infection and that of HIV (p = 0.001) and hepatitis B virus (p = 0.013) infections. CONCLUSIONS--Intravenous drug misusers have a high risk of acquiring hepatitis C virus, hepatitis B virus, and HIV infections, but the presence of hepatitis C virus infection seems to be unrelated to the presence of the other two viruses. Homosexual men have a high prevalence of HIV and hepatitis B virus infections with a low prevalence of hepatitis C virus infection, the presence of which is not related to that of the other two infections. Conversely, heterosexual partners of intravenous drug misusers have low prevalences of the three virus infections, but the presence of hepatitis C virus infection correlates significantly with the presence of HIV and hepatitis B infections. The rate of sexual transmission of hepatitis C virus seems to be low, even in partners of people known to be seropositive for this virus. 
Traumatic asphyxia and blunt cardiac injury: case report and selected review. An unusual case is described featuring traumatic asphyxia and blunt cardiac injury. An association between these is possible but not previously described. Coronary artery contusion, malignant arrhythmias, and a normal electrocardiogram were also noted and discussed. The relevant literature was reviewed. 
Transesophageal color Doppler echocardiography of the normal St. Jude Medical mitral valve prosthesis. Transesophageal color flow Doppler findings are reported in 36 patients with a St. Jude Medical mechanical mitral valve prosthesis who had no auscultatory evidence for prosthetic valve dysfunction. Multiple jets consistent with mitral regurgitation originating from the central and lateral portion of the prosthesis were found in all patients. Maximum jet length ranged from 11 to 51 mm (mean 21 +/- 9 mm). Maximum jet area ranged from 0.2 to 4.1 cm3 (mean 1.2 +/- 0.9 cm2). The color M-mode Doppler interrogation showed two distinct components of the regurgitant jet: brief early systolic flow consistent with valve closure followed by holosystolic regurgitant flow consistent with transvalvular leakage. Four patients (11%) had a maximum regurgitant jet length exceeding 30 mm and absence of early systolic closure regurgitant flow by M-mode color imaging, suggesting clinically silent paravalvular leakage. Two pin-sized paravalvular suture line defects were confirmed in one patient at cardiac transplantation. We conclude that transesophageal echocardiography is a highly sensitive method for detection of mitral regurgitation in the St. Jude Medical mitral prosthesis. Clinically silent paravalvular leakage should be suspected if the maximum jet length exceeds 30 mm and color M-mode interrogation fails to demonstrate an early systolic closure regurgitant flow component. 
Total hip replacement for juvenile chronic arthritis. We review the results of 96 primary total hip replacements in 54 patients with juvenile chronic arthritis at five years or longer after surgery. The mean age at operation was 16.7 years (range 11.25 to 26.6); the follow-up period averaged 11.5 years. The clinical results in terms of pain, range of movement, mobility and function are presented. A revision procedure was required in 24 hips (25%) in 18 patients at an average of 9.5 years after the primary operation. A further 17 hips had radiographic signs of loosening. The factors thought to contribute to this relatively high failure rate in patients with juvenile chronic arthritis are discussed. 
History of epilepsy in Chinese traditional medicine. The first known document on epilepsy in China appeared in The Yellow Emperor's Classic of Internal Medicine, Huang Di Nei Ching, written by a group of physicians around 770-221 B.C. The description of epilepsy in this book and in many others later published was confined to generalized convulsive seizures. No documentation of absence or simple partial seizures was provided. The first classification of epilepsy, probably by Cao Yuan Fang in A.D. 610, listed five types of epilepsy: "Yang Dian," "Yin Dian," "Feng (Wind) Dian," "Shih (Wet) Dian," and "Lao (Labor) Dian." Later, other classifications named seizures after the cry of animals whose cry the "epileptic cry" resembled, or after "visceral organs" believed to be responsible for the seizures. The concept of partial versus generalized seizures, however, was not observed in any of these classifications. The treatment of epilepsy, based on principles of "Yin Yang Wu Xing," consisted of herbs, acupuncture, and massage. 
A phase I trial of recombinant human interleukin-1 beta alone and in combination with myelosuppressive doses of 5-fluorouracil in patients with gastrointestinal cancer. We studied escalating doses of recombinant human interleukin-1 beta (IL-1 beta) alone and after a myelosuppressive dose of 5-fluorouracil (5-FU) in patients with gastrointestinal cancer. Transient neutropenia, monocytopenia, and lymphocytopenia were observed followed by a 1.3- to 6.0-fold (mean, 3.46-fold) dose-dependent neutrophil leukocytosis (P less than .00001) on the days of IL-1 beta administration. Increases in platelet counts were observed at a median of 14 days (range, 6 to 23) after IL-1 beta administration. Transient hypoglycemia, rebound hyperglycemia, elevations in serum cortisol, and C-reactive protein were observed. Side effects included fever, rigors, and headache in the majority of patients. Hypotension was observed in three of five patients at the highest dose level (0.1 micrograms/kg) and was dose-limiting. Fewer days of neutropenia were noted after 5-FU plus IL-1 beta than after 5-FU alone; however, this difference did not reach statistical significance. These data show that IL-1 beta has stimulatory effects in human hematopoiesis. 
Lewis blood group antigens (a and b) in human breast tissues. Loss of Lewis-b in breast cancer cells and correlation with tumor grade. The Lewis blood group antigens (Lewis-a [Lea] and Lewis-b [Leb]) and their precursors are present on various normal human epithelial cell surfaces. The authors examined 35 benign and malignant human breast lesions using mouse monoclonal antibodies to synthetic Lea and Leb carbohydrate antigens. Normal breast lobular and ductal epithelium and benign breast lesions showed Leb staining but only occasional Lea staining. In invasive ductal carcinomas of breast, of all grades, a loss of Leb antigen staining was found in 80% of the breast cancer cases. This reduced Leb antigen expression increased with the grade of malignancy. Therefore, the loss of Leb blood group antigens on breast cancer cell surfaces may suggest altered fucosylation patterns in malignant cells and reflect the degree of malignancy and/or invasiveness. 
Infarction in focal nodular hyperplasia of the liver. A case report. An unusual case of focal nodular hyperplasia of the liver with infarction is presented. The patient, a 16-year-old girl with a three-year history of oral contraceptive use, presented with a two-week history of intermittent abdominal pain. Focal nodular hyperplasia of the liver and the role of estrogens in the development of this lesion are discussed. 
Autofluorescence of normal and malignant bronchial tissue. In vivo autofluorescence spectra were obtained in 5 patients with carcinoma in situ, 26 patients with invasive tumors, and 1 patient with severe dysplasia. Significant spectral differences were observed between pre-cancerous, cancerous, and normal bronchial tissues. This difference may afford a method to image and/or detect early lung cancer by using tissue autofluorescence alone. 
Mapping of human microtubule-associated protein 1B in proximity to the spinal muscular atrophy locus at 5q13. A polyclonal antiserum directed against the C-terminal domain of dystrophin was used to isolate a cDNA clone encoding an antigenically cross-reactive protein, microtubule-associated protein 1B (MAP-1B). Physical mapping of the human MAP-1B locus places its chromosomal location at 5q13, in proximity to the spinal muscular atrophy (SMA) locus. SMA is a degenerative disorder primarily affecting motor neurons. Genetic linkage analysis of SMA families using a human dinucleotide repeat polymorphism just 3' of the MAP-1B gene has shown tight linkage to SMA mutations. These mapping data together with the postulated role of MAP-1B in neuronal morphogenesis and its localization in anterior horn motor neurons suggest a possible association with SMA. 
Current approaches to chronic pain in older patients. As the population ages, primary care physicians face an increasing number of individuals who suffer from the effects of chronic diseases, including the accompanying chronic pain. This article reviews the common causes of pain in the elderly and suggests a system for assessing its severity. Five different approaches to treating pain in this population are outlined, as are guidelines for managing the potential side effects of treatment. 
Magnetic resonance imaging and late-onset epilepsy. The value of magnetic resonance imaging (MRI) in investigation of patients with late-onset epilepsy has not been studied systematically. We evaluated prospectively the usefulness of MRI in 50 patients with late-onset epilepsy in whom a computed tomography (CT) scan was normal (32), did not allow a definitive diagnosis to be made (12), or showed irrelevant lesions (6). Patients were assessed clinically and had an EEG, and CT and MRI scans were reported by one neuroradiologist blinded to clinical and laboratory data. Of the 32 patients with a normal CT scan, MRI was normal in 20, showed irrelevant ischemic lesions in 8, and showed the cause of seizures in 4 patients. Of the 12 patients with nondiagnostic CT, MRI clarified the diagnosis in 5 and was normal in 2 patients. In 6 patients, both scans showed irrelevant ischemic lesions, and in 1 patient MRI showed a relevant additional lesion. The incidence of MRI-detected white matter ischemic lesions was no greater than in an age- and sex-matched group of subjects without seizures. MRI was diagnostic in 32% of the patients with partial seizures and/or focal EEG findings, as compared with 0% of patients without focal features (p less than 0.01). We conclude that MRI is useful in investigation of patients with late-onset epilepsy with focal features. 
Acute nonhemodynamic pulmonary edema with nifedipine in primary pulmonary hypertension. A 34-year-old man with primary pulmonary hypertension developed acute nonhemodynamic pulmonary edema after a loading dose of nifedipine. Changes of the vascular permeability induced by the drug acting on the arteriolar wall of the capillary system could be an explanation. 
Staging carcinoma: its value in cancer of the larynx. Three thousand four hundred and forty-five cases of cancer of the larynx were examined and 3,235 assigned to their TNM group. While good correlation with prognosis could be seen, the value of the detailed subsite (as opposed to the main laryngeal regions) was limited to defining T1a and T1b and aiding that of T2. T status gives some indication of prognosis, but the N status is of almost overriding importance. 
Control of blood gas measurements in intensive-care units. The frequency of blood gas measurement in two adult intensive-care units was assessed for 7 months before and 12 months after introduction of a protocol of indications for such investigation. Demographic, diagnostic, outcome, and intervention data were collected prospectively. There were no differences in demographic characteristics, severity or type of illness, survival, or frequency of arterial or pulmonary artery catheter use between the two observation periods, but the frequency of blood gas analysis fell by 44% (p less than 0.001) after the protocol was introduced. 
Myocardial perfusion imaging with technetium-99m-labeled agents. Thallium-201 (201Tl) is suboptimal as a single-photon emitting agent for myocardial perfusion imaging, in view of its low-energy photons and long half-life. To circumvent these limitations, two new myocardial perfusion imaging agents labeled with technetium-99m (99mTc) have been developed. They are Tc-sestamibi and Tc-teboroxime. Clinical trials of myocardial perfusion with both tracers have shown results similar to those obtained with 201Tl for detection of coronary artery disease. Results to date indicate that Tc-sestamibi accurately detects and locates myocardial infarction and can accurately assess both left and right ventricular ejection fractions by the first-pass technique. In addition, research has shown that rest-stress studies can be performed on the same day and that Tc-sestamibi can be used to assess the results of thrombolytic therapy. Tc-teboroxime has excellent myocardial tracer uptake characteristics but is cleared very rapidly from the myocardium. These features make Tc-teboroxime well suited to rapid serial studies. These new technetium myocardial perfusion agents have just become available for routine clinical use and are likely to replace 201Tl in many of its clinical applications. 
Novel approach to iatrogenic bile peritonitis. Bile peritonitis after injury to the biliary tree is a serious complication that requires exploratory laparotomy. Our patient had an obstructing ampullary carcinoma, and generalized bile peritonitis developed from attempted percutaneous transhepatic cholangiography. The patient's condition was managed by peritoneal lavage and endoscopic transampullary stenting, with immediate relief of pain and toxicity. Exploratory laparotomy was avoided, and an eventual pylorus-sparing Whipple resection was the definitive treatment. We believe this to be the first report of successful nonoperative treatment of a patient with bile peritonitis with obstructive jaundice. 
Hepatic lesions in alcoholic HBV carriers. Liver biopsies were taken from 54 alcoholic HBV carriers with liver dysfunction to assess whether HBV infection or habitual drinking was the main cause of their illness. In 28 cases, ultrastructural studies were done. Results showed that 50% of the cases predominantly displayed virus-related histological changes, whereas 13% of them mainly had alcohol-related ones. Both pathological changes were evenly distributed in four cases. The remaining 15 cases showed nonspecific or other histological changes. Electron microscopy revealed that HBV core and Dane particles were seen with Mallory bodies in the same hepatocytes. Thus, we postulate that HBV-related changes are more often encountered than alcoholic ones in alcoholic HBV carriers and that HBV replication can occur even in hepatocytes bearing Mallory bodies. 
Elevated intravesical pressure causes arterial hypoperfusion in canine colocystoplasty: a fluorometric assessment. Since 1988 there have been 15 reported cases of late, spontaneously ruptured intestinal cystoplasties at bowel sites remote from the anastomosis. Ischemic necrosis has been suggested as a possible etiology. We examined this hypothesis by quantifying the uptake of intravascular fluorescein in the augmented bowel of adult mongrel canines. There was a statistically significant decrease in fluorescein uptake at high intravesical pressures, which appeared to be most pronounced at the antimesenteric border. This laboratory study supports a recent clinical report of histological changes pathognomonic for chronic ischemia in the augmented bowel of patients with spontaneous rupture. 
Endorectal sonography in the evaluation of rectal and perirectal disease. Endorectal sonography initially was developed for evaluation of the prostate and now has been adapted for evaluation of rectal and perirectal disease. We used endorectal sonography to evaluate a spectrum of diseases, including primary and recurrent rectal carcinoma, metastases, villous adenoma, leiomyosarcoma, endometriosis, sacrococcygeal teratoma, chordoma, retroperitoneal cystic hamartoma, pelvic lipomatosis, diverticulitis, and perirectal abscess. The technique has been useful in localization of perirectal abscesses and in sonographically guided biopsy of perirectal masses. Knowledge of normal sonographic anatomy of the rectum is essential in the evaluation of rectal and perirectal disease. In this essay, we describe the technique of endorectal sonography and illustrate the sonographic findings in a variety of diseases. 
Geniculate neuralgia: the surgical management of primary otalgia. Intractable, unexplained deep-ear pain presents a rare, albeit significant problem in otolaryngological and neurosurgical practice. The authors review their experience with 18 cases of primary otalgia during the past 15 years. A total of 31 surgical procedures were performed. Seventeen patients had sequential rhizotomies and one patient had microvascular decompression alone. Based on the clinical diagnosis, the nerves sectioned were singly or in combination: the nervus intermedius (14 patients), geniculate ganglion (10 patients), ninth nerve (14 patients), 10th nerve (11 patients), tympanic nerve (four patients), and chorda tympani nerve (one patient). Microvascular decompression of the involved nerves was undertaken in nine patients, in whom vascular loops were discovered. Adhesions (six patients), thickened arachnoid (three patients), and benign osteoma (one patient) were other intraoperative abnormalities noted. The overall success of these procedures in providing pain relief was 72.2%, and the mean follow-up period was 3.3 years (range 1 month to 14.5 years). There was no surgical mortality. Expected side effects were: decreased lacrimation, salivation, and taste related to nervus intermedius nerve section, and transient hoarseness and diminished gag related to ninth and 10th nerve section. Four patients developed sequelae consisting of sensorineural hearing loss, vertigo, and transient facial nerve paresis. One patient had a cerebrospinal fluid leak and another developed aseptic meningitis as postoperative complications. Except when primary glossopharyngeal neuralgia is the working diagnosis, a combined posterior cranial fossa-middle cranial fossa approach is recommended for adequate exploration and/or section of the fifth, ninth, and 10th cranial nerves as well as the geniculate ganglion and nervus intermedius. 
Clinical utility of transesophageal echocardiography. Routine transthoracic echocardiography fails to generate images of diagnostic quality in a significant number of patients who are obese, uncooperative, or unable to be properly positioned (eg, patients receiving ventilatory assistance), and in those with severe chronic obstructive pulmonary disease, chest wall deformities, or recent thoracic surgical procedures. In addition, posterior structures in the heart such as the left atrium, left atrial appendage, atrial septum, and mitral valve are seen with poorer resolution than structures closer to the anterior chest wall. Placement of a sonographic transducer in the esophagus immediately behind the heart circumvents these limitations. Newly developed probes are well tolerated by sedated conscious patients as well as by patients receiving ventilatory assistance in the intensive care unit and those under general anesthesia. Consequently, transesophageal echocardiography is now available for further enhancement of cardiac diagnosis in outpatients, for evaluating the hemodynamic status of critically ill patients in the intensive care unit, for intraoperative assessment of cardiac repairs, and for intraoperative cardiac monitoring in noncardiac surgical procedures. A series of case examples from our practice during a recent 1-year period illustrates the clinical utility of this technique in these settings. 
A pseudoaneurysm of the superficial femoral artery as a late complication of a stab wound. Limited arteriography based on clinical indications has become increasingly popular. We present the case of a patient with pseudoaneurysm formation of the superficial femoral artery as a late consequence of a lateral stab wound to the thigh. This case demonstrates the need for postinjury follow-up to identify missed injuries before they are limb threatening. 
Reduction to homozygosity involving p53 in esophageal cancers demonstrated by the polymerase chain reaction. Loss of heterozygosity affecting chromosome 17p has been detected at high frequencies in a variety of human tumors, including cancers of the colon, breast, lung, and brain. One presumed target of these losses is p53, a tumor suppressor gene located on 17p. To our knowledge, loss of heterozygosity has not yet been reported at any locus, including p53, in human esophageal cancer. Moreover, current methods of detecting loss of heterozygosity depend on the availability of large amounts of high molecular weight DNA, making the study of small biopsy specimens or paraffin-embedded tissues problematic. We examined 52 primary human esophageal neoplasms for loss of heterozygosity affecting the p53 gene by using the polymerase chain reaction. Loss of one allele was detected in 52% of informative cases and was more common in squamous carcinomas than in adenocarcinomas. Southern blot analysis was used to confirm polymerase chain reaction-derived data. The identification of allelic loss in approximately half of the tumors analyzed supports the hypothesis that inactivation of p53 is involved in the pathogenesis of esophageal cancer. 
Photodynamic therapy for multiple primary bronchogenic carcinoma. In recent years, multiple primary lung cancers have been reported with greater frequency, partly as a result of technologic advances in the detection of lung cancer and therapeutic achievements in its management. Photodynamic therapy (PDT) is a relatively new therapy used with increasing frequency in the treatment of a wide variety of malignancies, including central lung cancers. In PDT, the differential retention of an injected photosensitizer by malignant tissue is exploited by treatment with a low-power laser beam delivered endoscopically. Since 1980, 145 patients with central lung cancers, including 35 cases of endoscopically evaluated early-stage lesions were treated with PDT at Tokyo Medical College. Thirteen of these 145 patients had multiple primary bronchogenic carcinomas, five cases of which were synchronous with the rest, metachronous. Three of 13 patients with multiple tumors had early-stage lesions and were treated with endoscopic PDT alone. In the other ten cases, PDT was used to treat accessible early-stage foci although operative excision was required for advanced lesions. Mean survival after PDT, alone or in combination with surgery, was 38 months (range, 14 to 87 months), and seven patients remain alive to date. It was concluded that PDT is useful in extending the therapeutic options for, and improving the prognosis of patients with, multiple primary bronchogenic carcinomas. 
Electrothrombosis of saccular aneurysms via endovascular approach. Part 1: Electrochemical basis, technique, and experimental results. Eleven experimental saccular aneurysms were created on the common carotid artery of swine. Between 3 and 15 days after creation of these aneurysms, they were thrombosed via an endovascular approach, using a very soft detachable platinum coil delivered through a microcatheter positioned within the aneurysm. This detachable platinum coil was soldered to a stainless steel delivery guidewire. Intra-aneurysmal thrombosis was then initiated by applying a low positive direct electric current to the delivery guidewire. Thrombosis occurred because of the attraction of negatively charged white blood cells, red blood cells, platelets, and fibrinogen to the positively charged platinum coil positioned within the aneurysm. The passage of electric current detached the platinum coil within the clotted aneurysm in 4 to 12 minutes. This detachment was elicited by electrolysis of the stainless steel wire nearest to the thrombus-covered platinum coil. Control angiograms obtained 2 to 6 months postembolization confirmed permanent aneurysm occlusion as well as patency of the parent artery in all cases. No angiographic manifestation of untoward distal embolization was noted. Due to the encouraging results of this research, this technique has been applied in selected clinical cases which are described in Part 2 of this study. 
Non-Q- and Q-wave infarction after thrombolytic therapy with intravenous streptokinase for chest pain and anterior ST-segment elevation The clinical features of patients treated with streptokinase for chest pain and anterior ST-segment elevation who subsequently develop non-Q-wave infarction are unknown. Of the 75 consecutive patients who initially presented with chest pain and ST-segment elevation in the anterior leads (V1-V6, I, aVL) and were treated with intravenous streptokinase (time from symptoms to treatment averaged less than 3 hours), 32 (43%) developed a non-Q-wave and 43 (57%) a Q-wave myocardial infarction. Twenty seven of 32 patients (84%) from the non-Q-wave group and 39 of 43 (91%) from the Q-wave group were studied by angiography at 5.16 +/- 2.88 days after the onset of myocardial infarction. Left ventricular end-diastolic pressure was 13 +/- 6 vs 20 +/- 7 mm Hg (p less than 0.001), left ventricular ejection fraction was 60 +/- 8 vs 49 +/- 14% (p less than 0.001) and the infarct vessel patency rate was 85 vs 72% (p = 0.44) in patients with a non-Q versus a Q-wave infarction, respectively. In summary, when patients presenting with chest pain and ST-segment elevation are treated with streptokinase, a significant portion of these symptoms will evolve into a non-Q-wave infarction. Patients with a non-Q-wave infarction will have a better preserved left ventricular function than patients who develop a Q-wave infarction. This suggests the need for equal distribution of such patients in randomized trials of thrombolytic therapy for acute myocardial infarction to avoid misinterpreting data between groups. 
Cardiac sources of embolism and cerebral infarction--clinical consequences and vascular concomitants: the Lausanne Stroke Registry. We studied clinical characteristics and coexisting causes of stroke in 305 patients admitted to a population-based primary care center with an initial ischemic stroke and a potential cardiac source of embolism (PCSE). Using systematic standardized cardiac, arterial, and cerebral investigations and the logistics of the prospective Lausanne Stroke Registry, we found that nonprogressive onset, hemianopia without hemiparesis or hemisensory disturbances, Wernicke's aphasia, ideomotor apraxia, involvement of specific territories (posterior division of middle cerebral artery, anterior cerebral artery, cerebellum, multiple territories), and a hemorrhagic component were associated with the presence of a PCSE, as compared with 1,006 initial ischemic stroke patients without PCSE. Although age and sex did not differ, the frequency of hypertension, diabetes, cigarette smoking, elevated blood cholesterol, and deep hemispheric or brainstem infarcts was higher in the patients without a PCSE. Nearly one-fourth of the patients with a PCSE had a coexisting potential arterial cause of stroke (large artery greater than or equal to 50% stenosis or small-vessel disease). In the majority of patients with a PCSE (76.7%), cardioembolism was the most likely cause of stroke, although a direct source of embolism was uncommon (4.3%) and intracranial embolic occlusions were present in less than one-half of the patients who were angiographed. 
Clinical factors affecting the immediate outcome of PTCA in patients with unstable angina and poor candidates for surgery. Percutaneous Transluminal Coronary Angioplasty (PTCA) has been successfully applied in unstable angina to carefully selected patients. In this study, PTCA was performed in 277 consecutive patients suffering from unstable angina and for whom bypass surgery was not a valid alternative because either of inoperable conditions or of emergency, or because surgery was not the best option. All patients were admitted first to the intensive care unit where an attempt was made to control unstable angina under conventional medical therapy using at least iv nitroderivative, heparin, and calcium blockers. After a standardized preparation PTCA was performed either as an emergency procedure in medically refractory unstable angina (107 cases) or as an elective procedure in controlled situations after a 7 to 10 days symptom-free period. Three hundred fifty-three coronary vessels were attempted. Results of this group are compared with those of a control group made of 670 consecutive stable patients recruited during the same period, and clinical characteristics are envisaged as potential predictive factors. Unstable angina is undoubtedly associated with a higher overall complication rate, but the immediate outcome is strongly affected by the clinical context. As an example, respective success and mortality rates are: 93% and 0% when a full revascularization is attempted; 91% and 0% in elective procedures in patients under 60; 87% and 1.2% in elective PTCA for multiple vessel disease; 80% and 6.5% in emergency PTCA; 80% and 11% in the overall triple vessel disease; 84% and 16% in patients with deeply altered ejection fraction; and 58% and 26% in triple vessel disease with 2 previously occluded coronary arteries. 
Different types of chronic hepatitis in alcoholic patients: does chronic hepatitis induced by alcohol exist? To verify the existence of chronic hepatitis induced by alcohol, the clinicopathological features of chronic hepatitis in heavy drinkers were studied using various viral markers. Histological features of chronic active hepatitis were seen in 27 heavy drinkers. These patients were divided into four groups. The AL group (seven cases) consisted of alcoholics who were negative for both hepatitis C antibody and HBsAg; the HB group (four cases) was positive for HBsAg; the HC1 group (seven cases) was positive for hepatitis C antibody but negative for hepatitis C virus-RNA genome; and the HC2 group (nine cases) was positive both for hepatitis C antibody and hepatitis C virus-RNA genome. Serum AST and ALT activity declined during 4 wk of abstinence in most patients in the AL group and in the HC1 group. The response of serum AST and ALT to abstinence was poor in most patients in the HB group and the HC2 group. Serum desialo-transferrin and alcohol liver membrane antibodies were detected more frequently in the sera of patients in the AL group and HC1 group. A trend toward increased frequency of centrilobular ballooning existed in the AL group, but this did not reach statistical significance. These results suggest that chronic active hepatitis in patients in the AL group, in whom markers of HBV and hepatitis C virus were absent, may be caused by alcohol. Patients in the HC1 group who had hepatitis C antibody but not hepatitis C virus-RNA may represent cases where both alcohol and hepatitis C virus are involved. 
Clinical evaluation of stenosis of the carotid bifurcation with magnetic resonance angiographic techniques. We evaluated the images of 60 carotid artery bifurcations in 31 patients suspected to have carotid artery disease who underwent invasive carotid angiography and combined two-dimensional, phase-sensitive and a gradient-echo magnetic resonance angiography. The phase scans consisted of seven serial projections that were obtained at 20 degrees intervals (11.0 minutes) around the carotid bifurcation; the gradient-echo (GRASS) scans were composed of 11 axial images (2.4 minutes) acquired through the bifurcation. The two magnetic resonance angiographic techniques yielded complementary pieces of information and were used together to compare magnetic resonance angiography with invasive angiography. Comparison of magnetic resonance and invasive angiograms of the 60 carotid arteries shows that the sensitivity (86%) and specificity (92%) of the magnetic resonance angiographic techniques we used to diagnose clinically significant carotid stenosis approach but do not reach those of invasive angiography. 
Radionuclide assessment of infarct size and left ventricular function in clinical trials of thrombolysis. Mortality, left ventricular ejection fraction, and infarct size are important end points in evaluating the efficiency of thrombolytic treatment in clinical trials. Radionuclide assessment of ejection fraction and infarct size is safe, accurate, reproducible, and readily available. Its use in clinical trials supplements mortality data and allows meaningful results in trials with smaller patient numbers. Single photon emission computed tomography improves the detection and quantification of infarct size, and its use with new radiopharmaceuticals will assume an important role in future trials. For an 8-year period, these radionuclide techniques have been used in the Western Washington Thrombolysis Trials and have generally shown smaller infarct size and higher ejection fractions in patients receiving streptokinase and tissue-type plasminogen activator. However, in the most recent trial there was no direct relation between these end points and the time between symptom onset and initiation of treatment. Future trials that direct efforts to treatment in the first hour after symptom onset should further clarify this observation. 
Klippel-Trenaunay syndrome: the risks and benefits of vascular interventions. Our experience with Klippel-Trenaunay syndrome (KTS), a rare congenital malformation, has increased considerably in recent years and now includes 144 patients (65 male and 79 female patients). Hemangioma was present in 137 patients (95.1%), varicosity in 110 (76.4%), and hypertrophy of the soft tissues or bones in 134 (93.1%). In most patients (71.5%) the disease involved one lower extremity. Diagnostic workup included roentgenogram to document limb length discrepancy, noninvasive arterial and venous evaluation, contrast venography, and nuclear magnetic resonance imaging. Most patients did well without treatment or with elastic compression only. Surgical treatment for the vascular malformation in KTS is rarely needed and it continues to be controversial. To evaluate the risks and benefits of vascular interventions, we examined in detail the clinical histories of nine patients who in the last decade underwent operation for a vascular malformation of the lower extremity. In seven patients we removed varicose veins or resected hemangioma of the lower extremity. Although none was cured, all five who underwent resection of varicose veins and one of the two patients who underwent resection of a hemangioma improved. Two additional patients, however, who underwent resection of varicose veins in another institution had worsening of the symptoms. In one patient we performed deep venous reconstruction for atresia of the superficial femoral vein, using the contralateral saphenous vein. Such operation in KTS has not been reported previously. The patient has a patent graft with a competent valve and clinical improvement 6 months after the operation. Although patients with severe chronic venous insufficiency, disturbing cosmetic appearance, or complications of hemangioma may benefit from surgical treatment, detailed preoperative imaging of the extremity and pelvis with magnetic resonance imaging and contrast venography is needed to decrease complications. Rarely, reconstruction for atresia or hypoplasia of the deep veins may be needed. 
DNA ploidy pattern of flat adenomas of the large bowel. In an attempt to clarify the nature of "flat adenomas," DNA content was measured by means of microspectrophotometry. Thirty-nine flat adenomas (FA), 13 with mild, 22 with moderate, and 4 with severe atypia, were collected for this study. In FA, diploidy (D), polyploidy (P), and aneuploidy (A) were found 100, 0, and 0 percent in mild atypia, 41.9, 4.5, and 54.5 percent in moderate atypia, and 0, 0, and 100 percent in severe atypia, respectively. It is assumed that FA have a much higher malignancy potential than previously expected since, histologically, benign-appearing FA with moderate atypia have already contained malignant DNA patterns. In particular, those more than 5 mm in diameter show aneuploidy in 80 percent. These data suggest that FA with moderate atypia play an important role in the pathogenesis of small colonic carcinomas. 
Failure of MR imaging to detect reflex sympathetic dystrophy of the extremities. Reflex sympathetic dystrophy of the extremities is a disease with a wide spectrum of clinical manifestations. It is characterized by pain, hyperthermia, and cutaneous changes and has been linked to an abnormality of regional blood flow. The disease is associated with previous injury or trauma including surgery, but also has been found in association with myocardial infarctions and tumors. The final diagnosis can be made only on the basis of the clinical course, which is characterized either by regression without sequel or the appearance of aponeurotic and tendinous retractions including bony sclerosis in the affected region occurring over many months to years. The literature and our own results show that MR imaging has high sensitivity for diagnosing transient osteoporosis of the hip, which is generally thought to be a form of reflex sympathetic dystrophy. Therefore we investigated the usefulness of MR imaging for diagnosing sympathetic dystrophy of the extremities. Twenty-five patients underwent T1- and T2-weighted MR imaging of the affected body region. They were selected on the basis of the initial clinical findings and positive findings on scintigraphy, which is known to be a sensitive, but not very specific, imaging method for sympathetic dystrophy. The final diagnosis was established on the basis of the clinical course in 17 of the 25 patients. In 10 of these, findings on MR images were completely normal, in six the MR images showed only nonspecific soft-tissue changes or bone marrow sclerosis, and in one patient they showed changes in bone marrow signal. Of the remaining eight patients without a final diagnosis of sympathetic dystrophy, MR showed soft-tissue or bone marrow alterations in six. MR imaging appears to be of little value in establishing the diagnosis of sympathetic dystrophy, but it may improve diagnostic specificity when used in conjunction with scintigraphy. 
Hypertensives' pressor response to norepinephrine. Analysis by infusion rate and plasma levels. After 5 days of a 10 mEq sodium diet or 4 days of a 200 mEq sodium diet, 15 hypertensives and 11 normotensive control subjects received pressor doses of intravenous norepinephrine (NE). Analysis of pressor responses to the rate of NE infusion showed that the high salt diet sensitized subjects so that they needed less NE to raise systolic blood pressure (SBP) 20 mm Hg (P = .005). There was a complex interaction of salt intake, black race, and hypertension on NE pressor sensitivity (P = .03). Hypertensives attained lower plasma NE levels during the stepwise NE infusion, so we reanalyzed NE sensitivity in terms of the changes in plasma NE levels. This analysis also showed that during the high salt diet, subjects initiated a pressor response at lower plasma NE levels (P = .017) and raised SBP 20 mm Hg at lower NE levels (P = .007). The reanalysis showed that hypertensives initiated a pressor response at lower plasma NE levels (P = .03) and raised SBP 20 mm Hg at lower NE levels (P = .002). Plasma NE levels should provide a better guide to the concentration of NE at cardiovascular receptors than the rate of NE infusion. Analysis of pressor responses to plasma NE levels demonstrated that the hypertensives had an exaggerated pressor response to NE. 
Chaos, balance, and development: thoughts on selected childhood epilepsy syndromes. Age-specific epilepsy syndromes raise important questions about developmental susceptibility to seizures and epileptogenesis and about the effect of seizures on function. The diagnosis and treatment of these syndromes has been enhanced by the use of modern science and technology. Epidemiologic studies have changed our approach to febrile convulsions. This developmental seizure disorder is benign and self-limited. We have been forced to think carefully about threshold, therapy, and whether other seizures in childhood may be equally benign. This framework of developmental specificity can also be applied to West syndrome, especially with respect to neurophysiology, neurochemistry, neuroimaging, and epidemiology--the types of seizures, clustering, variations associated with sleep, PET scans, and therapy. Rasmussen's syndrome and other unilateral developmental epilepsies are progressive but remain confined to a single hemisphere. However, they usually are devastating to global neurologic function. They are models for examining the impact of epilepsy in one pathologic hemisphere on the function of the entire brain. Current therapy for this condition is hemispherectomy. Recovery of function after this major surgery is striking and provides clues to brain organization. The analysis of these three syndromes provides windows on the dynamic, changing central nervous system of the child and may lead to better understanding and therapy for other seizure disorders. 
Classification of epilepsies and epileptic syndromes in two different samples of patients. We attempted to classify, according to the International Classification of Epilepsies and Epileptic Syndromes, 986 patients consecutively examined during a 13-month period either in a specialized private practice (n = 642) or in an adult neurology unit in a university hospital (n = 344). Without major difficulty, we classified 97% of patients in more or less clearly defined syndromes. Benign frontal and benign psychomotor epilepsies of childhood were represented in this sample of patients. In either partial or generalized idiopathic epilepsies, a diagnosis of epilepsy appears justified even after a single epileptic event when sufficient electroclinical characteristics are present. Patients with symptomatic generalized epilepsies often have to be classified under two or three headings. Many children with a symptomatic generalized epilepsy also experience partial seizures. Alcoholic epilepsy is described as a veritable epileptic syndrome. The distribution of epileptic syndromes was clearly different in the two samples, casting doubt on the value of some epidemiologic surveys based on selected groups of patients. 
Factors influencing postoperative recurrence of Crohn's disease in childhood. We have reviewed the outcome of all patients undergoing their first intestinal resection for Crohn's disease at this hospital between 1970 and 1987. Recurrence rates, defined by recurrent intestinal symptoms and radiological confirmation of mucosal disease, were calculated using survival analysis. Age, sex, anatomical location of disease, indication for surgery, preoperative duration of symptomatic disease, use of preoperative bowel rest, and pathological features of the resected bowel were analysed individually and jointly as potential risk factors influencing postoperative recurrence of disease. Eighty two patients (age, mean (SD) 14.8 (2.5) years) underwent intestinal resection and were followed postoperatively for a minimum of one year (mean 5.3 (3.3) years). Anatomical location of disease, indication for surgery, and preoperative duration of symptomatic disease were the only factors that significantly influenced the duration of the recurrence free interval. Patients with diffuse ileocolonic inflammation experienced earlier recurrence (50% at one year) than children with predominantly small bowel disease (50% recurrence at five years, p less than 0.0001). Failure of medical therapy independent of disease location as the sole indication for surgery was associated with an earlier relapse than when surgery was performed for a specific intestinal complication such as abscess or obstruction (p less than 0.003). Patients undergoing resection within one year of onset of symptoms experienced delayed recrudescence of active disease (30% recurrence by eight years) compared with patients whose preoperative duration of symptomatic disease was longer (50% recurrence by four years when preoperative duration of disease was one to four years and 50% by three years when disease had been present greater than four years preoperatively, p = 0.03). 
Clinical follow-up and progression of carotid atherosclerosis determined by duplex scanning in patients suffering from TIA. We investigated the clinical outcomes and the progression of the internal carotid arterial lesions of a group of patients presenting with hemispheric TIAs. The cumulative frequency of TIAs during a mean follow-up period of 40 +/- 14 months was 14%, and no relationship was found between new TIAs and the presence of known cardiovascular risk factors or plaque characteristics as determined by duplex scanning. With the exception of one patient who died of stroke, none of the patients developed a permanent neurologic deficit. The cumulative death rate was 6.5%; myocardial infarction was the most common cause (3 out of 7). Anatomic progression of plaques was determined by duplex scanning in 22% of the internal carotid arteries. No relationship between progression of these plaques and the development of new TIAs was evident. We conclude that, in this group of patients, TIAs do not inevitably lead to stroke and that TIAs are not predictable based on risk factors or plaques characteristics. 
Proopiomelanocortin gene expression in normal and tumoral human lung. Proopiomelanocortin (POMC) gene expression is not restricted to the pituitary corticotroph cell, but also takes place in many normal and tumoral nonpituitary tissues. In contrast, the ectopic ACTH syndrome is a rare event. Because it is most often associated with lung tumors, we specifically studied this tissue, analyzing the different forms of POMC RNAs in normal specimens as well as in various types of tumors. The endocrine nature of the tumors was assessed by both histological examination and measurements of secretogranin-I fragments in the tissue extracts. POMC RNA was first detected by Northern blot analysis; its absolute amounts and its various molecular forms were more precisely quantified and discriminated by S1 mapping studies using a single stranded DNA probe located at the 5' end of exon 3. In five bronchial carcinoid tumors associated with the ectopic ACTH syndrome, a highly predominant, if not single, POMC RNA identical to the 1200-nucleotide (nt) pituitary message was present, the high amounts of which were correlated with those of POMC peptides in the same tissues. In five bronchial carcinoid tumors not associated with the ectopic ACTH syndrome, the same message was detected (four of five), with a second, often predominant, short RNA of about 800 nt (five of five), and the overall amounts of POMC RNAs were low. Similar patterns of POMC RNAs were observed in squamous cell tumors, adenocarcinomas, and normal lung, where the short 800-nt RNA tended to be predominant. These results show that POMC gene expression can be demonstrated in normal lung tissue and in all types of lung tumors. The ectopic ACTH syndrome only occurs with tumors capable of generating high amounts of the pituitary-like message, a phenomenon that seems to be restricted to an occasional tumor with features of neuroendocrine differentiation. 
Autoantibody-encoding kappa L chain genes frequently rearranged in lambda L chain-expressing chronic lymphocytic leukemia. Patients with kappa L chain expressing chronic lymphocytic leukemia (CLL) frequently have leukemia cells reactive with a murine mAb, designated 17.109. Raised against a monoclonal IgM rheumatoid factor autoantibody, this mAb recognizes a major kappa-L chain-associated cross reactive Id, designated 17.109-CRI. Molecular studies reveal that the 17.109-CRI in CLL is a serologic marker for expression of a conserved kappa L chain V region gene (V Kappa gene) of the V Kappa 3 subgroup, designated Humkv325. We isolated an upstream gene fragment of Humkv325 to examine for Ig gene rearrangements of this and other closely related V Kappa 3 genes by Southern analyses. Consistent with Humkv325 encoding the 17.109-CRI, we find that the genomic DNA from all 17.109-reactive leukemia cell populations have gene rearrangements that are detected using this probe. In addition, we observe V Kappa 3 gene rearrangements frequently in the genomic DNA of lambda L chain-expressing leukemia cells. Of the genomic DNA from 33 lambda-L chain-expressing CLL samples, 8 (24%) had additional nongerm-line bands detected with the Humkv325 probe. Consistent with these bands representing Ig gene rearrangements, the additional band in each but one sample also hybridized with probes specific for the J Kappa region and/or the kappa-deleting element. Using the polymerase chain reaction (PCR), we examined the genomic DNA from all lambda L chain-expressing CLL for V Kappa 3 gene rearrangements to J Kappa and/or Kde. PCR on each DNA sample with V Kappa 3 gene rearrangements detected by Southern analysis generated gene fragments that hybridized specifically with oligonucleotides corresponding to framework or CDR of the Humkv325 gene. Nucleic acid sequence analyses of representative samples confirmed that these DNA contained abortive Humkv325 gene rearrangements. PCR for rearranged V Kappa 3 genes in the DNA of other lambda-L chain-expressing CLL either did not generate any PCR product or produced fragments that failed to hybridize with all Humkv325 oligonucleotide probes. Nucleic acid sequence analyses of the latter demonstrated that these represent abortive V Kappa gene rearrangements involving another conserved V Kappa 3 gene, designated Vg. These studies indicate that Humkv325 and Vg frequently may undergo Ig gene rearrangement independent of their expression. As such, the frequent use of Humkv325 in CLL may be secondary, in part, to an enhanced propensity of this V Kappa 3 gene to undergo genetic rearrangement during B cell ontogeny. 
Relationship between redistribution on exercise thallium-201 scintigraphy and repetitive ventricular premature beats in patients with recent myocardial infarction. The relationship between myocardial ischemia detected by exercise thallium-201 scintigraphy and repetitive ventricular premature beats (VPBs) during ambulatory monitoring was evaluated in 57 patients with recent myocardial infarction. Multivariate analysis was performed to obtain the relatively important factor related to repetitive VPBs with the use of the following variables: age, redistribution, left ventricular ejection fraction, serum potassium and magnesium concentration, QRS score, left ventricular aneurysm, and the number of diseased vessels. Thirty-five patients had redistribution, but only three of them had repetitive VPBs during exercise testing. The average heart rate before 79% of 398 episodes of repetitive VPBs during ambulatory monitoring was in the range of 56 to 70/min. These data indicate that most of repetitive VPBs during ambulatory monitoring were not provoked by exercise-induced acute myocardial ischemia. However, redistribution was found to be an important factor associated with repetitive VPBs. The electrical abnormality relating to a substrate characterized by chronic reversible ischemia may explain the association between redistribution and repetitive VPBs. 
Prediction of subclinical tumor infiltration in basal cell carcinoma. Two thousand-sixteen basal cell carcinomas (BCCs) were documented in terms of age, anatomic location, tumor diameter, initial excision depth, safety margin, histologic type, and the position of tumor outgrowths as determined by three-dimensional histologic study of the tumor margins in paraffin sections (micrographic surgery). The extent of each subsequent excision was recorded until tumor-free tissue was reached. The results showed that BCCs have a highly irregular infiltration pattern and a predilection for small, fingerlike outgrowths whose bases occupy 1-30 degrees of the tumor circumference. When superficial extension was expressed mathematically, the resulting exponential functions varied highly significantly (P = .001) according to histologic tumor type and diameter. The resulting curves permitted very precise prediction of the probability of tumor-positive margins (ie, subtotal excision), depending on the safety margin, histologic tumor type, and tumor diameter. For example, the probability of tumor-positive margins after excision of a BCC up to 10 mm in diameter is 30% with a safety margin of 2 mm, 16% with a safety margin of 3 mm, and 5% with a safety margin of 5 mm. The probability of tumor-positive margins for fibrosing primary BCCs 10-20 mm in diameter is 48, 34, and 18% with safety margins of 2, 3, and 5 mm, respectively. Recurrent tumors have a significantly higher probability of positive margins (P = .001) than primary ones. Anatomic location and tumor age affect subclinical extension only indirectly. 
Effect of antitumor surgery on soluble interleukin-2 receptor serum levels. Surgically induced immunosuppression may play a role in cancer, because of the possible existence of micrometastases at the time of surgical removal of tumors. Antitumor immune reactions are mediated by interleukin-2 (IL-2). IL-2 acts on a specific IL-2 cell surface receptor; moreover, a soluble form of IL-2 receptor (sIL-2R) can be released in the blood. This study was carried out to evaluate the effect of surgery on sIL-2R serum levels in patients with operable solid tumors. A total of 48 patients with cancer and 11 controls who underwent major surgery for non-neoplastic disease were evaluated before and 7 days after surgery. Serum mean levels of sIL-2R were significantly higher after than before surgery in both the cancer and control groups. No correlation was seen between surgery-induced changes in sIL-2R and in T lymphocyte subsets. Because of its capacity of binding to IL-2, the increased blood concentrations of sIL-2R could reduce the IL-2 availability and negatively affect antitumor immune reactions. 
Maternal reproductive history and birth characteristics in childhood acute lymphoblastic leukemia. Using birth-registration data, a case-control study was done to investigate the possible associations of childhood acute lymphoblastic leukemia (ALL) with birth characteristics and maternal reproductive history. The data included cases born and diagnosed in Minnesota since 1969. Matched analyses were conducted using 337 cases and 1336 birth year-matched controls. There was a statistically significant increased odds of ALL for birth to older (greater than 35 years) mothers (odds ratio (OR) = 2.14, 95% confidence interval (CI) = 1.28, 3.58), older fathers (OR = 1.62, 95% CI = 1.14, 2.30), mothers with at least a high school education (OR = 1.61, 95% CI = 1.05, 2.48), and larger intervals (greater than 5 years) between the birth of the proband and the preceding sibling (OR = 1.86, 95% CI = 1.12, 3.09). The increased odds of ALL for birth by Caesarean section approached significance (OR = 1.42, P = 0.06). No overall association was found for: gender, race, paternal education, fetal-loss history, birth order, prenatal care history, pregnancy complications, inducement of labor, multiple birth, gestational age, or birth weight. Age at diagnosis was an important effect modifier of some analyses. For cases diagnosed before age 2 years, there was a 2.7-fold increased odds of ALL if the last pregnancy had resulted in a fetal loss (P = 0.03). For cases diagnosed before age 4 years, birth weight greater than 3800 g was associated with a significant 2.05-fold increased odds of ALL. These data strengthen the hypothesis that prenatal events may play a causative role in childhood ALL, particularly in those cases diagnosed at a younger age. 
Laser uvulopalatoplasty in treatment of habitual snoring. Velopharyngeal sonorous snoring is best treated with uvulopalatopharyngoplasty (UPPP). To reduce surgical risks and minimize the morbidity, a simplified carbon dioxide laser uvulopalatoplasty (LUPP) was performed under local anesthesia. Among a total of 146 patients who had a LUPP performed, there was no significant bleeding or postoperative episodes of asphyxia. The procedure was well tolerated even by those patients with strong vomiting reflexes. The operation time was halved, as was the convalescence. Two patients (1.4%) developed scarring with nasal obstruction, but the impact of factors other than the laser approach itself seemed to be the cause. By scored questionnaires the effect on snoring, family complaints, and daytime somnolence was evaluated in two comparable random groups of patients. Sixty-three patients had LUPP procedures, and 37 had UPPP. The short-term results showed that about 90% of the patients considered themselves essentially improved as regarded snoring and that most patients felt more alert, irrespective of the surgical method used. 
Cerebral granular cell tumor occurring with glioblastoma multiforme: case report. A 65-year-old man presented with 4 weeks of partial right visual field loss. A left occipital granular cell tumor was diagnosed via open biopsy. No specific tumoricidal therapy was given, and the patient returned 2 weeks later with fluent dysphasia and mild right hemiparesis, and formed visual hallucinations. A large left parietotemporal mass, separate from the granular cell tumor, was diagnosed as a glioblastoma multiforme by stereotactic biopsy. The histogenesis of cerebral granular cell tumors is controversial; this case supports recent speculation of their possible glial origin. 
The parietal cell autoantibodies recognized in neonatal thymectomy-induced murine gastritis are the alpha and beta subunits of the gastric proton pump. Murine autoimmune gastritis, induced by neonatal thymectomy, bears a striking similarity in pathology to the human autoimmune disease, pernicious anemia. Autoantibodies to parietal cells are found in both murine and human diseases. Monoclonal immunoglobulin G autoantibodies, obtained from neonatally thymectomized mice, have previously been shown to recognize two groups of gastric parietal cell antigens. In the present study, it is shown that two of these monoclonal autoantibodies, designated 1H9 and 2B6, are directed against the alpha subunit and beta subunit, respectively, of the gastric hydrogen-potassium-stimulated adenosine triphosphatase (H+,K(+)-ATPase; proton pump). Monoclonal antibody 1H9 showed reactivity by immunoblotting with a 95-kilodalton component of dog gastric tubulovesicular membranes and with a fusion protein containing the hydrophilic domain of the alpha subunit of the H+,K(+)-ATPase. Monoclonal antibody 2B6 reacted by immunoblotting with the 60-90-kilodalton glycoprotein (beta subunit) of the tomato lectin-purified dog H+,K(+)-ATPase and with the 60-90-kilodalton autoantigen purified with human parietal cell autoantibodies. Monoclonal antibody 2B6 also reacted with the deglycosylated 35-kilodalton core protein of the tomato lectin-purified 60-90-kilodalton beta subunit and of the purified 60-90-kilodalton autoantigen. Parietal cell autoantibody-positive sera from 20 mice with experimentally induced gastritis showed reactivity predominantly with the alpha and/or beta subunit of the gastric H+,K(+)-ATPase. Therefore, it is concluded that the major molecules targeted by parietal cell autoantibodies from mice with neonatal thymectomy-induced murine autoimmune gastritis and from humans with pernicious anemia are identical. 
Immunohistochemical staining of CA 50 antigen in human bladder cancer. Relation to histologic grade, clinical stage, and prognosis. The immunohistochemical detection of tumor marker CA 50 was studied in bladder cancer of WHO grades I-III. The material consisted of tumors in 83 patients and the mean clinical follow-up time was thirteen years (range 9.6-22 years). The fraction of CA 50-positive cells (FPtot) in microscopic image was scored 0-100 percent. Also the maximally staining region was selected, and the fraction of CA 50-positive cells in this region was scored 0-100 percent (FPmax). The average staining intensity of CA 50-positive cells was scored from 0 to 3 in the whole section (ASItot) and in the maximally staining area (ASImax). The inverse relation between histologic grade, FPtot (p = 0.0001), and ASItot (p = 0.006) was statistically significant. FPtot (p = 0.039) and ASItot (p = 0.018) were also inversely related to clinical stage. Occurrence of metastasis during the follow-up was associated with low CA 50 positivity (FPtot, p = 0.003; ASItot, p = 0.002). The lower the staining intensity or the lower the fraction of CA 50-positive cells, the more aggressive was the tumor. In survival analysis, low FPtot (p = 0.002) and ASItot (p = 0.007) values were related to high risk of bladder cancer death. The results show that immunohistochemical staining of bladder tumor specimens with CA 50 can be used to predict bladder cancer aggressiveness and survival. 
The bottom end. Handling of the perineal wound after abdominoperineal resection. There are a number of options for handling the perineal wound following abdominoperineal resection, including open packing or primary closure with suction drainage. Open packing has not been widely accepted, fearing that it may delay perineal wound healing. The purpose of this paper, therefore, was to retrospectively evaluate, the experience at Ferguson Hospital with abdominoperineal resection from 1977 through 1986. The study population consisted of 288 patients undergoing abdominoperineal resection for rectal adenocarcinoma. Forty-six patients had the perineal wound closed primarily and 242 had the perineal wound packed open. Ninety-four patients had the pelvic peritoneum left open and 194 underwent closure of the pelvic peritoneum. Overall operative mortality was 2.1 per cent, and there was no significant difference between primary closure and open packing of the perineal wound with respect to hospital stay, operating time, operative blood loss, perioperative mortality, incidence of postoperative bowel obstruction, incidence of postoperative complications, or average time for perineal wound healing. Therefore, it would appear that packing the perineal wound following abdominoperineal resection is a viable means of handling the bottom end. 
Potential role of PFOB enhanced sonography of the kidney. II. Detection of partial infarction. Aside from its ability to assess flow velocity within vessels, color Doppler and gray-scale sonography cannot distinguish perfused from non-perfused tissues. In this study we evaluated whether Perfluorooctylbromide (PFOB), a sonographic contrast agent given i.v., could aid sonography with this recognition. Partial renal infarction was produced by a 1 mm bead embolized in the right, the left, or both renal arteries of 20 normal rabbits. The sonographer, unaware of rabbit assignment, attempted to diagnose the infarct 24 hours later. All 20 rabbits were studied with gray-scale and color Doppler sonography, 10 before and after PFOB and 10 only after PFOB. Angiography and post-mortem examination were done for confirmation. Of the 20 kidneys evaluated before PFOB, the sonographer was unable to diagnose the 10 partial infarctions. Color Doppler identified five of the ten infarcted kidneys, but accurately localized the infarction in only two. Of the 40 kidneys evaluated after PFOB infusion, 20 scanned before and 20 scanned only after PFOB, all 20 partial infarctions were accurately diagnosed with both gray-scale and color Doppler. PFOB enhanced the echogenicity of perfused renal tissue allowing the easy detection of the unenhanced infarct. Because of the increased signal from vessels after PFOB, color Doppler displayed the entire vascular tree, allowing the detection of the truncated embolized branch. The ability of PFOB to enhance Doppler signals and the echogenicity of perfused tissues improved the diagnostic accuracy of sonography when used to detect partial renal infarctions. 
Sarcoid neuropathy. In a case of subacute sensory and motor polyneuropathy associated with sarcoidosis, multiple epineurial and endoneurial granulomas were demonstrated in a sural nerve. Neighbouring nerve fibres were displaced by the granulomas and some were undergoing axonal degeneration. Ultrastructural and teased fibre studies showed axonal atrophy and degeneration with secondary demyelination. Histochemical studies indicated the presence of HLA-DR antigen on epithelioid cells in the granulomas. A non-specific inflammatory process in the nerve does not cause significant primary demyelination. 
Measurement of in vivo urological tumour cell kinetics using multiparameter flow cytometry. Preliminary study. The in vivo labelling of urological tumour cells using the S phase marker bromodeoxyuridine (BRdU) for histochemical studies is reported. The use of multiparameter flow cytometry (FCM) with BRdU labelling to study tumour proliferation offers significant advantages. It provides simultaneous measurements of the DNA ploidy (DI), the duration of the S phase (Ts), the potential doubling time (Tpot) and the total and aneuploid tumour labelling indices (LI) from a single specimen. Heterogenous tumour cell populations can be measured with high sensitivity. We report a preliminary study to evaluate the method in the measurement of the kinetics of transitional cell carcinoma of the bladder (TCCB). Nineteen patients with TCCB, 1 with leukoplakia of the bladder, 2 with renal carcinoma, 1 with prostatic carcinoma and 1 with a squamous carcinoma of the penis were studied. Of the bladder tumours, 3 were aneuploid, DI = 1.32, 1.58 and 1.89. BRdU uptake was detected in all tumours. The median LI was 1.5% (range 0.5-10.0). In 15/19 tumours the labelling profile was satisfactory for calculation of the Ts and Tpot. The median Ts was 6.2 h and the median Tpot was 17.1 days. This study demonstrates that measurement of multiple parameters of urological tumour proliferation in vivo is possible. These parameters require further assessment as indices of biological aggressiveness and clinical prognosis. 
Fate of patients with acute myocardial infarction with patency of the infarct-related vessel achieved with successful thrombolysis versus rescue angioplasty. Patients with failure of infarct-related artery recanalization after thrombolytic therapy have a poor clinical outcome. These patients have been considered for rescue angioplasty 90 min after thrombolytic therapy at the time of emergency catheterization in the course of five Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) trials. The outcome of 776 patients with patent infarct-related vessels after emergency catheterization was analyzed--607 with thrombolysis-mediated patency of the infarct-related vessel and 169 with patency achieved by angioplasty. Baseline characteristics of the thrombolysis and angioplasty patency groups were similar except for a higher acute left ventricular ejection fraction (51.3% versus 48.2%) in the thrombolysis group (p = 0.003). Seven to 10 day left ventricular ejection fraction was higher (52.3% versus 48.1%), infarct zone functional recovery was greater (0.44 versus 0.21 standard deviation/chord, or 18% versus 7%, p = 0.001) and reocclusion was less (11% versus 21%) in the thrombolysis compared with the angioplasty group. Despite these differences, angioplasty patency was associated with the same low in-hospital mortality rate (5.9% versus 4.6%) and long-term mortality rate (3% versus 2%) as thrombolysis patency. Reocclusion adversely affected the mortality rate and ventricular functional recovery. Technical failure of rescue angioplasty was associated with a much higher mortality rate than was technical success (39.1% versus 5.9%). Thrombolysis patency was preferable to angioplasty patency after thrombolytic therapy in acute myocardial infarction, but both were associated with the same low in-hospital and long-term mortality rates, suggesting that rescue angioplasty is beneficial in some patients with failure of infarct-related artery recanalization after thrombolytic therapy. 
Cerebral ischemic events associated with endocarditis, retinal vascular disease, and lupus anticoagulant. PURPOSE: A group of young patients presenting with cerebral ischemic events, endocardial lesions, and lupus anticoagulant is described in order to highlight the common clinical laboratory features. PATIENTS AND METHODS: Fourteen consecutive patients (10 females, age range 17 to 53 years [mean 38 years]) at onset of symptoms of cerebral ischemia who had evidence of the lupus anticoagulant syndrome and were being followed prospectively are reviewed. All patients had abnormal phospholipid-dependent coagulation test results, and most had anticardiolipin antibody at the time of presentation. Three of 14 had four or more American Rheumatism Association criteria for definite systemic lupus erythematosus and the remaining patients were considered to have primary lupus anticoagulant syndrome. RESULTS: The common features among these patients included at least one cerebral ischemic event at presentation (stroke or transient ischemic attack), or recurrent episodes suggesting cerebral ischemia (amaurosis fugax, recurrent severe migraine headaches), livedo reticularis, endocardial valvular lesions noted on echocardiography (11 mitral, two aortic valve) that were often associated with discrete vegetations, retinal vascular lesions, and computed tomographic/magnetic resonance imaging scanning or angiographic evidence of multiple cerebral infarction. Venous thromboembolic events were uncommon (three of 14). Common laboratory studies included thrombocytopenia (10 of 14), positive direct Coombs' test result (11 of 14), and hypocomplementemia (11 of 14). Follow-up after initial treatment with either salicylates or anticoagulant therapy (warfarin) for up to 10 years indicated that while many patients had recurrent symptoms suggesting cerebral ischemia, major stroke syndromes did not recur nor new episodes emerge. CONCLUSION: The combination of multiple cerebral ischemic lesions and endocardial lesions, including valvular vegetations, suggests that these cerebral ischemic events represent cerebral emboli, and that these cerebral embolic events originate from vegetative lesions on the mitral or, less commonly, aortic valve, in association with lupus anticoagulant. 
Admission alcohol level: a predictor of the course of alcohol withdrawal. BACKGROUND. Little is known about how to predict the course of alcohol withdrawal. This study explores relationships between alcohol levels at admission to a detoxification unit and the severity and outcome of alcohol withdrawal. METHODS. A retrospective cohort study was conducted in two institutions, the Mid-Missouri Mental Health Center (MMMHC) and the Harry S Truman Memorial Veterans Hospital (HSTMVH), of individuals admitted during 1 year. RESULTS. The alcohol levels at admission of the 86 clients at the Mental Health Center and the 99 patients at the HSTMVH, correlated with withdrawal severity over the first 48 hours after admission (R2 = .26 at MMMHC, .41 at HSTMVH, P less than .0001 for both), and remained significantly associated even after adjustment for other variables. Furthermore, individuals who had lower alcohol levels at the time of admission were more likely to stay for rehabilitation following detoxification (P less than .001 for both institutions). CONCLUSIONS. A patient's alcohol level at the time of admission to a detoxification unit may help predict the severity of withdrawal and the treatment outcome. 
Electrode system influence on biphasic waveform defibrillation efficacy in humans. BACKGROUND. Several clinical studies have demonstrated a general superiority of biphasic waveform defibrillation compared with monophasic waveform defibrillation using epicardial lead systems. To test the breadth of utility of biphasic waveforms in humans, a prospective, randomized evaluation of defibrillation efficacy of monophasic and single capacitor biphasic waveform pulses was performed for two distinct nonthoracotomy lead systems as well as for an epicardial electrode system in 51 cardiac arrest survivors undergoing automatic defibrillator implantation. METHODS AND RESULTS. The configurations tested consisted of a right ventricular-left ventricular (RV-LV) epicardial patch-patch system, an RV catheter-chest patch (CP) nonthoracotomy system, and a coronary sinus (CS) catheter-RV catheter nonthoracotomy system. For each configuration, the defibrillation current and voltage waveforms were recorded via a digital oscilloscope to measure defibrillation threshold voltage, current, resistance, and stored energy. Biphasic waveform defibrillation proved more efficient than monophasic waveform defibrillation for the epicardial RV-LV system (4.8 +/- 4.1 versus 6.7 +/- 4.9 J, p = 0.047) and the nonthoracotomy RV-CP system (23.4 +/- 11.1 versus 34.3 +/- 10.4 J, p = 0.0042). Biphasic waveform defibrillation thresholds were not significantly lower than monophasic waveform defibrillation thresholds for the CS-RV nonthoracotomy system (15.6 +/- 7.2 versus 20.0 +/- 11.5 J, p = 0.11). Biphasic waveform defibrillation proved more efficacious than monophasic waveform defibrillation in 13 of 20 patients (65%) with RV-LV epicardial patches, 10 of 15 patients (67%) with an RV-CP nonthoracotomy system, and nine of 16 patients (56%) with an RV-CS nonthoracotomy system. CONCLUSIONS. Biphasic pulsing was useful with nonthoracotomy lead systems as well as with epicardial lead systems. However, the degree of biphasic waveform defibrillation superiority appeared to be electrode system dependent. Furthermore, for a few individuals, biphasic waveform defibrillation proved less efficient than monophasic waveform defibrillation, regardless of the lead system used. 
Guillain-Barre syndrome associated with human immunodeficiency virus infection in Zimbabwe. We studied the clinical features and human immunodeficiency virus (HIV) serology of 32 consecutive adults with inflammatory demyelinating polyneuropathy (IDP) admitted to the teaching hospitals in Harare, Zimbabwe. Twenty-nine of the IDP patients had Guillain-Barre syndrome (GBS), and the other three had chronic IDP. Sixteen of 29 (55%) GBS patients were HIV-seropositive, a higher frequency of HIV infection than in blood donors drawn from the population served by these hospitals. All three chronic IDP patients were HIV-seronegative. In all HIV-seropositive patients, GBS was the initial illness that brought the patient to medical attention and led to the diagnosis of HIV infection. Compared with seronegative patients, the HIV-seropositive GBS patients were more likely to have generalized lymphadenopathy, CSF pleocytosis, coexistent CNS disturbance, and prior sexually transmitted disease. GBS in this region of Africa is frequently associated with HIV infection. 
Composition of atherosclerotic plaques in the four major epicardial coronary arteries in patients greater than or equal to 90 years of age. The composition of atherosclerotic plaques in 733 five-mm segments of the 4 major (left main, left anterior descending, left circumflex and right) epicardial coronary arteries of 18 patients greater than or equal to 90 years of age was determined by computerized planimetric analysis. By analysis of all coronary segments of all patients greater than 90, the plaques consisted primarily of fibrous tissue (87 +/- 8%) with calcific deposits (7 +/- 6%), pultaceous debris (5 +/- 4%) and foam cells (1 +/- 1%) occupying a much smaller percentage of plaque area. Analysis of composition according to the 4 degrees of luminal cross-sectional area narrowing revealed marked step-wise increases in pultaceous debris (from 0 +/- 0% at 0 to 25% narrowing to 18 +/- 22% at 76 to 100% narrowing, p = 0.0001) and calcific deposits (from 0 +/- 0 to 10 +/- 15%, p = 0.002), and decreases in fibrous tissue (from 99 +/- 3 to 71 +/- 23%, p = 0.0001) and area occupied by the media (from 35 +/- 8 to 16 +/- 8%, p = 0.0001). When the analysis was restricted to sections narrowed greater than 75%, no significant differences were found in plaque components or medial area between patients with (11 patients) and without (7 patients) myocardial infarcts at necropsy. 
Mortality among petrochemical science and engineering employees. This is a study of a dynamic cohort of 13 250 commercial research and development personnel for whom information on occupational and educational background and smoking was available. Their age-, sex-, race-, and period-adjusted death rates were compared with New Jersey rates and with an internal comparison population. The overall results were favorable. The study groups had significantly fewer deaths from most major disease categories compared with other New Jersey residents. Among white male scientists and engineers, age-adjusted overall mortality and ischemic heart disease mortality were comparable to white male managers and support staff studied, whereas mortality from leukemia and lymphatic cancer was significantly elevated. Mechanics, however, had a significantly lower leukemia and lymphatic cancer mortality rate than did the comparison group. In a Poisson regression model in which white males and females from the study population were used, and for which the effects of age, smoking, college education category, period of hire, and years employed were controlled, scientists, engineers, and research technicians had elevated (nonsignificantly) mortality rates for leukemia and lymphatic cancer compared with managers and support staff. Smoking was an independent risk factor for leukemia and lymphatic cancer. Further work is needed to assess if specific environmental factors, such as benzene, other aromatics, radiation, medical treatment, and smoking habits, might have contributed to the above findings. 
Extracolonic manifestations of the familial adenomatous polyposis syndromes. The classic prototypes of the gastrointestinal polyposis syndromes are familial polyposis coli and Gardner syndrome. Extracolonic manifestations have been described in both diseases, and the distinction between them has become less clear. In fact, some authorities have suggested that familial polyposis coli and Gardner syndrome may represent a spectrum of the same disease. In both conditions, extracolonic expressions are the rule rather than the exception, and familiarity with them is essential for accurate diagnosis and correct patient management. In this pictorial essay, we discuss familial polyposis coli and Gardner syndrome together under the heading familial adenomatous polyposis syndromes. The colonic characteristics of these syndromes will be reviewed briefly, followed by examples of the most common extracolonic manifestations. 
Electrophysiological improvement following decompression surgery in tarsal tunnel syndrome. Plantar nerve conduction studies 14 months to 3.5 years after decompression surgery in 3 cases of tarsal tunnel syndrome showed an improvement in motor conduction as well as in sensory nerve conduction. This electrophysiological improvement was associated with clinical improvement. However, minor abnormalities still existed in sensory nerve conduction in all 3 cases. 
SWIFT trial of delayed elective intervention v conservative treatment after thrombolysis with anistreplase in acute myocardial infarction. SWIFT (Should We Intervene Following Thrombolysis?) Trial Study Group. OBJECTIVE--To see whether early elective angiography with a view to coronary angioplasty or bypass grafting of a stenosed infarct related vessel would improve outcome in acute myocardial infarction treated by thrombolysis with anistreplase. DESIGN--Randomised study of two treatment strategies with analysis of results over 12 months. SETTING--21 district hospitals and regional cardiac centres in Britain and Ireland. SUBJECTS--800 of 993 patients presenting with clinical and electrocardiographic features of acute myocardial infarction up to three hours after the onset of major symptoms. TREATMENT STRATEGIES--Intravenous anistreplase 30 units followed by a standard regimen of heparin, warfarin, and timolol and (in patients so randomised) early angiography plus appropriate intervention. MAIN OUTCOME MEASURE--Death or reinfarction within 12 months. RESULTS--397 patients were randomised to receive early angiography plus appropriate intervention (coronary angioplasty in 169 cases, coronary grafting in 59) and 403 patients to receive conservative care (of these, 12 had angioplasty and seven bypass grafting during the initial admission). By 12 months mortality (5.8% (23 patients) in the intervention group v 5.0% (20) in the conservative care group; p = 0.6) and rates of reinfarction (15.1% (60 patients) v 12.9% (52); p = 0.4) were similar in the two groups. No significant differences in rates of angina or rest pain were found at 12 months. Left ventricular ejection fraction at three and 12 months was the same in both groups. Median hospital stay was longer in the intervention group (11 days v 10 days; p less than 0.0001). CONCLUSION--For most patients given thrombolytic treatment for acute myocardial infarction a strategy of angiography and intervention is appropriate only when required for clinical indications. 
Calcium for resuscitation? Calcium ions are essential for myocardial excitation-contraction coupling and for increasing contractility of the heart. Because of these physiological effects, use of calcium has been recommended in the treatment of electromechanical dissociation, asystole and ventricular fibrillation. Recently, however, the use of calcium during cardiac arrest has come into dispute, as there are no controlled clinical trials supporting a favourable haemodynamic effect. It has rather been suggested that, in resuscitation, calcium may have detrimental effects. In order to evaluate the role of calcium in cardiopulmonary resuscitation, it is important to know the serum concentrations of calcium and the haemodynamic effects in this situation. Measurements in some patients with cardiac arrest have demonstrated that severe hypocalcaemia may not be uncommon. In these patients, calcium may augment myocardial contractility, decrease intracardiac filling pressures and increase mean arterial pressure. At present, the more or less established indications for use of calcium during cardiopulmonary resuscitation are in treating patients with proven hypocalcaemia, hyperkalaemia, calcium channel blocker overdose and, possibly, electromechanical dissociation combined with a wide QRS complex. There is no good evidence supporting the routine use of calcium in resuscitation. 
Natural course of Graves' disease after subtotal thyroidectomy and management of patients with postoperative thyroid dysfunction. The Natural course of Graves' disease after subtotal thyroidectomy was studied in 67 patients who had subtotal thyroidectomy for Graves' disease and did not receive any medical treatment for 8 to 12 years after surgery. Postoperative thyroid status was determined by serum free thyroxine (T4), free triiodothyronine (T3), and thyrotropin (TSH) levels in the first period (1 year after surgery), second period (3.9 +/- 1.0 years), and third period (8.8 +/- 1.5 years). Serum thyroid stimulating antibody (TSAb) and TSH binding inhibitor immunoglobulin (TBII) activities were also measured. A total of 53 patients (79%) changed thyroid status during the observation period. One year after surgery, 50 percent of euthyroid subjects developed abnormal thyroid function in the next period. Reversible latent hypothyroidism was the most common type of thyroid dysfunction seen in up to 46% of patients. Interestingly, hyperthyroidism and hypothyroidism that developed in the postoperative period were temporary disorders in most cases. Serum TSAb and TBII activities did not help predict the postoperative changes of thyroid status. Our study indicates that the instability of the thyroid function is common after subtotal thyroidectomy. 
Plasma prostanoids in neonates with pulmonary hypertension treated with conventional therapy and with extracorporeal membrane oxygenation. Thromboxane may be a mediator of pulmonary hypertension in the neonate. Acute thromboxane-mediated pulmonary hypertension has been described in sheep receiving extracorporeal membrane oxygenation, which raises concerns about a potential thromboxane-mediated exacerbation of pulmonary hypertension in human neonates with severe pulmonary hypertension who are treated with extracorporeal membrane oxygenation. We measured plasma levels of thromboxane, prostaglandin F2 alpha, and 6-keto-prostaglandin F1 alpha in infants with pulmonary hypertension, some of whom were treated medically and some of whom were treated with extracorporeal membrane oxygenation. Plasma levels of all three prostanoids were elevated in infants with pulmonary hypertension and decreased with time, whether the neonates were treated with extracorporeal membrane oxygenation or with medical management alone. In infants treated with extracorporeal membrane oxygenation, we collected samples simultaneously from preoxygenator sites, postoxygenator sites, and umbilical artery catheter. We could demonstrate no significant difference in plasma prostanoid levels across the oxygenator. In two patients, plasma thromboxane and prostaglandin F2 alpha levels measured shortly after a platelet transfusion were distinctly higher in the umbilical artery catheter than in venous samples. 
Median and ulnar neuropathy after streptokinase infusion. In a patient treated with intravenous streptokinase, inflammation developed at the infusion site followed by permanent ulnar and median neuropathy. Although adverse streptokinase infusion site reactions have been reported to the Food and Drug Administration, no other cases have been reported in the medical literature. We suggest that extravasated streptokinase may produce permanent ulnar and median neuropathy. 
Ki-1-positive large cell lymphomas, a heterogenous group of neoplasms. Morphologic, immunophenotypic, genotypic, and clinical features of 24 cases. Clinical and pathologic features of 24 patients with large cell lymphomas that expressed the activation antigen Ki-1 are described. Phenotypic and/or genotypic studies characterized these neoplasms as T-cell (16 cases), B-cell (six cases), or null cell (two cases) type. Males predominantly were affected. Age of patients ranged from 19 to 73 years, with a bimodal distribution, with peaks in the third and seventh decades. Lymphadenopathy was present in nearly all patients. Extranodal involvement, including skin, soft tissue, bone, central nervous system, lung, or small intestine was observed in a total of 54% of the patients, either at presentation or during the course of disease. "Prototypic" features of large cell anaplastic lymphomas were observed for eight T-cell lymphomas, with morphologic heterogeneity noted for the remainder. Eight patients, all with T-cell neoplasms (only one with prototypic morphology), have died of lymphoma (median survival, 5 months). An antecedent history of a lymphoproliferative disorder (mycosis fungoides, B-cell lymphoma, immunoblastic lymphadenopathy) was apparent in seven patients. An 8-year history of Crohn's disease occurred in one patient with a T-cell lymphoma involving small intestine. Phenotypically, loss of one or more markers was typically noted for T-cell neoplasms. Leukocyte common antigen was detected in all cases, although partial loss of immunoreactivity was noticed in some cases. Nearly all cases evaluated for Ia antigen or alpha-1-antichymotrysin were reactive. Eleven of 16 T-cell, two of six B-cell, and two null cell lymphomas expressed epithelial membrane antigen. Ki-1-positive large cell lymphomas are characterized by clinical, morphologic, and immunophenotypic heterogeneity. 
Isoflurane anesthesia and myocardial ischemia: comparative risk versus sufentanil anesthesia in patients undergoing coronary artery bypass graft surgery. The SPI (Study of Perioperative Ischemia) Research Group. Whether isoflurane has the potential to produce coronary artery steal and associated myocardial ischemia is still controversial. Previous studies addressing this issue in humans did not purposefully control hemodynamics or use continuous measures of myocardial ischemia. The authors used transesophageal echocardiography (TEE) and continuous Holter electrocardiography (ECG) to study the relative risk of myocardial ischemia during isoflurane or sufentanil anesthesia under strict control of hemodynamics in 186 high-risk patients undergoing elective coronary artery bypass graft (CABG) surgery. Overall, hemodynamics were well controlled (increased heart rate = 9.8%; increased systolic blood pressure = 7.1%; decreased systolic blood pressure = 10.8% of total prebypass time compared with preoperative baseline values), with no difference between the two anesthetics. In the 162 patients with interpretable TEE recordings, moderate to severe TEE ischemic episodes (grade change greater than or equal to 2) developed in 33 (21%) during the prebypass period, with no difference between isoflurane (12 of 56 = 21%) and sufentanil (21 of 106 = 20%) (P = 0.97). The duration and severity of TEE episodes were not significantly different between the two groups. No correlation was observed between TEE ischemic episodes and isoflurane concentrations (range 0.47-1.75%). In the 181 patients with interpretable ECG recordings, ECG evidence of ischemia developed in 34 (19%) during the prebypass period, with no difference between isoflurane (12 of 59 = 20%) and sufentanil (22 of 122 = 18%) (P = 0.87). The duration and severity of electrocardiographic ischemic episodes were also similar in patients receiving either isoflurane or sufentanil. Four of the 62 patients (6%) who received isoflurane had an adverse cardiac outcome versus 15 of 124 patients (12%) who received sufentanil (P = 0.34). The authors' findings demonstrate that, when hemodynamics are controlled, the incidence of myocardial ischemia (TEE or ECG) during isoflurane and sufentanil anesthesia is similar. 
Multisystem failure and hepatic microvesicular fatty metamorphosis associated with tolmetin ingestion. Multisystem toxicity including both renal and hepatic failure has been reported with the use of nonsteroidal anti-inflammatory drugs. We report a fatal case of multisystem failure associated with tolmetin ingestion in a 15-year-old girl. Microvesicular fatty change was found in the liver at autopsy. To our knowledge, this is the first reported case of nonsteroidal anti-inflammatory drug-associated multisystem failure to have this histopathologic finding. 
Effect of antitumor surgery on soluble interleukin-2 receptor serum levels. Surgically induced immunosuppression may play a role in cancer, because of the possible existence of micrometastases at the time of surgical removal of tumors. Antitumor immune reactions are mediated by interleukin-2 (IL-2). IL-2 acts on a specific IL-2 cell surface receptor; moreover, a soluble form of IL-2 receptor (sIL-2R) can be released in the blood. This study was carried out to evaluate the effect of surgery on sIL-2R serum levels in patients with operable solid tumors. A total of 48 patients with cancer and 11 controls who underwent major surgery for non-neoplastic disease were evaluated before and 7 days after surgery. Serum mean levels of sIL-2R were significantly higher after than before surgery in both the cancer and control groups. No correlation was seen between surgery-induced changes in sIL-2R and in T lymphocyte subsets. Because of its capacity of binding to IL-2, the increased blood concentrations of sIL-2R could reduce the IL-2 availability and negatively affect antitumor immune reactions. 
Computed tomography for patient management in coronary artery disease. Computed tomography (CT) represents the optimum theoretical approach to x-ray imaging. This conclusion results from an awareness of CT's capacity to solve the fundamental limitation of all forms of x-ray imaging--the superimposition of anatomic structures. Because CT is potentially a fully three-dimensional method, this problem is addressed in a manner not subject to the risks, complications, and technical limitations of selective angiography, subtraction angiography, tomography, and other techniques. Ultrafast CT provides a broad spectrum of useful quantitative cardiac data during one minimally invasive procedure. Therefore, the optimism for cine CT imaging of the heart is well founded. Apart from the demonstration of anatomic structures in any reconstructed plane and in movie format, without the need for any form of electrocardiographic gating, this new generation of millisecond CT scanners offers a unique potential for measuring myocardial mechanics and perfusion. Myocardial integrity can be evaluated by measuring myocardial wall thickening, which is a sensitive indicator of blood flow. It can also be assessed by time-density changes derived from analyzing the passage of contrast medium through thin slices of myocardium. Feasibility studies have demonstrated that this should be possible in the clinical setting by use of fast CT scanning. The radiation exposure to the patient with cine CT is low and comparable to, or less than, that of conventional CT and 10-15% of that received during angiocardiography; therefore, it is not a practical limitation. Further clinical and research studies are needed to determine the future role of this exciting new modality in the diagnosis and management of patients with heart disease. 
Propranolol in the management of recurrent migraine: a meta-analytic review. We used meta-analytic statistical techniques to synthesize findings from studies that evaluated propranolol HCI for the prevention of recurrent migraine (2,403 treated patients). The modal migraine sufferer treated in these studies was a female, about 37 years of age, who suffered from common (rather than classical) migraines and reported a 17-year history of problem migraines. The modal treatment was 160 mg. propranolol per day. Meta-analysis revealed that, on average, propranolol yielded a 44% reduction in migraine activity when daily headache recordings were used to assess treatment outcome, and a 65% reduction in migraine activity when less conservative measures (e.g., clinical ratings of improvement, global patient reports) were used. Meta-analysis thus revealed substantial support for short-term effectiveness of propranolol. However, little information was available concerning the long-term effectiveness of propranolol. 
Large vessel vasculitis of the central nervous system in systemic lupus erythematosus: report and review of the literature. Large vessel vasculitis rarely involves the central nervous system in patients with systemic lupus erythematosus. We describe an exemplary case, along with its dramatic cerebral angiogram, and review the literature on this unusual entity. 
Squamous cell carcinoma occurring in the wall of a chronic aspergilloma. An aspergilloma that occurred within an area of bronchiectasis in a 52 year old man persisted for 12 years despite medical and surgical treatment. A squamous cell carcinoma developed in the wall of the cavity. 
DNA ploidy patterns of tumors diagnosed as metachronous or recurrent lung cancers. The relationship between the first tumor and the second tumor resected in 8 patients with non-small cell lung cancer was analyzed using deoxyribonucleic acid (DNA) flow cytometry. Of the 8 patients, 6 were clinically diagnosed as having metachronous lung cancers and 2, local recurrent tumors. The mean interval between operations in patients with metachronous lung cancers was 62 months (range, 15 to 128 months). Both tumors showed the same histology in 4 patients and a different histology in 2. In the 2 patients with local recurrent tumors, the interval between operations was 9 months and 39 months. In the analysis of DNA flow cytometry of the first and second tumors in the same patient, the tumors were defined as independent of each other when one tumor showed diploidy and the other, aneuploidy, or when each DNA index of abnormal clones between two aneuploid tumors was different. When both tumors showed diploidy or when at least one DNA index of abnormal clones between two aneuploid tumors was identical, the tumors were defined to be related to each other. According to these criteria, in 5 (83%) of the 6 patients clinically diagnosed as having metachronous lung cancers, the second tumor was classified as independent of the first tumor. On the other hand, in the 2 patients clinically diagnosed as having recurrent tumors, the second tumor was judged to be related to the first tumor. These data suggest that DNA flow cytometric analysis of tumors may be of value in the diagnosis of metachronous lung cancers. 
Intravenous nitroglycerine in the management of posttreatment hypertension during electroconvulsive therapy. Intravenous nitroglycerine is not described in the psychiatric literature for management of the inevitable and potentially dangerous pressor response encountered in electroconvulsive treatment. However, the anesthesia literature has documented the use of nitroglycerine for the management of similar catecholamine-based hypertension. Unlike other approaches, nitroglycerine creates a controlled, significant, brief vasodilatation after convulsive treatment accompanied by desirable coronary vasodilatation without increased cardiac stress. A review of a series of treatments in which this technique was used confirms the clinical efficacy and safety of this approach. 
Raised exercise diastolic blood pressure as indicator of ischaemic left ventricular dysfunction. 91 (16.8%) of 541 consecutive patients investigated for chest pain or after recent uncomplicated myocardial infarction had a rise in diastolic blood pressure (DBP) of more than 15 mm Hg during a symptom-limited treadmill test. 63 also had electrocardiographic evidence of ischaemia, but 28 did not have 1 mm ST segment depression, of whom 24 had angiographic evidence of more than 70% stenosis of two or more major coronary arteries. 55 of these 91 patients underwent coronary artery bypass surgery; repeat angiography in 22 at 12 months showed an improved left ventricular ejection fraction in 18 who had a normal postoperative DBP response, but no change in ejection fraction in the 4 who still had an abnormal rise in DBP on exercise. Exercise-induced ischaemia may cause a reversible fall in cardiac output that sometimes leads to reflex vasoconstriction and a rise in DBP before a fall in systolic blood pressure or ECG evidence of ST segment depression. An abnormal DBP response to exercise may identify some patients at high risk of myocardial infarction who might otherwise have false-negative exercise tests. 
The lack of relationship between hepatotoxicity and lithocholic-acid sulfation in biliary bile acids during chenodiol therapy in the National Cooperative Gallstone Study. To test whether hepatotoxicity occurring in National Cooperative Gallstone Study patients was caused by a toxic effect of chenodiol per se or of lithocholate caused by defective sulfation, bile samples were analyzed using a new high-performance liquid chromatography method that measures the proportions of the four individual lithocholate amidates (sulfated and unsulfated lithocholylglycine and lithocholyltaurine) and all common bile acid amidates. Samples were obtained from National Cooperative Gallstone Study patients (n = 17) with abnormal light microscopic liver biopsy results or major aminotransferase elevations and from a matched control group of patients (n = 14) who received similar chenodiol doses but had no evidence of liver injury. Bile samples from 45 healthy subjects were also analyzed. The analytical method was validated by showing that the percentage of chenodiol and cholic and deoxycholic acid obtained by high-performance liquid chromatography correlated highly (r greater than 0.94) with previous gas-liquid chromatography analyses of these samples by the National Cooperative Gallstone Study Reference Laboratory. No significant differences were seen between gallstone patients with and without evidence of liver injury for percent total lithocholate amidates, percent sulfated or unsulfated lithocholate amidates or percent chenodiol amidates. Lithocholate was partially sulfated in all bile samples (52% +/- 17% [mean +/- S.D., n = 50]), but the extent of sulfation varied widely between and within patients during the course of therapy. Mean values of healthy subjects were similar and also showed a wide range in the extent of lithocholate sulfation. It is concluded that (a) liver injury caused by these doses of chenodiol could not be attributed to the accumulation of unsulfated lithocholate per se in circulating bile acids; (b) liver injury appeared to be, directly or indirectly, caused by enrichment in circulating bile acids with chenodiol or chenodiol together with lithocholate, suggesting that the hepatocytes of those patients with hepatotoxicity were injured by the change induced in bile-acid metabolism by the feeding of chenodiol; and (c) about half of lithocholate amidates in bile samples were sulfated, but the extent of sulfation was highly variable both in gallstone patients and healthy subjects. 
Effects of rigidity of an internal fixation device. A comprehensive biomechanical investigation. Internal fixation with instrumentation often accompanies surgical fusion to augment spinal stability, provide temporary fixation while the surgical fusion mass unites, and enhance postoperative mobilization of a patient. Some surgeons, however, feel that the existing plate-screw designs are too rigid and are the primary cause of "iatrogenic" adverse effects clinically observed. A three-part study, involving in vitro experimental protocol, analytical finite-element-based models, and an in vivo canine investigation, was undertaken to study the role of decreasing rigidity of a device on the biomechanical response of the stabilized segments. Two alternatives--the use of one variable screw placement (Steffee plate [unilateral, 1VSP model]) as opposed to two VSP plates (bilateral, 2VSP model) and two VSP plates with polymer washers placed in between the integral nut and plate (2MVSP model)--were considered for achieving a reduction in the rigidity of the conventional VSP system. The load-displacement data obtained from the in vitro experiments and the stress distributions within the stabilized and intact models predicted by the finite-element models revealed that the unilateral VSP system is less rigid and is likely to reduce stress shielding of the vertebral bodies compared with the 2VSP model. The undesirable effects associated with the use of the 1VSP plate system are the presence of coupled motions due to the inherent asymmetry and the likely inability to provide enough rigidity for decompression procedures requiring a complete excision of the disc. The use of two MVSP plates overcomes these deficiencies. 
Natural history of acquired renal cystic disease in dialysis patients: a prospective longitudinal CT study. Patients with end-stage kidney disease, particularly those treated with dialysis, develop proliferative processes in their native kidneys that result in the formation of multiple acquired renal cysts, renal adenomas, and carcinomas. Data about these abnormalities have been acquired mainly from retrospective studies. We undertook a longitudinal prospective study in which the native kidneys of 30 dialysis patients were surveyed by serial CT during a 7-year period to study the natural history of acquired renal cystic disease and the frequency of associated complications. Acquired cysts were seen in 87% of patients at the end of the study compared with 57% at the study's onset, and a significant increase was seen in mean renal volume with time. Five patients (17%) developed large hemorrhagic renal cysts and four (13%) developed large perinephric hematomas. Renal cell carcinomas developed in two patients (7%) without renal symptoms. One carcinoma invaded the renal capsule, but did not cause metastases. The other carcinoma was widely metastatic. Our findings are consistent with those of earlier studies documenting an increased prevalence of renal cell carcinoma in dialysis patients as compared with the general population. However, our conclusions are limited because the study sample is small and no control population was studied. We conclude that acquired renal cystic disease in dialysis patients is a progressive disorder often associated with cyst hemorrhage. Dialysis patients may also have an increased prevalence of renal cell carcinoma. 
Long-term nonsteroidal antiinflammatory drug use and Helicobacter pylori infection. This study investigates whether patients who take nonsteroidal antiinflammatory drugs are more likely to have Helicobacter pylori gastritis than age-matched individuals who do not take nonsteroidal antiinflammatory drugs, and whether patients who take nonsteroidal antiinflammatory drugs who are also infected with H. pylori are more likely to have dyspepsia, mucosal damage, or ulcers than those who are not infected. Two studies were performed, one serological and the other endoscopic, both in arthritis patients receiving nonsteroidal antiinflammatory drugs chronically. The presence of H. pylori was identified with a sensitive enzyme-linked immunosorbent assay test. One hundred eighty-three patients participated in the serological study and 75 patients in the endoscopic study. The frequency of H. pylori infection increased with age, independent of nonsteroidal antiinflammatory drug use; the age-adjusted frequency of H. pylori infection in arthritis patients paralleled that of 351 asymptomatic individuals without arthritis. The frequency of H. pylori infection increased from 30.7% in age group 21-30 years to 73.4% in age group 61-75 years. Nonsteroidal antiinflammatory drug-induced mucosal injury, either hemorrhages or erosions, was more frequent in those without H. pylori infection than with infection (61% vs. 32% for hemorrhages and 57% vs. 34% for erosions for those without and with H. pylori infection; only the difference in the frequency of hemorrhages was significant, P less than 0.05). No difference was observed in the presence of dyspeptic symptoms between those with and without H. pylori infection. These data suggest that nonsteroidal antiinflammatory drug-induced damage to the gastroduodenal mucosa does not increase the susceptibility to H. pylori infection. 
Prominent meningeal "tail sign" in a patient with a metastatic tumor. A prominent enhancement of the dura adjacent to meningiomas has been described as being pathognomonic of these tumors. We describe a case where a classic meningeal "tail sign" was associated with an extra-axial metastatic tumor attached to the tentorium. There was no tumor invasion of the dura. We conclude that this sign is nonspecific and can be seen with dural-based tumors other than meningiomas. 
Enhanced detection of intracardiac sources of cerebral emboli by transesophageal echocardiography. We performed transesophageal echocardiography in 50 consecutive hospitalized patients with recent transient ischemic attack or stroke of embolic origin to determine whether transesophageal echocardiography is more sensitive than transthoracic echocardiography in detection of possible intracardiac sources of embolism. Twenty-six of 50 patients with a negative transthoracic echocardiogram for potential source of emboli had a transesophageal echocardiography study that demonstrated at least one intracardiac abnormality. Abnormalities noted by transesophageal echocardiography included five of 50 patients with either a left atrial or left atrial appendage clot, four patients with a patent foramen ovale, and nine patients with spontaneous echocardiographic contrast. In 11 of 50 patients with no other source of embolism, we found highly mobile filamentous strands on the mitral valve, which have not been described previously. These mitral valve echo strands may represent a fissured surface or fibrosis that can serve as a nidus for thrombus formation. We detected no unexpected left ventricular thrombus or left atrial myxoma. Factors significantly associated with a greater likelihood of a positive transesophageal echocardiography study included left atrial enlargement, atrial fibrillation, and a calcified or thickened mitral valve. Our study suggests that transesophageal echocardiography is a valuable addition to transthoracic echocardiography in investigating potential intracardiac sources of embolism. 
Incidental microvesicular steatosis due to valproic acid anticonvulsant therapy. Valproic acid has been implicated in at least 100 cases of fatal acute liver failure. Most cases have occurred in patients less than 10 yr old; however, at least seven have involved adults. Microvesicular steatosis has been uniformly observed, but its incidence in less severe liver disease and in asymptomatic patients receiving valproate is unknown. We report two patients receiving maintenance valproate, one with resolving acute hepatitis C and the other with chronic persistent hepatitis C, with incidental microvesicular steatosis demonstrated on oil-red O stains. We conclude that microvesicular steatosis does not necessarily signify hepatotoxicity in patients on chronic valproic acid, and should not lead to discontinuation of the drug until other causes of acute or chronic liver disease have been excluded. 
Safety and efficacy of alfentanil and halothane in paediatric surgical patients. Alfentanil, a congener of the opioid fentanyl, possesses properties that make it an attractive choice for use during short operative procedures. Since the pharmacodynamic aspects of alfentanil have not been well documented in children, this study was undertaken to evaluate the safety, efficacy, and dose requirements of alfentanil when used with nitrous oxide or halothane in paediatric patients. Eighty unpremedicated patients, ASA physical status I or II and aged 2-12 yr were studied. Patients were randomly assigned to one of four groups. After induction of anaesthesia with nitrous oxide, oxygen, and halothane, the groups were treated as follows. In Group 1 (n = 19), after halothane was discontinued, alfentanil 50 micrograms.kg-1 was infused over 30 sec. In Group 2 (n = 20), the end-tidal halothan was maintained at 0.5% and alfentanil 25 micrograms.kg-1 was infused. In Group 3 (n = 20), the end-tidal halothane concentration was maintained at 1% and alfentanil 12.5 micrograms.kg-1 was infused. In Group 4 (n = 21), the end-tidal halothane concentration was maintained at 1.5% and no alfentanil was administered. Patients in Groups 1, 2, and 3 received bolus doses of alfentanil 12.5 micrograms.kg-1 as needed to maintain haemodynamic stability. After alfentanil administration, there were transient decreases in systolic blood pressure in Groups 1 and 2, and in heart rate in Group 2. With surgical stimulation, haemodynamic stability was well maintained except in patients in Group 1, who had an increase in systolic blood pressure. Children Group 1 were alert sooner and their tracheas were extubated earlier than those in Groups 2, 3, and 4. 
Effect of propofol on the incidence of postoperative vomiting after strabismus surgery in pediatric outpatients. Vomiting is a common problem after strabismus surgery in pediatric outpatients. We compared the effects of propofol with and without N2O and droperidol to the effects of a conventional regimen consisting of halothane-N2O-droperidol on the recovery characteristics and the incidence of postoperative emesis after strabismus surgery in 120 ASA physical status 1 or 2 children. After induction of anesthesia with halothane-N2O, patients were randomly assigned to one of four groups. Group A (control) received halothane, 66% N2O, and droperidol 75 micrograms.kg-1; group B, propofol 2 mg.kg-1 bolus followed by infusion of 160 microgram.kg-1.min-1; group C, propofol (as in group B) and 66% N2O; and group D, propofol (as in group B), 66% N2O (as in group C), and droperidol 75 micrograms.kg-1. Patients in group B had more episodes of intraoperative oculocardiac reflex responses than patients in group A, but had shorter times to extubation, oral intake, ambulation, and discharge, as well as a lower incidence of postoperative emesis (P less than 0.05). The addition of N2O to the propofol anesthetic regimen (group C) was associated with an increased incidence of emesis (P less than 0.05), whereas the addition of droperidol to the propofol-N2O regimen (group D) did not affect the incidence of emesis compared to the other three groups. We conclude that maintenance of anesthesia with a total intravenous regimen using propofol results in a more rapid recovery and less postoperative emesis than with a halothane-N2O-droperidol regimen. 
Choledocholithiasis. Endoscopic sphincterotomy or common bile duct exploration. A prospective randomized trial was conducted of preoperative endoscopic sphincterotomy and surgery (ES&S) or surgery alone (SA) in 52 patients with cholecystolithiasis and choledocholithiasis that were candidates for elective surgery. After ES&S 65% of patients were stone free. Eighty-eight per cent of patients with SA were stone free after surgery (p less than 0.05). Three patients in each group had residual stones at the completion of the operation. Five of these six had more than 20 common bile duct (CBD) stones. There was one episode of major hemorrhage in a patient in each group and no deaths. Costs were essentially equal for the individual patient with a successful ES as compared to SA. Societal costs of a program of preoperative endoscopic retrograde cholangiopancreatography and ES would be higher because of the cost of screening for patients with CBD stones. These results do not support preoperative ES as a technique for clearance of the CBD of stones on the basis of efficacy, morbidity rate, or cost. 
Inoperable recurrence after breast-conserving surgical treatment and radiotherapy. Factors associated with inoperable local recurrence were investigated by a clinical and pathologic review of 596 patients with Stages I and II carcinoma of the breast treated by breast-conserving operations and megavoltage radiotherapy. After a median follow-up period of 71 months, 13 of 70 local recurrences observed were anatomically unsuitable for salvage surgical treatment, affecting 2.2 per cent of patients initially treated. In most, inoperable recurrences clinically resembled primary inflammatory carcinoma of the breast. All inoperable failures occurred in patients with invasive ductal carcinoma and were associated with the presence of unfavorable prognostic features (positive nodes, histologic grade 3, negative estrogen receptor, vascular invasion and lymphocytic stromal reaction). Despite doxorubicin-based chemotherapy, prognosis after inoperable recurrence was quite poor, although survival time in excess of two years was seen in receptor positive, lower grade recurrent tumors in which treatment included hormone therapy. 
Exophytic signet-ring cell carcinoma of the colorectum Previous studies have assessed colorectal signet-ring cell carcinomas of the linitis plastica variant but not of the exophytic subtype. We retrospectively reviewed 20 cases of colorectal signet-ring cell carcinoma of the exophytic subtype (greater than 50% signet-ring cells). The patients ranged in age from 14 to 79 years (mean, 51.8 years); 10 were male; 17 were white; and three were black. Ten tumors were colonic (eight, right sided; two, left sided) and 10 were rectal; seven were stage B and 12 were stage C. One patient presented with distant metastases. Eleven of 16 tumors assessed by flow cytometry were diploid. Parenchymal hepatic metastases developed in only two patients. The overall 5-year survival rate was 36%, and matched cases did not vary significantly in survival from typical nonmucinous adenocarcinomas. There was a trend toward poorer survival for patients with advanced-stage tumor. Survival was not affected by primary site, ploidy, presence of vascular/lymphatic invasion or residual adenoma, or percentage of extracellular mucin or signet-ring cells. Our cases were somewhat lower stage than literature cases of signet-ring cell carcinoma of the lintis plastica variant. 
The relationship between MMPI cluster membership and diagnostic category in headache patients. Only one study has examined MMPI cluster profiles in the headache population. The present study expanded on this previous investigation by using a large sample size (N = 485) and a greater number of diagnostic categories. The five MMPI clusters replicated previous findings in the chronic pain literature. These MMPI cluster groups were compared to 5 diagnostic categories (migraine, cluster, post-trauma, tension, mixed). No relationship was found between cluster type and headache diagnosis. While the diagnostic groups were found to differ on measures of pain severity, sex and age, cluster groups did not. It is proposed that MMPI scale types reflect a patient's response to pain and are more likely to be the result of coping resources than headache-related personality style. Future research with additional, non-pain populations and prospective studies is suggested. 
Skin acceptance of transcutaneous nitroglycerin patches: a prospective study of 33 patients. Transdermal nitroglycerin is commonly used and may induce contact dermatitis. The frequency of adverse skin reactions is controversial and may vary from 10% to 75%, according to various authors. 33 patients using transdermal nitroglycerin for more than 7 days were examined and patch tested (nitroglycerin 0.5% aq., 2% pet. and TTS in toto). 5 patients (15%) had adverse reactions. The patch tests were all negative in the 33 patients. Contact dermatitis occurs in many cases, about 15% of the cases with the newly available TTS, and even if patients respect the conditions for using TTS. These contact dermatitides are mainly irritant reactions and do not require transdermal nitroglycerin treatment to be stopped. Nevertheless, since some cases of allergic contact dermatitis have been reported, a contact dermatitis from transdermal nitroglycerin should lead to patch testing. 
Intravascular papillary endothelial hyperplasia of superior vena cava: a rare cause of the superior vena cava syndrome. The superior vena cava syndrome associated with an intraluminal vascular proliferative lesion is extremely rare. A case of intravascular papillary endothelial hyperplasia of the superior vena cava causing obstructive symptoms is reported that was successfully managed by surgical excision. 
Pancytopenia associated with hypothermia. This is the first report of pancytopenia associated with moderate hypothermia occurring in an elderly patient, where no other etiologic or associated factors could account for the hematologic abnormalities found. Reversible pancytopenia should be added to the list of hematologic abnormalities that can be seen in patients with hypothermia. 
The decline of mortality due to stroke: a competitive and deterministic perspective. Although stroke mortality has been declining since the first part of this century, the rate of decline increased sharply during the early 1970s. The basis for the fall in stroke mortality is often attributed to effective management of risk factors, particularly hypertension. However, some investigators have questioned whether risk factor reduction alone can adequately account for the magnitude of the recent decline in stroke mortality. When viewed from the perspective of competitive and deterministic mortality dynamics, the major force decreasing stroke mortality is the decreasing deterministic competitiveness of stroke and the increasing deterministic competitiveness of various malignant neoplasms and degenerative diseases as causes of mortality. These reciprocal trends are a natural consequence of the competitive deterministic mortality dynamics which describe these diseases in an environment that is becoming more conducive to human survival. The competitive nature of human mortality makes drawing etiopathogenic conclusions based upon single disease mortality data hazardous. 
Clinical course of idiopathic dilated cardiomyopathy in children Previous studies in adults with dilated cardiomyopathy suggest that the presence of arrhythmia, especially ventricular tachycardia, correlates with increased mortality. We performed a retrospective analysis of 63 children with idiopathic dilated cardiomyopathy to determine the prognostic significance of arrhythmias and other findings with respect to mortality. The mean age at diagnosis of the cardiomyopathy was 4.96 +/- 5.3 years. The overall mortality rate was 16% over a 10 year follow-up period. Persistent congestive heart failure and ST-T wave changes correlated with increased mortality (p less than 0.05). No other variables affected outcome. Arrhythmias were found in 46% of the patients; of the arrhythmias, 48% were atrial arrhythmias. Ventricular tachycardia was present in six patients. Death occurred in 4 (14%) of 29 patients with known arrhythmia; 1 of the 5 died suddenly. The remaining 6 deaths in the series occurred in the 34 patients without a documented arrhythmia. It is concluded that 1) arrhythmias are frequently seen in children with dilated cardiomyopathy but are not predictive of outcome; 2) sudden death in children with this disease is rare; and 3) persistent congestive heart failure portends a poor prognosis. 
Bleeding complications following initiation of thrombolytic therapy for acute myocardial infarction: a comparison of helicopter-transported and nontransported patients. STUDY OBJECTIVE: To evaluate the effect of helicopter transport of acute myocardial infarction (AMI) patients after initiation of thrombolysis on bleeding complications through hospital discharge. DESIGN: Prospectively identified incidence (cohort) study. SETTING: Air medical service of tertiary-care teaching hospital. TYPES OF PARTICIPANTS: Ninety-five consecutive AMI patients transported within 12 hours of the initiation of thrombolysis with recombinant tissue-type plasminogen activator were compared with 119 nontransported AMI patients treated in a similar manner. RESULTS: The transported and nontransported populations were similar with regard to age, sex, and infarct location. Transport was well tolerated with no episodes of cardiac arrest or cardioversion occurring during transport. Hypotension requiring fluids or increased pressors occurred in 18 patients. Bleeding complications of all types occurred in 43.2% of the transported and 49.6% of the nontransported patients, respectively (relative risk, 0.87; 95% confidence interval, 0.65 to 1.17). CONCLUSION: Helicopter transport of AMI patients after initiation of thrombolysis appears to be safe acutely and without a clinically significant increase in risk of bleeding complications through hospital discharge when accomplished by a highly skilled team. 
Strongyloides stercoralis hyperinfection and central nervous system involvement in a patient with relapsing polychondritis. Infections caused by Strongyloides stercoralis are not uncommon in the United States. Because of the many different manifestations of hyperinfection with this nematode, a high index of suspicion is essential, especially in immunocompromised patients, for whom such infections are frequently fatal. Patients originating from endemic areas and those who have traveled to such areas, even in the distant past, should have the possibility of strongyloidiasis evaluated before initiation of immunosuppressive therapy. Once considered, the diagnosis is not difficult and can be accomplished using readily available techniques and methods. Although thiabendazole has a high incidence of side effects and may not always eradicate infection, it remains the drug of choice for disseminated strongyloidiasis. 
Percutaneous transluminal angioplasty of the subclavian arteries: long-term results in 52 patients. We studied the long-term results of percutaneous transluminal angioplasty of the subclavian artery in treating stenosis (43 patients) or occlusion (nine patients). In all 52 patients, the blood pressure before treatment in the arm on the involved side was at least 30 mm Hg lower than that in the opposite arm. Thirty-nine patients (75%) had symptoms of vertebrobasilar insufficiency (dizziness, blurred vision, ataxia). Angioplasty was successful in 40 (93%) of 43 patients with stenosis and in five (56%) of nine patients with occlusion. In the successfully treated patients, follow-up angiograms showed absence of narrowing greater than 30% stenosis, and the blood pressure in the treated arm equaled that in the opposite arm. The patients were followed up for 6-48 months (mean, 29 months). During this time, the blood pressure in the treated arm remained normal in 41 (91%) of 45 patients. The symptoms of vertebrobasilar insufficiency subsided in 28 (72%) of 39 patients. These results suggest that percutaneous transluminal angioplasty is useful for treating subclavian artery stenosis or occlusion. 
The growth hormone, prolactin and TSH response to TRH and L-dopa in patients with hyperprolactinaemia and a normal-sized sella turcica may denote a pituitary adenoma. Forty-one patients with hyperprolactinaemia and suspected prolactinomas were studied. Growth hormone (GH) and thyrotropin (TSH) secretory patterns after thyrotropin releasing hormone (TRH) were affected in the majority of patients. The disturbances were observed regardless of tumour size as indicated by the radiological sella size. In patients with hyperprolactinaemia and normal-sized sella turcica, an abnormal GH and TSH response to TRH can be helpful in the diagnosis of a microadenoma. The hyperprolactinaemia per se and its effect on dopaminergic hypothalamic neurones may be the cause of the GH and TSH response. By contrast, many patients with macroprolactinomas showed insufficient GH secretory capacity. 
Complications following ventilation of the middle ear using Goode T tubes. This is a 3.5-year retrospective review on the insertion of 210 Goode T tubes into 182 ears of 93 patients. Otorrhea was noted postoperatively in 35.2% of the ears treated, with chronic drainage lasting longer than 4 months developing in more than 7% of the cases. Perforations were found in 34 ears (18.7%) following removal or extrusion of the T tubes; in 13 (7.1%) of these patients, chronic perforations requiring tympanoplasties developed. The literature was screened for additional studies addressing the complications associated with tympanostomy tubes. The documented incidence of perforations between conventional tubes and Goode T tubes was emphasized, and comparisons were made. Our findings indicate that, even with the immediate placement of paper patches following removal of all Goode T tubes, the percentage of tympanic membrane perforations resulting from the use of Goode T tubes is significantly greater than previously reported. 
Gut bacterial translocation via the portal vein: a clinical perspective with major torso trauma. Animal studies implicate gut bacterial translocation via the portal vein as a major factor in the pathogenesis of postinjury multiple organ failure (MOF). We therefore inserted portal vein catheters for sequential blood sampling in the operating room, at 6, 12, 24, and 48 hours, and 5 days postoperatively in 20 injured patients (13 blunt, seven penetrating; mean age, 34 years) requiring emergent laparotomy and who were at known risk for MOF. The mean Revised Trauma Score was 6.4 +/- 0.4, and the Injury Severity Score, 29.3 +/- 2.3. Twelve (60%) patients arrived in shock (SBP less than 90 torr). Eight (2%) of 212 portal blood cultures were positive; seven were presumed contaminants. The only positive systemic culture (total, 212) was a Staphylococcus aureus on day 5 in a patient with a concurrent staphyloccal pneumonia. In the first 48 hours, we could not detect endotoxin in portal or systemic blood. Additionally, simultaneous portal and systemic blood levels of complement fragment C3a, tumor necrosis factor, and interleukin-6 were nearly identical and, specifically, were not different in those patients who developed MOF. In summary, this prospective clinical study has not confirmed portal or systemic bacteremia within the first 5 days postinjury, despite an eventual 30% incidence of MOF. 
Gallbladder function and gastric liquid emptying in achalasia. Because of evidence that the abnormalities in achalasia are not restricted to the distal esophagus, we investigated gallbladder function by cholescintigraphy in the steady state and in response to CCK and the scintigraphic gastric emptying of a liquid caloric meal in 10 individuals with achalasia and 10 normal controls. No abnormalities were found during the filling phase of the gallbladder but seven of the 10 patients showed a 50% reduction in the ejection fraction (39.4% +/- 30.4 vs 80.3 +/- 8.3 of controls, mean +/- SD, P = 0.007) and a slower than normal ejection phase (9.1%/min +/- 6.6 vs 18.1 +/- 4.5, P = 0.02. In eight of the 10 patients, gastric liquid emptying was accelerated with a T1/2 of 41.5 min +/- 15.4 vs 74.7 min +/- 11.5 in the controls (P = 0.007). It is concluded that in some achalasia patients extraesophageal functional abnormalities of the gastrointestinal tract may be found. Whether these findings are promoted by degenerative charges of extraesophageal nerve fibers as well as their clinical significance require further investigations. 
Detection of mediastinitis after heart transplantation by gallium-67 scintigraphy. We report the findings of a patient with post-cardiac transplant mediastinitis detected by 67Ga-citrate imaging. Fever and leukocytosis were the first clinical signs suggesting infection. The usual diagnostic modalities, including CT and ultrasound, failed to identify the site of infection. A 67Ga scan showed intense abnormal uptake behind the sternum. The site of uptake was shown by necropsy to be necrotic tissue involving cardiac sutures, pulmonary arteries, and the aorta due to infection with Haemophilus aphrophilus. 
Gallbladder and pancreatic metastases from bilateral renal carcinoma presenting with hematobilia and anemia. A case of bilateral metachronous renal cell carcinoma with gallbladder and pancreatic metastases, presenting with hematobilia and anemia is presented. The presentation of metastatic renal cell carcinoma with hematobilia and anemia is previously unreported. This case illustrates (1) the occasionally very long interval between metachronous renal carcinoma; (2) this tumor's propensity to unusual metastases and unpredictable presentation; and (3) the significant palliation which may be achieved by appropriate surgical resection of these metastases. 
Uveal melanoma: development of metastases after helium ion irradiation. Forty-two (16%) of 261 patients with ocular melanoma who were treated with helium ions between January 1978 and November 1986 have developed metastatic disease. The time between start of helium ion treatment and recognition of metastatic disease ranged from 3 to 67 months (median, 27 months). The mean pretreatment tumor height in the patients with metastases was 7.7 mm. All 42 patients who developed metastatic disease have died. The median survival after diagnosis of metastatic disease was 5 months; the longest survival was 49 months. The most common site of metastasis was the liver (n = 34). Four (10%) of the 42 patients with metastases also had local recurrence of the tumor. Multivariate analysis identified three variables that predicted independently the development of metastases and lack of survival. These variables are anterior location of tumor (P = .027), tumor height greater than 5 mm (P = .02), and tumor diameter greater than 10 mm (P = .0075). 
Abnormal coronary vasoconstriction as a predictor of restenosis after successful coronary angioplasty in patients with unstable angina pectoris. BACKGROUND. High rates of restenosis after coronary angioplasty have been reported in patients with vasospastic angina. This study was designed to determine whether the occurrence of abnormal coronary vasoconstriction, detected by means of hyperventilation testing before angioplasty, influences the risk of restenosis after successful dilation. METHODS. Hyperventilation testing was performed 0 to 4 days before coronary angioplasty in 106 consecutive patients with unstable angina and single-vessel coronary artery disease. Abnormal coronary vasoconstriction was considered present if hyperventilation-induced myocardial ischemia occurred during the recovery phase of the test. All patients had follow-up angiography 8 to 12 months after angioplasty. RESULTS. Abnormal coronary vasoconstriction was observed in 48 patients (group 1), whereas 58 patients (group 2) had either a negative response throughout the test or a positive response only during the overbreathing phase of the hyperventilation test. Angioplasty was successful in 40 patients in group 1 and 51 in group 2. Restenosis was documented in 29 patients (73 percent) in group 1 and 13 (25 percent) in group 2 (relative risk of restenosis, 2.84; 95 percent confidence interval, 1.69 to 4.28; P less than 0.001). In a multivariate analysis, the following three characteristics were independently related to the risk of restenosis (in descending order of importance): ST-segment elevation during spontaneous ischemic attacks (P less than 0.001), hyperventilation-induced abnormal coronary vasoconstriction (P less than 0.001), and the presence of a lesion more than 10 mm long in the left anterior descending coronary artery (P less than 0.05). CONCLUSIONS. In patients with unstable angina and single-vessel coronary artery disease who have been selected for coronary angioplasty, the presence of hyperventilation-induced abnormal coronary vasoconstriction identifies a subgroup at high risk for restenosis. 
Somatosensory evoked potentials in intracranial hypertension: analysis of the effects of hypoxia. The loss of somatosensory evoked potentials (SSEP's) was investigated in a feline model of intracranial hypertension. Threshold values of cerebral perfusion pressure (CPP) and cerebral blood flow (CBF) required for maintenance of SSEP's are defined using a mathematical model. The model describes loss of amplitude of SSEP's using the form of a dose-response curve. Amplitude of the SSEP's declined to 50% of control values at a CBF of 15 ml/100 gm/min and a CPP of 20 mm Hg in the normoxic animal; in the presence of mild hypoxia (8 to 9 kPa), a significant increase in these values to 18 ml/100 gm/min and 32 mm Hg, respectively, occurred. No reliable changes in latency or central conduction time were demonstrated. It is concluded that given adequate oxygenation, evoked electrical activity is lost at too low a level of CPP for this parameter to be useful in clinical monitoring. However, even mild hypoxia, when combined with intracranial hypertension, produces a major risk to neuronal integrity. 
Intermediate-term effectiveness of balloon valvuloplasty for congenital aortic stenosis. A prospective follow-up study. BACKGROUND. Percutaneous balloon valvuloplasty has proven to be acutely effective in the treatment of congenital valvar aortic stenosis; however, the intermediate- and long-term effectiveness of the procedure remain to be documented. METHODS AND RESULTS. To assess the intermediate-term effectiveness of balloon valvuloplasty, repeat catheterization was performed in 27 of 30 children 1.7 +/- 0.1 years after balloon valvuloplasty for congenital aortic stenosis (AS). In 33 children the peak AS gradient was reduced acutely by 55% from 77 +/- 4 to 35 +/- 3 mm Hg (p less than 0.001), and left ventricular systolic pressure was reduced from 176 +/- 4 to 138 +/- 4 mm Hg (p less than 0.001). Despite a technically adequate valvuloplasty procedure, three patients had inadequate relief of obstruction and required complex surgical intervention. Twenty-seven of the 30 patients available for late reevaluation (90%) enrolled in the follow-up study. The peak AS gradient remained significantly reduced compared with that present before valvuloplasty (29 +/- 3 versus 77 +/- 4 mm Hg, p less than 0.001). Furthermore, there was no difference in peak AS gradient at follow-up compared with that immediately after valvuloplasty. The greatest increase in gradient at reevaluation was 14 mm Hg. Twenty of 27 patients (74%) had no change in the degree of aortic insufficiency at follow-up compared with that present before valvuloplasty. At follow-up, 16 patients had no aortic insufficiency at all, and only two had moderate-to-severe (3-4+) insufficiency. Femoral artery injury was documented in four patients, three of whom were under 12 months of age at valvuloplasty. CONCLUSIONS. Balloon aortic valvuloplasty provides safe and effective intermediate-term gradient relief without early restenosis in children and adolescents with congenital AS. 
A pilot study of fluticasone propionate in untreated coeliac disease. Although gluten withdrawal is likely to remain the mainstay of treatment for adult coeliac disease, many patients find the diet inconvenient and unpalatable and compliance among asymptomatic patients is often poor. Oral corticosteroids have been used for patients who seem to be resistant to gluten withdrawal but preparations with low systemic bioavailability might be preferable. We have given a new glucocorticoid (fluticasone propionate) to 12 adults with untreated coeliac disease for six weeks while they were on a normal diet. One patient defaulted and one suffered a relapse in a pre-existing neoplasm. Excluding these, there was an improvement of symptoms, a mean weight gain of 2 kg, and a rise in albumin of 5.4 g/l. There was a significant improvement in the lactulose/mannitol excretion ratio (p less than 0.05) and in all histological variables examined in paired biopsy specimens (surface and crypt intraepithelial lymphocyte/enterocyte and goblet cell/enterocyte ratios and enterocyte height, p less than 0.01 or better). In six paired specimens sucrase and alkaline phosphatase activity increased in all (p less than 0.05) and lactase in five of six. No appreciable side effects were observed, but two patients had suppressed cortisol values and synacthen responses at six weeks. A further three, with normal pretrial results, had a blunted tetracosactrin response at six weeks. Fluticasone propionate seems worthy of further assessment in the treatment of coeliac disease as an adjunct to gluten withdrawal. 
Fetal cardiovascular morphology of truncus arteriosus with or without truncal valve insufficiency in the rat. BACKGROUND. Recent advances in fetal echocardiography have necessitated further study on fetal in situ cardiovascular morphology of truncus arteriosus and the effects of truncal valve insufficiency. METHODS AND RESULTS. We studied 55 fetal rats with truncus arteriosus among 300 fetuses from 40 virgin females treated with 200 mg fertilysin on the 10th day of pregnancy. After rapid whole-body freezing on the 21st day, the fetuses were studied by means of serial cross-sectional photographs of the frozen thorax. Thirty-five fetuses with a normal heart treated with fertilysin served as controls. Truncus arteriosus was characterized by a large ventricular septal defect, a solitary artery (truncus arteriosus) overriding the ventricular septum, the right and left pulmonary arteries originating from the truncus arteriosus with or without a common trunk (main pulmonary artery), and absent ductus arteriosus. Fetuses with truncal valve insufficiency had thick truncal valves, a large truncus arteriosus, and large ventricles. The subgroup of 12 fetuses with a large truncus (truncal diameter greater than 160% of the ascending aorta diameter in the controls) showed significantly greater values for right ventricular volume (200% of control) and mass (120% of control), left ventricular volume (170% of control) and mass (110% of control), right (120% of control) and left (110% of control) atrial volume, and pericardial fluid (140% of control) than the controls. These changes were less prominent and ventricular volumes were not increased in the remaining subgroup with a truncal diameter of 160% or less of aorta diameter in the controls. CONCLUSIONS. In fetal truncus arteriosus, truncal valve insufficiency was associated with increased ventricular volume load and incomplete cardiac compensation in rats. 
Maffucci's syndrome associated with intracranial enchondroma and aneurysm: case report. Maffucci's syndrome is a rare, congenital mesodermal dysplasia combined with dyschondroplasia and hemangiomatosis. Enchondromatous involvement of the skull bones is rare in this syndrome. A rare case of Maffucci's syndrome associated with enchondroma at the skull base, left internal carotid artery aneurysm, and goiter is reported. Two other previously reported cases of Maffucci's syndrome with associated aneurysms and the present case suggest that Maffucci's syndrome may be associated with aneurysm. 
Myotonia and neuromuscular transmission in the mouse. The role of neuromuscular transmission and acetylcholine receptors in the phenotypic expression of hereditary myotonia was reinvestigated in two mutants of the mouse, ADR (adr/adr) and MTO (adrmto/adrmto). Three neuromuscular blockers, curare, flaxedil, and alpha-bungarotoxin, did not prevent mechanical myotonia of EDL and soleus muscles from the two mutants. Furthermore, electrical myotonia was demonstrated in isolated ADR muscle fibers devoid of nerve endings. We conclude that neither release nor reception of acetylcholine are important for the mechanism of myotonia in mouse mutants. The previously described suppression of myotonic aftercontractions by high concentrations of curare (Muscle & Nerve 1987;10:293-298) could not be reproduced; rather, a prolongation of aftercontractions was found. The other drugs had no significant effect on myotonic aftercontractions. Because neuromuscular transmission is not involved in human myotonias, this result supports the use of myotonic mice as a model, at least for recessive generalized myotonia (Becker). 
Accuracy of computer-interpreted electrocardiography in selecting patients for thrombolytic therapy. MITI Project Investigators. A prehospital computer-interpreted electrocardiogram (ECG) was obtained in 1,189 patients with chest pain of suspected cardiac origin during an ongoing trial of prehospital thrombolytic therapy in acute myocardial infarction. Electrocardiograms were performed by paramedics 1.5 +/- 1.2 h after the onset of symptoms. Of 391 patients with evidence of acute myocardial infarction, 202 (52%) were identified as having ST segment elevation (acute injury) by the computer-interpreted ECG compared with 259 (66%) by an electrocardiographer (p less than 0.001). Of 798 patients with chest pain but no infarction, 785 (98%) were appropriately excluded by computer compared with 757 (95%) by an electrocardiographer (p less than 0.001). The positive predictive value of the computer- and physician-interpreted ECG was, respectively, 94% and 86% and the negative predictive value was 81% and 85%. Prehospital screening of possible candidates for thrombolytic therapy with the aid of a computerized ECG is feasible, highly specific and with further enhancement can speed the care of all patients with acute myocardial infarction. 
In vivo measurements of the fraction of dose of bleomycin labeled with cobalt 57 delivered to human tumors. Concentrations of bleomycin labeled with cobalt 57 (Co-bleo) over time were measured in vivo in 17 patients with 32 sites of lymphoma and 18 patients with lung tumors after administration of the same dose of bleomycin. There were marked variations in individual tumor drug concentrations even among tumors with the same histologic type, indicating that the tumor concentration of this drug in individuals cannot be predicted from the administered dose. Also, tumor concentration could not be predicted from the area under the concentration over time curve (AUC) of Co-bleo in the blood; there was no correlation (r = 0.53) between the AUC and the concentration in the tumor at any point in time between 30 minutes and 8 hours after injection. There was no significant difference in the percent of the injected dose per milliliter (%ID/ml) which was delivered to the tumor when low and high amounts of bleomycin were administered to the same patient. Also, a good correlation (r = 0.88) between the %ID/ml over time was found when injection of low and high doses of bleomycin were compared. The results indicate that using quantitative single photon emission computed tomography (SPECT) and a labeled tracer dose it is possible to predict what fraction of the dose of a chemotherapeutic drug will concentrate in an individual patient's tumor in vivo. They also show that, for bleomycin, escalation of dose will result in a proportional increase of tumor concentration. This increase depends on individual properties of tumors which can be measured quantitatively in vivo by SPECT and are expressed as percent of %ID/ml of tumor tissue. 
Miosis and internal ophthalmoplegia as a manifestation of partial seizures. We present a patient whose only physical manifestation of a partial sensory seizure was bilateral pupillary constriction and internal ophthalmoplegia. The onset and offset of each attack corresponded distinctly with an electroencephalographic discharge of the left temporo-occipital region. We propose involvement of a cortical pupillary constrictive center in the temporal-occipital area. 
Non-Menkes-type copper deficiency with regression, lactic acidosis, and granulocytopenia. A 2-year-old girl with granulocytopenia developed fever followed by truncal ataxia and progressive neurologic regression. CT demonstrated symmetric low-density areas in the cerebral white matter. Sural nerve biopsy revealed axonal degeneration. Blood lactate levels were high, and serum levels of copper and ceruloplasmin and urinary excretion of copper were low. Cultured skin fibroblasts showed normal copper uptake. Treatment with oral copper administration normalized serum copper and ceruloplasmin levels, blood lactate levels, and granulocyte count. However, copper levels in the CSF were still low, and the patient showed no clinical improvement. We speculated that copper transport across the intestinal wall and across the blood-brain barrier was impaired. 
Risk factors for candidemia in patients with acute lymphocytic leukemia. Between 1983 and 1987 the overall incidence of candidemia at the Institut Gustave Roussy, a tertiary care referral hospital for patients with cancer, increased from 0.1% (7 of 6,801) to 0.32% (24 of 7,515) (P = .009). Because acute lymphocytic leukemia (ALL) was the most common underlying disease in patients with candidemia, risk factors for candidemia were analyzed in this subset of patients. A case-control study comparing the eight ALL patients who had candidemia with 18 ALL control patients revealed that previous bacteremia, prolonged neutropenia, prolonged fever, prolonged administration of antimicrobial agents, treatment with multiple antimicrobial agents, and a relatively high concentration of Candida organisms in stool were significant risk factors for candidemia. In a logistic regression analysis, however, only receipt of vancomycin and/or imipenem was identified as an independent risk factor for candidemia. Further analysis showed that administration of vancomycin promoted proliferation of Candida organisms in the gastrointestinal tract and that this proliferation was associated with an increased risk of candidemia. 
The effects of alcohol on the female brain: a neuropathological study. This quantitative neuropathological study compared the brains of seventeen alcoholic females with twenty non-alcoholic female controls. There was a significant (P less than 0.001) increase in the pericerebral space value (control 9.5; alcoholic 16.3) indicating shrinkage of the brain. Cerebral grey and white matter volumes were determined morphometrically. There was a significant decrease in the cerebral white matter volume (P less than .02) in the alcoholics. The cerebral grey matter volume was unchanged. These changes parallel those described previously in male alcoholics. Further studies will be necessary to establish the relative severity of the brain damage in males and females. 
Perirenal lipoma versus renal cell carcinoma. Pure renal and perirenal lipomas are rare. They arise from renal cortex, capsule, or perirenal tissue, and may be difficult to distinguish from renal adenocarcinomas. We report on a patient who presented with a renal mass that had the radiologic findings suggestive of a renal cell carcinoma, but proved to be a simple lipoma. 
Natural history of recurrent urinary tract infections in women. To evaluate the natural history of uncomplicated urinary tract infections in women, we observed 51 infection-prone women in a standardized fashion for a median of 9 years. During intervals when patients were not receiving antimicrobial prophylaxis, infections occurred at an average rate of 2.6 per patient-year, but the rate varied widely from patient to patient (range 0.3-7.6 episodes per year). Seventy-three percent of the observed episodes were symptomatic, with an 18:1 ratio of cystitis to pyelonephritis episodes. Infectious episodes were strikingly clustered, and rates of infection decreased in the winter months. Antimicrobial prophylaxis was highly effective in preventing acute cystitis, asymptomatic bacteriuria, and acute pyelonephritis, even when used for as long as 5 years. The proportions of infecting strains resistant in vitro to ampicillin (19%-32%) and nitrofurantoin (5%-18%) were unchanged over the 15-year observation period, while resistance to trimethoprim-sulfamethoxazole increased in the last 5 years of the study. 
Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. The SOLVD Investigators BACKGROUND. Patients with congestive heart failure have a high mortality rate and are also hospitalized frequently. We studied the effect of an angiotensin-converting-enzyme inhibitor, enalapril, on mortality and hospitalization in patients with chronic heart failure and ejection fractions less than or equal to 0.35. METHODS. Patients receiving conventional treatment for heart failure were randomly assigned to receive either placebo (n = 1284) or enalapril (n = 1285) at doses of 2.5 to 20 mg per day in a double-bind trial. Approximately 90 percent of the patients were in New York Heart Association functional classes II and III. The follow-up averaged 41.4 months. RESULTS. There were 510 deaths in the placebo group (39.7 percent), as compared with 452 in the enalapril group (35.2 percent) (reduction in risk, 16 percent; 95 percent confidence interval, 5 to 26 percent; P = 0.0036). Although reductions in mortality were observed in several categories of cardiac deaths, the largest reduction occurred among the deaths attributed to progressive heart failure (251 in the placebo group vs. 209 in the enalapril group; reduction in risk, 22 percent; 95 percent confidence interval, 6 to 35 percent). There was little apparent effect of treatment on deaths classified as due to arrhythmia without pump failure. Fewer patients died or were hospitalized for worsening heart failure (736 in the placebo group and 613 in the enalapril group; risk reduction, 26 percent; 95 percent confidence interval, 18 to 34 percent; P less than 0.0001). CONCLUSIONS. The addition of enalapril to conventional therapy significantly reduced mortality and hospitalizations for heart failure in patients with chronic congestive heart failure and reduced ejection fractions. 
Percutaneous transluminal coronary angioplasty in the elderly: early and long-term results. The immediate and long-term efficacy of coronary angioplasty in the elderly was determined by studying 752 patients greater than or equal to 65 years old and comparing patients greater than or equal to 75 years old with those 65 to 74 years old. The oldest patients were more highly symptomatic, were more likely to be in heart failure, had more multivessel disease and were more likely to undergo multivessel dilation. The immediate success rate of angioplasty was higher in the oldest patients (92.8% versus 82%) (p = 0.0003). The hospital mortality rate was also higher (6.2% versus 1.6%) (p less than 0.001). Long-term overall survival was high. However, long-term event-free survival was lowest in the oldest patients, and recurrent severe angina was particularly common. Thus, in very elderly patients, coronary angioplasty is usually successful, but extra caution is warranted; also, long-term relief from angina is less common than in younger patients. 
Patients with a high defibrillation threshold: clinical characteristics, management, and outcome. Of 125 patients prepared to receive implantable cardioverter-defibrillators (ICDs) with the patch-patch configuration of the difibrillating electrodes, 23 (18%) had high (greater than or equal to 25 joules) defibrillation thresholds (DFTs). These patients had lower left ventricular ejection fractions (27 +/- 12 vs 34 +/- 13; p less than 0.03) and a higher incidence of previous heart surgery (47% vs 19%; p less than 0.01) than patients with normal DFTs but did not differ in age, type of heart disease, incidence of concomitant heart surgery, or use of antiarrhythmic medication. Defibrillators were implanted in 18 of these 23 patients, 12 during the initial surgery and six after repeat DFT testing 2 weeks later. After 22 +/- 11 months of follow-up, four patients with ICDs died (two suddenly, and two of nonsudden cardiac causes). Two patients without ICDs died of nonsudden cardiac causes. Appropriate shocks were received by five patients (29%) including both who died suddenly later. A high DFT may be more common than previously stated. It is associated with poor ventricular function and previous heart surgery. Repeated DFT testing may be useful in some patients. A high DFT does not preclude successful ICD shocks, but other therapies may provide better results. 
Calcium oxalate microcalcifications in the breast. Calcium oxalate calcifications can be difficult to detect with routine histologic procedures. In the reported case, microcalcifications that were evident with radiography of the specimen and of the paraffin blocks could not be detected with light microscopy. Polarized light microscopy, however, revealed the calcifications to be calcium oxalate crystals. Use of polarized light microscopy may resolve radiologic-pathologic discrepancies in such cases. 
Effect of a new monoclonal antibody, TA-2, that inhibits lymphocyte adherence to cytokine stimulated endothelium in the rat. An important event in the migration of lymphocytes out of the blood is their adherence to endothelial cells (EC). In inflammatory sites cytokines activate EC and promote lymphocyte EC adherence and migration. Small peritoneal exudate lymphocytes (sPEL) preferentially migrate from the blood to cutaneous delayed-type hypersensitivity reactions and to sites injected with IFN-gamma, IFN-alpha/beta, and TNF-alpha, rather than to peripheral lymph nodes. The basis of this migration is sPEL adherence to cytokine-activated EC. To study this adhesion mAb to rat sPEL were screened for inhibition of sPEL adherence to IFN-gamma-stimulated EC. One mAb, TA-2, inhibited IFN-gamma-stimulated adherence to EC by 60%. This antibody had no effect on the baseline adherence of sPEL to unstimulated EC. Treatment of sPEL, but not EC, with TA-2-inhibited adhesion. TA-2 also inhibited adhesion to EC activated with mIL-1 alpha, TNF-alpha, and LPS, and the adhesion of spleen T cells to activated EC. The TA-2 Ag was expressed on virtually all lymph node, spleen, and sPEL lymphocytes but sPEL expressed two to three times higher levels than lymph node lymphocytes, and the highest levels were found on CD4+ and CD45R- memory T cells. TA-2 immunoprecipitated a group of four polypeptides with molecular mass of 150, 130, 83, and 66 kDa. Finally, TA-2 inhibited sPEL adhesion to TNF-alpha and IL-1 stimulated human umbilical vein EC to the same extent as an anti-human VCAM-1 mAb, and combinations of TA-2 and anti-VCAM-1 were not different from treatment with either antibody alone. Thus, TA-2 appears to recognize rat VLA-4 based on immunoprecipitation, immunofluorescence, and lymphocyte EC studies. VLA-4 mediates the adhesion of rat lymphocytes to rat microvascular EC stimulated with IFN-gamma, mIL-1 alpha, TNF-alpha, and LPS. VLA-4 is important in the increased adhesion of sPEL to EC and the enhanced sPEL migration to inflammation may in part be explained by increased expression of VLA-4 on these cells. 
The significance of circulating cells carrying t(14;18) in long remission from follicular lymphoma Peripheral blood mononuclear cell fractions from 15 patients in continuous clinical remission from follicular lymphoma for longer than 10 years were examined for cells carrying the t(14;18) translocation using the polymerase chain reaction (PCR). The assay used was able to detect one positive cell in approximately 5 x 10(5) cells (a single 14q+ molecule in 2.5 micrograms DNA). Cells positive for t(14;18) were found in six of eight patients initially presenting with stage III or IV disease, compared with zero of seven of those with stage I or II disease (P less than .05). In two cases 14q+ junction regions were also successfully amplified from formalin-fixed biopsy material obtained at presentation 12 and 17 years previously. In both, sequence analysis demonstrated that the cells circulating in remission belonged to the original clone. These results indicate that cells bearing t(14;18) frequently persist in the peripheral blood in long remission of advanced follicular lymphoma and question the value of their presence as a predictor of relapse. 
Prevention of adult heart disease beginning in childhood: intervention programs. Multiple strategies are available to affect children's cardiovascular health. From clinic-based high-risk counseling to broad-based school or community programs, intervention strategies are being developed and tested to find the most effective means of changing the risk factors of youth to assure a healthier future for our children. Since adoption of new behaviors is improved by consistent messages from multiple sources, a concerted effort is needed. The involvement of health professionals, educators, community organizations, industry, and government together will be important to support the adoption of healthy lifestyles for succeeding generations. Intervention through cardiovascular health promotion for school children may well be the future direction for preventive cardiology. 
A new surgical classification system for shoulder-girdle resections. Analysis of 38 patients. A new, six-stage surgical classification system is described for shoulder-girdle resections for patients being treated by limb-sparing procedures for bone and soft-tissue tumors. The classification is based upon current concepts of oncological surgery, the structures removed, the type of resection performed, and the relationship of the resection to the glenohumeral joint, and it indicates the increasing surgical magnitude of the procedure. Data from 38 patients with an average follow-up period of 4.6 years (range, two to 8.4 years) were analyzed. Thirty-two tumors were in bone and six in soft tissue. Eighty-seven percent (33 of the 38 tumors) were malignant. Twenty-four lesions were located in the proximal humerus and 14 in the scapula. The system permitted classification of all shoulder girdle resections done in this study's institutions. The classification is proposed as a means of establishing a uniform terminology in the comparison of such data. 
Antibiotic prophylaxis of wound infections in skin surgery A controlled prospective study of 2165 outpatients undergoing skin surgery was performed to evaluate the utility and the effects of several antibiotic schedules for prophylaxis of wound infections. The patients were divided into four groups. Twenty-three of the 541 group A patients, given no antibiotics, had wound infections. Eight of the 542 group B patients, given systemic antibiotics from immediately after surgery until the third day, had wound infections. Four of the 540 group C patients, treated only with local sterile antibiotic powder sprinkled into the wound during surgery, had wound infections develop, and only one infection occurred in the 542 group D patients given systemic antibiotics from 2 days before surgery until the second day after surgery. This last schedule was the best for prophylaxis of wound infections in contamination-prone regions. Local antibiotic administration is a simple method for prevention of infections in routine skin surgery. 
Coexistent hemangioblastoma and arteriovenous malformation of the cerebellum. Case report. A case of cerebellar hemangioblastoma and coexistent arteriovenous malformation (AVM) is presented. Angiography displayed the AVM, but histological examination revealed a coexisting hemangioblastoma. Various theories concerning the etiology of this condition are discussed. 
PET study of carbon-11-PK 11195 binding to peripheral type benzodiazepine sites in glioblastoma: a case report. The utility of the peripheral type benzodiazepine site ligand 11C-PK 11195, for imaging human glioma in conjunction with Positron Emission Tomography, relies on a high specific binding of the tracer to tumoral peripheral type benzodiazepines sites. In a patient with glioblastoma, we found that 11C-PK 11195 binding was two-fold higher in the tumor than in normal gray matter and that 30% of tumoral binding could be displaced by a large excess of unlabeled drug. These findings suggest that tumoral retention of the ligand is due, in part, to specific binding. 
Myocardial lactate dehydrogenase and its isoenzyme activities in transplanted human hearts. Lactate dehydrogenase and its heart (H) and muscle (M) subunit activities were studied in right ventricular endomyocardial biopsies from eight transplanted human hearts and compared with five chronically failing hearts and six normal human hearts from brain-dead liver/kidney donors. Of the 17 transplant biopsies (taken 5-95 weeks postoperatively), only two showed histologic signs of chronic rejection: They were excluded from the group analysis. A higher proportion of the M subunit of lactate dehydrogenase (M%) was found in the transplanted and the chronically failing hearts than in the normal hearts, presumably reflecting increased myocardial anaerobic glycolytic stress. In the early post-transplantation period, M% was higher in the transplanted than in the chronically failing hearts. Thereafter M% gradually fell, but had not reached normal levels 1-2 years after transplantation. During that time it was similar to the values in the chronic-failure hearts. In the two biopsies with chronic rejection, M% was nearly twice as high as in contemporaneous biopsies showing mild or no rejection. Monitoring of enzymatic adaptation from endomyocardial biopsies may be of clinical interest. 
Transcutaneous electrical nerve stimulation decreases lower esophageal sphincter pressure in patients with achalasia. Vasoactive intestinal peptide (VIP) is believed to be an inhibitory neurotransmitter responsible for lower esophageal sphincter (LES) relaxation. In patients with achalasia the concentration of VIP and the number of VIP-containing nerve fibers are reduced or absent. It has been suggested that the response to low-frequency transcutaneous electrical nerve stimulation (TENS) may be mediated by a nonadrenergic noncholinergic pathway in which the release of VIP is responsible for the smooth muscle relaxation. The present study was designed to evaluate the effect of TENS on LES pressure and on VIP plasma concentrations in six patients with achalasia (five female, one male). TENS was performed daily during one week for 45-min sessions with a pocket stimulator that delivered low-frequency pulses (6.5 Hz), at 10 pulses/sec of 0.1-msec duration at intensities of 10-20 mA until rhythmic flexion of the fingers was obtained without producing pain. LES pressure and VIP levels were obtained before TENS, after the first 45-min session, and after a week of daily stimulation. After 45-min, TENS produced a significant reduction (P less than 0.01) in LES resting pressure from the mean value 56 +/- 6.4 mm Hg to 42.3 +/- 6.4 mm Hg; with LES relaxation improvement from 50.6 +/- 3% to 63.1 +/- 3.2% (P less than 0.01). After one week of daily TENS, an additional reduction in LES resting pressure (40.3 +/- 4 mm Hg) was observed (P less than 0.01). 
Epibulbar choristoma and microphthalmia: a report of two cases. The simultaneous ipsilateral presence of an epibulbar choristoma and microphthalmia has rarely been reported. We present two such cases, one of which is associated with bone formation, and we consider a possible pathogenetic mechanism. 
Inflammatory pseudotumor of the choroid plexus in Sjogren's disease. We report an unusual case of inflammatory pseudotumor of the choroid plexus of the right lateral ventricle, manifesting as an intraventricular mass and causing unilateral hydrocephalus in a 48-year-old man who suffered from Sjogren's disease and subacute cutaneous lupus erythematosus. The lesion obliterated the normal choroidal architecture by a mixed chronic inflammatory process that was associated with reactive connective tissue changes. Immunohistochemical studies showed no light-chain restriction in the cells, and residual islands of transthyretin-positive epithelial cells were identified, implicating the choroid plexus origin of the mass. 
An economic evaluation of lovastatin for cholesterol lowering and coronary artery disease reduction. The costs and benefits of cholesterol lowering in the primary prevention of coronary artery disease (CAD) were considered using lifetime lovastatin therapy as the intervention model for adults between 35 and 55 years of age. The analysis projected the benefits of CAD risk reduction using estimates from the Framingham Heart Study. The chosen analytic perspective was that of the patient. For average-risk men with total serum cholesterol levels between 5.69 and 9.83 mmol/liter (220 and 380 mg/dl), the cost per life-year saved ranged from $9,000 to $106,000, whereas for average-risk women, the cost ranged from $35,000 to $297,000 (1989 U.S. dollars). In high-risk men (with smoking habit and hypertension), the cost per life-year saved values ranged from 6,000 to $53,000, whereas in high-risk women the cost per life-year saved values ranged from $19,000 to $160,000. The results were more favorable than those found in previous studies of alternate medication therapies for hypercholesterolemia. Even using conservative parameter assumptions, at least 800,000 Americans aged 35 to 55 years are at sufficiently high risk for CAD, so that the net cost of lovastatin therapy can be favorably compared with other widely used medical interventions. 
Effect of age on use of thrombolytic therapy and mortality in acute myocardial infarction. The MITI Project Group. The findings in 3,256 consecutive patients hospitalized for acute myocardial infarction were tabulated to assess the history, treatments and outcome in the elderly; 1,848 patients (56%) were greater than 65 years of age, including 28% who were aged greater than or equal to 75 years. The incidence of prior angina, hypertension and heart failure (only 3% of patients less than 55 years of age had a history of heart failure compared with 24% greater than or equal to 75 years old) was found to increase with age. Twenty-nine percent of patients less than 75 years of age were treated with a systemic thrombolytic drug compared with only 5% of patients older than 75 years. Mortality rates increased strikingly with advanced age (less than 2% in patients less than or equal to 55, 4.6% in those 55 to 64, 12.3% in those 65 to 74 and 17.8% in those greater than or equal to 75 years). Both the incidence of complicating illness and a nondiagnostic electrocardiogram (ECG) increased with age. In a multivariate analysis of outcome in older patients (greater than or equal to 65 years), adverse events were related to both prior history of heart failure (odds ratio 3.9) and increasing age (odds ratio 1.4 per each decade of age). Outcome was not improved by treatment with thrombolytic drugs, but these agents were prescribed to only 12% of patients greater than 65 years of age, thereby reducing the power for detecting such an effect. 
Resection of intrinsic tumors from nondominant face motor cortex using stimulation mapping: report of two cases. We report two right-handed patients who underwent resection of intrinsic glial tumors from the nondominant hemisphere, face motor cortex. Both patients underwent preoperative assessment with computed tomography and magnetic resonance imaging localizing the tumor in the inferior region of the Rolandic cortex. With the patients under general anesthesia and without muscular paralysis, the tumor volume was determined by intraoperative ultrasound and resective surgery accomplished with the aid of cortical and subcortical stimulation mapping techniques. Radical resection of the tumor from the face motor cortex was achieved in both patients. A transient contralateral facial weakness and apraxia were noted in each patient, and this resolved within 6 to 8 weeks following surgery. Removal of intrinsic tumors involving the nondominant face motor cortex may be safely achieved using brain mapping techniques to localize inferior Rolandic cortex and avoid resection of the hand motor cortex and descending subcortical motor pathways. Permanent disability will be prevented due to the bilateral representation of face motor function at the neocortical level. However, due to language localization in cortical zones contiguous with the dominant hemisphere, face motor cortex, we do not recommend resection of this region. 
Transfusion-related chronic liver disease in sickle cell anemia. The medical records and liver biopsies of nine sickle cell patients with chronically elevated liver function tests were retrospectively reviewed to determine the etiology of chronic liver disease. There were eight women and one man with a mean age of 30 yr. All patients had hemoglobin SS. Eight patients were referred for elevated aminotransferases and one for an elevated alkaline phosphatase. Hemosiderosis was present in all of the biopsies. Two patients had cirrhosis. Chronic hepatitis was noted in two patients, and five patients had cholestasis. Two patients had serologic markers demonstrating HBV exposure but no patients were HBsAg positive. Erythrophagocytosis, sinusoidal dilatation, and Kupffer cell hyperplasia were present in all of the liver biopsies. Transfusion-related causes were the most common significant pathologic findings in our patients, and appeared to be the etiologies of chronic liver disease in sickle cell patients. 
Sinus bradycardia related to temporomandibular joint surgery. The carotid artery lies in close relationship to the temporomandibular joint (TMJ). Manipulation of the mandible during TMJ surgery has been observed in several cases to be directly associated with the development of sinus bradycardia as the joint is distracted during arthrotomy and arthroplasty procedures. We report several cases and discuss differential diagnosis of sinus bradycardia associated with positional changes of the TMJ. This report emphasizes the importance to the surgeon and to the anesthesiologist of recognition of this cardiac phenomenon, mediated through the trigeminovagal reflex, to appropriately manage the patients during TMJ surgery. 
Resection of the inferior vena cava or intraluminal vena caval tumor thrombectomy during retroperitoneal lymph node dissection for metastatic germ cell cancer: indications and results. A total of 42 patients underwent inferior vena caval resection (40) or intraluminal tumor thrombectomy (2) during retroperitoneal lymph node dissection for bulky abdominal metastatic nonseminomatous germ cell cancer (7% of all post-chemotherapy retroperitoneal lymph node dissection cases). The 3 indications for vena caval resection included tumor clearance (38%), vena caval scar occlusion (14%) and vena caval tumor thrombus (48%). En bloc vena caval resection to achieve tumor clearance was justified by subsequent nodal pathology (cancer in 63% of the specimens and teratoma in 31%). Vena caval resection in the presence of scar occlusion was de facto required by virtue of its incorporation in the specimen. Vena caval resection or thrombectomy is indicated for intraluminal tumor thrombus because thrombus pathology (cancer 35%, teratoma 45% and fibrosis 20%) reflected nodal pathology in 71% of the patients with cancer, 78% with teratoma and 100% with fibrosis. The complications of vena caval resection were generally transitory. The 71% survival rate justifies this intensive surgical approach because these patients had exhausted all chemotherapy options. 
Effects of embolus size on hemodynamics and gas exchange in canine embolic pulmonary hypertension. We examined the effects of different-sized glass-bead embolization on pulmonary hemodynamics and gas exchange in 12 intact anesthetized dogs. Pulmonary hemodynamics were evaluated by multipoint pulmonary arterial pressure (Ppa)/cardiac output (Q) plots before and 60 min after sufficient amounts of 100-microns (n = 6 dogs) or 1,000-microns (n = 6 dogs) glass beads to triple baseline Ppa were given and again 20 min after 5 mg/kg hydralazine in all the animals. Gas exchange was assessed using the multiple inert gas elimination technique in each of these experimental conditions. Embolization increased both the extrapolated pressure intercepts (by 6 mmHg) and the slopes (by 5 mmHg.l-1.min.m2) of the linear Ppa/Q plots, together with an 80% angiographic pulmonary vascular obstruction. These changes were not significantly different in the two subgroups of dogs. However, arterial PO2 was most decreased after the 100-microns beads, and arterial PCO2 was most increased after the 1,000-microns beads. Both bead sizes deteriorated the distribution of ventilation (VA)/perfusion (Q) ratios, with development of lung units with higher as well as with lower than normal VA/Q. Only 100-microns beads generated a shunt. Only 1,000-microns beads generated a high VA/Q mode and increased inert gas dead space. Hydralazine increased the shunt and decreased the slope of the Ppa/Q plots after 100-microns beads and had no effect after 1,000-microns beads. We conclude that in embolic pulmonary hypertension, Ppa/Q characteristics are unaffected by embolus size up to 1,000 microns. 
Anterograde amnesia with fornix damage following removal of IIIrd ventricle colloid cyst. Two patients developed anterograde amnesia following the apparently uncomplicated transcallosal-transventricular removal of a colloid cyst. Damage to the fornical columns was demonstrated on CT and MRI scans, whilst other memory related structures were entirely normal. Longitudinal neuropsychological evaluation, over 12-24 months, has revealed a very similar pattern of deficit in the two cases: verbal memory has remained persistently impaired whilst nonverbal anterograde memory has improved to some degree. Formal tests of remote public (famous faces and events) and personal autobiographical memory have supported the clinical impression that neither patient has a temporally extensive retrograde amnesia. These findings address the role of the fornix, and the dissociation of memory processes in humans. 
Hypertension in blacks: clinical overview. Although the decline in stroke and other cardiovascular morbid and mortal events has been occurring since the 1940s, the steeper decline since 1968 has been attributed to improved hypertension awareness, treatment, and control. However, in spite of this encouraging trend from the population in general, surveys from the 1970s and our more recent survey from the Maryland Hypertension Program indicate that hypertension control among blacks remains unacceptably poor, particularly in view of the high prevalence. Of special concern are black men, who have the highest prevalence of any group and the poorest control rate (see Tables 6-1 through 6-4). According to Gillum and Gillum, "High rates of non-compliance with follow-up and drug therapy seriously compromised the efforts of community-wide programs. Indeed, non-compliance with therapeutic or preventive health advice is now the major barrier to effective hypertension control in the United States." Impediments to ideal hypertension control in black communities can be divided into three categories 1. Severity of hypertension in blacks. 2. Barriers related to the medical care system, including inadequate financial resources (see also Chapter 5), inconveniently located health care facilities, long waiting times, and inaccessibility to health education, specifically as it relates to hypertension. 3. Barriers related to the social, psychosocial, and sociopolitical environment, which include problems of underemployment, unemployment, racism, and strained racial relationships. In summary, one could say that, in spite of generally improved hypertension control in the United States, the group that has the worse problems (blacks, especially males) is not benefiting as much as the general population. The strategy for treating black patients with hypertension is little different from that applied to all other patients. However, consideration must be given to the patients' lifestyle. The cultural differences in diet especially must be taken into account. Finally, economic considerations must always be an important component in managing black hypertensive patients. For a detailed discussion of treatment alternatives, see Chapter 11. 
Increase in atherosclerosis and adventitial mast cells in cocaine abusers: an alternative mechanism of cocaine-associated coronary vasospasm and thrombosis. Coronary vasospasm has been implicated as a cause of myocardial ischemia and sudden cardiac death in cocaine abusers. However, the mechanism or mechanisms remain unknown. Autopsy records (n = 5,871) from the medical examiner's files at Baltimore, Maryland and northern Virginia were examined and 495 persons (8.4%) were identified with positive toxicologic findings for cocaine. Of these, six subjects (1.2%) had total thrombotic occlusion, involving primarily the left anterior descending coronary artery. The mean number of adventitial mast cells per coronary segment and the degree of atherosclerosis were determined. These observations were compared with findings in age- and gender-matched subjects who died from cocaine overdose and in patients who had sudden cardiac death (acute thrombosis) without a history of illicit drug abuse. There were significantly more mast cells in subjects with cocaine-associated thrombosis than in the other groups. The number of mast cells showed a significant correlation with the degree of cross-sectional luminal narrowing (r = 0.68) in subjects with cocaine-associated thrombosis but not in subjects with sudden death due to thrombosis (r = 0.34, p less than 0.03). Subjects with cocaine-associated thrombosis also had significant coronary atherosclerosis without plaque hemorrhage (five had one or more vessels with greater than 75% cross-sectional area luminal narrowing) despite a mean age of 29 +/- 2 years. These findings suggest that adventitial mast cells may potentiate atherosclerosis and vasospasm, thrombosis and premature sudden death in long-term cocaine abusers. 
Transesophageal Doppler echocardiography of pulmonary venous flow: a new marker of mitral regurgitation severity. Pulmonary venous flow varies with different cardiac conditions. Flow patterns in response to mitral regurgitation have not been well studied, but flows may vary enough to differentiate among different grades of regurgitation. Accordingly, pulmonary venous flow velocities were recorded in 50 consecutive patients referred for outpatient (n = 26) or intraoperative (mitral valve repair; n = 24) echocardiographic examination for mitral regurgitation. Recordings were made of right and left upper pulmonary veins with pulsed wave Doppler transesophageal echocardiography. Mitral regurgitation was graded from 1+ to 4+ by an independent observer using transesophageal color flow mapping. The results of cardiac catheterization performed 5 weeks earlier in 43 of the patients were also graded for mitral regurgitation by an independent observer. Pulmonary venous flow patterns, the presence of reversed systolic flow and peak systolic and diastolic flow velocities were compared with the severity of mitral regurgitation indicated by each technique. Of the 28 patients with 4+ regurgitation by transesophageal color flow mapping, 26 (93%) had reversed systolic flow. The sensitivity of reversed systolic flow in detecting 4+ mitral regurgitation by transesophageal color flow mapping was 93% and the specificity was 100%. The sensitivity and specificity of reversed systolic flow in detecting 4+ mitral regurgitation by cardiac catheterization were 86% and 81%, respectively. Discordant flows were observed in 9 (24%) of 38 patients; the left vein usually showed blunted systolic flow and the right showed reversed systolic flow. In 22 intraoperative patients, there was "normalization" of pulmonary venous systolic flow after mitral valve repair in the postcardiopulmonary bypass study compared with the prebypass study after the mitral regurgitant leak was corrected. 
Excision of exposed cartilage for management of Mohs surgery defects of the ear. Cartilage of the ear is often exposed during Mohs surgical procedures. Fenestration of the cartilage with a skin punch has been recommended to stimulate granulation tissue where the perichondrium has been destroyed. This article describes an alternative method--the excision of a window through the exposed cartilage, fully exposing the perichondrium on the other side of the cartilage. This promotes the rapid healing by second intention or provides a vascular bed for immediate skin grafting. Also, aggressive excision of nonviable cartilage helps prevent chondritis or perichondritis. 
Prognostic significance of a predischarge exercise test in risk stratification after unstable angina pectoris The prognostic significance of exercise testing was compared with clinical and electrocardiographic (ECG) variables in a prospective study of 107 patients with unstable angina discharged from the hospital on medical therapy. During a follow-up period of 12.8 +/- 1.4 months, 10 patients (9%) had a nonfatal myocardial infarction (n = 8) or died (n = 2) and 22 (20%) were readmitted with recurrent unstable angina. The relation between 20 clinical, ECG and exercise test variables and the risk of adverse outcome (death, nonfatal myocardial infarction or recurrent unstable angina) was analyzed using both univariate and multivariate (logistic regression) analysis. Univariate predictors of adverse outcome included diabetes mellitus, evolutionary T wave changes, T wave changes on the preexercise ECG and low maximal rate-pressure product during exercise. Independent predictors of adverse outcome in multivariate analysis included diabetes mellitus, evolutionary T wave changes after admission, rest pain during hospitalization, ST depression during exercise and low maximal rate-pressure product. A predictive model constructed using the regression equation and all independent predictors stratified patients into high and low risk groups (41% and 5% risk of adverse outcome, respectively). The result of a predischarge exercise test adds independent prognostic information to clinical and ECG data in medically treated patients with unstable angina and could be used in combination with clinical and ECG data to identify patients at risk of adverse events. 
The glucocorticoid hormone signal transduction pathway in mice homozygous for chromosomal deletions causing failure of cell type-specific inducible gene expression. Wild-type newborn mice are characterized by the ability of certain liver-specific genes encoding various enzymes and mapping on different chromosomes to respond to glucocorticoid induction. Newborn mice homozygous for deletions at and around the albino locus on chromosome 7 fail to develop this competence for hormone-inducible gene expression even through they do show normal constitutive expression of the same genes. Studies of the glucocorticoid hormone signal transduction pathway reported here show identical expression of glucocorticoid receptor mRNA and protein in deletion homozygotes and normal littermates. Furthermore, the receptor interacts normally with the 90-kDa heat shock protein hsp90. Elevated glucocorticoid hormone levels in newborn deletion homozygotes, most likely resulting from their stressed condition, provide an explanation for the reduced binding activities of receptors reported previously. The elimination of receptors and hormones as direct targets of the chromosomal deletion effects suggests that the failure of inducible gene expression might reside in defective competence of the affected structural genes to respond to the hormonal stimulus. 
Platelet antiaggregate activity. Calcium ions act as a second messenger to platelet agonists, with increases in intracellular calcium bringing about changes in shape, aggregation, and release reactions. Changes in platelet function have been reported previously in migraine sufferers and there is evidence that hyperaggregability occurs during a migraine attack. It was decided to assess platelet aggregation with platelet-rich plasma (PRP) from nicardipine-treated migraine sufferers because dihydropyridine derivatives are known to inhibit adenosine diphosphate (ADP)- and epinephrine-induced aggregation. Aggregation induced by 1.4 mumol/L arachidonic acid was similar in PRP from control subjects and untreated migraine sufferers, whereas 1 or 2 mumol/L ADP-induced aggregation was lower in PRP from migraine sufferers. Treatment with 20 mg of nicardipine three times daily for 2 months significantly (p less than 0.05) increased 2 mumol/L ADP-induced aggregation. It is concluded that nicardipine was acting either on migraine pathogenic mechanisms or directly on the platelets. 
Detection of Epstein-Barr virus sequences in Hodgkin's disease by the polymerase chain reaction. The authors examined paraffin-embedded lymph node biopsies from 65 cases of Hodgkin's disease for the presence of Epstein-Barr virus (EBV) DNA, using the highly sensitive polymerase chain reaction technique. Overall 40% of the cases were positive for EBV DNA; there were no statistically significant differences in the frequency of EBV positivity among the different subtypes of Hodgkin's disease. These results are in agreement with those of previous studies that employed less sensitive detection techniques and suggest that EBV either is present in pathologic tissues only in some phases of the evolution of Hodgkin's disease or is a pathogenetic factor involved in only a portion of cases. 
A comparison of the KTP/532-laser tonsillectomy vs. traditional dissection/snare tonsillectomy. This study compared tonsillectomy by potassium-titanyl-phosphate (KTP/532) laser with tonsillectomy by traditional dissection and snare. Eighty-three consecutive patients who were candidates for a tonsillectomy were randomly assigned to one of four groups in a prospective study. The four treatments were bilateral traditional dissection/snare tonsillectomy, bilateral KTP/532-laser tonsillectomy, left laser tonsillectomy and right dissection/snare tonsillectomy, and left dissection/snare tonsillectomy and right laser tonsillectomy. Intraoperative comparisons were made between the two methods with regard to blood loss and operating time. Postoperatively bleeding and healing time were also recorded. A questionnaire answered on a daily basis assessed the patient's pain. Disadvantages of the KTP/532 tonsillectomy included increased cost, increased total operating time as a result of increased setup time and laser malfunctions, delayed healing, and no statistically significant improvement in level of pain. The sole advantage associated with the KTP/532 laser tonsillectomy was decreased blood loss, which may be significant for patients with a coagulopathy. 
Dipyridamole thallium scanning in the evaluation of coronary artery disease in elective abdominal aortic surgery. Dipyridamole thallium scanning was routinely performed on 68 consecutive patients who presented for elective aortic surgery. All 68 patients were judged by clinical assessment to be at low risk for perioperative cardiac complications. In addition, 42 of 68 patients had a history of myocardial infarction, stable angina, or abnormal echocardiographic findings (group 1). Twenty-six of 68 patients did not have a history of myocardial infarction, angina, or abnormal echocardiographic findings (group 2). In group 1, 34 of 4 patients had positive results on dipyridamole thallium scanning, and 15 of these patients were found to have critical coronary artery disease on subsequent cardiac catheterization; nine underwent immediate coronary artery bypass grafting, and six had their coronary artery disease treated medically and their vascular operations cancelled. The remaining 27 patients in group 1 underwent elective operations, with six (22%) of 27 sustaining postoperative cardiac complications. None of the group 2 patients was found to have critical coronary artery disease. All patients in group 2 underwent aortic operation without cardiac complication. Routine dipyridamole thallium scanning detected a 22% (15 of 68) incidence of critical coronary artery disease overall. There was a 36% (15 of 42) incidence of critical coronary artery disease in group 1 patients vs 0% in group 2 patients (95% confidence interval, 21% to 50%). We conclude that the use of dipyridamole thallium scanning in low-risk patients for cardiac screening prior to elective aortic operations is beneficial in selected patients who have a history of myocardial infarction, angina, or abnormal echocardiographic findings, but is not necessary in patients with no history of coronary artery disease. 
Adhesion formation after ovarian electrocauterization on patients with polycystic ovarian syndrome. The rate of adhesion formation after ovarian electrocauterization has been described in two selective and unselective groups of patients with PCOS. The rate of this complication in the selective group was 0 from 16 ovaries and in the unselective group (5/25). However, the rate of major adnexal adhesion in the unselective group was 1 from 25 ovaries. 
Human fetal hepatocytes respond to inflammatory mediators and excrete bile. Under strict observation of the ethical guidelines of the 1975 Declaration of Helsinki Human Research Committee, primary hepatocyte cultures were prepared from second-trimester fetal liver specimens. We have shown for the first time that fetal hepatocytes have the capacity to produce an acute-phase response on treatment with inflammatory mediators. Addition of interleukin-6 to the cultures resulted in strong induction of C-reactive protein and alpha-1-antichymotrypsin expression, whereas albumin expression was repressed. In contrast to interleukin-6, transforming growth factor-beta did not induce C-reactive protein expression. However, as in adult hepatocytes, fetal cells responded to transforming growth factor-beta by reduced albumin synthesis. We were able to show by virtue of fluorescein excretion into sealed clefts that fetal hepatocytes have the functional capacity to form bile. Our findings indicate that second-trimester hepatocytes can be regarded as fairly mature liver cells. 
Aminoglycoside toxicity--a survey of retinal specialists. Implications for ocular use. Surveyed members of the Retina, Macula, and Vitreous Societies reported 93 cases of macular infarction they believed to be related to administration of gentamicin sulfate; five, to administration of amikacin sulfate; and three, to administration of tobramycin sulfate. Most cases of infarction after administration of gentamicin occurred in eyes that received an intravitreous injection of 0.4 mg after vitrectomy, but a surprisingly high number, 17, occurred after injection of 0.1 or 0.2 mg, doses that are considered safe by many ophthalmologists. Four additional cases of infarction occurred in eyes that did not undergo vitrectomy after injection of 0.1 or 0.2 mg. Four of the five cases related to administration of amikacin occurred after intravitreous injection of 0.4 mg, and one of these four occurred in an eye that did not undergo vitrectomy. Twenty-three cases of macular infarction occurred in eyes that were treated with prophylactic subconjunctival injections of aminoglycosides after routine ocular surgery. Responses from this survey suggest that aminoglycoside-induced retinal infarction is widely recognized and more common than indicated from the small number of cases reported in the literature. The role of aminoglycosides in the prophylaxis of ocular infections and the management of endophthalmitis should be reevaluated. 
Cerebrovascular regulation and neonatal brain injury. Neuropathology occurring as a result of hemodynamic injury occurs in up to 25% of preterm newborns of less than 1,500 gm birth weight and in a much smaller, but nonetheless meaningful, proportion of more mature infants. Abnormalities in cerebrovascular regulation have been proposed as major contributing factors to both ischemic and hemorrhagic injuries in the newborn brain. In this review we explore several factors that play a role in cerebrovascular regulation in the immature brain and relate them to what is known about vascular regulation in the mature brain and to the types of pathology that occur in the newborn brain. One goal in this "decade of the brain" should be to increase our basic and clinical knowledge about the cerebrovasculature of the newborn in order to enhance our ability to predict and prevent perinatal brain injury. 
Emergency intubation for paralysis of the uncooperative trauma patient. The impact of paralysis followed by intubation was studied in patients who had been traumatized and subsequently admitted to Lehigh Valley Hospital Center. Trauma admission records between January 1987 and June 1988 were reviewed. Fifty-seven patients, intubated for control of agitation and combativeness, were divided into high injury severity (HIS) and low injury severity (LIS) subgroups using admission trauma (TS) and injury severity scores (ISS). Thirty-eight (70%) were classified as HIS and 19 (30%) as LIS. All HIS patients had significant injuries diagnosed following paralysis with intubation (PWI). Mortality in the HIS group was 9%. The LIS subgroup was compared to a randomly selected group of similarly injured blunt trauma patients who did not require PWI. There were significant differences (P less than 0.05) in age, hospital cost, hours per day of nursing care, and percent of patients with an ETOH level greater than 100 mg%. Emergency paralysis with intubation is an effective method for controlling the uncooperative, combative, seriously injured patient. However, patients with low injury severity who require restraint have higher costs and require more care if they are paralyzed and intubated than if they are not. 
Ultrasonography in the diagnosis of gynecologic disorders. Ultrasonographic examination is being used with progressively greater frequency as an aid in diagnosis of gynecologic disorders but too often without consideration of whether information other than that obtained from clinical examination is needed and whether ultrasonography can supply it. The size, number, and position of pelvic masses and, in some instances, the type of tumor can be identified, but it is not often necessary when operation is clearly indicated. Ultrasonographic screening for diseases of the reproductive organs has been proposed, but its use for this purpose is limited and it is not cost-effective. It should be used as an adjunct to clinical diagnosis, not as a primary diagnostic procedure. 
Molecular genetic considerations in osteosarcoma. Osteosarcoma tumorigenesis is consistent with a model by which tumorigenesis results if both alleles at the retinoblastoma susceptibility locus (RBI) are altered. Additional genetic evidence strongly suggests that another obligate event in osteosarcoma tumorigenesis is the homozygous alteration of another gene, p53. Both the RB1 gene and p53 have been proposed to act as tumor-suppressor genes, suggesting that, in this instance, tumorigenesis is the result of the loss of gene function of these two genes, rather than a gain of function. 
Risk factors for acute non-A, non-B hepatitis in the United States and association with hepatitis C virus infection. The Centers for Disease Control conducted intensive surveillance for acute non-A, non-B hepatitis in four sentinel counties over a 7-year period. Testing for antibody to hepatitis C virus was performed with the newly developed enzyme immunoassay. The incidence of non-A, non-B hepatitis remained relatively stable (average, 7.1 cases per 100,000, but there were significant changes in disease transmission patterns. The proportion of patients with a history of blood transfusion declined from 17% to 6%, but the proportion with a history of parenteral drug use increased from 21% to 42%. The proportion of patients with histories of sexual exposure (6%), household exposure (3%), occupational exposure to blood (2%), or hemodialysis (0.6%) did not change over time. Antibody to hepatitis C virus was found in 45% of patients within 6 weeks of onset of illness and in 68% of patients followed up for at least 6 months. Patients with no history of transfusions were just as likely to be positive for antibody to hepatitis C virus as patients with transfusion-associated hepatitis, indicating that hepatitis C virus is the major causative agent of all non-A, non-B hepatitis in the United States. 
Update on functional anatomy and pathology of human eustachian tube related to otitis media with effusion. New anatomic and histopathologic information regarding the eustachian tube and its surrounding structure as well as possible mechanisms of opening and closing function and dysfunction are discussed in this article. In the past two decades, much light has been shed on the relationship between anomalies of the eustachian tube and the pathogenesis of otitis media with effusion. Now that a technique for obtaining specimens for any histopathologic study that includes the temporal bone as well as the eustachian tube is available, it is hoped that, by harvesting and examining a large number of such specimens, more information will be gained about the relation between eustachian tube pathology and eustachian tube dysfunction, particularly as it relates to otitis media effusion. Only in this way can the clinical management of otitis media be improved. 
Nucleolar organizer regions in vascular and neoplastic cells of human gliomas. The number of nucleolar organizer regions in vascular cells and neoplastic cells of human gliomas was counted by a combined staining technique: one-step silver colloid method for nucleolar organizer region-associated argyrophilic protein (AgNOR) and periodic acid-Schiff staining for basement membrane of vascular components. The number of AgNORs (mean +/- SD) in the vascular and neoplastic cells of various tumors tested was as follows: benign astrocytoma (Grade 2, n = 4), 1.52 +/- 0.07 and 1.80 +/- 0.13, respectively; anaplastic astrocytoma (Grade 3, n = 7), 1.98 +/- 0.23 and 2.87 +/- 0.50; and glioblastoma multiforme (Grade 4, n = 11), 2.05 +/- 0.29 and 3.13 +/- 1.13. AgNOR scores in vascular cells of benign astrocytomas, anaplastic astrocytomas, and glioblastomas were significantly higher than those of vascular cells in normal brain tissue without neoplastic alteration (1.26 +/- 0.05; n = 3; P less than 0.01, P less than 0.001, and P less than 0.001, respectively). Moreover, the AgNOR scores of vascular cells in high-grade gliomas (Grades 3 and 4) were significantly higher than those in low-grade gliomas (Grade 2) (P less than 0.01). These results indicate that the proliferative activity of both vascular and neoplastic cells in gliomas increased as histological malignancy advanced, and that the quantification of AgNORs was useful in evaluating proliferative activity in vascular cells as well as in assessing the malignancy of neoplastic tissues. 
Immunoblotting and culture positive endocarditis. Serum samples from patients with endocarditis due to Streptococcus mutans, Streptococcus pneumoniae, Streptococcus agalactiae, Streptococcus lactis and a "nutritionally" variant streptococcus were immunoblotted against antigenic extracts from all five species. In S mutans endocarditis there was an endocarditis specific pattern of IgM against bands of 220, 200, and 190 kilodaltons. In S pneumoniae IgM against antibody of a molecular weight greater than 150 kilodaltons was specific to endocarditis. In S agalactiae IgM against bands at 82, 71, and 66-67 kilodaltons was endocarditis specific. In S lactis endocarditis specific IgM was present against antigenic bands at 105, 66, 61 and 58 kilodaltons. With the "nutritionally" variant streptococcus it was impossible to distinguish between cases of endocarditis and controls. 
Acquired progressive lymphangioma. Acquired progressive lymphangioma is rare and can histologically mimic well-differentiated angioendothelioma. In a 9-year-old boy with acquired progressive lymphangioma, we demonstrated that the neoplasm consists of at least a vascular component and a smooth muscle component. The presence of type IV collagen around many vascular channels suggests that an intermediate stage of differentiation between blood vessels and lymphatics may be present. Our findings indicate that acquired progressive lymphangioma is most likely a complex hamartoma composed of vascular channels and smooth muscle. 
Brachial plexus anesthesia in pediatric patients. Between 1980 and 1988 at our institution, brachial plexus anesthesia (BPA) was used in 109 pediatric patients who underwent 142 surgical procedures on an upper extremity, including 134 axillary blocks. Most patients older than 6 years of age had their blocks and surgical procedures with moderate sedation. The success rate was high--92.4% of axillary blocks and 100% of other blocks were adequate for surgical intervention in patients who required only intravenous sedation. The postoperative course in the BPA group was compared with that in 109 age-matched control subjects who underwent 188 procedures on an upper extremity during general anesthesia (GA). Admission to the recovery room after anesthesia occurred less frequently in the BPA group than in the GA group (27.5% versus 91.0%; P less than 0.01). Furthermore, nausea and vomiting were less frequent in the BPA group than in the GA group (P less than 0.01). Outpatients in the BPA group were less likely to require narcotic analgesics before dismissal than were those in the GA group (12% versus 31%; P less than 0.05). Admission of outpatients was infrequent in both groups (2% for BPA and 9% for GA). No significant difference was noted in 24-hour postoperative narcotic requirements between the BPA and GA groups. 
Massive evisceration: a complication following sacrospinous vaginal vault fixation. This report describes a spontaneous vaginal vault prolapse in association with massive evisceration following sacrospinous vaginal vault fixation. Careful attention to surgical technique is critical to the success of the operation. In particular, good apposition of the vaginal vault to the sacrospinous ligament and adequate repair of an enterocele should avoid this complication. 
Hip disarticulation: factors affecting outcome. Hip disarticulation, especially in patients with peripheral vascular disease, has been associated with high morbidity and mortality rates. This report describes patient characteristics that influence the clinical outcome of hip disarticulation. The medical records of all patients undergoing hip disarticulation from 1966 to 1989 were reviewed for surgical indication, perioperative wound complications, and postoperative deaths. Fifty-three patients underwent hip disarticulation for limb ischemia (10), infection (12), infection and ischemia (14), or tumor (17). The overall incidence of wound complications was 60%, and no significant differences were found among the groups. Prior above-knee amputation and urgent/emergent operations were significantly associated with increased wound complications (p less than 0.05). The overall mortality rate was 21%, ranging from 0% (tumor) to 50% (ischemia) and differed significantly among the groups (p less than 0.02). Mortality was significantly associated with urgent/emergent operations (p less than 0.01). Age, diabetes mellitus, and previous inflow procedures did not influence mortality rates. The presence of limb ischemia influenced mortality rates to a greater extent than did infection, and a history of cardiac disease was statistically predictive of death. Wound complications frequently accompanied hip disarticulation, regardless of operative indication, and were significantly increased by urgent/emergent operations and prior above-knee amputation. Hip disarticulation can be performed with low mortality rates in selected patients. Both limb ischemia and infection substantially increase operative mortality rates. 
Benefit of a stroke unit: a randomized controlled trial. In a randomized controlled trial we compared the clinical outcome of acute stroke patients, 110 of whom were allocated to treatment in a stroke unit and 110 to treatment in general medical wards. No significant difference existed between these groups with regard to sex, age, marital status, medical history, or functional impairment on admission. Outcome was measured at 6 and 52 weeks after the stroke by the proportion of patients at home, the proportion of patients in an institution, the mortality, and the functional state. After 6 weeks 56.4% of the patients randomized to the stroke unit and 32.7% of the patients randomized to the general medical wards were at home (p = 0.0004), and after 52 weeks 62.7% and 44.6%, respectively, were at home (p = 0.002). After 6 weeks 36.3% of the patients from the stroke unit and 50.0% from the general medical wards were in an institution (p = 0.02); after 52 weeks 12.7% and 22.7%, respectively, were institutionalized (p = 0.016). After 6 weeks mortality was 7.3% for the stroke unit group and 17.3% for the general medical wards group (p = 0.027). After 52 weeks mortality was 24.6% for the stroke unit group and 32.7% for the general medical wards group (difference not significant). Functional state was significantly better for patients treated in the stroke unit after both 6 and 52 weeks. We conclude that care of patients with acute stroke in a stroke unit improves clinical outcome compared with treatment in general medical wards. 
Cost and quality trade-offs in the treatment of hypertension. The cost-effectiveness of treatment for hypertension is positively related to the level of pretreatment blood pressure and to the level of success in achieving patient adherence to prescribed medical regimens. Opportunities to improve the cost-effectiveness of treatment include limiting treatment to patients with well-documented sustained increases in blood pressure, giving higher priority to the treatment of patients with diastolic blood pressures of 100 mm Hg and above, and relying on lower-cost medications if clinical responses to treatment permit. In patients with mild hypertension, a comparison of strategies for initiating pharmacological treatment that takes into account potential side effects as well as the costs of medications indicates a difference of $270/patient-yr between the least and most expensive alternatives. Whether the additional costs of more expensive treatment strategies are "worth it" depend on any additional health benefits actually conferred. Moreover, higher-cost strategies may have negative influences on patients' decisions to adhere to prescribed regimens or to continue in treatment. Cost is a particular problem for the treatment of chronic conditions like hypertension because of inadequate insurance coverage for medications, especially for the poor. 
Acupuncture in angina pectoris: does acupuncture have a specific effect? To overcome the methodological problems of blinding the patients and the acupuncturist in acupuncture trials, 33 patients with stable angina pectoris, who were randomized to either genuine or sham acupuncture, received electroacupuncture by another acupuncturist, and the change in skin temperature was recorded. It was found that the change in skin temperature correlated significantly with the degree of improvement following both genuine and sham acupuncture. Fourteen patients with no decrease in skin temperature exhibited a significantly better response to acupuncture than 19 patients who showed a decrease in skin temperature (G II). In the former group, there was a 15% median improvement in exercise tolerance (G II 0%), a 67% improvement in anginal attack rate (G II 38%), and an 84% improvement in nitroglycerine consumption (G II 50%). A significant correlation was found between the duration of disease and the effect of acupuncture. It is concluded that both genuine and sham acupuncture have a specific effect on some angina pectoris patients in addition to the effect of pharmacological therapy. 
Nasal positive pressure ventilation in patients with acute respiratory failure. Difficult and time-consuming procedure for nurses. Intubation and mechanical ventilation are well-established techniques in the management of patients with acute respiratory failure; however, there are situations in which these procedures cannot be used safely for various reasons. A recently described noninvasive technique, nasal positive-pressure ventilation (NPPV), has been developed for home ventilation of certain patients with chronic ventilatory insufficiency. We hypothesized that NPPV could be used in selected patients in whom intubation and mechanical ventilation were clearly indicated, but not immediately possible, or even contraindicated. Six patients were treated with NPPV during an episode of acute respiratory failure and enrolled in a prospective study. We found that NPPV was successful in avoiding intubation, but only in the three patients suffering from a restrictive pulmonary disorder, whereas the procedure was unsuccessful in patients with obstructive disorders. Moreover, in every patient, acute NPPV was very time-consuming for the nursing staff: in patients with restrictive disorders, a nurse had to monitor a patient submitted to NPPV during 41 +/- 9 percent of the duration of ventilation and during 91 +/- 9 percent of the NPPV time in patients with obstructive disorders. We conclude that acute NPPV may be attempted in selected patients with acute respiratory failure, predominantly patients with restrictive respiratory disorders, but that this procedure is very time-consuming for nurses. 
Emergency esophagogastrectomy for treatment of hydrochloric acid injury. Eight patients with severe hydrochloric acid injury of the esophagus and stomach had early esophagogastrectomy. Four patients survived and 6 to 8 weeks later underwent successful substernal colon replacement. The value of early diagnosis and subsequent aggressive surgical management of patients who have ingested hydrochloric acid is stressed. 
Treatment of refractory chronic Lyme arthritis with arthroscopic synovectomy. Of 20 patients who underwent arthroscopic synovectomy for refractory chronic Lyme arthritis of the knee, 16 (80%) had resolution of joint inflammation during the first month after surgery or soon thereafter, and they have remained well during the 3-8-year followup period. Three of these 16 patients who were more disabled preoperatively, still had mild functional limitation at long-term followup. The remaining 4 patients (20%) had persistent or recurrent synovitis. We conclude that arthroscopic synovectomy is effective in treating chronic Lyme arthritis in patients in whom the disease does not respond to antibiotic therapy. 
Ultrasonography in the diagnosis of acute appendicitis. Ultrasonography with graded compression was performed in 525 patients with clinical signs of acute appendicitis. Of 207 patients with surgically proven appendicitis the inflamed appendix (diameter greater than or equal to 6 mm) had been visualized sonographically in 177 (86 per cent). The score for non-perforated appendicitis (91 per cent) was higher than for perforated appendicitis (55 per cent). Twenty-four patients in whom an inflamed appendix was seen on ultrasonography did not undergo surgery because of rapidly subsiding symptoms ('abortive appendicitis'). Four of these 24 developed recurrent appendicitis warranting surgery. Two underwent elective appendectomy and 18 have remained symptom-free. Of 155 patients with a subsequently confirmed alternative condition, ultrasonography made the correct diagnosis in 140: bacterial ileocaecitis (69), mesenteric lymphadenitis (eight), gynaecological conditions (34), urological conditions (eight), caecal diverticulitis (six), perforated peptic ulcer (six), Crohn's disease (two) and miscellaneous conditions (seven). Of 139 patients in whom no definite diagnosis was made ultrasonography showed no abnormalities in 138. In four patients a false positive sonographic diagnosis of appendicitis was made and in two patients with appendicitis an alternative condition was incorrectly diagnosed. During the last 3 years of the study the negative appendicectomy rate was 7 per cent and delay beyond 6 h after admission occurred in only 2 per cent of patients with surgically proven appendicitis. When used to complement the clinical diagnosis ultrasonography improves the diagnostic accuracy and patient management in those suspected of having acute appendicitis. 
Lactose intolerance. Pinpointing the source of nonspecific gastrointestinal symptoms. Lactose intolerance is a common condition that can cause nonspecific gastrointestinal symptoms. A reliable diagnosis cannot be made on the basis of the patient's history. The breath hydrogen test is simple, noninvasive, accurate, and inexpensive and is the diagnostic method of choice. In addition to traditional dietary restriction of lactose, treatment may consist of alterations in dietary fat content or caloric density to reduce symptoms and use of dairy products or additives that provide lactase activity. 
Comparison of speech perception abilities in deaf children with hearing aids or cochlear implants. The speech perception abilities of deaf children with a single- or multi-channel cochlear implant are compared with those of deaf children who derive substantial benefit from conventional hearing aids. The children with hearing aids have unaided pure-tone thresholds ranging from 90- to 110-dB HL through at least 2000 Hz, and aided thresholds of 30- to 60-dB HL. The group data show that the speech perception scores of the subjects with hearing aids were significantly higher than those of the subjects with implants on a range of speech perception measures. Although a few subjects with implants achieved scores as high as those who used hearing aids, the majority did not. Even though the children with implants receive substantial benefit from their devices, they continue to have limited auditory perception abilities relative to their peers who derive benefit from conventional hearing aids. The data highlight the importance of establishing hearing aid benefit in potential candidates for implant. 
Intermittent ischemia potentiates intestinal reperfusion injury. We hypothesized that even brief periods of reperfusion interjected between ischemic episodes would increase tissue injury. Studies were performed in a rat small intestine preparation in which metabolic, hemodynamic, and histologic responses to ischemia have been well characterized. Animals were subjected to a total of 30 or 45 minutes of complete intestinal ischemia. Flow interruption was continuous (C, single episode) or intermittent (I, two or three episodes of 15-minute ischemia separated by 5 minutes of reperfusion). In some experiments 5-minute reperfusions were performed with arterial blood depleted of leukocytes (IL). This additional perturbation was included to determine the role of neutrophils that have been strongly implicated in reperfusion injury. In all three protocols histologic sections were obtained after each ischemic insult and after 1 hour of reperfusion with arterial blood. Villous histology was graded in a blinded fashion with 1 = normal and 5 = severe injury. No significant differences were found between groups in immediate postischemic histologies before reperfusion. After 1 hour of reperfusion, intermittent episodes of ischemia were associated with significantly worse histologic injury than that seen with comparable durations of continuous ischemia (30 min: I, 4.4 +/- 0.5 vs C, 2.7 +/- 0.4; 45 min: I, 4.9 +/- 0.2 vs C, 2.8 +/- 0.3). However, if 5-minute reperfusions were with leukopenic blood, this effect was markedly reduced (30 min IL, 3.4 +/- 0.3; 45 min IL, 3.6 +/- 0.2). Even short periods of reperfusion during an ischemic insult greatly increased mucosal injury. 
Immunohistochemical analysis of estrogen receptors, progesterone receptors, Ki-67 antigen, and human papillomavirus DNA in normal and neoplastic epithelium of the uterine cervix. To investigate the relationship between the sex steroid receptor (estrogen receptor [ER] and progesterone receptor [PR]) status and the cell proliferation kinetics during the menstrual cycle in normal and neoplastic epithelium of the uterine cervix, immunohistochemical localization of ER, PR, and cell proliferation-associated antigen, Ki-67, was investigated in 35 normal cervical specimens, 3 condylomas, 26 cervical intraepithelial neoplasia (CIN) samples, and 22 invasive squamous carcinoma samples. The presence of human papillomavirus (HPV) DNA was also studied. In the normal cervix, basal cells were usually ER positive, PR negative, and Ki-67 negative throughout the menstrual cycle. Parabasal cells were ER positive and PR negative in the follicular phase, but ER negative and PR positive, and Ki-67 positive in the luteal phase, and Ki-67-positive cells increased in number in the luteal phase. In contrast, PR positivity was observed in the cells of condyloma (2 of 2 cases), CIN (19 of 26 cases), and invasive squamous carcinoma (13 of 22 cases) irrespective of the menstrual phase. Moreover, most neoplastic cells containing HPV DNA type 16/18 were ER negative, whereas several lesions containing HPV DNA type 31/33/35 were weakly ER positive. Many Ki-67-labeled cells were observed in the neoplastic lesions. These results suggest that reduced ER expression and increased PR expression are associated with the proliferation of normal cervical squamous epithelium, and this proliferation-related receptor status, which is probably induced by HPV infection, is usually expressed in neoplastic cervical squamous cells. 
Maintenance treatment of duodenal ulceration: ranitidine 300 mg at night is better than 150 mg in cigarette smokers. Two hundred patients received either ranitidine 150 mg or 300 mg at night for 18 months to prevent duodenal ulcer relapse. Recurrence rates were lower in patients receiving the higher dose of ranitidine (3.1% v 9.7%, p = 0.78; 6.5% v 16.7%, p = 0.037; and 8.9% v 17.0%, p = 0.121 at six, 12, and 18 months respectively). In patients receiving ranitidine 150 mg, recurrences were significantly more common in smokers than non-smokers after 12 and 18 months, while in patients receiving ranitidine 300 mg recurrence rates were similar in smokers and non-smokers. Ranitidine 300 mg at night abolishes the adverse effect of smoking observed during maintenance treatment with ranitidine 150 mg at night and may therefore be an appropriate maintenance dose for smokers who relapse during standard dose maintenance treatment. 
Primary cardiac sarcomas. In marked contrast to benign cardiac tumors, primary cardiac sarcomas occur infrequently. Moreover, there is no uniform approach to treating such patients, and the benefits of postoperative chemotherapy are unclear. Between 1964 and 1989, 21 patients with primary cardiac sarcomas underwent surgical resection alone (n = 7), chemotherapy alone (n = 1), or combined operation and postoperative chemotherapy based on adriamycin (n = 13). Twenty-four operations were performed on 20 patients with relief of symptoms in all. Eleven patients had complete resection. Operative mortality was 8.3% (2/24). Histology and originating chamber(s) included angiosarcoma (n = 7; 6/7 in right atrium, 1 in left atrium), malignant fibrous histocytoma (7; all in left atrium), fibrosarcoma (2; 2/2 in left atrium), rhabdomyosarcoma (2; 1 in left atrium, 1 in right ventricle), leiomyosarcoma (2; 1 in left atrium, 1 in left ventricle); and one undifferentiated sarcoma (right atrium). Overall actuarial survival was 14% at 24 months after resection. Patients with complete resection had a median survival of 24 months compared with only 10 months in all other patients (p = 0.035). Postoperative chemotherapy did not enhance survival in patients with incomplete resection. At this time, aggressive and complete surgical resection seems to offer the best hope for palliation and survival in an otherwise fatal disease. 
Decreased serum growth hormone-binding protein in patients with liver cirrhosis. The recently characterized GH-binding protein (GH-BP) has an amino acid sequence identical to the extracellular domain of the GH receptor. Serum GH-BP reflects the amount of GH receptors, and the liver seems to be their main source. To evaluate the effect of liver disease on GH-BP, 52 patients with liver cirrhosis were studied. Serum GH-BP was measured by a binding assay with dextran-coated charcoal separation. Levels of GH-BP were correlated against the clinical state, assessed by Pugh's score. The GH-BP of 31 Pugh's class A patients was 9.7 +/- 0.5%/50 microL serum, and that of 21 Pugh's class B and C patients was 7.2 +/- 0.5%/50 microL serum compared to 11.3 +/- 0.5%/50 microL serum in age-matched controls. GH-BP correlated negatively with Pugh's score and serum bilirubin, and positively with serum albumin. It did not correlate with serum liver enzymes or serum insulin-like growth factor-I. Scatchard analysis of GH binding to the GH-BP revealed similar binding affinities in Pugh's A, B, and C patients and controls. The binding capacity in cirrhosis was significantly lower than that in controls. We conclude that serum GH-BP is controlled mainly by the liver and can provide an additional measure of disease severity in liver cirrhosis. 
Teaching intubation skills using newly deceased infants. This prospective study was designed to (1) test the hypothesis that the majority of families of newly dead infants in a tertiary neonatal intensive care unit would consent to their infants' being intubated for teaching purposes, (2) determine factors related to family consent, and (3) determine the effects of participation on resident physicians and respiratory therapists. Family consent for intubation was requested following 44 (80%) of the 55 deaths that occurred during the 10-month study period. Of these requests, 32 (73%) were granted. Proportionately more white than black families consented and consent was positively related to autopsy permission. Fifty-three (75%) of 71 trainees completed a mailed questionnaire after their first intubation experience. Although each respondent found the experience helpful, many reported mixed feelings categorized as doubt about participating, apprehension and discomfort, respect for the body, appreciation for the opportunity, a sense of achievement, and feelings of comfort knowing that consent had been obtained. These findings confirm our initial hypothesis and suggest that (1) newly dead infants can be a valuable resource for teaching intubation skills, and (2) others considering a similar approach need to be aware of and sensitive to trainees' feelings. 
Reflex anal dilatation: effect of parting the buttocks on anal function in normal subjects and patients with anorectal and spinal disease. Anal dilatation in response to gentle parting of the buttocks has been advocated as a sign of sexual abuse in children, but nothing is known of the physiology of this response or its existence in normal subjects, in patients with spinal disease, and in patients with a weak sphincter and whether it can be elicited after training. To answer these questions we investigated the effect of parting the buttocks on anal function. Combined anal manometry and electromyography was conducted in six normal subjects (five men, one woman, aged 19-53 years), in 18 patients with faecal incontinence (three men, 15 women, aged 30-80 years), and in seven paraplegic patients (six men, one woman, aged 25-36 years), in four of whom the posterior sacral roots had been cut. Parting the buttocks in normal subjects reduced the pressure in the anal canal from 102 (20) to 14 (3) cm H2O (mean (SEM), p less than 0.00001), but did not cause the anus to gape. This drop in pressure was associated with increased electrical activity in the external anal sphincter. Normal subjects could consciously relax the external anal sphincter and reduce the anal pressure but not so as to result in anal gaping during traction on the buttocks, even after anal dilatation. Stimulation of the anal lining by moving a probe in and out of the anal canal increased the activity of the external anal sphincter, raising anal pressures. Paraplegic patients who had lost conscious control of their external sphincters showed anal gaping when the buttocks were parted. 
Blood warming: current applications and techniques. Active blood warming is a recent practice and arises out of conflicting needs. On the one hand, the safety and preservation of blood require refrigerated storage and delivery up to the moment of transfusion. On the other hand, modern methods of very rapid transfusion in resuscitation would cause clinically dangerous hypothermia if unmodified, ice-cold blood were to be so transfused. These needs must be reconciled in the interest of adequate patient care--hence the need for blood warming. Nevertheless, blood warming creates risks of its own and should not be used without justifying clinical indications. Within limits that extend somewhat above normal body temperature, the application of heat does no harm to stored RBC, a fact that is not reflected in current standards for blood warmers. Bearing in mind the human tendency to "stretch" standards and the fallibility of mechanical devices, caution is always wise. But perhaps the time has come for reconsideration of the present upper limit of 38 degrees C. Many varieties of blood warmers are available in the US, but none at this time is based on electromagnetic activity. The most common systems now in use are in-line warmers, most of which are not adequate for the type of rapid-transfusion systems currently available. Countercurrent in-line blood warmers and the method of rapid warm saline admixture can both be used successfully for rapid, massive transfusions. Blood warming is seldom necessary or desirable for elective transfusions at conventional rates, even for patients with cold autoagglutinins. 
Echinococcus granulosus cysts in the liver: management with percutaneous drainage. Twenty-one hepatic Echinococcus granulosus cysts (maximal diameter, 7.5 cm +/- 4.0) in 12 patients were aspirated and irrigated with hypertonic (20%) saline under sonographic guidance. All patients had signs and symptoms of a hepatic mass caused by the cysts, which had a prominent fluid component that appeared anechoic or hypoechoic, with marked enhancement of back wall echoes. The amounts of cyst fluid aspirated and of hypertonic saline used were 190 mL +/- 240 and 120 mL +/- 90, respectively. Separation of the endocyst from the pericyst and nonviability of scoleces were observed in all cysts. Mean hospital stay was 4.0 days +/- 3.4. Serial sonographic examinations revealed high-level echoes in the cyst cavity (heterogeneous echo pattern), which ultimately became uniformly echogenic (pseudotumor). After follow-up of 14.0 months +/- 5.5, maximal cyst diameter decreased to 4.1 cm +/- 3.1 (P less than .001). One patient died of unrelated causes; the remaining 11 patients experienced relief of symptoms and a decrease in liver span. 
Reduction of canine myocardial infarct size by a diffusible reactive oxygen metabolite scavenger. Efficacy of dimethylthiourea given at the onset of reperfusion. A number of scavengers of reactive oxygen metabolites reduce myocardial injury when given before ischemia and reperfusion, but few, if any, have proven to be effective when given near the onset of reperfusion. This is particularly true when infarct size is measured after at least 48 hours of reperfusion, when the full extent of myocardial damage has become apparent. Dimethylthiourea (DMTU) is an extremely diffusible, potent scavenger of hydroxyl radical, hydrogen peroxide, and hypochlorous acid, with a long half-life of 43 hours. Sixteen chloralose-anesthetized dogs underwent 90 minutes of left anterior descending coronary artery (LAD) occlusion followed by 48 hours of reperfusion. Collateral flow was measured by radioactive microspheres. Infarct size and risk area were measured by a postmortem dual-perfusion technique using triphenyl tetrazolium chloride and Evan's blue dye. In eight dogs, therapy with DMTU (500 mg/kg i.v.) was given during the last 15 minutes of ischemia and the first 15 minutes of reperfusion. In eight control dogs, the same volume of 0.9% saline was given during the last 15 minutes of ischemia through the first 15 minutes of reperfusion. Infarct size as a percent of risk area was reduced in the DMTU-treated group compared with the saline-treated controls (DMTU = 42 +/- 4% versus saline = 59 +/- 4%, p less than 0.01). 
Mucosal IgA recognition of Helicobacter pylori 120 kDa protein, peptic ulceration, and gastric pathology. The gastric IgA response to Helicobacter pylori was examined in 100 dyspeptic patients by means of immunoblotting of supernatants from antral biopsy and gastric mononuclear cell cultures. 76 of 78 patients with chronic gastritis, 2 of 8 with reactive gastritis, and 1 of 14 subjects with normal mucosa showed positive responses. Of patients with chronic gastritis, 75%, 83%, 97% and 76%, respectively, showed responses to the 120 kDa, 90 kDa, 61 kDa, and 31 kDa proteins. None of the 19 patients with chronic gastritis who did not recognise the 120 kDa protein had peptic ulcers, whereas 25 of 57 with positive recognition had peptic ulcers (p less than 0.001). Mucosal recognition of the H pylori 120 kDa protein was also positively associated with the activity of gastritis (polymorph infiltration) (p less than 0.002) and with the extent of surface degeneration (p less than 0.01). These findings suggest that 120-kDa-positive strains of H pylori have pathogenic features associated with active gastritis and peptic ulceration. Infection with 120-kDa-negative strains may explain why peptic ulceration develops in only a proportion of subjects infected with H pylori. 
Surgical cure of cardiac arrhythmia. 1969. The first surgical procedure undertaken for the intended purpose of curing a patient with recurrent tachycardia was performed by Sealy in 1968, and the report of that operation was published in The Annals of Thoracic Surgery in 1969. The first attempted accessory bundle ablation was successful, marked the beginning of cardiac arrhythmia surgery, and has set the standard against which other methods of arrhythmia control must be measured. 
Traumatic esophageal rupture: unusual cause of acute mediastinal widening. We have presented the case of a 32-year-old man who sustained blunt trauma to the chest in a motor vehicle accident. Plain roentgenograms showed a widened mediastinum and pneumomediastinum, and an esophagogram with water-soluble contrast material showed an esophageal laceration at the T-4 level. 
Prognostic factors in invasive bladder carcinoma in a prospective trial of preoperative adjuvant chemotherapy and radiotherapy Clinical and pathologic factors were analyzed in 40 patients with localized muscle-invasive bladder carcinoma treated in a prospective bladder-preserving program consisting of transurethral tumor resection, neoadjuvant chemotherapy (methotrexate, cisplatin, and vinblastine [MCV]), and 4,000 cGy radiotherapy with concurrent cisplatin. Patients with biopsy-proven complete response after chemotherapy and 4,000 cGy radiation received full-dose radiotherapy (6,480 cGy) with cisplatin. Cystectomy was recommended to patients with residual disease. Distant metastasis rate was associated with tumor stage and size: 0% in T2 patients, 39% in T3-4 patients (P = .035), 6% for tumors less than 5 cm, and 59% for tumors greater than or equal to 5 cm (P = .002). Risk of bladder tumor recurrence was higher in patients with tumor-associated carcinoma in situ (CIS; 40%) than those without CIS (6%; P = .075). Papillary tumors and solid tumors both had similar treatment outcomes. By multivariate analysis, tumor stage T2 (P = .04) and absence of CIS (P = .03) were significant predictors of complete response; CIS was predictive of local bladder recurrence (P = .07); and tumor size (P = .03), response after chemoradiotherapy (P = .02), and vascular invasion (P = .08) were associated with distant metastasis. Six of eight local bladder tumor recurrences were superficial tumors. The low actuarial distant metastasis rate of T2 patients (0% at 3 years), the 3-year actuarial overall survival rates for T2 (89%) and T3-4 (50%) patients, and the similar treatment outcomes for papillary versus solid tumors are encouraging when compared with published historical controls. These results provide preliminary evidence (median follow-up, 30 months) that the current chemoradiotherapy regimen may have beneficial effects in the treatment of muscle-invasive bladder carcinoma. The true efficacy of neoadjuvant chemotherapy remains to be proven by ongoing randomized trials. 
Anaesthetic-induced ventricular tachyarrhythmia in Jervell and Lange-Nielsen syndrome. A four-year-old deaf girl with a history of convulsions developed polymorphous ventricular tachycardia during induction of anaesthesia. The arrhythmia reverted to sinus rhythm spontaneously. Post-anaesthetic ECG showed marked prolongation of the QTc interval (570-690 msec). Deafness and prolonged QTc interval in association with microcytic-hypochromic anaemia confirmed the diagnosis of the Jervell and Lange-Nielsen syndrome. This case report highlights the potentially lethal complication of halothane anaesthesia in patients with long QTc interval syndrome. 
N-(fluorenyl-9-methoxycarbonyl) amino acids, a class of antiinflammatory agents with a different mechanism of action [published erratum appears in Proc Natl Acad Sci U S A 1991 Mar 15;88(6):2612] Several members of a series of N-(fluorenyl-9-methoxycarbonyl) amino acids were found to possess a broad spectrum of antiinflammatory activity. The compounds were active against oxazolone dermatitis in mice and adjuvant arthritis in rats, models in which activated T lymphocytes are implicated. The compounds also inhibited T-lymphocyte activation in vitro, assessed by using the mixed lymphocyte reaction. The compounds inhibited the reversed passive Arthus reaction in rats and arachidonic acid-induced dermatitis in mice, models in which leukocyte infiltration is responsible for the inflammatory reaction. More complete evaluation was made of one compound, N-(fluorenyl-9-methoxycarbonyl)leucine (NPC 15199). On histologic examination after arachidonic acid administration, NPC 15199 was found to block recruitment of neutrophils into the inflammatory site. The compound was not a general myelotoxin. Prolonged treatment of animals did not alter bone-marrow progenitor number or the numbers of circulating white blood cells. Further, several white cell functions were not inhibited in vitro, including neutrophil respiratory burst and macrophage phagocytosis. NPC 15199 was effective in blocking antigen arthritis in rabbits and was effective in a therapeutic protocol, reversing oxazolone edema. These studies suggest that N-(fluorenyl-9-methoxycarbonyl) amino acids may be valuable therapeutic agents for inflammatory diseases. 
10 year review of invasive aspergillosis detected at necropsy. Between 1980 and 1989, 32 cases of invasive aspergillosis were identified out of 2315 consecutive necropsies, an incidence of 1.4%. The incidence in immunosuppressed "high risk" patients was 10.7%. Twenty out of 32 cases showed spread beyond the lungs, with the brain the most common site. There was an increase in cases in the second half of the decade, attributable to the start of a liver transplantation programme. Liver transplant recipients and patients with haematological malignancies were at significantly greater risk of acquiring aspergillosis than kidney transplant recipients or those with solid malignancies treated with chemotherapy. There was also a greater risk of haematogenous dissemination in liver transplant recipients than in all other groups, and this was significantly associated with the use of high dose steroids as anti-rejection treatment. Aspergillus was isolated during life in only eight cases, which indicates a continuing need for and emphasises the value of necropsy. 
Antibodies to cytoplasmic sequences of cloned liver growth hormone (GH) receptors recognize GH receptors associated with tyrosine kinase activity. GH stimulates tyrosyl phosphorylation of GH receptors in 3T3-F442A fibroblasts, and highly purified GH receptor preparations exhibit tyrosine kinase activity. Paradoxically, however, the GH receptor cloned from liver exhibits no sequence similarity to receptors with known signal transduction mechanisms, including those exhibiting ligand-activated tyrosine kinase activity. These observations raise the possibility that there are two kinds of receptors for GH: the first represented by the cloned liver GH receptor, and the second by a tyrosine kinase-containing GH receptor. To inquire into the possibility of two distinct GH receptors, we determined whether the cloned liver GH receptor shares structural similarities with the tyrosine kinase-associated GH receptor. When the cloned rabbit liver GH receptor is expressed in human kidney 293 cells, it migrates with a mol wt appropriate for the tyrosine kinase-associated GH receptor, despite the calculated mol wt of the cloned GH receptor being 60,000 smaller than that of the tyrosine kinase-associated GH receptor. The recognition of tyrosine kinase-associated GH receptor by antipeptide antibodies to three different epitopes on the cytoplasmic domain of the cloned liver GH receptor was also tested. Tyrosyl phosphorylated [125I]human GH-receptor complexes were prepared by immunoprecipitation with phosphotyrosyl-binding antibody; this subpopulation of GH-receptor complexes was recognized by all three antipeptide antibodies. The antibodies also recognized similarly isolated tyrosyl phosphorylated GH-receptor complexes, which had been further phosphorylated in solution on tyrosyl residues upon addition of [gamma 32P] ATP. Furthermore, highly purified GH receptors prepared by sequential immunoprecipitation using phosphotyrosyl-binding antibody and any one of the three antipeptide antibodies incorporated 32P into tyrosyl residues upon the addition of [gamma 32P] ATP. These results provide evidence that tyrosine kinase-associated GH receptors share sequence similarity in the cytoplasmic domain with the cloned liver GH receptor. The cloned GH receptor and the tyrosine kinase-associated GH receptor, therefore, are likely to be the same receptor or related receptor isoforms. 
Malignant potential of the cryptorchid testis. A follow-up study of 224 male patients from Rochester, Minnesota, diagnosed with cryptorchidism during the period from 1935 through 1974 was conducted to assess the frequency of subsequent testicular neoplasms. Age-specific rates for testicular neoplasm in this community were used to estimate an expected number for comparison with that observed. Two malignant testicular neoplasms have occurred in this cohort; thus, the standardized morbidity ratio was 11.4 (95% confidence interval, 1.4 to 41.1). Of the 158 patients born in the community, 11% were known to have birth weights of less than 2,500 g, approximately twice the expected occurrence. Increased risks were also noted for inguinal hernia, hypospadias, Down's syndrome, cleft lip or palate (or both), clubfoot, and congenital heart disease, for which the standardized morbidity ratios were 3.6, 4.7, 17.8, 11.3, 11.7, and 2.7, respectively. The increased risk for malignant neoplasms observed in this cohort of patients with cryptorchidism is consistent with that found in earlier studies. 
An analysis of sequential physiologic changes in hypoxic cor pulmonale during long-term oxygen therapy. Physiologic changes were studied retrospectively in 37 patients with hypoxic cor pulmonale who died during long-term oxygen therapy (LTOT). The subjects were assessed during periods of clinical stability for each year on LTOT. At the onset of treatment, their mean age (+/- SEM) was 60.0 +/- 1.3 years, and at the time of death, they were aged 65.0 +/- 1.3 years. The median duration of LTOT was five years. For each year leading up to death, mean values of FEV1, PaO2, and PaCO2 were obtained. A rate of decline of FEV1 of 73 +/- 10 ml/yr was observed, and this was accompanied by a decline in PaO2 of 0.47 +/- 0.01 kPa/yr. Patients died with a mean FEV1 of 0.55 +/- 0.04 L and a PaO2 of 5.1 +/- 0.2 kPa. A small rise in PaCO2 occurred, on average 0.25 +/- 0.09 kPa/yr, throughout the study, but accelerating in many cases during the three years before death. Hypoxic cor pulmonale appears to be associated with a rapid deterioration in airway function, a steady decline in PaO2, and a slow rise in PaCO2 during the years leading up to death. These physiologic changes measured in a stable clinical state while breathing air appear to occur in spite of LTOT. The LTOT may merely prevent death from episodes of severe hypoxemia while the pathophysiologic changes in the lung progress. Hence the benefit to be expected from LTOT is only temporary. Generally, those patients with lower levels of FEV1 will obtain diminishing clinical benefit, inversely related to the severity of airflow obstruction at the time of commencement of LTOT. 
Non-infective verrucous endocarditis in a patient with 'primary' antiphospholipid syndrome. A 27-year-old women with 'primary' antiphospholipid syndrome, who developed a haemodynamically significant non-infective verrucous endocarditis is reported. Her mother suffered from antiphospholipid syndrome associated with systemic lupus erythematosus. A pathogenetic role of antiphospholipid antibodies in heart valve lesions is suggested. 
Homozygous prion protein genotype predisposes to sporadic Creutzfeldt-Jakob disease [published erratum appears in Nature 1991 Aug 8;352(6335):547] The human prion diseases, Creutzfeldt-Jakob disease (CJD) and Gerstmann-Straussler syndrome (GSS), are neurodegenerative diseases that are unique in being both infectious and genetic. Transmission of both diseases and the animal spongiform encephalopathies (for example, scrapie and bovine spongiform encephalopathy) to experimental animals by intracerebral inoculation with brain homogenates is well documented. Despite their experimental transmissibility, missense and insertional mutations in the prion protein gene are associated with both GSS and familial CJD, demonstrating that the human familial cases are autosomal dominant diseases. More than 80% of CJD cases occur sporadically, however, and are not known to be associated with mutations. Here we report that 21 of 22 sporadic CJD cases and a further 19 of 23 suspected sporadic CJD cases are homozygous at the polymorphic amino-acid residue 129; 51% of the normal population are heterozygous at this site. We argue that homozygosity predisposes towards sporadic CJD and that this directly supports the hypothesis that interaction between prion protein molecules underlies the disease process. 
Radiation therapy for primary carcinoma of the extrahepatic biliary system. An analysis of 63 cases. From 1976 to 1988, 63 patients received radiation therapy for primary cancers of the extrahepatic biliary system (eight gallbladder and 55 extrahepatic biliary duct). Twelve patients underwent orthotopic liver transplantation. Chemotherapy was administered to 13 patients. Three patients underwent intraluminal brachytherapy alone (range, 28 to 55 Gy). Sixty patients received megavoltage external-beam radiation therapy (range, 5.4 to 61.6 Gy; median, 45 Gy), of whom nine received additional intraluminal brachytherapy (range, 14 to 45 Gy; median, 30 Gy). The median survival of all patients was 7 months. Sixty patients died, all within 39 months of radiation therapy. One patient is alive 11 months after irradiation without surgical resection, and two are alive 50 months after liver transplantation and irradiation. Symptomatic duodenal ulcers developed after radiation therapy in seven patients but were not significantly related to any clinical variable tested. Extrahepatic biliary duct cancers, the absence of metastases, increasing calendar year of treatment, and liver transplantation with postoperative radiation therapy were factors significantly associated with improved survival. 
Correlation of the antiproliferative effect and the Mx-homologous protein induction by IFN in patients with malignant melanoma. The human interferon-induced intracellular protein homologous to the murine Mx-protein has recently been identified by means of a specific monoclonal antibody. Three of six melanoma cell lines elicited this intracellular human Mx-homolog upon incubation with IFN-alpha or IFN-gamma, yet all six melanoma cell lines tested were susceptible to the antiproliferative effect of IFN-alpha and IFN-gamma. Compared per antiviral unit, IFN-gamma had weaker Mx-inducing but stronger antiproliferative activity than IFN-alpha. These data suggest that the IFN-induced Mx-homologous protein is not involved in the antiproliferative action of IFN on malignant melanoma cell lines. Furthermore, 51 patients with advanced malignant melanoma were treated thrice weekly with 10 x 10(6) IU rIFN-alpha-2b and 6 x 10(6) nIFN-alpha, respectively. Nine of the 51 patients experienced systemic objective tumor responses (3 complete response, 6 partial response), but had Mx concentrations in their mononuclear cells equal to the Mx levels of non-responders during IFN-alpha therapy. Therefore, the level of Mx-homologous protein induced during IFN therapy is not a predictive marker for an antitumor response in malignant melanoma. 
A preliminary report of ticarcillin and clavulanate versus triple antibiotic therapy in children with ruptured appendicitis. Standard therapy for childhood ruptured appendicitis includes combination antibiotic therapy with ampicillin, gentamicin and clindamycin. Complicated dosing schedules and the possibility of aminoglycoside toxicity make alternatives desirable. One such alternative is Timentin (a combination agent of ticarcillin disodium and clavulanate potassium). This agent has a more convenient dose schedule than standard therapy and eliminates the possibility of aminoglycoside ototoxicity and nephrotoxicity. It is active in vitro against most pathogens associated with ruptured appendicitis in children. The preliminary results of an ongoing prospective, open label, randomized trial comparing ticarcillin and clavulanate with ampicillin, gentamicin and clindamycin in childhood ruptured appendicitis are reported herein. While further evaluation is necessary, we have found single agent therapy with ticarcillin and clavulanate to be equivalent in safety and efficacy to standard combination therapy. Also discussed are the relative merits of immediate versus delayed primary closure of the abdominal wound after appendectomy. 
Spondyloepiphyseal dysplasia congenita. Caesarean section under epidural anaesthesia. Spondyloepiphyseal dysplasia congenita is a rare condition with several features of concern to the anaesthetist. The patients are of extremely short stature and the presence of kyphoscoliosis may lead to significant respiratory impairment. Cervical vertebral body changes can result in spinal cord compression and laryngotracheal stenosis may be present. The management of such a patient presenting for elective Caesarean section under epidural anaesthesia is described. 
Peripheral odontogenic fibroma: a clinicopathologic study. The clinicopathologic features of 30 cases of peripheral odontogenic fibroma are reviewed. The age distribution is wide (11 to 76 years), and there is a slight predilection for males. The majority of the lesions (93%) occurred in blacks on the attached gingiva, and with equal frequency in the maxilla and mandible. Size varied between 1 and 3 cm in diameter. One case recurred after 14 months. Histologically, the lesions are nonencapsulated and poorly delineated. The amount of odontogenic epithelium varies considerably and consists usually of small islands or strands, although larger follicles are sometimes present. In one case the epithelial cells had a clear cytoplasm, whereas in another it was granular and eosinophilic. Origin from the surface oral mucosa can sometimes be seen. The connective tissue component is usually cellular, but collagenous, myxomatous, and mixed forms occur. Calcifications were present in 22 cases and consisted of tissue interpreted as either dentinoid, cementum, bone, or dystrophic calcific material. 
Early constrictive pericarditis and anemia after Dressler's syndrome and inferior wall myocardial infarction. Early constrictive pericarditis and anaemia developed in a 52 year old man after he had an inferior wall myocardial infarction complicated by Dressler's syndrome. Total pericardiectomy at the time of coronary artery bypass surgery resulted in complete resolution of signs and symptoms. 
Spontaneous hepatic copper accumulation in Long-Evans Cinnamon rats with hereditary hepatitis. A model of Wilson's disease. Long-Evans Cinnamon (LEC) rats, an inbred strain of a mutant rat isolated from Long-Evans rats, develop hereditary hepatitis. To elucidate the role of copper metabolism in the development of the hepatitis in LEC rats, we examined the copper concentration in the tissues and serum levels of copper and ceruloplasmin. Copper concentration in the liver of LEC rats was over 40 times that of normal Long-Evans Agouti (LEA) rats, while the serum ceruloplasmin and copper concentrations in LEC rats decreased significantly. The hepatocytes of LEC rats show steatosis in cytoplasm and pleomorphism of mitochondria, resembling the histologic features of the liver in Wilson's disease. These findings suggest that the hereditary hepatitis in LEC rats is closely associated with copper toxicity, and may be dealing with a rat form of Wilson's disease. Thus the LEC rats will provide a unique and useful animal model for clarifying the mechanism and for developing treatment strategies for Wilson's disease and other abnormal copper metabolism in humans. 
Dietary fiber and bowel function in tube-fed patients. In tube-fed patients, dietary fiber is often used to manage constipation/diarrhea. Dietary fiber consists of water-soluble and insoluble plant compounds that are resistant to digestion by small-bowel enzymes but are fermented to varying degrees by colonic bacteria. Many physiologic effects of fiber may be related to the degree of fermentation. Few controlled studies of fiber-containing tube feedings have been performed. These studies have limitations and are nondefinitive as to whether fiber prevents or controls constipation/diarrhea. Constipation in tube-fed patients has not been shown to respond to mixed soluble/insoluble fiber in the few studies performed to date. Likewise, fiber may be of only limited benefit in controlling diarrhea in acute illness because of such factors as stress or medication. Fiber does play a role in maintaining gut integrity in all patients, whether they have diarrhea or not. Fiber may be recommended as part of a standard tube-feeding regimen to help assure gut mucosal integrity but not specifically to treat constipation/diarrhea. Further studies are necessary before the role of fiber in the management of constipation/diarrhea in tube-fed patients is determined. 
Interrelationship of blood transfusion, non-A, non-B hepatitis and hepatocellular carcinoma: analysis by detection of antibody to hepatitis C virus. To clarify the relationship between hepatitis C virus infection and the development of hepatocellular carcinoma as sequelae of non-A, non-B posttransfusion hepatitis, 231 patients with chronic non-A, non-B hepatitis (96 with chronic hepatitis, 81 with cirrhosis and 54 with hepatocellular carcinoma) were analyzed for antibody to hepatitis C virus and were compared with 125 patients with chronic hepatitis B (50 with chronic hepatitis, 46 with cirrhosis and 29 with hepatocellular carcinoma). Antibody to hepatitis C virus was detected in 89.6%, 86.4% and 94.4% of patients with non-A, non-B hepatitis-related chronic hepatitis, cirrhosis and hepatocellular carcinoma, respectively, compared with 6%, 17.4% and 34.5% with similar diseases related to hepatitis B. A history of transfusion was documented in 52%, 33% and 42% of anti-hepatitis C virus-positive cases of chronic hepatitis, cirrhosis and hepatocellular carcinoma. The mean intervals between the date of transfusion and the date of diagnosis of anti-hepatitis C virus-positive chronic hepatitis, cirrhosis and hepatocellular carcinoma were 10, 21.2 and 29 yr, respectively. In 21 patients with transfusion-associated hepatocellular carcinoma, anti-hepatitis C virus was present in each serial sample available for testing, including samples obtained up to 14 yr before the diagnosis of hepatocellular carcinoma. These data suggest the slow, sequential progression from acute hepatitis C virus-related non-A, non-B hepatitis through chronic hepatitis and cirrhosis to hepatocellular carcinoma and support a causal association between hepatitis C virus and hepatocellular carcinoma. 
Efficient management of adrenal tumors. A retrospective analysis was carried out on 121 patients with primary adrenal tumors operated on at 2 Vancouver hospitals between the years 1970 and 1990. The purpose of the study was to identify discriminating factors between the various diagnoses in order to minimize both the time and the cost of the investigative process. There were 57 cortical adenomas, 35 pheochromocytomas, 15 carcinomas, 8 cases of cortical hyperplasia, and 6 miscellaneous tumors. The mean time from the onset of symptoms to diagnosis of those patients presenting with an identifiable syndrome was 48.3 months. Those with a hypertensive syndrome presented significantly later than those with Cushing's syndrome (57.7 months versus 22.8 months, p less than 0.01). There was a significant delay in diagnosis in those patients with hypertension on the basis of an aldosteronoma as compared with those with hypertension secondary to a pheochromocytoma (75.4 months versus 36.1 months, p = 0.02). Cortical carcinomas were significantly larger than benign cortical tumors (12.7 cm versus 5.5 cm). No malignant neoplasm measured less than 5 cm in diameter. Diagnostic sensitivity for intravenous pyelogram (IVP) was 59%, for ultrasound 71%, for venography 50%, for meta-iodobenzylguanidine (MIGB) (pheochromocytoma only) 80%, and for angiography 70%. However, for those patients with adrenal carcinomas, angiography was positive in 100% of cases. Computed tomography (CT) was the most sensitive localizing investigation with a sensitivity of 98%. While other localizing techniques were less sensitive than CT, they may still play a useful role in selected situations. Factors causing delay in diagnosis and the role of the various imaging modalities are discussed. 
Epicardial coronary artery tone and reactivity in patients with normal coronary arteriograms and reduced coronary flow reserve (syndrome X) The vasomotor response of proximal and distal angiographically normal coronary artery segments was studied in 12 patients with syndrome X, 17 age- and gender-matched patients with chronic stable angina and 10 control subjects with atypical chest pain and a normal coronary arteriogram. Ergonovine (300 micrograms by intravenous injection) and isosorbide dinitrate (1 mg by intracoronary injection) were administered to all patients. Computerized coronary artery diameter measurement (angiographically normal segments only) was carried out before and after the administration of ergonovine and nitrate. Baseline intraluminal diameters (mean +/- SEM) of proximal and distal coronary segments were not significantly different in control subjects and patients with syndrome X or coronary artery disease (proximal 2.88 +/- 0.19, 3.01 +/- 0.13 and 2.86 +/- 0.13 mm; distal 1.57 +/- 0.09, 1.70 +/- 0.10 and 1.61 +/- 0.06 mm, respectively). With ergonovine, proximal segments constricted by 10 +/- 2%, 7 +/- 2% and 11 +/- 3% and distal segments by 12 +/- 3%, 14 +/- 3% and 14 +/- 2% in control subjects and patients with syndrome X or coronary artery disease, respectively (p = NS). With isosorbide dinitrate, proximal coronary segments dilated by 11 +/- 2%, 10 +/- 2% and 8 +/- 2% (p = NS) and distal segments by 15 +/- 2%, 11 +/- 3% and 13 +/- 2% (p = NS) in control subjects and patients with syndrome X or coronary artery disease, respectively. Within groups, constriction in response to ergonovine and dilation in response to nitrate were not significantly different in proximal and distal segments. 
Safety of alcohol after viral hepatitis. To test the validity of the generally held belief that moderate consumption of alcohol during convalescence from acute viral hepatitis adversely affects outcome, 87 adults recovering from acute viral hepatitis (hepatitis A in 36, hepatitis B in 34, hepatitis non-A, non-B in 17) were studied. Criteria for entry to the study attempted to ensure that no patient was a chronic hepatitis B carrier. Patients were randomised either to a moderate alcohol intake, or to continued complete abstention. Drinkers consumed 26 g alcohol daily (mean) and none remained abstinent. At 3 months all patients were well, with normal liver function tests. There were no significant differences between the two groups at anytime. The findings suggest that moderate alcohol intake during convalescence from acute viral hepatitis does not seem to be harmful. 
Involvement of the retinoblastoma gene in primary osteosarcomas and other bone and soft-tissue tumors. The retinoblastoma (Rb) gene, thought by some to be associated with tumor formation of retinoblastoma as a recessive human oncogene, was investigated in 57 cases using DNA and RNA from primary osteosarcomas and other bone and soft-tissue tumors. Eight of 23 osteosarcoma cases (35%) showed structural alterations of the Rb gene. Three of the eight demonstrated homozygous deletions, and the remaining five cases showed heterozygous deletions. Seven out of eight cases represented deletion of a 7.5-kb HindIII fragment. Northern blot analysis of five cases of osteosarcoma showed that four demonstrated no detectable Rb gene transcription, and one case had a truncated 3.5-kb fragment with a faint 4.7-kb band. In the other 34 cases of bone and soft-tissue tumors, two cases of three malignant fibrous histiocytomas showed an Rb gene abnormality by Southern blot analysis. These results strongly suggest that Rb gene alteration is pertinent to the tumorigenesis of most osteosarcoma cases and some other bone and soft-tissue tumors. 
Identification of alloimmunized patients: use of radiolabeled allogeneic platelet kinetic measurements and platelet antibody tests. In a group of stable, nonthrombocytopenic leukemia patients awaiting bone marrow transplantation, results of paired allogeneic radiolabeled platelet kinetic measurements were correlated with the results of several different platelet and lymphocytotoxic antibody tests to determine which parameters could be used to identify patients who were alloimmunized to platelets. Seven patients with acute leukemia who had been transfused during induction therapy were used as the test group, and, as a control group, five untransfused patients with chronic myelogenous leukemia were also studied. Concurrent fibrinogen survival measurements were performed in all patients to assess whether hemostatic factor consumption (ie, disseminated intravascular coagulation) was present. Allogeneic platelet survival measurements were reduced from normal in all 12 study patients. In 8 of 12 patients, fibrinogen and platelet survival measurements were comparably reduced, suggesting disease-related platelet consumption. In four heavily transfused patients with acute leukemia, allogeneic platelet survivals were markedly reduced to less than or equal to 2.1 days, compared with the 3.5- to 7.4-day platelet survival measurements found in the other eight patients. The disproportionately short platelet survivals compared with fibrinogen survival measurements in these four patients, combined with documented positive antibody tests to their donors' platelets in the three patients with evaluable tests, suggested that these patients had become alloimmunized to platelets because of their prior transfusions. There was substantial concordance between the two radiolabeled allogeneic donor platelet survival measurements performed in each of these patients, suggesting that host rather than donor factors have a major influence on transfusion outcome (r = .93, P less than .001). The platelet cross-match tests, using the radiolabeled protein Staph A assay combined with the IgG enzyme-linked immunosorbent assay test, had the best correlation with the posttransfusion recovery and survival of the donors' platelets. 
Comparison of IgG antibody profiles by immunoblotting in patients with acute and previous Toxoplasma gondii infection. The IgG antibody profile to Toxoplasma gondii proteins of less than 37 kilodaltons in sera from patients with acute and previous infection was studied by immunoblotting. Bands at 28, 29, and 36 kilodaltons were more common in acute infection (10 out of 10, nine out of 10, and nine out of 10, respectively) compared with previous infection (five out of 10, four out of 10, and one out of 10, respectively). The 6 kilodalton band was present in 10 out of 10 sera from patients with acute infection and five out of 10 sera from those with previous infection. A new observation is a doublet of bands of 22-25 kilodaltons present only in sera from patients with acute infection. This doublet may be a more reliable indicator of acute infection than the 6 kilodalton band. 
Effect of enteral nutrition on exocrine pancreatic function. Twelve patients with chronic pancreatitis underwent a pancreatoduodenectomy in which the pylorus was preserved. The effects of parenteral and enteral nutrition on pancreatic secretion were compared. Postoperative nutrition was administered by needle-catheter jejunostomy in seven patients and by total parenteral nutrition in five patients. Pancreatic juice, drained directly from the pancreatic duct, was collected in 4-hour fractions. Volume, bicarbonate, protein, amylase, and chymotrypsin were measured. In the first two postoperative days, there was a slow increase in all measured indices. On the third postoperative day, an abrupt rise occurred, after which pancreatic secretion stabilized. No differences in exocrine pancreatic secretion were observed between the enteral and parenteral methods of feeding. 
Cytogenetic abnormalities associated with renal cell carcinoma. Cytogenetic analysis was performed on 23 renal cell carcinomas (21 sporadic and 2 associated with von Hippel-Lindau's disease). Clonal chromosomal abnormalities were found in 19 of 21 of the sporadic tumors. The most frequent abnormalities were a loss or rearrangement of material in 3p (11 of 21 cases) or an extra chromosome 7 (7 of 21 cases). Correlation between specific chromosomal abnormalities and clinical presentation was absent with the exception of trisomy 7 and -Y, which occurred only in patients more than 60 years old. An increasing number of cytogenetic abnormalities were associated with a greater likelihood of renal vein and/or capsule involvement. Both patients with von Hippel-Lindau's disease had tumors with a normal karyotype. 
Endothoracic endoesophageal pull-through operation. A new approach to cancers of the esophagus and proximal stomach. Many thoracic surgeons have expressed concern about the complications inherent in transhiatal esophagectomy without thoracotomy. The technique of endothoracic endoesophageal pull-through uses a mucosal coring of normal esophagus beyond the tumor and leaves a muscular tube through which the substitute organ is passed. Mediastinal hemorrhage, tracheal injury, and chylothorax are eliminated. 
Effect of anticoagulant on biocompatibility in membrane plasmapheresis. The effect of heparin or citrate anticoagulation on blood cellular, complement pathway and coagulation pathway was investigated in a membrane plasma exchange procedure. Two membrane plasma separators constructed of cellulose di-acetate (CA) and polyvinyl chloride (PVC) were evaluated with heparin or citrate alone for anticoagulation in a 26 year old male with myasthenia gravis. Maximum white blood cell counts decrease was 21% at 30 min for the CA with heparin while no decrease was observed for the other schemes. Platelet counts changes were comparable between heparin and citrate, while the PVC groups showed less changes than the CA groups. The CA groups, regardless of the type of anticoagulant used, indicated that complement activation occurred via the classical pathway within the module in addition to the activation via alternative pathway for the CA with heparin. In the PVC groups, complement activation was noted to occur only when heparin was used for anticoagulation. PT and PTT showed slight increases with citrate, while they were remarkably prolonged with heparin. Citrate showed less changes in cellular and humoral factors compared to heparin. CA with heparin was the most activating combination of membrane material and anticoagulant, while the PVC with citrate was the least activating combination. 
An innovative method for neuraxis radiotherapy using partial transmission block technique. Whole CNS (neuraxis) radiotherapy is an important part of therapy for certain CNS tumours which seed via the CSF. Many, if not the majority, of these predominantly young patients are cured but the neuropsychometric, neuroendocrine and growth morbidity of neuraxis radiotherapy on children by conventional methods may be considerable; patients receiving such therapy at an early age often are eventually in the educationally subnormal category. Recent radiobiological data support the concept that all aspects of CNS radiation tolerance are heavily dependent on daily fraction size. We describe a new radiotherapy technique that allows lower daily fraction sizes to be delivered to the neuraxis without prejudicing the total dose to the neuraxis or primary area and without prolonging the overall treatment time. Published radiobiological data support the concept that all the major morbidities attributed to conventional neuraxis radiotherapy will be reduced by the currently described technique without reducing tumour control rates. 
Surgical anatomy of the sacrum. A guide for rational screw fixation. Anterior sacral anatomy was studied to allow safe sacral screw placement. The study included 27 bony sacra. Intrapelvic dissections were performed. Cadaveric specimens were dissected and photographed. The position and angulation of the first sacral foramen was extremely variable. After the position of the L5 root, sacral roots, and iliac vessels, was considered, safe posterior sacral screw implantation could be assured through placement above the level of the first sacral foramen directed medially toward the promontory, parallel to the superior sacral end-plate. Complications of indiscriminate screw placement included L5-root damage, iliac vein penetration, and intractable perineal pain due to sacral root injury. Preoperative computed tomography with the scanner gantry tilted to parallel the superior sacral end-plate defined the great vessels, neural foramens, inclination of the superior sacral end-plate, and prominence of the posterior ileum. Surgical accuracy was evaluated after surgery with computed tomography. 
Facial resurfacing in xeroderma pigmentosum with monoblock full-thickness skin graft. A case of xeroderma pigmentosum with multiple skin tumors on the face that was treated with total excision and replacement of face skin except the eyelids with a monoblock full-thickness abdominal skin graft is reported. The quality and tumor-free features of the monoblock full-thickness skin graft in xeroderma pigmentosum are indicated. Despite the increased morbidity of the donor region, the radical surgical approach advocated here has improved the prognosis in the case reported. 
Comparison of dexamethasone and ondansetron in the prophylaxis of emesis induced by moderately emetogenic chemotherapy. A multicentre, randomised, double-blind, cross-over trial was done to compare the efficacy and safety of a serotonin receptor antagonist--ondansetron--and dexamethasone in the prophylaxis of acute and delayed emesis and nausea induced by moderately emetogenic non-platinum-containing chemotherapy regimens. Patients were treated as outpatients and received intravenous ondansetron 4 mg or dexamethasone 8 mg before chemotherapy and oral maintenance (ondansetron 4 mg every 6 h and dexamethasone reducing from 4 mg to 1 mg 6-hourly between days 1 and 5) for 5 days. 112 patients were treated (38 men, 73 women, 1 with no gender recorded; age range 30-73 years) and 100 were evaluable for cross-over analysis. Patients taking ondansetron or dexamethasone reported no significant difference in complete and major control of acute (83% vs 79%, p = 0.46) or delayed (82% vs 88%, p = 0.214) emesis (vomiting plus retches). Significantly more patients on dexamethasone (87%) than on ondansetron (72%) reported control of delayed nausea (days 2-5) (p = 0.003). Both drugs were well tolerated with no significant difference in the number of adverse events, and this is reflected by similar patient preference for ondansetron (40%) and dexamethasone (30%) (p = 0.244). Both drugs offer adequate out-patient control of chemotherapy-induced emesis; however, dexamethasone has an advantage in the control of delayed nausea, and also in terms of cost and resource allocation. 
Menstrual symptoms in women with pelvic endometriosis. OBJECTIVE--To investigate menstrual symptoms in relation to pelvic pathology. DESIGN--A prospective questionnaire-based study. SETTING--Aberdeen Royal Infirmary, Scotland. SUBJECTS--1250 questionnaires were sent out prior to planned admission and 1200 women (96%) brought the completed questionnaires. They comprised 598 women undergoing laparoscopic sterilization, 312 having laparoscopy because of infertility, 156 having laparoscopy because of chronic pelvic pain and 134 women undergoing abdominal hysterectomy for dysfunctional uterine bleeding. MAIN OUTCOME MEASURES--The occurrence of dysmenorrhoea, menorrhagia, menstrual regularity, premenstrual spotting, deep dyspareunia and pelvic pain in women with either endometriosis and post infective pelvic adhesions or a normal pelvis. RESULTS--Menorrhagia, menstrual irregularity and premenstrual spotting occurred with equal frequency in all groups. Deep dyspareunia, pain after intercourse and recurrent pain unrelated to menstruation or coitus was more common in women with endometriosis and those with post infective pelvic adhesions than in those with a normal pelvis. Dysmenorrhoea appears to be more prevalent among women having endometriosis. CONCLUSIONS--Menstrual symptoms, while raising a high index of suspicion for endometriosis, are not entirely reliable as indicators of disease. Dysmenorrhoea is the most common reported symptom in endometriosis sufferers. Diagnostic laparoscopy should be considered before institution of treatment in women complaining of pelvic pain and menstrual symptoms. 
Increased postoperative pain and consumption of analgesics following acupuncture. Acupuncture was given to patients before (preoperative-acupuncture group, PRE-ACU, n = 25) or after (postoperative-acupuncture group, POST-ACU, n = 25) operative removal of impacted mandibular third molars. Sixty patients did not receive acupuncture and participated as a control group (CG). All patients completed a questionnaire in order to characterize state tension and stress, degrees of neuroticism, extroversion, depression and psychosomatic disorders. We also recorded intraoperative discomfort and pain intensity, postoperative pain intensity and consumption of analgesics for 72 h. The PRE-ACU was significantly more tense following surgery and found the operative procedure more unpleasant than the other two groups. The PRE-ACU further rated intraoperative pain intensity higher than the CG and experienced higher pain intensity immediately postoperatively compared with POST-ACU and CG. Of the PRE-ACU patients 15/24 needed additional local anesthesia intraoperatively while none in the POST-ACU or CG requested extra lidocaine. Postoperatively patients in both PRE- and POST-ACU reported a higher total sum of pain scores (pain intensity) and the PRE-ACU consumed more analgesics compared with the CG. A significantly larger number of patients suffering from "dry socket" (a complication during wound healing) was found in both PRE- and POST-ACU compared with the CG. No correlation was found between assessed personality characteristics and reported postoperative pain/consumption of analgesics in any group and could thus not explain the observed differences between the groups. The reason for our unexpected "negative" findings is unclear but some hypothetical explanations are discussed. 
Reduced D2 dopamine and muscarinic cholinergic receptor densities in caudate specimens from fluctuating parkinsonian patients. Binding of spiperone and 3-quinuclidinyl benzilate (QNB), both labeled with hydrogen 3 (3H), were measured in caudate tissue obtained from 8 living parkinsonian patients at the time of cerebral transplantation. This was clinically homogeneous group of patients. All remained predominantly responsive to levodopa, although with marked disability secondary to clinical fluctuations (short-duration responses) and medication-induced dyskinesias; all were receiving substantial doses of levodopa and 6 of the 8 patients were additionally receiving bromocriptine or pergolide. Binding densities of dopamine D2 receptors, as measured by [3H]spiperone binding, were reduced in this group of patients, compared to caudate specimens from autopsy control subjects. This findings may reflect medication-induced receptor downregulation. Parallel changes occurred with muscarinic cholinergic receptors; [3H]QNB binding was significantly reduced, compared to autopsy control values. This reduction of muscarinic receptors might be due to loss of nigrostriatal terminals that are known to contain muscarinic receptors. Alternatively, muscarinic receptors may have been downregulated by increased corticostriatal glutamatergic input to cholinergic cells, inferred to be present based on the prominent levodopa-induced dyskinesias. Finally, receptor deficits could have been a reflection of more widespread degenerative cerebral disease, although levodopa-refractory symptoms were generally not pronounced in these patients. 
Familial Ebstein's anomaly: a report of six cases in two generations associated with mild skeletal abnormalities. In a family of 11 persons in three generations six had Ebstein's anomaly. Five of the six showed mild skeletal anomalies--that is, restricted finger extension, with or without limitation of larger joints, and externally rotated little toes. Two other members of the family had the skeletal features without Ebstein's anomaly. The findings suggest a dominantly inherited syndrome of Ebstein's anomaly and skeletal abnormalities. The four female patients were all mildly affected whereas three of the four male patients were severely affected. 
Excimer laser-assisted femoral angioplasty: early results. The ability to ablate atheroma without generating heat makes the excimer laser wavelength a promising intraluminal technique for the treatment of arterial occlusive disease. This series reviews a preliminary experience treating patients with superficial femoral arterial disease admitted with limb-threatening ischemia or claudication. Twenty-six diseased superficial femoral arteries (5 stenotic and 21 occluded) were treated in 23 consecutive patients. Patients with claudication (18) reluctant to undergo bypass or with limb-threatening ischemia (8) at extremely high risk for surgery were included. There were 10 men and 13 women with a mean age of 67 years. A 308 nm excimer laser with an over-the-wire catheter (19) or balloon-centered end-on catheter (7) was used followed by balloon angioplasty. Twenty-four procedures were performed percutaneously, and two were performed with the vessel open in the operating room. Technical success, defined as disobliteration confirmed by angiography and greater than 0.15 increase of the ankle/brachial index, was achieved in 15 of 26. Eleven of 21 occlusions (52%) and four of five stenoses (80%) were opened. Only two of 11 lesions longer than 10 cm were successfully treated. Unsuccessful attempts (technical failure) occurred in 11 of 26 patients and resulted in four elective and one emergency femoral-popliteal bypass. Five patients were discharged with their claudication unchanged, and one had an elective amputation. Six arterial perforations with three arteriovenous fistulas occurred, all resolved without operation. No unanticipated limb loss occurred. In the 15 successful cases, the mean ankle/brachial index increase was 0.34. Seven (47%) of these 15 remain patent with a mean follow-up of 9.5 months (1.5 to 14 months). 
The transmandibular implant: a 13-year survey of its use. During the period from August 1976 until July 1989 the transmandibular implant was introduced in a total of 31 oral and maxillofacial surgery departments in the Netherlands and 1,466 patients were treated. This study includes 1,356 treated patients from 28 departments. The treatment course of 1,201 patients (89.6%) was uneventful. Of the 157 complications, 58 related to the anatomic contour of the mandible, 49 to the surgery, 25 to the prosthetic reconstruction, 8 to the psychosocial attitude of the patient, 8 to the use of medication, 5 to trauma, and 4 to the presence of a skin graft. Treatment of the complications included removal of the implant in 44 patients; in 106 patients the complication was treated satisfactorily. In the remaining 7 patients, hypesthesia was present. The reasons for the removal of the 44 implants were infection (11), operative error (5), premature loading of the implant (3), insufficient width of the mandible after a visor osteotomy (1), loss of osseointegration caused by the prosthesis (14), psychological problems (4), trauma (3), drug-related gingival hyperplasia (2), and inexplicable pain (1). The present survey shows a consistent success rate of 96.8%. 
Sinus of Valsalva aneurysm eroding into the interventricular septum. We report a case of erosion of an aneurysm of the right sinus of Valsalva into the interventricular septum. The mode of presentation, the preoperative evaluation, and the echocardiographic and nuclear magnetic resonance imaging features are presented, and the cardiac catheterization findings and surgical management of this very rare cardiac pathology are discussed. 
Some perspectives on peptic ulcer. In this article, the author comments on the following topics: whether peptic ulcer is a disease or just the sign of another process; whether the crater has a multifactorial origin; the ubiquity of Helicobacter pylori and the conclusion that a specific strain will doubtless prove to be the cause of some, but not all, ulcers; the inherent definitional problem of "nonulcer dyspepsia"; and the controversy over how much gastric acid needs to be reduced to speed the healing of peptic ulcer. 
Overlapping loss of heterozygosity by mitotic recombination on mouse chromosome 7F1-ter in skin carcinogenesis. A significant role for mouse chromosome 7 abnormalities during chemically induced skin carcinogenesis has been advanced based on previous cytogenetic and molecular studies. To determine the frequency of allelic losses at different loci of chromosome 7 in skin tumors induced in the outbred SENCAR mouse stock by a two-stage initiation-promotion protocol, we compared the constitutional and tumor genotypes of premalignant papillomas and squamous cell carcinomas for loss of heterozygosity at different informative loci. In a previous study, these tumors had been analyzed for their allelic composition at the Harvey ras-1 (Ha-ras-1) locus and it was found that 39% of squamous cell carcinomas had lost the normal Ha-ras-1 allele exhibiting 3 or 2 copies of the mutated counterpart or gene amplification. In the present study, by combining Southern blot and polymerase chain reaction fragment length polymorphism analyses, we detected complete loss of heterozygosity at the beta-globin (Hbb) locus, distal to Ha-ras-1, in 15 of 20 (75%) skin carcinomas. In addition, 5 of 5 informative cases attained homozygosity at the int-2 locus, 27 centimorgans distal to Hbb. Polymerase chain reaction analysis of DNA extracted from papillomas devoid of stromal contamination by fluorescence-activated sorting of single cell dispersions immunolabeled with anti-keratin 13 antibody revealed loss of heterozygosity at the Hbb locus, demonstrating that this event occurs during premalignant stages of tumor development. Interestingly, loss of heterozygosity was only detected in late-stage lesions exhibiting a high degree of dysplasia and areas of microinvasion. Analysis of allelic ratios by densitometric scanning of tumors that had become homozygous at Hbb but retained heterozygosis at Ha-ras-1 indicated mitotic recombination as the mechanism underlying loss of heterozygosity on mouse chromosome 7 during chemically induced skin carcinogenesis. These findings are consistent with the presence of a putative tumor suppressor gene linked to the Hbb locus in the 7F1-ter region of mouse chromosome 7, the functional inactivation of which may constitute a critical event in skin tumor progression, possibly during the malignant conversion stage. 
Human papillomavirus types 16 and 18 in adenocarcinoma of the uterine cervix. Many reports have shown a link between human papillomavirus (HPV) and cervical squamous neoplasia. However, the association of HPV with cervical adenocarcinoma has been studied less extensively. The authors evaluated the presence of HPV-DNA in 106 patients with adenocarcinoma of the uterine cervix by in situ hybridization, using 35S-labeled probes for HPV 16 DNA and HPV 18 DNA. The overall prevalence of HPV-DNA was 18% (19 of 106). HPV 16 was present in 2 (2%) cases, HPV 18 was observed in 15 (14%) cases, and both HPV 16 and HPV 18 were found in 2 (2%) cases. There was a correlation between HPV-DNA positivity and tumor stage (P less than 0.01) and tumor size (P less than 0.05), but there was no relationship between HPV-DNA positivity and tumor differentiation, proliferation (S-phase fraction), ploidy, lymph node metastases, or five-year survival rate. These results suggest that HPV 18 DNA is associated with cervical adenocarcinoma but the presence of HPV 18 has no influence on overall survival. 
Effects of hypoxaemia and bradycardia on neonatal cerebral haemodynamics. Near infrared spectroscopy has been used to assess the effects of bradycardia and hypoxia on the cerebral circulation in the premature neonate. The technique is well tolerated and can be applied in almost any infant. Continuous monitoring of changes in cerebral oxygenated, deoxygenated, and total haemoglobin is possible. Total haemoglobin is analogous to cerebral blood volume; thus information on circulatory changes as well as oxygenation state can be obtained. Twenty five babies had cerebral monitoring carried out using this technique. During episodes of hypoxia, both spontaneous and induced, impairment of haemoglobin oxygenation within the brain was detected together with an overall increase in the total mean haemoglobin concentration, which was 0.8 x 10(-2) mmol/l. Bradycardia with apnoea also led to impairment of cerebral oxygenation, and to a rapid fall in the concentration of total mean haemoglobin to 1.4 x 10(-2) mmol/l, which was followed in some cases by an increase to above the resting value on recovery of the heart rate to a mean of 0.7 x 10(-2) mmol/l. These disturbances to total haemoglobin concentration represent abnormalities of cerebral blood volume that may be implicated in the pathogenesis of neonatal cerebral injury. 
Role of combination drug therapy with a class IC antiarrhythmic agent and mexiletine for ventricular tachycardia. The combination of mexiletine and a class IC antiarrhythmic agent (encainide, propafenone or flecainide) was evaluated by electrophysiologic testing in 14 patients with a history of sustained ventricular tachycardia whose tachycardia remained inducible during therapy with the class IC drug alone. During the control drug-free state, all patients had inducible ventricular tachycardia, with a mean cycle length of 260 ms (range 190 to 400). During monotherapy with the IC agent the tachycardia remained inducible in each patient, but there was a significant increase in the cycle length to 340 ms (240 to 500) (p less than 0.001). The effective refractory period of the ventricle was not altered. Treatment with mexiletine (oral in 13 and intravenous in 1) was begun and electrophysiologic testing was repeated. Ventricular tachycardia in one patient was rendered noninducible and one patient had arrhythmia aggravation. The tachycardia in the remaining 12 patients remained inducible but its average cycle length increased further to 392 ms (340 to 460) (p = NS). Nine patients had rate slowing and the average cycle length of the ventricular tachycardia in this group was significantly increased (302 to 388 ms, p less than 0.05). The average effective refractory period was significantly increased during combination therapy (267 ms) compared with no drug therapy (235 ms) and therapy with the class IC drug alone (247 ms) (p less than 0.05). After a mean follow-up interval of 22 months, seven patients continue on the combined treatment and have no ventricular tachycardia. 
Congestive heart failure in diabetes with hypertension may be due to uncoupling of the atrial natriuretic peptide receptor-effector system in the kidney basolateral membrane. Hypertension is known to potentiate the risk of congestive heart failure (CHF) in diabetic individuals. Receptor-effector systems for atrial natriuretic peptide (ANP), which is known to regulate intracellular calcium (Ca2+), were studied in the kidney during hypertensive-diabetic cardiomyopathy in rats. Animals were divided into four groups: control, diabetic (D), hypertensive (H), and diabetic plus hypertensive (D + H). Diabetes was induced by a streptozotocin (65 mg/kg) injection and hypertension was induced by abdominal aortic constriction; studies were done at 1 and 6 weeks. Plasma ANP was increased at 1 week in the D, H, and D + H groups. There was a significant increase in the activity of Ca2+ + magnesium (Mg2+) adenosine triphosphatase (ATPase), which acts as a Ca2+ pump, in the kidney basolateral membrane from D, H, and D + H group at the 1 week study. Ca2+ + Mg2+ ATPase, on the other hand, was significantly decreased in the D + H group only at 6 weeks. This was associated with a decrease in plasma ANP, an increase in the kidney ANP receptor number, and a decrease in guanylate cyclase activity. The response of the Ca2+ pump to ANP was also attenuated. Since ANP is known to mediate its cellular effects in part by increasing Ca2+ + Mg2+ ATPase, the observed changes in the D + H group may contribute to the development of nephropathy and CHF. 
Gastrointestinal lipoma and malignancies. Twenty gastrointestinal lipomata in 18 patients are reviewed: 15 located in the colon, 3 in the distal ileum, one in the duodenum, and one in the stomach. They were found most frequently in European-born, elderly women and presented with variable abdominal symptomatology. Four lipomata were removed during endoscopy, the remainder at laparotomy, partial colectomy being performed in 10 cases. All, except 2 subserosal types, were located in the submucosa, and their average size was 2.7 cm diameter. Microscopically, none showed true encapsulation, and all were composed of mature fat cells without cellular atypia. In spite of nonspecific changes at endoscopy, one-half of the cases showed, on microscopic examination, atrophy of the overlying glands and a prominent eosinophilic and/or lymphoplasmocytic infiltration of the lamina propria. Two large subserosal lipomata were associated with Crohn's disease. In addition, in 39% of cases, malignant tumours, either single or double, were present in the gastrointestinal tract or elsewhere. Gastrointestinal "lipomata" are located in the sites of normal fatty infiltration in the elderly; these growths could be a local aging or reactive process of the intestinal wall rather than true neoplasms without any potential malignancy. However, coexistent malignancies should be carefully searched for in elderly patients with colonic lipoma. 
Acute abdomen as the first presentation of pseudomembranous colitis. Acute abdomen was the presenting manifestation of pseudomembranous colitis in six men who had previously been treated with antibiotics and presented with abdominal distention, pain, fever, and leukocytosis with absent or mild diarrhea. Plain abdominal radiographs revealed megacolon in two, combined small and large bowel dilation in three, with one of them showing volvuluslike pattern, and isolated small bowel ileus in one. Emergency colonoscopy was performed successfully in all patients and revealed pseudomembranes in five and nonspecific colitis in one. All patients had positive latex test results for Clostridium difficile, and two tested positive for cytotoxicity. All patients were treated with IV metronidazole, resulting in resolution of symptoms and abdominal findings. In addition, two patients underwent colonoscopic decompression with improvement. Endoscopically, complete resolution of the pseudomembranes occurred at 4 weeks in all cases. No patient had a recurrence. It is concluded that (a) pseudomembranous colitis may present as abdominal distention mimicking small bowel ileus. Ogilvie's syndrome, volvulus, or ischemia; (b) in such cases, emergency colonoscopy is safe and useful for diagnosis and therapeutic decompression and may obviate the need for surgery; and (c) treatment with IV metronidazole is effective. Colitis due to C. difficile should be considered in the differential diagnosis of acute abdomen in patients previously treated with antibiotics. 
Endoscopic assessment of mucosal hemodynamic changes in a canine model of gastric ulcer. In studying the side effects of sclerosants injected into the gastric submucosa in dogs (N = 7), we noted that 3 ml of absolute ethanol induced a large gastric ulceration. We describe the time course of change in the ulcer size, and suggest that such ulceration can be used for the endoscopic assessment of factors important in ulcer genesis and healing. Endoscopic reflectance spectrophotometric measurement of indices of mucosal hemoglobin concentration (IHB) and oxygen saturation (ISO2) were performed in a separate group of dogs (N = 4) with ethanol-induced gastric ulceration. We found a significant difference (p less than 0.05) in IHB and ISO2 immediately before (97 +/- 8 and 37 +/- 3, respectively) and after (138 +/- 7 and 21 +/- 5, respectively) the ethanol injection. At 24 hours after the ethanol injection, the IHB at the lesion margin (141 +/- 14) was significantly higher (p less than 0.05) than that at the adjacent mucosa (101 +/- 4), whereas the ISO2 measurements were not significantly different in these two locations, 34 +/- 2 and 31 +/- 2, respectively. We conclude that (1) injection of 3 mol of absolute ethanol into the submucosa of the canine stomach provides an animal model of gastric ulceration in which the ulcer can be examined repeatedly with the aid of the endoscope; (2) in this ulcer model, ischemia with congestion (increases IHB, decreases ISO2) precedes the development of gross mucosal ulcerations; and (3) the margin of the established ulceration in this model exhibits hyperemia (increases IHB, normal ISO2) which mimics that of a healing gastric ulcer. 
Lateral pharyngeal space abscess as a consequence of regional anesthesia. Trismus may be a complication from local anesthesia. Patients with trismus of unknown cause after dental treatment should be evaluated thoroughly. The dentist should perform a complete examination and establish a differential diagnosis to avoid missing a serious or life-threatening infection. A right lateral pharyngeal space infection developed after a general restorative procedure that involved an inferior alveolar nerve injection on the same side. The patient's severe trismus required awake intubation, incision and drainage while the patient was under general anesthesia, treatment with antibiotics and ten days of hospitalization. 
Interdependence of blood pressure and heart period regulation in mild hypertension. Blood pressure and heart period variability have been measured directly in 142 subjects with mild hypertension over 24 h. The variabilities have been expressed as the standard deviation of 2 min averages of all beats over 24 h. Baroreflex sensitivity was assessed in 102 subjects by the phenylephrine method. Blood pressure varies over a range of approximately 40% around the mean by day and by approximately 20% at night. The variability of blood pressure by day was inversely proportional to the sensitivity of the baroreflex (r = -0.33, P less than .001), while the variability of heart period was directly related to the sensitivity of the reflex (r = 0.27, P less than .01). Neither of these relationships was significant at night. An inverse relationship between heart period and blood pressure was shown by regression analysis of blood pressure and heart period averages over 24 h. The steepness of the slope of the heart period-systolic blood pressure relationship was strongly correlated with the baroreflex sensitivity (r = -0.55, P less than .001), suggesting that blood pressure variations are substantially buffered by changes in heart frequency. Thus, a more stable heart rate that results from an ineffective baroreflex is associated with a more variable systolic blood pressure. 
Bleeding after endoscopic sphincterotomy as an underestimated entity. Hemorrhage is the most frequent complication of endoscopic sphincterotomy, with a reported incidence of 2 to 9 per cent. Previous reports have generally defined this complication clinically, leaving the issue of occult bleeding after sphincterotomy essentially unaddressed. Seventy-five serial sphincterotomies were reviewed to further assess this complication. Nine patients had clinically evident hemorrhage and 27 patients had occult bleeding manifested only by a decrement in hematologic parameters, for a total postsphincterotomy bleeding rate of 48 per cent. No statistically significant risk factors for bleeding were delineated. Endoscopically recognized bleeding at the time of the sphincterotomy was 47 per cent sensitive and 85 per cent specific in predicting postprocedural bleeding. Significant delayed hemorrhage was manifest in three patients, one of whom had clinically occult bleeding. We conclude that bleeding complicates endoscopic sphincterotomy much more frequently than previously reported, although often in a clinically occult manner. Significant delayed bleeding can occur, and may not be clinically apparent. Bleeding recognized endoscopically at the time of sphincterotomy is an insensitive but relatively specific predictor of postprocedural bleeding. As use of endoscopic sphincterotomy increases, careful surveillance for hemorrhagic complications, as well as efforts to identify factors predisposing to the same, will be of increasing importance. 
Correlation between sexual abuse and somatization in women with somatic and nonsomatic chronic pelvic pain. After a comprehensive clinical and psychological evaluation, 99 women with pelvic pain of at least 6 months' duration and normal findings at laparoscopy were divided into two groups, including 47 women with probable somatic causes of pain (group 1) and 52 women without identifiable somatic abnormality (group 2). Women without identifiable somatic abnormality (group 2) were younger, had higher mean somatization scores, and reported an earlier mean age at first intercourse, a higher number of total sexual partners, and a higher prevalence of sexual abuse before the age of 20. Within group 2 (nonsomatic pain) but not within group 1, mean somatization scores were significantly higher among women with a history of sexual abuse than among women with a negative history. When analyzed as risks for nonsomatic pelvic pain, the positive predictive value of both a history of sexual abuse and a high somatization score was 78% (relative risk compared with that of women with zero or one risk factor, 2.1; p less than 0.0001). These data suggest that the psychosocial profile of women with nonsomatic pelvic pain differs from that of women with somatic pelvic pain and that previous sexual abuse is a significant predisposing risk for somatization and non-somatic chronic pelvic pain. 
Cardiovascular neural regulation explored in the frequency domain. A consistent link appears to exist between predominance of vagal or sympathetic activity and predominance of HF or LF oscillations, respectively: RR variability contains both of these rhythms, and their relative powers appear to subserve a reciprocal relation like that commonly found in sympathovagal balance. In this respect, it is our opinion that rhythms and neural components always interact, just like flexor and extensor tones or excitatory and inhibitory cardiovascular reflexes, and that it is misleading to separately consider vagal and sympathetic modulations of heart rate. In humans and experimental animals, functional states likely to be accompanied by an increased sympathetic activity are characterized by a shift of the LF-HF balance in favor of the LF component; the opposite occurs during presumed increases in vagal activity. In addition, LF oscillation evaluated from SAP variability appears to be a convenient marker of the sympathetic modulation of vasomotor activity. Although based on indirect markers, the exploration in the frequency domain of cardiovascular neural regulation might disclose a unitary vision hard to reach through the assemblage of more specific but fragmented pieces of information. 
Pancreatic-portal vein fistula with disseminated fat necrosis treated by pancreaticoduodenectomy. I have reported the case of a 62-year-old man with chronic alcoholic pancreatitis and a rare pseudocyst-portal vein fistula. Even though he experienced no abdominal symptoms, he had severe metastatic fat necrosis manifested as subcutaneous fat necrosis, polyarthritis, medullary bone necrosis, and mental status changes. Remote tissue destruction continued until relief was gained by pancreaticoduodenectomy and repair of the necrotic portal vein. Disseminated fat necrosis is a rare syndrome that can be the only presenting feature in patients with pancreatitis and pancreatic cancer. Early recognition and treatment of the underlying pancreatic disease may decrease the high morality rate associated with this syndrome. 
Direct sequencing from touch preparations of human carcinomas: analysis of p53 mutations in breast carcinomas A new technique for characterizing somatic mutations in very small samples of cellularly heterogeneous human cancer tissue was developed and tested using mutations in the p53 gene in breast carcinomas as a model system. The technique combines touch preparation of specimens to obtain homogeneous clusters of carcinoma cells free of normal cells with a nested pair of polymerase chain reaction (PCR) amplifications of DNA to increase the amount of target gene sequence sufficiently to permit direct sequencing of the p53 gene. Touch preparations of fresh or previously frozen tissue from human adenocarcinomas derived from several organs were stained, and clusters of 10-50 malignant cells were transferred by pipette into microfuge tubes for PCR amplification. Exons 5-9 of the p53 gene, which contain the major mutational hot spots associated with most human cancers, were sequenced by the following steps: 1) two rounds of PCR amplification using DNA Taq polymerase and two sets of oligonucleotide primers, the second set being nested within the segment amplified by the first set and having attached T7 and SP6 phage promoter sequences, 2) transcription of the amplified DNA sequences with T7 and SP6 RNA polymerases, and 3) dideoxy sequencing of single-stranded RNA transcripts with reverse transcriptase and with additional oligonucleotide primers to achieve specificity for this unique region of the genome. The utility of this approach is illustrated by our success in detecting and analyzing point mutations in cell clusters from four of 11 primary adenocarcinomas of the human breast. 
Changing pattern of bone and joint infections due to Staphylococcus aureus: study of cases of bacteremia in Denmark, 1959-1988. Of the 15,170 cases of bacteremia due to Staphylococcus aureus that occurred in Denmark between 1959 and 1988, we review 525 cases of acute hematogenous osteomyelitis and 185 cases of septic arthritis that developed subsequent to the bacteremia and 134 cases of contiguous osteomyelitis in which the bacteremia developed secondarily. The pattern of acute infections of bones and joints has changed over the three decades studied. The frequency of secondary bone or joint infections due to S. aureus bacteremia has changed, as have the phage-type pattern and antibiotic resistance of the infective strains. The prevalence of hospital-acquired cases has increased and the age distribution of patients has changed, as is reflected in an increasing number of older patients. The localization of hematogenous osteomyelitis has shifted, and the vertebral column is now the most common site of infection. The rate of chronic cases of osteomyelitis that occur following acute hematogenous osteomyelitis has been reduced from 34% to 6%. The mortality associated with S. aureus bacteremic infections of bones or joints is low compared to that associated with other cases of S. aureus bacteremia. 
Generalized pustular psoriasis. A review of 63 cases. BACKGROUND--Sixty-three patients with generalized pustular psoriasis were hospitalized during a 29-year period. They were classified into four subgroups on the basis of onset and morphologic pattern of disease: acute (von Zumbusch), subacute annular, chronic (acral), and mixed. This division provides a better understanding of the variability of the disease and helps in choosing treatment. OBSERVATIONS--The average age at onset was 50 years; male and female patients were affected about equally. In 11 patients, flares were precipitated by localized infections. Approximately one fourth of the patients had complications; most were superinfections. The average stay in the hospital was 30 days; factors correlating with a long hospitalization were hypocalcemia, female sex, and a previous history of psoriasis vulgaris or pustular psoriasis. CONCLUSIONS--Whereas topical therapy was helpful, systemic medications were often needed. Coal tar, ultraviolet light, and psoralen-ultraviolet A may be effective; however, they must be used with caution, because they may exacerbate the disease. 
Hormone replacement therapy in general practice: a survey of doctors in the MRC's general practice research framework. OBJECTIVES--To survey current prescribing practice for hormone replacement therapy among general practitioners and to elicit their views on the role of hormone replacement therapy in the prevention of osteoporosis and cardiovascular disease; to determine whether they would participate in randomised controlled trials to evaluate the long term beneficial and adverse effects of hormone replacement therapy. DESIGN--Postal questionnaires to general practitioners throughout the United Kingdom. PARTICIPANTS--1268 general practitioners in the Medical Research Council's general practice research framework. RESULTS--1081 (85%) doctors in 220 (95%) practices responded. The doctors were currently prescribing hormone replacement therapy to an estimated 9% of their female patients aged 40 to 64, and 55% of doctors were prescribing opposed hormone replacement therapy (oestrogen plus progestogen) to more patients than a year previously. Over half the doctors would consider prescribing hormone replacement therapy for prevention of osteoporosis (670, 62%) and cardiovascular disease (611, 57%) to asymptomatic women. Overall, 79% of the doctors (851) would definitely or probably consider entering women who have had a hysterectomy into a randomised controlled trial comparing unopposed (oestrogen only) hormone replacement therapy with opposed hormone replacement therapy; 49% (524) would enter patients with a uterus into such a trial. Among a subsample, 85% (180/210) would consider entering patients without menopausal symptoms into a trial comparing hormone replacement therapy with no treatment (unopposed in patients who have had a hysterectomy, opposed in those with a uterus). CONCLUSION--There is considerable uncertainty among general practitioners as to the balance of beneficial and harmful effects of hormone replacement therapy in the long term, particularly relating to its use for prevention of osteoporosis and cardiovascular disease. Most of these doctors would be prepared to participate in randomised controlled trials to determine the long term effects of this increasingly widely used treatment. 
Coronary patency, infarct size and left ventricular function after thrombolytic therapy for acute myocardial infarction: results from the tissue plasminogen activator: Toronto (TPAT) placebo-controlled trial. TPAT Study Group Infarct size, left ventricular function and infarct-related coronary artery patency were examined in 108 patients who took part in a previously reported placebo-controlled trial of recombinant tissue-type plasminogen activator (rt-PA) in acute myocardial infarction. Coronary angiography was performed 17 +/- 0.8 h after initiation of treatment in 47 patients (group A) or at 10 days in 61 patients (group B). Both groups underwent radionuclide ventriculography 3.8 +/- 0.8 h and again on day 9 after treatment and quantitative thallium scintigraphy on day 8. In group A, the infarct-related artery was patent in 53%; these patients had a smaller global (15.1 +/- 2.5% vs. 25.7 +/- 4.7%, p = 0.029) and regional (14.7 +/- 2.5% vs. 24.1 +/- 4.7%, p = 0.044) fixed thallium defect than did those with an occluded artery. Infarct regional ejection fraction improved by 10.1 +/- 2.1% between early and late studies when the infarct-related artery was patent and by 4.8 +/- 1.4% if it was occluded (p = 0.048); changes in global and noninfarct regional ejection fraction were similar irrespective of perfusion status. Infarct regional ejection fraction and fixed thallium defect were inversely related only when the infarct-related artery was occluded (r = -0.83, p less than 0.0001). In group B, 10 day patency of the infarct-related artery was 67%; there was no difference in patency by treatment assignment or in left ventricular function or infarct size between patients with and without infarct-related artery patency. There was no evidence of an effect of rt-PA therapy beyond that expressed through coronary patency alone in either group A or group B. 
CT and pathologic predictive features of residual mass histologic findings after chemotherapy for nonseminomatous germ cell tumors: can residual malignancy or teratoma be excluded? Forty-eight patients with disseminated nonseminomatous germ cell tumors were studied retrospectively to determine whether initial pathologic features and pre- and post-chemotherapy computed tomographic (CT) features could be used to exclude malignancy or teratoma in residual masses that were excised after chemotherapy. Neither CT findings (residual mass size, attenuation, and degree of shrinkage during chemotherapy) nor type of primary testicular tumor cell was significantly correlated with malignancy or teratoma versus necrosis in residual masses. No significant correlation was demonstrated between the combined features of (a) the absence of teratoma in a histologic specimen of the primary testicular tumor and (b) greater than 90% shrinkage of masses during chemotherapy and the absence of malignancy or teratoma in residual masses as suggested in the literature. Of nine patients with both of these findings, two had malignancy and two had teratoma. Radiographic and pathologic features cannot be used to reliably exclude malignancy or teratoma in residual abdominal masses after chemotherapy for nonseminomatous testicular cancer. 
Primary soft tissue tumours of the pelvis causing referred pain in the leg. Referred pain in the leg is occasionally due to a pelvic soft tissue tumour. Among 11 patients who presented this way, one had a lymphoma, one had a benign schwannoma, and nine had soft tissue sarcomas. Most patients had undergone a variety of procedures, including laminectomy, before the correct diagnosis was established. In five cases, an accurate diagnosis was obtained by needle biopsy. The lymphoma responded to chemotherapy, and the benign schwannoma was excised. Of the nine patients with soft tissue sarcoma, six underwent marginal/intracapsular excision, three receiving supplementary radiotherapy, and two were treated by nonsurgical means. Hindquarter amputation was technically impossible or inappropriate in these cases. All those with high-grade tumours have died or have metastases. Of four patients with low-grade tumours, three have exhibited only slow disease progression. Careful judgment and a precise histopathological diagnosis are required in planning treatment for patients with pelvic soft tissue tumours causing referred pain in the leg. 
Prevalence and prognostic significance of silent and symptomatic ischemia after coronary bypass surgery: a report from the Coronary Artery Surgery Study (CASS) randomized population. The prevalence and prognostic significance of postoperative myocardial ischemia, as detected by exercise testing, were prospectively assessed in 174 patients from the Coronary Artery Surgery Study (CASS) randomized surgical population who had exercise testing before and 6 months after coronary artery bypass graft surgery. Whereas the prevalence of symptomatic ischemia significantly decreased postoperatively (52% vs. 6%, p less than 0.001), the frequency of silent myocardial ischemia did not change (30% vs. 29%). Survival at 12 years after bypass surgery based on the 6-month postoperative exercise test results was significantly better for the 112 patients with no ischemia (80%) than for the 51 patients with silent ischemia (68%) or the 11 patients with symptomatic ischemia (45%). These data show that coronary artery bypass graft surgery diminishes the overall prevalence of symptomatic but not silent ischemia and that both silent and symptomatic ischemia adversely affect the postoperative prognosis of these patients. 
Genetic predisposition to iatrogenic Creutzfeldt-Jakob disease. The spongiform encephalopathy Creutzfeldt-Jakob disease (CJD) has been transmitted to man via administration of growth hormone and gonadotropin extracted from large pooled batches of human cadaveric pituitary glands. In the UK, 1908 individuals were exposed to potentially contaminated growth hormone, of whom 6 have so far manifested CJD. Examination of the prion protein genes of all these cases and of a single case of gonadotropin-related CJD showed that 4 had the uncommon valine 129 homozygous genotype indicating genetic susceptibility to prion infection. Such genetic susceptibility may be important in the aetiology of sporadic CJD disease. 
The mast cell in health and disease. The presence of mast cells, often in an activated state or increased numbers, has been noted in various cutaneous disorders. Recent studies suggest that mast cells are of primary importance in these conditions and their presence does not merely represent a secondary event. This review focuses on atopic dermatitis, contact hypersensitivity reactions, bullous pemphigoid, fibrosing conditions, neurofibromatosis, wound healing, polycythemia vera, and psoriasis, in which there is significant evidence to indicate a pathophysiologic role for mast cells. 
Evaluation of restenosis after balloon dilatation in adult aortic stenosis by repeat catheterization. To evaluate the restenosis rate after successful balloon aortic valvuloplasty, clinical evaluation and repeat catheterization were performed in 96 patients who had undergone balloon dilatation 7 +/- 5 months earlier. Restenosis, defined as a loss of greater than 50% of the benefit in aortic valve area obtained after balloon valvuloplasty, was observed in 48% of the patients. Actuarial analysis showed that the restenosis rate was time dependent and was 80% at 15 months. However, functional improvement was observed in most of the patients with or without restenosis. The restenosis rate was not correlated with the degree of enlargement of the aortic orifice produced by the valvuloplasty procedure. Because of the high incidence of restenosis, balloon aortic valvuloplasty should be limited to patients who have a contraindication to surgery or are at high risk for surgery, or as a bridge to surgery. 
Metabolic consequences of (regional) total pancreatectomy. Little information has been reported on the metabolic characteristics of the totally pancreatectomized patient or the efficacy of medical management after radical pancreatic surgery. The prospective evaluation of 49 such patients, with 31% followed for 48 or more months, forms the basis of this report. The major immediate postoperative challenge is control of diarrhea and weight stabilization. Chronically patients have an increased daily caloric requirement (mean +/- SE, 56 +/- 1 kcal/kg), not wholly explained by moderate steatorrhea (fecal fat excretion, 16% +/- 2% of unrestricted fat intake). Despite persistent malabsorption, deficiencies in fat-soluble vitamin, magnesium, and trace element serum levels can be prevented in most patients. Pancreatogenic diabetes is characterized by (1) absence of the major glucoregulatory hormones insulin and glucagon, (2) instability, and (3) frequent hypoglycemia, with the latter parameters improving with rigorous home glucose monitoring. No patient has developed clinically overt diabetic micro- or macrovascular disease. Performance status in long-term survivors has been reasonable. However adverse chronic sequelae of the operation occur and include an unusual frequency of liver disease, characterized by accelerated fatty infiltration, and osteopenia, with an 18% reduction in radial bone mineral content noted in pancreatectomized patients studied more than 5 years after surgery. 
A method for estimating catechol estrogen metabolism from excretion of noncatechol estrogens. The relationship of catechol estrogen metabolism to disease has seldom been investigated because of analytic difficulties. Estradiol (E2) and estrone (E1) are oxidized simultaneously at either ring A or ring D, and the rate of catechol estrogen formation (r2) is reciprocally related to the rate of 16 alpha-hydroxylation (r3). The rate of ovarian estrogen production (X10) can be summarized as to metabolic outcome: X10 = r10 + r2 + r3 + r(u), where r10 is the loss of E1 and E2 in urine, and ru is the fecal and urinary loss of unknown oxidative products. Assuming a constant r(u) between subjects: constancy of the X10 concentration between subjects during similar menstrual cycle phases. In the absence of xenobiotics, r2 x r3 are reciprocally interrelated: r2 x r3 = K (an oxidation constant whose limiting factor is the biologically available estrogen at the cell surface). To the extent that r10 approximates estrogens available for cellular metabolism, the rate of catechol estrogen metabolism may be determined from (Formula; see text) From published data K = 12.4 +/- 0.8 of the standard error of the mean. Pearson correlation coefficients between actual and estimated catechol estrogen excretion in groups of subjects ranged from 0.61 to 0.97 (median, 0.88). This method has been useful for clinical investigation of the relationship of catechol estrogen metabolism to disease until better methods to measure catechol estrogen directly are available. 
An autopsy study of the incidence of lacunes in relation to age, hypertension, and arteriosclerosis. We investigated selected features of lacunes in 1,086 necropsy cases. Lacunes were found in brains from patients above the age of 40 years and were most common in brains from persons in their sixties but decreased in number in brains from older persons. The most common site of lacunes was the frontal lobe white matter, followed by the putamen, pons, parietal lobe white matter, thalamus, and caudate nucleus in descending order of frequency. By dividing the 1,086 cases into three groups according to blood pressure, we found more lacunes in the hypertensive and borderline hypertensive groups than in the normotensive group; the average number of lacunes per brain in each group was 3.61, 2.77, and 1.15, respectively. Diastolic hypertension was more closely related to the number of lacunes than was systolic hypertension. The extent of arteriolosclerosis of the medullary arteries in the frontal lobe white matter was measured and compared with the number of lacunes. There was a close correlation between lacunes and arterioloslerosis in all age groups. 
Transoral decompression evaluated by cine-mode magnetic resonance imaging: a case of basilar impression accompanied by Chiari malformation. Cine-mode magnetic resonance imaging provides simultaneous images of cerebrospinal fluid flow dynamics. A patient with a basilar impression accompanied by a Chiari malformation and von Recklinghausen's disease who underwent transoral decompression is reported. Preoperative cine-mode magnetic resonance imaging visualized an associated obstruction of cerebrospinal fluid pulsatile flow at the level of the foramen magnum. Tonsilar herniation (Chiari I malformation) and hydrocephalus were also present. Postoperatively, the obstruction of cerebrospinal fluid flow was resolved concomitant with the correction of the cervicomedullary angulation. On the basis of observations made by magnetic resonance imaging, the surgical treatment of basilar impression accompanied by Chiari malformation is briefly discussed. 
Treatment of recurrent urethral strictures using clean intermittent self-catheterisation. The treatment of urethral strictures has been greatly improved by the use of the optical urethrotome. However, there remains a group of patients with recurrent strictures for whom the alternatives remain long-term dilatation/urethrotomy or urethroplasty. Over the last 3 years we have treated 65 such patients using clean intermittent self-catheterisation as a method of self-dilatation. This has resulted in a dramatic decrease in the number of operations performed on these patients, with no significant reduction in urinary flow rate over an average follow-up period of 20 months. The method offers the possibility of long-term cure and should be offered to all all such patients, reducing still further the number of patients who require urethroplasty. 
Immunoturbidimetric assay for estimating free light chains of immunoglobulins in urine and serum. An immunoturbidimetric assay for the assessment of free kappa and lambda light chains of immunoglobulins was developed using a commercial polyclonal antiserum with reactivity towards epitopes on the light chains, which are not expressed when they are bound to heavy chains. The assay, on a centrifugal analyser, is simple and rapid. The limit of detection is 5 mg/l of free light chain, with an assay range of 5-120 mg/l, intrabatch precisions from 1.5-6.4%, and interbatch precisions from 6.5-8.9%. The assay was only slightly less sensitive than colloidal gold staining of cellulose acetate electrophoreses for the detection of Bence-Jones protein in urine. For the serial monitoring of response to chemotherapy in patients with myeloma, the assay correlated well with serum paraprotein estimates obtained by densitometric scanning of Ponceau stained cellulose acetate electrophoreses, but not with serum beta-2 microglobulin measurements, even after correction for the effects of creatinine. These assays may prove to be of use for the monitoring of tumour response in the treatment of Bence-Jones myeloma. 
Avoidance of tolerance and lack of rebound with intermittent dose titrated transdermal glyceryl trinitrate. The Transdermal Nitrate Investigators. OBJECTIVES--To investigate the efficacy of transdermal glyceryl trinitrate given continuously and with a nocturnal nitrate free period. DESIGN--Double blind placebo controlled study with two parallel limbs. SETTING--Multicentre trial. PATIENTS--52 patients randomised to receive either continuous treatment (23 patients) or intermittent treatment with an individually titrated dose (29 patients) for 14 days: both treatments were compared with placebo in a cross-over fashion. INTERVENTION--Continuous treatment with 10 mg per 24 hours of transdermal glyceryl trinitrate or intermittent transdermal glyceryl trinitrate titrated to give an arbitrary 10 mm Hg drop in systolic blood pressure (mean dose 18.2 mg) given over approximately 16 hours. MAIN OUTCOME MEASURE--Treadmill exercise stress testing and ambulatory monitoring of the ST segment after 14 days' treatment. RESULTS--After 14 days' intermittent treatment resting supine and standing systolic blood pressure fell by 7.5 mm Hg (95% confidence interval 2.7 to 12.2) and 9.0 mm Hg (95% CI 3.4 to 14.5) respectively (p less than 0.01); resting heart rate was unchanged. Mean heart rate at 1 mm ST segment depression rose by 11.9 beats/min (CI 1.1 to 23.7) (p less than 0.05), mean time to onset of angina increased by 59 seconds (CI 10.8 to 108) (p less than 0.05), and total exercise duration increased by 40 seconds (p less than 0.05). These changes were not seen after continuous treatment. The frequency of ischaemic episodes was not reduced with either regimen nor was the circadian distribution of these episodes altered, in particular nocturnal episodes did not increase during intermittent treatment. CONCLUSION--Tolerance to glyceryl trinitrate was avoided by the use of individually titrated doses administered with a nocturnal nitrate free period. There was no evidence of "rebound" on ambulatory monitoring during this treatment. 
Physiologic stress and cellular ischemia: relationship to immunosuppression and susceptibility to sepsis. Multiple organ system failure secondary to infection is the most frequent cause of late mortality after hemorrhage, burns, and trauma. Although multiple immunologic abnormalities have been identified following injury, blood loss, and tissue ischemia, the mechanisms that produce these alterations in T- and B-cell function have not been completely defined. Physiologic stress and ischemia result in increased release of neuroendocrine peptides and hormones, capable of affecting normal neuroendocrine-immunologic balance and producing immunosuppression. Tissue ischemia leads to increased expression of heat shock proteins by hypoperfused cells, which can alter T-cell function. Injury also is followed by the appearance of serum immunosuppressive factors, which have been shown to inhibit T- and B-cell function. Future therapies directed at these and other cellular and molecular abnormalities initiated by tissue hypoperfusion may reverse the immunosuppressed state in critically ill patients and lead to improved outcome in this setting. 
Is routine CT scanning necessary in the preoperative evaluation of patients undergoing carotid endarterectomy? To evaluate the usefulness of CT scanning before carotid endarterectomy, a prospective study was performed on 469 consecutive patients considered for carotid endarterectomy during a 5-year period. All patients underwent carotid duplex scanning and CT scanning before carotid arteriography. Two hundred thirty-seven patients (51%) had transient ischemic attacks, 109 (23%) had a prior stroke, and 122 (26%) were asymptomatic. Results of the CT scan were abnormal in 68 (62%) of the 109 patients with stroke. Fifty-one of the 360 patients (14%) without a clinical history of stroke had an abnormal CT scan outcome. Of patients with a stroke documented by CT scanning, 27 had lacunar infarcts, and 92 had cortical infarcts; these findings did not change surgical management in any patient. CT scanning did not reveal any unsuspected infarcts or tumors. Two hundred thirty carotid endarterectomies were performed on 206 patients. Forty-seven patients (23%) in the operative group had abnormal CT scan findings, but the scan did not influence operative decisions or timing in any case. Seventy-two patients (27%) in the nonoperative group had abnormal CT scan results, but CT scan findings did not exclude any patient from arteriography or surgery. Three perioperative strokes (1.3%) occurred. CT scan findings did not correlate with postoperative neurologic complications. Cost of CT scanning was one-half million dollars in our study alone. Routine CT scanning is unnecessary before carotid endarterectomy and is not cost-effective. 
Double dissociation of short-term and long-term memory for nonverbal material in Parkinson's disease and global amnesia. A further analysis. The traditional concept of memory disorder is deficiency of the long-term (LTM) but not short-term (STM) component of memory. STM impairment with LTM sparing is seldom reported. The present study investigated STM and LTM for nonverbal material in three neurological conditions associated with memory impairment: bilateral medial temporal lobe lesions (patient H.M.), Parkinson's disease (PD) and Alzheimer's disease (AD). Subjects received 3 tests of nonverbal memory: forward block span, immediate and delayed recall of the Wechsler Memory Scale drawings, and immediate and delayed recognition of abstract designs. Compared with the normal control group, the patient groups displayed different patterns of sparing and loss of the two components of memory: in PD, only STM was impaired; in medial temporal lobe amnesia, only LTM was impaired; and in AD, STM and LTM were both impaired. The contrasting patterns of sparing and loss of STM and LTM in PD and global amnesia were present for both recognition and recall. These results provide evidence that STM and LTM are dissociable processes and are served by separate neurological systems: STM depends upon intact corticostriatal systems, whereas LTM depends upon intact medial temporal lobe systems. 
Traumatic anterior fossa cerebrospinal fluid fistulae and craniofacial considerations. Traumatic cerebrospinal fluid fistulae may present a diagnostic and treatment challenge to the head and neck surgeon. The clinical presentation may be obscured by associated injuries. This article serves as a guide in the understanding, diagnosis, and management of patients with dural fistulae of the anterior cranial fossa. 
Morphologic features and nuclide composition of infarction-associated cardiac myocyte mineralization in humans. Low dietary Mg results in Ca loading of cardiac myocytes, which increases the likelihood of myocyte calcification in the event of acute myocardial infarction (AMI), and possibly increases myocyte vulnerability to necrosis. Bloom and Peric-Golia1 previously reported an autopsy study of cases from the Washington, D.C. area (a region with low levels of Mg in the drinking water), demonstrating AMI-associated mineralization in myocytes with histologically normal nuclei and cross striations, as well as in obviously necrotic myocytes. The authors have re-examined mineralized myocytes from the same autopsy material, using electron probe microanalysis, light microscopy, and transmission electron microscopy. Microprobe analysis identified Ca and P as the nuclides composing the inorganic phase of the mineral deposits. Ultrastructurally, all Ca deposits, regardless of size or intracellular location, were composed of aggregates of needlelike hydroxyapatite crystals. The mildest form of intracellular Ca deposition was observed as small Ca deposits limited to some mitochondria of myocytes, which demonstrated intact nuclei and regular sarcomere pattern. More advanced stages of intracellular calcification, in the form of Ca deposits associated with mitochondria, Z-band regions and nuclei, were observed in other myocytes that also retained intact nuclei and sarcomeres. Massive Ca deposits were associated with myocytes which showed morphologic features of advanced necrosis, including loss of nuclei, disruption of sarcomere structure and masses of cellular debris. These observations support the theory originally proposed by Bloom and Peric-Golia1 suggesting that Ca loading of myocytes, possibly related to Mg deficiency in humans, increased vulnerability of the myocytes to subsequent AMI-associated necrosis and dystrophic calcification. In addition, the light microscopic impression of calcification of otherwise normal myocytes is contradicted by the electron microscopic identification of hydroxyapatite crystals free in the sarcoplasm, a condition unlikely to be compatible with viability. Lastly, the fact that all Ca deposits were in the form of hydroxyapatite supports the view that they were formed in a Mg-poor environment, which favors conversion of the more common amorphous form of Ca phosphate into the needlelike crystals of hydroxyapatite. 
Bacterial meningitis: T cell activation and immunoregulatory CD4+ T cell subset alteration. Meningitis is the most important cause of acquired postnatal deafness and neurologic disorders in children. To determine if cell-mediated immunity is casually related to the pathogenesis of bacterial meningitis, T cell subsets were quantitated from blood of the 29 children with clinical and bacteriologic diagnosis of Haemophilus influenzae, Streptococcus pneumoniae, and Neisseria meningitidis bacterial meningitis. The CD4+ T cells increased and CD8+ T cells decreased in patients with meningitis as compared to patient control subjects (bacterial infections without meningitis) and normal healthy control subjects. An elevated percentage of CD25+ (interleukin-2 receptors) and HLA-DR+ (immune-response gene-associated antigen) T cells were detected from all patients with meningitis. All 29 patients with meningitis had highly elevated CD4+ CD45R+ (suppressor-inducer) cells and reciprocally depressed CD4+ CDw29+ (helper-inducer) cells compared with healthy age-matched normal and patient control subjects. These findings indicate characteristic immunologic T cell abnormalities from meningitis. The abnormal increase in the CD4+ CD45R+ suppressor-inducer or "virgin" cells and expression of activation antigens on T cells may be of help in future understanding of abnormal immune reactions from bacterial meningitis. However, deficiency of the CD4+ CDw29+ helper-inducer or "memory" cells may contribute to the impaired helper function for B cell-induced protective antibody synthesis to bacterial capsular polysaccharides found in this disease. 
Androgen responses to acutely increased endogenous insulin levels in hyperandrogenic and normal cycling women. We examined androgen responses in hyperandrogenic (polycystic ovarian disease [PCOD]) and normal women after an acute endogenous insulin elevation. Standard intravenous glucose tolerance tests (IVGTTs), modified to include a tolbutamide injection 20 minutes after IVGTTs, were performed. Polycystic ovarian disease patients were studied in the untreated state, after 6 weeks of ovarian androgen suppression with leuprolide acetate, after a 6-week rest period, and after 6 weeks of antiandrogen therapy with spironolactone. Normal menstruating women were studied during the early follicular, midcycle, and luteal phases of a single cycle. An acute rise in insulin did not alter serum testosterone or androstenedione levels in PCOD or normal women. A significant rise in dehydroepiandrosterone sulfate after modified IVGTTs was found in both hyperandrogenic and normal cycling women. Although these results are not supportive of the theory that insulin acts on the ovary to stimulate androgen production, they may be because of the short time course of insulin elevation that occurs during an IVGTT. 
Hypersensitivity myocarditis. Autopsy tissue specimens of 69 cases of hypersensitivity myocarditis were studied to determine drug association, spectrum of histologic findings, distribution of infiltrates, and correlation between degree of infiltrates and cardiac symptoms. Hypersensitivity myocarditis was defined by the presence of eosinophils, a mixed lymphohistiocytic infiltrate along natural planes of separation, and an absence of fibrosis or granulation tissue in areas of infiltrate. Commonly implicated drugs were methyldopa, hydrochlorothiazide, ampicillin, furosemide, digoxin, tetracycline, aminophylline, phenytoin, benzodiazepines, and tricyclic antidepressants. Histiocytes composed the predominant cell type (in addition to eosinophils and lymphocytes). Lymphocytes were predominantly T cells in 12 cases studied immunohistochemically. Small foci of myocyte necrosis were present in 37 cases, and they correlated with the degree of infiltrate. A nonnecrotizing vasculitis was present in 28 cases. The right ventricle was involved in all but three cases. Cardiac arrhythmias or unexplained death occurred in 29 patients and did not correlate with the degree of myocardial infiltrate or presence of necrosis. Eosinophils were present in the livers of 30 of 58 patients, and their presence correlated with the degree of cardiac infiltration. A causative association between histologic findings and drugs is difficult to prove because of the common usage of many of the drugs implicated, multiple drug use, and the absence of clinical criteria of hypersensitivity. Symptoms do not appear related to the degree of infiltrate. In more than half the cases, infiltrates may be missed by endomyocardial biopsy due to focality of lesions. 
5-Fluorouracil after trabeculectomy and the iridocorneal endothelial syndrome. Nine patients (nine eyes) with iridocorneal endothelial (ICE) syndrome underwent trabeculectomy and received postoperative subconjunctival injections of 5-fluorouracil (5-FU) to enhance bleb formation (total 5-FU dose, 30-105 mg; mean, 53.8 mg). Eight eyes had undergone prior unsuccessful trabeculectomy. Four eyes had intraocular pressure (IOP) less than or equal to 21 mmHg on zero to two glaucoma medications after 6 to 54 months of follow-up (mean, 25.3 months). Five eyes required repeat surgery within 2 to 13 months and were considered failures. All five eyes that failed received a Molteno drainage implant. Progressive endothelial proliferation may explain late onset bleb failure and the relative ineffectiveness of 5-FU in this condition. 
Changes in portal blood flow consequent to partial hepatectomy: Doppler estimation. Hemodynamic changes in portal blood flow were investigated in 56 patients with hepatic tumors who underwent partial hepatectomy. Portal flow was measured with a Doppler ultrasound system before, during, and after surgery. The portal flow of patients who underwent massive hepatectomy decreased intraoperatively. The portal flow per unit of cardiac output decreased in patients who underwent massive or major hepatectomy, patients with a cirrhotic liver, and patients who had a satisfactory postoperative course. Postoperatively, the portal flow in patients with a poor clinical outcome (multiple organ failure, hepatic failure, and cardiorespiratory failure) decreased significantly. Monitoring portal hemodynamic values appears to be useful in providing an index of "hepatic functional reserve." Adequate portal flow is essential for postoperative hepatic regeneration; changes in portal hemodynamic values may be directly related to the patient's ability to survive surgery and to regain or maintain normal liver function. 
Angiotensin converting enzyme inhibitors and magnesium conservation in patients with congestive cardiac failure. OBJECTIVE--To investigate whether angiotensin converting enzyme inhibitors reduce diuretic induced magnesium excretion in patients in congestive cardiac failure. DESIGN--Cohort analytic study. SETTING--A London district general hospital. SUBJECTS--Thirty four patients with chronic congestive cardiac failure caused by ischaemic heart disease or cardiomyopathy selected consecutively from inpatients under the care of two consultant cardiologists. Nineteen patients (group 1) on diuretics alone were compared with 15 patients (group 2) taking diuretics plus either enalapril or captopril. All drug regimens were stable for at least three months before the study. Patients with impaired renal function (plasma creatinine greater than 120 mumol/l) were excluded. INTERVENTIONS--An intravenous loading dose of magnesium sulphate was given to minimise the variability in baseline magnesium state. MAIN OUTCOME MEASURE--Total urine magnesium excretion and creatinine clearance in 24 hour urine collections. RESULTS--Plasma magnesium was similar in the two groups. However, 24 hour urine magnesium excretion was significantly lower in group 2 than in group 1. Furthermore, creatinine clearance was also significantly lower in group 2 and correlated strongly with magnesium excretion. There was no such relation in group 1. There was no difference in fractional clearance of magnesium between groups. CONCLUSION--Angiotensin converting enzyme inhibitors have an important magnesium conserving action, possibly via their effect on glomerular filtration rate. 
Diagnostic x-ray procedures and risk of leukemia, lymphoma, and multiple myeloma [published erratum appears in JAMA 1991 Jun 5;265(21):2810] Exposure to diagnostic x-rays and the risk of leukemia, non-Hodgkin's lymphoma (NHL), and multiple myeloma were studied within two prepaid health plans. Adult patients with leukemia (n = 565), NHL (n = 318), and multiple myeloma (n = 208) were matched to controls (n = 1390), and over 25,000 x-ray procedures were abstracted from medical records. Dose response was evaluated by assigning each x-ray procedure a score based on estimated bone marrow dose. X-ray exposure was not associated with chronic lymphocytic leukemia, one of the few malignant conditions never linked to radiation (relative risk [RR], 0.66). For all other forms of leukemia combined (n = 358), there was a slight elevation in risk (RR, 1.17) but no evidence of a dose-response relationship when x-ray procedures near the time of diagnosis were excluded. Similarly, patients with NHL were exposed to diagnostic x-ray procedures more often than controls (RR, 1.32), but the RR fell to 0.99 when the exposure to diagnostic x-ray procedures within 2 years of diagnosis was ignored. For multiple myeloma, overall risk was not significantly high (RR, 1.14), but there was consistent evidence of increasing risk with increasing numbers of diagnostic x-ray procedures. These data suggest that persons with leukemia and NHL undergo x-ray procedures frequently just prior to diagnosis for conditions related to the development or natural history of their disease. There was little evidence that diagnostic x-ray procedures were causally associated with leukemia or NHL. The risk for multiple myeloma, however, was increased among those patients who were frequently exposed to x-rays. 
Urological aspects of Behcet's disease. Behcet's disease, affecting mostly young males in the Mediterranean countries and Japan, is a multi-system disease with urological manifestations. In this prospective study of 100 consecutive patients with newly diagnosed Behcet's disease, we found that 89% of the males had experienced scrotal ulceration and 6% had epididymitis. We also observed sterile urethritis in 3%. Other urological abnormalities appeared to be coincidental findings. 
A randomized trial of five cisplatin-containing treatments in patients with metastatic non-small-cell lung cancer: a Southwest Oncology Group study. Six hundred eighty assessable patients with measureable stage III M1, non-small-cell lung cancer (NSCLC) were randomized to one of five treatment arms including cisplatin, etoposide (VP-16) +/- methylglyoxal bisguanylhydrazone (MGBG; PVp, PVpM); cisplatin, vinblastine (PVe); or PVe alternating with vinblastine, mitomycin (PVeMi); or fluorouracil, vincristine, mitomycin/cyclophosphamide, doxorubicin, cisplatin (FOMi/CAP). The overall response rate was 20% with 3% complete responses and 17% partial remissions. The duration of these responses was not statistically different by treatment regimen and varied from 2.7 months to 5.0 months. The overall median survival for all patients was 5.3 months and is not different by treatment. Toxicity was greater in PVpM. The similarity of results for response, duration of response, and survival does not establish the superiority of any of these platinum-based regimens for standard clinical usage. 
Did prognosis after acute myocardial infarction change during the past 30 years? A meta-analysis. Much effort has been spent to improve survival after acute myocardial infarction. To investigate how effective this effort has been, a meta-analysis was performed of studies published between 1960 and 1987 concerning mortality after acute myocardial infarction. Thirty-six studies were analyzed. They were classified with respect to deaths in the hospital and at 1 month and the 5-year mortality rate starting at hospital discharge. Mortality was assessed from all studies by comparing studies from different institutions with use of identical inclusion criteria (externally controlled studies) and by analyzing studies reporting on changes in mortality in two or more comparable patient cohorts admitted to the same institution at different time periods (internally controlled studies). Reports on clinical trials (for example, thrombolytic therapy, beta-adrenergic blockade) in acute myocardial infarction were excluded. Average overall in-hospital mortality decreased from 29% during the 1960s to 21% during the 1970s and to 16% during the 1980s. The externally controlled studies also showed a declining trend: from 1960 to 1969, 32%, from 1970 to 1979, 19% and from 1980 to 1987, 15%. The 1-month overall mortality rate decreased from 31% during the 1960s to 25% during the 1970s and 18% during the 1980s externally controlled studies. Most internally controlled studies also showed significant improvement in in-hospital and 1-month survival. In contrast, 5-year mortality after hospital discharge did not significantly decrease (33% from 1960 to 1969 and 33% from 1970 to 1979). It is concluded that in the prethrombolytic era, short-term prognosis after acute myocardial infarction has improved since 1960. 
Detection of preclinical Parkinson's disease with PET. Putamen 18F-dopa uptake of patients with Parkinson's disease (PD) is reduced by at least 35% at onset of symptoms; therefore, positron-emission tomography (PET) can be used to detect preclinical disease in clinically unaffected twins and relatives of patients with PD. Three out of 6 monozygotic and 2 out of 3 dizygotic unaffected PD co-twins have shown reduced putamen 18F-dopa uptake to date. In addition, an intact sibling and a daughter of 1 of 4 siblings with PD both had low putamen 18F-dopa uptake. These preliminary findings suggest there may be a familial component to the etiology of PD. PET can also be used to detect underlying nigral pathology in patients with isolated tremor and patients who become rigid taking dopamine-receptor blocking agents (DRBAs). Patients with familial essential tremor have normal, and those with isolated rest tremor have consistently low, putamen 18F-dopa uptake. Drug-induced parkinsonism is infrequently associated with underlying nigral pathology. 
Recent advances in the treatment of breast cancer. Multidisciplinary efforts have defined a number of prognostic factors and newer strategies to improve the outcome of patients with breast cancer. Conservative surgery has led to improved functional and cosmetic results. The development of a number of effective adjuvant regimens has led to improved survival. In patients with stage I disease, several biological characteristics of tumor have been identified that are associated with increased risk of relapse. A multimodality approach to patients with locally advanced disease and inflammatory cancer has resulted in improved survival. A number of hormonal and cytotoxic drug contaminations can palliate metastatic disease, with a small fraction of patients remaining in extended remission. Dose-intensive programs may lead to further improvements in survival of selected patients with this disease. 
Tamoxifen in premenopausal patients with metastatic breast cancer: a review. The antiestrogen tamoxifen is the most widely used hormonal therapy for breast cancer. The drug exerts its antiproliferative effects primarily through estrogen receptor (ER)-mediated mechanisms, although other cellular actions may augment tumor inhibition. Clinically, tamoxifen has been less well studied in premenopausal than in postmenopausal patients. The drug has complex endocrine effects that are dependent on the treatment duration and dose, menopausal status, and target organ. In postmenopausal women receiving tamoxifen, serum estrogen levels remain low, and the normally elevated gonadotropin levels decrease. In contrast, serum estrogen levels are strikingly elevated in many premenopausal women, and gonadotropin concentrations are either unchanged or slightly increased. Large systematic trials in metastatic breast cancer have established tamoxifen as the recommended hormonal therapy for postmenopausal women with ER-positive tumors. Tamoxifen is also an active agent for premenopausal metastatic disease, and response rates are comparable to those reported for oophorectomy. Clinical experience with tamoxifen in this younger age group, however, is more limited. Few premenopausal women (less than 400) have been included in phase II and phase III trials. Two randomized trials (total of 160 patients) comparing oophorectomy with tamoxifen do not definitively establish therapeutic equivalence, and a survival advantage for either treatment cannot be excluded. Many questions remain concerning the appropriate role for tamoxifen in premenopausal patients. Still, tamoxifen has an attractive toxicity profile, and it offers a favorable therapeutic alternative for premenopausal women with ER-positive metastatic breast cancer who wish to avoid surgical or radiation castration. 
Structure and expression of the cDNA encoding human neutrophil collagenase. We have isolated and characterized a 2.4-kb cDNA clone encoding human neutrophil collagenase (HNC), a member of the family of matrix metalloproteinases restricted to secondary granules within neutrophils. Partial amino acid sequence was used to deduce oligonucleotide probes. These probes were used to screen a human granulocyte cDNA library derived from messenger RNA (mRNA) from a patient with chronic granulocytic leukemia. Cell-free translation of RNA produced from the cDNA produced a 52-Kd protein that was recognized by anti-HNC antibody. The cDNA clone was sequenced and shown to encode a 467-residue protein whose sequence matched those regions currently known for HNC. The enzyme exhibits 58% homology to human fibroblast collagenase and has the same domain structure. It consists of a 20-residue signal peptide, and an 80-residue propeptide that is lost on autolytic activation by cleavage of an M-L bond. Other regions identified include the autolytic degradation site, the "cysteine switch" residue that is involved in latency and activation, and a putative zinc binding sequence. HNC has six potential N-linked glycosylation sites. The cDNA hybridized to a 3.4-kb mRNA in RNA from a patient with chronic granulocytic leukemia, but not to RNA from uninduced HL60 cells or HL60 cells that had been induced to undergo granulocytic or monocytic maturation with dimethyl sulfoxide or 12-O-tetradecanoylphorbol 13-acetate, respectively. These results parallel those seen with lactoferrin and transcobalamin I, two other secondary granule proteins. 
Treatment of chronic pain by epidural spinal cord stimulation: a 10-year experience. Epidural spinal cord stimulation by means of chronically implanted electrodes was carried out on 121 patients with pain of varied benign organic etiology. In 116 patients, the pain was confined to the back and lower extremities and, of these, 56 exhibited the failed-back syndrome. Most patients were referred by a pain management service because of failure of conventional pain treatment modalities. Electrodes were implanted at varying sites, dictated by the location of pain. A total of 140 epidural implants were used: 76 unipolar, 46 Resume electrodes, 12 bipolar, and six quadripolar. Patients were followed for periods ranging from 6 months to 10 years, with a mean follow-up period of 40 months. Forty-eight patients (40%) were able to control their pain by neurostimulation alone. A further 14 patients (12%), in addition to following a regular stimulation program, needed occasional analgesic supplements to achieve 50% or more relief of the prestimulation pain. Pain secondary to arachnoiditis or perineural fibrosis following multiple intervertebral disc operations, when predominantly confined to one lower extremity, seemed to respond favorably to this treatment. Uniformly good results were also obtained in lower-extremity pain secondary to multiple sclerosis. Pain due to advanced peripheral vascular disease of the lower limbs was well controlled, and amputation below the knee was delayed for up to 2 years in some patients. Pain due to cauda equina injury, paraplegic pain, phantom-limb pain, pure midline back pain without radiculopathy, or pain due to primary bone or joint disease seemed to respond less well. Patients who responded to preliminary transcutaneous electrical nerve stimulation generally did well with electrode implants. Notable complications included wound infection, electrode displacement or fracturing, and fibrosis at the stimulating tip of the electrode. Three patients in this series died due to unrelated causes. Epidural spinal cord stimulation has proven to be an effective and safe means of controlling pain on a long-term basis in selected groups of patients. The mechanism of action of stimulation-produced analgesia remains unclear; further studies to elucidate it might allow spinal cord stimulation to be exploited more effectively in disorders that are currently refractory to this treatment modality. 
Coronary-heart-disease risk-factor status of the Cretan urban population in the 1980s. The traditional Cretan diet has been associated with low coronary-heart-disease (CHD) mortality rates. This study reports on the prevalence of CHD risk factors among 387 Cretan bank employees. Mean cholesterol concentration has risen by 36% over 26-y; dietary intake has changed: consumption of meat, fish, and cheese has increased and consumption of bread, fruit, and potatoes has decreased. Although the percentage contribution of fat to total energy intake has decreased from 40% to 36%, there has been a reduction in monounsaturated fatty acid consumption and an increase in the consumption of saturated fatty acids whereas the consumption of polyunsaturates has not been altered. Exception for diminished physical activity, the prevalence of other risk factors (smoking, blood pressure, and body mass index) remained relatively stable over this period. These changes in the CHD risk-factor status of the Cretan urban population occurred over a period in which CHD mortality rates are reported to have increased. 
Emergency treatment of headache. Headache is a frequent presenting complaint in the emergency department. Once a diagnosis is established, and significant organic disease can be ruled out, relief of pain must be addressed. Referral for follow-up care and narcotic habituation is a recurrent problem for the emergency physician. This article discusses the differential diagnosis of headache, evaluation of the emergency room patient, and treatment of the patient with headache. 
Isradipine for treatment of acute hypertension after myocardial revascularization. OBJECTIVE: To evaluate the efficacy and duration of action of iv isradipine in the control of postoperative hypertension immediately after myocardial revascularization. DESIGN: Prospective, phase 2 trial. SETTING: Surgical ICU, university hospital. PATIENTS: Twenty-one (15 male, six female) patients, ages 49 to 75 yr (mean 65 +/- 5), undergoing elective myocardial revascularization. INTERVENTIONS: Twenty-one patients with postoperative hypertension after coronary artery bypass graft surgery received iv isradipine, a new dihydropyridine calcium-channel antagonist. Mean duration of the isradipine infusion was 96.9 +/- 29 min. Mean dose of isradipine, indexed to weight, was 16.63 +/- 6.66 micrograms/kg (n = 20). MEASUREMENTS AND MAIN RESULTS: Twenty of the 21 patients achieved satisfactory BP control. The reduction in mean arterial pressure (MAP), first noted at the 15-min point, was maximal at 1 hr when MAP decreased from 102 +/- 9 mm Hg baseline to 81 +/- 5 mm Hg (p less than .01), accompanied by a significant (p less than .01) decrease in systemic vascular resistance from 1753 +/- 339 baseline to 1180 +/- 229 dyne.sec/cm5. The CVP, pulmonary artery diastolic pressure, and pulmonary artery occlusion pressure did not change significantly. Heart rate and cardiac index increased; however, stroke volume index did not change. CONCLUSIONS: Isradipine is an acceptable agent for the treatment of hypertension in this setting. 
Value of CT in determining the need for angiography when findings of mediastinal hemorrhage on chest radiographs are equivocal. The role of CT in determining the need for angiography in patients with possible thoracic vascular injury resulting from blunt trauma is controversial. During a 24-month period, we prospectively evaluated the results of CT to screen 90 patients with a history of decelerating thoracic trauma for evidence of mediastinal hemorrhage or great vessel abnormality. All patients either had equivocally abnormal mediastinal contours on chest radiographs (64%) or had technically suboptimal chest radiographs owing to body habitus or restriction to the supine projection (36%). Patients with unequivocal signs of mediastinal hemorrhage on chest radiographs underwent immediate arteriography without prior CT. Thoracic CT was interpreted as normal in 63 (77%) patients and no further imaging was performed. Five patients had technically suboptimal CT studies, and CT scans were interpreted as equivocal in six. These 11 patients had normal arteriograms. Sixteen CT scans (18%) demonstrated evidence of mediastinal hemorrhage and/or great vessel contour abnormality. Four (27%) of 15 patients who underwent arteriography had injury to the great vessels. One patient refused to undergo angiography. In 11 patients with CT evidence of mediastinal hemorrhage, major vascular injury was not seen on arteriography. These results suggest a valuable role for CT in determining the need for arteriography to detect potential great vessel injury in patients with blunt decelerating thoracic trauma and equivocally abnormal mediastinal contours on chest radiographs. 
Percutaneous intraarterial thrombolysis in the treatment of thrombosis of lower extremity arterial reconstructions. Vascular grafts may be salvaged with thrombolytic therapy after acute occlusion as an alternative to balloon catheter thrombectomy. From October 1987 to May 1990, 15 arterial bypasses to the lower extremity (infrainguinal saphenous vein [n = 7] or expanded polytetrafluoroethylene [n = 6], and Dacron aortofemoral bifurcation graft limbs [n = 2]) were treated for 30 occulsions with intraarterial urokinase (390,000 IU to 5,808,000 IU) infused from 3 to 40 hours. The origins of 15 graft occlusions were morphologic defects (intimal hyperplasia with anastomotic or conduit stricture), pseudoaneurysm, or progression of disease distal to the graft. Two occlusions were attributed to coagulation disorders. A cause could not be identified for 13 occlusions. Patency was initially restored to all grafts with use of thrombolytic therapy, however, adjunctive surgical thrombectomy to remove persistent thrombus from the graft or outflow vessels was required after six thrombolytic infusions. One graft in the series could not be salvaged leading to below-knee amputation. Graft defects were corrected by balloon angioplasty (n = 7) or surgical revision of the conduit (n = 8). Five significant hemorrhagic complications occurred from the catheter insertion site requiring four emergent surgical procedures and resulting in the death of a fifth patient from a myocardial infarction. This technique allows chemical thrombectomy of branch arteries distal to the graft and inaccessible to a balloon embolectomy catheter, and permits diagnosis of abnormal graft morphology that may be the cause of the graft occlusion. Graft reocclusion can be expected if technical defects in the arterial reconstruction are not revised or hypercoagulable states are not treated. 
Primary malignant melanoma of the oesophagus: case report and review of surgical pathology. Primary malignant melanoma of the oesophagus is both a rare presentation for melanoma and a cause of oesophageal neoplasm. It accounts for less than 0.1% of all primary oesophageal neoplasms. It was first recognised as a primary tumour by de la Pava et al who showed the presence of melanocytes within oesophageal mucosa. This case report includes a review of the surgical pathology. Even though it is a rare lesion it must be considered as a cause of polypoidal oesophageal lesions as both its diagnosis and treatment can present problems. It is usually fatal within one year. 
Incidence and characteristics of preventable iatrogenic cardiac arrests We studied the contribution of iatrogenic illness to cardiac arrest among patients hospitalized in 1981 in a university teaching hospital. During this 1-year period, 28 (14%) of 203 arrests in which resuscitation was attempted followed an iatrogenic complication. Seventeen (61%) of the 28 patients died. The demographic characteristics of patients with iatrogenic arrest did not differ strikingly from those of other patients who arrested. However, patients with iatrogenic arrest were less likely to be in cardiogenic shock or to have suffered an acute myocardial infarction prior to arrest. They were more likely to survive to discharge from the hospital and to be taking digoxin or antiarrhythmic medication prior to arrest. Among the 28 cases of iatrogenic cardiac arrest, 18 (9% of all arrests) might have been prevented by stricter attention to the patient's history, findings on physical examination, and laboratory data. The most common causes of potentially preventable arrest were medication errors and toxic effects (44%) as well as suboptimal response by physicians to clinical signs and symptoms (28%), most frequently dyspnea and tachypnea. Rapid, appropriate response to abnormal drug levels, to electrocardiographic signs of adverse drug effects, and to signs and symptoms of congestive heart failure or toxic effects from digoxin might decrease the incidence of cardiac arrest among hospitalized patients. 
Long-term maintenance treatment of reflux esophagitis with omeprazole. Prospective study in patients with H2-blocker-resistant esophagitis. Thirty-four patients with H2-blocker-resistant reflux esophagitis subsequently healed by 40 mg omeprazole daily entered a maintenance study with 20 mg omeprazole. In 31 evaluable cases the observation period was at least 12 months (mean 24 months). Esophagitis remained in remission in two thirds of patients despite dose reduction. Relapses of esophagitis occurred in 10 cases within six months, which rapidly healed by increasing the omeprazole dose to 40 mg. No further recurrence with 20 mg omeprazole was found later than six months. Peptic strictures primarily requiring repeated dilatation in six patients during healing with omeprazole did not reappear while on omeprazole maintenance. Major side effects that could be attributed to omeprazole were not observed. Gastrin levels remained within or slightly above the normal range in the vast majority. It is concluded that omeprazole maintenance treatment in severe reflux esophagitis is an effective and safe therapy. 
Assessment of the defunctioning efficiency of the loop ileostomy. The defunctioning efficiency of the loop ileostomy has been assessed using a radioisotope and dye technique. The median defunctioning capacity in patients without episodes of fecal discharge per rectum (n = 18) was 99.99 percent and was not affected by body position or the formation of a dependent stoma. In patients (n = 4) who passed fecal material per rectum but who had no stomal retraction, the median defunctioning efficiency was 99.99 percent, and continued fecal discharge was considered to be due to mucopurulent secretion from active distal disease. In patients who passed fecal material per rectum and also had a retracted stoma (n = 4), the defunctioning efficiency was significantly reduced (median = 84.70 [31.2-99.10 percent; P less than 0.01]), owing to the overspill into the distal limb. Two patients underwent stomal revision, with an improvement in defunctioning efficiency to 99.99 percent. 
Endocrine responses to long-term administration of the antiprogesterone RU486 in patients with pelvic endometriosis. OBJECTIVE: To examine endocrine and clinical responses to long-term administration of RU486 in patients with endometriosis. DESIGN: Prospective open trial. SETTING: Faculty practice of the authors. PATIENTS, PARTICIPANTS: Six normally cycling women with endometriosis were recruited. INTERVENTIONS: Subjects received RU486 100 mg/d for 3 months. MAIN OUTCOME MEASURE(S): Hormonal changes during RU486 were compared with control data obtained in the preceding cycle during the early follicular phase. Clinical responses were determined by patient assessment and second-look laparoscopy. RESULTS: All women became amenorrheic, and daily urinary levels of ovarian steroid metabolites remained acyclic. Mean luteinizing hormone (LH) (P less than 0.02) and LH pulse amplitude (P less than 0.05) were increased without changes in LH pulse frequency. An antiglucocorticoid effect was demonstrated by an increase in serum cortisol (P less than 0.01) and adrenocorticotropic hormone (P less than 0.05) levels. Treatment resulted in an improvement in pelvic pain in all subjects without significant change in the extent of disease as evaluated by follow-up laparoscopy. CONCLUSIONS: Daily administration of RU486 results in acyclic ovarian function and improvement in the subjective painful symptoms of endometriosis. 
Fluconazole: a new triazole antifungal agent. Fluconazole is a recently approved agent for the treatment of certain fungal infections. Based on available studies, the drug is clearly effective in oropharyngeal candidiasis in immunosuppressed hosts. Current evidence suggests it may be more efficacious than other azole drugs for oropharyngeal disease. It is probably also effective in other infections due to Candida species, but controlled studies are lacking. Fluconazole is also efficacious in the treatment of cryptococcal meningitis, but recent reports question its use as initial therapy in HIV-infected patients with this illness. The drug, however, is clearly more effective than amphotericin B in the suppression of cryptococcal meningitis in AIDS patients and is the treatment of choice in this situation. 
Hypophysectomy inhibits the synthesis of tumor necrosis factor alpha by rat macrophages: partial restoration by exogenous growth hormone or interferon gamma. We recently demonstrated that GH and interferon-gamma (IFN gamma) act in a similar manner to prime macrophages in vitro and in vivo for enhanced superoxide anion release. In this report we investigated the physiological role of the pituitary gland and GH in in vivo priming of resident peritoneal macrophages for the synthesis of tumor necrosis factor-alpha (TNF alpha) in vitro. Compared to normal rats, hypophysectomized animals had an 83% reduction in macrophage production of TNF alpha after in vitro stimulation with lipopolysaccharide. Sham operation had no significant effect on the ability of macrophages to secrete TNF alpha in response to lipopolysaccharide. Both native pituitary-derived porcine GH (48 micrograms/rat.9 days) and native pituitary-derived rat GH (96 micrograms/rat.9 days) more than tripled the in vitro production of TNF alpha by macrophages from hypophysectomized rats (342 and 358 vs. 112 U/mg protein for placebo-treated rats, respectively). Each of these preparations of GH also increased growth more than 6-fold in hypophysectomized rats (32 and 30 g vs. 5 g in placebo controls). Heat inactivation of native pituitary-derived porcine GH significantly reduced its in vivo ability to augment both TNF alpha synthesis by macrophages and body growth. Recombinant rat IFN gamma (2000 U/rat.9 days) more than tripled the production of TNF alpha by macrophages from hypophysectomized rats (343 vs. 112 U/mg protein). In contrast to its in vivo effects, addition of GH in vitro to macrophages from hypophysectomized rats did not prime these cells for the synthesis of TNF alpha, indicating an indirect mechanism of action for GH. To further test the biological relevancy of GH with respect to synthesis of TNF alpha, hemorrhagic necrosis of TNF alpha-sensitive murine methyl-cholanthrene-induced tumors was assessed in pituitary-intact mice. Native porcine GH (133 micrograms/mouse.7 days) significantly augmented both the necrosis to tumor ratio and the hemorrhage to tumor ratio. These findings establish the physiological relevance of the pituitary gland and GH in the priming of macrophages for TNF alpha synthesis. 
Mentally retarded individuals--a population at risk? When comparing the aging process of mentally retarded (MR) persons with the nondisabled population, researchers have established an earlier lower limit for the onset of old age for MR persons and a higher mortality rate. The reason for early senescence has not been successfully resolved, but the finding that cardiovascular disorders are the most prevalent form of disease among elderly MR persons suggests a relationship between lifestyles and higher mortality rate. Indeed, studies that evaluated the cardiovascular fitness (CVF) of MR individuals demonstrated substandard levels of fitness. The results of these studies, however, are not conclusive due to variation in test methodologies, motivational factors, and issues of test validity and reliability. Training studies which have purported to determine trainability of this population have also shown confusing results, perhaps attributed to the same protocol inconsistencies. Therefore, the purposes of this article are 1) to review previous methods of evaluating CVF of MR adults and determine whether testing methodologies invalidate the results of these studies, 2) to review training studies involving adult MR individuals and determine whether this population is capable of improving their CVF, and 3) to identify areas where further research is needed to fully describe the functional cardiovascular characteristics of MR adults. 
Case report: cisplatin-induced hemolytic uremic syndrome. Two patients developed noncardiogenic pulmonary edema (NCPE), following red blood cell transfusion in a setting of acute cisplatin nephropathy. One manifested the full picture of hemolytic uremic syndrome, the other had transient features following blood transfusion. We further reviewed the clinical records on blood transfusion for all patients with cisplatin nephropathy. A third case of (NCPE) was identified in a patient with acute renal dysfunction. However, none of the 16 patients with cisplatin-induced, mild stable chronic renal impairment had pulmonary dysfunction or other laboratory evidence for microangiopathy following transfusion. Hemolytic uremic syndrome may be a rare manifestation of cisplatin toxicity. Caution is indicated in transfusing patients with acute platinum nephropathy even in the absence of overt microangiopathy. The pathogenesis of this syndrome and the cause for NCPE is unclear. The literature is reviewed and discussed. 
Ventriculoatrial shunts for hydrocephalus and cardiac valvulopathy: an echocardiographic evaluation. A group of 20 patients with ventriculoatrial shunts placed as surgical treatment for hydrocephalus were evaluated for cardiac lesions, particularly of the tricuspid valve. Patients with histories of septic or thromboembolic events were excluded. In each patient a clinical history, complete physical examination, electrocardiogram, chest x-ray film and M-mode, two-dimensional and pulsed continuous wave and color-coded Doppler echocardiography were performed. Eight patients were found to have cardiac abnormalities including tricuspid valve insufficiency, tricuspid stenosis and insufficiency, and the catheter passing through the foramen ovale into the left atrium. These findings demonstrate that tricuspid valvular lesions are frequent in patients with ventriculoatrial shunts, and that periodic echocardiographic evaluation should be performed routinely. 
Extensive pulmonary embolism presenting as severe adult respiratory distress syndrome after surgical resection of a cornual pregnancy. A rare case of severe adult respiratory distress syndrome associated with a Po2 of 9 mm Hg after surgical resection of a cornual pregnancy at 10 weeks' gestation was treated successfully with positive end-expiratory pressure. The underlying cause, extensive pulmonary embolism, was subsequently revealed. The patient survived without residual brain damage. The possible causes of adult respiratory distress syndrome in pregnancy are discussed. 
Comparison of rubidium-82 positron emission tomography and thallium-201 SPECT imaging for detection of coronary artery disease. The diagnostic performance of rubidium-82 (Rb-82) positron emission tomography (PET) and thallium-201 (Tl-201) single-photon emission-computed tomography (SPECT) for detecting coronary artery disease was investigated in 81 patients (52 men, 29 women). PET studies using 60 mCi of Rb-82 were performed at baseline and after intravenous infusion of 0.56 mg/kg dipyridamole in conjunction with handgrip stress. Tl-201 SPECT was performed after dipyridamole-handgrip stress and, in a subset of patients, after treadmill exercise. Sensitivity, specificity and overall diagnostic accuracy were assessed using both visually and quantitatively interpreted coronary angiograms. The overall sensitivity, specificity and accuracy of PET for detection of coronary artery disease (greater than 50% diameter stenosis) were 84, 88 and 85%, respectively. In comparison, the performance of SPECT revealed a sensitivity of 84%, specificity of 53% (p less than 0.05 vs PET) and accuracy of 79%. Similar results were obtained using either visual or quantitative angiographic criteria for severity of coronary artery disease. In 43 patients without prior myocardial infarction, the sensitivity for detection of disease was 71 and 73%, respectively, similar for both PET and SPECT. There was no significant difference in diagnostic performance between imaging modalities when 2 different modes of stress (exercise treadmill vs intravenous dipyridamole plus handgrip) were used with SPECT imaging. Thus, Rb-82 PET provides improved specificity compared with Tl-201 SPECT for identifying coronary artery disease, most likely due to the higher photon energy of Rb-82 and attenuation correction provided by PET. However, post-test referral cannot be entirely excluded as a potential explanation for the lower specificity of Tl-201 SPECT. 
Treatment of snoring and obstructive sleep apnea with a dental orthosis. A dental orthosis, designed to increase the size of the upper airway by advancing the mandible, was used in 68 patients to treat snoring and varying degrees of obstructive sleep apnea. The orthosis increased the posterior airway space, as assessed by lateral cephalograms. Seven months (range 2 to 25) after beginning use, 75 percent of patients were using the orthosis regularly. Snoring, by report, was improved in all patients but one (p less than 0.001) and was eliminated in 42 percent (95 percent confidence interval 30 to 55 percent). Sleep quality and sleepiness were also reported improved. Apneas and hypopneas, measured before and after use in 20 patients with obstructive sleep apnea, were reduced from an average of 47 to 20 events per hour (p less than 0.001). Oxygenation and sleep disturbance were also improved. Apnea-hypopnea frequency was reduced with treatment to less than 20/h in 13 patients. Residual frequencies greater than 20/h were associated with higher initial frequencies of apneas and hypopneas. Side effects of orthosis use were minor, and no serious complications were observed. The dental orthosis is an effective treatment for the symptom of snoring and can also effectively treat obstructive sleep apnea of moderate severity. 
Prolactin reduction after combined therapy for prolactin macroadenomas. The ability of surgery or bromocriptine to produce endocrine control of a prolactin macroadenoma decreases as the prolactin level increases. Guidelines for the use of multimodality therapy have not been developed for tumors associated with markedly elevated prolactin levels. We reviewed the records of 21 patients with prolactin levels greater than 200 ng/ml treated by transsphenoidal surgery and postoperative radiotherapy with or without a dopamine agonist. Values before and after treatment were available for 19 patients (13 men and 6 women). The mean basal prolactin level before treatment for the entire group was 2410 ng/ml. Surgery and radiotherapy resulted in a 90% reduction and serum prolactin levels within normal limits in 0 of 7 patients, versus the combination of surgery, radiotherapy, and dopamine agonist, which resulted in a 99.5% reduction and values within the normal range in 12 of 12 patients. Spontaneous physiological improvement was not often observed. One woman and two men were able subsequently to have children. A plan for these patients is discussed. 
Stereotactic brain biopsy in the diagnosis of malignant lymphoma. Fifteen patients with cerebral involvement by malignant non-Hodgkin's lymphoma were identified, among more than 200 patients who underwent stereotactic biopsy at The Johns Hopkins Hospital. All but one of these cases were diagnosed accurately by the stereotactic biopsy procedure. In 12 of 14 patients, the material was adequate to classify the lymphoma according to the Working Formulation. Because all but one of the lesions were intermediate or high-grade neoplasms, a diagnosis of lymphoma was often possible by conventional light microscopic examination alone. Monotypic light chain expression was demonstrated by immunohistochemical techniques in six patients, and positivity for B-cell markers was observed in an additional case. In one instance, two stereotactic biopsy specimens were interpreted as being suggestive of lymphoma, but necrosis and inflammation prevented a definitive diagnosis. Nine patients had no known risk factors for cerebral lymphoma, and the diagnosis often was unsuspected clinically. 
Multivariate clinical models and quantitative dipyridamole-thallium imaging to predict cardiac morbidity and death after vascular reconstruction. Patients with peripheral vascular disease have a high prevalence of coronary artery disease and are at increased risk for cardiac morbidity and death after vascular reconstruction. The present study was undertaken to assess the value of 18 clinical parameters, of 7 clinical scoring systems, and of quantitative dipyridamole-thallium imaging for predicting the occurrence of postoperative myocardial infarction or cardiac death. Vascular surgery was performed in 125 patients. Thirteen postoperative cardiac events occurred, including 10 cardiac deaths and 3 nonfatal infarctions. Clinical parameters were not useful in predicting postoperative outcome. All 63 patients with normal scan results or fixed perfusion defects underwent surgery uneventfully, whereas 21% (13/62) of patients with reversible defects had a postoperative cardiac complication. By use of quantitative scintigraphic indexes we found that patients with reversible defects could be stratified into intermediate and high-risk subgroups with postoperative event rates of 5% (2/47) and 85% (11/13), respectively, despite intensive postoperative monitoring and antianginal medication. Thus in patients unable to complete a standard exercise stress test, postoperative outcome cannot be predicted clinically, whereas dipyridamole-thallium imaging successfully identified all patients who had a postoperative cardiac event. By use of quantification we found that patients with reversible defects can be stratified into an intermediate risk subgroup that can undergo surgery with minimal complication rate and a high-risk subgroup that requires coronary angiography. 
A randomized, controlled trial of treatment of alcoholic hepatitis with parenteral nutrition and oxandrolone. II. Short-term effects on nitrogen metabolism, metabolic balance, and nutrition. Patients with moderately severe or severe alcoholic hepatitis, described in a companion paper in this issue, had serial studies of energy and protein metabolism and elemental balances before and during treatment for 21 days with one of four randomly assigned regimens: 1) standard therapy, consisting of abstinence, a balanced, nutritionally adequate diet, and multivitamins; 2) oxandrolone (20 mg orally four times a day) plus standard therapy; 3) nutritional supplementation, consisting of 2 liters of 3.5% crystalline amino acids in 5% dextrose given by peripheral vein (PPN) plus standard therapy; and 4) a combination of the other three treatments. Dietary and intravenous intakes and weights were recorded daily, and weekly averages were calculated. Anthropometric measurements and blood studies were done weekly; blood studies included white blood cell counts and differentials, serum prealbumin, transferrin, and total protein and plasma aminograms. Four-days complete balance studies and measures of 15N,1-13C-leucine metabolism also were performed at baseline and after the treatment period. Major findings were as follows: a) Intakes of total calories and protein were significantly higher in PPN-treated than in other groups. b) All patients had positive elemental balances, both at baseline and at the end of the treatment period. However, those treated with PPN (with or without oxandrolone) had higher positive balances of nitrogen, potassium, phosphorus, and magnesium, indicating improvement in lean body mass. c) Anthropometric measurements showed no significant changes, but measures of the visceral protein compartment (serum prealbumin, transferrin, total protein, total lymphocyte count) improved significantly with time. For most of these variables, increases were significantly greater in those treated with PPN with or without oxandrolone than in the other groups. However, for prealbumin, the increase was greatest in the oxandrolone-treated group d) PPN treatment produced dramatic increases in levels of branched-chain amino acids and improvement in the ratio of plasma branched chain to aromatic amino acids. Other treatments had no effect on plasma aminograms. e) Metabolism of 15N,1-13C-leucine was normal and was not affected significantly by treatment. Therapy with PPN and/or oxandrolone was tolerated well. We conclude that PPN has favorable effects on energy and protein metabolism in florid alcoholic hepatitis; oxandrolone has lesser effects, although it may exert some additional action and particularly increases serum prealbumin levels. The results support the use of nutritional supplementation in therapy of moderately severe or severe alcoholic hepatitis. 
Reversal of a dense, persistent, holohemispheric neurological deficit after an endarterectomy of the carotid artery: case report. The role and timing of a carotid endarterectomy in the setting of an acute ischemic stroke-in-evolution remain controversial. Although computed tomographic (CT) scans typically show no abnormalities in the acute stage, it is generally agreed that a dense neurological deficit (hemiplegia) and/or multiple modality neurological disturbance (involving motor, sensory, gaze, and visual field impairment) represent contraindications to surgical intervention. We present a case of an acute right holohemispheric neurological deficit including dense hemiplegia, hemisensory loss, gaze disturbance, hemineglect, and impaired level of consciousness. This persisted for 4 days while serial CT scans showed no evidence of infarction. Angiography revealed pre-occlusive stenosis of the right internal carotid artery with sluggish antegrade flow. The anterior collaterals of the circle of Willis were impaired, and the right middle cerebral artery territory filled via the posterior communicating artery. Despite the dense neurological deficit persisting for 4 days, a carotid endarterectomy was performed. Gradual neurological improvement was noted within hours of the operation, and all neurological deficits resolved within the subsequent 3 days. This case is consistent with prolonged holohemispheric hemodynamic compromise below the threshold of neurological dysfunction, but above the threshold of tissue infarction ("idling neurons"). Features assisting in the recognition of this unusual scenario and the indications and risks of revascularization in this setting are discussed. 
William Heberden and Myron Prinzmetal: angina pectoris. The most significant accounts of angina pectoris appeared in the medical literature separated by nearly two centuries. They were Heberden's initial description of classic angina and Prinzmetal's report of the variant form. Angina pectoris represents a transient myocardial oxygen deficiency. It is usually related to atherosclerotic coronary artery disease, but there are a number of less common etiologies, most notably aortic stenosis. Stable and unstable forms exist, with stable angina being further subclassified as being of one of four patterns: classic, variant, atypical, and angina equivalent. 
The Purkinje cell and its afferents in human hereditary ataxia. The cerebellar cortex in patients with autosomal dominant and recessive ataxia was studied by Golgi impregnation and immunocytochemistry in order to gain further insight into the pathogenesis of neuronal atrophy which accompanies these disorders. Monoclonal antisera were used to visualize phosphorylated and non-phosphorylated neurofilament proteins, and a synapse-specific protein (P38; synaptophysin). Golgi stain and immunocytochemistry for non-phosphorylated neurofilament protein revealed partial or complete loss of distal Purkinje cell dendrities in the dominant cases and in one recessive case. Many preserved parallel fibres were shown by the monoclonal antibody to phosphorylated neurofilament protein. This antibody also gave strong reaction product in torpedoes. Axosomatic and axodendritic terminals on Purkinje cells were reduced in number, and loss of mossy fiber terminals was revealed by monoclonal anti-P38. The described methods provided additional morphological evidence of the heterogeneity of the hereditary ataxias. Purkinje cell atrophy progressed from loss and simplification of the dendritic tree to disappearance of the cell body. While these cells appeared to be especially vulnerable, other neurons of the molecular and granular layers were not exempt. There was evidence that at least some extracerebellar afferents, such as mossy fibers, were also affected by the disease process. 
Salvage therapy with high-dose chemotherapy and autologous bone marrow support in the treatment of primary nonseminomatous mediastinal germ cell tumors. The authors reported their experience with the use of high-dose chemotherapy and autologous bone marrow rescue (ABMR) as salvage therapy in the treatment of patients with recurrent and refractory primary nonseminomatous mediastinal germ cell tumors (PMGCT). Since 1987, the authors have treated 12 patients with PMGCT with high-dose carboplatin (1500 mg/m2 to 1800 mg/m2) and etoposide (1200 mg/m2 to 1350 mg/m2) (in two patients ifosfamide [10 g/m2] was added) with ABMR. Patients were either in second relapse or cisplatin refractory (progression within 4 weeks of last cisplatin dosing). They had received a median of two prior chemotherapy regimens (range, one to three), all had had prior cisplatin therapy, and most had failed ifosfamide-based therapy. Six patients were cisplatin refractory and of these only one achieved a partial response (PR) that was of short duration. It was planned that all patients would undergo two rounds of therapy; however, only 5 of 12 patients received two courses. The remainder had only one round of therapy either because of inadequate response (three patients) or excessive toxicity (four patients). There were four patients who died in the peritransplant period due to sepsis (two patients) or bleeding (two patients). The median survival of the group was 107 days (range, 14 days to 347 days). No patient achieved a complete remission, but there were six partial remissions, four with stable disease, and two with progressive disease. The use of high-dose carboplatin and etoposide with or without ifosfamide and ABMR was not effective in the treatment of this group of patients with PMGCT who were in second relapse or cisplatin refractory. 
Predictors of physical functioning after a cardiac event. An increased understanding of the factors that promote or hinder patients' return to optimal activity levels after a cardiac event is necessary to help them achieve this goal. Accordingly, the purpose of this study was to examine psychologic resources, depression, physical recovery, and illness severity for their relationships with subjective and objective physical functioning (exercise data). A correlational survey design was used to assess patients' (n = 46) illness responses 9 weeks after the cardiac event. Patients also participated in a symptom-limited exercise test. The findings suggested that the individual's return to greater activity levels after a cardiac illness was associated with less depression and illness severity, and higher levels of objective physical functioning, physical recovery, and self-esteem. Further, patients' objective physical functioning was associated not only with greater subjective physical functioning but also with greater levels of physical recovery and mastery. 
Electronic fetal heart monitoring, auscultation, and neonatal outcome. In a large randomized, controlled study of fetal heart rate monitoring with either continuous electronic fetal heart monitoring or auscultation at specified intervals, only one pattern of deviation in the fetal heart rate correlated significantly with neonatal neurologic examinations at 0 to 48 hours and 72 hours to 1 week: late decelerations in stage 1 and in stage 2. Other variables from labor and delivery, specifically, duration of labor after hospital admission, failure of labor to progress, number of fetal scalp pH values, and presence of meconium were important predictors of neonatal outcome in the regression analyses. The fetal heart rate deviations did contribute significantly to the percent variance accounted for in the regression analyses with neonatal outcomes of Apgar scores at 1 and 5 minutes and serial neonatal neurologic examinations. 
Hydrocortisone inhibits rat basophilic leukemia cell mediator release induced by neutrophil-derived histamine releasing activity as well as by anti-IgE. We determined the ability of hydrocortisone to inhibit rat basophilic leukemia cell mediator release induced by anti-IgE and by neutrophil-derived histamine-releasing activity (HRA-N). Serotonin release induced by HRA-N and anti-IgE was inhibited by 78 +/- 5 and 70 +/- 4%, respectively (IC50 7.5 x 10(-7)M) by hydrocortisone (10(-5)M). HRA-N does not cause arachidonic acid metabolism, however, anti-IgE induced the generation of PGD2 and leukotriene (LT)C4, and the generation of both mediators was inhibited by 10(-5)M hydrocortisone (IC50 = 4.8 x 10(-7)M, and 3.6 x 10(-9)M, respectively). Inhibition required at least 5 to 6 h of hydrocortisone exposure and was maximal after 22 h. The observed effects of hydrocortisone could be reproduced by human recombinant lipocortin-I (5 x 10(-7)M). Hydrocortisone, 10(-5)M, was a less potent inhibitor of calcium ionophore A23187-mediated serotonin release and PGD2 and LTC4 generation (inhibition of 20 +/- 2, 17 +/- 10, and 37 +/- 10%, respectively). Inasmuch as A23187-induced stimulation is not dependent on receptor coupling, the enhanced ability of hydrocortisone to inhibit IgE- and HRA-N-mediated events as compared with A23187 suggests that one possible site of action of hydrocortisone may be interruption of receptor-effector signals. In the presence of arachidonic acid, hydrocortisone-treated cells released as much LTB4 and PGD2 as control cells, however, serotonin release and LTC4 generation were inhibited 50 and 55%, respectively. Thus, these data suggest that hydrocortisone has three possible sites of action: 1) inhibition of phospholipase A2 activity, 2) inhibition of glutathione-s-transferase, and 3) inhibition of serotonin release by a third mechanism, possibly by interrupting the coupling of receptor and effector systems. 
Geographic variations in the histologic characteristics of the gastric mucosa. Histologic sections of 205 gastrectomy specimens, which were obtained for benign and malignant diseases, were reviewed. All patients were Mexican nationals. The following histologic features were recorded: intestinal metaplasia, intramucosal cysts, ciliated gastric cells, and different types of pyloric cells ("ordinary"; with granular cytoplasm; with small cytoplasmic vacuoles; with large cytoplasmic vacuoles; or with homogeneous "glassy" cytoplasm). The percentage of specimens showing intestinal metaplasia was similar in those containing gastric ulcers (42.7%) or adenocarcinomas (50.0%). Intestinal metaplasia was decreased in men 59 years of age or older and in women 69 years of age or older. Diffuse-type adenocarcinoma accounted for 90% of the gastric tumors. Only 3 of the 205 specimens (1.9%) contained intramucosal cysts, and only 1 (0.4%) showed ciliated cells. Pyloric cells with granular cytoplasm were observed in 21.2% of the specimens, and pyloric cells with small cytoplasmic vacuoles were seen in 1.9%. Pyloric cells with large vacuoles or "glassy" cytoplasm were not found in any case. These results indicate differences in the proportions of several histopathologic findings in the gastric mucosa, between Mexicans and other ethnic groups that have been investigated in previous surveys. The authors' findings support the hypothesis that different environmental factors, acting in disparate geographic regions, may account for dissimilarities in the histologic appearance of "normal gastric mucosa.". 
T-lymphocyte dysfunctions occurring together with apical gut epithelial cell autoantibodies. Gut epithelial cell autoantibodies have been considered a hallmark of autoimmune enteropathy, a disorder occurring in children with protracted diarrhea of unknown etiology. Four patients (two male and two female) with such autoantibodies were studied. Immunofluorescence analysis showed two different disjunctive staining patterns: complement-fixing apical (three of four) and cytoplasmic (the remaining fourth one), which are shown to be directed against different structures. All three patients positive for complement-fixing apical gut epithelial cell autoantibodies had abnormal T-cell responses in vitro, one of them with an immunoglobulin G2 immunoglobulin deficiency and another with an immunoglobulin A deficiency. An immunoglobulin A deficiency without T-cell alterations was also diagnosed in the cytoplasmic gut epithelial cell autoantibody-positive patient. These findings suggest that different immunologic alterations (either a T-cell abnormality or immunoglobulin deficiency) may favor the appearance of gut epithelial cell autoantibodies (complement-fixing apical or cytoplasmic, respectively). Furthermore, these autoantibodies should not be considered a specific marker of autoimmune enteropathy, because they may not always be associated with such a disease: two patients with apical gut epithelial cell autoantibodies showed no signs of intestinal lesion or diarrhea. 
Age-related complications and optimal choice of artificial heart valves in elderly patients. The use of bioprosthetic heart valves in elderly patients is presently advocated by many since implanting mechanical valves are considered to result in unacceptable rates of thromboembolism and bleeding. However the somewhat limited durability of bioprostheses has to be acknowledged since a group of elderly patients will eventually require a reoperation due to tissue failure. We have evaluated our policy to implant mechanical heart valve prostheses even in elderly patients based on the conception that we believe that anticoagulation in this group of patients can be handled with a low rate of complications. 
Massive incisional hernia: abdominal wall replacement with Marlex mesh. Marlex (polypropylene) mesh was used to replace the abdominal wall in massive incisional herniation in 50 patients. Seventeen unsuccessful attempts at primary repair had previously been made on nine patients. Patient follow-up ranged from 6 to 120 months (mean = 45 months). There was minor hernia recurrence in four (8 per cent) patients. In each instance it was due to partial detachment of the peripheral fixation of the patch. Complications were: wound infection, four (8 per cent); wound seroma, two (4 per cent); wound haematoma, one (2 per cent); and wound sinus, six (12 per cent). Complications did not necessitate removal of the patch in any case. Inadequate peripheral attachment of the patch has been the only cause of hernia recurrence and should be avoidable. 
Clinical characteristics of transient ischemic attacks in black patients. We analyzed the clinical, CT, and angiographic findings in 50 black patients with carotid transient ischemic attacks (TIAs). Thirty-two percent had TIAs lasting less than 1 hour, 26% had TIAs lasting 1 to 6 hours, and 42% had TIAs lasting 6 to 24 hours. Fifty-two percent of TIA patients had CT evidence of cerebral infarction despite complete clinical recovery. CT was abnormal in two of 16 (13%) patients with TIAs lasting less than 1 hour; however, CT was abnormal in 24 of 34 (70%) patients with TIAs lasting longer than 1 hour. Angiographic findings of extracranial carotid disease appropriate to TIA symptoms were present in 12 (24%) patients. Two patients in whom the TIA episode lasted less than 1 hour later had clinical cerebral infarction, whereas 20 patients with longer-duration TIAs developed ischemic stroke within 4 months. Of these black TIA patients, 22 (44%) developed clinical cerebral infarction. 
Bilateral spontaneous perilymph fistulae: a diagnostic and management dilemma. In this article, we present a case of bilateral perilymph fistulae. This entity is rare and always presents a diagnostic problem. Bilateral perilymph fistulae are more common in children and should be suspected when bilateral ear symptoms and congenital temporal bone radiographic anomalies are present. Previous trauma or barotrauma may be absent. When a patient manifests bilateral ear symptoms and a fistula has been identified and repaired in one ear, a second fistula should be suspected in the contralateral ear, especially if the fistula test is positive. 
Influence of dilated cardiomyopathy, myocarditis and cardiac transplantation on the relation between plasma atrial natriuretic factor and atrial pressures. To determine whether dilated cardiomyopathy, myocarditis or cardiac transplantation affect the relation between plasma immunoreactive atrial natriuretic factor (ANF) and cardiac filling pressures, right atrial plasma ANF concentration, pulmonary arterial wedge pressure and right atrial pressure were measured in patients with dilated cardiomyopathy (n = 48), dilated cardiomyopathy secondary to myocarditis (n = 20) and prior cardiac transplantation (n = 34). ANF level significantly correlated with both pulmonary arterial wedge and right atrial pressures in patients with dilated cardiomyopathy; however, the presence or absence of myocarditis did not significantly alter these relations (p = 0.88 and p = 0.33 for interaction terms, respectively). For the combined group the ANF-pulmonary arterial wedge pressure relation had a slope of 8.1 pg/ml/mm Hg (95% confidence interval (CI), 5.4 to 10.8; p = 0.0001) and the ANF-right atrial pressure relation a slope of 13.6 pg/ml/mm Hg (CI, 8.5 to 18.7; p = 0.0001). Receiver operator curve analysis identified an optimal dividing point of ANF 150 pg/ml with 100% (CI, 72 to 100%) of patients with right atrial pressure greater than or equal to 8 mm Hg having ANF greater than or equal to 150 pg/ml, but only 56% (CI, 42 to 69%) with pressure less than 8 mm Hg having ANF less than 150 pg/ml. Unlike the patients with cardiomyopathy (with or without myocarditis), cardiac transplant recipients displayed no correlation between ANF level and either pulmonary arterial wedge pressure (p = 0.50) or right atrial pressure (p = 0.29) despite similarly elevated ANF concentrations (mean +/- standard deviation 168 (83) pg/ml in transplant patients versus 185 (114) pg/ml in cardiomyopathy patients). It is concluded that left and right intracardiac pressures are important determinants of circulating ANF level unaffected by inflammation in patients with cardiomyopathy. 
Cyst of the ligamentum flavum: report of six cases. Six cases of cyst of the ligamentum flavum with compression of a lumbar nerve root are reported. All patients exhibited recurrent back pain and sciatica. Investigation included computed tomography, myelography, or both. The correct diagnosis was reached before operation in only half the patients. High-resolution computed tomography performed in the four last patients outlined the cystic lesion with its low-density center. Surgical excision was performed in all patients. Microscopic examination showed a dense fibrous cyst arising from the ligamentum flavum. The lumen contained myxoid or necrotic material, but no epithelial lining. Cysts of the ligamentum flavum must be considered in the differential diagnosis of causes of sciatica. A firm radiological diagnosis may, at present, still require myelography combined with high-resolution computed tomography. Differentiation from synovial or ganglion cysts of the spine is discussed. 
Histopathology of incipient fundus flavimaculatus. A 9-year-old boy was diagnosed with fundus flavimaculatus in his left eye. The boy's fellow eye was enucleated at 16 months of age for retinoblastoma. The authors reviewed the material submitted for histopathologic examination and found that the retinal pigment epithelial cells demonstrated increased autofluorescence and increased reactivity to periodic acid-Schiff staining. Many cells had their melanin granules displaced toward the cell apex. The retinal pigment epithelial changes are consistent with previous histopathologic findings in fundus flavimaculatus and imply that the structural changes are seen in early life. 
Head-injured patients who talk and deteriorate into coma. Analysis of 211 cases studied with computerized tomography. Of 838 patients with severe head injuries admitted since the introduction of computerized tomography, 211 (25.1%) talked at some time between trauma and subsequent deterioration into coma. Of these 211 patients, 89 (42.2%) had brain contusion/hematoma, 46 (21.8%) an epidural hematoma, 35 (16.6%) a subdural hematoma, and 41 (19.4%) did not show focal mass lesions. Thus, four of every five patients who deteriorated into coma after suffering an apparently nonsevere head injury had a mass lesion potentially requiring surgery: the mass was intracerebral in 52.3% of the cases and extracerebral in 47.6%. Patients aged 20 years or less had a 39% chance of having a nonfocal mass lesion (diffuse brain damage), a 29% chance of having an epidural hematoma, and a 32% chance of having an intradural mass lesion; patients over 40 years had only a 3% chance of having a nonfocal mass lesion, an 18% chance of having an epidural hematoma, and a 79% chance of having a intradural mass lesion. Sixty-eight (32.2%) patients died and 143 (67.8%) survived. The following were independent outcome predictors (in order of significance): Glasgow Coma Scale score following deterioration into coma, the highest intracranial pressure during the patient's course, the degree of midline shift, the type of intracranial lesion, and the age of the patient. In contrast, the mechanism of injury, the verbal Glasgow Coma Scale score during the lucid interval, and the length of time until deterioration or until operative intervention did not influence the final result. 
Transformation-dependent activation of urokinase-type plasminogen activator by a plasmin-independent mechanism: involvement of cell surface membranes. Transformed cells produce elevated levels of the urokinase-type plasminogen activator (u-PA), which has been linked with the invasive or migratory phenotype of these cells. The u-PA is secreted and normally maintained in the inactive, single-chain form (scu-PA) and it has been assumed that natural activation occurs via a plasmin-mediated cleavage converting scu-PA to the active, two-chain form (tcu-PA). We now demonstrate that secreted scu-PA in Rous sarcoma virus-transformed chicken embryo fibroblast (RSVCEF) cultures is activated by an endogenous, plasmin-independent mechanism. Normal CEFs and CEFs infected with a temperature-sensitive RSV mutant and incubated at the nonpermissive temperature do not activate scu-PA. Conditioned medium harvested from plasmin-free cultures of RSVCEFs contains active tcu-PA as determined by two independent methods. The scu-PA is progressively converted with time in culture and requires the presence of intact cells or a plasma membrane-enriched fraction. When added to RSVCEF cultures, a synthetic peptide corresponding to residues 20-41 of the growth factor domain of chicken u-PA blocks the conversion to tcu-PA, and scu-PA accumulates in the cultures. These results suggest that scu-PA is secreted by cells, becomes bound to a u-PA receptor, and is proteolytically converted to active tcu-PA by a catalytic mechanism on the surface of RSV-transformed fibroblasts. 
Early prevention of left ventricular dysfunction after myocardial infarction with angiotensin-converting-enzyme inhibition [published erratum appears in Lancet 1991 May 11;337(8750):1174] Left ventricular dysfunction can be improved with angiotensin-converting-enzyme inhibition started 1 week after myocardial infarction or later. To see whether earlier intervention may confer greater benefit, a double-blind study was carried out in which 100 patients with Q wave myocardial infarction, but without clinical heart failure, were randomly allocated treatment with captopril 50 mg twice daily or placebo starting 24-48 h after onset of symptoms. Left ventricular volumes were measured regularly during 3 months of treatment and after a 48 h withdrawal period by means of two-dimensional echocardiography. The placebo group showed significant increases in left ventricular end-diastolic (LVEDVI) and end-systolic (LVESVI) volume indices, with the ejection fraction unchanged. By contrast, the captopril group showed a slight but not significant rise in LVEDVI and a significant reduction in LVESVI with ejection fraction increased significantly. At 3 months there was a 4.6% difference in the change in ejection fraction from baseline between the groups (p less than 0.0001). Most of the treatment benefit was evident at 1 month and there were no changes in left ventricular volumes after 48 h withdrawal of treatment at 3 months. Heart failure requiring treatment with frusemide developed in 7 patients in each group during the study period; 3 of these (1 captopril-treated, 2 placebo-treated) had to be withdrawn from the trial with severe heart failure requiring open treatment. Thus early treatment with captopril is effective in preventing the ventricular dilatation that can occur after Q wave myocardial infarction. 
Loss of heterozygosity on the short arm of chromosome 17 is associated with high proliferative capacity and DNA aneuploidy in primary human breast cancer. Loss of heterozygosity (LOH) on the short arm of chromosome 17 (17p) was found in 27 of 52 (52%) previously untreated primary breast cancers. There was a significant correlation between this 17p allelic loss and two parameters associated with aggressive tumor behavior: high cellular proliferative fraction and DNA aneuploidy. These correlations with high cellular proliferative fraction and DNA aneuploidy were not found in tumors with LOH at nine other chromosome locations. The p53 gene, a putative tumor suppressor gene located at 17p13, was examined for aberrations to determine whether it is the target for the 17p LOH in breast cancer. Unlike other types of human cancer, there were no homozygous deletions or rearrangements of the p53 gene, and only 2 of 13 (15%) were mutated in the conserved region where mutational "hot spots" have been previously located. Therefore, we hypothesize that, in breast cancer, either loss or inactivation of gene(s) on chromosome 17p other than the p53 gene or a different mechanism of p53 gene inactivation may be responsible for the observed high labeling index and DNA aneuploidy associated with LOH at 17p. 
Transurethral resection of prostate prior to definitive irradiation for prostate cancer. Lack of correlation with treatment outcome. From 1970 through 1983, 107 patients with newly diagnosed adenocarcinoma of the prostate were treated with radiotherapy with curative intent at Duke University Medical Center. Forty-five patients (42%) underwent transurethral resection of the prostate (TURP) for diagnostic and/or therapeutic purposes prior to beginning radiotherapy. Sixty-one patients (57%) were diagnosed by needle biopsy. TURP and needle biopsy groups were comparable (age, elevated acid phosphatase, early [A2, B] and late [C, D1] disease stages, and follow-up). TURP patients were more likely to have poorly differentiated tumors and were more often given concurrent hormonal therapy. Both univariate and multivariate analyses to study the effect of TURP on patients with prostate cancer treated with radiotherapy were done. We were unable to demonstrate any adverse impact of TURP on the outcome of radiation therapy for prostate cancer. This issue remains controversial and should be addressed in a prospective, randomized trial. 
Cerebral potentials evoked by painful, laser stimuli in patients with syringomyelia. Brief cutaneous heat stimuli generated by a CO2 laser were used to elicit late somatosensory evoked cerebral potentials (SEPc) in 10 patients with syringomyelia. For comparison, early and late cerebral potentials in response to electrical nerve stimuli (SEPn) were recorded in the same session. In 8 patients with localized impairment of pain and temperature sensitivity we found complete absence of SEPc after stimulation of the affected area; in another patient with similar sensory deficits, the SEPc was grossly attenuated and delayed. In 1 patient with intact pain sensitivity but absent temperature sensitivity, a well defined SEPc could be recorded. Both early cortical SEPn and late SEPn in response to conventional nerve stimuli were normal in all patients and thus did not differentiate control and affected areas. These data indicate that alteration of SEPc correlates with altered pain sensitivity in patients with a circumscribed spinal lesion. SEPc may thus be used as a neurophysiological test in the assessment of hypalgesic dermatomes. 
The role of the transcerebellar view in the detection of fetal central nervous system anomaly. The current resolution of antenatal ultrasonography permits the sonologist to visualize and critically evaluate the cerebellum and cisterna magna. Abnormalities in the size and shape of these structures will assist the sonologist in the detection of the majority of central nervous system malformations. 
Invasive aspergillosis of the maxilla in an immunocompromised patient. Patients who are immunocompromised have a high susceptibility to infection, which can be fatal. Studies have shown that patients receiving chemotherapeutic and adjunctive medications have inhibited inflammatory response to microbes, particularly those increasing the potential for the development of invasive infection. Aspergillus is a fungus often found in the atmosphere. Colonization of Aspergillus in the upper respiratory tract is common. In the immunocompromised patient, Aspergillus flavus is found to be the most frequent fungus cultured in the maxillary sinus. Because of the depressed immunologic state of the patient, A. flavus can differentiate into hyphal forms producing toxins that destroy epithelial tissues. Penetration of Aspergillus into connective and vascular tissue produces thrombosis and ultimately necrosis of hard and soft tissue. 
Total parenteral nutrition and tumor metastasis. A major clinical concern with providing total parenteral nutrition to the tumor-bearing host is the potential to stimulate tumor growth. This study was performed to determine the effect of total parenteral nutrition on primary tumor growth and spontaneous pulmonary metastasis in Lobund rats with subcutaneous prostate adenocarcinoma (PA-III) implants. Significant acceleration of primary tumor growth and tumor metastasis occurred in animals receiving parenteral nutrition consisting of amino acids, dextrose, and lipid or standard enteral nutrition compared to control animals. This study represents the first report of stimulating tumor metastasis with specific parenteral nutrients and clearly indicates that both primary tumor growth and tumor metastasis can be altered by exogenous substrate administration. 
Peptic ulcer pathophysiology. Despite extensive research, the etiology of peptic ulcer disease remains unclear. Given the multiple processes that control acid and pepsin secretion and defense and repair of the gastroduodenal mucosa, it is likely that the cause of ulceration differs between individuals. Acid and pepsin appear to be necessary but not sufficient ingredients in the ulcerative process. It is clear that the majority of gastric ulcers and a substantial number of duodenal ulcers do not have increased gastric acid secretion. Recent research has focused more on protection and repair of the stomach and duodenum. NSAIDs cause a significant number of gastric and duodenal ulcers; this is probably due to inhibition of prostaglandin production with loss of its protective effects. In the absence of NSAIDs and gastrinoma, it appears that most gastric ulcers and all duodenal ulcers occur in the setting of H. pylori infection. Evidence is mounting in support of H. pylori as a necessary ingredient in the ulcerative process, similar to acid and pepsin. It is not known whether the bacteria or the accompanying inflammation is the more important factor in the pathophysiology. Although the pathophysiology of gastric ulcer and duodenal ulcer is similar, there are clearly differences between the two groups. Duodenal ulcer is typified by H. pylori infection and duodenitis and in many cases impaired duodenal bicarbonate secretion in the face of moderate increases in acid and peptic activity. These facts suggest the following process: increased peptic activity coupled with decreased duodenal buffering capacity may lead to increased mucosal injury and result in gastric metaplasia. In the presence of antral H. pylori, the gastric metaplasia can become colonized and inflamed. The inflammation or the infection itself then disrupts the process of mucosal defense or regeneration resulting in ulceration. A cycle of further injury and increased inflammation with loss of the framework for regeneration may then cause a chronic ulcer. Gastric ulcer often occurs with decreased acid-peptic activity, suggesting that mucosal defensive impairments are more important. The combination of inflammation, protective deficiencies, and moderate amounts of acid and pepsin may be enough to induce ulceration. Many questions remain in understanding the pathophysiology of peptic ulcer disease. The physiology and pathophysiology of mucosal regeneration and the mechanisms by which H. pylori and inflammation disrupt normal gastroduodenal function will be fruitful areas of future investigation. 
Prostaglandin-stimulated recovery of the human duodenal epithelium: effects of misoprostol on ethanol damage. This study was designed to determine whether prostaglandins can stimulate the repair of human duodenal epithelium. Ten healthy volunteers were given 50 ml 40% ethanol through an endoscope onto the duodenal mucosa 1-7 cm from the pyloric sphincter; 3 min later, misoprostol (200 micrograms) or inert vehicle (5 ml) was given locally in the same way. One and 5 h later, endoscopy was repeated to evaluate the damage. The conditions of the mucosa were evaluated by endoscopy and by scanning and transmission electron microscopy in biopsies taken at time 0 and 3 min, 1 and 5 h after ethanol. The study was double-blind with a cross-over balanced design. Three minutes after ethanol administration, the duodenal mucosa showed hyperemia with hemorrhagic lesions. Under the electron microscope, the lesions were caused by vascular engorgement or red blood cell extravasation into the submucosa; the epithelium underlining lesions showed loss of superficial cells and damage to the upper layer of the mucosa. One hour after ethanol, there was a striking difference between the two treatment groups, with a substantial recovery of the duodenal epithelium in the misoprostol-treated volunteers. Although spontaneous recovery was evident in the control group, there was also a significant difference at 5 h. Our results suggest that prostaglandins are able to stimulate the recovery of the duodenal epithelium after acute damage. 
Relation between p53 overexpression and established prognostic factors in breast cancer. The nuclear phosphoprotein p53 is expressed in all normal cells and appears to function in cell cycle regulation. Abnormally high levels of the protein are found in many different types of cancer. In breast carcinoma overexpression of p53 is associated with point mutations within highly conserved regions of the p53 gene. These altered genes encode stable p53 proteins that can be detected by standard immunohistochemical techniques unable to detect rapidly degraded wild-type protein. The level of p53 expression in 184 primary breast cancer specimens was assessed by immunohistochemical analysis and related to the following established prognostic factors for breast cancer: age, stage, metastatic involvement, concentration of estrogen and progesterone receptors, proliferative index, and HER-2/neu overexpression. Fifty (27%) of these primary breast cancer specimens had widespread overexpression of p53. Highly significant associations were found between p53 overexpression and late stage, metastatic spread, and low concentration of progesterone receptors. The presence of elevated levels of mutant p53 may itself be a prognostic factor in human breast cancer and activation of this oncogene may be important in the ability of a tumor to metastasize. 
Angiographic management of retroperitoneal hemorrhage from renal angiomyolipoma in polycystic kidney disease. Angiographic management of bilateral angiomyolipomas complicated by hemorrhage in autosomal dominant polycystic kidney disease is presented. The patient had mild stigmata of tuberous sclerosis, and a family history of tuberous sclerosis and autosomal dominant polycystic kidney disease. The radiographic features at diagnosis, and those present during and after embolization are described. Radiological criteria for diagnosis and successful control of bleeding with intra-arterial selective embolization are discussed. Radiographic features before, during and after embolization are exhibited. 
Combined interferon alfa and doxorubicin in the treatment of advanced cervical cancer. Interferon alfa and doxorubicin have been shown to have synergistic effects when tested in vitro with cells derived from cervical cancers. A clinical trial was designed, testing interferon alfa plus doxorubicin in patients with advanced or recurrent cervical cancers. Twenty-one patients were given interferon alfa, 10 million units per square meter intramuscularly and 10 million units per square meter intravenously over a 30-minute infusion period. One hour later 20 mg/m2 doxorubicin was given intravenously slowly over a 2-hour period. Treatments were repeated once weekly for 3 weeks. Initial response evaluation was done at week 5, and treatment was continued on an every-other-week schedule for patients showing favorable responses or stable disease. Bone marrow, hepatic, and renal toxicities were minimal. Fever and malaise were the major sources of toxicity. Of the 17 evaluable patients, six had clinical partial responses. Two of the responders have enjoyed more than 5 years' survival. This regimen is well tolerated and does have efficacy in some patients with advanced cervical cancers. 
Proteus syndrome. Ultrastructural study of linear verrucous and depigmented nevi. Proteus syndrome is a rare hamartomatous disorder characterized by multifocal overgrowths that can involve any structure of the body. Clinical manifestations include macrodactyly, hemihypertrophy, subcutaneous masses, exostosis, cerebroid thickening of palms and soles, and linear skin lesions. About 50 cases have been described, but the ultrastructural features of the linear skin lesions have not been characterized. We describe the clinical, histologic, and ultrastructural findings for a 30-year-old patient who had a mild form of Proteus syndrome with linear lesions characterized by a mixed pattern of hyperkeratosis and depigmentation. Light microscopy of the linear nevus showed acanthosis and hyperorthokeratosis. Electron microscopy revealed extensive vacuolation at the interface between melanocytes and keratinocytes, with large aggregations of densely packed granules in the intercellular space. Melanocytes showed only slight degenerative changes. An immunohistochemical study of the expression of epidermal growth factor receptors revealed no significant abnormalities. 
Causes of death in patients with tuberous sclerosis. Of the 355 patients with tuberous sclerosis complex (TSC) examined at the Mayo Clinic, 49 had died (9 of causes other than TSC). We attempted to determine what pattern of organ involvement occurred most often in the 40 patients who died of TSC. One baby died of cardiac failure due to cardiac rhabdomyomas, and one child died of rupture of an aneurysm of the thoracic aorta. Eleven patients died of renal disease, which was the commonest cause of death. Ten patients died as a result of brain tumors, and four patients (who were 40 years of age or older) died of lymphangiomyomatosis of the lung. Thirteen patients with severe mental handicaps died of either status epilepticus or bronchopneumonia; in all but one of these patients, the only source of information was the death certificate. Survival curves show a decreased survival for patients with TSC in comparison with that for the general population. Patients with TSC need lifelong follow-up for early detection of potentially life-threatening complications. 
Descriptive epidemiologic study of epilepsy syndromes in a district of northwest Tuscany, Italy. To evaluate the prevalence of epilepsy syndromes in a district in Northwest Tuscany (Vecchiano, 9,952 inhabitants) we identified all suspected cases (probable epilepsy) from several information sources: files of local doctors, prescriptions of antiepileptic drugs (AEDs), hospital files from the center for epilepsy at the University of Pisa, medical files from university and hospital departments in Pisa, and files of the school doctors and social workers in the district of Vecchiano. All persons suspected of having epilepsy were examined; 51 cases of epilepsy were found, i.e., a prevalence rate of 5.1 in 1,000. During a previous study performed in the same district with the "house-to-house" method, a lower rate was found. Our study confirms that use of different epidemiologic investigational methods can produce different results. 
Future directions of laser phototherapy for diagnosis and treatment of malignancies: fantasy, fallacy, or reality? A new and highly promising adjunctive modality for the diagnosis and therapy of malignancies is under development using lasers and tumor targeting dyes. To reach the eventual goal of clinical treatment, several current "fantasies and fallacies" regarding laser applications in medicine must be identified and their problems clearly outlined. A multidisciplinary scientific approach is also required to enable the clinical practicality of this laser targeting approach. Many new dyes and laser wavelengths are being tested to improve specific tumor uptake and/or retention, lower systemic toxicity, increase tissue penetration, and identify fluorochromes with synergistic properties to further enhance laser tumoricidal effects. Rapid technological advancements in magnetic resonance imaging may now provide an extremely sensitive way to detect and monitor laser-tissue effects, and allow efficient interstitial laser phototherapy of deep and sometimes inaccessible tumors. The current and future prospectives of the emerging field of laser phototherapy are described. 
Cardiomyopathy of the aging human heart. Myocyte loss and reactive cellular hypertrophy. To determine the effects of aging on the human myocardium, 67 hearts were obtained from individuals who died from causes other than cardiovascular disease. The age interval examined was 17-90 years. Regression analysis demonstrated that the aging process was characterized by a loss of 38 million and 14 million myocyte nuclei/yr in the left and right ventricular myocardium, respectively. This loss in muscle mass was accompanied by a progressive increase in myocyte cell volume per nucleus in both ventricles. Left ventricular myocytes enlarged by 110 microns3/yr, whereas right ventricular myocytes increased by 118 microns3/yr, resulting in a preservation of ventricular wall thickness. However, the cellular hypertrophic response was unable to maintain normal cardiac mass. Left and right ventricular weights decreased by 0.70 and 0.21 g/yr, respectively. In conclusion, loss of cells and enlargement of the remaining myocytes may represent the structural basis for the reduced compensatory capacity of the aged heart and together may contribute to the development of myocardial dysfunction and failure in the elderly. 
Age-related changes in the clinical and electrophysiologic characteristics of patients with Wolff-Parkinson-White syndrome: comparative study between young and elderly patients. The natural history of patients with Wolff-Parkinson-White (WPW) syndrome remains an intriguing question with respect to clinical decision-making, since serial electrophysiologic data spread over several decades in the same patient are not available in the literature. To study the age-related changes in WPW syndrome, we compared two separate groups of patients referred to this Medical Center for electrophysiologic studies because of a clinical presentation with significant arrhythmias. An elderly group of 42 patients aged 50 years or more were compared with a younger group of 51 patients aged 15 to 30 years. The groups were comparable in terms of clinical presentation, including the number of patients who had reported syncopal episodes and those requiring cardioversion of their tachyarrhythmias. Baseline electrophysiologic variables such as sinus rate; sinoatrial conduction time; corrected sinus node recovery time; AH interval; and effective refractory periods of the right atrium, atrioventricular (AV) node, and right ventricular muscle, were significantly greater in the elderly group. Similarly, the anterograde effective refractory period of the bypass tract, the shortest atrial pacing cycle length with 1:1 anterograde conduction via the bypass tract, retrograde effective refractory period of the bypass tract, the shortest ventricular pacing cycle length with 1:1 retrograde conduction via the bypass tract, the shortest consecutive preexcited R-R interval during atrial fibrillation, and the cycle length of orthodromic atrial ventricular reciprocating tachycardia were significantly greater in the elderly group. 
Focal nodular hyperplasia of the liver: MR findings in 35 proved cases. MR images of 28 patients with 35 lesions of hepatic focal nodular hyperplasia were reviewed to determine the frequency of findings considered typical of this condition (isointensity on T1- and T2-weighted pulse sequences, a central hyperintense scar on T2-weighted images, and homogeneous signal intensity). Fifteen lesions were imaged at 0.6 T with T1- and T2-weighted spin-echo (SE) pulse sequences; 20 lesions were imaged at 1.5 T with T1-weighted SE and gradient-echo pulse sequences and T2-weighted SE pulse sequences. Diagnosis of focal nodular hyperplasia was made pathologically in 25 patients, with nuclear scintigraphy in four, and with follow-up imaging in six. Only seven lesions (20%) were isointense relative to normal liver on both T1- and T2-weighted images. On T1-weighted SE images, 21 lesions (60%) were isointense relative to normal liver, 12 (34%) were hypointense, and two (6%) were hyperintense. On T2-weighted SE images, 12 lesions (34%) were isointense and 23 (66%) were hyperintense relative to normal liver. A central scar was present in 17 lesions (49%) and was hypointense relative to the lesion on T1-weighted images and hyperintense on T2-weighted images. Twenty lesions (57%) were of homogeneous signal intensity throughout the lesion, except for the presence of a central scar. All three MR imaging characteristics were present in three cases (9%). We conclude that hepatic focal nodular hyperplasia has a wide range of signal intensity on MR imaging. 
Mixed venous oxygen saturation for differentiating stable from unstable tachycardias. Current antitachycardia systems are incapable of adequately distinguishing stable from unstable tachycardias. Previously, integration of a pressure sensor or an impedance sensor, together with electrogram analysis, has been investigated as an improved method of identifying unstable arrhythmias. A mixed venous oxygen saturation sensor was investigated for differentiating stable from unstable paced and induced tachycardias in 10 patients. During rapid pacing at 600, 500, 400, 350, 300, and 250 msec cycle lengths, mixed venous oxygen saturation decreased as cycle length decreased. For any given cycle length, rapid ventricular pacing tended to result in greater mixed venous oxygen desaturation compared with atrial pacing. Mixed venous oxygen saturation decreased similarly during induced ventricular tachycardias at cycle lengths greater than 230 msec. However, ventricular tachycardias at cycle lengths less than or equal to 230 msec and ventricular fibrillation had no effect on mixed venous oxygen saturation until after termination. Subsequently, a mixed venous oxygen saturation-tiered therapy algorithm (cycle length less than or equal to 230 msec = unstable; cycle length greater than 230 msec and MVO2 greater than or equal to 6% over 30 seconds = unstable) was developed and was tested retrospectively in 113 paced and induced tachyarrhythmias in these 10 patients for detecting unstable tachycardias (defined as a decrease from baseline systolic arterial pressure of greater than or equal to 50 mm Hg at 15 seconds). The mixed venous oxygen algorithm had 93% sensitivity and 96% specificity compared with rate-only (rate greater than or equal to 170 beats/min) detection with 93% sensitivity and 71% specificity. 
Recombinant human granulocyte-macrophage colony-stimulating factor after chemotherapy in patients with acute myeloid leukemia at higher age or after relapse. To reduce critical neutropenia after chemotherapy (CT) for acute myeloid leukemia (AML) we administered recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) to patients over the age of 65 years with newly diagnosed AML and to patients with early or second relapse. CT was 9-day 6-thioguanine, ara-C, and daunorubicin (TAD9) in newly diagnosed AML and sequential high-dose ara-C and mitoxantrone (S-HAM) for relapse. In patients whose bone marrow was free from blasts a continuous intravenous infusion of GM-CSF 250 micrograms/m2/d started on day 4 after CT. Thirty-six patients entered the study and 30 of them did receive GM-CSF. For comparison, a historical control group of 56 patients was used. Complete remission rate was 50% (18 of 36) versus 32% in controls (P = .09), and early death rate was 14% versus 39% (P = .009). Treatment with GM-CSF was not associated with major adverse events. Two patients showed a marked leukemic regrowth that was completely reversible in one patient and appeared to be GM-CSF independent in the other patient. Remission duration does not seem to be reduced after GM-CSF. Under GM-CSF the blood neutrophils recovered 6 and 9 days earlier in the TAD9 (P = .009) and S-HAM (P = .043) groups associated with a rapid clearance of infections in most patients. We conclude that GM-CSF was of therapeutic benefit to our patients and this provides a basis for larger controlled trials. 
HTLV-I-associated myelopathy in a patient with adult T-cell leukemia. Disseminated erythematous papules and plaques developed in a 60-year-old man 3 years before the appearance of neurologic manifestations. A biopsy specimen of the plaque revealed Pautrier's microabscess and a dense mononuclear cell infiltration with atypical convoluted nuclei in the papillary dermis. These cells were helper/inducer T lymphocytes that expressed the interleukin 2 receptor. The patient's white blood cell count was normal, but 1% atypical lymphocytes and a high titer of anti-human T-lymphotropic virus (HTLV)-I antibody were detected in his serum. A smoldering type of adult T-cell leukemia was diagnosed. While he was being treated with PUVA, a gait disturbance developed. A high titer of anti-HTLV-I antibody, characteristic of HTLV-I-associated myelopathy, was demonstrated in his cerebrospinal fluid. 
Venous thrombosis after long-term transvenous pacing in the Chinese. To determine the incidence of venous thrombosis after long-term transvenous pacing in the Chinese, venograms were performed in 50 consecutive Chinese patients seen at the pacemaker clinic. There were 25 women and 25 men. The mean age was sixty-six years (range thirty-two to eighty-one). The indications for pacing were complete heart block in 16 patients and sick sinus syndrome in the remainder. All pacemakers were of the single-chamber ventricular pacing type and had been implanted for a mean period of four years (range two to seven). In 27 patients the route of entry for the pacing electrode was through the cephalic vein and in the other 23 patients the subclavian veins were used. Of the 50 venograms, 1 showed partial and 1 showed total obstruction at the subclavian vein. Both patients (4%) were asymptomatic. All others (96%) were normal. The incidence of venous thrombosis was not related to the routes of entry of the pacing electrodes. All patients tolerated the procedure well and had no complications. It is concluded that the incidence of venous thrombosis after long-term transvenous pacing is extremely low in the Chinese (4%), and venograms are both safe and useful for identifying venous thrombosis related to transvenous pacing. 
The 10-y incidence of obesity and major weight gain in black and white US women aged 30-55 y. Although the prevalence of obesity in US women is well-described, data are limited on the incidence of major weight gain and obesity. We used data from the First National Health and Nutrition Examination Survey Epidemiologic Follow-up Study to estimate the 10-y incidence of major weight gain (greater than or equal to 10 kg) and obesity [body mass index (BMI, in kg/m2) greater than or equal to 29] in a cohort of US women aged 30-55 y (n = 535 blacks and 2976 whites). In women not obese at baseline, blacks were 60% more likely to become obese than whites [incidence in blacks = 15.5%, 95% confidence interval (CI) = 11.2-19.7; incidence in whites = 9.7%, 95% CI = 8.6-10.8]. This higher incidence of obesity in blacks was largely due to their higher average BMI at baseline. The incidence of major weight gain was 50% higher in blacks than in whites (in blacks, 17.3%; 95% CI = 13.6-21.0; in whites, 11.7%; 95% CI = 10.3-13.1). We estimate that in black and white women, respectively, 16% and 12% of coronary heart disease is attributed to major weight gain whereas 35% and 21% is attributed to being obese. 
Development of the pulmonary vasculature in newborn lambs: structure-function relationships. Our objectives were 1) to describe the quantitative light microscopy and ultrastructure of newborn lamb lungs and 2) to correlate hemodynamic changes during normoxia and hypoxia with the morphology. By light microscopy, we measured the percent muscle thickness (%MT) and peripheral muscularization of pulmonary arteries and veins from 25 lambs aged less than 24 h, 2-4 days, 2 wk, and 1 mo. At the same ages, lungs were isolated and perfused in situ and, after cyclooxygenase blockade with indomethacin, total, arterial (delta Pa), middle (delta Pm), and venous pressure gradients at inspired O2 fractions of 0.28 (mild hyperoxia) and 0.04 (hypoxia) were determined with inflow-outflow occlusion. During mild hyperoxia, delta Pa and delta Pm fell significantly between 2-4 days and 2 wk, whereas during hypoxia, only delta Pm fell. The %MT of all arteries (less than 50 to greater than 1,000 microns diam) decreased, and peripheral muscularization of less than 100-microns-diam arteries fell between less than 4 days and greater than 2 wk. Our data suggest that 1) the %MT of arteries determines normoxic pulmonary vascular resistance, because only arterial and middle segment resistance fell, 2) peripheral muscularization is a major determinant of hypoxic pulmonary vasoconstriction, because we observed a fall with age in peripheral muscularization of less than 100-micron-diam arteries and in delta Pm with hypoxia, and 3) the arterial limit of the middle segment defined by inflow-outflow occlusion lies in 100- to 1,000-microns-diam arteries. 
IgA antigliadin antibodies, cellobiose/mannitol sugar test, and carotenemia in the diagnosis of and screening for celiac disease. Serum IgA antigliadin antibodies (IgAAGA) assay, cellobiose/mannitol sugar permeability test (ST), and carotenemia were evaluated prospectively as diagnostic tests in 60 consecutive adult patients with suspected celiac disease (CD). CD was confirmed histologically in 26 patients. IgAAGA, ST, and carotenemia had a sensitivity of 65.4%, 96.2%, and 76.9%, a specificity of 97.1%, 73.5%, and 70.6%, and positive likelihood ratio of 22.2, 3.6, and 2.6, respectively. Multivariate logistic regression showed that IgAAGA and ST had a sensitivity and specificity of 96.2% and 70.6% and a positive likelihood ratio of 47.3 if both were positive. Assuming a prevalence of CD of 1:2000 in the general population, for every 89 positive IgAAGA and 549 altered ST there would be one celiac patient, whereas, if both tests were positive, the patient was certain to have CD. We conclude that, of the tests studied, IgAAGA and ST are respectively the most specific and the most sensitive and that, used together, they can diagnose CD. 
Conjunctival cysts in anophthalmic orbits. Five out of 149 patients (3%) who received an intraorbital implant to prevent or treat the disfiguring symptoms associated with the postenucleation socket syndrome developed intraorbital conjunctival cysts. All five patients had received a secondary implant two 14 months previously. After excision of the cysts four patients required additional surgery for lack of conjunctiva and/or recurrent cyst formation. The clinical findings, mechanism of development, and management of this rare but serious complication of socket surgery are described. 
GM1-gangliosidosis (genetic beta-galactosidase deficiency): identification of four mutations in different clinical phenotypes among Japanese patients. GM1-gangliosidosis is a genetic neurological disorder caused by mutations in the lysosomal acid beta-galactosidase gene. While its phenotypic expression is complex, it is usually classified as being of infantile, juvenile, or adult form, on the basis of age at onset, the rate of symptomatic progression, and severity of central nervous system involvement. We have analyzed the acid beta-galactosidase gene in 12 Japanese patients from nine families. The aim was to identify mutations in individual patients and then to examine possible correlation between the mutations and the clinical phenotypes. Northern blotting studies with a full-length human beta-galactosidase cDNA showed that the mRNA ranged from undetectable to substantially decreased in the infantile patients but was normal in quantity and size in all juvenile and adult patients. Four distinct missense mutations have been identified, each limited to the respective clinical forms within our small-size samples. In the infantile patient with decreased but detectable mRNA, a point mutation was found resulting in Arg49----Cys. In the infantile patient with nearly undetectable mRNA, mutation Arg457----Ter was identified. The mutation Arg201----Cys was found in all four of the juvenile patients, while all six adult patients were homozygous for the point mutation Ile51----Thr. The mutations found in the juvenile and adult patients alter restriction sites in the normal gene and thus are amendable to quick screening. The prediction that these mutations are responsible for the clinical disease was confirmed by no expression of the catalytic activity of the mutant proteins in the COS-I cell expression system. 
Biocompatibility of radiolucent breast implants. Current implants for breast augmentation containing silicone gel, saline, or both are radiopaque on mammographic examination and can totally obscure microcalcifications and soft-tissue masses. The effect of these implants on the detection of early breast cancers in patients who have undergone augmentation mammaplasty remains unproven and controversial. Implants filled with medium-chain triglycerides (peanut oil) are radiolucent on mammographic examination and allow visualization of both soft-tissue masses and microcalcifications. To investigate the biocompatibility of radiolucent implants, 10 cc of sterile, nonpyrogenic peanut oil was injected subcutaneously into rats using silicone gel as a control. Twenty-one rabbits had two 125-cc silicone shell implants inserted on either side of the chest wall. The right-sided shell was filled with 125 cc of sterile saline, and the left-sided shell was filled with 125 cc of sterile, nonpyrogenic peanut oil. Results were determined by both histologic and radiographic examination. Rats injected with peanut oil equivalent to 7 percent of their body weight rapidly absorbed the freely injected oil without detriment. Histologic examination of the lungs, liver, kidneys, and tissues adjacent to the injection sites demonstrated no abnormalities. There was no evidence of allergic, toxic, inflammatory, or neoplastic response. Eighteen of 21 rabbits survived more than 3 months. Radiographs showed the oil-filled implants to be radiolucent, whereas the saline-filled controls obscured the surrounding soft and bony tissues. Histologic examination demonstrated a fibrous capsule surrounding both types of implants. Histologic examination of the lungs, liver, and kidneys showed no significant abnormalities. These and previous studies have shown peanut oil to be biocompatible when freely injected either intramuscularly or subcutaneously. This study demonstrates that a radiolucent, peanut oil-filled implant is biocompatible in animals and that further long-term studies for its use in humans are merited. 
Metabolic and destructive brain disorders in children: findings with localized proton MR spectroscopy. The diagnostic potential of volume-selective proton magnetic resonance (MR) spectroscopy in vivo was evaluated in 20 children and young adults with various neurodegenerative brain disorders. All patients were examined with MR spectroscopy in conjunction with MR imaging of the brain on a whole-body imager at 1.5 T. Comparison of spectra in our patients with those of children with normal myelination (prominent signals from N-acetylaspartate [NAA], creatine/phosphocreatine, and choline) revealed a marked decrease of NAA in 12 of 17 patients with focal or generalized demyelination. In patients with Canavan disease, NAA signal intensity was markedly increased, but no choline signal was found. Increased signal intensity from lactate occurred in patients with Leigh disease, neuroaxonal dystrophy, Schilder disease, and Cockayne disease, which indicated a disturbed energy metabolism in the examined region. These results demonstrate that proton MR spectroscopy can be applied in a clinical environment to facilitate diagnosis of hereditary and acquired brain disorders in children. 
Longitudinal followup of patients with Meniere's disease. The etiology, pathophysiology, and natural history of Meniere's syndrome are poorly understood. The reported studies have had inadequate followup or insufficient numbers of patients to allow conclusions about the natural history. Our study group was 119 patients who had the classic symptom complex of episodic vertigo, tinnitus, and hearing loss in the year 1970. After initial review of these charts, follow-up information was obtained by questionnaire, telephone interview, chart review, or repeat examination, when possible, both in 1983 and in 1988, for a total followup of 18 years. In the patients with followups of at least 14 years, vertiginous episodes had disappeared completely in 50% of patients and somewhat resolved in 28%; hearing was absent in 48% and worse in 21%. Surprisingly, 43% of patients underwent surgery at some point for control of vertigo. Bilateral disease was present initially in 13% and developed subsequently in 45% of patients. Other areas reviewed included the efficacy of long-term medical treatment, frequency and severity of vertiginous attacks, and contralateral ear symptoms. 
Increased intestinal permeability in endotoxic pigs. Mesenteric hypoperfusion as an etiologic factor. Infusing pigs with lipopolysaccharide (LPS) decreases superior mesenteric artery blood flow (Qsma), suggesting that mesenteric hypoperfusion may be responsible for LPS-induced alterations in gut mucosal permeability. To test this hypothesis, we studied four groups of anesthetized swine. Group 1 animals (N = 6) were infused with LPS (250 micrograms/kg over 1 hour beginning at 60 minutes) and continuously resuscitated with Ringer's lactate (48 mL/kg per hour). In group 2 (N = 5), Qsma was decreased by 50% by means of a mechanical occluder to mimic the LPS-induced alterations in Qsma observed in group I. Group 3 (N = 5) was included to document our ability to detect ischemia/reperfusion-induced alterations in mucosal permeability; in these pigs, Qsma was decreased in steps to zero flow (at 150 to 210 minutes) and then perfusion was restored (at 210 to 270 minutes). Pigs in group 4 (N = 6) served as normal controls; these animals were resuscitated with Ringer's lactate at the same rate as in group 1 but were not infused with LPS. To assess mucosal permeability, we measured plasma-to-lumen clearances for two markers, chromium 51-labeled edetic acid monohydrate (EDTA) and urea. Loading and maintenance infusions of the markers were given intravenously, and a 20-cm isolated segment of small intestine was continuously perfused at 2 mL/min with Ringer's lactate at 37 degrees C. Results were expressed as the ratio of the clearances for the two probes (CEDTA/CUREA). In group 3, CEDTA/CUREA was 999% +/- 355% of baseline at 270 minutes. In group 1, CEDTA/CUREA was 572% +/- 235% of baseline at 270 minutes. In groups 2 and 4, however, CEDTA/CUREA did not change significantly from the baseline value over the duration of the study. These data suggest that increased mucosal permeability after LPS is due to factors other than (or in addition to) mesenteric hypoperfusion. 
Characteristics of patients resistant to antihypertensive drug therapy. In order to determine the features that characterize refractory hypertension (RH), patients aged less than 65 years in a hypertension clinic were screened. Thirty-six patients on triple drug therapy with a supine diastolic blood pressure (DBP) of greater than or equal to 5 mmHg above an identified target pressure (90-100 mmHg), or a systolic blood pressure (SBP) greater than or equal to 170 mmHg for the last 6 months (greater than or equal to 3 measurements) underwent a thorough clinical investigation. The frequency of renal artery stenosis (RAS) in the RH patients was 30%. The non-RAS patients had a low occupational status, 76% being either manual workers or unskilled non-manual workers (reference group: 42%; P less than 0.01). They were more obese (body mass index (BMI) 28.8 vs. 25.8; P less than 0.01), and had a longer duration of hypertensive disease. RH patients had a higher prevalence of non-insulin-dependent diabetes mellitus (18 vs. 6%; P less than 0.05), and showed a higher prevalence of nervous complaints and mental distress (44% vs. 12%; P less than 0.001) and musculo-skeletal pain (39% vs. 7%: P less than 0.001). It is suggested that refractory hypertension should be investigated and treated bearing psychosocial factors in mind, concurrently with a screening for secondary hypertension. 
Transcanal infracochlear approach to the petrous apex. Computerized tomography and magnetic resonance imaging have now made it possible to reliably differentiate cholesteatoma from cholesterol granuloma of the petrous apex. The treatment for cholesteatoma is complete surgical excision when possible, whereas cholesterol granuloma needs only adequate drainage for control. A new transcanal infracochlear approach for drainage of cholesterol granuloma involving the anterior petrous apex is described. Absolute measurements from 10 cadaveric temporal bones were obtained to determine the distances between the cochlea, jugular bulb, carotid artery, and facial nerve. In all specimens the petrous apex was entered without invading the cochlea, carotid, or jugular bulb. Advantages of this technique include a more direct route to the petrous apex, dependent drainage, and preservation of the normal hearing mechanism, including the tympanic membrane. Clinical indications for this technique include failure of other treatment approaches and a high jugular bulb obstructing an infralabyrinthine approach. Experience to date shows that patients experience little difficulty from the procedure. 
Insulin pulses less effective than continuous insulin in inhibiting PEPCK mRNA levels stimulated by cAMP and dexamethasone in perifused hepatoma cells. Hepatic glucose production is stimulated in vitro twice as effectively by pulsatile as by continuous glucagon, given equivalent time-averaged doses. Efficacy studies of pulsatile insulin have yielded conflicting results. In the rat hepatoma cell line H-4-II-E-C3, insulin rapidly (t1/2 15 min) inhibits transcription of the gene and lowers mRNA levels for the gluconeogenic enzyme. PEPCK via a receptor-mediated process. We attached H-4-II-E-C3 cells to Cytodex-3 microcarriers and used a perifusion column system to test whether pulsatile insulin is more or less effective than equivalent time-averaged doses of continuous insulin. PEPCK transcription was induced by inclusion of cAMP analogue 8-(4-chlorophenyl-thio)-cAMP (0.1 mM) and dexamethasone (0.5 microM) in the perifusion medium. Three columns were exposed either to continuous, pulsatile, or no insulin. After 3 h, total nucleic acid was extracted, and mRNA(PEPCK) was measured with a sensitive-solution hybridization assay. Continuous insulin inhibited PEPCK expression in a dose-dependent fashion with EC50 1 x 10(-11) M. Equivalent time-averaged amounts of insulin delivered as pulses achieved significant inhibition but less effectively than continuous insulin. The apparent EC50 for pulsatile insulin increased from 2 x 10(-11) M to 5 x 10(-11) M as the oscillatory period was raised from 5 to 20 min, respectively. These observations suggest that insulin-mediated inhibition of PEPCK gene transcription is diminished by a pulsatile mode of administration in marked contrast to the pulse enhancement demonstrated for glucagon-mediated hepatic glucose production. 
The clinical utility of prostate-specific antigen and bone scintigraphy in prostate cancer follow-up. To assess the value of serum prostate-specific antigen (PSA) in prostate cancer follow-up, we prospectively studied 107 consecutive patients with: (1) pathologically confirmed prostate cancer; (2) definitive prostatectomy and/or radiation therapy greater than or equal to 3 mo prior to bone scanning; and (3) one bone scan and serum PSA sampling within 3 mo of each other. The mean and range of patient follow-up since definitive therapy was 1.6 and 0.5-8 yr, respectively. Abnormal bone scans were correlated with pertinent radiographs. Of 107 bone scans, 16 demonstrated metastatic bone disease. A PSA value of less than or equal to 8 ng/ml excluded bone metastases with a predictive value of a negative test of 98.5%. Without radiographic correlation, abnormal bone scans rarely represented metastases if the PSA value was less than or equal to 8 ng/ml. In summary, serum PSA concentration determines the need for follow-up bone scanning and assists in scan interpretation in patients status post definitive therapy for prostate cancer. 
Inflammatory edema induced by interactions between IL-1 and the neuropeptide calcitonin gene-related peptide. The neuropeptide calcitonin gene-related peptide (CGRP) is a potent vasodilator with a long duration of action. CGRP is widely distributed and is present in perivascular nerves of tissues that include skin and the synovium. In this study we have investigated the possibility that CGRP can modulate the inflammatory actions of the cytokine IL-1 by using an inflammatory model in rabbit skin. The intradermal injection of IL-1 (1.4 x 10(-14) mol/site) alone stimulated little edema formation. However, when IL-1 was injected with CGRP (10(-11) mol/site), a highly significant edema was observed, and neutrophil accumulation induced by IL-1 was potentiated. These results suggest that the action of IL-1 as a potent mediator of increased microvascular permeability is only observed when skin blood flow is increased in this model. This was confirmed by experiments in which PGE2 (3 x 10(-9) mol/site) at a dose with a similar duration of vasodilator action as CGRP (10(-11) mol/site) also potentiated edema induced by IL-1. Further experiments investigated the mechanism by which IL-1 increased microvascular permeability. Edema induced by IL-1 was dependent on de novo protein synthesis and the presence of circulating neutrophils. However, selective platelet-activating factor and histamine H1 antagonists had no inhibitory effect on this response. Thus it appears that when a microvascular bed is dilated by the long-lasting vasodilator CGRP, edema induced by IL-1 is clearly observed. These results highlight a potentially important synergistic interaction between cytokines and neuropeptides in inflammation. 
Propranolol compared with propranolol plus isosorbide-5-mononitrate for portal hypertension in cirrhosis. A randomized controlled study. OBJECTIVE: To investigate whether isosorbide-5-mononitrate (Is-5-Mn) given with propranolol reduces hepatic portal pressure more than does propranolol alone in patients with cirrhosis. DESIGN: A randomized controlled trial. PATIENTS: Fifty patients with cirrhosis and esophageal varices entered and 42 completed the study. INTERVENTION: Twenty-one patients received oral propranolol at increasing doses until their resting heart rate was reduced by 25%, and 21 patients received oral propranolol (on the same schedule) plus oral Is-5-Mn, 40 mg twice a day. MEASUREMENTS: Hepatic vein pressure gradient, liver function, and splanchnic and systemic hemodynamics before and after 3 months of continuous therapy. MAIN RESULTS: At 3 months, the hepatic venous pressure gradient decreased more (P less than 0.01) in patients given propranolol plus Is-5-Mn (19%, from 18.4 +/- 3.9 to 14.9 +/- 3.8 mm Hg; 95% CI, -2.4 to -4.5 mm Hg) than in those given propranolol alone (10%, from 18.2 +/- 3.5 to 16.3 +/- 3.1 mm Hg; CI, -1.1 to -2.7 mm Hg). The hepatic venous pressure gradient decreased by more than 20% of the baseline value in 10% of patients receiving propranolol, but in 50% of patients receiving combined therapy (P less than 0.02). There were statistically significant decreases in hepatic blood flow and the intrinsic clearance of indocyanine green after propranolol therapy, but not after combined therapy. The treatments caused similar reductions in azygos blood flow and cardiac output. CONCLUSIONS: The long-term combined administration of propranolol plus Is-5-Mn reduces portal pressure more than propranolol alone without adverse effects on hepatic perfusion and liver function. Whether this greater hemodynamic effect translates into better clinical efficacy should be determined in randomized controlled trials. 
Assessment of competency: the role of neurobehavioral deficits. We present a practical set of guidelines for assessing competency in patients with cognitive deficits due to neurologic disorders such as stroke, head injury, Alzheimer disease, and multi-infarct dementia. Our focus is the evaluation of cognitive processes underlying the ability to make competent decisions, with an emphasis on the identification of areas of preserved function that may be used to bypass intellectual deficits. The assessment of the cognitive processes underlying competency involves a series of steps designed to evaluate attention, language, memory, and frontal lobe function. The examiner must first show that the patient has an adequate level of attention for participation in the further testing of specific cognitive functions; second, that the patient is able to comprehend relevant instructions, retain information long enough to evaluate it in relation to relevant recent and remote experiences, and express his or her wishes; and finally, that the patient has sufficiently intact judgment and awareness. The examiner must determine whether the patient's preserved cognitive abilities are sufficient for him or her to make an adequate judgment in relation to the specific question being asked. If cognitive function is found to be significantly impaired, the examiner should do a detailed assessment for the presence of compensatory abilities that can be used to bypass the deficits. For example, the examiner should assess whether patients who cannot speak are still able to express their wishes by pointing, using gesture, or even by drawing pictures. Unless such an assessment has been done, patients should not be considered incompetent. 
Entire ABL gene is joined with 5'-BCR in some patients with Philadelphia-positive leukemia. In four patients, the chromosome 9 breakpoint of the t(9; 22)(q34;q11) had occurred at different sites within an 8.25-kilobase (kb) region situated 5' of ABL exon 1B. Chromosome in situ hybridization and field inversion gel electrophoresis (FIGE) studies showed that ABL exons 1A and 1B were present on the Ph chromosome. Yet this large fusion gene produced an mRNA conventional for chronic myelogenous leukemia (CML). Splicing from BCR exon 3 to ABL exon 2 crossed more than 200 kb and deleted exons 1A and 1B. This breakpoint site may occur in about 10% of all CML patients. Three of our patients have pronounced thrombocytosis, and two had been diagnosed as having Ph-positive essential thrombocythemia. The platelet count of the other patient was not available. 
Value and limitations of secondary femoropopliteal bypasses with polytetrafluoroethylene. Secondary femoropopliteal bypasses with polytetrafluoroethylene (PTFE) grafts are widely regarded to be of questionable value. This has prompted some to abandon all attempts at secondary revascularization with PTFE and others to recommend that primary femoropopliteal bypasses be performed preferentially with PTFE grafts so that vein may be used for secondary procedures. Because we questioned both of these views, we reviewed all femoropopliteal bypasses done at our institution in the past 12 years and identified 73 secondary PTFE femoropopliteal procedures performed after a failed ipsilateral infrainguinal bypass (69 failed femoropopliteal; 4 failed femorodistal). Seventy (96%) secondary bypasses were performed for limb salvage and 3 (4%) for severe disabling claudication. Insertion of grafts to the popliteal artery was above the knee in 26 (36%) and below the knee in 47 (64%). Primary life-table graft patency at 4 years was only 38%. Forty-eight reinterventions in 34 limbs were required to restore or maintain graft patency in thrombosed or failing grafts. For thrombosed grafts, 20 interventions consisted of 9 simple thrombectomies and 11 thrombectomies with additional revision procedures (5 distal or proximal extensions, 6 patch angioplasties). Twenty-eight lesions threatening graft patency were treated by percutaneous transluminal angioplasty in 3, proximal or distal extensions in 20, and patch angioplasty in 5. As a result of these reinterventions, the overall secondary patency rate was 55% at 4 years, and the limb salvage rate was 74% at 4 years. Although aggressive follow-up and reintervention may be required, the use of secondary PTFE conduits in the femoropopliteal position is a viable option in patients undergoing limb salvage procedures who are at high risk. 
Responsiveness to phenobarbital in an adult with Crigler-Najjar disease associated with neurological involvement and skin hyperextensibility. We present the case of a 23-yr-old man who had had since birth marked and sustained unconjugated non-hemolytic hyperbilirubinemia and who had had several attacks of grand mal seizures. Analysis of serum bilirubin by diazoreactive methods showed serum levels of unconjugated bilirubin as high as 445 mumol/L that were not affected by phenobarbital administration. However, analysis of serum bile pigments by high-pressure liquid chromatography demonstrated marked decrease of unconjugated bilirubin after phenobarbital treatment (from 432.4 mumol/L to 291.0 mumol/L) associated with slight increase of bilirubin monoconjugates and disconjugates (from 0.25 mumol/L to 0.42 mumol/L). Furthermore, in the past few years the patient had exhibited striking skin hyperextensibility and diaphragm eventration. This case confirms that alkaline methanolysis-high-pressure liquid chromatography is the most reliable method for assessment of serum fraction bilirubin levels; that clinical parameters such as neurological signs do not unequivocally discriminate between type I and II Crigler-Najjar disease and that response to phenobarbital treatment remains the main diagnostic tool. 
Myocardial infarction in childhood: clinical analysis of 17 cases and medium term follow up of survivors. Between 1979 and 1989 17 patients aged two months to 12 years with acute myocardial infarction of any cause (other than after cardiac surgery) were seen at a children's hospital. Eight died from three days to three years after diagnosis (overall mortality 47%). The nine survivors, now aged 2-17 years, have been followed for one to 10 years (mean follow up five years) after infarction. The commonest causes of myocardial infarction in this series were anomalous origin of left coronary artery from the pulmonary artery (six patients (35%] and Kawasaki disease (five patients (27%]. The main symptoms of acute myocardial infarction were dyspnoea, vomiting, and difficulty feeding. Diagnosis was made in all patients by electrocardiography and confirmed by echocardiography, cardiac catheterisation, or at operation. All survivors were symptom free with excellent exercise capacity. The left ventricular ejection fraction in survivors ranged from 21% to 66%, and only one child was on regular cardiac medications. There were no cases of late sudden death. Twenty four hour Holter monitoring performed on survivors was normal (seven) or showed minor abnormalities only (one), suggesting that serious arrhythmia is rare after paediatric myocardial infarction. Myocardial infarction in children had a high early mortality; however, the incidence of serious arrhythmia was low in the survivors, who had a good exercise tolerance even when the left ventricular ejection fraction was low. 
Post stenotic aneurysm in popliteal artery entrapment syndrome. In a retrospective review of 74 cases of Popliteal Entrapment Syndrome collected over a 16 year period, 10 cases of aneurysm were found (13.5%). This represents an incidence of 26% of the 38 cases of popliteal aneurysm of any etiology seen during the same period of time. In contrast to atherosclerotic aneurysms, these aneurysms were seen in a young age group (21-30 years of age) and all were associated with popliteal entrapment. Evidence is presented to support our opinion that these aneurysms are post-stenotic in origin. We feel that young adults with symptoms of leg ischaemia and evidence of an aneurysm of the popliteal artery should be investigated for popliteal entrapment and treated before complications occur. We have found a posterior approach to be the most satisfactory method of exploring the popliteal fossa. 
Polyneuropathy induced by m-tolyl methyl carbamate intoxication. A 55-year-old woman who attempted suicide by ingesting 200 ml of m-tolyl methyl carbamate (MTMC) is reported. She was comatose for 3 days and, upon recovery, had notable paraesthesia in her lower limbs and difficulty in walking. Neurological examination revealed sensorimotor polyneuropathy. Sural nerve biopsy revealed marked axonal degeneration with a moderate decrease of myelinated fibres. 
Pseudoaneurysm of the popliteal artery as a complication of an osteochondroma. A review of the literature and a case report. False aneurysm of the femoral artery was associated with a solitary osteochondroma of the femur in a 22-year-old man. An extensive review of the literature and the problems related to diagnosis revealed that the aneurysm was apparently unique. Contrary to previous reports, computed tomography and angiography did not establish the diagnosis. The physical findings were more informative. 
Mammographic and CT findings after breast reconstruction with a rectus abdominis musculocutaneous flap. This essay illustrates the radiologic appearance of the reconstructed breast and the abdominal wall after breast reconstruction with a transverse rectus abdominis musculocutaneous (TRAM) flap. The findings are based on a retrospective study of 42 mammograms, 17 abdominal CT scans, and two CT scans each of the chest and pelvis of patients who underwent this procedure. 
Surgical management of severe aortic outflow obstruction in lesions other than the hypoplastic left heart syndrome: use of a pulmonary artery to aorta anastomosis. Between December 1985 and April 1990, 50 infants with a variety of congenital cardiac lesions other than the hypoplastic left heart syndrome underwent surgical relief of aortic outflow obstruction by creation of a pulmonary artery to aorta anastomosis. The patients were grouped anatomically by ventriculoarterial alignment. Nineteen had normally aligned great arteries (group I); 25 had transposition of the great arteries, all with a univentricular heart of left ventricular morphology (group II); and 6 had a double-outlet right ventricle (group III). All patients had either aortic stenosis with atresia, subaortic stenosis or a restrictive ventricular septal defect. Sixteen had normal arch anatomy; 34 had arch anomalies consisting of arch hypoplasia (n = 17), coarctation (n = 11), interruption of the arch (n = 4) and complex arch anomalies (n = 2). Surgery was performed at a median age of 10 days (range 2 to 184). Of the 50 infants, 33 survived. No significant difference in early survival (30 days) was noted among the groups of varying ventriculoarterial alignment (68% group I, 72% group II, 83% group III) (p greater than 0.05). Overall actuarial survival was 63% at 18 months. Analysis of actuarial survival by arch anatomy, although not statistically significant, revealed a trend toward better survival at 18 months postoperatively in infants with normal arch anatomy (81%) than in infants with arch anomalies (54%). Of the 33 survivors, 26 have proceeded to the next surgical stage, including the Fontan procedure in 8, superior cavopulmonary anastomosis in 13 and biventricular repair in 5. 
Complete infarction of the eye complicating a choroidal malignant melanoma. Infarction of malignant melanoma of the choroid has been previously reported, but infarction of the whole eye in association with infarction of melanoma is a rare event that has not been previously described. We present such a case and discuss the possible pathogenesis. 
Sudden death in infants sleeping on polystyrene-filled cushions. BACKGROUND. Infants are at risk for both the sudden infant death syndrome (SIDS) and accidental suffocation. On postmortem examination, however, it is difficult to distinguish one from the other without information from the scene of death. Healthy infants are assumed to be able to turn their heads and, if not otherwise restrained, to obtain fresh air. We assessed this assumption in an investigation of infant deaths that occurred during sleep on cushions filled with polystyrene beads. METHODS. We obtained data on 25 deaths from the U.S. Consumer Product Safety Commission. We also used mechanical and animal models to study physiologic aspects of ventilation relevant to these results, by simulating the effects on an infant of breathing into a cushion. We measured the effects of softness, malleability (molding of the cushion about an infant's head), airflow resistance, and rebreathing of expired gases. RESULTS. All 25 study infants were prone when found dead, and at least 88 percent were face down with nose and mouth obstructed by the cushion. SIDS was the diagnosis in 19 of the 23 infants who underwent autopsy. Our findings show, however, that the cushion would have limited movement of the infant's head to obtain fresh air, and the amount of rebreathing we estimated to have occurred in the infants was lethal in a rabbit model. CONCLUSIONS. Accidental suffocation by rebreathing was the most likely cause of death in most of the 25 infants studied. Consequently, there is a need to reassess the cause of death in the 28 to 52 percent of the victims of SIDS who are found with their faces straight down. Safety regulations setting standards for softness, malleability, and the potential for rebreathing are needed for infant bedding. 
Complications of tissue plasminogen activator therapy after vitrectomy for diabetes. Human recombinant tissue plasminogen activator (25 micrograms) was injected into seven eyes of six patients who had developed massive fibrin deposition after vitrectomy surgery for diabetes. Six eyes had developed pupillary membranes and recurrence of tractional retinal detachment from fibrin membranes, and one eye had developed only a pupillary membrane. All pupillary membranes resolved within one hour of administration of tissue plasminogen activator, and five tractional retinal detachments resolved within 24 hours. All eyes developed evidence of intraocular bleeding after tissue plasminogen activator injection. Subsequently, six of seven eyes developed recurrence of fibrin accumulation and tractional retinal detachment. 
Diet and nutrition in ulcer disease. In this era of H2-inhibitors, the available evidence does not support the need to place peptic ulcer disease patients on restrictive diets. The major goal of diet is to avoid extreme elevations of gastric acid secretion and the direct irritation of gastric mucosa. In view of this, only slight modifications in the patient's usual diet are recommended. Table 1 depicts a sample menu for chronic peptic ulcer disease. Frequent milk ingestion as previously prescribed is not encouraged. This is owing to the transient buffering effect and significant gastric acid secretion effect of milk. The fat content of milk has no influence on these effects. Spices, in particular black pepper, red pepper, and chili powder, may produce dyspepsia. One study shows red chili powder to have no detrimental effect on duodenal ulcer healing. It has also been proposed that daily pepper ingestion may have a beneficial adaptive cytoprotective response. While still controversial and under evaluation, peptic ulcer patients should avoid any spice that causes discomfort, especially during exacerbation of peptic disease. Currently, studies indicate that it is prudent to avoid alcohol. This is especially true for the concentrated forms, such as 40% (80 proof) alcohol. Coffee should be avoided on the basis of its strong acid secretagogue property. Coffee can induce dyspepsia. Whether noncoffee caffeine-containing beverages (tea, soft drinks) induce peptic ulcer is unknown, but they are acid secretion stimulators. Decaffeinated coffee has an acid stimulating effect as well. It is reasonable to have peptic ulcer patients restrict decaffeinated coffee and all caffeine-containing beverages. There appears to be no evidence to restrict dietary fiber. Some fiber-containing foods may possess factors that are protective against ulcer disease. According to the Mayo Clinic Diet Manual, previously recommended small frequent feedings have not been shown to be more effective than three meals per day in the treatment of chronic peptic ulcer disease. This reference cites authorities advising against extra feedings because of increased acid secretion and unnecessary complication of eating patterns. However, some patients claim to be relieved of symptoms with more frequent feedings, especially during acute phases. Citric acid juices may induce reflux and cause discomfort in selective patients. Stomach distention with large quantities of food should be discouraged. Although there is now little role for dietary therapy, one should note that bland and ulcer diets probably are not detrimental to most persons if they are used for a short time and may have some psychological benefit.(ABSTRACT TRUNCATED AT 400 WORDS). 
Risk factors for gastrointestinal ulcers caused by nonsteroidal anti-inflammatory drugs (NSAIDs) [published erratum appears in J Fam Pract 1991 Jul;33(1):16] Thirteen million individuals in the United States take nonsteroidal anti-inflammatory drugs (NSAIDs) chronically for the relief of pain and inflammation caused by arthritis and related conditions. NSAIDs are valuable and in many cases essential to the management of arthritis pain. Long-term use of NSAIDs, however, can cause gastrointestinal (GI) ulcers and potentially life-threatening ulcer complications. Factors such as older age (greater than or equal to 60 years), a history of peptic ulcer disease, concomitant corticosterid use, cigarette smoking, alcohol use, and high dose or multiple NSAID therapy can increase the risk of GI damage and complications in the chronic NSAID user. Physician awareness of these risk factors is crucial so that the benefits and hazards of NSAID therapy in high-risk patients can be properly weighed. When the decision is made to prescribe NSAIDs, despite the presence of risk factors for NSAID-induced ulcers, patients should be closely monitored, and, in some cases, effective prophylaxis should be initiated. This is especially important since NSAID-induced gastrointestinal ulcers can be asymptomatic, causing serious ulcer complications without warning. 
Nesidioblastosis: evidence for autosomal recessive inheritance. The risk of recurrence of nesidioblastosis is unclear. Thirty patients from 28 families were studied; the marriages were consanguineous in five families. The ratio of subsequent affected to unaffected siblings was similar to that of an autosomal recessive condition and the sex ratio was close to 1. 
Isolated serum-free perfused rat kidneys release immunoreactive erythropoietin in response to hypoxia. The renal glycoprotein hormone erythropoietin (Epo) interacts with erythrocytic progenitors to stimulate their proliferation and differentiation in the bone marrow. The renal O2-sensing mechanism in the control of the synthesis of Epo is still poorly understood. Therefore, the capacity of isolated rat kidneys to produce Epo during hypoxic and anemic perfusion was studied. The kidneys were perfused at a constant perfusion pressure of 100 mm Hg with a substrate-enriched Krebs-Henseleit solution containing 60 g/liter BSA and freshly drawn human erythrocytes. Epo was measured by RIA. When the kidneys were perfused at an arterial pO2 of 720 or 150 mm Hg (hematocrit, 5%), Epo production was very low (0.1-0.2 U/g kidney within 3 h of perfusion). When the arterial pO2 was lowered to 35 or 20 mm Hg, Epo production increased to 0.4 and 0.9 U/g kidney, respectively. The release of Epo during hypoxic perfusion (pO2 35 and 20 mm Hg) was little affected by changes in the hematocrit, i.e. the O2-carrying capacity of the perfusion medium over a wide range (0-40%). These results indicate that the production of Epo in the isolated perfused kidney depends on the availability of O2 and can be modulated by changes in the arterial pO2. 
Flexible sigmoidoscopy may be ineffective for secondary prevention of colorectal cancer in asymptomatic, average-risk men. Asymptomatic men (N = 114) 50 years of age or older had screening for colorectal neoplasia with flexible sigmoidoscopy followed by colonoscopy regardless of the sigmoidoscopic result. Our study objective was to determine the prevalence of patients having isolated adenomatous polyps in a proximal colonic segment in the absence of a distal index neoplasm within reach of the sigmoidoscope. Through the combined use of sigmoidoscopy and colonoscopy, adenomatous polyps were detected in 47 of 114 individuals (41%). A total of 88 adenomas was found. Seventeen patients had isolated neoplasms in proximal colonic segments in the absence of distal adenomas. These patients represented 15% of screened subjects (17 of 114) and 20% of individuals who lacked adenomas on sigmoidoscopy (17 of 84). The majority of proximal neoplasms were small (less than 1.0 cm), tubular adenomas. Flexible sigmoidoscopy may be ineffective for screening asymptomatic men for neoplasia. However, it remains to be determined if a 20% miss rate (for those with a normal sigmoidoscopic examination) is significant and whether small proximal adenomas are worth finding. 
Temporal thresholds for neocortical infarction in rats subjected to reversible focal cerebral ischemia. We investigated the temporal threshold for focal cerebral infarction in the spontaneously hypertensive rat. The right middle cerebral artery and common carotid artery were occluded for 0, 1, 2, 3, 4, or 24 hours, and all the animals were sacrificed 24 hours after the onset of ischemia. Cortical infarct volumes and edema volumes were quantified in serial frozen sections of hematoxylin and eosin-stained tissue using image analysis. Upon occlusion, blood flow in the core of the ischemic zone, measured with laser-Doppler flowmetry, fell to a mean +/- standard deviation of 21 +/- 7% of the preocclusion baseline value (n = 26). During the first hour of ischemia, blood flow in the densely ischemic zone rose to 27 +/- 8% of baseline (n = 25). Release of the middle cerebral artery and common carotid artery occlusions rapidly restored cortical blood flow to 213 +/- 83% of baseline (n = 21). Focal ischemia of 1 hour's duration caused little or no infarction, while ischemic intervals of 2 and 3 hours produced successively larger volumes of infarcted cortex. Ischemic intervals of 3-4 hours' duration followed by approximately 20 hours of recirculation yielded infarct volumes that were not significantly different from those after 24 hours of permanent focal ischemia. The results indicate that 3-4 hours of focal cerebral ischemia in this rat model is sufficient to attain maximal infarction and suggest that recirculation or pharmacological interventions after this time will provide little benefit. 
Air esophagogram and intestinal pseudoocclusion in a patient with scleroderma. Air in the esophagus is unusual because it is collapsible. Its finding on a chest roentgenogram, particularly when not associated with a fluid level indicative of stricture, should strongly suggest systemic sclerosis (scleroderma). We describe a patient with scleroderma with intestinal pseudoocclusion and an air esophagogram. Study of chest roentgenograms of 83 patients with scleroderma, including those of 7 with pseudoocclusion, revealed no other instance of air esophagogram. This radiological sign, although rare, should suggest scleroderma and may be particularly useful in patients with "systemic sclerosis sine scleroderma.". 
Local anesthesia blocks the antiemetic action of P6 acupuncture. The incidence of postoperative illness was monitored for 6 hours in 74 women premedicated with nalbuphine, 10 mg, and undergoing short gynecologic operations of similar duration under methohexitalnitrous oxide-oxygen anesthesia. Each patient received P6 acupuncture for 5 minutes at the time of administration of premedication. In random order the site of the acupuncture had been previously infiltrated with normal saline solution in half of the patients and 1% lidocaine in the remaining patients. Postoperative emetic sequelae occurred significantly more often in those who received lidocaine compared with the group that received saline solution. This demonstrates the ability of a local anesthetic administered at the point of stimulation to block the antiemetic action of P6 acupuncture in a manner similar to that shown by others for analgesia. 
Immunolocalization of the Bcl-2 protein within hematopoietic neoplasms. The Bcl-2 proto-oncogene was discovered at the t(14;18) breakpoint found in most follicular B-cell lymphomas and some diffuse large-cell lymphomas. Bcl-2 is unique among proto-oncogenes, being localized to mitochondria and extending cell survival by blocking programmed cell death. We examined Bcl-2 protein expression in 82 hematologic malignancies and reactive lymphoid processes. All lymphomas with Bcl-2 rearrangement demonstrated high levels of Bcl-2 protein. However, most follicular and diffuse lymphomas without Bcl-2 rearrangement also displayed intense Bcl-2 staining. In these cases, mechanisms other than classic translocation may be deregulation Bcl-2. The pattern of Bcl-2 staining in follicular lymphoma is the inverse of the pattern in reactive hyperplasia, confirming a role for Bcl-2 immunolocalization in routine diagnosis. Small lymphocytic malignancies, including small lymphocytic lymphoma, mantle zone lymphoma, and chronic lymphocytic leukemia, expressed intermediate levels of Bcl-2. Bcl-2 protein varied in plasma cell dyscrasias. Bcl-2 protein levels in T-cell lymphomas reflected their corresponding stage of development. No substantial Bcl-2 was present in the Reed-Sternberg cells of nodular sclerosing Hodgkin's disease. Chronic myelogenous leukemia was strongly positive for Bcl-2, consistent with the presence of Bcl-2 in normal myeloid progenitors. Immunohistochemistry identified an expanded spectrum of hematopoietic neoplasms in which Bcl-2 may provide a cell survival advantage. 
Intestinal lymphonodular hyperplasia of childhood: patterns of presentation. In this retrospective analysis we searched for a constellation of signs or symptoms attributable to childhood lymphonodular hyperplasia (LNH). Of 147 children with documented LNH reviewed, 43% had lesions in the small bowel, and 57% in the large bowel. Children in this study presented with complaints of abdominal pain (58%) and bright red blood per rectum (32%). Physical examination revealed little except right lower quadrant (RLQ) abdominal tenderness and "fullness" in 35%. The pain was periumbilical, dull-cramping, rarely acute, and nonradiating. The hematochezia was most commonly streaky red in mucoid strands adhering to the stools, with no associated tenesmus. Three clinical patterns emerged: (a) Under 1 year of age most patients were male, with painless bleeding and pancolonic LNH. (b) Between 2 and 6 years, although the LNH was predominantly colonic, pain and bleeding occurred equally. (c) From 7 years old on, the main symptom was abdominal pain, but LNH distribution was nearly equal between the small bowel and the colon. To date, our long-term follow-up of the children with isolated LNH has revealed no sequelae. 
Gastric carcinoids and their precursor lesions. A histologic and immunohistochemical study of 23 cases. A histologic and immunohistochemical study was carried out in 23 unselected nonantral gastric carcinoids and their precursor lesions classified according to Solcia et al. None of the patients showed Zollinger-Ellison syndrome. Two variants of carcinoids showing distinctive pathologic and pathogenetic characteristics were identified on the basis of presence or absence of associated chronic atrophic gastritis type A (A-CAG). Chronic atrophic gastritis type A was found in 19 cases showing either single or multiple neoplasms, tumor extension limited to the mucosa or submucosa, consistent endocrine cell precursor changes in extratumoral mucosa, and consistent hypergastrinemia and/or G cell hyperplasia. Associated precursor lesions were only hyperplastic in all but two cases with single carcinoids whereas they were also dysplastic in all but one case with multiple carcinoids. The four tumors arising in nonatrophic mucosa were all single, more aggressive, and not associated with extratumoral endocrine cell proliferations or with signs of gastrin hypersecretion. Tumor cells were diffusely immunoreactive for chromogranin A and synaptophysin but usually negative for chromogranin B or HISL-19. Scattered serotonin cells were found in ten carcinoids. They were more frequent in infiltrating than in intramucosal tumors as were the less represented pancreatic polypeptide cells whereas the reverse was found for alpha-subunit-containing cells. These results are of relevance for tumor pathogenesis and may provide the rationale for a less aggressive therapeutic approach in the patients. 
Facial dystonia, essential blepharospasm and hemifacial spasm. Movement disorders, or dyskinesias, in the facial region may be categorized in several ways. Dystonic movement disorders in the cranial-cervical region, including essential blepharospasm, Meige syndrome and spasmodic torticollis, are characterized by uncontrollable squeezing movements in the face and neck. These disorders typically present in the fifth and sixth decades of life. Essential blepharospasm is particularly debilitating, as the involuntary eyelid closure that accompanies this condition may result in functional blindness with an otherwise normal visual pathway. Hemifacial spasm is an intermittent, unilateral, spasmodic contraction of the muscles innervated by the facial nerve. This disorder usually presents in the third or fourth decade and has a different underlying pathophysiology than the dystonias. Botulinum A toxin therapy has largely supplanted surgical intervention in the treatment of essential blepharospasm and hemifacial spasm. 
S-adenosyl-L-methionine in the treatment of patients with intrahepatic cholestasis of pregnancy: a randomized, double-blind, placebo-controlled study with negative results. S-Adenosyl-L-methionine has been reported to induce beneficial effects in intrahepatic cholestasis of pregnancy. Because cholestasis of pregnancy has a high prevalence in Chile and a deleterious effect on fetal prognosis, we decided to verify the efficacy of S-adenosyl-L-methionine in this disease. Eighteen patients with pruritus that appeared during pregnancy and with elevated serum levels of bile salts (68.1 +/- 15.9 mumol/L; mean +/- S.E.M.) and ALT (226 +/- 50 KU/L) were enrolled in a prospective double-blind study comparing the effects of the drug with a placebo. S-Adenosyl-L-methionine, 900 mg, or placebo was administered in daily intravenous infusions for 20 days. Every 5 days liver function tests were done and pruritus was assessed using a preestablished score. No significant differences in pruritus or in serum levels of bile salts, ALT, bilirubin and alkaline phosphatases were seen during or after treatment between patients who received S-adenosyl-L-methionine (n = 9) or placebo (n = 9). No relevant adverse reactions were detected. Most patients had cesarean sections because of reasons unrelated to the therapeutic trial. All newborns had Apgar scores greater than 7 and normal postnatal development. Our patients had moderately severe to severe cholestasis of pregnancy as indicated by the onset of pruritus before wk 32 of pregnancy. Seven of nine multiparous patients had a past history of recurrent cholestasis of pregnancy. In this study, the administration of S-adenosyl-L-methionine during 20 days did not improve intrahepatic cholestasis of pregnancy. 
Fabry disease: detection of 13-bp deletion in alpha-galactosidase A gene and its application to gene diagnosis of heterozygotes. Polymerase chain reaction amplification of reverse-transcribed messenger RNA from a patient with Fabry disease revealed a 13-base pair deletion in the 5' region (exon 1) of alpha-galactosidase A complementary DNA. This gene rearrangement was not detected by Southern or Northern analysis. Short direct repeats were present around the breakpoints, and considered to be of pathogenetic significance. Gene diagnosis of the mother and a female cousin was successfully achieved by polymerase chain reaction amplification of genomic DNA; the former as a Fabry disease heterozygote and the latter as a normal homozygote. 
Breast conservation therapy. Severe breast fibrosis after radiation therapy in patients with collagen vascular disease. Two patients with collagen vascular disease (rheumatoid arthritis and scleroderma) had extremely poor cosmetic results after breast radiation therapy (RT). The patient with rheumatoid arthritis received 5251 cGy at 210 cGy per day, followed by a 1600 cGy iridium-192 implant boost. Between 8 and 11 months post-RT she had severe breast fibrosis, retraction, and pain that required a mastectomy for relief. The patient with scleroderma received 5040 cGy at 180 cGy per day without a boost. Between 1 and 4 months post-RT the systemic symptoms of scleroderma progressed and the breast became hard and retracted. Both rheumatoid arthritis and scleroderma are chronic systemic diseases characterized by severe inflammation and an autoimmune component. The presence of scleroderma at or before treatment should be considered a contraindication to breast RT, whereas the presence of active rheumatoid arthritis should be considered a relative contraindication. An autoimmune mechanism will be presented to explain both the fibrosis and the systemic progression of collagen vascular disease that was observed. 
Urinary pepsinogen I as a tumor marker of stomach cancer after total gastrectomy. The possibility that urinary pepsinogen I is a tumor marker of stomach cancer after total gastrectomy was examined. To decide the cutoff level of urinary pepsinogen I after total gastrectomy, urine samples from 15 patients who had undergone total gastrectomy for stomach cancer in the early or advanced stages and had been free from recurrence for more than 5 years were examined by pepsinogen I-specific radioimmunoassay. The mean concentration of urinary pepsinogen I was 17.5 +/- 7.4 ng/ml and the cutoff level of urinary pepsinogen after total gastrectomy was set at 32 ng/ml (mean + 2 SD). Twenty-two of 74 cases who had undergone total gastrectomy for stomach cancer were regarded as positive. And 20 of these 22 positive cases had definite clinical signs of recurrence of stomach cancer. There were only two false-positive cases. These results suggest that urinary pepsinogen I will be an useful tumor marker in detecting the recurrence of stomach cancer after total gastrectomy. 
Acute postinfarction septal rupture: long-term results. From 1973 to 1989, 66 patients received early surgical repair for acute postinfarction ventricular septal rupture. Mean age was 64 +/- 7 years (range, 45 to 80 years). Ventricular septal rupture occurred soon after acute myocardial infarction (3.4 +/- 4 days), and the first medical treatment occurred 6.7 +/- 7 days after onset of acute myocardial infarction. Three patients had a previous myocardial infarction. The site of the rupture was anterior in 38 patients (57%) and posterior in 28 (43%). Forty-four patients (67%) were in shock at the time of admission. Intraaortic balloon pumping was used preoperatively in 28. Operation was performed at the time of maximal efficacy of medical treatment. The same technique was used in all cases. Associated procedures included coronary bypass grafting in 5 patients and valvar operation in 5. The patients have been carefully followed up for up to 16 years. Hospital mortality was 45% (30 patients) and was cardiac related or due to acute renal failure in 25 patients (83%). No correlation could be revealed between early death and age, sex, preoperative intraaortic balloon pumping, or year of operation. Location of the ventricular septal rupture (early mortality of 57% for posterior versus 37% for anterior ventricular septal rupture) and shock at the time of admission (52% versus 32%) showed a trend toward significance (0.08 less than or equal to p less than 0.10). Response to initial active therapy has a strong predictive value (mortality of 70% in unresponsive patients versus 14% in responders; p less than 0.001). 
Endothelial modulation of vascular tone: relevance to coronary angioplasty and restenosis. The vascular endothelium importantly modulates many biochemical and physiologic properties of the vascular wall, including the release of potent vasoactive factors, maintenance of an anticoagulant state and modulation of vascular growth by the release of both proliferative and antiproliferative substances. Prominent among these endothelial roles is the production of a potent vasodilator or family of vasodilators termed the endothelium-derived relaxing factor, one of which has been identified to be nitric oxide or a closely related compound. Several diseases that commonly occur in patients undergoing coronary angioplasty alter many facets of endothelial function and may predispose to adverse clinical sequelae of angioplasty, including immediate thrombosis, restenosis and vascular spasm. Several features of the endothelium-derived relaxing factor, how it is altered by pathologic processes and how these considerations relate to the immediate and late postangioplasty periods are discussed. 
Iontophoresis versus subcutaneous injection: a comparison of two methods of local anesthesia delivery in children. The relative efficacy of local lidocaine anesthesia administered by subcutaneous injection and by iontophoresis was studied in 13 pediatric renal dialysis patients (ages 11-19 years: mean age 15.8 years). Each patient served as his own control at 3 assessment periods. Each type of anesthetic delivery method was administered to either of 2 fistula sites. Patients used visual analogue scales to rate pain, anxiety, and satisfaction for each method. Behavioral observations were made by an observer and a nurse. Paired sample t tests were used to compare the 2 drug delivery methods for patient, observer, and nurse ratings across assessment periods. There were no significant differences between methods for ratings of anxiety before or during the procedure. The injection of lidocaine was rated as more painful by the observer and nurse (with a trend for patients) than the use of iontophoresis. But, the patients and nurse rated the injection method as more effective. Iontophoresis was never rated as superior to the injection method, even after turning over control of drug delivery by iontophoresis to the patient (sessions 2 and 3). Patients were more satisfied with iontophoresis at session 2 when they took over control, but lost enthusiasm by session 3. Three subjects withdrew from the study due to cutaneous burns and prolonged anesthesia delivery time with iontophoresis. Iontophoresis appears to be effective in reducing the pain of dialysis needle insertion but requires further investigation before it can be considered a viable alternative to subcutaneous injection. 
Thrombocytosis in adults: analysis of 777 patients. A total of 777 patients with thrombocytosis, defined as a platelet count of greater than 500 x 10(9)l-1, seen in a University hospital over a 1-year period, were studied prospectively for aetiology. The most frequent causes of thrombocytosis were infection (21.9%), rebound thrombocytosis (19.4%), tissue damage (17.9%), chronic inflammatory disorders (13.1%) and malignancy (5.9%). Thrombocytosis associated with multiple causative factors, occurring simultaneously, was seen in 6.1% of cases. Thrombocytosis of greater than or equal to 1 million x 10(9)l-1 was found most frequently in patients with multiple aetiological factors occurring at the same time, in myeloproliferative disorders, or in postsplenectomy patients. 
Late recovery of function after oculomotor nerve palsy. We studied three patients who developed oculomotor nerve paresis from different causes. Each patient improved somewhat over several months, after which there was no further improvement for at least six months. Although the pareses were thought to be stable after the period of no improvement, each patient subsequently had further improvement in both motility and alignment with resolution of diplopia in primary position and in more than one of the cardinal positions of gaze. Patients with oculomotor nerve paresis may improve further after an initial period of improvement followed by several months of stability. 
Maintenance therapy in peptic ulcer disease. The maxim "once an ulcer, always an ulcer" is still an appropriate description for the chronic nature of peptic ulcer disease. The goals for treating patients with ulcer disease are to relieve symptoms, heal the acute ulcer, reduce the risk of ulcer recurrence and complications, and decrease the economic impact of this chronic disease while maintaining the patient's quality of life. Patients with documented peptic ulcer disease should be carefully evaluated and a treatment plan devised that takes into account the possible need for maintenance therapy. Risk factors that seem to reflect a high likelihood of ulcer recurrence should be identified early in all ulcer patients and attempts made to minimize or correct them in the future. Assuming that a diagnosis of peptic ulcer disease has been firmly established and an adequate period of drug treatment makes complete ulcer healing likely, a reasonable way to proceed is outlined in Figure 4. If the patient is young and generally healthy, has an uncomplicated ulcer and few risk factors favoring ulcer relapse, either no treatment or symptomatic selfcare would be reasonable. If one chooses the latter course, the patient can be given a prescription for 3 to 6 months of medication and told to take full therapy for any recurrent symptoms, continuing the treatment until symptoms are relieved. The failure of such treatment to relieve symptoms after 2 to 3 weeks, the onset of alarming symptoms such as intense pain, vomiting, or melena, or possibly the exhaustion of the 6-month supply of medication with continued mild symptoms should lead to reevaluation. Alternatively, such a patient could be managed with no therapy and seen again if ulcer symptoms recur and reevaluated for further diagnosis and treatment. Obviously, patients who are candidates for these approaches to postulcer healing management are those with a low risk for ulcer recurrence and who are likely to be compliant with follow-up advice. Accordingly, careful patient selection seems most important in prescribing symptomatic self-care or intermittent full-dose maintenance treatment. On the other hand, if the patient has had a complicated course of ulcer disease, such as bleeding, or has a significant number of risk factors that would make early ulcer relapse highly likely, it would be prudent to institute continuous maintenance therapy while working to reduce or eliminate the adverse risk factors. Any relapse of symptomatic ulcer disease during noncontinuous maintenance therapy should indicate the need for return to a continuous dosing program.(ABSTRACT TRUNCATED AT 400 WORDS). 
Immunodepletion of extrinsic pathway inhibitor sensitizes rabbits to endotoxin-induced intravascular coagulation and the generalized Shwartzman reaction. We have reported earlier that immunodepletion of extrinsic pathway inhibitor (EPI) sensitizes rabbits to disseminated intravascular coagulation (DIC) induced by infusing a low concentration of tissue factor (TF). We now describe the effect of immunodepletion of EPI in rabbits administered endotoxin. Cortisone-treated rabbits were administered anti-rabbit EPI immunoglobulin (IgG) or Fab fragments or were administered control nonimmune material before an injection of endotoxin. In four of seven rabbits administered anti-EPI, plasma EPI activity levels were reduced by 70% to 80% of initial levels for 6 to 8 hours. In these rabbits the endotoxin induced extensive DIC, as evidenced by substantial decreases in fibrinogen, factor V, factor VIII, and platelets, and gross hemorrhagic necrosis of the kidneys due to massive deposition of fibrin in the glomerular microcirculation (the generalized Shwartzman reaction). In three rabbits administered anti-EPI, plasma EPI levels were only transiently reduced. In these rabbits and in four rabbits administered nonimmune IgG or Fab, endotoxin induced minimal to moderate intravascular clotting and deposits of fibrin were not found in the glomerular capillaries. Because it is believed that TF expressed on monocytes triggers endotoxin-induced coagulation, these data are taken as evidence that EPI functions as a natural anticoagulant that can regulate factor VIIa/TF activity expressed on cell surfaces in vivo. They support a hypothesis that EPI prevents thrombotic complications that might otherwise result from exposure of blood to cytokine-induced generation of small amounts of TF on cell surfaces in many inflammatory and infectious disease states. 
Testicular plasmacytoma. A case report with immunohistochemical studies and literature review. Plasmacytomas of the testes are extremely rare tumors, especially when occurring in the absence of a previous or concurrent diagnosis of multiple myeloma. We present a case of solitary testicular plasmacytoma in a 71-year-old man who had no clinical evidence of myeloma. Immunohistochemical stains showed monoclonal cytoplasmic production of IgA-kappa within tumor cells. A summary of the other reported cases of testicular plasmacytoma is presented. Plasmacytoma of the testes, while occasionally manifesting as a solitary, primary lesion, most likely is a precocious, highly unusual manifestation of systemic multiple myeloma. 
The effect of prostacyclin on intracranial pressure in patients with acute hepatic and renal failure. Prostacyclin was administered on 20 occasions to 12 patients with fulminant hepatic failure complicated by acute renal failure prior to commencing dialysis at a dose of 5 ng/kg.min. Intracranial pressure was noted to increase during the infusion from a median of 12 mmHg (95% confidence limits 9-14) to 17 mmHg (12-25), p less than 0.01, at the same time the mean arterial blood pressure declined from 79 mmHg (65-82) to 64 (56-70), p less than 0.01, and the cerebral perfusion pressure from 62 mmHg (53-67) to 44 mmHg (41-55), p less than 0.01. The changes were greater for those patients who subsequently died from cerebral edema. Patients with fulminant hepatic and acute renal failure are at risk of dying from cerebral edema. The direct administration of prostacyclin, used for extracorporeal anticoagulation, may cause a further increase in intracranial pressure and reduce cerebral perfusion, thus resulting in patient morbidity and mortality. 
Combined thoracic aortic dissection and abdominal aortic fusiform aneurysm. Certain clinical and autopsy findings are described in 13 patients who had both aortic dissection (AD) and fusiform abdominal aortic aneurysm (AAA). All 13 patients had severe and extensive aortic atherosclerosis. The AAA was diagnosed clinically in 9 patients, and 5 had the AAA resected. The AD was diagnosed clinically in 5 patients, and 2 underwent attempted operative repair. Two patients who had the AAA resected because of suspected rupture were found later to have ruptured a more proximal AD. Thus, AD occurs occasionally in patients who have AAA. In older persons with suspected rupture of an AAA, a more proximal rupture of an AD should be ruled out. When both AAA and AD are present in the same patient, the AD is more likely the cause of cardiovascular collapse than is rupture of the AAA. 
Enterocutaneous fistulas following laparotomy for trauma. Enterocutaneous fistulas (ECF) are recognized complications of various bowel diseases. Trauma is reported as a rare cause of ECF. ECF following laparotomy for abdominal injury was studied in 15 patients to determine whether traditional principles of management for ECF are applicable in posttraumatic ECF. Thirty-three per cent of patients with posttraumatic ECF spontaneously healed fistulas with appropriate nutritional support without operative intervention. Sixty-six per cent of patients required operative intervention, either because of associated sepsis or failure to spontaneously heal. Five patients had fistulas originate from areas of bowel not injured in the initial injury. This study suggests traditional principles of management for ECF are applicable in ECF following laparotomy for abdominal injury and result in a spontaneous closure of fistulas in one-third of patients. In addition, sepsis is the main indication for early aggressive operative treatment of these fistulas. 
Stroke prevention in women: role of aspirin versus ticlopidine. Stroke is the third leading cause of death in North America. Most studies indicate that women are just as likely as men to have an initial stroke but less likely to have a recurrent stroke. Aspirin and ticlopidine are two antiplatelet drugs that reduce the risk of recurrent stroke by 25% to 30%. In some stroke prevention trials, aspirin has been shown to be more effective for men than for women. In contrast, major stroke prevention trials using ticlopidine have demonstrated equal benefit in women and in men. The overall incidence of adverse effects seen with ticlopidine is not significantly different from that observed with aspirin. There are now two effective agents useful in stroke prevention in both men and women. 
Neutrophil accumulation in ischemic canine myocardium. Insights into time course, distribution, and mechanism of localization during early reperfusion. BACKGROUND. We have previously demonstrated that chemotactic factors released from the ischemic canine myocardium peak early during reperfusion and that they elicit neutrophil adherence reactions in vitro that are dependent on the CD18 glycoprotein family. In this study we investigated the hypothesis that neutrophil localization in ischemic canine myocardium in vivo occurs over a similar time course during early reperfusion and involves a CD18-dependent mechanism. METHODS AND RESULTS. We occluded the circumflex coronary artery for 1 hour in acute, open-chest dogs, followed by reperfusion for 1, 2, 3, or 4 hours. Regional myocardial blood flow was determined using radiolabeled microspheres, and localization was traced using technetium-99m-labeled autologous neutrophils. In the first hour of reperfusion, neutrophil localization occurred preferentially within the subendocardial region and was inversely related to flow. Neutrophil localization diminished across the ischemic myocardium from endocardium to epicardium but remained negatively related to flow in the midmyocardial region. Regardless of flow, little neutrophil localization occurred in the subepicardial region. Neutrophil localization was greatest in the first hour of reperfusion and diminished thereafter. By 4 hours of reperfusion, the rate of localization was markedly attenuated relative to 1 hour. Dogs given anti-CD18 monoclonal antibody R15.7 (1 mg/kg i.v.) before occlusion underwent 1 hour of occlusion followed by 1 hour of reperfusion. When compared with 1-hour reperfusion controls, the R15.7-treated dogs demonstrated significant attenuation of neutrophil localization in the subendocardial region. CONCLUSIONS. These data support the concepts that rapid neutrophil localization during reperfusion occurs within regions of previous myocardial ischemia and that neutrophils preferentially localize within the subendocardial region. The rate of neutrophil localization is greatest within the first hour after the initiation of reperfusion, and localization is, at least in part, CD18 dependent. Therapies directed against neutrophil-mediated reperfusion injury should be initiated with these considerations in mind.